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Sample records for nuclear export features

  1. Featured Article: Nuclear export of opioid growth factor receptor is CRM1 dependent.

    Science.gov (United States)

    Kren, Nancy P; Zagon, Ian S; McLaughlin, Patricia J

    2016-02-01

    Opioid growth factor receptor (OGFr) facilitates growth inhibition in the presence of its specific ligand opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin. The function of the OGF-OGFr axis requires the receptor to translocate to the nucleus. However, the mechanism of nuclear export of OGFr is unknown. In this study, endogenous OGFr, as well as exogenously expressed OGFr-EGFP, demonstrated significant nuclear accumulation in response to leptomycin B (LMB), an inhibitor of CRM1-dependent nuclear export, suggesting that OGFr is exported in a CRM1-dependent manner. One consensus sequence for a nuclear export signal (NES) was identified. Mutation of the associated leucines, L217 L220 L223 and L225, to alanine resulted in decreased nuclear accumulation. NES-EGFP responded to LMB, indicating that this sequence is capable of functioning as an export signal in isolation. To determine why the sequence functions differently in isolation than as a full length protein, the localization of subNES was evaluated in the presence and absence of MG132, a potent inhibitor of proteosomal degradation. MG132 had no effect of subNES localization. The role of tandem repeats located at the C-terminus of OGFr was examined for their role in nuclear trafficking. Six of seven tandem repeats were removed to form deltaTR. DeltaTR localized exclusively to the nucleus indicating that the tandem repeats may contribute to the localization of the receptor. Similar to the loss of cellular proliferation activity (i.e. inhibition) recorded with subNES, deltaTR also demonstrated a significant loss of inhibitory activity indicating that the repeats may be integral to receptor function. These experiments reveal that OGFr contains one functional NES, L217 L220 L223 and L225 and can be exported from the nucleus in a CRM1-dependent manner.

  2. Nuclear Export of Messenger RNA

    Science.gov (United States)

    Katahira, Jun

    2015-01-01

    Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP) particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex. PMID:25836925

  3. European Nuclear Features

    Energy Technology Data Exchange (ETDEWEB)

    Barre, B.; Gonzalez, E.; Diaz Diaz, J.L.; Jimenez, J.L.; Velarde, G.; Navarro, J.M.; Hittner, D.; Dominguez, M.T.; Bollini, G.; Martin, A.; Suarez, J.; Traini, E.; Lang-Lenton, J.

    2004-09-01

    ''European Nuclear Features - ENF'' is a joint publication of the three specialized technical journals, Nuclear Espana (Spain), Revue General Nucleaire (France), and atw - International Journal of Nuclear Power (Germany). The ENF support the international Europeen exchange of information and news about energy and nuclear power. News items, comments, and scientific and technical contributions will cover important aspects of the field. The second issue of ENF contains contributions about theses topics, among others: Institutional and Political Changes in the EU. - CIEMAT Department of Nuclear Fission: A General Overview. - Inertial Fusion Energy at DENIM. - High Temperature Reactors. European Research Programme. - On Site Assistance to Khmelnitsky NPP 1 and 2 (Ukraine). - Dismantling and Decommissioning of Vandellos I. (orig.)

  4. Nuclear export of L-periaxin, mediated by its nuclear export signal in the PDZ domain.

    Directory of Open Access Journals (Sweden)

    Yawei Shi

    Full Text Available Myelinating Schwann cells specifically express L-periaxin (L-PRX in the mammalian peripheral nervous system. Several loss-of-function mutations in periaxin have been described and linked to autosomal recessive Dejerine Sottas neuropathy and to demyelinating Charcot-Marie-Tooth disease. The localization of L-periaxin is developmentally regulated in the nucleus and the plasma membrane of Schwann cells. In this study, L-periaxin, which contains a PDZ domain, a nuclear localization signal (NLS domain, a repeat domain, and an acidic domain, was localized in the cytoplasm of RSC96 cells. By contrast, a mutant L-periaxin with a deleted PDZ domain was localized mainly in the nucleus of RSC96 cells. After a nuclear cyclin A1, which is localized exclusively in the nucleus, was fused with the PDZ domain, cyclinA1was found in the cytoplasm of RSC96 cells. Treatment with leptomycin B (LMB, a specific inhibitor of nuclear export mediated by leucine-rich nuclear export signal (NES, also causes nuclear accumulation of wild-type L-periaxin. Double leucine mutation (L83, 85Q in the putative NES in the PDZ domain prevented L-periaxin nuclear export and induced nuclear accumulation. These results suggested that the localization of L-periaxin in the cytoplasm is supported by NES in the PDZ domain.

  5. The nuclear export protein of H5N1 influenza A viruses recruits Matrix 1 (M1) protein to the viral ribonucleoprotein to mediate nuclear export.

    Science.gov (United States)

    Brunotte, Linda; Flies, Joe; Bolte, Hardin; Reuther, Peter; Vreede, Frank; Schwemmle, Martin

    2014-07-18

    In influenza A virus-infected cells, replication and transcription of the viral genome occurs in the nucleus. To be packaged into viral particles at the plasma membrane, encapsidated viral genomes must be exported from the nucleus. Intriguingly, the nuclear export protein (NEP) is involved in both processes. Although NEP stimulates viral RNA synthesis by binding to the viral polymerase, its function during nuclear export implicates interaction with viral ribonucleoprotein (vRNP)-associated M1. The observation that both interactions are mediated by the C-terminal moiety of NEP raised the question whether these two features of NEP are linked functionally. Here we provide evidence that the interaction between M1 and the vRNP depends on the NEP C terminus and its polymerase activity-enhancing property for the nuclear export of vRNPs. This suggests that these features of NEP are linked functionally. Furthermore, our data suggest that the N-terminal domain of NEP interferes with the stability of the vRNP-M1-NEP nuclear export complex, probably mediated by its highly flexible intramolecular interaction with the NEP C terminus. On the basis of our data, we propose a new model for the assembly of the nuclear export complex of Influenza A vRNPs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

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

    2017-02-01

    HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding.

  7. RNA Nuclear Export: From Neurological Disorders to Cancer.

    Science.gov (United States)

    Hautbergue, Guillaume M

    2017-01-01

    The presence of a nuclear envelope, also known as nuclear membrane, defines the structural framework of all eukaryotic cells by separating the nucleus, which contains the genetic material, from the cytoplasm where the synthesis of proteins takes place. Translation of proteins in Eukaryotes is thus dependent on the active transport of DNA-encoded RNA molecules through pores embedded within the nuclear membrane. Several mechanisms are involved in this process generally referred to as RNA nuclear export or nucleocytoplasmic transport of RNA. The regulated expression of genes requires the nuclear export of protein-coding messenger RNA molecules (mRNAs) as well as non-coding RNAs (ncRNAs) together with proteins and pre-assembled ribosomal subunits. The nuclear export of mRNAs is intrinsically linked to the co-transcriptional processing of nascent transcripts synthesized by the RNA polymerase II. This functional coupling is essential for the survival of cells allowing for timely nuclear export of fully processed transcripts, which could otherwise cause the translation of abnormal proteins such as the polymeric repeat proteins produced in some neurodegenerative diseases. Alterations of the mRNA nuclear export pathways can also lead to genome instability and to various forms of cancer. This chapter will describe the molecular mechanisms driving the nuclear export of RNAs with a particular emphasis on mRNAs. It will also review their known alterations in neurological disorders and cancer, and the recent opportunities they offer for the potential development of novel therapeutic strategies.

  8. Analysis and prediction of leucine-rich nuclear export signals

    DEFF Research Database (Denmark)

    La Cour, T.; Kiemer, Lars; Mølgaard, Anne;

    2004-01-01

    We present a thorough analysis of nuclear export signals and a prediction server, which we have made publicly available. The machine learning prediction method is a significant improvement over the generally used consensus patterns. Nuclear export signals (NESs) are extremely important regulators...... this analysis is that the most important properties of NESs are accessibility and flexibility allowing relevant proteins to interact with the signal. Furthermore, we show that not only the known hydrophobic residues are important in defining a nuclear export signals. We employ both neural networks and hidden...

  9. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mohamed El-Tanani

    2016-03-01

    Full Text Available Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1, and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  10. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy.

    Science.gov (United States)

    El-Tanani, Mohamed; Dakir, El-Habib; Raynor, Bethany; Morgan, Richard

    2016-03-14

    Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES) to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1), and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  11. Nuclear export of RNA: Different sizes, shapes and functions.

    Science.gov (United States)

    Williams, Tobias; Ngo, Linh H; Wickramasinghe, Vihandha O

    2017-09-01

    Export of protein-coding and non-coding RNA molecules from the nucleus to the cytoplasm is critical for gene expression. This necessitates the continuous transport of RNA species of different size, shape and function through nuclear pore complexes via export receptors and adaptor proteins. Here, we provide an overview of the major RNA export pathways in humans, highlighting the similarities and differences between each. Its importance is underscored by the growing appreciation that deregulation of RNA export pathways is associated with human diseases like cancer. Copyright © 2017. Published by Elsevier Ltd.

  12. Study on the establishment of effective nuclear export system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byung Koo; So, Dong Sup; Baik, Dae Hyun; Kwack, Eun Ho; Shin, Jang Soo; Yoon, Wan Ki; Park, Wan Soo; Kim, Hyun Tae

    1997-02-01

    To improve Korean nuclear export control system, the modification of the present export license procedure for the nuclear equipment and materials and the classification of control items and their related technologies are required. And it is also necessary to make a database of the original countries who have the right of prior consent. For the efficient export control of LWR items to DPRK, it is desirable to manage the export license scheme of nuclear reactor facility as a total package, and to prepare a control regime for the retransfer of nuclear reactor component such as reactor coolant pump and nuclear fuel whose technologies are not self-reliant. It is especially essential to prepare a systematic procedure for the supply of nuclear equipment and materials to DPRK in order to meet international guidelines of NSG and others through an accord on the nuclear cooperation between Republic of Korea (ROK) and DPRK. The principal elements to be included in the accord are the range of cooperation, the restriction within the peaceful uses, prior consent right in case of retransfer of important nuclear reactor components and of storage, transfer and changes of nuclear fuels, application of safeguards to the supplied Trigger list items, physical protection of nuclear material, requirement of the return of nuclear equipment and materials, and restriction right for the suspension or termination of the agreement. (author). 40 refs., 5 tabs., 8 figs.

  13. Ran-dependent nuclear export mediators: a structural perspective.

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    Güttler, Thomas; Görlich, Dirk

    2011-08-31

    Nuclear export is an essential eukaryotic activity. It proceeds through nuclear pore complexes (NPCs) and is mediated by soluble receptors that shuttle between nucleus and cytoplasm. RanGTPase-dependent export mediators (exportins) constitute the largest class of these carriers and are functionally highly versatile. All of these exportins load their substrates in response to RanGTP binding in the nucleus and traverse NPCs as ternary RanGTP-exportin-cargo complexes to the cytoplasm, where GTP hydrolysis leads to export complex disassembly. The different exportins vary greatly in their substrate range. Recent structural studies of both protein- and RNA-specific exporters have illuminated how exportins bind their cargoes, how Ran triggers cargo loading and how export complexes are disassembled in the cytoplasm. Here, we review the current state of knowledge and highlight emerging principles as well as prevailing questions.

  14. Defense Exportability Features Initiative: A New Paradigm for International Cooperation

    Science.gov (United States)

    2015-02-01

    exportability process. Consequently DEF should en- hance these traditional benefits in two important ways: • By providing advanced capability to allies and...Defense AT&L: January–February 2015 24 Defense Exportability Features Initiative A New Paradigm for International Cooperation Frank D. Kenlon n...Jay Mandelbaum Kenlon is a professor of international acquisition management (intermittent) in the Defense Systems Management College’s International

  15. The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

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    Booth, David S; Cheng, Yifan; Frankel, Alan D

    2014-12-08

    The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

  16. Analysis and prediction of leucine-rich nuclear export signals

    DEFF Research Database (Denmark)

    la Cour, Tanja; Kiemer, Lars; Mølgaard, Anne

    2004-01-01

    We present a thorough analysis of nuclear export signals and a prediction server, which we have made publicly available. The machine learning prediction method is a significant improvement over the generally used consensus patterns. Nuclear export signals (NESs) are extremely important regulators...... of the subcellular location of proteins. This regulation has an impact on transcription and other nuclear processes, which are fundamental to the viability of the cell. NESs are studied in relation to cancer, the cell cycle, cell differentiation and other important aspects of molecular biology. Our conclusion from...... this analysis is that the most important properties of NESs are accessibility and flexibility allowing relevant proteins to interact with the signal. Furthermore, we show that not only the known hydrophobic residues are important in defining a nuclear export signals. We employ both neural networks and hidden...

  17. Nuclear imprisonment: viral strategies to arrest host mRNA nuclear export.

    Science.gov (United States)

    Kuss, Sharon K; Mata, Miguel A; Zhang, Liang; Fontoura, Beatriz M A

    2013-07-01

    Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses.

  18. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Science.gov (United States)

    Kuss, Sharon K.; Mata, Miguel A.; Zhang, Liang; Fontoura, Beatriz M. A.

    2013-01-01

    Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses. PMID:23872491

  19. 77 FR 27113 - Export and Import of Nuclear Equipment and Material; Export of International Atomic Energy Agency...

    Science.gov (United States)

    2012-05-09

    ... / Wednesday, May 9, 2012 / Rules and Regulations#0;#0; ] NUCLEAR REGULATORY COMMISSION 10 CFR Part 110 RIN 3150-AJ04 Export and Import of Nuclear Equipment and Material; Export of International Atomic Energy Agency Safeguards Samples AGENCY: Nuclear Regulatory Commission. ACTION: Final rule. SUMMARY: The U.S...

  20. 10 CFR 110.26 - General license for the export of nuclear reactor components.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false General license for the export of nuclear reactor components. 110.26 Section 110.26 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Licenses § 110.26 General license for the export of nuclear...

  1. Three-Dimensional Mapping of mRNA Export through the Nuclear Pore Complex

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    Steven J. Schnell

    2014-11-01

    Full Text Available The locations of transcription and translation of mRNA in eukaryotic cells are spatially separated by the nuclear envelope (NE. Plenty of nuclear pore complexes (NPCs embedded in the NE function as the major gateway for the export of transcribed mRNAs from the nucleus to the cytoplasm. Whereas the NPC, perhaps one of the largest protein complexes, provides a relatively large channel for macromolecules to selectively pass through it in inherently three-dimensional (3D movements, this channel is nonetheless below the diffraction limit of conventional light microscopy. A full understanding of the mRNA export mechanism urgently requires real-time mapping of the 3D dynamics of mRNA in the NPC of live cells with innovative imaging techniques breaking the diffraction limit of conventional light microscopy. Recently, super-resolution fluorescence microscopy and single-particle tracking (SPT techniques have been applied to the study of nuclear export of mRNA in live cells. In this review, we emphasize the necessity of 3D mapping techniques in the study of mRNA export, briefly summarize the feasibility of current 3D imaging approaches, and highlight the new features of mRNA nuclear export elucidated with a newly developed 3D imaging approach combining SPT-based super-resolution imaging and 2D-to-3D deconvolution algorithms.

  2. p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1.

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    Santiago, Aleixo; Li, Dawei; Zhao, Lisa Y; Godsey, Adam; Liao, Daiqing

    2013-09-01

    Chromosomal region maintenance 1 (CRM1) mediates p53 nuclear export. Although p53 SUMOylation promotes its nuclear export, the underlying mechanism is unclear. Here we show that tethering of a small, ubiquitin-like modifier (SUMO) moiety to p53 markedly increases its cytoplasmic localization. SUMO attachment to p53 does not affect its oligomerization, suggesting that subunit dissociation required for exposing p53's nuclear export signal (NES) is unnecessary for p53 nuclear export. Surprisingly, SUMO-mediated p53 nuclear export depends on the SUMO-interacting motif (SIM)-binding pocket of SUMO-1. The CRM1 C-terminal domain lacking the NES-binding groove interacts with tetrameric p53, and the proper folding of the p53 core domain, rather than the presence of the N- or C-terminal tails, appears to be important for p53-CRM1 interaction. The CRM1 Huntington, EF3, a subunit of PP2A, and TOR1 9 (HEAT9) loop, which regulates GTP-binding nuclear protein Ran binding and cargo release, contains a prototypical SIM. Remarkably, disruption of this SIM in conjunction with a mutated SIM-binding groove of SUMO-1 markedly enhances the binding of CRM1 to p53-SUMO-1 and their accumulation in the nuclear pore complexes (NPCs), as well as their persistent association in the cytoplasm. We propose that SUMOylation of a CRM1 cargo such as p53 at the NPCs unlocks the HEAT9 loop of CRM1 to facilitate the disassembly of the transporting complex and cargo release to the cytoplasm.

  3. Exportin-5 mediates nuclear export of SRP RNA in vertebrates.

    Science.gov (United States)

    Takeiwa, Toshihiko; Taniguchi, Ichiro; Ohno, Mutsuhito

    2015-04-01

    The signal recognition particle is a ribonucleoprotein complex that is essential for the translocation of nascent proteins into the endoplasmic reticulum. It has been shown that the RNA component (SRP RNA) is exported from the nucleus by CRM1 in the budding yeast. However, how SRP RNA is exported in higher species has been elusive. Here, we show that SRP RNA does not use the CRM1 pathway in Xenopus oocytes. Instead, SRP RNA uses the same export pathway as pre-miRNA and tRNA as showed by cross-competition experiments. Consistently, the recombinant Exportin-5 protein specifically stimulated export of SRP RNA as well as of pre-miRNA and tRNA, whereas an antibody raised against Exportin-5 specifically inhibited export of the same RNA species. Moreover, biotinylated SRP RNA can pull down Exportin-5 but not CRM1 from HeLa cell nuclear extracts in a RanGTP-dependent manner. These results, taken together, strongly suggest that the principal export receptor for SRP RNA in vertebrates is Exportin-5 unlike in the budding yeast.

  4. Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen.

    Science.gov (United States)

    Huang, Cheng; Jiang, Jia-Yin; Chang, Shin C; Tsay, Yeou-Guang; Chen, Mei-Ru; Chang, Ming-Fu

    2013-02-01

    Nuclear export is an important process that not only regulates the functions of cellular factors but also facilitates the assembly of viral nucleoprotein complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of proteins bearing the classical leucine-rich nuclear export signal (NES) is the best-characterized nuclear export receptor. Recently, several CRM1-independent nuclear export pathways were also identified. The nuclear export of the large form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis delta virus (HDV), which contains a CRM1-independent proline-rich NES, is mediated by the host NES-interacting protein (NESI). The mechanism of the NESI protein in mediating nuclear export is still unknown. In this study, NESI was characterized as a highly glycosylated membrane protein. It interacted and colocalized well in the nuclear envelope with lamin A/C and nucleoporins. Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI was detected for the wild-type protein but not for the nuclear export-defective HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These data indicate that by forming complexes with lamin A/C and nucleoporins, NESI facilitates the CRM1-independent nuclear export of HDAg-L.

  5. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Directory of Open Access Journals (Sweden)

    Beatriz M. A. Fontoura

    2013-07-01

    Full Text Available Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses.

  6. 37 CFR 5.20 - Export of technical data relating to sensitive nuclear technology.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Export of technical data... LICENSES TO EXPORT AND FILE APPLICATIONS IN FOREIGN COUNTRIES Licenses for Foreign Exporting and Filing § 5.20 Export of technical data relating to sensitive nuclear technology. Under regulations (10 CFR...

  7. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona, E-mail: moroianu@bc.edu

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.

  8. HIV-1 and M-PMV RNA Nuclear Export Elements Program Viral Genomes for Distinct Cytoplasmic Trafficking Behaviors.

    Science.gov (United States)

    Pocock, Ginger M; Becker, Jordan T; Swanson, Chad M; Ahlquist, Paul; Sherer, Nathan M

    2016-04-01

    Retroviruses encode cis-acting RNA nuclear export elements that override nuclear retention of intron-containing viral mRNAs including the full-length, unspliced genomic RNAs (gRNAs) packaged into assembling virions. The HIV-1 Rev-response element (RRE) recruits the cellular nuclear export receptor CRM1 (also known as exportin-1/XPO1) using the viral protein Rev, while simple retroviruses encode constitutive transport elements (CTEs) that directly recruit components of the NXF1(Tap)/NXT1(p15) mRNA nuclear export machinery. How gRNA nuclear export is linked to trafficking machineries in the cytoplasm upstream of virus particle assembly is unknown. Here we used long-term (>24 h), multicolor live cell imaging to directly visualize HIV-1 gRNA nuclear export, translation, cytoplasmic trafficking, and virus particle production in single cells. We show that the HIV-1 RRE regulates unique, en masse, Rev- and CRM1-dependent "burst-like" transitions of mRNAs from the nucleus to flood the cytoplasm in a non-localized fashion. By contrast, the CTE derived from Mason-Pfizer monkey virus (M-PMV) links gRNAs to microtubules in the cytoplasm, driving them to cluster markedly to the centrosome that forms the pericentriolar core of the microtubule-organizing center (MTOC). Adding each export element to selected heterologous mRNAs was sufficient to confer each distinct export behavior, as was directing Rev/CRM1 or NXF1/NXT1 transport modules to mRNAs using a site-specific RNA tethering strategy. Moreover, multiple CTEs per transcript enhanced MTOC targeting, suggesting that a cooperative mechanism links NXF1/NXT1 to microtubules. Combined, these results reveal striking, unexpected features of retroviral gRNA nucleocytoplasmic transport and demonstrate roles for mRNA export elements that extend beyond nuclear pores to impact gRNA distribution in the cytoplasm.

  9. Adducin family proteins possess different nuclear export potentials.

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    Liu, Chia-Mei; Hsu, Wen-Hsin; Lin, Wan-Yi; Chen, Hong-Chen

    2017-05-10

    The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are actin-binding proteins that play important roles in the stabilization of membrane cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly conserved bipartite nuclear localization signal (NLS) at the carboxyl termini, but only ADD1 can localize to the nucleus. The reason for this discrepancy is not clear. To avoid the potential effect of cell-cell junctions on the distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were transiently expressed in NIH3T3 fibroblasts and their distribution in the cytoplasm and nucleus was examined by immunofluorescence staining. Several nuclear proteins were identified to interact with ADD1 by mass spectrometry, which were further verified by co-immunoprecipitation. In this study, we found that ADD1 was detectable both in the cytoplasm and nucleus, whereas ADD2 and ADD3 were detected only in the cytoplasm. However, ADD2 and ADD3 were partially (~40%) sequestered in the nucleus by leptomycin B, a CRM1/exportin1 inhibitor. Upon the removal of leptomycin B, ADD2 and ADD3 re-distributed to the cytoplasm. These results indicate that ADD2 and ADD3 possess functional NLS and are quickly transported to the cytoplasm upon entering the nucleus. Indeed, we found that ADD2 and ADD3 possess much higher potential to counteract the activity of the NLS derived from Simian virus 40 large T-antigen than ADD1. All the ADD proteins appear to contain multiple nuclear export signals mainly in their head and neck domains. However, except for the leucine-rich motif ((377)FEALMRMLDWLGYRT(391)) in the neck domain of ADD1, no other classic nuclear export signal was identified in the ADD proteins. In addition, the nuclear retention of ADD1 facilitates its interaction with RNA polymerase II and zinc-finger protein 331. Our results suggest that ADD2 and ADD3 possess functional NLS and shuttle between the cytoplasm and nucleus. The discrepancy in the

  10. 5-Flurouracil disrupts nuclear export and nuclear pore permeability in a calcium dependent manner.

    Science.gov (United States)

    Higby, Kelly J; Bischak, Melissa M; Campbell, Christina A; Anderson, Rebecca G; Broskin, Sarah A; Foltz, Lauren E; Koper, Jarrett A; Nickle, Audrey C; Resendes, Karen K

    2017-03-01

    Regulation of nuclear transport is an essential component of apoptosis. As chemotherapy induced cell death progresses, nuclear transport and the nuclear pore complex (NPC) are slowly disrupted and dismantled. 5-Fluorouracil (5-FU) and the camptothecin derivatives irinotecan and topotecan, are linked to altered nuclear transport of specific proteins; however, their general effects on the NPC and transport during apoptosis have not been characterized. We demonstrate that 5-FU, but not topotecan, increases NPC permeability, and disrupts Ran-mediated nuclear transport before the disruption of the NPC. This increased permeability is dependent on increased cellular calcium, as the Ca(2+) chelator BAPTA-AM, abolishes the effect. Furthermore, increased calcium alone was sufficient to disrupt the Ran gradient. Combination treatments of 5-FU with topotecan or irinotecan, similarly disrupted nuclear transport before disassembly of the NPC. In both single and combination treatments nuclear transport was disrupted before caspase 9 activation, indicating that 5-FU induces an early caspase-independent increase in NPC permeability and alteration of nuclear transport. Because Crm1-mediated nuclear export of tumor suppressors is linked to drug resistance we also examined the effect of 5-FU on the nuclear export of a specific target, topoisomerase. 5-FU treatment led to accumulation of topoisomerase in the nucleus and recovered the loss nuclear topoisomerase induced by irinotecan or topotecan, a known cause of drug resistance. Furthermore, 5-FU retains its ability to cause nuclear accumulation of p53 in the presence of irinotecan or topotecan. Our results reveal a new mechanism of action for these therapeutics during apoptosis, opening the door to other potential combination chemotherapies that employ 5-FU as a calcium mediated inhibitor of Crm1-induced nuclear export of tumor suppressors.

  11. A second CRM1-dependent nuclear export signal in the influenza A virus NS2 protein contributes to the nuclear export of viral ribonucleoproteins.

    Science.gov (United States)

    Huang, Shengping; Chen, Jingjing; Chen, Quanjiao; Wang, Huadong; Yao, Yanfeng; Chen, Jianjun; Chen, Ze

    2013-01-01

    Influenza A virus NS2 protein, also called nuclear export protein (NEP), is crucial for the nuclear export of viral ribonucleoproteins. However, the molecular mechanisms of NEP mediation in this process remain incompletely understood. A leucine-rich nuclear export signal (NES2) in NEP, located at the predicted N2 helix of the N-terminal domain, was identified in the present study. NES2 was demonstrated to be a transferable NES, with its nuclear export activity depending on the nuclear export receptor chromosome region maintenance 1 (CRM1)-mediated pathway. The interaction between NEP and CRM1 is coordinately regulated by both the previously reported NES (NES1) and now the new NES2. Deletion of the NES1 enhances the interaction between NEP and CRM1, and deletion of the NES1 and NES2 motifs completely abolishes this interaction. Moreover, NES2 interacts with CRM1 in the mammalian two-hybrid system. Mutant viruses containing NES2 alterations generated by reversed genetics exhibit reduced viral growth and delay in the nuclear export of viral ribonucleoproteins (vRNPs). The NES2 motif is highly conserved in the influenza A and B viruses. The results demonstrate that leucine-rich NES2 is involved in the nuclear export of vRNPs and contributes to the understanding of nucleocytoplasmic transport of influenza virus vRNPs.

  12. Mechanistic Insights from Structural Analyses of Ran-GTPase-Driven Nuclear Export of Proteins and RNAs.

    Science.gov (United States)

    Matsuura, Yoshiyuki

    2016-05-22

    Understanding how macromolecules are rapidly exchanged between the nucleus and the cytoplasm through nuclear pore complexes is a fundamental problem in biology. Exportins are Ran-GTPase-dependent nuclear transport factors that belong to the karyopherin-β family and mediate nuclear export of a plethora of proteins and RNAs, except for bulk mRNA nuclear export. Exportins bind cargo macromolecules in a Ran-GTP-dependent manner in the nucleus, forming exportin-cargo-Ran-GTP complexes (nuclear export complexes). Transient weak interactions between exportins and nucleoporins containing characteristic FG (phenylalanine-glycine) repeat motifs facilitate nuclear pore complex passage of nuclear export complexes. In the cytoplasm, nuclear export complexes are disassembled, thereby releasing the cargo. GTP hydrolysis by Ran promoted in the cytoplasm makes the disassembly reaction virtually irreversible and provides thermodynamic driving force for the overall export reaction. In the past decade, X-ray crystallography of some of the exportins in various functional states coupled with functional analyses, single-particle electron microscopy, molecular dynamics simulations, and small-angle solution X-ray scattering has provided rich insights into the mechanism of cargo binding and release and also begins to elucidate how exportins interact with the FG repeat motifs. The knowledge gained from structural analyses of nuclear export is being translated into development of clinically useful inhibitors of nuclear export to treat human diseases such as cancer and influenza.

  13. Assessing mRNA nuclear export in mammalian cells by microinjection.

    Science.gov (United States)

    Lee, Eliza S; Palazzo, Alexander F

    2017-08-15

    The nuclear export of mRNAs is an important yet little understood part of eukaryotic gene expression. One of the easiest methods for monitoring mRNA export in mammalian tissue culture cells is through the microinjection of DNA plasmids into the nucleus and monitoring the distribution of the transcribed product over time. Here we describe how to setup a microscope equipped with a micromanipulator used in cell microinjections, and we explain how to perform a nuclear mRNA export assay and obtain the nuclear export rate for any given mRNA. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Analysis of World Nuclear Market and Strategy of Korean NPP's Competitiveness Improvement for Exportation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae Young; Jeong, Yong Hoon [KAIST, Daejeon (Korea, Republic of); Roh, Seungkook [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Chang, Soon Heung [Handong Global University, Pohang (Korea, Republic of)

    2016-10-15

    China, India and USA (nuclear adopted countries) are planning tremendous number of NPPs to meet their increasing electricity demand and Saudi Arabia, Vietnam (nuclear adopting countries) are also planning to include nuclear power in their energy mix as a long-term plan. Korea has exported 4 units of APR1400 to the UAE in December, 2009. Korea became sixth NPP supplier country and our economic feasibility and safety features were started to evaluate worldwide. Nuclear industries became a new driver of Korea’s export and nuclear industries in Korea are now expecting another NPP export to Middle-eastern countries, including UAE and Saudi Arabia, based on the first-mover’s advantage at the UAE. In 2000s, five countries (Japan, USA, France, Russia and Korea), which are able to build NPP, focused on NPP export more than domestic construction. Global trend of world nuclear market changed rapidly, especially after NPP export to the UAE. By the global trend, hegemony of nuclear market migrated from supplier country to buyer country. Nuclear companies started cooperating rather than competing. Financing to developing countries become more important. In general, one of the considerable combinations is Korea-Japan-USA alliance. Korea is in charge of EPC, Japan supports financing and deficient technology (with USA partner), and Japan-USA handles fuel supply and back-end fuel cycle based on new agreed terms of ROK-US Nuclear Cooperation Agreement. This combination was judged to best way to collaborate with global companies. Paying attention to many delayed (or potentially delayed) constructions from Russia, intercepting the construction work will be available in case of contracted countries. Korea can emphasize the short construction time, high responsiveness and mild/equal diplomatic position to the target countries.

  15. Therapeutic Targeting of Nuclear Export Inhibition in Lung Cancer.

    Science.gov (United States)

    Gupta, Arjun; Saltarski, Jessica M; White, Michael A; Scaglioni, Pier P; Gerber, David E

    2017-09-01

    Intracellular compartmentalization and trafficking of molecules plays a critical role in complex and essential cellular processes. In lung cancer and other malignancies, aberrant nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators results in tumorigenesis and inactivation of apoptosis. Pharmacologic agents targeting this process, termed selective inhibitors of nuclear export (SINE), have demonstrated antitumor efficacy in preclinical models and human clinical trials. Exportin-1 (XPO1), which serves as the sole exporter of several tumor suppressor proteins and cell cycle regulators, including retinoblastoma, adenomatous polyposis coli, p53, p73, p21, p27, forkhead box O, signal transducer and activator of transcription 3, inhibitor of κB, topoisomerase II, and protease activated receptor 4-is the principal focus of development of SINE. The most extensively studied of the SINE to date, the exportin-1 inhibitor selinexor (KPT-330 [Karyopharm Therapeutics, Inc., Newton Centre, MA]), has demonstrated single-agent anticancer activity and synergistic effects in combination regimens against multiple cancer types, with principal toxicities of low-grade cytopenias and gastrointestinal effects. SINE may have particular relevance in KRAS-driven tumors, for which this treatment strategy demonstrates significant synthetic lethality. A multicenter phase 1/2 clinical trial of selinexor in previously treated advanced KRAS-mutant NSCLC is under way. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  16. A high-throughput screening system targeting the nuclear export pathway via the third nuclear export signal of influenza A virus nucleoprotein.

    Science.gov (United States)

    Kakisaka, Michinori; Mano, Takafumi; Aida, Yoko

    2016-06-02

    Two classes of antiviral drugs, M2 channel inhibitors and neuraminidase (NA) inhibitors, are currently approved for the treatment of influenza; however, the development of resistance against these agents limits their efficacy. Therefore, the identification of new targets and the development of new antiviral drugs against influenza are urgently needed. The third nuclear export signal (NES3) of nucleoprotein (NP) is the most important for viral replication among seven NESs encoded by four viral proteins, NP, M1, NS1, and NS2. NP-NES3 is critical for the nuclear export of NP, and targeting NP-NES3 is therefore a promising strategy that may lead to the development of antiviral drugs. However, a high-throughput screening (HTS) system to identify inhibitors of NP nuclear export has not been established. Here, we developed a novel HTS system to evaluate the inhibitory effects of compounds on the nuclear export pathway mediated by NP-NES3 using a MDCK cell line stably expressing NP-NES3 fused to a green fluorescent protein from aequorea coerulescens (AcGFP-NP-NES3) and a cell imaging analyzer. This HTS system was used to screen a 9600-compound library, leading to the identification of several hit compounds with inhibitory activity against the nuclear export of AcGFP-NP-NES3. The present HTS system provides a useful strategy for the identification of inhibitors targeting the nuclear export of NP via its NES3 sequence.

  17. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.

    Science.gov (United States)

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

    2017-07-01

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. A study on establishing export system of nuclear related equipments to the IAEA

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ki Dong; Lee, Man Ki; Moon, Ki Hwan; Kim, Seung Soo; Lim, Chae Young; Kim, Hwa Sup; Min, Tae Sik [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2002-04-01

    In spite of the advanced status in the international nuclear society, exports of domestic nuclear industries to procurement market of the international organizations has been negligible. This study briefly explained the role and the structure of the IAEA. Then, this study surveyed the size of procurement market, major procurement items, and procurement process. This study also gave an export example to the IAEA from Korea Atomic Energy Research Institute for the ease of understanding the procurement process. Based on these surveys and analysis, this study established the goal and strategy for exports of nuclear equipments to the IAEA. Besides, this study surveyed domestic nuclear industries that have potential to export their products to the IAEA. Then, Korea Atomic Energy Research Institute, by a cooperation with Korea Atomic Industrial Forum Inc., held workshop on 'export of nuclear equipments to IAEA' in May 2001 for them. 4 refs., 1 fig., 10 tabs. (Author)

  19. Murine Leukemia Virus Uses TREX Components for Efficient Nuclear Export of Unspliced Viral Transcripts

    Directory of Open Access Journals (Sweden)

    Toshie Sakuma

    2014-03-01

    Full Text Available Previously we reported that nuclear export of both unspliced and spliced murine leukemia virus (MLV transcripts depends on the nuclear export factor (NXF1 pathway. Although the mRNA export complex TREX, which contains Aly/REF, UAP56, and the THO complex, is involved in the NXF1-mediated nuclear export of cellular mRNAs, its contribution to the export of MLV mRNA transcripts remains poorly understood. Here, we studied the involvement of TREX components in the export of MLV transcripts. Depletion of UAP56, but not Aly/REF, reduced the level of both unspliced and spliced viral transcripts in the cytoplasm. Interestingly, depletion of THO components, including THOC5 and THOC7, affected only unspliced viral transcripts in the cytoplasm. Moreover, the RNA immunoprecipitation assay showed that only the unspliced viral transcript interacted with THOC5. These results imply that MLV requires UAP56, THOC5 and THOC7, in addition to NXF1, for nuclear export of viral transcripts. Given that naturally intronless mRNAs, but not bulk mRNAs, require THOC5 for nuclear export, it is plausible that THOC5 plays a key role in the export of unspliced MLV transcripts.

  20. NESbase version 1.0: a database of nuclear export signals

    DEFF Research Database (Denmark)

    la Cour, T.; Gupta, Ramneek; Rapacki, Krzysztof

    2003-01-01

    Protein export from the nucleus is often mediated by a Leucine-rich Nuclear Export Signal (NES). NESbase is a database of experimentally validated Leucine-rich NESs curated from literature. These signals are not annotated in databases such as SWISS-PROT, PIR or PROSITE. Each NESbase entry contains...... information of whether NES was shown to be necessary and/or sufficient for export, and whether the export was shown to be mediated by the export receptor CRM1. The compiled information was used to make a sequence logo of the Leucine-rich NESs, displaying the conservation of amino acids within a window of 25...

  1. 77 FR 51581 - Request for a License To Export Nuclear Grade Graphite

    Science.gov (United States)

    2012-08-24

    ... COMMISSION Request for a License To Export Nuclear Grade Graphite Pursuant to 10 CFR 110.70 (b) ``Public...,000.0 kilograms Nuclear grade China. June 26, 2012, June 27, 2012, graphite for of nuclear grade graphite to the XMAT424, 11006032. nuclear end use. graphite. Shanghai Institute of Applied Physics in...

  2. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway.

    Science.gov (United States)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP-8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76IRTFQELLF84, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Korea nuclear exports: Why did the Koreans win the UAE tender? Will Korea achieve its goal of exporting 80 nuclear reactors by 2030?

    Energy Technology Data Exchange (ETDEWEB)

    Berthelemy, Michel; Leveque, Francois

    2011-04-12

    The success of Korea in winning, in December 2009, a USD 18.6 billion nuclear tender in the United Arab Emirates (UAE) has led to a growing interest in the organization and strengths of the Korean nuclear industry. In this paper, we present the main economic and political factors that explain the success of the Korean consortium. In particular, thanks to an active national program of Nuclear Power Plant (NPP) construction, Korea has developed distinct competitive advantages in terms of low cost, high credibility and high performance. At the same time, due to the important barriers to enter into the nuclear export market in the UAE, Korea has had to sacrifice its profit margin and has benefited from a strong political support from its government through export financing. More importantly, Korea's success is also due to its alliance with Westinghouse and the support of the US diplomacy. Subsequently, we show that while Korea has recently experienced setbacks in nuclear tenders, it will most certainly try to win in the short run a second nuclear tender with another aggressive price. In the longer run, Korea could take a growing share of the international market for NPPs. However, the extent to which Korea can achieve its long term export target will depend upon its capacity to finance nuclear export through export credits and upon the development of its alliance with Westinghouse. It is important to note that this paper was written before the Fukushima nuclear disaster. The scale of the human and environmental consequences of this accident are still unknown, and will undoubtedly have short and long term consequences on nuclear safety requirements and public attitude toward nuclear energy, which will most certainly impact the outlooks for nuclear new-builds. (authors)

  4. A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export.

    Science.gov (United States)

    Gong, Danyang; Kim, Yong Hoon; Xiao, Yuchen; Du, Yushen; Xie, Yafang; Lee, Kevin K; Feng, Jun; Farhat, Nisar; Zhao, Dawei; Shu, Sara; Dai, Xinghong; Chanda, Sumit K; Rana, Tariq M; Krogan, Nevan J; Sun, Ren; Wu, Ting-Ting

    2016-11-09

    Nuclear mRNA export is highly regulated to ensure accurate cellular gene expression. Viral inhibition of cellular mRNA export can enhance viral access to the cellular translation machinery and prevent anti-viral protein production but is generally thought to be nonselective. We report that ORF10 of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. Nuclear export inhibition by ORF10 requires an interaction with an RNA export factor, Rae1. Genome-wide analysis reveals a subset of cellular mRNAs whose nuclear export is blocked by ORF10 with the 3' UTRs of ORF10-targeted transcripts conferring sensitivity to export inhibition. The ORF10-Rae1 interaction is important for the virus to express viral genes and produce infectious virions. These results suggest that a nuclear DNA virus can selectively interfere with RNA export to restrict host gene expression for optimal replication. Published by Elsevier Inc.

  5. A subset of FG-nucleoporins is necessary for efficient Msn5-mediated nuclear protein export

    Science.gov (United States)

    Finn, Erin M.; DeRoo, Elise P.; Clement, George W.; Rao, Sheila; Kruse, Sarah E.; Kokanovich, Kate M.; Belanger, Kenneth D.

    2013-01-01

    The transport of proteins between the cytoplasm and nucleus requires interactions between soluble transport receptors (karyopherins) and phenylalanine-glycine (FG) repeat domains on nuclear pore complex proteins (nucleoporins). However, the role of specific FG repeat-containing nucleoporins in nuclear protein export has not been carefully investigated. We have developed a novel kinetic assay to investigate the relative export kinetics mediated by the karyopherin Msn5/Kap142 in yeast containing specific FG-Nup mutations. Using the Msn5 substrate Crz1 as a marker for Msn5-mediated protein export, we observe that deletions of NUP100 or NUP2 result in decreased rates of Crz1 export, while nup60Δ and nup42Δ mutants do not vary significantly from wild type. The decreased Msn5 export rate in nup100Δ was confirmed using Mig1-GFP as a transport substrate. A nup100ΔGLFG mutant shows defects in nuclear export kinetics similar to a nup100Δ deletion. Removal of FG-repeats from Nsp1 also decreases export kinetics, while a loss of Nup1 FXFGs does not. To confirm that our export data reflected functional differences in protein localization, we performed Crz1 transcription activation assays using a CDRE::LacZ reporter gene that is upregulated upon increased transcription activation by Crz1 in vivo. We observe that expression from this reporter increases in nup100ΔGLFG and nsp1ΔFGΔFXFG strains that exhibit decreased Crz1 export kinetics but resembles wild-type levels in nup1ΔFXFG strains that do not exhibit export defects. These data provide evidence that the export of Msn5 is likely mediated by a specific subset of FG-Nups and that the GLFG repeat domain of Nup100 is important for Msn5-mediated nuclear protein export. PMID:23295456

  6. A subset of FG-nucleoporins is necessary for efficient Msn5-mediated nuclear protein export.

    Science.gov (United States)

    Finn, Erin M; DeRoo, Elise P; Clement, George W; Rao, Sheila; Kruse, Sarah E; Kokanovich, Kate M; Belanger, Kenneth D

    2013-05-01

    The transport of proteins between the cytoplasm and nucleus requires interactions between soluble transport receptors (karyopherins) and phenylalanine-glycine (FG) repeat domains on nuclear pore complex proteins (nucleoporins). However, the role of specific FG repeat-containing nucleoporins in nuclear protein export has not been carefully investigated. We have developed a novel kinetic assay to investigate the relative export kinetics mediated by the karyopherin Msn5/Kap142 in yeast containing specific FG-Nup mutations. Using the Msn5 substrate Crz1 as a marker for Msn5-mediated protein export, we observe that deletions of NUP100 or NUP2 result in decreased rates of Crz1 export, while nup60Δ and nup42Δ mutants do not vary significantly from wild type. The decreased Msn5 export rate in nup100Δ was confirmed using Mig1-GFP as a transport substrate. A nup100ΔGLFG mutant shows defects in nuclear export kinetics similar to a nup100Δ deletion. Removal of FG-repeats from Nsp1 also decreases export kinetics, while a loss of Nup1 FXFGs does not. To confirm that our export data reflected functional differences in protein localization, we performed Crz1 transcription activation assays using a CDRE::LacZ reporter gene that is upregulated upon increased transcription activation by Crz1 in vivo. We observe that expression from this reporter increases in nup100ΔGLFG and nsp1ΔFGΔFXFG strains that exhibit decreased Crz1 export kinetics but resembles wild-type levels in nup1ΔFXFG strains that do not exhibit export defects. These data provide evidence that the export of Msn5 is likely mediated by a specific subset of FG-Nups and that the GLFG repeat domain of Nup100 is important for Msn5-mediated nuclear protein export.

  7. Development of Export Control Comprehensive Management Model for Nuclear Power Plants and Others Projects

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chansuh; Seo, Hana; Choi, Sundo [Korea Institute of Nuclear Nonproliferation And Control, Daejeon (Korea, Republic of)

    2014-05-15

    It is required that there are lots of managements of care and concern if the project contains strategic items such as NPPs. The Korean nuclear industry and its related companies, such as the Korea Hydro and Nuclear Power (KHNP), are promoting greater exports of NPPs. It is likely that Korea will export more this technology to newcomer states in the future. As a result, the ROK has been improving its export control management system for NPPs. In keeping with this national effort, Korea Institute of Nuclear Nonproliferation And Control (KINAC) developed comprehensive export control management model for NPPs and other projects, in preparation for this projected growth in the industry. This model also applies to the nuclear export case of the UAE, aims to manage the project from bidding to the end of the contract. The recent Export Licensing of Nuclear Facility Technology was reflected in the Notice on Export and Import of Strategic Items in January 2014. Through this license, the large-scale project legislation framework was established. It can also minimize nonproliferation concerns of the international community through strict management. It is expected that the Korea will be able to enhance transparency and secure the nuclear use, while meeting nonproliferation purpose.

  8. The signal sequence coding region promotes nuclear export of mRNA.

    Science.gov (United States)

    Palazzo, Alexander F; Springer, Michael; Shibata, Yoko; Lee, Chung-Sheng; Dias, Anusha P; Rapoport, Tom A

    2007-12-01

    In eukaryotic cells, most mRNAs are exported from the nucleus by the transcription export (TREX) complex, which is loaded onto mRNAs after their splicing and capping. We have studied in mammalian cells the nuclear export of mRNAs that code for secretory proteins, which are targeted to the endoplasmic reticulum membrane by hydrophobic signal sequences. The mRNAs were injected into the nucleus or synthesized from injected or transfected DNA, and their export was followed by fluorescent in situ hybridization. We made the surprising observation that the signal sequence coding region (SSCR) can serve as a nuclear export signal of an mRNA that lacks an intron or functional cap. Even the export of an intron-containing natural mRNA was enhanced by its SSCR. Like conventional export, the SSCR-dependent pathway required the factor TAP, but depletion of the TREX components had only moderate effects. The SSCR export signal appears to be characterized in vertebrates by a low content of adenines, as demonstrated by genome-wide sequence analysis and by the inhibitory effect of silent adenine mutations in SSCRs. The discovery of an SSCR-mediated pathway explains the previously noted amino acid bias in signal sequences and suggests a link between nuclear export and membrane targeting of mRNAs.

  9. 10 CFR 110.21 - General license for the export of special nuclear material.

    Science.gov (United States)

    2010-01-01

    ... per year to any one country. (2) Special nuclear material in fuel elements as replacements for damaged or defective unirradiated fuel elements previously exported under a specific license, subject to the same terms as the original export license and the condition that the replaced fuel elements must...

  10. 77 FR 39521 - Application for a License To Export Nuclear Reactor Major Components and Equipment

    Science.gov (United States)

    2012-07-03

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Application for a License To Export Nuclear Reactor Major Components and Equipment Pursuant to 10... Reactor internals, Components and For use in Braka nuclear power Company LLC reactor coolant equipment...

  11. 10 CFR 110.8 - List of nuclear facilities and equipment under NRC export licensing authority.

    Science.gov (United States)

    2010-01-01

    ... under NRC export licensing authority. (a) Nuclear reactors and especially designed or prepared equipment and components for nuclear reactors. (See Appendix A to this part.) (b) Plants for the separation of... plants. (See Appendix N to this part.) (d) Plants for the reprocessing of irradiated nuclear reactor...

  12. Study on international publicity and export strategy establishment of nuclear technology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Bok; Choi, C.O.; Park, K. B.; Chang, M. H.; Kim, K. K.; Yang, M. S.; Jung, I. H.; Kim, K. P.; Wu, J. S.; Jang, C. I.; Han, B. O.; Sim, J. H.; Chung, M.; Chung, J.K

    1999-05-01

    The objective of this study is to devise a proper measure for international publicity and technology export strategy. Analysed and summaries in detail are other countries nuclear policy trend and the current technology development status of Korea Standard Nuclear Plant that we developed on our own technology, design and construction technology for research reactor, System-integrated Modular Advanced Reactor of which design is in progress, Direct use of Spent PWR Fuel in CANDU Reactors, and Radioisotopes. Based on that, the measures are proposed for the export industrialization of nuclear technology and establishment of the export basis. Also the international nuclear cooperation and publicity strategy are suggested to support the technology export basis. By surveying the world nuclear status, the direction for the international cooperation and publicity is settled and the specific publicity strategy is proposed for the cooperation with IAEA and multi-countries and the establishment of the nuclear technology export basis. As part of this project, the panel on major technologies such as Korea Standard Nuclear Plant, HANARO, and System-integrated Modular Advanced Reactor was displayed successfully at the IAEA meeting, which contribute much to the publicity of our nuclear technology to the international nuclear society. (author)

  13. Dynamical features of nuclear fission

    Indian Academy of Sciences (India)

    Santanu Pal

    2015-08-01

    It is now established that the transition-state theory of nuclear fission due to Bohr and Wheeler underestimates several observables in heavy-ion-induced fusion–fission reactions. Dissipative dynamical models employing either the Langevin equation or equivalently the Fokker–Planck equation have been developed for fission of heavy nuclei at high excitations (T ∼1 MeV or higher). Here, we first present the physical picture underlying the dissipative fission dynamics. We mainly concentrate upon the Kramers’ prescription for including dissipation in fission dynamics. We discuss, in some detail, the results of a statistical model analysis of the pre-scission neutron multiplicity data from the reactions 19F+194,196,198Pt using Kramers’ fission width. We also discuss the multi-dimensional Langevin equation in the context of kinetic energy and mass distribution of the fission fragments.

  14. p54nrb/NonO and PSF promote U snRNA nuclear export by accelerating its export complex assembly.

    Science.gov (United States)

    Izumi, Hiroto; McCloskey, Asako; Shinmyozu, Kaori; Ohno, Mutsuhito

    2014-04-01

    The assembly of spliceosomal U snRNPs in metazoans requires nuclear export of U snRNA precursors. Four factors, nuclear cap-binding complex (CBC), phosphorylated adaptor for RNA export (PHAX), the export receptor CRM1 and RanGTP, gather at the m(7)G-cap-proximal region and form the U snRNA export complex. Here we show that the multifunctional RNA-binding proteins p54nrb/NonO and PSF are U snRNA export stimulatory factors. These proteins, likely as a heterodimer, accelerate the recruitment of PHAX, and subsequently CRM1 and Ran onto the RNA substrates in vitro, which mediates efficient U snRNA export in vivo. Our results reveal a new layer of regulation for U snRNA export and, hence, spliceosomal U snRNP biogenesis.

  15. Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer strategy.

    Science.gov (United States)

    Tan, David S P; Bedard, Philippe L; Kuruvilla, John; Siu, Lillian L; Razak, Albiruni R Abdul

    2014-05-01

    In cancer cells, the nuclear-cytoplasmic transport machinery is frequently disrupted, resulting in mislocalization and loss of function for many key regulatory proteins. In this review, the mechanisms by which tumor cells co-opt the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug resistance, and tumor progression will be elucidated, with a particular focus on the role of the nuclear-cytoplasmic export protein. The recent development of a new generation of selective inhibitors of nuclear export (XPO1 antagonists) and how these novel anticancer drugs may bring us closer to the implementation of this therapeutic strategy in the clinic will be discussed.

  16. Influenza polymerase encoding mRNAs utilize atypical mRNA nuclear export.

    Science.gov (United States)

    Larsen, Sean; Bui, Steven; Perez, Veronica; Mohammad, Adeba; Medina-Ramirez, Hilario; Newcomb, Laura L

    2014-08-28

    Influenza is a segmented negative strand RNA virus. Each RNA segment is encapsulated by influenza nucleoprotein and bound by the viral RNA dependent RNA polymerase (RdRP) to form viral ribonucleoproteins responsible for RNA synthesis in the nucleus of the host cell. Influenza transcription results in spliced mRNAs (M2 and NS2), intron-containing mRNAs (M1 and NS1), and intron-less mRNAs (HA, NA, NP, PB1, PB2, and PA), all of which undergo nuclear export into the cytoplasm for translation. Most cellular mRNA nuclear export is Nxf1-mediated, while select mRNAs utilize Crm1. Here we inhibited Nxf1 and Crm1 nuclear export prior to infection with influenza A/Udorn/307/1972(H3N2) virus and analyzed influenza intron-less mRNAs using cellular fractionation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We examined direct interaction between Nxf1 and influenza intron-less mRNAs using immuno purification of Nxf1 and RT-PCR of associated RNA. Inhibition of Nxf1 resulted in less influenza intron-less mRNA export into the cytoplasm for HA and NA influenza mRNAs in both human embryonic kidney cell line (293 T) and human lung adenocarcinoma epithelial cell line (A549). However, in 293 T cells no change was observed for mRNAs encoding the components of the viral ribonucleoproteins; NP, PA, PB1, and PB2, while in A549 cells, only PA, PB1, and PB2 mRNAs, encoding the RdRP, remained unaffected; NP mRNA was reduced in the cytoplasm. In A549 cells NP, NA, HA, mRNAs were found associated with Nxf1 but PA, PB1, and PB2 mRNAs were not. Crm1 inhibition also resulted in no significant difference in PA, PB1, and PB2 mRNA nuclear export. These results further confirm Nxf1-mediated nuclear export is functional during the influenza life cycle and hijacked for select influenza mRNA nuclear export. We reveal a cell type difference for Nxf1-mediated nuclear export of influenza NP mRNA, a reminder that cell type can influence molecular mechanisms. Importantly, we

  17. High-content screening of natural products reveals novel nuclear export inhibitors.

    Science.gov (United States)

    Cautain, Bastien; de Pedro, Nuria; Murillo Garzón, Virginia; Muñoz de Escalona, María; González Menéndez, Victor; Tormo, José R; Martin, Jesús; El Aouad, Noureddine; Reyes, Fernando; Asensio, Francisco; Genilloud, Olga; Vicente, Francisca; Link, Wolfgang

    2014-01-01

    Natural products are considered an extremely valuable source for the discovery of new drugs against diverse pathologies. As yet, we have only explored a fraction of the diversity of bioactive compounds, and opportunities for discovering new natural products leading to new drugs are huge. In the present study, U2nesRELOC, a previously established cell-based imaging assay, was employed to screen a collection of extracts of microbial origin for nuclear export inhibition activity. The fluorescent signal of untreated U2nesRELOC cells localizes predominantly to the cytoplasm. Upon treatment with the nuclear export inhibitor leptomycin B, the fluorescent-tagged reporter proteins appear as speckles in the nucleus. A proprietary collection of extracts from fungi, actinomycetes, and unicellular bacteria that covers an uncommonly broad chemical space was used to interrogate this nuclear export assay system. A two-step image-based analysis allowed us to identify 12 extracts with biological activities that are not associated with previously known active metabolites. The fractionation and structural elucidation of active compounds revealed several chemical structures with nuclear export inhibition activity. Here we show that substrates of the nuclear export receptor CRM1, such as Rev, FOXO3a and NF-κB, accumulate in the nucleus in the presence of the fungal metabolite MDN-0105 with an IC50 value of 3.4 µM. Many important processes in tumor formation and progression, as well as in many viral infections, critically depend on the nucleocytoplasmic trafficking of proteins and RNA molecules. Therefore, the disruption of nuclear export is emerging as a novel therapeutic approach with enormous clinical potential. Our work highlights the potential of applying high-throughput phenotypic imaging on natural product extracts to identify novel nuclear export inhibitors.

  18. Genome analysis reveals interplay between 5'UTR introns and nuclear mRNA export for secretory and mitochondrial genes.

    Directory of Open Access Journals (Sweden)

    Can Cenik

    2011-04-01

    Full Text Available In higher eukaryotes, messenger RNAs (mRNAs are exported from the nucleus to the cytoplasm via factors deposited near the 5' end of the transcript during splicing. The signal sequence coding region (SSCR can support an alternative mRNA export (ALREX pathway that does not require splicing. However, most SSCR-containing genes also have introns, so the interplay between these export mechanisms remains unclear. Here we support a model in which the furthest upstream element in a given transcript, be it an intron or an ALREX-promoting SSCR, dictates the mRNA export pathway used. We also experimentally demonstrate that nuclear-encoded mitochondrial genes can use the ALREX pathway. Thus, ALREX can also be supported by nucleotide signals within mitochondrial-targeting sequence coding regions (MSCRs. Finally, we identified and experimentally verified novel motifs associated with the ALREX pathway that are shared by both SSCRs and MSCRs. Our results show strong correlation between 5' untranslated region (5'UTR intron presence/absence and sequence features at the beginning of the coding region. They also suggest that genes encoding secretory and mitochondrial proteins share a common regulatory mechanism at the level of mRNA export.

  19. Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents

    OpenAIRE

    Joel G. Turner; Dawson, Jana; Cubitt, Christopher L.; Baz, Rachid; Daniel M. Sullivan

    2014-01-01

    Nuclear-cytoplasmic trafficking of proteins is a significant factor in the development of cancer and drug resistance. Subcellular localization of exported proteins linked to cancer development include those involved in cell growth and proliferation, apoptosis, cell cycle regulation, transformation, angiogenesis, cell adhesion, invasion, and metastasis. Here, we examined the basic mechanisms involved in the export of proteins from the nucleus to the cytoplasm. All proteins over 40 kDa use the ...

  20. China sets sights on exporting an affordable nuclear solution

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, David [NucNet, Bruessel (Belgium)

    2016-03-15

    Since the Fukushima-Daiichi accident in 2011 few western countries have been building nuclear reactors. China, however, seems to be going on something of a spree, sensing a solution for pollution at home - and unprecedented commercial opportunities abroad. There might be a general feeling in the industry that nuclear energy is on the wane in the West, but the same industry is casting increasingly envious glances to the East. A minimum of 60 nuclear power reactors are expected to start up in China over the next decade. By 2050, nuclear power should exceed 350 GW in China, with about 400 new nuclear reactors and total nuclear investment of over a trillion dollars.

  1. Multiple Novel Signals Mediate Thyroid Hormone Receptor Nuclear Import and Export*

    OpenAIRE

    Mavinakere, Manohara S.; Powers, Jeremy M.; Subramanian, Kelly S.; Roggero, Vincent R.; Allison, Lizabeth A.

    2012-01-01

    Thyroid hormone receptor (TR) is a member of the nuclear receptor superfamily that shuttles between the cytosol and nucleus. The fine balance between nuclear import and export of TR has emerged as a critical control point for modulating thyroid hormone-responsive gene expression; however, sequence motifs of TR that mediate shuttling are not fully defined. Here, we characterized multiple signals that direct TR shuttling. Along with the known nuclear localization signal in the hinge domain, we ...

  2. Voluntary Code of Conduct for Nuclear Export Control by Private Sector

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Seong Youn; Shin, Dong Hoon [Korea Institute of Nuclear Non-Prolferation and Control Daejeon (Korea, Republic of)

    2011-10-15

    The nuclear renaissance offered a good opportunity to overcome energy crisis that we are bound to confront in the near future. At the opposite end, however, our world might be exposed to a new threat which could be resulted from the boost of nuclear power. The expansion of nuclear power plants worldwide inevitably makes the countries involve more transaction in nuclear items, which could lead to increase in nuclear proliferation risk. The international efforts to prevent proliferation attempts have been mainly being focused on limitation of nuclear sensitive technology and nuclear material. Considering the governments of major nuclear suppliers' key roles in the stage, it should be notable that a new initiative by private nuclear companies has been raised for the purpose of strengthening nuclear export control

  3. Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition.

    Science.gov (United States)

    Chen, Zhi; Liu, Shaoning; Sun, Wenbo; Chen, Lei; Yoo, Dongwan; Li, Feng; Ren, Sufang; Guo, Lihui; Cong, Xiaoyan; Li, Jun; Zhou, Shun; Wu, Jiaqiang; Du, Yijun; Wang, Jinbao

    2016-12-01

    The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response. Copyright © 2016. Published by Elsevier Inc.

  4. Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.

    Science.gov (United States)

    Yanai, Mako; Sakai, Madoka; Makino, Akiko; Tomonaga, Keizo

    2017-07-11

    Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear. We examined the subcellular localization, viral polymerase activity, and P-binding ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV) harboring an NES mutation of N. BoDV-N with four alanine-substitutions in the leucine and isoleucine residues of the NES impaired its cytoplasmic localization and abolished polymerase activity and P-binding ability. Although an alanine-substitution at position 131 markedly enhanced viral polymerase activity as determined by a minigenome assay, rBoDV harboring this mutation showed expression of viral RNAs and proteins relative to that of wild-type rBoDV. Our results demonstrate that BoDV-N NES has a dual function in BoDV replication, i.e., nuclear export of N and an interaction with P, affecting viral polymerase activity in the nucleus.

  5. Selective nuclear export of specific classes of mRNA from mammalian nuclei is promoted by GANP.

    Science.gov (United States)

    Wickramasinghe, Vihandha O; Andrews, Robert; Ellis, Peter; Langford, Cordelia; Gurdon, John B; Stewart, Murray; Venkitaraman, Ashok R; Laskey, Ronald A

    2014-04-01

    The nuclear phase of the gene expression pathway culminates in the export of mature messenger RNAs (mRNAs) to the cytoplasm through nuclear pore complexes. GANP (germinal- centre associated nuclear protein) promotes the transfer of mRNAs bound to the transport factor NXF1 to nuclear pore complexes. Here, we demonstrate that GANP, subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex, promotes selective nuclear export of a specific subset of mRNAs whose transport depends on NXF1. Genome-wide gene expression profiling showed that half of the transcripts whose nuclear export was impaired following NXF1 depletion also showed reduced export when GANP was depleted. GANP-dependent transcripts were highly expressed, yet short-lived, and were highly enriched in those encoding central components of the gene expression machinery such as RNA synthesis and processing factors. After injection into Xenopus oocyte nuclei, representative GANP-dependent transcripts showed faster nuclear export kinetics than representative transcripts that were not influenced by GANP depletion. We propose that GANP promotes the nuclear export of specific classes of mRNAs that may facilitate rapid changes in gene expression.

  6. Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

    Science.gov (United States)

    Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

    2010-05-21

    NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

  7. Translocation Biosensors - Cellular System Integrators to Dissect CRM1-Dependent Nuclear Export by Chemicogenomics.

    Science.gov (United States)

    Fetz, Verena; Knauer, Shirley K; Bier, Carolin; von Kries, Jens Peter; Stauber, Roland H

    2009-01-01

    Fluorescent protein biosensors are powerful cellular systems biology tools for dissecting the complexity of cellular processes with high spatial and temporal resolution. As regulated nucleo-cytoplasmic transport is crucial for the modulation of numerous (patho)physiological cellular responses, a detailed understanding of its molecular mechanism would open up novel options for a rational manipulation of the cell. In contrast to genetic approaches, we here established and employed high-content cellular translocation biosensors applicable for dissecting nuclear export by chemicogenomics. A431 cell lines, stably expressing a translocation biosensor composed of glutathione S-transferase, GFP and a rational combination of nuclear import and export signals, were engineered by antibiotic selection and flow cytometry sorting. Using an optimized nuclear translocation algorithm, the translocation response could be robustly quantified on the Cellomics Arrayscan(®) VTI platform. Subsequent to assay optimization, the assay was developed into a higher density 384-well format high-content assay and employed for the screening of the 17K ChemBioNet compound collection. This library was selected on the basis of a genetic algorithm used to identify maximum common chemical substructures in a database of annotated bioactive molecules and hence, is well-placed in the chemical space covered by bioactive compounds. Automated multiparameter data analysis combined with visual inspection allowed us to identify and to rationally discriminate true export inhibitors from false positives, which included fluorescent compounds or cytotoxic substances that dramatically affected the cellular morphology. A total of 120 potential hit compounds were selected for Cellomics Arrayscan(®) VTI based rescreening. The export inhibitory activity of 20 compounds effective at concentrations export receptor CRM1-mediated nuclear export not only in an irreversible, but also in a reversible fashion. In sum

  8. Export Control Guide: Loose Parts Monitoring Systems for Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Langenberg, Donald W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2012-12-01

    This report describes a typical LPMS, emphasizing its application to the RCS of a modern NPP. The report also examines the versatility of AE monitoring technology by describing several nuclear applications other than loose parts monitoring, as well as some non-nuclear applications. In addition, LPMS implementation requirements are outlined, and LPMS suppliers are identified. Finally, U.S. export controls applicable to LPMSs are discussed.

  9. Phosphorylation of Serine 271 on 5-Lipoxygenase and Its Role in Nuclear Export*

    OpenAIRE

    Flamand, Nicolas; Luo, Ming; Peters-Golden, Marc; Brock, Thomas G.

    2009-01-01

    The enzyme 5-lipoxygenase (5-LO) initiates the biosynthesis of leukotrienes, inflammatory mediators involved in immune diseases and defense. The subcellular localization of 5-LO is regulated, with nuclear import commonly leading to increased leukotriene production. We report here that 5-LO is constitutively phosphorylated on Ser-271 in transfected NIH 3T3 cells. This residue is nested in a classical nuclear export sequence, and phosphorylated Ser-271 5-LO was exclusive...

  10. Identification of CRM1-dependent Nuclear Export Cargos Using Quantitative Mass Spectrometry.

    Science.gov (United States)

    Thakar, Ketan; Karaca, Samir; Port, Sarah A; Urlaub, Henning; Kehlenbach, Ralph H

    2013-03-01

    Chromosome region maintenance 1/exportin1/Exp1/Xpo1 (CRM1) is the major transport receptor for the export of proteins from the nucleus. It binds to nuclear export signals (NESs) that are rich in leucines and other hydrophobic amino acids. The prediction of NESs is difficult because of the extreme recognition flexibility of CRM1. Furthermore, proteins can be exported upon binding to an NES-containing adaptor protein. Here we present an approach for identifying targets of the CRM1-export pathway via quantitative mass spectrometry using stable isotope labeling with amino acids in cell culture. With this approach, we identified >100 proteins from HeLa cells that were depleted from cytosolic fractions and/or enriched in nuclear fractions in the presence of the selective CRM1-inhibitor leptomycin B. Novel and validated substrates are the polyubiquitin-binding protein sequestosome 1, the cancerous inhibitor of protein phosphatase 2A (PP2A), the guanine nucleotide-binding protein-like 3-like protein, the programmed cell death protein 2-like protein, and the cytosolic carboxypeptidase 1 (CCP1). We identified a functional NES in CCP1 that mediates direct binding to the export receptor CRM1. The method will be applicable to other nucleocytoplasmic transport pathways, as well as to the analysis of nucleocytoplasmic shuttling proteins under different growth conditions.

  11. Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway*

    Science.gov (United States)

    Grespin, Matthew E.; Bonamy, Ghislain M. C.; Roggero, Vincent R.; Cameron, Nicole G.; Adam, Lindsay E.; Atchison, Andrew P.; Fratto, Victoria M.; Allison, Lizabeth A.

    2008-01-01

    The thyroid hormone receptor α1 (TRα) exhibits a dual role as an activator or repressor of its target genes in response to thyroid hormone (T3). Previously, we have shown that TRα, formerly thought to reside solely in the nucleus bound to DNA, actually shuttles rapidly between the nucleus and cytoplasm. An important aspect of the shuttling activity of TRα is its ability to exit the nucleus through the nuclear pore complex. TRα export is not sensitive to treatment with the CRM1-specific inhibitor leptomycin B (LMB) in heterokaryon assays, suggesting a role for an export receptor other than CRM1. Here, we have used a combined approach of in vivo fluorescence recovery after photobleaching experiments, in vitro permeabilized cell nuclear export assays, and glutathione S-transferase pull-down assays to investigate the export pathway used by TRα. We show that, in addition to shuttling in heterokaryons, TRα shuttles rapidly in an unfused monokaryon system as well. Furthermore, our data show that TRα directly interacts with calreticulin, and point to the intriguing possibility that TRα follows a cooperative export pathway in which both calreticulin and CRM1 play a role in facilitating efficient translocation of TRα from the nucleus to cytoplasm. PMID:18641393

  12. Thyroid hormone receptor alpha1 follows a cooperative CRM1/calreticulin-mediated nuclear export pathway.

    Science.gov (United States)

    Grespin, Matthew E; Bonamy, Ghislain M C; Roggero, Vincent R; Cameron, Nicole G; Adam, Lindsay E; Atchison, Andrew P; Fratto, Victoria M; Allison, Lizabeth A

    2008-09-12

    The thyroid hormone receptor alpha1 (TRalpha) exhibits a dual role as an activator or repressor of its target genes in response to thyroid hormone (T(3)). Previously, we have shown that TRalpha, formerly thought to reside solely in the nucleus bound to DNA, actually shuttles rapidly between the nucleus and cytoplasm. An important aspect of the shuttling activity of TRalpha is its ability to exit the nucleus through the nuclear pore complex. TRalpha export is not sensitive to treatment with the CRM1-specific inhibitor leptomycin B (LMB) in heterokaryon assays, suggesting a role for an export receptor other than CRM1. Here, we have used a combined approach of in vivo fluorescence recovery after photobleaching experiments, in vitro permeabilized cell nuclear export assays, and glutathione S-transferase pull-down assays to investigate the export pathway used by TRalpha. We show that, in addition to shuttling in heterokaryons, TRalpha shuttles rapidly in an unfused monokaryon system as well. Furthermore, our data show that TRalpha directly interacts with calreticulin, and point to the intriguing possibility that TRalpha follows a cooperative export pathway in which both calreticulin and CRM1 play a role in facilitating efficient translocation of TRalpha from the nucleus to cytoplasm.

  13. Mechanism for G2 phase-specific nuclear export of the kinetochore protein CENP-F.

    Science.gov (United States)

    Loftus, Kyle M; Cui, Heying; Coutavas, Elias; King, David S; Ceravolo, Amanda; Pereiras, Dylan; Solmaz, Sozanne R

    2017-08-03

    Centromere protein F (CENP-F) is a component of the kinetochore and a regulator of cell cycle progression. CENP-F recruits the dynein transport machinery and orchestrates several cell cycle-specific transport events, including transport of the nucleus, mitochondria and chromosomes. A key regulatory step for several of these functions is likely the G2 phase-specific export of CENP-F from the nucleus to the cytosol, where the cytoplasmic dynein transport machinery resides; however, the molecular mechanism of this process is elusive. Here, we have identified 3 phosphorylation sites within the bipartite classical nuclear localization signal (cNLS) of CENP-F. These sites are specific for cyclin-dependent kinase 1 (Cdk1), which is active in G2 phase. Phosphomimetic mutations of these residues strongly diminish the interaction of the CENP-F cNLS with its nuclear transport receptor karyopherin α. These mutations also diminish nuclear localization of the CENP-F cNLS in cells. Notably, the cNLS is phosphorylated in the -1 position, which is important to orient the adjacent major motif for binding into its pocket on karyopherin α. We propose that localization of CENP-F is regulated by a cNLS, and a nuclear export pathway, resulting in nuclear localization during most of interphase. In G2 phase, the cNLS is weakened by phosphorylation through Cdk1, likely resulting in nuclear export of CENP-F via the still active nuclear export pathway. Once CENP-F resides in the cytosol, it can engage in pathways that are important for cell cycle progression, kinetochore assembly and the faithful segregation of chromosomes into daughter cells.

  14. A global survey of CRM1-dependent nuclear export sequences in the human deubiquitinase family.

    Science.gov (United States)

    García-Santisteban, Iraia; Bañuelos, Sonia; Rodríguez, Jose A

    2012-01-01

    The mechanisms that regulate the nucleocytoplasmic localization of human deubiquitinases remain largely unknown. The nuclear export receptor CRM1 binds to specific amino acid motifs termed NESs (nuclear export sequences). By using in silico prediction and experimental validation of candidate sequences, we identified 32 active NESs and 78 inactive NES-like motifs in human deubiquitinases. These results allowed us to evaluate the performance of three programs widely used for NES prediction, and to add novel information to the recently redefined NES consensus. The novel NESs identified in the present study reveal a subset of 22 deubiquitinases bearing motifs that might mediate their binding to CRM1. We tested the effect of the CRM1 inhibitor LMB (leptomycin B) on the localization of YFP (yellow fluorescent protein)- or GFP (green fluorescent protein)-tagged versions of six NES-bearing deubiquitinases [USP (ubiquitin-specific peptidase) 1, USP3, USP7, USP21, CYLD (cylindromatosis) and OTUD7B (OTU-domain-containing 7B)]. YFP-USP21 and, to a lesser extent, GFP-OTUD7B relocated from the cytoplasm to the nucleus in the presence of LMB, revealing their nucleocytoplasmic shuttling capability. Two sequence motifs in USP21 had been identified during our survey as active NESs in the export assay. Using site-directed mutagenesis, we show that one of these motifs mediates USP21 nuclear export, whereas the second motif is not functional in the context of full-length USP21.

  15. The actin binding cytoskeletal protein Moesin is involved in nuclear mRNA export.

    Science.gov (United States)

    Kristó, Ildikó; Bajusz, Csaba; Borsos, Barbara N; Pankotai, Tibor; Dopie, Joseph; Jankovics, Ferenc; Vartiainen, Maria K; Erdélyi, Miklós; Vilmos, Péter

    2017-10-01

    Current models imply that the evolutionarily conserved, actin-binding Ezrin-Radixin-Moesin (ERM) proteins perform their activities at the plasma membrane by anchoring membrane proteins to the cortical actin network. Here we show that beside its cytoplasmic functions, the single ERM protein of Drosophila, Moesin, has a novel role in the nucleus. The activation of transcription by heat shock or hormonal treatment increases the amount of nuclear Moesin, indicating biological function for the protein in the nucleus. The distribution of Moesin in the nucleus suggests a function in transcription and the depletion of mRNA export factors Nup98 or its interacting partner, Rae1, leads to the nuclear accumulation of Moesin, suggesting that the nuclear function of the protein is linked to mRNA export. Moesin localizes to mRNP particles through the interaction with the mRNA export factor PCID2 and knock down of Moesin leads to the accumulation of mRNA in the nucleus. Based on our results we propose that, beyond its well-known, manifold functions in the cytoplasm, the ERM protein of Drosophila is a new, functional component of the nucleus where it participates in mRNA export. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Unprecedented NES non-antagonistic inhibitor for nuclear export of Rev from Sida cordifolia.

    Science.gov (United States)

    Tamura, Satoru; Kaneko, Masafumi; Shiomi, Atsushi; Yang, Guang-Ming; Yamaura, Toshiaki; Murakami, Nobutoshi

    2010-03-15

    Bioassay-guided separation from the MeOH extract of the South American medicinal plant Sida cordifolia resulted in isolation of (10E,12Z)-9-hydroxyoctadeca-10,12-dienoic acid (1) as an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev. This mechanism of action was established by competitive experiment by the biotinylated probe derived from leptomycin B, the known NES antagonistic inhibitor. Additionally, structure-activity relationship analysis by use of the synthesized analogs clarified cooperation of several functionalities in the Rev-export inhibitory activity of 1. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery.

    Science.gov (United States)

    Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Sohn, Hye Seon; Blanchet-Cohen, Alexis; Osborne, Michael J; Borden, Katherine L B

    2017-06-01

    The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date, over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ∼50-nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end. While eIF4E associates with the cap, an unknown factor recognizes the 4ESE element. We previously identified cofactors that functionally interacted with eIF4E in mammalian cell nuclei including the leucine-rich pentatricopeptide repeat protein LRPPRC and the export receptor CRM1/XPO1. LRPPRC simultaneously interacts with both eIF4E bound to the 5' mRNA cap and the 4ESE element in the 3' UTR. In this way, LRPPRC serves as a specificity factor to recruit 4ESE-containing RNAs within the nucleus. Further, we show that CRM1 directly binds LRPPRC likely acting as the export receptor for the LRPPRC-eIF4E-4ESE RNA complex. We also found that Importin 8, the nuclear importer for cap-free eIF4E, imports RNA-free LRPPRC, potentially providing both coordinated nuclear recycling of the export machinery and an important surveillance mechanism to prevent futile export cycles. Our studies provide the first biochemical framework for the eIF4E-dependent mRNA export pathway. © 2017 Volpon et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  18. RanBP3 Regulates Melanoma Cell Proliferation via Selective Control of Nuclear Export.

    Science.gov (United States)

    Pathria, Gaurav; Garg, Bhavuk; Wagner, Christine; Garg, Kanika; Gschaider, Melanie; Jalili, Ahmad; Wagner, Stephan N

    2016-01-01

    Chromosome region maintenance 1-mediated nucleocytoplasmic transport has been shown as a potential anticancer target in various malignancies. However, the role of the most characterized chromosome region maintenance 1 cofactor ran binding protein 3 (RanBP3) in cancer cell biology has never been investigated. Utilizing a loss-of-function experimental setting in a vast collection of genetically varied melanoma cell lines, we observed the requirement of RanBP3 in melanoma cell proliferation and survival. Mechanistically, we suggest the reinstatement of transforming growth factor-β (TGF-β)-Smad2/3-p21(Cip1) tumor-suppressor axis as part of the RanBP3 silencing-associated antiproliferative program. Employing extensive nuclear export sequence analyses and immunofluorescence-based protein localization studies, we further present evidence suggesting the requirement of RanBP3 function for the nuclear exit of the weak nuclear export sequence-harboring extracellular signal-regulated kinase protein, although it is dispensable for general CRM1-mediated nuclear export of strong nuclear export sequence-harboring cargoes. Rendering mechanistic support to RanBP3 silencing-mediated apoptosis, consequent to extracellular signal-regulated kinase nuclear entrapment, we observed increased levels of cytoplasmically restricted nonphosphorylated/active proapoptotic Bcl-2-antagonist of cell death (BAD) protein. Last, we present evidence suggesting the frequently activated mitogen-activated protein kinase signaling in melanoma as a potential founding basis for a deregulated post-translational control of RanBP3 activity. Collectively, the presented data suggest RanBP3 as a potential target for therapeutic intervention in human melanoma.

  19. Sequence and structural analyses of nuclear export signals in the NESdb database.

    Science.gov (United States)

    Xu, Darui; Farmer, Alicia; Collett, Garen; Grishin, Nick V; Chook, Yuh Min

    2012-09-01

    We compiled >200 nuclear export signal (NES)-containing CRM1 cargoes in a database named NESdb. We analyzed the sequences and three-dimensional structures of natural, experimentally identified NESs and of false-positive NESs that were generated from the database in order to identify properties that might distinguish the two groups of sequences. Analyses of amino acid frequencies, sequence logos, and agreement with existing NES consensus sequences revealed strong preferences for the Φ1-X(3)-Φ2-X(2)-Φ3-X-Φ4 pattern and for negatively charged amino acids in the nonhydrophobic positions of experimentally identified NESs but not of false positives. Strong preferences against certain hydrophobic amino acids in the hydrophobic positions were also revealed. These findings led to a new and more precise NES consensus. More important, three-dimensional structures are now available for 68 NESs within 56 different cargo proteins. Analyses of these structures showed that experimentally identified NESs are more likely than the false positives to adopt α-helical conformations that transition to loops at their C-termini and more likely to be surface accessible within their protein domains or be present in disordered or unobserved parts of the structures. Such distinguishing features for real NESs might be useful in future NES prediction efforts. Finally, we also tested CRM1-binding of 40 NESs that were found in the 56 structures. We found that 16 of the NES peptides did not bind CRM1, hence illustrating how NESs are easily misidentified.

  20. Antiviral activity of KR-23502 targeting nuclear export of influenza B virus ribonucleoproteins.

    Science.gov (United States)

    Jang, Yejin; Lee, Hye Won; Shin, Jin Soo; Go, Yun Young; Kim, Chonsaeng; Shin, Daeho; Malpani, Yashwardhan; Han, Soo Bong; Jung, Young-Sik; Kim, Meehyein

    2016-10-01

    The spiro compound 5,6-dimethyl-3H,3'H-spiro(benzofuran-2,1'-isobenzofuran)-3,3'-dione (KR-23502) has antiviral activity against influenza A and more potently B viruses. The aim of this study is to elucidate its mechanism of action. Subcellular localization and time-course expression of influenza B viral proteins, nucleoprotein (NP) and matrix protein 1 (M1), showed that KR-23502 reduced their amounts within 5 h post-infection. Early steps of virus life cycle, including virus entry, nuclear localization of NP and viral RNA-dependent RNA replication, were not affected by KR-23502. Instead it interrupted a later event corresponding to nuclear export of NP and M1 proteins. Delivery of viral ribonucleoprotein (vRNP)-M1 complex has been known to be mediated by the viral nuclear export protein (NEP) through interaction with cellular chromosomal maintenance 1 (CRM1) protein. In this study, we experimentally demonstrated that the compound targets the nuclear export of vRNP. Moreover, a single mutation (aspartate to glycine) at amino acid position 54 in M1 [M1(D54G)] was detected after 18 passages in the presence of KR-23502 with a 2-fold increase in 50% effective concentration indicating that this compound has a relatively high genetic barrier to resistance. Interestingly, it was observed that proteasome-mediated degradation of M1(D54G) was attenuated by KR-23502. In conclusion, we suggest that KR-23502 shows its anti-influenza activity by downregulating NEP/CRM1-mediated nuclear export of influenza vRNP and M1. KR-23502 provides a core chemical skeleton for further structure-based design of novel antivirals against influenza viruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Influenza virus targets the mRNA export machinery and the nuclear pore complex.

    Science.gov (United States)

    Satterly, Neal; Tsai, Pei-Ling; van Deursen, Jan; Nussenzveig, Daniel R; Wang, Yaming; Faria, Paula A; Levay, Agata; Levy, David E; Fontoura, Beatriz M A

    2007-02-01

    The NS1 protein of influenza A virus is a major virulence factor that is essential for pathogenesis. NS1 functions to impair innate and adaptive immunity by inhibiting host signal transduction and gene expression, but its mechanisms of action remain to be fully elucidated. We show here that NS1 forms an inhibitory complex with NXF1/TAP, p15/NXT, Rae1/mrnp41, and E1B-AP5, which are key constituents of the mRNA export machinery that interact with both mRNAs and nucleoporins to direct mRNAs through the nuclear pore complex. Increased levels of NXF1, p15, or Rae1 revert the mRNA export blockage induced by NS1. Furthermore, influenza virus down-regulates Nup98, a nucleoporin that is a docking site for mRNA export factors. Reduced expression of these mRNA export factors renders cells highly permissive to influenza virus replication, demonstrating that proper levels of key constituents of the mRNA export machinery protect against influenza virus replication. Because Nup98 and Rae1 are induced by interferons, down-regulation of this pathway is likely a viral strategy to promote viral replication. These findings demonstrate previously undescribed influenza-mediated viral-host interactions and provide insights into potential molecular therapies that may interfere with influenza infection.

  2. RNA-guided assembly of Rev-RRE nuclear export complexes.

    Science.gov (United States)

    Bai, Yun; Tambe, Akshay; Zhou, Kaihong; Doudna, Jennifer A

    2014-08-27

    HIV replication requires nuclear export of unspliced and singly spliced viral transcripts. Although a unique RNA structure has been proposed for the Rev-response element (RRE) responsible for viral mRNA export, how it recruits multiple HIV Rev proteins to form an export complex has been unclear. We show here that initial binding of Rev to the RRE triggers RNA tertiary structural changes, enabling further Rev binding and the rapid formation of a viral export complex. Analysis of the Rev-RRE assembly pathway using SHAPE-Seq and small-angle X-ray scattering (SAXS) reveals two major steps of Rev-RRE complex formation, beginning with rapid Rev binding to a pre-organized region presenting multiple Rev binding sites. This step induces long-range remodeling of the RNA to expose a cryptic Rev binding site, enabling rapid assembly of additional Rev proteins into the RNA export complex. This kinetic pathway may help maintain the balance between viral replication and maturation.DOI: http://dx.doi.org/10.7554/eLife.03656.001.

  3. Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

    Directory of Open Access Journals (Sweden)

    Andrea Cerutti

    Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS, but no nuclear export signal (NES has yet been identified.We show here that the aa(109-133 region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126 in the identified NES or in the sequence encoding the mature core aa(1-173 significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection.

  4. Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

    Science.gov (United States)

    Cerutti, Andrea; Maillard, Patrick; Minisini, Rosalba; Vidalain, Pierre-Olivier; Roohvand, Farzin; Pecheur, Eve-Isabelle; Pirisi, Mario; Budkowska, Agata

    2011-01-01

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS), but no nuclear export signal (NES) has yet been identified.We show here that the aa(109-133) region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126) in the identified NES or in the sequence encoding the mature core aa(1-173) significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection.

  5. ATM induces MacroD2 nuclear export upon DNA damage

    Science.gov (United States)

    Golia, Barbara; Moeller, Giuliana Katharina; Jankevicius, Gytis; Schmidt, Andreas; Hegele, Anna; Preißer, Julia; Tran, Mai Ly; Imhof, Axel; Timinszky, Gyula

    2017-01-01

    ADP-ribosylation is a dynamic post-translation modification that regulates the early phase of various DNA repair pathways by recruiting repair factors to chromatin. ADP-ribosylation levels are defined by the activities of specific transferases and hydrolases. However, except for the transferase PARP1/ARDT1 little is known about regulation of these enzymes. We found that MacroD2, a mono-ADP-ribosylhydrolase, is exported from the nucleus upon DNA damage, and that this nuclear export is induced by ATM activity. We show that the export is dependent on the phosphorylation of two SQ/TQ motifs, suggesting a novel direct interaction between ATM and ADP-ribosylation. Lastly, we show that MacroD2 nuclear export temporally restricts its recruitment to DNA lesions, which may decrease the net ADP-ribosylhydrolase activity at the site of DNA damage. Together, our results identify a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. PMID:28069995

  6. Nuclear export of the influenza virus ribonucleoprotein complex: Interaction of Hsc70 with viral proteins M1 and NS2.

    Science.gov (United States)

    Watanabe, Ken; Shimizu, Teppei; Noda, Saiko; Tsukahara, Fujiko; Maru, Yoshiro; Kobayashi, Nobuyuki

    2014-01-01

    The influenza virus replicates in the host cell nucleus, and the progeny viral ribonucleoprotein complex (vRNP) is exported to the cytoplasm prior to maturation. NS2 has a nuclear export signal that mediates the nuclear export of vRNP by the vRNP-M1-NS2 complex. We previously reported that the heat shock cognate 70 (Hsc70) protein binds to M1 protein and mediates vRNP export. However, the interactions among M1, NS2, and Hsc70 are poorly understood. In the present study, we demonstrate that Hsc70 interacts with M1 more strongly than with NS2 and competes with NS2 for M1 binding, suggesting an important role of Hsc70 in the nuclear export of vRNP.

  7. Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents.

    Science.gov (United States)

    Turner, Joel G; Dawson, Jana; Cubitt, Christopher L; Baz, Rachid; Sullivan, Daniel M

    2014-08-01

    Nuclear-cytoplasmic trafficking of proteins is a significant factor in the development of cancer and drug resistance. Subcellular localization of exported proteins linked to cancer development include those involved in cell growth and proliferation, apoptosis, cell cycle regulation, transformation, angiogenesis, cell adhesion, invasion, and metastasis. Here, we examined the basic mechanisms involved in the export of proteins from the nucleus to the cytoplasm. All proteins over 40kDa use the nuclear pore complex to gain entry or exit from the nucleus, with the primary nuclear export molecule involved in these processes being chromosome region maintenance 1 (CRM1, exportin 1 or XPO1). Proteins exported from the nucleus must possess a hydrophobic nuclear export signal (NES) peptide that binds to a hydrophobic groove containing an active-site Cys528 in the CRM1 protein. CRM1 inhibitors function largely by covalent modification of the active site Cys528 and prevent binding to the cargo protein NES. In the absence of a CRM1 inhibitor, CRM1 binds cooperatively to the NES of the cargo protein and RanGTP, forming a trimer that is actively transported out of the nucleus by facilitated diffusion. Nuclear export can be blocked by CRM1 inhibitors, NES peptide inhibitors or by preventing post-translational modification of cargo proteins. Clinical trials using the classic CRM1 inhibitor leptomycin B proved too toxic for patients; however, a new generation of less toxic small molecule inhibitors is being used in clinical trials in patients with both hematological malignancies and solid tumors. Additional trials are being initiated using small-molecule CRM1 inhibitors in combination with chemotherapeutics such as pegylated liposomal doxorubicin. In this review, we present evidence that combining the new CRM1 inhibitors with other classes of therapeutics may prove effective in the treatment of cancer. Potential combinatorial therapies discussed include the use of CRM1 inhibitors and

  8. Structural determinants of nuclear export signal orientation in binding to exportin CRM1.

    Science.gov (United States)

    Fung, Ho Yee Joyce; Fu, Szu-Chin; Brautigam, Chad A; Chook, Yuh Min

    2015-09-08

    The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). Comparison of minus and plus NESs identified structural and sequence determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.

  9. Nuclear exports. Parliamentary control and confidentiality; Parlamentarische Kontrolle und Geheimhaltungsbeduerftigkeit bei Nuklearexporten. Zum Urteil des Bundesverfassungsgerichts vom 21. Oktober 2014

    Energy Technology Data Exchange (ETDEWEB)

    Feldmann, Ulrike

    2015-03-15

    With its decision taken on 21. October 2014 (Az.: 2 BvE 5/11) the Federal Constitutional Court (BVerfG) decided during court proceedings between administrative bodies on the scope and limits of the parliamentary right of information. Even though the proceeding did not deal with nuclear exports but arm exports, foreign trade law, however, does not only designate an export licence obligation for military weapons but also for so called dual-use goods meaning goods, which can be used both for friendly as well as for military purposes. The export of these goods requires according to the so-called Dual-Use Regulation (EG) 428/2009 a licence. Annex I category 0 of the regulation (EG) 428/2009 lists a variety of nuclear materials, plants and equipment items for which this licence applies. In the same manner as arm exports, also exports of nuclear dual-use goods are being discussed in a special cabinet committee, the Federal Security Council (BSR), which shall coordinate cross-departmentally the German security and defence policy under consideration of economic interests and which categorises its results, according to the rules of procedure, as confidential. Also legally not regulated but common ''preliminary enquiries'' at the responsible Federal Ministry or rather Federal Office of Economics and Export Control by companies which plan an export and want to affirm the general approval for their export business prior to conclusion of contract take not only place for arm exports but also for nuclear dual-use goods. The decision by the Federal Constitutional Court can be applied to consultations about the authorisation of nuclear dual-use goods.

  10. The BRO proteins of Bombyx mori nucleopolyhedrovirus are nucleocytoplasmic shuttling proteins that utilize the CRM1-mediated nuclear export pathway.

    Science.gov (United States)

    Kang, WonKyung; Kurihara, Masaaki; Matsumoto, Shogo

    2006-06-20

    The BRO proteins of Bombyx mori nucleopolyhedrovirus (BmNPV) display a biphasic pattern of intracellular localization during infection. At early times, they reside in the nucleus but then show both cytoplasmic and nuclear localization as the infection proceeds. Therefore, we examined the possibility of nuclear export. Using inhibitors, we reveal that BmNPV BRO proteins shuttle between the nucleus and cytoplasm. Mutations on the leucine-rich region of BRO proteins resulted in nuclear accumulation of transiently expressed proteins, suggesting that this region functions as a CRM1-dependent nuclear export signal (NES). On the contrary, mutant BRO-D with an altered NES did not show nuclear accumulation in infected cells, although protein production seemed to be reduced. RT-PCR analysis showed that the lower level of protein production was due to a reduction in RNA synthesis. Taken together, our results suggest that BRO proteins are nucleocytoplasmic shuttling proteins that utilize the CRM1-mediated nuclear export pathway.

  11. Intranuclear targeting and nuclear export of the adenovirus E1B-55K protein are regulated by SUMO1 conjugation

    OpenAIRE

    Kindsmüller, Kathrin; Groitl, Peter; Härtl, Barbara; Blanchette, Paola; Hauber, Joachim; Dobner, Thomas

    2007-01-01

    We have investigated the requirements for CRM1-mediated nuclear export and SUMO1 conjugation of the adenovirus E1B-55K protein during productive infection. Our data show that CRM1 is the major export receptor for E1B-55K in infected cells. Functional inactivation of the E1B-55K CRM1-dependent nuclear export signal (NES) or leptomycin B treatment causes an almost complete redistribution of the viral protein from the cytoplasm to the nucleus and its accumulation at the periphery of the viral re...

  12. RNA-binding proteins of the NXF (nuclear export factor) family and their connection with the cytoskeleton.

    Science.gov (United States)

    Mamon, L A; Ginanova, V R; Kliver, S F; Yakimova, A O; Atsapkina, A A; Golubkova, E V

    2017-04-01

    The mutual relationship between mRNA and the cytoskeleton can be seen from two points of view. On the one hand, the cytoskeleton is necessary for mRNA trafficking and anchoring to subcellular domains. On the other hand, cytoskeletal growth and rearrangement require the translation of mRNAs that are connected to the cytoskeleton. β-actin mRNA localization may influence dynamic changes in the actin cytoskeleton. In the cytoplasm, long-lived mRNAs exist in the form of RNP (ribonucleoprotein) complexes, where they interact with RNA-binding proteins, including NXF (Nuclear eXport Factor). Dm NXF1 is an evolutionarily conserved protein in Drosophila melanogaster that has orthologs in different animals. The universal function of nxf1 genes is the nuclear export of different mRNAs in various organisms. In this mini-review, we briefly discuss the evidence demonstrating that Dm NXF1 fulfils not only universal but also specialized cytoplasmic functions. This protein is detected not only in the nucleus but also in the cytoplasm. It is a component of neuronal granules. Dm NXF1 marks nuclear division spindles during early embryogenesis and the dense body on one side of the elongated spermatid nuclei. The characteristic features of sbr mutants (sbr(10) and sbr(5) ) are impairment of chromosome segregation and spindle formation anomalies during female meiosis. sbr(12) mutant sterile males with immobile spermatozoa exhibit disturbances in the axoneme, mitochondrial derivatives and cytokinesis. These data allow us to propose that the Dm NXF1 proteins transport certain mRNAs in neurites and interact with localized mRNAs that are necessary for dynamic changes of the cytoskeleton. © 2017 Wiley Periodicals, Inc.

  13. Efficient nuclear export of p65-IkappaBalpha complexes requires 14-3-3 proteins.

    Science.gov (United States)

    Aguilera, Cristina; Fernández-Majada, Vanessa; Inglés-Esteve, Julia; Rodilla, Verónica; Bigas, Anna; Espinosa, Lluís

    2006-09-01

    IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NFkappaB activation to terminate the signal. We now show that 14-3-3 proteins regulate the NFkappaB signaling pathway by physically interacting with p65 and IkappaBalpha proteins. We identify two functional 14-3-3 binding domains in the p65 protein involving residues 38-44 and 278-283, and map the interaction region of IkappaBalpha in residues 60-65. Mutation of these 14-3-3 binding domains in p65 or IkappaBalpha results in a predominantly nuclear distribution of both proteins. TNFalpha treatment promotes recruitment of 14-3-3 and IkappaBalpha to NFkappaB-dependent promoters and enhances the binding of 14-3-3 to p65. Disrupting 14-3-3 activity by transfection with a dominant-negative 14-3-3 leads to the accumulation of nuclear p65-IkappaBalpha complexes and the constitutive association of p65 with the chromatin. In this situation, NFkappaB-dependent genes become unresponsive to TNFalpha stimulation. Together our results indicate that 14-3-3 proteins facilitate the nuclear export of IkappaBalpha-p65 complexes and are required for the appropriate regulation of NFkappaB signaling.

  14. Sustainability Features of Nuclear Fuel Cycle Options

    Directory of Open Access Journals (Sweden)

    Stefano Passerini

    2012-09-01

    Full Text Available The nuclear fuel cycle is the series of stages that nuclear fuel materials go through in a cradle to grave framework. The Once Through Cycle (OTC is the current fuel cycle implemented in the United States; in which an appropriate form of the fuel is irradiated through a nuclear reactor only once before it is disposed of as waste. The discharged fuel contains materials that can be suitable for use as fuel. Thus, different types of fuel recycling technologies may be introduced in order to more fully utilize the energy potential of the fuel, or reduce the environmental impacts and proliferation concerns about the discarded fuel materials. Nuclear fuel cycle systems analysis is applied in this paper to attain a better understanding of the strengths and weaknesses of fuel cycle alternatives. Through the use of the nuclear fuel cycle analysis code CAFCA (Code for Advanced Fuel Cycle Analysis, the impact of a number of recycling technologies and the associated fuel cycle options is explored in the context of the U.S. energy scenario over 100 years. Particular focus is given to the quantification of Uranium utilization, the amount of Transuranic Material (TRU generated and the economics of the different options compared to the base-line case, the OTC option. It is concluded that LWRs and the OTC are likely to dominate the nuclear energy supply system for the period considered due to limitations on availability of TRU to initiate recycling technologies. While the introduction of U-235 initiated fast reactors can accelerate their penetration of the nuclear energy system, their higher capital cost may lead to continued preference for the LWR-OTC cycle.

  15. Regulation of the Drosophila Hypoxia-Inducible Factor α Sima by CRM1-Dependent Nuclear Export

    Science.gov (United States)

    Romero, Nuria M.; Irisarri, Maximiliano; Roth, Peggy; Cauerhff, Ana; Samakovlis, Christos; Wappner, Pablo

    2008-01-01

    Hypoxia-inducible factor α (HIF-α) proteins are regulated by oxygen levels through several different mechanisms that include protein stability, transcriptional coactivator recruitment, and subcellular localization. It was previously reported that these transcription factors are mainly nuclear in hypoxia and cytoplasmic in normoxia, but so far the molecular basis of this regulation is unclear. We show here that the Drosophila melanogaster HIF-α protein Sima shuttles continuously between the nucleus and the cytoplasm. We identified the relevant nuclear localization signal and two functional nuclear export signals (NESs). These NESs are in the Sima basic helix-loop-helix (bHLH) domain and promote CRM1-dependent nuclear export. Site-directed mutagenesis of either NES provoked Sima nuclear retention and increased transcriptional activity, suggesting that nuclear export contributes to Sima regulation. The identified NESs are conserved and probably functional in the bHLH domains of several bHLH-PAS proteins. We propose that rapid nuclear export of Sima regulates the duration of cellular responses to hypoxia. PMID:18332128

  16. The function of the inner nuclear envelope protein SUN1 in mRNA export is regulated by phosphorylation.

    Science.gov (United States)

    Li, Ping; Stumpf, Maria; Müller, Rolf; Eichinger, Ludwig; Glöckner, Gernot; Noegel, Angelika A

    2017-08-22

    SUN1, a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, functions in mammalian mRNA export through the NXF1-dependent pathway. It associates with mRNP complexes by direct interaction with NXF1. It also binds to the NPC through association with the nuclear pore component Nup153, which is involved in mRNA export. The SUN1-NXF1 association is at least partly regulated by a protein kinase C (PKC) which phosphorylates serine 113 (S113) in the N-terminal domain leading to reduced interaction. The phosphorylation appears to be important for the SUN1 function in nuclear mRNA export since GFP-SUN1 carrying a S113A mutation was less efficient in restoring mRNA export after SUN1 knockdown as compared to the wild type protein. By contrast, GFP-SUN1-S113D resembling the phosphorylated state allowed very efficient export of poly(A)+RNA. Furthermore, probing a possible role of the LINC complex component Nesprin-2 in this process we observed impaired mRNA export in Nesprin-2 knockdown cells. This effect might be independent of SUN1 as expression of a GFP tagged SUN-domain deficient SUN1, which no longer can interact with Nesprin-2, did not affect mRNA export.

  17. Postage for the messenger: Designating routes for Nuclear mRNA Export

    Science.gov (United States)

    Natalizio, Barbara J.; Wente, Susan R.

    2013-01-01

    Transcription of messenger(m) RNA occurs in the nucleus, making the translocation of mRNA across the nuclear envelope (NE) boundary a critical determinant of proper gene expression and cell survival. A major mRNA export route occurs via the NXF1-dependent pathway through the nuclear pore complexes (NPCs) embedded in the NE. However, recent findings have discovered new evidence supporting the existence of multiple mechanisms for crossing the NE, including both NPC-mediated and NE budding-mediated pathways. An analysis of the trans-acting factors and cis components that define these pathways reveals shared elements as well as mechanistic differences. We review here the current understanding of the mechanisms that characterize each pathway and highlight the determinants that influence mRNA transport fate. PMID:23583578

  18. ValidNESs: a database of validated leucine-rich nuclear export signals.

    Science.gov (United States)

    Fu, Szu-Chin; Huang, Hsuan-Cheng; Horton, Paul; Juan, Hsueh-Fen

    2013-01-01

    ValidNESs (http://validness.ym.edu.tw/) is a new database for experimentally validated leucine-rich nuclear export signal (NES)-containing proteins. The therapeutic potential of the chromosomal region maintenance 1 (CRM1)-mediated nuclear export pathway and disease relevance of its cargo proteins has gained recognition in recent years. Unfortunately, only about one-third of known CRM1 cargo proteins are accessible in a single database since the last compilation in 2003. CRM1 cargo proteins are often recognized by a classical NES (leucine-rich NES), but this signal is notoriously difficult to predict from sequence alone. Fortunately, a recently developed prediction method, NESsential, is able to identify good candidates in some cases, enabling valuable hints to be gained by in silico prediction, but until now it has not been available through a web interface. We present ValidNESs, an integrated, up-to-date database holding 221 NES-containing proteins, combined with a web interface to prediction by NESsential.

  19. Mapping regions in Ste5 that support Msn5-dependent and -independent nuclear export.

    Science.gov (United States)

    Hu, Zhenhua; Wang, Yunmei; Yu, Lu; Mahanty, Sanjoy K; Mendoza, Natalia; Elion, Elaine A

    2016-04-01

    Careful control of the available pool of the MAPK scaffold Ste5 is important for mating-pathway activation and the prevention of inappropriate mating differentiation in haploid Saccharomyces cerevisiae. Ste5 shuttles constitutively through the nucleus, where it is degraded by a ubiquitin-dependent mechanism triggered by G1 CDK phosphorylation. Here we narrow-down regions of Ste5 that mediate nuclear export. Four regions in Ste5 relocalize SV40-TAgNLS-GFP-GFP from nucleus to cytoplasm. One region is N-terminal, dependent on exportin Msn5/Ste21/Kap142, and interacts with Msn5 in 2 hybrid assays independently of mating pheromone, Fus3, Kss1, Ptc1, the NLS/PM, and RING-H2. A second region overlaps the PH domain and Ste11 binding site and 2 others are on the vWA domain and include residues essential for MAPK activation. We find no evidence for dependence on Crm1/Xpo1, despite numerous potential nuclear export sequences (NESs) detected by LocNES and NetNES1.1 predictors. Thus, Msn5 (homolog of human Exportin-5) and one or more exportins or adaptor molecules besides Crm1/Xpo1 may regulate Ste5 through multiple recognition sites.

  20. Drosophila caliban, a nuclear export mediator, can function as a tumor suppressor in human lung cancer cells.

    Science.gov (United States)

    Bi, Xiaolin; Jones, Tamara; Abbasi, Fatima; Lee, Heuijung; Stultz, Brian; Hursh, Deborah A; Mortin, Mark A

    2005-12-15

    We previously showed that the Drosophila DNA binding homeodomain of Prospero included a 28 amino-acid sequence (HDA) that functions as a nuclear export signal. We describe here the identification of a protein we named Caliban, which can directly interact with the HDA. Caliban is homologous to human Sdccag1, which has been implicated in colon and lung cancer. Here we show that Caliban and Sdccag1 are mediators of nuclear export in fly and human cells, as interference RNA abrogates export of EYFP-HDA in normal fly and human lung cells. Caliban functions as a bipartite mediator nuclear export as the carboxy terminus binds HDA and the amino terminus itself functions as an NES, which directly binds the NES receptor Exportin. Finally, while non-cancerous lung cells have functional Sdccag1, five human lung carcinoma cell lines do not, even though Exportin still functions in these cells. Expression of fly Caliban in these human lung cancer cells restores EYFP-HDA nuclear export, reduces a cell's ability to form colonies on soft agar and reduces cell invasiveness. We suggest that Sdccag1 inactivation contributes to the transformed state of human lung cancer cells and that Caliban should be considered a candidate for use in lung cancer gene therapy.

  1. Ribosome-stalk biogenesis is coupled with recruitment of nuclear-export factor to the nascent 60S subunit.

    Science.gov (United States)

    Sarkar, Anshuk; Pech, Markus; Thoms, Matthias; Beckmann, Roland; Hurt, Ed

    2016-12-01

    Nuclear export of preribosomal subunits is a key step during eukaryotic ribosome formation. To efficiently pass through the FG-repeat meshwork of the nuclear pore complex, the large pre-60S subunit requires several export factors. Here we describe the mechanism of recruitment of the Saccharomyces cerevisiae RNA-export receptor Mex67-Mtr2 to the pre-60S subunit at the proper time. Mex67-Mtr2 binds at the premature ribosomal-stalk region, which later during translation serves as a binding platform for translational GTPases on the mature ribosome. The assembly factor Mrt4, a structural homolog of cytoplasmic-stalk protein P0, masks this site, thus preventing untimely recruitment of Mex67-Mtr2 to nuclear pre-60S particles. Subsequently, Yvh1 triggers Mrt4 release in the nucleus, thereby creating a narrow time window for Mex67-Mtr2 association at this site and facilitating nuclear export of the large subunit. Thus, a spatiotemporal mark on the ribosomal stalk controls the recruitment of an RNA-export receptor to the nascent 60S subunit.

  2. Nuclear export and import of human hepatitis B virus capsid protein and particles.

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    Hung-Cheng Li

    Full Text Available It remains unclear what determines the subcellular localization of hepatitis B virus (HBV core protein (HBc and particles. To address this fundamental issue, we have identified four distinct HBc localization signals in the arginine rich domain (ARD of HBc, using immunofluorescence confocal microscopy and fractionation/Western blot analysis. ARD consists of four tight clustering arginine-rich subdomains. ARD-I and ARD-III are associated with two co-dependent nuclear localization signals (NLS, while ARD-II and ARD-IV behave like two independent nuclear export signals (NES. This conclusion is based on five independent lines of experimental evidence: i Using an HBV replication system in hepatoma cells, we demonstrated in a double-blind manner that only the HBc of mutant ARD-II+IV, among a total of 15 ARD mutants, can predominantly localize to the nucleus. ii These results were confirmed using a chimera reporter system by placing mutant or wild type HBc trafficking signals in the heterologous context of SV40 large T antigen (LT. iii By a heterokaryon or homokaryon analysis, the fusion protein of SV40 LT-HBc ARD appeared to transport from nuclei of transfected donor cells to nuclei of recipient cells, suggesting the existence of an NES in HBc ARD. This putative NES is leptomycin B resistant. iv We demonstrated by co-immunoprecipitation that HBc ARD can physically interact with a cellular factor TAP/NXF1 (Tip-associated protein/nuclear export factor-1, which is known to be important for nuclear export of mRNA and proteins. Treatment with a TAP-specific siRNA strikingly shifted cytoplasmic HBc to nucleus, and led to a near 7-fold reduction of viral replication, and a near 10-fold reduction in HBsAg secretion. v HBc of mutant ARD-II+IV was accumulated predominantly in the nucleus in a mouse model by hydrodynamic delivery. In addition to the revised map of NLS, our results suggest that HBc could shuttle rapidly between nucleus and cytoplasm via a novel

  3. In silico analyses of dystrophin Dp40 cellular distribution, nuclear export signals and structure modeling

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    Alejandro Martínez-Herrera

    2015-09-01

    Full Text Available Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular dystrophy gene. This protein is unique since it lacks the C-terminal end of dystrophins. In this data article, we describe the subcellular localization, nuclear export signals and the three-dimensional structure modeling of putative Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear. Changes L93P and L170P are involved in the nuclear localization of Dp40n4 protein. A close analysis of Dp40 protein scored that amino acids 93LEQEHNNLV101 and 168LLLHDSIQI176 could function as NES sequences and the scores are lost in Dp40n4. In addition, the changes L93/170P modify the tertiary structure of putative Dp40 mutants. The analysis showed that changes of residues 93 and 170 from leucine to proline allow the nuclear localization of Dp40 proteins. The data described here are related to the research article entitled “EF-hand domains are involved in the differential cellular distribution of dystrophin Dp40” (J. Aragón et al. Neurosci. Lett. 600 (2015 115–120 [1].

  4. Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA.

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    Pereira, Carina F; Read, Eliot K C; Wise, Helen M; Amorim, Maria J; Digard, Paul

    2017-08-01

    Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted with cellular NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1 polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1 facilitates late viral gene expression by acting as an adaptor between viral mRNAs and the cellular nuclear export machinery to promote their nuclear export.IMPORTANCE Influenza A virus is a major pathogen of a wide variety of mammalian and avian species that threatens public health and food security. A fuller understanding of the virus life cycle is important to aid control strategies. The virus has a small genome that encodes relatively few proteins that are often multifunctional. Here, we characterize a new function for the NS1 protein, showing that, as well as

  5. Importance of dimer formation of myocardin family members in the regulation of their nuclear export.

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    Hayashi, Ken'ichiro; Morita, Tsuyoshi

    2013-01-01

    Myocardin (Mycd) family members function as a transcriptional cofactor for serum response factor (SRF). Dimer formation is necessary to exhibit their function, and the coiled-coil domain (CC) plays a critical role in their dimerization. We have recently revealed a detailed molecular mechanism for their Crm1 (exportin1)-mediated nuclear export. Here, we found other unique significances of the dimerization of Mycd family members. Introduction of mutations in the CC of myocardin-related transcription factor A (MRTF-A) and truncated Mycd resulted in significant decreases in their cytoplasmic localization and increases in their nuclear localization. In accordance with such subcellular localization changes, their binding to Crm1 were reduced. These results indicate that the dimerization of Mycd family members is necessary for their Crm1-mediated nuclear export. We have recently found that the N-terminal region of Mycd consisting of 128 amino acids (Mycd N128) self-associates to Mycd via the central basic domain (CB), resulting in masking the Crm1-binding site. Such self-association of MRTF-A would be unlikely. In this study, we also revealed that the dimerization of Mycd was also necessary for this self-association. Wild-type Mycd activated SRF-mediated transcription more potently than Mycd lacking the Mycd N128 (Mycd ΔN128) did. These results suggest two possible functions of the Mycd N128: 1) stabilization of Mycd dimer to enhance SRF-mediated transcription and 2) positive regulation of the transactivation ability of Mycd. These findings provide a new insight into the functional regulation of Mycd family members.

  6. Presence of a functional but dispensable Nuclear Export Signal in the HTLV-2 Tax protein

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    Kiemer Lars

    2005-11-01

    Full Text Available Abstract Background Human T-cell leukemia virus type 1 and type 2 are related human retroviruses. HTLV-1 is the etiological agent of the Adult T-cell Leukemia/Lymphoma and of the Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy, whereas, HTLV-2 infection has not been formally associated with any T-cell malignancy. HTLV-1 and 2 genomes encode, respectively, the Tax1 and Tax2 proteins whose role is to transactivate the viral promoter. HTLV-1 and HTLV-2 Tax sequences display 28% divergence at the amino acid level. Tax1 is a shuttling protein that possesses both a non canonical nuclear import (NLS and a nuclear export (NES signal. We have recently demonstrated that Tax1 and Tax2 display different subcellular localization and that residues 90–100 are critical for this process. We investigate in the present report, whether Tax2 also possesses a functional NES. Results We first used a NES prediction method to determine whether the Tax2 protein might contain a NES and the results do suggest the presence of a NES sequence in Tax2. Using Green Fluorescent Protein-NES (GFP-NES fusion proteins, we demonstrate that the Tax2 sequence encompasses a functional NES (NES2. As shown by microscope imaging, NES2 is able to mediate translocation of GFP from the nucleus, without the context of a full length Tax protein. Furthermore, point mutations or leptomycin B treatment abrogate NES2 function. However, within the context of full length Tax2, similar point mutations in the NES2 leucine rich stretch do not modify Tax2 localization. Finally, we also show that Tax1 NES function is dependent upon the positioning of the nuclear export signal "vis-à-vis" GFP. Conclusion HTLV-2 Tax NES is functional but dispensable for the protein localization in vitro.

  7. Nuclear Successor States of the Soviet Union, Nuclear Weapon and Sensitive Export Status Report

    Science.gov (United States)

    2016-03-24

    Jane’s Defense Weekly, March 27, 1993, p. 7; "Lineup of Russian Aerospace Power , 1992," Air Force Magazine , July 1993, p. 65; "Nuclear Notebook," The...also JPRS-TND 12/ 8 /93, p. 46] 11/9193 - UNCLASSIFIED REPORT FROM THE U.S. DEPARTMENT OF ENERGY ON BELARUSIAN DELEGATION ATTENDING WORKSHOP (SEPT. 13-17...director of Chernobyl nuclear power plant, in conjunction with the heads of the State Committee on Atomic Energy Usage, the public should not be overly

  8. Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export

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    Marriott Susan J

    2007-12-01

    . Ubiquitination of these residues facilitates the dissociation of Tax from sc35-containing nuclear foci, and stimulates nuclear export of Tax through the CRM1 pathway.

  9. Cellular Nuclear Export Factors TAP and Aly Are Required for HDAg-L-mediated Assembly of Hepatitis Delta Virus.

    Science.gov (United States)

    Huang, Hsiu-Chen; Lee, Chung-Pei; Liu, Hui-Kang; Chang, Ming-Fu; Lai, Yu-Heng; Lee, Yu-Ching; Huang, Cheng

    2016-12-09

    Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus (HBV). HDV genome encodes two forms of hepatitis delta antigen (HDAg), small HDAg (HDAg-S), which is required for viral replication, and large HDAg (HDAg-L), which is essential for viral assembly. HDAg-L is identical to HDAg-S except that it bears a 19-amino acid extension at the C terminus. Both HDAgs contain a nuclear localization signal (NLS), but only HDAg-L contains a CRM1-independent nuclear export signal at its C terminus. The nuclear export activity of HDAg-L is important for HDV particle formation. However, the mechanisms of HDAg-L-mediated nuclear export of HDV ribonucleoprotein are not clear. In this study, the host cellular RNA export complex TAP-Aly was found to form a complex with HDAg-L, but not with an export-defective HDAg-L mutant, in which Pro(205) was replaced by Ala. HDAg-L was found to colocalize with TAP and Aly in the nucleus. The C-terminal domain of HDAg-L was shown to directly interact with the N terminus of TAP, whereas an HDAg-L mutant lacking the NLS failed to interact with full-length TAP. In addition, small hairpin RNA-mediated down-regulation of TAP or Aly reduced nuclear export of HDAg-L and assembly of HDV virions. Furthermore, a peptide, TAT-HDAg-L(198-210), containing the 10-amino acid TAT peptide and HDAg-L(198-210), inhibited the interaction between HDAg-L and TAP and blocked HDV virion assembly and secretion. These data demonstrate that formation and release of HDV particles are mediated by TAP and Aly. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Tus, an E. coli protein, contains mammalian nuclear targeting and exporting signals.

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    Kaczmarczyk, Stanislaw J; Sitaraman, Kalavathy; Hill, Thomas; Hartley, James L; Chatterjee, Deb K

    2010-01-26

    Shuttling of proteins between nucleus and cytoplasm in mammalian cells is facilitated by the presence of nuclear localization signals (NLS) and nuclear export signals (NES), respectively. However, we have found that Tus, an E. coli replication fork arresting protein, contains separate sequences that function efficiently as NLS and NES in mammalian cell lines, as judged by cellular location of GFP-fusion proteins. The NLS was localized to a short stretch of 9 amino acids in the carboxy-terminus of Tus protein. Alterations of any of these basic amino acids almost completely abolished the nuclear targeting. The NES comprises a cluster of leucine/hydrophobic residues located within 21 amino acids at the amino terminus of Tus. Finally, we have shown that purified GFP-Tus fusion protein or GFP-Tus NLS fusion protein, when added to the culture media, was internalized very efficiently into mammalian cells. Thus, Tus is perhaps the first reported bacterial protein to possess both NLS and NES, and has the capability to transduce protein into mammalian cells.

  11. Design data and safety features of commerical nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Heddleson, F.A.

    1976-06-01

    Design data, safety features, and site characteristics are summarized for 34 nuclear power units in 17 power stations in the United States. Six pages of data are presented for each plant, consisting of thermal-hydraulic and nuclear factors, containment features, emergency-core-cooling systems, site features, circulating water system data, and miscellaneous factors. An aerial perspective is also presented for each plant. This volume covers Light Water Reactors (LWRs) with dockets 50-508 through 50-549, four HTGRs--50-171, 50-267, 50-450/451, 50-463/464, the Atlantic Floating Station 50-477/478, and the Clinch River Breeder 50-537.

  12. Comparative analysis of seven viral nuclear export signals (NESs reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP in influenza A virus replication.

    Directory of Open Access Journals (Sweden)

    Nopporn Chutiwitoonchai

    Full Text Available The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Φ residues within this NES consensus sequence (Φ1, Φ2, Φ3, or Φ4 was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP-NES3 Φ2 or Φ3 mutants could be rescued. Consistent with this, the NP-NES3 Φ2 and Φ3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Φ2 and Φ3 residues (along with other Φ residues within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Φ2 and Φ3 residues within the NP-NES3 protein are important for its nuclear export function

  13. Comparative analysis of seven viral nuclear export signals (NESs) reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP) in influenza A virus replication.

    Science.gov (United States)

    Chutiwitoonchai, Nopporn; Kakisaka, Michinori; Yamada, Kazunori; Aida, Yoko

    2014-01-01

    The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES) consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Φ) residues within this NES consensus sequence (Φ1, Φ2, Φ3, or Φ4) was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP-NES3 Φ2 or Φ3 mutants could be rescued. Consistent with this, the NP-NES3 Φ2 and Φ3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Φ2 and Φ3 residues (along with other Φ residues) within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Φ2 and Φ3 residues within the NP-NES3 protein are important for its nuclear export function during viral

  14. Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells.

    Science.gov (United States)

    Lundberg, Lindsay; Pinkham, Chelsea; de la Fuente, Cynthia; Brahms, Ashwini; Shafagati, Nazly; Wagstaff, Kylie M; Jans, David A; Tamir, Sharon; Kehn-Hall, Kylene

    2016-11-01

    The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible. Chemically inhibiting CRM1 with these compounds enhanced capsid localization to the nucleus compared to the inactive compound KPT-301, as indicated by immunofluorescent confocal microscopy. Differences in extracellular versus intracellular viral RNA, as well as decreased capsid in cell free supernatants, indicated the inhibitors affected viral assembly, which led to a decrease in viral titers. The decrease in viral replication was confirmed using a luciferase-tagged virus and through plaque assays. SINE compounds had no effect on VEEV TC83_Cm, which encodes a mutated form of capsid that is unable to enter the nucleus. Serially passaging VEEV in the presence of KPT-185 resulted in mutations within the nuclear localization and nuclear export signals of capsid. Finally, SINE compound treatment also reduced the viral titers of the related eastern and western equine encephalitis viruses, suggesting that CRM1 maintains a common interaction with capsid proteins across the New World alphavirus genus.

  15. Transfection of influenza A virus nuclear export protein induces the expression of tumor necrosis factor alpha.

    Science.gov (United States)

    Lara-Sampablo, Alejandra; Flores-Alonso, Juan Carlos; De Jesús-Ortega, Nereyda; Santos-López, Gerardo; Vallejo-Ruiz, Verónica; Rosas-Murrieta, Nora; Reyes-Carmona, Sandra; Herrera-Camacho, Irma; Reyes-Leyva, Julio

    2014-06-24

    Influenza A virus genomic segments eight codes for non-structural 1 (NS1) protein that is involved in evasion of innate antiviral response, and nuclear export protein (NEP) that participates in the export of viral ribonucleoprotein (RNP) complexes, transcription and replication. Tumor necrosis factor alpha (TNF-α) is highly expressed during influenza virus infections and is considered an anti-infective cytokine. NS1 and NEP proteins were overexpressed and their role on TNF-α expression was evaluated. Both TNF-α mRNA and protein increased in cells transfected with NEP but not with NS1. We further investigate if NS1 or NEP regulates the activity of TNF-α promoter. In the presence of NEP the activity of TNF-α promoter increased significantly compared with the control (83.5±2.9 vs. 30.9±2.8, respectively; p=0.001). This effect decreased 15-fold when the TNF-α promoter distal region was deleted, suggesting the involvement of mitogen-activated protein kinases (MAPK) and NF-kB response elements. This was corroborated by testing the effect produced on TNF-α promoter by the treatment with Raf/MEK/ERK (U0126), NF-kB (Bay-11-7082) and PI3K (Ly294-002) cell signaling inhibitors. Treatment with U0126 and Bay-117082 reduced the activity of TNF-α promoter mediated by NEP (41.5±3.2, 70% inhibition; and 80.6±7.4, 35% inhibition, respectively) compared to mock-treated control. The results suggest a new role for NEP protein that participates in the transcriptional regulation of human TNF-α expression.

  16. Decreased activity and enhanced nuclear export of CCAAT-enhancer-binding protein beta during inhibition of adipogenesis by ceramide.

    Science.gov (United States)

    Sprott, Kam M; Chumley, Michael J; Hanson, Janean M; Dobrowsky, Rick T

    2002-07-01

    To identify novel molecular mechanisms by which ceramide regulates cell differentiation, we examined its effect on adipogenesis of 3T3-L1 preadipocytes. Hormonal stimulation of 3T3-L1 preadipocytes induced formation of triacylglycerol-laden adipocytes over 7 days; in part, via the co-ordinated action of CCAAT-enhancer-binding proteins alpha, beta and delta (C/EBP-alpha, -beta and -delta) and peroxisome-proliferator-activated receptor gamma (PPARgamma). The addition of exogenous N-acetylsphingosine (C2-ceramide) or increasing endogenous ceramide levels inhibited the expression of C/EBPalpha and PPARgamma, and blocked adipocyte development. C2-ceramide did not decrease the cellular expression of C/EBPbeta, which is required for expression of C/EBPalpha and PPARgamma, but significantly blocked its transcriptional activity from a promoter construct after 24 h. The ceramide-induced decrease in the transcriptional activity of C/EBPbeta correlated with a strong decrease in its phosphorylation, DNA-binding ability and nuclear localization at 24 h. However, ceramide did not change the nuclear level of C/EBPbeta after a period of 4 or 16 h, suggesting that it was not affecting nuclear import. CRM1 (more recently named 'exportin-1') is a nuclear membrane protein that regulates protein export from the nucleus by binding to a specific nuclear export sequence. Leptomycin B is an inhibitor of CRM1/exportin-1, and reversed the ceramide-induced decrease in nuclear C/EBPbeta at 24 h. Taken together, these data support the hypothesis that ceramide may inhibit adipogenesis, at least in part, by enhancing dephosphorylation and premature nuclear export of C/EBPbeta at a time when its maximal transcriptional activity is required to drive adipogenesis.

  17. Erythropoietin and carbamylated erythropoietin promote histone deacetylase 5 phosphorylation and nuclear export in rat hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Hye-Ryeong [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Kim, Yong-Seok [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791 (Korea, Republic of); Son, Hyeon, E-mail: hyeonson@hanyang.ac.kr [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791 (Korea, Republic of)

    2016-01-29

    Erythropoietin (EPO) produces neurotrophic effects in animal model of neurodegeneration. However, clinical use of EPO is limited due to thrombotic risk. Carbamylated EPO (cEPO), devoid of thrombotic risk, has been proposed as a novel neuroprotective and neurotrophic agent although the molecular mechanisms of cEPO remain incomplete. Here, we show a previously unidentified role of histone deacetylase 5 (HDAC5) in the actions of EPO and cEPO. EPO and cEPO regulate the HDAC5 phosphorylation at two critical sites, Ser259 and Ser498 through a protein kinase D (PKD) dependent pathway. In addition, EPO and cEPO rapidly stimulates nuclear export of HDAC5 in rat hippocampal neurons which expressing HDAC5-GFP. Consequently, EPO and cEPO enhanced the myocyte enhancer factor-2 (MEF2) target gene expression. Taken together, our results reveal that EPO and cEPO mediate MEF2 target gene expression via the regulation of HDAC5 phosphorylation at Ser259/498, and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of EPO and cEPO.

  18. AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.

    Science.gov (United States)

    Corum, Daniel G; Tsichlis, Philip N; Muise-Helmericks, Robin C

    2014-01-01

    Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1α and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1α nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1α target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (~5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ~1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.

  19. [Polyadenylated RNA and mRNA export factors in extrachromosomal nuclear domains of vitellogenic oocytes of the insect Tenebrio molitor].

    Science.gov (United States)

    Bogoliubov, D S; Kiselev, A M; Shabel'nikov, S V; Parfenov, V N

    2012-01-01

    The nucleus ofvitellogenic oocytes of the yellow mealworm, Tenebrio molitor, contains a karyosphere that consists of the condensed chromatin embedded in an extrachromosomal fibrogranular material. Numerous nuclear bodies located freely in the nucleoplasm are also observed. Amongst these bodies, counterparts of nuclear speckles (= interchromatin granule clusters, IGCs) can be identified by the presence of the marker protein SC35. Microinjections of fluorescently tagged methyloligoribonucleotide probes 2'-O-Me(U)22, complementary to poly(A) tails of RNAs, revealed poly(A)+ RNA in the vast majority of IGCs. We found that all T. molitor oocyte IGCs contain heterogeneous ribonucleoprotein (hnRNP) core protein Al that localizes to IGCs in an RNA-dependent manner. The extrachromosomal material of the karyosphere and a part of nucleoplasmic IGCs also contain the adapter protein Aly that is known to provide a link between pre-mRNA splicing and mRNA export. The essential mRNA export factor/receptor NXF1 was observed to colocalize with Aly. In nucleoplasmic IGCs, NXF1 was found to localize in an RNA-dependent manner whereas it is RNA-independently located in the extrachromosomal material of the karyosphere. We believe our data suggest on a role of the nucleoplasmic IGCs in mRNA biogenesis and retention in a road to nuclear export.

  20. Heterozygous mutation of cysteine528 in XPO1 is sufficient for resistance to selective inhibitors of nuclear export.

    Science.gov (United States)

    Neggers, Jasper Edgar; Vanstreels, Els; Baloglu, Erkan; Shacham, Sharon; Landesman, Yosef; Daelemans, Dirk

    2016-10-18

    Exportin-1 (CRM1/XPO1) is a crucial nuclear export protein that transports a wide variety of proteins from the nucleus to the cytoplasm. These cargo proteins include tumor suppressors and growth-regulatory factors and as such XPO1 is considered a potential anti-cancer target. From this perspective, inhibition of the XPO1-mediated nuclear export by selective inhibitor of nuclear export (SINE) compounds has shown broad-spectrum anti-cancer activity. Furthermore, the clinical candidate SINE, selinexor, is currently in multiple phase I/II/IIb trials for treatment of cancer. Resistance against selinexor has not yet been observed in the clinic, but in vitro selection of resistance did not reveal any mutations in the target protein, XPO1. However, introduction of a homozygous mutation at the drug's target site, the cysteine 528 residue inside the XPO1 cargo-binding pocket, by genetic engineering, confers resistance to selinexor. Here we investigated whether this resistance to selinexor is recessive or dominant. For this purpose we have engineered multiple leukemia cell lines containing heterozygous or homozygous C528S substitutions using CRISPR/Cas9-mediated genome editing. Our findings show that heterozygous mutation confers similar resistance against selinexor as homozygous substitution, demonstrating that SINE resistance can be obtained by a single and dominant mutation of the cysteine528 residue in XPO1.

  1. SCW Pressure-Channel Nuclear Reactor Some Design Features

    Science.gov (United States)

    Pioro, Igor L.; Khan, Mosin; Hopps, Victory; Jacobs, Chris; Patkunam, Ruban; Gopaul, Sandeep; Bakan, Kurtulus

    Concepts of nuclear reactors cooled with water at supercritical pressures were studied as early as the 1950s and 1960s in the USA and Russia. After a 30-year break, the idea of developing nuclear reactors cooled with SuperCritical Water (SCW) became attractive again as the ultimate development path for water cooling. The main objectives of using SCW in nuclear reactors are: 1) to increase the thermal efficiency of modern Nuclear Power Plants (NPPs) from 30-35% to about 45-48%, and 2) to decrease capital and operational costs and hence decrease electrical energy costs (˜1000 US/kW or even less). SCW NPPs will have much higher operating parameters compared to modern NPPs (pressure about 25 MPa and outlet temperature up to 625°C), and a simplified flow circuit, in which steam generators, steam dryers, steam separators, etc., can be eliminated. Also, higher SCW temperatures allow direct thermo-chemical production of hydrogen at low cost, due to increased reaction rates. Pressure-tube or pressure-channel SCW nuclear reactor concepts are being developed in Canada and Russia for some time. Some design features of the Canadian concept related to fuel channels are discussed in this paper. The main conclusion is that the development of SCW pressure-tube nuclear reactors is feasible and significant benefits can be expected over other thermal-energy systems.

  2. eEF1A Mediates the Nuclear Export of SNAG-Containing Proteins via the Exportin5-Aminoacyl-tRNA Complex

    Directory of Open Access Journals (Sweden)

    José Manuel Mingot

    2013-11-01

    Full Text Available Exportin5 mediates the nuclear export of double-stranded RNAs, including pre-microRNAs, adenoviral RNAs, and tRNAs. When tRNAs are aminoacylated, the Exportin5-aminoacyl (aa-tRNA complex recruits and coexports the translation elongation factor eEF1A. Here, we show that eEF1A binds to Snail transcription factors when bound to their main target, the E-cadherin promoter, facilitating their export to the cytoplasm in association with the aa-tRNA-Exportin5 complex. Snail binds to eEF1A through the SNAG domain, a protein nuclear export signal present in several transcription factor families, and this binding is regulated by phosphorylation. Thus, we describe a nuclear role for eEF1A and provide a mechanism for protein nuclear export that attenuates the activity of SNAG-containing transcription factors.

  3. eEF1A mediates the nuclear export of SNAG-containing proteins via the Exportin5-aminoacyl-tRNA complex.

    Science.gov (United States)

    Mingot, José Manuel; Vega, Sonia; Cano, Amparo; Portillo, Francisco; Nieto, M Angela

    2013-11-14

    Exportin5 mediates the nuclear export of double-stranded RNAs, including pre-microRNAs, adenoviral RNAs, and tRNAs. When tRNAs are aminoacylated, the Exportin5-aminoacyl (aa)-tRNA complex recruits and coexports the translation elongation factor eEF1A. Here, we show that eEF1A binds to Snail transcription factors when bound to their main target, the E-cadherin promoter, facilitating their export to the cytoplasm in association with the aa-tRNA-Exportin5 complex. Snail binds to eEF1A through the SNAG domain, a protein nuclear export signal present in several transcription factor families, and this binding is regulated by phosphorylation. Thus, we describe a nuclear role for eEF1A and provide a mechanism for protein nuclear export that attenuates the activity of SNAG-containing transcription factors.

  4. New Features in the Computational Infrastructure for Nuclear Astrophysics

    Science.gov (United States)

    Smith, Michael S.; Lingerfelt, Eric J.; Hix, W. Raphael; Nesaraja, Caroline D.; Thomsen, Kyle

    2011-10-01

    The Computational Infrastructure for Nuclear Astrophysics (CINA) is a platform- independent suite of computer codes that are freely available online at http://nucastrodata.org. The system enhances the utilization of nuclear data by streamlining the process to include the latest data into astrophysics simulations. Users can upload measured or calculated cross sections, process them into reaction rates, incorporate rates into libraries, run simulations with these custom libraries, and store and visualize the results -- all with a simple graphical user interface. New features in CINA include: automated studies of the sensitivity of astrophysical predictions on nuclear input; calculation of thermonuclear reaction rates from resonance information; and the ability to extract information from several additional international databases. Several utilizations of, and future plans for, this software suite will be given.

  5. NXT1, a Novel Influenza A NP Binding Protein, Promotes the Nuclear Export of NP via a CRM1-Dependent Pathway.

    Science.gov (United States)

    Chutiwitoonchai, Nopporn; Aida, Yoko

    2016-07-28

    Influenza remains a serious worldwide public health problem. After infection, viral genomic RNA is replicated in the nucleus and packed into viral ribonucleoprotein, which will then be exported to the cytoplasm via a cellular chromosome region maintenance 1 (CRM1)-dependent pathway for further assembly and budding. However, the nuclear export mechanism of influenza virus remains controversial. Here, we identify cellular nuclear transport factor 2 (NTF2)-like export protein 1 (NXT1) as a novel binding partner of nucleoprotein (NP) that stimulates NP-mediated nuclear export via the CRM1-dependent pathway. NXT1-knockdown cells exhibit decreased viral replication kinetics and nuclear accumulated viral RNA and NP. By contrast, NXT1 overexpression promotes nuclear export of NP in a CRM1-dependent manner. Pull-down assays suggest the formation of an NXT1, NP, and CRM1 complex, and demonstrate that NXT1 binds to the C-terminal region of NP. These findings reveal a distinct mechanism for nuclear export of the influenza virus and identify the NXT1/NP interaction as a potential target for antiviral drug development.

  6. An essential nuclear protein in trypanosomes is a component of mRNA transcription/export pathway.

    Directory of Open Access Journals (Sweden)

    Mariana Serpeloni

    Full Text Available In eukaryotic cells, different RNA species are exported from the nucleus via specialized pathways. The mRNA export machinery is highly integrated with mRNA processing, and includes a different set of nuclear transport adaptors as well as other mRNA binding proteins, RNA helicases, and NPC-associated proteins. The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, a widespread and neglected human disease which is endemic to Latin America. Gene expression in Trypanosoma has unique characteristics, such as constitutive polycistronic transcription of protein-encoding genes and mRNA processing by trans-splicing. In general, post-transcriptional events are the major points for regulation of gene expression in these parasites. However, the export pathway of mRNA from the nucleus is poorly understood. The present study investigated the function of TcSub2, which is a highly conserved protein ortholog to Sub2/ UAP56, a component of the Transcription/Export (TREX multiprotein complex connecting transcription with mRNA export in yeast/human. Similar to its orthologs, TcSub2 is a nuclear protein, localized in dispersed foci all over the nuclei -except the fibrillar center of nucleolus- and at the interface between dense and non-dense chromatin areas, proposing the association of TcSub2 with transcription/processing sites. These findings were analyzed further by BrUTP incorporation assays and confirmed that TcSub2 is physically associated with active RNA polymerase II (RNA pol II, but not RNA polymerase I (RNA pol I or Spliced Leader (SL transcription, demonstrating participation particularly in nuclear mRNA metabolism in T. cruzi. The double knockout of the TcSub2 gene is lethal in T. cruzi, suggesting it has an essential function. Alternatively, RNA interference assays were performed in Trypanosoma brucei. It allowed demonstrating that besides being an essential protein, its knockdown causes mRNA accumulation in the nucleus and

  7. Integration of renewable energies and nuclear power into North African Energy Systems: An analysis of energy import and export effects

    Energy Technology Data Exchange (ETDEWEB)

    Supersberger, Nikolaus, E-mail: nikolaus.supersberger@giz.de [Wuppertal Institute for Climate, Environment, Energy, P.O. Box 10 04 80, 42004 Wuppertal (Germany); Fuehrer, Laura, E-mail: laura.fuhrer@sciences-po.org [Sciences Po Paris, College Universitaire, Campus de Menton, du College Chemin du College, 06500 Menton (France)

    2011-08-15

    The North African countries Morocco, Algeria, Tunisia, Libya and Egypt have been and are currently experiencing rapid growth in energy demand. This development confronts their political leaders with the question of how to expand or diversify their countries' generation capacities. In this context, renewable energies and nuclear power constitute options that have rarely been exploited so far in the region. This article analyzes the drawbacks and benefits of both alternatives, with a special focus on import and export dynamics. When attempting to make the strategic decision between renewables and atomic power, North African regional specifics and circumstances have to be taken into account. Hence, in a first step, the article characterizes the energy systems of the North African countries and presents scenarios for their future development. In a second step, it scrutinizes the energy challenges these states face in terms of domestic concerns and foreign affairs. Finally, a case study of Algeria is used to demonstrate how renewable energies, but not nuclear power, are able to respond to North African energy challenges. - Research Highlights: > Using nuclear power would require fuel imports over the entire operation time. > Hence, energy exporters (Algeria, Libya) would become dependent on fuel imports. > Renewable energies can make North African countries less fuel import dependent. > Nuclear technologies would have to be imported over the whole life cycle of plants. > Domestic production for renewables technologies could be established after a first phase of technology imports.

  8. Nuclear export regulation of COP1 by 14-3-3σ in response to DNA damage

    Directory of Open Access Journals (Sweden)

    Chen Jian

    2010-09-01

    Full Text Available Abstract Mammalian constitutive photomorphogenic 1 (COP1 is a p53 E3 ubiquitin ligase involved in regulating p53 protein level. In plants, the dynamic cytoplasm/nucleus distribution of COP1 is important for its function in terms of catalyzing the degradation of target proteins. In mammalian cells, the biological consequence of cytoplasmic distribution of COP1 is not well characterized. Here, we show that DNA damage leads to the redistribution of COP1 to the cytoplasm and that 14-3-3σ, a p53 target gene product, controls COP1 subcellular localization. Investigation of the underlying mechanism suggests that COP1 S387 phosphorylation is required for COP1 to bind 14-3-3σ. Significantly, upon DNA damage, 14-3-3σ binds to phosphorylated COP1 at S387, resulting in COP1's accumulation in the cytoplasm. Cytoplasmic COP1 localization leads to its enhanced ubiquitination. We also show that N-terminal 14-3-3σ interacts with COP1 and promotes COP1 nuclear export through its NES sequence. Further, we show that COP1 is important in causing p53 nuclear exclusion. Finally, we demonstrate that 14-3-3σ targets COP1 for nuclear export, thereby preventing COP1-mediated p53 nuclear export. Together, these results define a novel, detailed mechanism for the subcellular localization and regulation of COP1 after DNA damage and provide a mechanistic explanation for the notion that 14-3-3σ's impact on the inhibition of p53 E3 ligases is an important step for p53 stabilization after DNA damage.

  9. Water monitoring as a safety feature for nuclear desalination

    Energy Technology Data Exchange (ETDEWEB)

    Masriera, N.A. [Nuclear Engineering Department, INVAP, Bariloche, Rio Negro (Argentina)]. E-mail: masriera@invap.com.ar; Doval, A.S.; Di Tada, M.L. [Nuclear Engineering Department, INVAP, Bariloche, Rio Negro (Argentina)

    2006-07-01

    It is widely accepted that the general safety approach for nuclear facilities is valid for a Nuclear Desalination Plant (NDP), thus IAEA standards and guides are applicable. The coupling of a NDP should be designed with the safety objective of ensuring that it results in no adverse effect on the Nuclear Power Plant (NPP) safety. The first objective (provisions of barriers) is complied with by the known NDP design, so the relevant issue becomes the design features preventing the transfer of radioactive material to the product water, even in the event of system failures. This presentation drafts a coupling-system safety assessment, from fundamentals and general requirements down to specific design requirements. The state of the art of monitoring systems imposes constraints on the coupling design, in terms of hold-up capability and piping interconnection. This conceptual design shows the system's complexity implied in having monitoring of product water as a safety feature, and conclusions are extremely relevant when drafting general user requirements for a NDP project. (author)

  10. Cooperation of nuclear manpower development between Viet Nam and Korea in order to enhance establishment of infrastructure in exporting nuclear technology to Viet Nam

    Energy Technology Data Exchange (ETDEWEB)

    Lee, E. J.; Han, K. W.; Park, J. K.; Kim, Y. T.; Nam, Y. M.; Jang, Y. H.; Yang, M. H

    2003-08-15

    Through this project, KAERI provided OJT Programme to 3 nuclear experts of Viet Nam at the KAERI for 3 months as a cooperation of human resource development in the field of nuclear policy, nuclear safety analysis and thermo hydraulic. We could have publicity activities of S/W and H/W then achieve an advantage position of economical and technical in exporting nuclear technology to Viet Nam. Also we have provided a training course and seminar for a high-level delegation of nuclear policy decision makers, which is consisted of 5 deputy ministers and general directors of Viet Nam in Korea. Thus we could have Vietnamese who are favoring Korea. The KAERI will also prepare a data base of trained Vietnamese in Korea for the maximum utilization of them in cooperating with Viet Nam. We accomplished the cooperation of human resource development and providing program and curriculum of the nuclear education and training in Viet Nam. Furthermore, it is expected that the enhancement of nuclear technical cooperation between Viet Nam and Korea and the nuclear human resource development.

  11. Structural Basis for the Function of the Saccharomyces cerevisiae Gfd1 Protein in mRNA Nuclear Export* ♦

    OpenAIRE

    Zheng, Chao; Fasken, Milo B.; Marshall, Neil J.; Brockmann, Christoph; Rubinson, Max E.; Wente, Susan R.; Corbett, Anita H.; Stewart, Murray

    2010-01-01

    Following transcription, mRNA is processed, packaged into messenger ribonucleoprotein (mRNP) particles, and transported through nuclear pores (NPCs) to the cytoplasm. At the NPC cytoplasmic face, Dbp5 mediates mRNP remodeling and mRNA export factor dissociation, releasing transcripts for translation. In Saccharomyces cerevisiae, the conserved poly(A) RNA-binding protein, Nab2, facilitates NPC targeting of transcripts and also modulates poly(A) tail length. Dbp5 removes Nab2 from mRNPs at the ...

  12. Updated Mars Mission Architectures Featuring Nuclear Thermal Propulsion

    Science.gov (United States)

    Rodriguez, Mitchell A.; Percy, Thomas K.

    2017-01-01

    Nuclear thermal propulsion (NTP) can potentially enable routine human exploration of Mars and the solar system. By using nuclear fission instead of a chemical combustion process, and using hydrogen as the propellant, NTP systems promise rocket efficiencies roughly twice that of the best chemical rocket engines currently available. The most recent major Mars architecture study featuring NTP was the Design Reference Architecture 5.0 (DRA 5.0), performed in 2009. Currently, the predominant transportation options being considered are solar electric propulsion (SEP) and chemical propulsion; however, given NTP's capabilities, an updated architectural analysis is needed. This paper provides a top-level overview of several different architectures featuring updated NTP performance data. New architectures presented include a proposed update to the DRA 5.0 as well as an investigation of architectures based on the current Evolvable Mars Campaign, which is the focus of NASA's current analyses for the Journey to Mars. Architectures investigated leverage the latest information relating to NTP performance and design considerations and address new support elements not available at the time of DRA 5.0, most notably the Orion crew module and the Space Launch System (SLS). The paper provides a top level quantitative comparison of key performance metrics as well as a qualitative discussion of improvements and key challenges still to be addressed. Preliminary results indicate that the updated NTP architectures can significantly reduce the campaign mass and subsequently the costs for assembly and number of launches.

  13. Functional Significance of the Interaction between the mRNA-binding Protein, Nab2, and the Nuclear Pore-associated Protein, Mlp1, in mRNA Export* S⃞

    OpenAIRE

    Fasken, Milo B.; Stewart, Murray; Corbett, Anita H.

    2008-01-01

    Nuclear export of mRNA requires several key mRNA-binding proteins that recognize and remodel the mRNA and target it for export via interactions with the nuclear pore complex. In Saccharomyces cerevisiae, the shuttling heterogeneous nuclear ribonucleoprotein, Nab2, which is essential for mRNA export, specifically recognizes poly(A) RNA and binds to the nuclear pore-associated protein, myosin-like protein 1 (Mlp1), which functions in mRNA export and quality control. Specifically, the N-terminal...

  14. Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p.

    Science.gov (United States)

    Koyama, Masako; Hirano, Hidemi; Shirai, Natsuki; Matsuura, Yoshiyuki

    2017-08-08

    Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif. The crystal structure of Xpo1p-PKI-Nup42p-Gsp1p-GTP complex identified three binding sites for the SxFG/PxFG repeats on HEAT repeats 14-20 of Xpo1p. Mutational analyses of Nup42p showed that the conserved serines and prolines in the SxFG/PxFG repeats contribute to Xpo1p-Nup42p binding. Our structural and biochemical data suggest that SxFG/PxFG-Nups such as Nup42p and Nup159p at the cytoplasmic face of NPCs provide high-affinity docking sites for the Xpo1p nuclear export complex in the terminal stage of NPC passage and that subsequent disassembly of the nuclear export complex facilitates recycling of free Xpo1p back to the nucleus. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  15. A method for quantification of exportin-1 (XPO1) occupancy by Selective Inhibitor of Nuclear Export (SINE) compounds.

    Science.gov (United States)

    Crochiere, Marsha L; Baloglu, Erkan; Klebanov, Boris; Donovan, Scott; Del Alamo, Diego; Lee, Margaret; Kauffman, Michael; Shacham, Sharon; Landesman, Yosef

    2016-01-12

    Selective Inhibitor of Nuclear Export (SINE) compounds are a family of small-molecules that inhibit nuclear export through covalent binding to cysteine 528 (Cys528) in the cargo-binding pocket of Exportin 1 (XPO1/CRM1) and promote cancer cell death. Selinexor is the lead SINE compound currently in phase I and II clinical trials for advanced solid and hematological malignancies. In an effort to understand selinexor-XPO1 interaction and to establish whether cancer cell response is a function of drug-target engagement, we developed a quantitative XPO1 occupancy assay. Biotinylated leptomycin B (b-LMB) was utilized as a tool compound to measure SINE-free XPO1. Binding to XPO1 was quantitated from SINE compound treated adherent and suspension cells in vitro, dosed ex vivo human peripheral blood mononuclear cells (PBMCs), and PBMCs from mice dosed orally with drug in vivo. Evaluation of a panel of selinexor sensitive and resistant cell lines revealed that resistance was not attributed to XPO1 occupancy by selinexor. Administration of a single dose of selinexor bound XPO1 for minimally 72 hours both in vitro and in vivo. While XPO1 inhibition directly correlates with selinexor pharmacokinetics, the biological outcome of this inhibition depends on modulation of pathways downstream of XPO1, which ultimately determines cancer cell responsiveness.

  16. Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats

    Science.gov (United States)

    Choi, Miyeon; Lee, Seung Hoon; Wang, Sung Eun; Ko, Seung Yeon; Song, Mihee; Choi, June-Seek; Duman, Ronald S.; Son, Hyeon

    2015-01-01

    Ketamine produces rapid antidepressant-like effects in animal assays for depression, although the molecular mechanisms underlying these behavioral actions remain incomplete. Here, we demonstrate that ketamine rapidly stimulates histone deacetylase 5 (HDAC5) phosphorylation and nuclear export in rat hippocampal neurons through calcium/calmodulin kinase II- and protein kinase D-dependent pathways. Consequently, ketamine enhanced the transcriptional activity of myocyte enhancer factor 2 (MEF2), which leads to regulation of MEF2 target genes. Transfection of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 replaced by Ala259/Ala498, HDAC5-S/A), resulted in resistance to ketamine-induced nuclear export, suppression of ketamine-mediated MEF2 transcriptional activity, and decreased expression of MEF2 target genes. Behaviorally, viral-mediated hippocampal knockdown of HDAC5 blocked or occluded the antidepressant effects of ketamine both in unstressed and stressed animals. Taken together, our results reveal a novel role of HDAC5 in the actions of ketamine and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of ketamine. PMID:26647181

  17. The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export.

    Science.gov (United States)

    Port, Sarah A; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H

    2016-10-28

    Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A)(+) RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A)(+) RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors.

  18. Project for export system construction of nuclear equipment to IAEA; survey on current market status of the nuclear related international organizations and the domestic possible suppliers

    Energy Technology Data Exchange (ETDEWEB)

    Min, T. S.; Cho, H. K.; Kim, H. J. [Korea Atomic Industrial Forum, Seoul (Korea)

    2001-05-01

    Republic of Korea are keeping the dynamic activities in IAEA as the 8th advanced nuclear country over the world but has occupied very low late less than 0.01% in supplying the equipments to IAEA. About 6,000 nuclear equipment suppliers are registered in IAEA Supply Roster over the world but only 3 Suppliers of our country are registered in IAEA Supply Roster. The supply of nuclear industrial products equivalent to about 100 million dollars into IAEA market will endorse not only the international authorization for our technology and products but also give contribution to activate the domestic nuclear industries in order to increase its expert. The explanation for IAEA procurement market to the 53 nuclear companies will be made on May 16, 2001, and the participants for the export of their goods will be selected. And then we will do all possible supports by the government and related organizations for them to register in IAEA Supply Roster. 21 refs. (Author)

  19. Nuclear export of human hepatitis B virus core protein and pregenomic RNA depends on the cellular NXF1-p15 machinery.

    Science.gov (United States)

    Yang, Ching-Chun; Huang, Er-Yi; Li, Hung-Cheng; Su, Pei-Yi; Shih, Chiaho

    2014-01-01

    Hepatitis B virus (HBV) core protein (HBc) can shuttle between nucleus and cytoplasm. Cytoplasm-predominant HBc is clinically associated with severe liver inflammation. Previously, we found that HBc arginine-rich domain (ARD) can associate with a host factor NXF1 (TAP) by coimmunoprecipitation. It is well known that NXF1-p15 heterodimer can serve as a major export receptor of nuclear mRNA as a ribonucleoprotein complex (RNP). In the NXF1-p15 pathway, TREX (transcription/export) complex plays an important role in coupling nuclear pre-mRNA processing with mRNA export in mammalian cells. Here, we tested the hypothesis whether HBc and HBV specific RNA can be exported via the TREX and NXF1-p15 mediated pathway. We demonstrated here that HBc can physically and specifically associate with TREX components, and the NXF1-p15 export receptor by coimmunoprecipitation. Accumulation of HBc protein in the nucleus can be induced by the interference with TREX and NXF1-p15 mediated RNA export machinery. HBV transcripts encodes a non-spliced 3.5 kb pregenomic RNA (pgRNA) which can serve as a template for reverse transcription. Cytoplasmic HBV pgRNA appeared to be reduced by siRNA treatment specific for the NXF1-p15 complex by quantitative RT-qPCR and Northern blot analyses. This result suggests that the pgRNA was also exported via the NXF1-p15 machinery. We entertain the hypothesis that HBc protein can be exported as an RNP cargo via the mRNA export pathway by hijacking the TREX and NXF1-p15 complex. In our current and previous studies, HBc is not required for pgRNA accumulation in the cytoplasm. Furthermore, HBc ARD can mediate nuclear export of a chimeric protein containing HBc ARD in a pgRNA-independent manner. Taken together, it suggests that while both pgRNA and HBc protein exports are dependent on NXF1-p15, they are using the same export machinery in a manner independent of each other.

  20. Overexpression of Ran GTPase Components Regulating Nuclear Export, but not Mitotic Spindle Assembly, Marks Chromosome Instability and Poor Prognosis in Breast Cancer.

    Science.gov (United States)

    Vaidyanathan, Srividya; Thangavelu, Pulari U; Duijf, Pascal H G

    2016-10-01

    Ran GTPase regulates nuclear import, nuclear export, and mitotic spindle assembly. The multifunctional involvement of seventeen Ran GTPase components in these processes has complicated research into how each contributes to cancer development. To assess whether individual and process-specific misexpression of Ran GTPase components contribute to chromosome instability (CIN) and worsen breast cancer patient prognosis. Using publicly available datasets, we studied the degree of misexpression of all Ran GTPase signaling components in breast cancer, assessed their involvement in CIN and used four clinical tests to evaluate whether their misregulation may constitute independent prognostic predictors. A significant majority of Ran GTPase signaling components is overexpressed in breast cancer. Strikingly, spindle assembly components are overexpressed and associated with CIN with only marginal significance and four independent tests indicate that this does not worsen patient outcome. Overexpression of nuclear import components is neither CIN-associated nor clinically significant. In sharp contrast, overexpression of nuclear export components constitutes a strong independent marker for both CIN and poor patient prognosis. We identify Exportin 2/CSE1L, Exportin 3/XPOT, Exportin 5/XPO5, and RANBP1 as novel potential targets. We find that overexpression of Ran GTPase components involved in nuclear export, but not nuclear import or mitotic spindle assembly, is a strong CIN-associated marker for poor breast cancer prognosis. This could mean that increased nuclear export (of, for instance, pRb, p53, p73, BRCA1, p21, p27, E2F4, IκB, survivin), rather than spindle defects, mainly drives CIN and tumorigenesis. Hence, selective inhibitors of nuclear export may be effective for treating the most aggressive and chromosomally unstable breast cancers.

  1. Elevated expression of the nuclear export protein, Crm1 (exportin 1), associates with human oesophageal squamous cell carcinoma.

    Science.gov (United States)

    van der Watt, Pauline J; Zemanay, Widaad; Govender, Dhirendra; Hendricks, Denver T; Parker, M I; Leaner, Virna D

    2014-08-01

    The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components. Crm1 has recently been reported to be highly expressed in certain types of cancers, yet its expression in oesophageal cancer has not been investigated to date. We investigated the expression of Crm1 in normal and tumour tissues derived from 56 patients with human oesophageal squamous cell carcinoma and its functional significance in oesophageal cancer cell line models. Immunohistochemistry revealed that Crm1 expression was significantly elevated in oesophageal tumour tissues compared to normal tissues and its localisation shifted from predominantly nuclear to nuclear and cytoplasmic. Real‑time RT‑PCR revealed that Crm1 expression was elevated at the mRNA level. To determine the functional significance of elevated Crm1 expression in oesophageal cancer, its expression was inhibited using siRNA, and a significant decrease in cell proliferation was observed associated with G1 cell cycle arrest and the induction of apoptosis. Similarly, leptomycin B (LMB) treatment resulted in the effective killing of oesophageal cancer cells at nanomolar concentrations. Normal oesophageal epithelial cells, however, were much less sensitive to Crm1 inhibition with siRNA and LMB. Together, this study reveals that Crm1 expression is increased in oesophageal cancer and is required for the proliferation and survival of oesophageal cancer cells.

  2. The Anti-inflammatory Prostaglandin 15-Deoxy-Δ12,14-PGJ2 Inhibits CRM1-dependent Nuclear Protein Export*

    OpenAIRE

    Hilliard, Mark; Frohnert, Cornelia; Spillner, Christiane; Marcone, Simone; Nath, Annegret; Lampe, Tina; Fitzgerald, Desmond J; Kehlenbach, Ralph H.

    2010-01-01

    The signaling molecule 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has been described as the “anti-inflammatory prostaglandin.” Here we show that substrates of the nuclear export receptor CRM1 accumulate in the nucleus in the presence of 15d-PGJ2, identifying this prostaglandin as a regulator of CRM1-dependent nuclear protein export that can be produced endogenously. Like leptomycin B (LMB), an established fungal CRM1-inhibitor, 15d-PGJ2 reacts with a conserved cysteine residue in the CRM1 se...

  3. Expanded polyglutamine domain possesses nuclear export activity which modulates subcellular localization and toxicity of polyQ disease protein via exportin-1.

    Science.gov (United States)

    Chan, Wing Man; Tsoi, Ho; Wu, Chi Chung; Wong, Chi Hang; Cheng, Tat Cheung; Li, Hoi Yeung; Lau, Kwok Fai; Shaw, Pang Chui; Perrimon, Norbert; Chan, Ho Yin Edwin

    2011-05-01

    Polyglutamine (polyQ) diseases are a group of late-onset, progressive neurodegenerative disorders caused by CAG trinucleotide repeat expansion in the coding region of disease genes. The cell nucleus is an important site of pathology in polyQ diseases, and transcriptional dysregulation is one of the pathologic hallmarks observed. In this study, we showed that exportin-1 (Xpo1) regulates the nucleocytoplasmic distribution of expanded polyQ protein. We found that expanded polyQ protein, but not its unexpanded form, possesses nuclear export activity and interacts with Xpo1. Genetic manipulation of Xpo1 expression levels in transgenic Drosophila models of polyQ disease confirmed the specific nuclear export role of Xpo1 on expanded polyQ protein. Upon Xpo1 knockdown, the expanded polyQ protein was retained in the nucleus. The nuclear disease protein enhanced polyQ toxicity by binding to heat shock protein (hsp) gene promoter and abolished hsp gene induction. Further, we uncovered a developmental decline of Xpo1 protein levels in vivo that contributes to the accumulation of expanded polyQ protein in the nucleus of symptomatic polyQ transgenic mice. Taken together, we first showed that Xpo1 is a nuclear export receptor for expanded polyQ domain, and our findings establish a direct link between protein nuclear export and the progressive nature of polyQ neurodegeneration.

  4. Nuclear Factor 90, a cellular dsRNA binding protein inhibits the HIV Rev-export function

    Directory of Open Access Journals (Sweden)

    St-Laurent Georges

    2006-11-01

    Full Text Available Abstract Background The HIV Rev protein is known to facilitate export of incompletely spliced and unspliced viral transcripts to the cytoplasm, a necessary step in virus life cycle. The Rev-mediated nucleo-cytoplasmic transport of nascent viral transcripts, dependents on interaction of Rev with the RRE RNA structural element present in the target RNAs. The C-terminal variant of dsRNA-binding nuclear protein 90 (NF90ctv has been shown to markedly attenuate viral replication in stably transduced HIV-1 target cell line. Here we examined a mechanism of interference of viral life cycle involving Rev-NF90ctv interaction. Results Since Rev:RRE complex formations depend on protein:RNA and protein:protein interactions, we investigated whether the expression of NF90ctv might interfere with Rev-mediated export of RRE-containing transcripts. When HeLa cells expressed both NF90ctv and Rev protein, we observed that NF90ctv inhibited the Rev-mediated RNA transport. In particular, three regions of NF90ctv protein are involved in blocking Rev function. Moreover, interaction of NF90ctv with the RRE RNA resulted in the expression of a reporter protein coding sequences linked to the RRE structure. Moreover, Rev influenced the subcellular localization of NF90ctv, and this process is leptomycin B sensitive. Conclusion The dsRNA binding protein, NF90ctv competes with HIV Rev function at two levels, by competitive protein:protein interaction involving Rev binding to specific domains of NF90ctv, as well as by its binding to the RRE-RNA structure. Our results are consistent with a model of Rev-mediated HIV-1 RNA export that envisions Rev-multimerization, a process interrupted by NF90ctv.

  5. Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export of unspliced RNA.

    Science.gov (United States)

    Rajanala, Kalpana; Nandicoori, Vinay Kumar

    2012-01-01

    Nucleoporin Tpr is a component of the nuclear pore complex (NPC) that localizes exclusively to intranuclear filaments. Tpr functions as a scaffolding element in the nuclear phase of the NPC and plays a role in mitotic spindle checkpoint signalling. Export of intron-containing mRNA in Mason Pfizer Monkey Virus is regulated by direct interaction of cellular proteins with the cis-acting Constitutive Transport Element (CTE). In mammalian cells, the transport of Gag/Pol-CTE reporter construct is not very efficient, suggesting a regulatory mechanism to retain this unspliced RNA. Here we report that the knockdown of Tpr in mammalian cells leads to a drastic enhancement in the levels of Gag proteins (p24) in the cytoplasm, which is rescued by siRNA resistant Tpr. Tpr's role in the retention of unspliced RNA is independent of the functions of Sam68 and Tap/Nxf1 proteins, which are reported to promote CTE dependent export. Further, we investigated the possible role for nucleoporins that are known to function in nucleocytoplasmic transport in modulating unspliced RNA export. Results show that depletion of Nup153, a nucleoporin required for NPC anchoring of Tpr, plays a role in regulating the export, while depletion of other FG repeat-containing nucleoporins did not alter the unspliced RNA export. Results suggest that Tpr and Nup153 both regulate the export of unspliced RNA and they are most likely functioning through the same pathway. Importantly, we find that localization of Tpr to the NPC is necessary for Tpr mediated regulation of unspliced RNA export. Collectively, the data indicates that perinuclear localization of Tpr at the nucleopore complex is crucial for regulating intron containing mRNA export by directly or indirectly participating in the processing and degradation of aberrant mRNA transcripts.

  6. A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K.

    Science.gov (United States)

    García-Santisteban, Iraia; Arregi, Igor; Alonso-Mariño, Marián; Urbaneja, María A; Garcia-Vallejo, Juan J; Bañuelos, Sonia; Rodríguez, Jose A

    2016-12-01

    The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclear export has not yet been evaluated in a cellular setting. Here, we describe SRV100, a cellular reporter to interrogate CRM1 nuclear export activity. Using this novel tool, we provide evidence further validating the model of NES binding and release by CRM1. Furthermore, using both SRV100-based cellular assays and in vitro biochemical analyses, we investigate the functional consequences of a recurrent cancer-related mutation, which targets a residue near CRM1 NES-binding cleft. Our data indicate that this mutation does not necessarily abrogate the nuclear export activity of CRM1, but may increase its affinity for NES sequences bearing a more negatively charged C-terminal end.

  7. Functional characterization of nuclear localization and export signals in hepatitis C virus proteins and their role in the membranous web.

    Directory of Open Access Journals (Sweden)

    Aviad Levin

    Full Text Available The hepatitis C virus (HCV is a positive strand RNA virus of the Flavivirus family that replicates in the cytoplasm of infected hepatocytes. Previously, several nuclear localization signals (NLS and nuclear export signals (NES have been identified in HCV proteins, however, there is little evidence that these proteins travel into the nucleus during infection. We have recently shown that nuclear pore complex (NPC proteins (termed nucleoporins or Nups are present in the membranous web and are required during HCV infection. In this study, we identify a total of 11 NLS and NES sequences in various HCV proteins. We show direct interactions between HCV proteins and importin α5 (IPOA5/kapα1, importin β3 (IPO5/kap β3, and exportin 1 (XPO1/CRM1 both in-vitro and in cell culture. These interactions can be disrupted using peptides containing the specific NLS or NES sequences of HCV proteins. Moreover, using a synchronized infection system, we show that these peptides inhibit HCV infection during distinct phases of the HCV life cycle. The inhibitory effects of these peptides place them in two groups. The first group binds IPOA5 and inhibits infection during the replication stage of HCV life cycle. The second group binds IPO5 and is active during both early replication and early assembly. This work delineates the entire life cycle of HCV and the active involvement of NLS sequences during HCV replication and assembly. Given the abundance of NLS sequences within HCV proteins, our previous finding that Nups play a role in HCV infection, and the relocation of the NLS double-GFP reporter in HCV infected cells, this work supports our previous hypothesis that NPC-like structures and nuclear transport factors function in the membranous web to create an environment conducive to viral replication.

  8. Analysis of nuclear export using photoactivatable GFP fusion proteins and interspecies heterokaryons.

    Science.gov (United States)

    Nakrieko, Kerry-Ann; Ivanova, Iordanka A; Dagnino, Lina

    2010-01-01

    In this chapter, we review protocols for the analysis of nucleocytoplasmic shuttling of transcription factors and nuclear proteins, using two different approaches. The first involves the use of photoactivatable forms of the protein of interest by fusion to photoactivatable green fluorescent protein to follow its movement out of the nucleus by live-cell confocal microscopy. This methodology allows for the kinetic characterization of protein movements as well as measurement of steady-state levels. In a second procedure to assess the ability of a nuclear protein to move into and out of the nucleus, we describe the use of interspecies heterokaryon assays, which provide a measurement of steady-state distribution. These technologies are directly applicable to the analysis of nucleocytoplasmic movements not only of transcription factors, but also other nuclear proteins.

  9. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Chao, E-mail: liuchao9@mail.sysu.edu.cn [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Zhang, Hui [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China)

    2015-12-15

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  10. Trypanosoma brucei RNA binding proteins p34 and p37 mediate NOPP44/46 cellular localization via the exportin 1 nuclear export pathway.

    Science.gov (United States)

    Hellman, Kristina; Prohaska, Kimberly; Williams, Noreen

    2007-12-01

    We have previously identified and characterized two novel nuclear RNA binding proteins, p34 and p37, which have been shown to interact with a family of nucleolar phosphoproteins, NOPP44/46, in Trypanosoma brucei. These proteins are nearly identical, the major difference being an 18-amino-acid insert in the N terminus of p37. In order to characterize the interaction between p34 and p37 and NOPP44/46, we have utilized an RNA interference (RNAi) cell line that specifically targets p34 and p37. Within these RNAi cells, we detected a disruption of a higher-molecular-weight complex containing NOPP44/46, as well as a dramatic increase in nuclear NOPP44/46 protein levels. We demonstrated that no change occurred in NOPP44/46 mRNA steady-state levels or stability, nor was there a change in cellular protein levels. These results led us to investigate whether p34 and p37 regulate NOPP44/46 cellular localization. Examination of the p34 and p37 amino acid sequences revealed a leucine-rich nuclear export signal, which interacts with the nuclear export factor exportin 1. Immune capture experiments demonstrated that p34, p37, and NOPP44/46 associate with exportin 1. When these experiments were performed with p34/p37 RNAi cells, NOPP44/46 no longer associated with exportin 1. Sequential immune capture experiments demonstrated that p34, p37, NOPP44/46, and exportin 1 exist in a common complex. Inhibiting exportin 1-mediated nuclear export led to an increase in nuclear NOPP44/46 proteins, indicating that they are exported from the nucleus via this pathway. Together, our results demonstrate that p34 and p37 regulate NOPP44/46 cellular localization by facilitating their association with exportin 1.

  11. Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export.

    Science.gov (United States)

    Heiber, Arlett; Kruse, Florian; Pick, Christian; Grüring, Christof; Flemming, Sven; Oberli, Alexander; Schoeler, Hanno; Retzlaff, Silke; Mesén-Ramírez, Paolo; Hiss, Jan A; Kadekoppala, Madhusudan; Hecht, Leonie; Holder, Anthony A; Gilberger, Tim-Wolf; Spielmann, Tobias

    2013-01-01

    Malaria blood stage parasites export a large number of proteins into their host erythrocyte to change it from a container of predominantly hemoglobin optimized for the transport of oxygen into a niche for parasite propagation. To understand this process, it is crucial to know which parasite proteins are exported into the host cell. This has been aided by the PEXEL/HT sequence, a five-residue motif found in many exported proteins, leading to the prediction of the exportome. However, several PEXEL/HT negative exported proteins (PNEPs) indicate that this exportome is incomplete and it remains unknown if and how many further PNEPs exist. Here we report the identification of new PNEPs in the most virulent malaria parasite Plasmodium falciparum. This includes proteins with a domain structure deviating from previously known PNEPs and indicates that PNEPs are not a rare exception. Unexpectedly, this included members of the MSP-7 related protein (MSRP) family, suggesting unanticipated functions of MSRPs. Analyzing regions mediating export of selected new PNEPs, we show that the first 20 amino acids of PNEPs without a classical N-terminal signal peptide are sufficient to promote export of a reporter, confirming the concept that this is a shared property of all PNEPs of this type. Moreover, we took advantage of newly found soluble PNEPs to show that this type of exported protein requires unfolding to move from the parasitophorous vacuole (PV) into the host cell. This indicates that soluble PNEPs, like PEXEL/HT proteins, are exported by translocation across the PV membrane (PVM), highlighting protein translocation in the parasite periphery as a general means in protein export of malaria parasites.

  12. Molecular features of the L-type amino acid transporter 2 determine different import and export profiles for thyroid hormones and amino acids.

    Science.gov (United States)

    Hinz, Katrin M; Neef, Dominik; Rutz, Claudia; Furkert, Jens; Köhrle, Josef; Schülein, Ralf; Krause, Gerd

    2017-03-05

    The L-type amino acid transporter 2 (LAT2) imports amino acids (AA) and also certain thyroid hormones (TH), e.g. 3,3'-T2 and T3, but not rT3 and T4. We utilized LAT2 mutations (Y130A, N133S, F242W) that increase 3,3'-T2 import and focus here on import and export capacity for AA, T4, T3, BCH and derivatives thereof to delineate molecular features. Transport studies and analysis of competitive inhibition of import by radiolabelled TH and AA were performed in Xenopus laevis oocytes. Only Y130A, a pocket widening mutation, enabled import for T4 and increased it for T3. Mutant F242W showed increased 3,3'-T2 import but no import rates for other TH derivatives. No export was detected for any TH by LAT2-wild type (WT). Mutations Y130A and N133S enabled only the export of 3,3'-T2, while N133S also increased AA export. Thus, distinct molecular LAT2-features determine bidirectional AA transport but only an unidirectional 3,3'-T2 and T3 import.

  13. Interactions between mRNA export commitment, 3'-end quality control, and nuclear degradation

    DEFF Research Database (Denmark)

    Libri, Domenico; Dower, Ken; Boulay, Jocelyne;

    2002-01-01

    elongation. Indeed, we find that a pool of heat shock HSP104 transcripts are 3'-end truncated in THO complex mutant as well as sub2 mutant backgrounds. Surprisingly, however, this defect can be suppressed by deletion of the 3'-5' exonuclease Rrp6p. This indicates that incomplete RNAs result from nuclear...... that the failure to retain and/or degrade defective mRNAs is deleterious. mRNAs produced in the 3'-end processing mutants rna14-3 and rna15-2, as well as an RNA harboring a 3' end generated by a self-cleaving hammerhead ribozyme, are also retained in Rrp6p-dependent transcription site foci. Taken together, our...

  14. The dependence of Ig class-switching on the nuclear export sequence of AID likely reflects interaction with factors additional to Crm1 exportin

    Science.gov (United States)

    Ellyard, Julia I; Benk, Amelie S; Taylor, Benjamin; Rada, Cristina; Neuberger, Michael S

    2011-01-01

    Activation-induced deaminase (AID) is a B lymphocyte-specific DNA deaminase that triggers Ig class-switch recombination (CSR) and somatic hypermutation. It shuttles between cytoplasm and nucleus, containing a nuclear export sequence (NES) at its carboxyterminus. Intriguingly, the precise nature of this NES is critical to AID's function in CSR, though not in somatic hypermutation. Many alterations to the NES, while preserving its nuclear export function, destroy CSR ability. We have previously speculated that AID's ability to potentiate CSR may critically depend on the affinity of interaction between its NES and Crm1 exportin. Here, however, by comparing multiple AID NES mutants, we find that – beyond a requirement for threshold Crm1 binding – there is little correlation between CSR and Crm1 binding affinity. The results suggest that CSR, as well as the stabilisation of AID, depend on an interaction between the AID C-terminal decapeptide and factor(s) additional to Crm1. PMID:21268017

  15. The dependence of Ig class-switching on the nuclear export sequence of AID likely reflects interaction with factors additional to Crm1 exportin.

    Science.gov (United States)

    Ellyard, Julia I; Benk, Amelie S; Taylor, Benjamin; Rada, Cristina; Neuberger, Michael S

    2011-02-01

    Activation-induced deaminase (AID) is a B lymphocyte-specific DNA deaminase that triggers Ig class-switch recombination (CSR) and somatic hypermutation. It shuttles between cytoplasm and nucleus, containing a nuclear export sequence (NES) at its carboxyterminus. Intriguingly, the precise nature of this NES is critical to AID's function in CSR, though not in somatic hypermutation. Many alterations to the NES, while preserving its nuclear export function, destroy CSR ability. We have previously speculated that AID's ability to potentiate CSR may critically depend on the affinity of interaction between its NES and Crm1 exportin. Here, however, by comparing multiple AID NES mutants, we find that - beyond a requirement for threshold Crm1 binding - there is little correlation between CSR and Crm1 binding affinity. The results suggest that CSR, as well as the stabilisation of AID, depend on an interaction between the AID C-terminal decapeptide and factor(s) additional to Crm1.

  16. Proteome-wide search for functional motifs altered in tumors: Prediction of nuclear export signals inactivated by cancer-related mutations.

    Science.gov (United States)

    Prieto, Gorka; Fullaondo, Asier; Rodríguez, Jose A

    2016-05-12

    Large-scale sequencing projects are uncovering a growing number of missense mutations in human tumors. Understanding the phenotypic consequences of these alterations represents a formidable challenge. In silico prediction of functionally relevant amino acid motifs disrupted by cancer mutations could provide insight into the potential impact of a mutation, and guide functional tests. We have previously described Wregex, a tool for the identification of potential functional motifs, such as nuclear export signals (NESs), in proteins. Here, we present an improved version that allows motif prediction to be combined with data from large repositories, such as the Catalogue of Somatic Mutations in Cancer (COSMIC), and to be applied to a whole proteome scale. As an example, we have searched the human proteome for candidate NES motifs that could be altered by cancer-related mutations included in the COSMIC database. A subset of the candidate NESs identified was experimentally tested using an in vivo nuclear export assay. A significant proportion of the selected motifs exhibited nuclear export activity, which was abrogated by the COSMIC mutations. In addition, our search identified a cancer mutation that inactivates the NES of the human deubiquitinase USP21, and leads to the aberrant accumulation of this protein in the nucleus.

  17. Oncoprotein p28GANK binds to RelA and retains NF-kB in the cytoplasm through nuclear export

    Institute of Scientific and Technical Information of China (English)

    Yao Chen; Hong Yang Wang; Hong Hai Li; Jing Fu; Xue Feng Wang; Yi Bin Ren; Li Wei Dong; Shan Hua Tang; Shu Qing Liu; Meng Chao Wu

    2007-01-01

    p2gGANK (also known as PSMD10, p28 and gankyrin) is an ankyrin repeat anti-apoptotic oncoprotein that is commonly overexpressed in hepatocellular carcinomas and increases the degradation of p53 and Rb. NF-kB (nuclear factor-KB) is known to be sequestered in the cytoplasm by IkB (inhibitor of NF-kB) proteins [1, 2], but much less is known about the cytoplasmic retention of NF-kB by other cellular proteins. Here we show that p28GANK inhibits NF-kB activity. As a nuclear-cytoplasmic shuttling protein, p28GANK directly binds to NF-KB/RelA and exports RelA from nucleus through a chromosomal region maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic retention of NF-KB/RelA. We demonstrate that all the ankyrin repeats of p28GANK are required for the interaction with RelA and that the N terminus of p28GANK, which contains the nuclear export sequence (NES), is responsible for suppressing NF-KB/RelA nuclear translocation. These results suggest that overexpression of p28GANK prevents the nuclear localization and inhibits the activity of NF-KB/RelA.

  18. Design Features and Technology Uncertainties for the Next Generation Nuclear Plant

    Energy Technology Data Exchange (ETDEWEB)

    John M. Ryskamp; Phil Hildebrandt; Osamu Baba; Ron Ballinger; Robert Brodsky; Hans-Wolfgang Chi; Dennis Crutchfield; Herb Estrada; Jeane-Claude Garnier; Gerald Gordon; Richard Hobbins; Dan Keuter; Marilyn Kray; Philippe Martin; Steve Melancon; Christian Simon; Henry Stone; Robert Varrin; Werner von Lensa

    2004-06-01

    This report presents the conclusions, observations, and recommendations of the Independent Technology Review Group (ITRG) regarding design features and important technology uncertainties associated with very-high-temperature nuclear system concepts for the Next Generation Nuclear Plant (NGNP). The ITRG performed its reviews during the period November 2003 through April 2004.

  19. Cytoplasmic localization of NPM in myeloid leukemias is dictated by gain-of-function mutations that create a functional nuclear export signal.

    Science.gov (United States)

    Mariano, A R; Colombo, E; Luzi, L; Martinelli, P; Volorio, S; Bernard, L; Meani, N; Bergomas, R; Alcalay, M; Pelicci, P G

    2006-07-20

    Nucleophosmin (NPM) is a nucleus-cytoplasmic shuttling protein that is implicated in centrosome duplication, cell cycle progression and stress response. At the steady state, NPM localizes mainly in the nucleolus, where it forms a complex with different cellular proteins. One-third of acute myeloid leukemias (AML) are characterized by aberrant cytoplasmic localization of NPM, due to mutations within its last coding exon (exon 12) that cause a frameshift and the formation of novel C-termini. We report here our investigations on the molecular basis for the aberrant localization of mutated NPM. Alignment of the C-terminus of the various NPM mutants revealed the obligatory presence of four amino-acid residues that match a CRM1-dependent nuclear export signal (NES). Single alanine-substitutions at these sites provoked nuclear re-localization, while fusion of the mutated C-terminus to a heterologous nuclear protein induced CRM1-dependent cytoplasmic localization. Molecular characterization of one exceptional AML carrying cytoplasmic NPM and germ line exon 12 revealed a somatic mutation in the splicing donor site of exon 9 that caused the formation of a functional NES. It appears, therefore, that AMLs are frequently characterized by gain-of-function mutations of NPM that create functional NES, suggesting that alterations of nuclear export might represent a general mechanism of leukemogenesis and a novel target for therapeutic intervention.

  20. FURTHER EVALUATION OF QUANTITATIVE NUCLEAR IMAGE FEATURES FOR CLASSIFICATION OF LUNG CARCINOMAS

    NARCIS (Netherlands)

    THUNNISSEN, FBJM; DIEGENBACH, PC; VANHATTUM, AH; TOLBOOM, J; VANDERSLUIS, DM; SCHAAFSMA, W; HOUTHOFF, HJ; BAAK, JPA

    1992-01-01

    The usefulness of quantitative nuclear image features (QNI) for the histological classification of lung carcinomas was investigated. As no clear distinction could be established between the distributions of these features for the nuclei of squamous cell, adenocarcinoma, and large cell carcinoma, the

  1. Mitsubishi PWR nuclear fuel with advanced design features

    Energy Technology Data Exchange (ETDEWEB)

    Kaua Goe, Toshiy Uki; Nuno kawa, Koi Chi [Mitsubishi Heavy Industries, Ltd., Tokyo (Japan)

    2008-10-15

    In the last few decades, the global warming has been a big issue. As the breakthrough in this crisis, advanced operations of the water reactor such as higher burn up, longer cycle, and up rating could be effective ways. From this viewpoint, Mitsubishi Heavy Industries (MHI) has developed the fuel for burn up extension, whose assembly burn-up limit is 55GWd/t(A), with the original and advanced designs such as corrosion resistant cladding material MDA, and supplied to Japanese PWR utilities. On the other hand, MHI intends to supply more advanced fuel assemblies not only to domestic market but to the global market. Actually MHI has submitted the application for standard design certification of USA . Advanced Pressurized Water Reactor on Jan. 2nd 2008. The fuel assembly for US APWR is 17x17 type with active fuel length of 14ft, characterized with three features, to {sup E}nhance Fuel Economy{sup ,} {sup E}nable Flexible Core Operation{sup ,} and to {sup I}mprove Reliability{sup .} MHI has also been conducting development activities for more advanced products, such as 70GWd/t(A) burn up limit fuel with cladding, guide thimble and spacer grid made from M-MDATM alloy that is new material with higher corrosion resistance, such as 12ft and 14ft active length fuel, such as fuel with countermeasure against grid fretting, debris fretting, and IRI. MHI will present its activities and advanced designs.

  2. Molecular Characterization of Viral Responsive Protein 15 and Its Possible Role in Nuclear Export of Virus in Black Tiger Shrimp Penaeus monodon

    OpenAIRE

    Jaturontakul, Krisadaporn; Jatuyosporn, Thapanan; Laohawutthichai, Pasunee; Kim, Sun-Yong; Mori, Tomoyuki; Supungul, Premruethai; Hakoshima, Toshio; Tassanakajon, Anchalee; Krusong, Kuakarun

    2017-01-01

    A viral responsive protein 15 from Penaeus monodon (PmVRP15) has been reported to be important for white spot syndrome virus (WSSV) infection in vivo. This work aims to characterize PmVRP15 and investigate its possible role in nuclear import/export of the virus. Circular dichroism spectra showed that PmVRP15 contains high helical contents (82%). Analytical ultracentrifugation suggested that PmVRP15 could possibly form oligomers in solution. A subcellular fractionation study showed that PmVRP1...

  3. The Prognostic Value of Adaptive Nuclear Texture Features from Patient Gray Level Entropy Matrices in Early Stage Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Birgitte Nielsen

    2012-01-01

    Full Text Available Background: Nuclear texture analysis gives information about the spatial arrangement of the pixel gray levels in a digitized microscopic nuclear image, providing texture features that may be used as quantitative tools for prognosis of human cancer. The aim of the study was to evaluate the prognostic value of adaptive nuclear texture features in early stage ovarian cancer.

  4. Safety features in nuclear power plants to eliminate the need of emergency planning in public domain

    Indian Academy of Sciences (India)

    P K Vijayan; M T Kamble; A K Nayak; K K Vaze; R K Sinha

    2013-10-01

    Following the Fukushima accident, the safety features of Nuclear Power Plants (NPP) are being re-examined worldwide including India to demonstrate capabilities to cope with severe accidents. In order to restore public confidence and support for nuclear power, it is felt necessary to design future NPPs with near zero impact outside the plant boundary and thus enabling elimination of emergency planning in public domain. Authors have identified a set of safety features which are needed to be incorporated in advanced reactors to achieve this goal. These features enabling prevention, termination, mitigation and containment of radioactivity for beyond design basis accidents arising from extreme natural events are essential for achieving the goal of elimination of emergency planning in public domain. Inherent safety characteristics, passive and engineered safety features to achieve these functions are discussed in this paper. Present trends and future developments in this direction are also described briefly.

  5. Automated local bright feature image analysis of nuclear proteindistribution identifies changes in tissue phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, David; Sudar, Damir; Bator, Carol; Bissell, Mina

    2006-02-01

    The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, the distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is an increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype, and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently-stained nuclear protein NuMA in different mammary phenotypes obtained using three-dimensional cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from three-dimensional confocal images. Prominent features of fluorescently-stained NuMA were detected using a novel local bright feature analysis technique, and their normalized spatial density calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features as non-neoplastic cells underwent phenotypically normal acinar morphogenesis. In contrast, we did not detect any reorganization of NuMA during the formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating non-neoplastic cells from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues.

  6. Updated nuclear export mechanism and significance of Nrf2%Nrf2出核转运机制及意义的研究进展

    Institute of Scientific and Technical Information of China (English)

    段家翔(综述); 甯交琳; 鲁开智(审校)

    2014-01-01

    Nuclear factor-E2-related factor 2(Nrf2)is a member of C′n′C transcription factor family.It is an important transcrip-tion factor for regulation of cellular redox status and can be seen in all kinds of tissues .Recent studies have demonstrated that rapid deg-radation of Nrf2 after gene-induced antioxidative stress is as important as transcription and activation of Nrf 2 and the nuclear export of Nrf2 is a prerequisite for rapid degradation of Nrf2 in the cytosol.This review focuses on the mechanism of nuclear export of Nrf 2.%核因子E2相关因子2(nuclear factor -E2-related factor 2, Nrf2)是C′n′C转录因子家族成员之一,在各种组织细胞中广泛表达,是细胞调节抗氧化应激反应的重要转录因子。近年来研究发现Nrf2完成抗氧化应激基因诱导后快速降解与其转录激活同样重要,而Nrf2的出核转运是在细胞质中快速降解的前提。文中就目前Nrf2出核转运机制的研究进展作一综述。

  7. Inhibition of Cd83 Cell Surface Expression during Dendritic Cell Maturation by Interference with Nuclear Export of Cd83 mRNA

    Science.gov (United States)

    Kruse, Monika; Rosorius, Olaf; Krätzer, Friedrich; Bevec, Dorian; Kuhnt, Christine; Steinkasserer, Alexander; Schuler, Gerold; Hauber, Joachim

    2000-01-01

    Dendritic cells (DCs), nature's adjuvant, must mature to sensitize T cells. However, although the maturation process is essential, it is not yet fully understood at the molecular level. In this study, we investigated the course of expression of the unique hypusine-containing protein eukaryotic initiation factor 5A (eIF-5A), which is part of a particular RNA nuclear export pathway, during in vitro generation of human DCs. We show that eIF-5A expression is significantly upregulated during DC maturation. Furthermore, an inhibitor of the hypusine modification, GC7 (N1-guanyl-1,7-diaminoheptane), prevents CD83 surface expression by apparently interfering with nucleocytoplasmic translocation of the CD83 mRNA and, importantly, significantly inhibits DC-mediated T lymphocyte activation. The data presented suggest that CD83 mRNA is transported from the nucleus to the cytoplasm via a specific nuclear export pathway and that hypusine formation appears to be essential for the maturation of functional DCs. Therefore, pharmacological interference with hypusine formation may provide a new possibility to modulate DC function. PMID:10790432

  8. 10 CFR Appendix A to Part 110 - Illustrative List of Nuclear Reactor Equipment Under NRC Export Licensing Authority

    Science.gov (United States)

    2010-01-01

    ... designed for inserting or removing fuel in an operating nuclear reactor. (3) Complete reactor control rod... contain fuel elements and the primary coolant in a nuclear reactor at an operating pressure in excess of... diffuser plates especially designed or prepared for use in a nuclear reactor. (8) Reactor control......

  9. Automatic classification of hepatocellular carcinoma images based on nuclear and structural features

    Science.gov (United States)

    Kiyuna, Tomoharu; Saito, Akira; Marugame, Atsushi; Yamashita, Yoshiko; Ogura, Maki; Cosatto, Eric; Abe, Tokiya; Hashiguchi, Akinori; Sakamoto, Michiie

    2013-03-01

    Diagnosis of hepatocellular carcinoma (HCC) on the basis of digital images is a challenging problem because, unlike gastrointestinal carcinoma, strong structural and morphological features are limited and sometimes absent from HCC images. In this study, we describe the classification of HCC images using statistical distributions of features obtained from image analysis of cell nuclei and hepatic trabeculae. Images of 130 hematoxylin-eosin (HE) stained histologic slides were captured at 20X by a slide scanner (Nanozoomer, Hamamatsu Photonics, Japan) and 1112 regions of interest (ROI) images were extracted for classification (551 negatives and 561 positives, including 113 well-differentiated positives). For a single nucleus, the following features were computed: area, perimeter, circularity, ellipticity, long and short axes of elliptic fit, contour complexity and gray level cooccurrence matrix (GLCM) texture features (angular second moment, contrast, homogeneity and entropy). In addition, distributions of nuclear density and hepatic trabecula thickness within an ROI were also extracted. To represent an ROI, statistical distributions (mean, standard deviation and percentiles) of these features were used. In total, 78 features were extracted for each ROI and a support vector machine (SVM) was trained to classify negative and positive ROIs. Experimental results using 5-fold cross validation show 90% sensitivity for an 87.8% specificity. The use of statistical distributions over a relatively large area makes the HCC classifier robust to occasional failures in the extraction of nuclear or hepatic trabecula features, thus providing stability to the system.

  10. Utp22p acts in concert with Utp8p to channel aminoacyl-tRNA from the nucleolus to the nuclear tRNA export receptor Los1p but not Msn5p.

    Science.gov (United States)

    Eswara, Manoja B K; Clayton, Ashley; Mangroo, Dev

    2012-12-01

    Utp8p is an essential nucleolar protein that channels aminoacyl-tRNAs from aminoacyl-tRNA synthetases in the nucleolus to the nuclear tRNA export receptors located in the nucleoplasm and nuclear pore complex in Saccharomyces cerevisiae. Utp8p is also part of the U3 snoRNA-associated protein complex involved in 18S rRNA biogenesis in the nucleolus. We report that Utp22p, which is another member of the U3 snoRNA-associated protein complex, is also an intranuclear component of the nuclear tRNA export machinery. Depletion of Utp22p results in nuclear retention of mature tRNAs derived from intron-containing and intronless precursors. Moreover, Utp22p copurifies with the nuclear tRNA export receptor Los1p, the aminoacyl-tRNA synthetase Tys1p and Utp8p, but not with the RanGTPase Gsp1p and the nuclear tRNA export receptor Msn5p. Utp22p interacts directly with Utp8p and Los1p in a tRNA-independent manner in vitro. Utp22p also interacts directly with Tys1p, but this binding is stimulated when Tys1p is bound to tRNA. However, Utp22p, unlike Utp8p, does not bind tRNA saturably. These data suggest that Utp22p recruits Utp8p to aminoacyl-tRNA synthetases in the nucleolus to collect aminoacyl-tRNA and then accompanies the Utp8p-tRNA complex to deliver the aminoacyl-tRNAs to Los1p but not Msn5p. It is possible that Nrap/Nol6, the mammalian orthologue of Utp22p, plays a role in channelling aminoacyl-tRNA to the nuclear tRNA export receptor exportin-t.

  11. Effect of Quantitative Nuclear Image Features on Recurrence of Ductal Carcinoma In Situ (DCIS of the Breast

    Directory of Open Access Journals (Sweden)

    Judith-Anne W. Chapman

    2008-01-01

    Full Text Available Background: Nuclear grade has been associated with breast DCIS recurrence and progression to invasive carcinoma; however, our previous study of a cohort of patients with breast DCIS did not find such an association with outcome. Fifty percent of patients had heterogeneous DCIS with more than one nuclear grade. The aim of the current study was to investigate the effect of quantitative nuclear features assessed with digital image analysis on ipsilateral DCIS recurrence.Methods: Hematoxylin and eosin stained slides for a cohort of 80 patients with primary breast DCIS were reviewed and two fields with representative grade (or grades were identified by a Pathologist and simultaneously used for acquisition of digital images for each field. Van Nuys worst nuclear grade was assigned, as was predominant grade, and heterogeneous grading when present. Patients were grouped by heterogeneity of their nuclear grade: Group A: nuclear grade 1 only, nuclear grades 1 and 2, or nuclear grade 2 only (32 patients, Group B: nuclear grades 1, 2 and 3, or nuclear grades 2 and 3 (31 patients, Group 3: nuclear grade 3 only (17 patients. Nuclear fi ne structure was assessed by software which captured thirty-nine nuclear feature values describing nuclear morphometry, densitometry, and texture. Step-wise forward Cox regressions were performed with previous clinical and pathologic factors, and the new image analysis features.Results: Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. The rate of correct classification of nuclear grading with digital image analysis features was similar in the two fields, and pooled assessment across both fields. In the pooled assessment, a discriminant function with one nuclear morphometric and one texture feature was significantly (p = 0.001 associated with nuclear grading, and provided correct jackknifed classification of a patient’s nuclear grade for Group A (78.1%, Group B (48.4%, and Group C (70.6%. The

  12. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice.

    Science.gov (United States)

    Etchin, J; Montero, J; Berezovskaya, A; Le, B T; Kentsis, A; Christie, A L; Conway, A S; Chen, W C; Reed, C; Mansour, M R; Ng, C E L; Adamia, S; Rodig, S J; Galinsky, I A; Stone, R M; Klebanov, B; Landesman, Y; Kauffman, M; Shacham, S; Kung, A L; Wang, J C Y; Letai, A; Look, A T

    2016-01-01

    Currently available combination chemotherapy for acute myeloid leukemia (AML) often fails to result in long-term remissions, emphasizing the need for novel therapeutic strategies. We reasoned that targeted inhibition of a prominent nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating cells (LICs) whose survival depends on timely XPO1-mediated transport of specific protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is currently in clinical trials, has strong activity against primary AML cells while sparing normal stem and progenitor cells. Importantly, limiting dilution transplantation assays showed that this cytotoxic activity is not limited to the rapidly proliferating bulk population of leukemic cells but extends to the LICs, whose inherent drug resistance and unrestricted self-renewal capacity has been implicated in the difficulty of curing AML patients with conventional chemotherapy alone.

  13. The Hotelling Trace Criterion Used for System Optimization and Feature Enhancement in Nuclear Medicine

    Science.gov (United States)

    Fiete, Robert Dean

    The Hotelling trace criterion (HTC) is a measure of class separability used in pattern recognition to find a set of linear features that optimally separate two classes of objects. In this dissertation we use the HTC not as a figure of merit for features, but as a figure of merit for characterizing imaging systems and designing filters for feature enhancement in nuclear medicine. If the HTC is to be used to optimize systems, then it must correlate with human observer performance. In our first study, a set of images, created by overlapping ellipses, was used to simulate images of livers. Two classes were created, livers with and without tumors, with noise and blur added to each image to simulate nine different imaging systems. Using the ROC parameter d_ {rm a} as our measure, we found that the HTC has a correlation of 0.988 with the ability of humans to separate these two classes of objects. A second study was performed to demonstrate the use of the HTC for system optimization in a realistic task. For this study we used a mathematical model of normal and diseased livers and of the imaging system to generate a realistic set of liver images from nuclear medicine. A method of adaptive, nonlinear filtering which enhances the features that separate two sets of images has also been developed. The method uses the HTC to find the optimal linear feature operator for the Fourier moduli of the images, and uses this operator as a filter so that the features that separate the two classes of objects are enhanced. We demonstrate the use of this filtering method to enhance texture features in simulated liver images from nuclear medicine, after using a training set of images to obtain the filter. We also demonstrate how this method of filtering can be used to reconstruct an object from a single photon-starved image of it, when the object contains a repetitive feature. When power spectrums for real liver scans from nuclear medicine are calculated, we find that the three

  14. Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is enhanced in non-Hodgkin lymphoma through combination with mTOR inhibitor and dexamethasone.

    Science.gov (United States)

    Muqbil, Irfana; Aboukameel, Amro; Elloul, Sivan; Carlson, Robert; Senapedis, William; Baloglu, Erkan; Kauffman, Michael; Shacham, Sharon; Bhutani, Divaya; Zonder, Jeffrey; Azmi, Asfar S; Mohammad, Ramzi M

    2016-12-28

    In previous studies we demonstrated that targeting the nuclear exporter protein exportin-1 (CRM1/XPO1) by a selective inhibitor of nuclear export (SINE) compound is a viable therapeutic strategy against Non-Hodgkin Lymphoma (NHL). Our studies along with pre-clinical work from others led to the evaluation of the lead SINE compound, selinexor, in a phase 1 trial in patients with CLL or NHL (NCT02303392). Continuing our previous work, we studied combinations of selinexor-dexamethasone (DEX) and selinexor-everolimus (EVER) in NHL. Combination of selinexor with DEX or EVER resulted in enhanced cytotoxicity in WSU-DLCL2 and WSU-FSCCL cells which was consistent with enhanced apoptosis. Molecular analysis showed enhancement in the activation of apoptotic signaling and down-regulation of XPO1. This enhancement is consistent with the mechanism of action of these drugs in that both selinexor and DEX antagonize NF-κB (p65) and mTOR (EVER target) is an XPO1 cargo protein. SINE compounds, KPT-251 and KPT-276, showed activities similar to CHOP (cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone) regimen in subcutaneous and disseminated NHL xenograft models in vivo. In both animal models the anti-lymphoma activity of selinexor is enhanced through combination with DEX or EVER. The in vivo activity of selinexor and related SINE compounds relative to 'standard of care' treatment is consistent with the objective responses observed in Phase I NHL patients treated with selinexor. Our pre-clinical data provide a rational basis for testing these combinations in Phase II NHL trials.

  15. Export strategy

    DEFF Research Database (Denmark)

    Knudsen, Thorbjørn; Koed Madsen, Tage

    2002-01-01

    It is argued here that traditional export strategy research (encompassing the study of internationalization processes and export performance) is characterized by weak theoretical foundations and could benefit from a reorientation towards a dynamic capabilities perspective (DCP). We seek to draw...... on insights from DCP in order to devise a theoretical basis that could enrich export strategy research. Although our development of DCP insights builds on previous work, it also adds a crucial distinction between knowledge stocks and informational architecture. Changes in architecture are of greater...... importance. Following this elaboration of the dynamic capabilities perspective, we outline some implications and guidelines for future export strategy research....

  16. RNA Export through the NPC in Eukaryotes.

    Science.gov (United States)

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-03-20

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC.

  17. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chang, So Young; Park, Ji Hoon [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of); Kim, Young Ho; Kang, Jong Seong [College of Pharmacy, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Min, Ji-Young, E-mail: jiyoung.min@ip-korea.org [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of)

    2016-03-04

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

  18. Cocaine induces nuclear export and degradation of neuronal retinoid X receptor-γ via a TNF-α/JNK- mediated mechanism.

    Science.gov (United States)

    Kovalevich, Jane; Yen, William; Ozdemir, Ahmet; Langford, Dianne

    2015-03-01

    Cocaine abuse represents an immense societal health and economic burden for which no effective treatment currently exists. Among the numerous intracellular signaling cascades impacted by exposure to cocaine, increased and aberrant production of pro-inflammatory cytokines in the CNS has been observed. Additionally, we have previously reported a decrease in retinoid-X-receptor-gamma (RXR-γ) in brains of mice chronically exposed to cocaine. Through obligate heterodimerization with a number of nuclear receptors, RXRs serve as master regulatory transcription factors, which can potentiate or suppress expression of a wide spectrum of genes. Little is known about the regulation of RXR levels, but previous studies indicate cellular stressors such as cytokines negatively regulate levels of RXRs in vitro. To evaluate the mechanism underlying the cocaine-induced decreases in RXR-γ levels observed in vivo, we exposed neurons to cocaine in vitro and examined pathways which may contribute to disruption in RXR signaling, including activation of stress pathways by cytokine induction. In these studies, we provide the first evidence that cocaine exposure disrupts neuronal RXR-γ signaling in vitro by promoting its nuclear export and degradation. Furthermore, we demonstrate this effect may be mediated, at least in part, by cocaine-induced production of TNF-α and its downstream effector c-Jun-NH-terminal kinase (JNK). Findings from this study are therefore applicable to both cocaine abuse and to pathological conditions characterized by neuroinflammatory factors, such as neurodegenerative disease.

  19. 中国新能源产业出口竞争力研究:核电产业%Study on the Export Competitiveness of New Energy Industry of China:The Nuclear Power Industry

    Institute of Scientific and Technical Information of China (English)

    刘明

    2013-01-01

    产业出口竞争力是产业经济学和国际贸易学中的一个重要议题,作为新能源产业之一的核电产业,其出口竞争力研究尚处于探索阶段。本文根据1998年至2010年全球主要经济体的核电产业出口数据,以描述性统计分析为基础,得到了如下研究结论:中国核电产业出口竞争力相对于发达国家较弱,但与新兴市场经济国家相比,处于领先地位;TC指数分析结果和第三方市场研究结果均表明,中国核电产业出口竞争力在逐步增强。%Export competitiveness of industry is an important issue of industrial economics and internation -al trade.The research of the export competitiveness of the nuclear power industry , which is part of the new energy industry , is still in the exploration stage .According to the nuclear power industry export data of the global main economic bodies from 1998 to 2010 , and based on description statistics , we got the findings as following .The export competitiveness of China ’ s nuclear power industry less relative to the developed countries , but compared to the emerging market countries , it is the leader .Mean while , the results of the TC index analysis and the third -party market researching have shown that the export com-petitiveness of China ’ s nuclear power industry is gradually increased .

  20. Entropy-based adaptive nuclear texture features are independent prognostic markers in a total population of uterine sarcomas.

    Science.gov (United States)

    Nielsen, Birgitte; Hveem, Tarjei Sveinsgjerd; Kildal, Wanja; Abeler, Vera M; Kristensen, Gunnar B; Albregtsen, Fritz; Danielsen, Håvard E

    2015-04-01

    Nuclear texture analysis measures the spatial arrangement of the pixel gray levels in a digitized microscopic nuclear image and is a promising quantitative tool for prognosis of cancer. The aim of this study was to evaluate the prognostic value of entropy-based adaptive nuclear texture features in a total population of 354 uterine sarcomas. Isolated nuclei (monolayers) were prepared from 50 µm tissue sections and stained with Feulgen-Schiff. Local gray level entropy was measured within small windows of each nuclear image and stored in gray level entropy matrices, and two superior adaptive texture features were calculated from each matrix. The 5-year crude survival was significantly higher (P Entropy-based adaptive nuclear texture was an independent prognostic marker for crude survival in multivariate analysis including relevant clinicopathological features (HR = 2.1, P = 0.001), and should therefore be considered as a potential prognostic marker in uterine sarcomas.

  1. Thermal and neutron-physical features of the nuclear reactor for a power pulsation plant for space applications

    Science.gov (United States)

    Gordeev, É. G.; Kaminskii, A. S.; Konyukhov, G. V.; Pavshuk, V. A.; Turbina, T. A.

    2012-05-01

    We have explored the possibility of creating small-size reactors with a high power output with the provision of thermal stability and nuclear safety under standard operating conditions and in emergency situations. The neutron-physical features of such a reactor have been considered and variants of its designs preserving the main principles and approaches of nuclear rocket engine technology are presented.

  2. The nuclear-cytoplasmic shuttling of virion host shutoff RNase is enabled by pUL47 and an embedded nuclear export signal and defines the sites of degradation of AU-rich and stable cellular mRNAs.

    Science.gov (United States)

    Shu, Minfeng; Taddeo, Brunella; Roizman, Bernard

    2013-12-01

    The herpes simplex virus host shutoff RNase (VHS-RNase) is the major early block of host responses to infection. VHS-RNase is introduced into cells during infection and selectively degrades stable mRNAs made before infection and the normally short-lived AU-rich stress response mRNAs induced by sensors of innate immunity. Through its interactions with pUL47, another tegument protein, it spares from degradation viral mRNAs. Analyses of embedded motifs revealed that VHS-RNase contains a nuclear export signal (NES) but not a nuclear localization signal. To reconcile the potential nuclear localization with earlier studies showing that VHS-RNase degrades mRNAs in polyribosomes, we constructed a mutant in which NES was ablated. Comparison of the mutant and wild-type VHS-RNases revealed the following. (i) On infection, VHS-RNase is transported to the nucleus, but only the wild-type protein shuttles between the nucleus and cytoplasm. (ii) Both VHS-RNases localized in the cytoplasm following transfection. On cotransfection with pUL47, a fraction of VHS-RNase was translocated to the nucleus, suggesting that pUL47 may enable nuclear localization of VHS-RNase. (iii) In infected cells, VHS-RNase lacking NES degraded the short-lived AU-rich mRNAs but not the stable mRNAs. In transfected cells, both wild-type and NES mutant VHS-RNases effectively degraded cellular mRNAs. Our results suggest that the stable mRNAs are degraded in the cytoplasm, whereas the AU-rich mRNAs may be degraded in both cellular compartments. The selective sparing of viral mRNAs may take place during the nuclear phase in the course of interaction of pUL47, VHS-RNase, and nascent viral mRNAs.

  3. Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE KPT-335 in spontaneous canine cancer: results of a phase I study.

    Directory of Open Access Journals (Sweden)

    Cheryl A London

    Full Text Available BACKGROUND: The purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1 against canine tumor cell lines and perform a Phase I clinical trial of KPT-335 in dogs with spontaneous cancer to provide a preliminary assessment of biologic activity and tolerability. METHODS AND FINDINGS: Canine tumor cell lines derived from non-Hodgkin lymphoma (NHL, mast cell tumor, melanoma and osteosarcoma exhibited growth inhibition and apoptosis in response to nanomolar concentrations of SINE compounds; NHL cells were particularly sensitive with IC50 concentrations ranging from 2-42 nM. A Phase I clinical trial of KPT-335 was performed in 17 dogs with NHL (naive or relapsed, mast cell tumor or osteosarcoma. The maximum tolerated dose was 1.75 mg/kg given orally twice/week (Monday/Thursday although biologic activity was observed at 1 mg/kg. Clinical benefit (CB including partial response to therapy (PR, n = 2 and stable disease (SD, n = 7 was observed in 9/14 dogs with NHL with a median time to progression (TTP for responders of 66 days (range 35-256 days. A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg KPT-335 Monday/Wednesday/Friday; CB was observed in 4/6 dogs with a median TTP for responders of 83 days (range 35-354 days. Toxicities were primarily gastrointestinal consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care, dose modulation and administration of low dose prednisone; hepatotoxicity, anorexia and weight loss were the dose limiting toxicities. CONCLUSIONS: This study provides evidence that the novel orally bioavailable XPO1 inhibitor KPT-335 is safe and exhibits activity in a relevant, spontaneous large animal model of cancer. Data from this study provides critical new information that lays the groundwork for evaluation of SINE compounds in human cancer.

  4. Rift Valley fever virus NS{sub S} gene expression correlates with a defect in nuclear mRNA export

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Anna Maria; Van Deusen, Nicole M.; Schmaljohn, Connie S., E-mail: Connie.s.schmaljohn.civ@mail.mil

    2015-12-15

    We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NS{sub S} gene, but not the N, G{sub N} or NS{sub M} genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NS{sub S}, confirming that expression of NS{sub S} is likely responsible for this phenomenon. - Highlights: • Rift Valley fever virus (RVFV) infection alters the localization of host mRNA. • mRNA accumulates in the nuclei of RVFV-infected but not mock-infected cells. • NS{sub S} is likely responsible for mRNA relocalization to the nucleus.

  5. New features and improved uncertainty analysis in the NEA nuclear data sensitivity tool (NDaST)

    Science.gov (United States)

    Dyrda, J.; Soppera, N.; Hill, I.; Bossant, M.; Gulliford, J.

    2017-09-01

    Following the release and initial testing period of the NEA's Nuclear Data Sensitivity Tool [1], new features have been designed and implemented in order to expand its uncertainty analysis capabilities. The aim is to provide a free online tool for integral benchmark testing, that is both efficient and comprehensive, meeting the needs of the nuclear data and benchmark testing communities. New features include access to P1 sensitivities for neutron scattering angular distribution [2] and constrained Chi sensitivities for the prompt fission neutron energy sampling. Both of these are compatible with covariance data accessed via the JANIS nuclear data software, enabling propagation of the resultant uncertainties in keff to a large series of integral experiment benchmarks. These capabilities are available using a number of different covariance libraries e.g., ENDF/B, JEFF, JENDL and TENDL, allowing comparison of the broad range of results it is possible to obtain. The IRPhE database of reactor physics measurements is now also accessible within the tool in addition to the criticality benchmarks from ICSBEP. Other improvements include the ability to determine and visualise the energy dependence of a given calculated result in order to better identify specific regions of importance or high uncertainty contribution. Sorting and statistical analysis of the selected benchmark suite is now also provided. Examples of the plots generated by the software are included to illustrate such capabilities. Finally, a number of analytical expressions, for example Maxwellian and Watt fission spectra will be included. This will allow the analyst to determine the impact of varying such distributions within the data evaluation, either through adjustment of parameters within the expressions, or by comparison to a more general probability distribution fitted to measured data. The impact of such changes is verified through calculations which are compared to a `direct' measurement found by

  6. China's Export Expansion, Export Structure and Energy Consumption

    Institute of Scientific and Technical Information of China (English)

    Lan Yisheng; Ning Xuemin

    2011-01-01

    Since the reform and opening up, China's export trade has maintained a rapid growth; meanwhile, China's energy consumption has been increasing sharply. "High export and high energy consumption" has become the feature of China's trade and economic development. In this paper, based on the input-output analysis approach, the authors have conducted an empirical study on the export trade and energy consumption of 21 trade industrial sectors. The results show that, China is a big net exporter of embodied energy. Assuming that the export growth rate of embodied energy maintains to be about 23.6%, the average annual growth rate of the past 32 years, and based on the input-output data of 2005, by 2030 China's net export of embodied energy would be over eight times more than the aggregate energy production, which is obviously infeasible. As a country of very low per capita en- ergy, China must change its export pattern, encourage or restrain the export of different industrial sectors according to their energy consumption intensity, and promote structural change of energy- efficient exported products, so as to achieve the sustainable development. Accordingly, the authors put forward some suggestions.

  7. Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma.

    Science.gov (United States)

    Jardin, Fabrice; Pujals, Anais; Pelletier, Laura; Bohers, Elodie; Camus, Vincent; Mareschal, Sylvain; Dubois, Sydney; Sola, Brigitte; Ochmann, Marlène; Lemonnier, François; Viailly, Pierre-Julien; Bertrand, Philippe; Maingonnat, Catherine; Traverse-Glehen, Alexandra; Gaulard, Philippe; Damotte, Diane; Delarue, Richard; Haioun, Corinne; Argueta, Christian; Landesman, Yosef; Salles, Gilles; Jais, Jean-Philippe; Figeac, Martin; Copie-Bergman, Christiane; Molina, Thierry Jo; Picquenot, Jean Michel; Cornic, Marie; Fest, Thierry; Milpied, Noel; Lemasle, Emilie; Stamatoullas, Aspasia; Moeller, Peter; Dyer, Martin J S; Sundstrom, Christer; Bastard, Christian; Tilly, Hervé; Leroy, Karen

    2016-09-01

    Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Sphingosine kinase 1 serves as a pro-viral factor by regulating viral RNA synthesis and nuclear export of viral ribonucleoprotein complex upon influenza virus infection.

    Directory of Open Access Journals (Sweden)

    Young-Jin Seo

    Full Text Available Influenza continues to pose a threat to humans by causing significant morbidity and mortality. Thus, it is imperative to investigate mechanisms by which influenza virus manipulates the function of host factors and cellular signal pathways. In this study, we demonstrate that influenza virus increases the expression and activation of sphingosine kinase (SK 1, which in turn regulates diverse cellular signaling pathways. Inhibition of SK suppressed virus-induced NF-κB activation and markedly reduced the synthesis of viral RNAs and proteins. Further, SK blockade interfered with activation of Ran-binding protein 3 (RanBP3, a cofactor of chromosome region maintenance 1 (CRM1, to inhibit CRM1-mediated nuclear export of the influenza viral ribonucleoprotein complex. In support of this observation, SK inhibition altered the phosphorylation of ERK, p90RSK, and AKT, which is the upstream signal of RanBP3/CRM1 activation. Collectively, these results indicate that SK is a key pro-viral factor regulating multiple cellular signal pathways triggered by influenza virus infection.

  9. Safety case for the disposal of spent nuclear fuel at Olkiluoto. Features, events and processes 2012

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-12-15

    Features, Events and Processes sits within Posiva Oy's Safety Case 'TURVA-2012' portfolio and has the objective of presenting the main features, events and processes (FEPs) that are considered to be potentially significant for the long-term safety of the planned KBS-3V repository for spent nuclear fuel at Olkiluoto. The primary purpose of this report is to support Performance Assessment, Formulation of Radionuclide Release Scenarios, Assessment of the Radionuclide Release Scenarios for the Repository System and Biosphere Assessment by ensuring that the scenarios are comprehensive and take account of all significant FEPs. The main FEPs potentially affecting the disposal system are described for each relevant subsystem component or barrier (i.e. the spent nuclear fuel, the canister, the buffer and tunnel backfill, the auxiliary components, the geosphere and the surface environment). In addition, a small number of external FEPs that may potentially influence the evolution of the disposal system are described. The conceptual understanding and operation of each FEP is described, together with the main features (variables) of the disposal system that may affect its occurrence or significance. Olkiluoto-specific issues are considered when relevant. The main uncertainties (conceptual and parameter/data) associated with each FEP that may affect understanding are also documented. Indicative parameter values are provided, in some cases, to illustrate the magnitude or rate of a process, but it is not the intention of this report to provide the complete set of numerical values that are used in the quantitative safety assessment calculations. Many of the FEPs are interdependent and, therefore, the descriptions also identify the most important direct couplings between the FEPs. This information is used in the formulation of scenarios to ensure the conceptual models and calculational cases are both comprehensive and representative. (orig.)

  10. DEAD-box RNA helicase DDX3 connects CRM1-dependent nuclear export and translation of the HIV-1 unspliced mRNA through its N-terminal domain.

    Science.gov (United States)

    Fröhlich, Alvaro; Rojas-Araya, Bárbara; Pereira-Montecinos, Camila; Dellarossa, Alessandra; Toro-Ascuy, Daniela; Prades-Pérez, Yara; García-de-Gracia, Francisco; Garcés-Alday, Andrea; Rubilar, Paulina S; Valiente-Echeverría, Fernando; Ohlmann, Théophile; Soto-Rifo, Ricardo

    2016-05-01

    DEAD-box RNA helicase DDX3 is a host factor essential for HIV-1 replication and thus, a potential target for novel therapies aimed to overcome viral resistance. Previous studies have shown that DDX3 promotes nuclear export and translation of the HIV-1 unspliced mRNA. Although the function of DDX3 during both processes requires its catalytic activity, it is unknown whether other domains surrounding the helicase core are involved. Here, we show the involvement of the N- and C-terminal domains of DDX3 in the regulation of HIV-1 unspliced mRNA translation. Our results suggest that the intrinsically disordered N-terminal domain of DDX3 regulates its functions in translation by acting prior to the recruitment of the 43S pre-initiation complex onto the viral 5'-UTR. Interestingly, this regulation was conserved in HIV-2 and was dependent on the CRM1-dependent nuclear export pathway suggesting a role of the RNA helicase in interconnecting nuclear export with ribosome recruitment of the viral unspliced mRNA. This specific function of DDX3 during HIV gene expression could be exploited as an alternative target for pharmaceutical intervention.

  11. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.

    Science.gov (United States)

    Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen

    2016-08-01

    Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments.

  12. Reliability study: digital engineered safety feature actuation system of Korean Standard Nuclear Power Plant

    Energy Technology Data Exchange (ETDEWEB)

    Sudarno [National Nuclear Energy Agency, Batan (Indonesia); Kang, H. G.; Jang, S. C.; Eom, H. S.; Ha, J. J. [KAERI, Taejon (Korea, Republic of)

    2003-04-01

    The usage of digital Instrumentation and Control (I and C) in a nuclear power plant becomes more extensive, including safety related systems. The PSA application of these new designs are very important in order to evaluate their reliability. In particular, Korean Standard Nuclear Power Plants (KSNPPs), typically Ulchin 5 and 6 (UCN 5 and 6) reactor units, adopted the digital safety-critical systems such as Digital Plant Protection System (DPPS) and Digital Engineered Safety Feature Actuation System (DESFAS). In this research, we developed fault tree models for assessing the unavailability of the DESFAS functions. We also performed an analysis of the quantification results. The unavailability results of different DESFAS functions showed that their values are comprised from 5.461E-5 to 3.14E-4. The system unavailability of DESFAS AFAS-1 is estimated as 5.461E-5, which is about 27% less than that of analog system if we consider the difference of human failure probability estimation between both analyses. The results of this study could be utilized in risk-effect analysis of KSNPP. We expect that the safety analysis result will contribute to design feedback.

  13. Export spillovers

    DEFF Research Database (Denmark)

    Choquette, Eliane; Meinen, Philipp

    2015-01-01

    -industry linkages. We do so by exploiting a unique data set covering the universe of manufacturing firms in Denmark for the period 1995–2006 which combines transaction-level export data, firm accounting data, employer–employee linked data and information from yearly input–output tables. We corroborate...

  14. Fixed Export Costs and Export Behavior

    OpenAIRE

    Castro, Luis; Li, Ben; Keith E. Maskus; Xie, Yiqing

    2014-01-01

    This paper provides a direct test of how fixed export costs and productivity jointly determine firm-level export behavior. Using Chilean data, we construct indices of fixed export costs for each industry-region-year triplet and match them to domestic firms. Our empirical results show that firms facing higher fixed export costs are less likely to export, while those with higher productivity export more. These outcomes are the foundation of the widely-used sorting mechanism in the trade models ...

  15. The Major Prognostic Features of Nuclear Receptor NR5A2 in Infiltrating Ductal Breast Carcinomas

    Directory of Open Access Journals (Sweden)

    Li-Yun Chang

    2015-01-01

    Full Text Available Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based upon their associated transcriptional networks. Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology. Results. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(− and ER(−/ER(+ mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(− breast tumors. The favorable prognostic feature of NR5A1 is predicted by NR5A1-mediated 8-gene signature.

  16. Current status and features of the T-2 Nuclear Information Service

    Energy Technology Data Exchange (ETDEWEB)

    MacFarlane, R.E.

    1998-04-24

    This service is run by Group T-2 (Nuclear Theory and Applications) of the Theoretical Division of the Los Alamos National Laboratory, which is operated by the University of California for the US Department of Energy. The author works on nuclear modeling, nuclear data, cross sections, nuclear masses, ENDF, NJOY data processing, nuclear astrophysics, radioactivity, radiation shielding, data for medical radiotherapy, data for high-energy accelerator applications, data and codes for fission and fusion systems, and more. For an introduction to the field of nuclear data and his site, take his Guided Tour. Much of this information can also be accessed using anonymous ftp t2.lanl.gov.

  17. The 'atom-splitting' moment of synthetic biology: Nuclear physics and synthetic biology share common features

    OpenAIRE

    Valentine, Alex J; Kleinert, Aleysia; Verdier, Jerome

    2012-01-01

    Synthetic biology and nuclear physics share many commonalities in terms of public perception and funding. Synthetic biologists could learn valuable lessons from the history of the atomic bomb and nuclear power.

  18. Contribution of nuclear morphometric features to differentiation of atypical complex type endometrial hyperplasia and low grade endometrial carcinoma

    Directory of Open Access Journals (Sweden)

    Onder Onguru

    2011-08-01

    Full Text Available Objective: The differentiation of atypical complex type endometrial hyperplasia (ACEH and low grade endometrial carcinoma (EC may be problematic in endometrial biopsy materials. Desmoplasia and stromal invasion are diagnostic for EC but they are not always demonstrated in endometrial biopsies. In this study, we investigated the contribution of nuclear morphometry to distinction of ACEH and low grade EC. Methods: Ten low grade EC and eight ACEH cases retrieved from the archives of the Department of Pathology. For each case at least 100 nuclei (totally 1000 for both groups were selected using hematoxylen-eosine stained sections and evaluated by a computer assisted system. Measured nuclear morphometric features were nuclear area, nuclear perimeter, circular form factor, diameter equivalent circle, minimum feret, maximum feret, area convex hull, perimeter convex hull. Results: There was no significant differences between these two groups for circular form factor (P=0.871. But all other morphometric features were statistically significant (P<0.05. Conclusion: Our findings suggest that nuclear morphometric features may be used as an ancillary diagnostic tool in addition to conventional histopathological findings in borderline lesion. These findings should be confirmed with expanded case series. [J Exp Integr Med 2011; 1(4.000: 277-280

  19. Multidrug-exporting secondary transporters.

    Science.gov (United States)

    Murakami, Satoshi; Yamaguchi, Akihito

    2003-08-01

    The major cause of intrinsic drug resistance in Gram-negative bacteria is a resistance nodulation division type multidrug exporter, which couples with an outer membrane channel and a membrane fusion protein and exports drugs out of the cell, bypassing the periplasm; this process is driven by proton motive force. A recent crystal structure determination of a major resistance nodulation division type multidrug exporter, AcrB in Escherichia coli, greatly advances our understanding of the multidrug export mechanism. The most striking feature of the AcrB trimer is the presence of three vestibules open to the periplasm at the boundary between the periplasmic headpiece and the transmembrane region. Substrates can gain access to the central cavity from the periplasmic surface of the cytoplasmic membrane and are then actively transported through the extramembrane pore into the outer membrane channel TolC, via the funnel at the top of the AcrB headpiece.

  20. Nuclear structure features of very heavy and superheavy nuclei—tracing quantum mechanics towards the ‘island of stability’

    Science.gov (United States)

    Ackermann, D.; Theisen, Ch

    2017-08-01

    The quantum-mechanic nature of nuclear matter is at the origin of the vision of a region of enhanced stability at the upper right end of the chart of nuclei, the so-called ‘island of stability’. Since the 1960s in the early second half of the last century, various models predict closed shells for proton numbers 114-126 and neutron numbers such as 172 or 184. Being stabilized by quantum-mechanic effects only, those extremely heavy man-made nuclear species are an ideal laboratory to study the origin of the strong nuclear interaction which is the driving force for matter properties in many fields ranging from microscopic scales like hadronic systems to cosmic scales in stellar environments like neutron stars. Since the 1950s, experiments on the synthesis of new elements and isotopes have also revealed various exciting nuclear structure features. The contribution of Bohr, Mottelson and Rainwater with, in particular, the development of the unified model played an essential role in this context. Although not anticipated in the region of the heaviest nuclei, many phenomena were subsequently discovered like the interplay of collective features manifesting themselves e.g. in nuclear deformation, ranging from spherical to prolate and oblate shapes with the possible occurrence of triaxial symmetries, and single particle states and their excitation into quasiparticle configurations. The continuous development of modern experimental techniques employing advanced detection set-ups was essential to reveal these exciting nuclear structure aspects in the actinide and transactinide regions since the production cross-section becomes extremely small with increasing mass and charge. Further technological progress, in particular, high intensity stable ion beam accelerator facilities presently under construction, as well as potentially in the farther future radioactive neutron rich ion beams provide a high discovery potential for the basic understanding of nuclear matter.

  1. Expanding Exports: Can Tennessee Double Its Exports?

    OpenAIRE

    Steven G. Livingston

    2010-01-01

    In this year's State of the Union Address, President Obama announced a National Export Initiative to double American exports over the next five years. He claimed that this could add two million jobs to the American economy. Could Tennessee actually double its exports over this period? And what would be the impact if it did?

  2. 76 FR 16459 - Prohibiting Exports Involving Libya by Executive Order

    Science.gov (United States)

    2011-03-23

    ... COMMISSION Prohibiting Exports Involving Libya by Executive Order AGENCY: Nuclear Regulatory Commission... Government of Libya. FOR FURTHER INFORMATION CONTACT: Grace Kim, Office of the General Counsel, U.S. Nuclear... . SUPPLEMENTARY INFORMATION: Exports Involving the Government of Libya Suspended by Executive Order Under...

  3. Hydrolysis Profiles of Formalin Fixed Paraffin-Embedded Tumors Based on IOD (Integrated Optical Density and Nuclear Texture Feature Measurements

    Directory of Open Access Journals (Sweden)

    Margareta Fležar

    1999-01-01

    Full Text Available The aim of the study was to determine optimal hydrolysis time for the Feulgen DNA staining of archival formalin fixed paraffin‐embedded surgical samples, prepared as single cell suspensions for image cytometric measurements. The nuclear texture features along with the IOD (integrated optical density of the tumor nuclei were analysed by an automated high resolution image cytometer as a function of duration of hydrolysis treatment (in 5 N HCl at room temperature. Tissue blocks of breast carcinoma, ovarian serous carcinoma, ovarian serous tumor of borderline malignancy and leiomyosarcoma were included in the study. IOD hydrolysis profiles showed plateau between 30 and 60 min in the breast carcinoma and leiomyosarcoma, and between 40 and 60 min in the ovarian serous carcinoma and ovarian serous tumor of borderline malignancy. Most of the nuclear texture features remained stable after 20 min of hydrolysis treatment. Our results indicate that the optimal hydrolysis time for IOD and for nuclear texture feature measurements, was between 40 and 60 min in the cell preparations from tissue blocks of three epithelial and one soft tissue tumor.

  4. On a distinctive feature of problems of calculating time-average characteristics of nuclear reactor optimal control sets

    Science.gov (United States)

    Trifonenkov, A. V.; Trifonenkov, V. P.

    2017-01-01

    This article deals with a feature of problems of calculating time-average characteristics of nuclear reactor optimal control sets. The operation of a nuclear reactor during threatened period is considered. The optimal control search problem is analysed. The xenon poisoning causes limitations on the variety of statements of the problem of calculating time-average characteristics of a set of optimal reactor power off controls. The level of xenon poisoning is limited. There is a problem of choosing an appropriate segment of the time axis to ensure that optimal control problem is consistent. Two procedures of estimation of the duration of this segment are considered. Two estimations as functions of the xenon limitation were plot. Boundaries of the interval of averaging are defined more precisely.

  5. Features of adsorbed radioactive chemical elements and their isotopes distribution in iodine air filters AU-1500 at nuclear power plants

    CERN Document Server

    Neklyudov, I M; Dikiy, N P; Ledenyov, O P; Lyashko, Yu V

    2013-01-01

    The main aim of research is to investigate the physical features of spatial distribution of the adsorbed radioactive chemical elements and their isotopes in the granular filtering medium in the iodine air filters of the type of AU1500 in the forced exhaust ventilation systems at the nuclear power plant. The gamma activation analysis method is applied to accurately characterize the distribution of the adsorbed radioactive chemical elements and their isotopes in the granular filtering medium in the AU1500 iodine air filter after its long term operation at the nuclear power plant. The typical spectrum of the detected chemical elements and their isotopes in the AU1500 iodine air filter, which was exposed to the bremsstrahlung gamma quantum irradiation, produced by the accelerating electrons in the tantalum target, are obtained. The spatial distributions of the detected chemical element 127I and some other chemical elements and their isotopes in the layer of absorber, which was made of the cylindrical coal granule...

  6. Demand Uncertainty: Exporting Delays and Exporting Failures

    DEFF Research Database (Denmark)

    Nguyen, Daniel Xuyen

    2012-01-01

    This paper presents a model of trade that explains why firms wait to export and why many exporters fail. Firms face uncertain demands that are only realized after the firm enters the destination. The model retools the timing of the resolution of uncertainty found in models with heterogeneity...... to forecast unknown demands in untested destinations. The option to forecast demands causes firms to delay exporting in order to gather more information about foreign demand. Third, since uncertainty is resolved after entry, many firms enter a destination and then exit after learning that they cannot profit....... This prediction reconciles the high rate of exit seen in the first years of exporting. Finally, when faced with multiple destinations to which they can export, many firms will choose to sequentially export in order to slowly learn more about its chances for success in untested markets....

  7. Autographa californica Multiple Nucleopolyhedrovirus Ac34 Protein Retains Cellular Actin-Related Protein 2/3 Complex in the Nucleus by Subversion of CRM1-Dependent Nuclear Export

    NARCIS (Netherlands)

    Mu, Jingfang; Zhang, Yongli; Hu, Yangyang; Hu, Xue; Zhou, Yuan; Zhao, He; Pei, Rongjuan; Wu, Chunchen; Chen, Jizheng; Zhao, Han; Yang, Kai; Oers, van Monique; Chen, Xinwen; Wang, Yun

    2016-01-01

    Actin, nucleation-promoting factors (NPFs), and the actin-related protein 2/3 complex (Arp2/3) are key elements of the cellular actin polymerization machinery. With nuclear actin polymerization implicated in ever-expanding biological processes and the discovery of the nuclear import mechanisms of ac

  8. Learning by Exporting

    DEFF Research Database (Denmark)

    Cruz, Antonio; Newman, Carol; Rand, John

    2017-01-01

    In this article, we analyse the learning-by-exporting (LBE) hypothesis in the Mozambican context. Due to the presence of the ‘Born-Global’ phenomenon among exporters, we address the endogeneity introduced by self-selection, combining a generalised Blinder–Oaxaca approach with results from...... traditional matching techniques. Our results show that very few manufacturing firms export, and that export participation is highly persistent. There is also evidence supporting the LBE hypothesis and the results suggest a significant export premium of between 17 and 21%, controlling for differences...... in observable characteristics between exporters and non-exporters. Finally, qualitative information on non-exporters seeking new markets suggests that ‘lack of knowledge of potential markets’ is the most severe constraint to international market entry. We conclude that the Mozambican Export Promotion Institute...

  9. Nuclear Exodus: Herpesviruses Lead the Way.

    Science.gov (United States)

    Bigalke, Janna M; Heldwein, Ekaterina E

    2016-09-29

    Most DNA viruses replicate in the nucleus and exit it either by passing through the nuclear pores or by rupturing the nuclear envelope. Unusually, herpesviruses have evolved a complex mechanism of nuclear escape whereby nascent capsids bud at the inner nuclear membrane to form perinuclear virions that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytosol. Although this general scheme is accepted in the field, the players and their roles are still debated. Recent studies illuminated critical mechanistic features of this enigmatic process and uncovered surprising parallels with a novel cellular nuclear export process. This review summarizes our current understanding of nuclear egress in herpesviruses, examines the experimental evidence and models, and outlines outstanding questions with the goal of stimulating new research in this area.

  10. Nuclear control

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Wan Kee [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-02-01

    International cooperation in nuclear industries requires nuclear control as prerequisites. The concept of nuclear control is based on the Treaty on the Non-proliferation of Nuclear Weapon (NPT). The International Atomic Energy Agency (IAEA) plays central role in implementing nuclear control. Nuclear control consists of nuclear safeguards, physical protection, and export/import control. Each member state of NPT is subject to the IAEA`s safeguards by concluding safeguards agreements with the IAEA. IAEA recommends member states to implement physical protection on nuclear materials by `The Physical Protection of Nuclear Material` and `The Convention on the Physical Protection of Nuclear Material` of IAEA. Export/Import Control is to deter development of nuclear weapons by controlling international trade on nuclear materials, nuclear equipments and technology. Current status of domestic and foreign nuclear control implementation including recent induction of national inspection system in Korea is described and functions of recently set-up Technology Center for Nuclear Control (TCNC) under the Korea Atomic Energy Research Institute (KAERI) are also explained. 6 tabs., 11 refs. (Author).

  11. Microinjection and Fluorescence In Situ Hybridization Assay for Studying mRNA Export in Mammalian Cells.

    Science.gov (United States)

    Wang, Ke; Shi, Min; Cheng, Hong

    2017-01-01

    Microinjection and Fluorescence in situ Hybridization (FISH) assay is a useful method for mRNA export studies, which can overcome the problems of traditional transfection in cells. Here, we describe the method of microinjection and FISH assay applied in investigation of mRNA export. By this method we can estimate the mRNA export kinetics, examining mRNA export in cells with low transfection efficiencies, and observing nuclear export of aberrant RNAs.

  12. Multiple Export Mechanisms for mRNAs

    Science.gov (United States)

    Delaleau, Mildred; Borden, Katherine L. B.

    2015-01-01

    Nuclear mRNA export plays an important role in gene expression. We describe the mechanisms of mRNA export including the importance of mRNP assembly, docking with the nuclear basket of the nuclear pore complex (NPC), transit through the central channel of the NPC and cytoplasmic release. We describe multiple mechanisms of mRNA export including NXF1 and CRM1 mediated pathways. Selective groups of mRNAs can be preferentially transported in order to respond to cellular stimuli. RNAs can be selected based on the presence of specific cis-acting RNA elements and binding of specific adaptor proteins. The role that dysregulation of this process plays in human disease is also discussed. PMID:26343730

  13. Familial partial lipodystrophy, mandibuloacral dysplasia and restrictive dermopathy feature barrier-to-autointegration factor (BAF) nuclear redistribution.

    Science.gov (United States)

    Capanni, Cristina; Squarzoni, Stefano; Cenni, Vittoria; D'Apice, Maria Rosaria; Gambineri, Alessandra; Novelli, Giuseppe; Wehnert, Manfred; Pasquali, Renato; Maraldi, Nadir M; Lattanzi, Giovanna

    2012-10-01

    Prelamin A processing impairment is a common feature of a restricted group of rare genetic alterations/disorders associated with a wide range of clinical phenotypes. Changes in histone posttranslational modifications, alterations in non-histone chromatin proteins and chromatin disorganization have been specifically linked to impairment of specific, distinct prelamin A processing steps, but the molecular mechanism involved in these processes is not yet understood . In this study, we show that the accumulation of wild-type prelamin A detected in restrictive dermopathy (RD), as well as the accumulation of mutated forms of prelamin A identified in familial partial lipodystrophy (FPLD) and mandibuloacral dysplasia (MADA), affect the nuclear localization of barrier-to-autointegration factor (BAF), a protein able to link lamin A precursor to chromatin remodeling functions. Our findings, in accordance with previously described results, support the hypothesis of a prelamin A involvement in BAF nuclear recruitment and suggest BAF-prelamin A complex as a protein platform usually activated in prelamin A-accumulating diseases. Finally, we demonstrate the involvement of the inner nuclear membrane protein emerin in the proper localization of BAF-prelamin A complex.

  14. Logistics and Exports

    OpenAIRE

    2008-01-01

    Drawing on a new and comprehensive measure of logistics quality, our gravity model suggests logistics in the exporting and partner-country can have an important impact on bilateral exports. A one standard deviation improvement in the exporter’s logistics quality, which for example would improve Gabon to the level of Guinea, would raise exports by almost 60%. Landlocked countries’ exports depend on their neighbours’ logistics, but their own logistics quality is not as important as for other co...

  15. Exporting RNA from the nucleus to the cytoplasm.

    Science.gov (United States)

    Köhler, Alwin; Hurt, Ed

    2007-10-01

    The transport of RNA molecules from the nucleus to the cytoplasm is fundamental for gene expression. The different RNA species that are produced in the nucleus are exported through the nuclear pore complexes via mobile export receptors. Small RNAs (such as tRNAs and microRNAs) follow relatively simple export routes by binding directly to export receptors. Large RNAs (such as ribosomal RNAs and mRNAs) assemble into complicated ribonucleoprotein (RNP) particles and recruit their exporters via class-specific adaptor proteins. Export of mRNAs is unique as it is extensively coupled to transcription (in yeast) and splicing (in metazoa). Understanding the mechanisms that connect RNP formation with export is a major challenge in the field.

  16. SGK1 affects RAN/RANBP1/RANGAP1 via SP1 to play a critical role in pre-miRNA nuclear export: a new route of epigenomic regulation

    Science.gov (United States)

    Dattilo, Vincenzo; D’Antona, Lucia; Talarico, Cristina; Capula, Mjriam; Catalogna, Giada; Iuliano, Rodolfo; Schenone, Silvia; Roperto, Sante; Bianco, Cataldo; Perrotti, Nicola; Amato, Rosario

    2017-01-01

    The serum- and glucocorticoid-regulated kinase (SGK1) controls cell transformation and tumor progression. SGK1 affects mitotic stability by regulating the expression of RANBP1/RAN. Here, we demonstrate that SGK1 fluctuations indirectly modify the maturation of pre-miRNAs, by modulating the equilibrium of the RAN/RANBP1/RANGAP1 axis, the main regulator of nucleo-cytoplasmic transport. The levels of pre-miRNAs and mature miRNAs were assessed by qRT-PCR, in total extracts and after differential nuclear/cytoplasmic extraction. RANBP1 expression is the limiting step in the regulation of SGK1-SP1 dependent nuclear export. These results were validated in unrelated tumor models and primary human fibroblasts and corroborated in tumor-engrafted nude mice. The levels of pri-miRNAs, DROSHA, DICER and the compartmental distribution of XPO5 were documented. Experiments using RANGTP conformational antibodies confirmed that SGK1, through RANBP1, decreases the level of the GTP-bound state of RAN. This novel mechanism may play a role in the epigenomic regulation of cell physiology and fate. PMID:28358001

  17. Design data and safety features of commercial nuclear power plants. Vol. I. Docket No. 50-3 through 50-295

    Energy Technology Data Exchange (ETDEWEB)

    Heddleson, F. A.

    1973-12-01

    BS>Design data, safety features, and site characteristics are summarized for thirty-two commercial nuclear power plants in the United States. Six pages of data are presented for each plant consisting of Thermal-Hydraulic and Nuclear Factors, Containment Features, Emergency Core Cooling Systems, Site Features, Circulating Water System Data, and Miscellaneous Factors. An aerial perspective is also presented for each plant. Those covered in this volume are Indian Point No. 1, Docket Number 50-3, and all subsequent plants finishing with Zion, Docket Number 50-295. (auth)

  18. Design data and safety features of commercial nuclear power plants. Vol. I. Docket No. 50-3 through 50-295

    Energy Technology Data Exchange (ETDEWEB)

    Heddleson, F. A.

    1973-12-01

    BS>Design data, safety features, and site characteristics are summarized for thirty-two commercial nuclear power plants in the United States. Six pages of data are presented for each plant consisting of Thermal-Hydraulic and Nuclear Factors, Containment Features, Emergency Core Cooling Systems, Site Features, Circulating Water System Data, and Miscellaneous Factors. An aerial perspective is also presented for each plant. Those covered in this volume are Indian Point No. 1, Docket Number 50-3, and all subsequent plants finishing with Zion, Docket Number 50-295. (auth)

  19. Ecosystem monitoring on dispersion and export dynamics of ¹³⁷Cs deposited on the forested area in Fukushima after the nuclear power stations accident in March 2011

    Energy Technology Data Exchange (ETDEWEB)

    Ohte, Nobuhito; Endo, Izuki; Iseda, Kohei; Tanoi, Keitaro [University of Tokyo, Bunkyo-ku, Tokyo, 113-8657 (Japan); Murakami, Masashi [Chiba University, Inage-ku, Chiba, 263-8522 (Japan); Ishii, Nobuyoshi [National Institute of Radiological Sciences, Inage-ku, Chiba, 263-8555 (Japan)

    2014-07-01

    The accident of the Fukushima Daiichi Nuclear Power Stations in March 2011 emitted 1.5x10¹⁷ Bq of ¹³¹I, 1.2x10¹⁶ Bq of ¹³⁷Cs into the surrounding environment. Those radioactive substances including ¹³⁷Cs deposited onto the forest areas of the northeastern region of the Honshu Island, Japan. Forests of these regions are especially important for the people not only for their forest production industry, but also for the source areas of drinking water. The first phase of the governmental survey and investigations showed that major portion of deposited ¹³⁷Cs is trapped on the canopies and litter layers of soil surface. As ¹³⁷Cs is easily adsorbed onto clay minerals in soil, major portion of those can be transported by eroded soils and particulate organic matters through the hydrological pathways. Dissolved ¹³⁷Cs which is relatively free from soil adsorption can be taken up by microbes, algae and plants in soil and aquatic systems. Then, those ¹³⁷Cs are eventually introduced into soil insects, worms, aquatic insects, fishes and birds through the food web. To clarify the mechanisms of dispersion and export of ¹³⁷Cs within and from a forested ecosystem, we started intensive field observations and samplings in a small catchment including forests and farmlands in the area ~50 km distant from the Nuclear Power Station. The study is conducted at the Kami-Oguni River catchment in the northern part of Fukushima Prefecture. Major land uses of the catchment are forests and paddy fields. Expected two major pathways of ¹³⁷Cs diffusion and export are investigated; 1) transportation by water movement with dissolved and particulate or colloidal forms through the hydrological processes, 2) dispersion through the food web including both detritus food chains based upon plant litters and grazing food chains based upon living plant leaves in the forest-stream ecological continuum. The ¹³⁷Cs concentrations of stream waters at several sampling

  20. A protein inventory of human ribosome biogenesis reveals an essential function of exportin 5 in 60S subunit export.

    Science.gov (United States)

    Wild, Thomas; Horvath, Peter; Wyler, Emanuel; Widmann, Barbara; Badertscher, Lukas; Zemp, Ivo; Kozak, Karol; Csucs, Gabor; Lund, Elsebet; Kutay, Ulrike

    2010-10-26

    The assembly of ribosomal subunits in eukaryotes is a complex, multistep process so far mostly studied in yeast. In S. cerevisiae, more than 200 factors including ribosomal proteins and trans-acting factors are required for the ordered assembly of 40S and 60S ribosomal subunits. To date, only few human homologs of these yeast ribosome synthesis factors have been characterized. Here, we used a systematic RNA interference (RNAi) approach to analyze the contribution of 464 candidate factors to ribosomal subunit biogenesis in human cells. The screen was based on visual readouts, using inducible, fluorescent ribosomal proteins as reporters. By performing computer-based image analysis utilizing supervised machine-learning techniques, we obtained evidence for a functional link of 153 human proteins to ribosome synthesis. Our data show that core features of ribosome assembly are conserved from yeast to human, but differences exist for instance with respect to 60S subunit export. Unexpectedly, our RNAi screen uncovered a requirement for the export receptor Exportin 5 (Exp5) in nuclear export of 60S subunits in human cells. We show that Exp5, like the known 60S exportin Crm1, binds to pre-60S particles in a RanGTP-dependent manner. Interference with either Exp5 or Crm1 function blocks 60S export in both human cells and frog oocytes, whereas 40S export is compromised only upon inhibition of Crm1. Thus, 60S subunit export is dependent on at least two RanGTP-binding exportins in vertebrate cells.

  1. NR-2L: a two-level predictor for identifying nuclear receptor subfamilies based on sequence-derived features.

    Directory of Open Access Journals (Sweden)

    Pu Wang

    Full Text Available Nuclear receptors (NRs are one of the most abundant classes of transcriptional regulators in animals. They regulate diverse functions, such as homeostasis, reproduction, development and metabolism. Therefore, NRs are a very important target for drug development. Nuclear receptors form a superfamily of phylogenetically related proteins and have been subdivided into different subfamilies due to their domain diversity. In this study, a two-level predictor, called NR-2L, was developed that can be used to identify a query protein as a nuclear receptor or not based on its sequence information alone; if it is, the prediction will be automatically continued to further identify it among the following seven subfamilies: (1 thyroid hormone like (NR1, (2 HNF4-like (NR2, (3 estrogen like, (4 nerve growth factor IB-like (NR4, (5 fushi tarazu-F1 like (NR5, (6 germ cell nuclear factor like (NR6, and (7 knirps like (NR0. The identification was made by the Fuzzy K nearest neighbor (FK-NN classifier based on the pseudo amino acid composition formed by incorporating various physicochemical and statistical features derived from the protein sequences, such as amino acid composition, dipeptide composition, complexity factor, and low-frequency Fourier spectrum components. As a demonstration, it was shown through some benchmark datasets derived from the NucleaRDB and UniProt with low redundancy that the overall success rates achieved by the jackknife test were about 93% and 89% in the first and second level, respectively. The high success rates indicate that the novel two-level predictor can be a useful vehicle for identifying NRs and their subfamilies. As a user-friendly web server, NR-2L is freely accessible at either http://icpr.jci.edu.cn/bioinfo/NR2L or http://www.jci-bioinfo.cn/NR2L. Each job submitted to NR-2L can contain up to 500 query protein sequences and be finished in less than 2 minutes. The less the number of query proteins is, the shorter the time will

  2. NR-2L: a two-level predictor for identifying nuclear receptor subfamilies based on sequence-derived features.

    Science.gov (United States)

    Wang, Pu; Xiao, Xuan; Chou, Kuo-Chen

    2011-01-01

    Nuclear receptors (NRs) are one of the most abundant classes of transcriptional regulators in animals. They regulate diverse functions, such as homeostasis, reproduction, development and metabolism. Therefore, NRs are a very important target for drug development. Nuclear receptors form a superfamily of phylogenetically related proteins and have been subdivided into different subfamilies due to their domain diversity. In this study, a two-level predictor, called NR-2L, was developed that can be used to identify a query protein as a nuclear receptor or not based on its sequence information alone; if it is, the prediction will be automatically continued to further identify it among the following seven subfamilies: (1) thyroid hormone like (NR1), (2) HNF4-like (NR2), (3) estrogen like, (4) nerve growth factor IB-like (NR4), (5) fushi tarazu-F1 like (NR5), (6) germ cell nuclear factor like (NR6), and (7) knirps like (NR0). The identification was made by the Fuzzy K nearest neighbor (FK-NN) classifier based on the pseudo amino acid composition formed by incorporating various physicochemical and statistical features derived from the protein sequences, such as amino acid composition, dipeptide composition, complexity factor, and low-frequency Fourier spectrum components. As a demonstration, it was shown through some benchmark datasets derived from the NucleaRDB and UniProt with low redundancy that the overall success rates achieved by the jackknife test were about 93% and 89% in the first and second level, respectively. The high success rates indicate that the novel two-level predictor can be a useful vehicle for identifying NRs and their subfamilies. As a user-friendly web server, NR-2L is freely accessible at either http://icpr.jci.edu.cn/bioinfo/NR2L or http://www.jci-bioinfo.cn/NR2L. Each job submitted to NR-2L can contain up to 500 query protein sequences and be finished in less than 2 minutes. The less the number of query proteins is, the shorter the time will

  3. Flexible feature interface for multimedia sources

    Science.gov (United States)

    Coffland, Douglas R [Livermore, CA

    2009-06-09

    A flexible feature interface for multimedia sources system that includes a single interface for the addition of features and functions to multimedia sources and for accessing those features and functions from remote hosts. The interface utilizes the export statement: export "C" D11Export void FunctionName(int argc, char ** argv,char * result, SecureSession *ctrl) or the binary equivalent of the export statement.

  4. A novel non-linear recursive filter design for extracting high rate pulse features in nuclear medicine imaging and spectroscopy.

    Science.gov (United States)

    Sajedi, Salar; Kamal Asl, Alireza; Ay, Mohammad R; Farahani, Mohammad H; Rahmim, Arman

    2013-06-01

    Applications in imaging and spectroscopy rely on pulse processing methods for appropriate data generation. Often, the particular method utilized does not highly impact data quality, whereas in some scenarios, such as in the presence of high count rates or high frequency pulses, this issue merits extra consideration. In the present study, a new approach for pulse processing in nuclear medicine imaging and spectroscopy is introduced and evaluated. The new non-linear recursive filter (NLRF) performs nonlinear processing of the input signal and extracts the main pulse characteristics, having the powerful ability to recover pulses that would ordinarily result in pulse pile-up. The filter design defines sampling frequencies lower than the Nyquist frequency. In the literature, for systems involving NaI(Tl) detectors and photomultiplier tubes (PMTs), with a signal bandwidth considered as 15 MHz, the sampling frequency should be at least 30 MHz (the Nyquist rate), whereas in the present work, a sampling rate of 3.3 MHz was shown to yield very promising results. This was obtained by exploiting the known shape feature instead of utilizing a general sampling algorithm. The simulation and experimental results show that the proposed filter enhances count rates in spectroscopy. With this filter, the system behaves almost identically as a general pulse detection system with a dead time considerably reduced to the new sampling time (300 ns). Furthermore, because of its unique feature for determining exact event times, the method could prove very useful in time-of-flight PET imaging.

  5. Contribution of Energetically Reactive Surface Features to the Dissolution of CeO2 and ThO2 Analogues for Spent Nuclear Fuel Microstructures

    OpenAIRE

    Corkhill, C.; Myllykyla, E.; Bailey, D. J.; Thornber, S.M.; Qi, J.; Maldonado, P.; Stennett, M.C.; Hamilton, A.; Hyatt, N.C.

    2014-01-01

    In the safety case for the geological disposal of nuclear waste, the release of radioactivity from the repository is controlled by the dissolution of the spent fuel in groundwater. There remain several uncertainties associated with understanding spent fuel dissolution, including the contribution of energetically reactive surface sites to the dissolution rate. In this study, we investigate how surface features influence the dissolution rate of synthetic CeO2 and ThO2, spent nuclear fuel analog...

  6. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

    2014-01-20

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

  7. Problems and Characteristics of Russian Platinum Metals Exporters

    Institute of Scientific and Technical Information of China (English)

    ANDREEV A. M.; KELCHEVSKAYA N. R.

    2012-01-01

    The paper revealed the place and role of Russia in the global market of platinum metals,highlighted features of pricing in the export of Russian platinum group metals,the main problems of pricing in the export contracts related to the instability of markets and imperfect currency and customs legislation of the Russian Federation,proposed innovative ways to solutions to existing problems in the preparation and conclusion of export contracts.

  8. Exporter Price Premia?

    DEFF Research Database (Denmark)

    Jäkel, Ina Charlotte; Sørensen, Allan

    -cut prediction on the sign of the exporter price premium. However, the model unambiguously predicts a negative exporter price premium in terms of quality-adjusted prices, i.e. prices per unit of quality. This prediction is broadly borne out in the Danish data: while the magnitude of the premium varies across...

  9. Industrialisation, Exports and Employment.

    Science.gov (United States)

    Sabolo, Yves

    1980-01-01

    After reviewing trends in industrial production, exports, and employment in the Third World since 1960, the author discusses industrialization strategies based on the local processing of raw materials for export. Such processing has proved to be a major factor in job creation. (Author/SK)

  10. Developing Refractories for Exporting

    Institute of Scientific and Technical Information of China (English)

    PANShang-xin

    1996-01-01

    The total output of China refractory products and export volume of China refractory raw materials rank the first in the world,In future the task is to improve the quality of the products to enlarge the variety and to expand export.

  11. Exports to Imports

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    China covers ground as it attempts to balance imports and exports after a trade deficit in the first quarter As China gears up to rebalance its economy,a key factor will be weaning its reliance on exports.The vigorous efforts are paying off as the country reported a trade deficit in the first

  12. Strong Support for Exporters

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ The sweeping international financial crisis has taken its toll on the Chinese economy,especially in the export sector.On the one hand,overseas demand has plummeted,while on the other,with the worsening credit environment and emerging trade protectionism,export enterprises are suffering from rising credit risks to the point where some dare not even accept orders.

  13. Markups and Exporting Behavior

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic Michel Patrick

    2012-01-01

    estimates of plant- level markups without specifying how firms compete in the product market. We rely on our method to explore the relationship be- tween markups and export behavior. We find that markups are estimated significantly higher when controlling for unobserved productivity; that exporters charge...

  14. An analysis on the export license criteria for NSG control items in the US and Japan

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Rok [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-06-01

    Korea has taken steps to join the Nuclear Suppliers Group (NSG) which is a major part of the international nuclear export control regime. In this connection, it is an urgent task to build a new Korean nuclear export control system that includes NSG guidelines and control items. In addition, it is necessary to review the developed supplier countries` experience in the field of export control. The main purpose of this study is to analyze how the US and Japan have controlled the items listed in NSG part 1 and 2 guidelines. To this end, various relevant regulations of the US and Japan were studied. Among those regulations, the US Export Administration Regulation, US 10 CFR 110 and 810, and the Japan`s Export Administration Order are included. Through the review process, this study identified NSG items which are controlled in the export control systems of the US and Japan. Furthermore, this study summarized and compared the export license criteria that must be satisfied before exporting each NSG item in the two countries. The export license criteria consist of permitted destinations, document requirements, and types of license. The results of this study are expected to contribute to establishing an appropriate Korean nuclear export control system and could be used as references to the practical export licensing policies of the US and Japan. 6 tabs., 13 refs., (Author) .new.

  15. Guide to software export

    CERN Document Server

    Philips, Roger A

    2014-01-01

    An ideal reference source for CEOs, marketing and sales managers, sales consultants, and students of international marketing, Guide to Software Export provides a step-by-step approach to initiating or expanding international software sales. It teaches you how to examine critically your candidate product for exportability; how to find distributors, agents, and resellers abroad; how to identify the best distribution structure for export; and much, much more!Not content with providing just the guidelines for setting up, expanding, and managing your international sales channels, Guide to Software

  16. Structural features and ligand binding properties of tandem WW domains from YAP and TAZ, nuclear effectors of the Hippo pathway.

    Science.gov (United States)

    Webb, Claire; Upadhyay, Abhishek; Giuntini, Francesca; Eggleston, Ian; Furutani-Seiki, Makoto; Ishima, Rieko; Bagby, Stefan

    2011-04-26

    The paralogous multifunctional adaptor proteins YAP and TAZ are the nuclear effectors of the Hippo pathway, a central mechanism of organ size control and stem cell self-renewal. WW domains, mediators of protein-protein interactions, are essential for YAP and TAZ function, enabling interactions with PPxY motifs of numerous partner proteins. YAP has single and double WW domain isoforms (YAP1 and YAP2) whereas only a single WW domain isoform of TAZ has been described to date. Here we identify the first example of a double WW domain isoform of TAZ. Using NMR, we have characterized conformational features and peptide binding of YAP and TAZ tandem WW domains (WW1-WW2). The solution structure of YAP WW2 confirms that it has a canonical three-stranded antiparallel β-sheet WW domain fold. While chemical shift-based analysis indicates that the WW domains in the tandem WW pairs retain the characteristic WW domain fold, 15N relaxation data show that, within the respective WW pairs, YAP WW1 and both WW1 and WW2 of TAZ undergo conformational exchange. 15N relaxation data also indicate that the linker between the WW domains is flexible in both YAP and TAZ. Within both YAP and TAZ tandem WW pairs, WW1 and WW2 bind single PPxY-containing peptide ligand concurrently and noncooperatively with sub-mM affinity. YAP and TAZ WW1-WW2 bind a dual PPxY-containing peptide with approximately 6-fold higher affinity. Our results indicate that both WW domains in YAP and TAZ are functional and capable of enhanced affinity binding to multi-PPxY partner proteins such as LATS1, ErbB4, and AMOT.

  17. Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Yi; Seo, Hyuk-Soo; Blobel, Günter; Hoelz, André (Rockefeller)

    2010-07-23

    The export of mRNAs is a multistep process, involving the packaging of mRNAs into messenger ribonucleoprotein particles (mRNPs), their transport through nuclear pore complexes, and mRNP remodeling events prior to translation. Ribonucleic acid export 1 (Rae1) and Nup98 are evolutionarily conserved mRNA export factors that are targeted by the vesicular stomatitis virus matrix protein to inhibit host cell nuclear export. Here, we present the crystal structure of human Rae1 in complex with the Gle2-binding sequence (GLEBS) of Nup98 at 1.65 {angstrom} resolution. Rae1 forms a seven-bladed {beta}-propeller with several extensive surface loops. The Nup98 GLEBS motif forms an {approx} 50-{angstrom}-long hairpin that binds with its C-terminal arm to an essentially invariant hydrophobic surface that extends over the entire top face of the Rae1 {beta}-propeller. The C-terminal arm of the GLEBS hairpin is necessary and sufficient for Rae1 binding, and we identify a tandem glutamate element in this arm as critical for complex formation. The Rae1 {center_dot} Nup98{sup GLEBS} surface features an additional conserved patch with a positive electrostatic potential, and we demonstrate that the complex possesses single-stranded RNA-binding capability. Together, these data suggest that the Rae1 {center_dot} Nup98 complex directly binds to the mRNP at several stages of the mRNA export pathway.

  18. Structural and Functional Analysis of the Interaction Between the Nucleoporin Nup98 and the mRNA Export Facto Rae1

    Energy Technology Data Exchange (ETDEWEB)

    Y Ren; H Seo; G Blobel; A Hoelz

    2011-12-31

    The export of mRNAs is a multistep process, involving the packaging of mRNAs into messenger ribonucleoprotein particles (mRNPs), their transport through nuclear pore complexes, and mRNP remodeling events prior to translation. Ribonucleic acid export 1 (Rae1) and Nup98 are evolutionarily conserved mRNA export factors that are targeted by the vesicular stomatitis virus matrix protein to inhibit host cell nuclear export. Here, we present the crystal structure of human Rae1 in complex with the Gle2-binding sequence (GLEBS) of Nup98 at 1.65 {angstrom} resolution. Rae1 forms a seven-bladed {beta}-propeller with several extensive surface loops. The Nup98 GLEBS motif forms an {approx}50-{angstrom}-long hairpin that binds with its C-terminal arm to an essentially invariant hydrophobic surface that extends over the entire top face of the Rae1 {beta}-propeller. The C-terminal arm of the GLEBS hairpin is necessary and sufficient for Rae1 binding, and we identify a tandem glutamate element in this arm as critical for complex formation. The Rae1 {center_dot} Nup98{sup GLEBS} surface features an additional conserved patch with a positive electrostatic potential, and we demonstrate that the complex possesses single-stranded RNA-binding capability. Together, these data suggest that the Rae1 {center_dot} Nup98 complex directly binds to the mRNP at several stages of the mRNA export pathway.

  19. Intermediation in Foreign Trade: When do Exporters Rely on Intermediaries?

    DEFF Research Database (Denmark)

    Schröder, Philipp; Trabold, Harald; Trübswetter, Parvati

    2003-01-01

    The paper explores theoretically and empirically why trade intermediaries (TIs) are frequently used as agents for exports to some countries but not to others. We adapt a standard intra-industry trade model with variable export costs (e.g. transport) and fixed export costs (e.g. market access......) to include a TI that is able to pool market access cost. From this framework explanatory factors for the TI share in a country's exports are derived and subsequently tested with a new data set based on French customs information. The paper finds that: (i) higher market access costs increase the TI share, (ii......) smaller export markets feature a larger TI share, (iii) the TI share is independent from variable (distance-dependent) export costs....

  20. Valie EXPORT Society Rooseumis

    Index Scriptorium Estoniae

    2002-01-01

    Malmös Rooseumi Kaasaegse Kunsti Keskuses näitus "Baltic Babel". Projekt koosneb Läänemeremaade linnades tegutsevate innovatiivsete gruppide aktsioonidest. Kuraator Charles Esche. Esinejatest (Eestist Valie Export Society: Kadi Estland, Killu Sukmit)

  1. Valie EXPORT Society. Overlok

    Index Scriptorium Estoniae

    2001-01-01

    Valie EXPORT Society asutasid 23. okt. 1999. a. Frankfurdis Kadi Estland, Killu Sukmit ja Mari Laanemets, kui olid külastanud austria naiskunstniku Valie Exporti näitust. Rühmituse aktsioonide kirjeldus

  2. Exporting Humanist Architecture

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2016-01-01

    values and ethical stands involved in the export of Danish Architecture. Abstract: Danish architecture has, in a sense, been driven by an unwritten contract between the architects and the democratic state and its institutions. This contract may be viewed as an ethos – an architectural tradition...... with inherent aesthetic and moral values. Today, however, Danish architecture is also an export commodity. That raises questions, which should be debated as openly as possible. What does it mean for architecture and architects to practice in cultures and under political systems that do not use architecture...... as a way of generating humanism, freedom or equality? The essay outlines the background story, identifies a number of positions in relation to architecture exports and discusses some of the dilemmas that arise when Danish architecture is seen in an export perspective....

  3. Valie EXPORT Society Rooseumis

    Index Scriptorium Estoniae

    2002-01-01

    Malmös Rooseumi Kaasaegse Kunsti Keskuses näitus "Baltic Babel". Projekt koosneb Läänemeremaade linnades tegutsevate innovatiivsete gruppide aktsioonidest. Kuraator Charles Esche. Esinejatest (Eestist Valie Export Society: Kadi Estland, Killu Sukmit)

  4. Valie EXPORT Society. Overlok

    Index Scriptorium Estoniae

    2001-01-01

    Valie EXPORT Society asutasid 23. okt. 1999. a. Frankfurdis Kadi Estland, Killu Sukmit ja Mari Laanemets, kui olid külastanud austria naiskunstniku Valie Exporti näitust. Rühmituse aktsioonide kirjeldus

  5. Slowed Exports Growth

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Ⅲ. Slowed export recovery in the second half Since the beginning of this year, global trade has maintained a recovery growth thanks to the worldwide economic rally.From January to April, the imports of three major Economics--the United States, the euro zone and Japan--rose 17.5 percent on average from a year ago. Import growths for the United States, the euro zone and Japan were 20.9 percent, 4.8 percent and 29 percent, respectively, which spurred China's exports to those regions. From January to June this year, China's exports totaled $705.09 billion, up 35.2 percent from the same period in 2009 and were 5.8 percent higher than the first half of 2008 when the crisis had yet to begin. Those figures indicated China's exports had rebounded to precrisis levels.

  6. Illegal Weapons Exports?

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Amnesty International, a human rights organization, released a report on June 11 accusing China of facilitating regional conflicts and human rights violations by exporting a large quantity of weapons to Sudan, Nepal, Myanmar and the Great Lakes countries of Africa. Responding to such charges, Teng Jianqun, a researcher with the China Arms Control and Disarmament Association, told the official Xinhua News Agency that China has always put its limited arms exports under strict control and surveillance, deno...

  7. Exploitative Learning by Exporting

    DEFF Research Database (Denmark)

    Golovko, Elena; Lopes Bento, Cindy; Sofka, Wolfgang

    Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies and learn......Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies...... and learning about new markets ? R&D investments and marketing investments, in search of novel insights into the content and process underlying learning by exporting. We draw from organizational learning theory for predicting changes in both R&D and marketing investment patterns that accompany firm entry...... into exporting and link these changes to firm productivity. Our results show that marketing investments are equally likely to be triggered by exporting as R&D investments. Furthermore, our results suggest that although export entry is accompanied by increases in both R&D and marketing expenditures...

  8. Export Taxes under Bertrand Duopoly

    OpenAIRE

    Clarke, Roger; Collie, David R.

    2006-01-01

    This article analyses export taxes in a Bertrand duopoly with product differentiation, where a home and a foreign firm both export to a third-country market. It is shown that the maximum-revenue export tax always exceeds the optimum-welfare export tax. In a Nash equilibrium in export taxes, the country with the low cost firm imposes the largest export tax. The results under Bertrand duopoly are compared with those under Cournot duopoly. It is shown that the absolute value of the export subsid...

  9. Nuclear structures in Tribolium castaneum oocytes.

    Science.gov (United States)

    Bogolyubov, Dmitry S; Batalova, Florina M; Kiselyov, Artyom M; Stepanova, Irina S

    2013-10-01

    The first ultrastructural and immunomorphological characteristics of the karyosphere (karyosome) and extrachromosomal nuclear bodies in the red flour beetle, Tribolium castaneum, are presented. The karyosphere forms early in the diplotene stage of meiotic prophase by the gathering of all oocyte chromosomes in a limited nuclear volume. Using the BrUTP assay, T. castaneum oocyte chromosomes united in the karyosphere maintain their transcriptional activity until the end of oocyte growth. Hyperphosphorylated RNA polymerase II and basal transcription factors (TFIID and TFIIH) were detected in the perichromatin region of the karyosphere. The T. castaneum karyosphere has an extrachromosomal capsule that separates chromosomes from the rest of the nucleoplasm. Certain structural proteins (F-actin, lamin B) were found in the capsule. Unexpectedly, the karyosphere capsule in T. castaneum oocytes was found to be enriched in TMG-capped snRNAs, which suggests that the capsule is not only a structural support for the karyosphere, but may be involved in biogenesis of snRNPs. We also identified the counterparts of 'universal' extrachromosomal nuclear domains, Cajal bodies (CBs) and interchromatin granule clusters (IGCs). Nuclear bodies containing IGC marker protein SC35 display some features unusual for typical IGCs. SC35 domains in T. castaneum oocytes are predominantly fibrillar complex bodies that do not contain trimethyl guanosine (TMG)-capped small nuclear (sn) RNAs. Microinjections of 2'-O-methyl (U)22 probes into the oocytes allowed revealing poly(A)+ RNAs in these nuclear domains. Several proteins related to mRNA export (heterogeneous ribonucleoprotein core protein A1, export adapters Y14 and Aly and export receptor NXF1) were also detected there. We believe that unusual SC35 nuclear domains of T. castaneum oocytes are possibly involved in mRNP but not snRNP biogenesis.

  10. Technical Features and Evolution Trend of High-Tech Products Export of China, Japan and South Korea——An Empirical Study Based on the Export Sophistication%中日韩高技术产品出口贸易技术特征和演进趋势研究——基于出口复杂度的实证研究

    Institute of Scientific and Technical Information of China (English)

    汤碧

    2012-01-01

    As the core of a country's technological strength, high-tech industries become more and more important. China, Japan and South Korea are the major exporter of high-tech products and the FTA negotiations among them are about to start. In this context, this paper described the status of high-tech products of China, Japan and South Korea. It applied the export Sophistication index constructed by Hausmann to estimate high-tech products export Sophistication of China, Japan and South Korea's with HS 4-digit. Then it analyzed the technical features and the evolution trend of high-tech products export in China, Japan and South Korea. The authors found that although China has become the world's largest high-tech products export country, Japan and South Korea's high-tech products embodied higher technology and their high- tech industry are more mature, while the technology gap of high-tech industry exports between China and Japan-Korea is expanding. Finally, the paper put forward relevant proposals in order to promote the technical level of China's high-tech industry.%高技术制造业作为一国技术实力的核心,日益受到各国的重视。中日韩三国均为高技术产品出口大国,而且中日韩FTA谈判即将启动。在此背景下,本文在描述了中日韩三国高技术产品现状的基础上,采用Hausmann构造的出口复杂度指数,按HS4位编码测算了中日韩三国高技术产品的出口复杂度,并据此分析了中日韩三国高技术产品出口的技术特征和发展趋势。我们发现,虽然中国已经成为全球最大的高技术产品出口国家,但日本和韩国的高技术产品技术含量更高,高技术产业发展更加成熟,而且中国与日韩高技术产业出口产品的技术含量差距正在扩大。最后,本文就此提出相关建议,以促进中国高技术产业的技术水平进一步提升。

  11. Nuclear power in the Baltic Sea region: the history of emergence and the political and economic features of its development

    Directory of Open Access Journals (Sweden)

    Kretinin G.

    2013-01-01

    Full Text Available This article focuses on the development of peaceful nuclear power. The author draws attention to the fact that nuclear power is a rather young branch of national economy. However, over recent decades, it has already seen rises and falls, and a number of states have had tragic experiences of nuclear emergencies. Nevertheless, many countries — including the three Baltic States of Estonia, Latvia and Lithuania — express a strong interest in development, generation, and application of nuclear power. In the Baltic States, nuclear power dates back to the Soviet times, but its development was suspended pursuant to the EU regulations (the Ignalina NPP. Lithuania, Latvia, and Estonia have been striving for energy independence from Russia — the principal supplier of energy carriers to these countries. For a long time, the three Baltic States have been proclaiming their unanimity on the general European path of development. However, the reality proved to be different. The touchstone for achieving common goals was the idea of constructing a new NPP at the site of the closed Ignalina NPP. The author concludes that the joint construction of a new NPP is quite questionable. When it comes to politics, each of the three Baltic States is ready to build its own NPP. Thus, the development of nuclear power in the Baltic Sea region requires joint coordinated actions independent of any bloc-inspired interests of the states involved. Moreover, this success may prove sustainable if the actions are based on innovative decisions and modern technologies.

  12. Inspection of the Department`s export licensing process for dual-use and munitions commodities

    Energy Technology Data Exchange (ETDEWEB)

    1993-08-10

    The purpose of our inspection was to review the Department of Energy`s (Energy) export licensing process for dual-use and military (munitions) commodities subject to nuclear nonproliferation controls. Specifically, we reviewed Energy`s authorities, procedures, and policies pertaining to the export licensing process and examined procedures for safeguarding data transmitted between Energy and other agencies involved in the export licensing process. We also reviewed Energy`s role as a member of the Subgroup on Nuclear Export Coordination. Our review of the sample of 60 export cases did not find evidence to lead us to believe that Energy`s recommendations for these cases were inappropriate or incorrect. We identified, however, problems regarding management systems associated with the export license review process. We found that without documentation supporting export licensing decisions by the Export Control Operations Division (ECOD), we could not determine whether ECOD analysts considered all required criteria in their review of export cases referred to Energy. For example, we found that the ECOD did not retain records documenting the bases for its advice, recommendations, or decisions regarding its reviews of export license cases or revisions to lists of controlled commodities and, therefore, was not in compliance with certain provisions of the Export Administration Act, as amended, and Energy records management directives. Additionally, we found that the degree of compliance by Energy with the export licensing review criteria contained in the Export Administration Regulations and the Nuclear Non-Proliferation Act of 1978 could not be determined because ECOD did not retain records documenting the bases for its advice and recommendations on export cases.

  13. Research study on typical feature of the media coverage on nuclear accidents in the national newspapers in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, T. [Univ. of Tokyo, Graduate School of Engineering, Tokyo (Japan); Kimura, H. [Univ. of Tokyo, Nuclear Professional School, Tokyo (Japan)

    2011-07-01

    This study focuses on survey of the characteristics of the media coverage on three well-known nuclear accidents. From a quantitative standpoint of the media reporting, it was revealed that the amount of the articles in the surveyed national newspapers tend to increase soon after accidents happen. Plus, as a qualitative research the author interviewed three leader writers, who suggested that the Japanese nuclear industry should prepare to distribute information more timely and sufficiently. They also answered the PR staff needs to contact journalists regularly in order to recognize their awareness and earn their trust. (author)

  14. An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export

    Science.gov (United States)

    Jackson, Brian R.; Boyne, James R.; Noerenberg, Marko; Taylor, Adam; Hautbergue, Guillaume M.; Walsh, Matthew J.; Wheat, Rachel; Blackbourn, David J.; Wilson, Stuart A.; Whitehouse, Adrian

    2011-01-01

    The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs. PMID:21814512

  15. Composition of Exports and Export Performance of Eurozone Countries

    NARCIS (Netherlands)

    Wierts, Peter; Van Kerkhoff, Henk; De Haan, Jakob

    2014-01-01

    This article investigates to what extent the composition of exports is related to the export performance of eurozone countries using a data set on exports from the oldest eurozone countries to their top 20 trade partners for the period 1988-2009. The results suggest that a higher share of high techn

  16. 77 FR 69789 - President's Export Council Subcommittee on Export Administration; Notice of Partially Closed Meeting

    Science.gov (United States)

    2012-11-21

    ... Bureau of Industry and Security President's Export Council Subcommittee on Export Administration; Notice of Partially Closed Meeting The President's Export Council Subcommittee on Export Administration... PECSEA provides advice on matters pertinent to those portions of the Export Administration Act,...

  17. Exporting to Russia?

    DEFF Research Database (Denmark)

    Thomsen, Lotte

    2016-01-01

    This article draws on extensive fieldwork conducted in Central Asia to explore food exports to Russia. It takes its theoretical starting point in global value chain theory and pinpoints chain entry barriers relating to financing, transportation and standards. The article also proposes rethinking...

  18. China Reshuffles Export Incentives

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    What it means for China's economy... Last month, the Chinese Government made sweeping changes to the export tax breaks that domestic companies receive. Here's what happened: On September 14, the Ministry of Finance, the General Administration of Customs, the National Development and Reform Commission, the Ministry of

  19. Intermediation in Foreign Trade: When do Exporters Rely on Intermediaries?

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Trabold, H.; Trübswetter, P.

    2005-01-01

    The paper explores the question of why trade intermediaries (TIs) are frequently used as agents for exports to some countries but not to others. First, we adapt a standard intra-industry trade model with variable export costs (e.g. transport) and fixed export costs (e.g. market access) to include...... a TI that is able to pool market access cost. This framework suggests explanatory factors for the TI share in a country's exports, which are largely in line with the literature. Second, we test these explanatory factors with a new data set based on French customs information. The paper finds that: (i......) higher market access costs increase the TI share, (ii) smaller export markets feature a larger TI share, (iii) network effects are important determinants of trade intermediation....

  20. Four-shell polyoxometalates featuring high-nuclearity Ln{sub 26} clusters. Structural transformations of nanoclusters into frameworks triggered by transition-metal ions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhong; Li, Xin-Xiong; Yang, Tao; Cai, Zhen-Wen; Zheng, Shou-Tian [State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fujian (China)

    2017-03-01

    A series of polyoxometalates (POMs) that incorporate the highest-nuclearity Ln clusters that have been observed in such structures to date (Ln{sub 26}, Ln=La and Ce) are described, which exhibit giant multishell configurations (Ln is contained in W{sub 6} is contained in Ln{sub 26} is contained in W{sub 100}). Their structures are remarkably different from known giant POMs that feature multiple Ln ions. In particular, the incorporated Ln-O clusters with a nuclearity of 26 are significantly larger than known high-nuclearity (≤10) Ln-O clusters in POM chemistry. Furthermore, they also contain the largest number of La and Ce centers for any POM reported to date and represent a new kind of rare giant POMs with more than 100 W atoms. Interestingly, the La{sub 26}-containing POM can undergo a single-crystal to single-crystal structural transformation in the presence of various transition-metal ions, such as Cu{sup 2+}, Co{sup 2+}, and Ni{sup 2+}, from an inorganic molecular nanocluster into an inorganic-organic hybrid extended framework that is built from POM building blocks with even higher-nuclearity La{sub 28} clusters bridged by transition-metal complexes. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Export Restructuring on Rebates Change

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Again, the Chinese governmenthas recently adjusted the export tax rebates upon 2831 categories of goods, accounting for 37% of the nation's total export products. Export rebates on most products have decreased by 2% to 4%, and some have had an even steeper reduction. For instance,the export tax rebate has plummeted from 11% or 13% to zero on cement and chemical products, which are called "high-energy-consumption.

  2. Physical features of small disperse coal dust fraction transportation and structurization processes in iodine air filters of absorption type in ventilation systems at nuclear power plants

    CERN Document Server

    Ledenyov, Oleg P; Poltinin, P Ya; Fedorova, L I

    2012-01-01

    The research on the physical features of transportation and structurization processes by the air-dust aerosol in the granular filtering medium with the cylindrical coal adsorbent granules in an air filter of the adsorption type in the heating ventilation and cooling (HVAC) system at the nuclear power plant is completed. The physical origins of the coal dust masses distribution along the absorber with the granular filtering medium with the cylindrical coal granules during the air-dust aerosol intake process in the near the surface layer of absorber are researched. The quantitative technical characteristics of air filtering elements, which have to be considered during the optimization of air filters designs for the application in the ventilation systems at the nuclear power plants, are obtained.

  3. Classification of endometrial lesions by nuclear morphometry features extracted from liquid-based cytology samples: a system based on logistic regression model.

    Science.gov (United States)

    Zygouris, Dimitrios; Pouliakis, Abraham; Margari, Niki; Chrelias, Charalampos; Terzakis, Emmanouil; Koureas, Nikolaos; Panayiotides, Ioannis; Karakitsos, Petros

    2014-08-01

    To investigate the potential of a computerized system for the discrimination of benign from malignant endometrial nuclei and lesions. A total of 228 histologically confirmed liquid-based cytological smears were collected: 117 within normal limits cases, 66 malignant cases, 37 hyperplasias without atypia, and 8 cases of hyperplasia with atypia. From each case we extracted nuclear morphometric features from about 100 nuclei using a custom image analysis system. Initially we performed feature selection, and subsequently we applied a logistic regression model that classified each nucleus as benign or malignant. Based on the results of the nucleus classification process, we constructed an algorithm to discriminate endometrium cases as benign or malignant. The proposed system had an overall accuracy for the classification of endometrial nuclei equal to 83.02%, specificity of 85.09%, and sensitivity of 77.01%. For the case classification the overall accuracy was 92.98%, specificity was 92.86%, and sensitivity was 93.24%. The proposed computerized system can be applied for the classification of endometrial nuclei and lesions as it outperformed the standard cytological diagnosis. This study highlights interesting diagnostic features of endometrial nuclear morphology, and the proposed method can be a useful tool in the everyday practice of the cytological laboratory.

  4. Some features of the technogenic pollution of the Kara Sea, with the example of the sunken nuclear submarine K-27

    Science.gov (United States)

    Dmitrievskiy, N. N.; Nikiforov, S. L.; Lobkovsky, L. I.; Ananiev, R. A.

    2015-11-01

    This article discusses the results of offshore operations undertaken during a cruise of the R/V Professor Shtokman (2013) during an expedition in the fjord Stepovoi of the Novaya Zemlya Archipelago k]where the nuclear submarine (NPS) K-27 was scuttled in 1981 k]An echo sounding of her hull showed signs of water destratification k]which may be caused by turbulence from gas or heat flows outgoing from the hull k]According to the hypothesis of the author k]the presence of the reactors and radioactive nuclear fuel remnants may lead to the continued heating of the inner cavities of the submarine and k]as a consequence k]to constant heat flow from its surface k]which is an obvious danger k]including risks associated with plans to refloat and transport the submarine for the further dismantlement.

  5. Particle number scale invariant feature of the states around the critical point of the first order nuclear shape phase transition

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    We study systematically the evolutive behaviors of some energy ratios,E2 transition rate ratios and isomer shift in the nuclear shape phase transitions.We find that the quantities sensitive to the phase transition and independent of free parameter(s) are approximately particle number N scale invariant around the critical point of the first order phase transition,similar to that in the second order phase transition.

  6. Particle number scale invariant feature of the states around the critical point of the first order nuclear shape phase transition

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu; HOU ZhanFeng; LIU YuXin

    2009-01-01

    We study systematically the evolutive behaviors of some energy ratios,E2 transition rate ratios and Isomer shift in the nuclear shape phase transitions.We find that the quantities sensitive to the phase transition and independent of free parameter(s) are approximately particle number N scale invariant around the critical point of the first order phase transition,similar to that in the second order phase transition.

  7. 10 CFR Appendix H to Part 110 - Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export...

    Science.gov (United States)

    2010-01-01

    ... Equipment and Components Under NRC Export Licensing Authority H Appendix H to Part 110 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Pt. 110, App. H Appendix H to Part 110—Illustrative List of Electromagnetic Enrichment Plant Equipment and Components...

  8. 10 CFR Appendix G to Part 110 - Illustrative List of Plasma Separation Enrichment Plant Equipment and Components Under NRC Export...

    Science.gov (United States)

    2010-01-01

    ... Equipment and Components Under NRC Export Licensing Authority G Appendix G to Part 110 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Pt. 110, App. G Appendix G to Part 110—Illustrative List of Plasma Separation Enrichment Plant Equipment and...

  9. Young investigator challenge: The morphologic analysis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on liquid-based cytology: Some insights into their identification.

    Science.gov (United States)

    Bizzarro, Tommaso; Martini, Maurizio; Capodimonti, Sara; Straccia, Patrizia; Lombardi, Celestino Pio; Pontecorvi, Alfredo; Larocca, Luigi Maria; Rossi, Esther Diana

    2016-10-01

    Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a challenge for the diagnosis and management of thyroid carcinoma. Some authors have proposed histological criteria that are able to distinguish NIFTPs from invasive follicular variant of papillary thyroid carcinoma (I-FVPTC). Hence, NIFTPs may have repercussions in the diagnostic categories on fine-needle aspiration. In the current study, the authors evaluated the criteria for NIFTPs on liquid-based cytology samples. The authors recorded all 61 liquid-based cytology samples proved to be histological FVPTC between January 2013 and March 2016 and analyzed the architectural, cytoplasmic, and nuclear parameters. They compared them with a cohort of 40 PTC cases and 20 follicular adenoma cases. The authors reported 37 NIFTP cases and 24 I-FVPTC cases at histology. The cytological diagnoses of follicular nodules in the NIFTP cases were twice those found in the I-FVPTC cases (54.1% vs 29.2%). The number of positive for malignancy cases among the NIFTPs were approximately half those of I-FVPTC cases. When compared with I-FVPTCs, 70% of the NIFTP cases demonstrated a nuclear size .05). A predominant microfollicular pattern was recognized in both NIFTPs and I-FVPTCs (97.3% vs 100%). The majority of NIFTPs appear to be devoid of nuclear pseudoinclusions and papillary structures, thereby allowing the inclusion in the follicular nodule cases. Nuclear size and microfollicular clusters may suggest the discrimination between NIFTPs and I-FVPCs. Cancer Cytopathol 2016;124:699-710. © 2016 American Cancer Society. © 2016 American Cancer Society.

  10. Do You Know What Export Control Reform Did WIth Those Crown Jewels?

    Energy Technology Data Exchange (ETDEWEB)

    Hagen, Gary D.

    2017-01-17

    Export Control Reform has been in motion for six years. In 2014, the ITAR regulations surrendered export control of nuclear weapons technology to the control of DOE. Yet no Federal Register notice by DOE detailed where those new regulations could be found. This article explains the disposition that occurred.

  11. 10 CFR 40.66 - Requirements for advance notice of export shipments of natural uranium.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Requirements for advance notice of export shipments of natural uranium. 40.66 Section 40.66 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE... natural uranium. (a) Each licensee authorized to export natural uranium, other than in the form of ore...

  12. Risk Taking Propensity and Export Performance of Croatian Exporters

    Directory of Open Access Journals (Sweden)

    Mirna Leko-Simic

    2006-12-01

    Full Text Available Export performance is today one of the most widely used measures of a company’s success, due to the globalization and market liberalization processes. The rather bad export performance of Croatian exporters can be explained by a number of factors, one of which is assumed to be the low level of risk taking propensity, which is one of the three major dimensions of entrepreneurial behavior. The aim of this paper is to analyze company age, size and type of business as determinants of risk taking propensity in Croatian exporting companies. Cluster analysis based on four variable criteria was used in order to determine risk and non-risk takers’ clusters and analyze the significant differences between them in relation to their export performance. The paper is based on research of 88 Croatian exporters.

  13. An Anatomy Of The Export Expansion Process

    OpenAIRE

    Reid, S

    1986-01-01

    This paper examines the export market strategies and export modes used by small and medium sized Italian manufacturing firms. The firms vary extensively in their extent and type of export dependence on different channel arrangements and export markets. Moreover, the exporting modes used do show some peculiar links with export objectives specifically higher dependence on direct sales is associated with planned export expansion and higher dependence on agent/representatives and distributors is ...

  14. Nuclear weapons, nuclear effects, nuclear war

    Energy Technology Data Exchange (ETDEWEB)

    Bing, G.F.

    1991-08-20

    This paper provides a brief and mostly non-technical description of the militarily important features of nuclear weapons, of the physical phenomena associated with individual explosions, and of the expected or possible results of the use of many weapons in a nuclear war. Most emphasis is on the effects of so-called ``strategic exchanges.``

  15. Contribution of energetically reactive surface features to the dissolution of CeO2 and ThO2 analogues for spent nuclear fuel microstructures.

    Science.gov (United States)

    Corkhill, Claire L; Myllykylä, Emmi; Bailey, Daniel J; Thornber, Stephanie M; Qi, Jiahui; Maldonado, Pablo; Stennett, Martin C; Hamilton, Andrea; Hyatt, Neil C

    2014-08-13

    In the safety case for the geological disposal of nuclear waste, the release of radioactivity from the repository is controlled by the dissolution of the spent fuel in groundwater. There remain several uncertainties associated with understanding spent fuel dissolution, including the contribution of energetically reactive surface sites to the dissolution rate. In this study, we investigate how surface features influence the dissolution rate of synthetic CeO2 and ThO2, spent nuclear fuel analogues that approximate as closely as possible the microstructure characteristics of fuel-grade UO2 but are not sensitive to changes in oxidation state of the cation. The morphology of grain boundaries (natural features) and surface facets (specimen preparation-induced features) was investigated during dissolution. The effects of surface polishing on dissolution rate were also investigated. We show that preferential dissolution occurs at grain boundaries, resulting in grain boundary decohesion and enhanced dissolution rates. A strong crystallographic control was exerted, with high misorientation angle grain boundaries retreating more rapidly than those with low misorientation angles, which may be due to the accommodation of defects in the grain boundary structure. The data from these simplified analogue systems support the hypothesis that grain boundaries play a role in the so-called "instant release fraction" of spent fuel, and should be carefully considered, in conjunction with other chemical effects, in safety performance assessements for the geological disposal of spent fuel. Surface facets formed during the sample annealing process also exhibited a strong crystallographic control and were found to dissolve rapidly on initial contact with dissolution medium. Defects and strain induced during sample polishing caused an overestimation of the dissolution rate, by up to 3 orders of magnitude.

  16. Comparative genomics of proteins involved in RNA nucleocytoplasmic export

    Directory of Open Access Journals (Sweden)

    Goldenberg Samuel

    2011-01-01

    Full Text Available Abstract Background The establishment of the nuclear membrane resulted in the physical separation of transcription and translation, and presented early eukaryotes with a formidable challenge: how to shuttle RNA from the nucleus to the locus of protein synthesis. In prokaryotes, mRNA is translated as it is being synthesized, whereas in eukaryotes mRNA is synthesized and processed in the nucleus, and it is then exported to the cytoplasm. In metazoa and fungi, the different RNA species are exported from the nucleus by specialized pathways. For example, tRNA is exported by exportin-t in a RanGTP-dependent fashion. By contrast, mRNAs are associated to ribonucleoproteins (RNPs and exported by an essential shuttling complex (TAP-p15 in human, Mex67-mtr2 in yeast that transports them through the nuclear pore. The different RNA export pathways appear to be well conserved among members of Opisthokonta, the eukaryotic supergroup that includes Fungi and Metazoa. However, it is not known whether RNA export in the other eukaryotic supergroups follows the same export routes as in opisthokonts. Methods Our objective was to reconstruct the evolutionary history of the different RNA export pathways across eukaryotes. To do so, we screened an array of eukaryotic genomes for the presence of homologs of the proteins involved in RNA export in Metazoa and Fungi, using human and yeast proteins as queries. Results Our genomic comparisons indicate that the basic components of the RanGTP-dependent RNA pathways are conserved across eukaryotes, and thus we infer that these are traceable to the last eukaryotic common ancestor (LECA. On the other hand, several of the proteins involved in RanGTP-independent mRNA export pathways are less conserved, which would suggest that they represent innovations that appeared later in the evolution of eukaryotes. Conclusions Our analyses suggest that the LECA possessed the basic components of the different RNA export mechanisms found today

  17. NEW APPROACHES TO EXPORT COMPETITIVENESS

    OpenAIRE

    Alina Petronela NEGREA

    2015-01-01

    The economic literature and the political discourse typically look at international competitiveness mainly by the means of export market shares. However, globalisation, production fragmentation and the growing importance of global value chains (GVCs) increasingly challenge traditional approaches of export competitiveness and call for a more accurate and disaggregated level of analysis. Due to the growing fragmentation of production, a country exports now include a significant amount of import...

  18. Minimum quality standards and exports

    OpenAIRE

    2015-01-01

    This paper studies the interaction of a minimum quality standard and exports in a vertical product differentiation model when firms sell global products. If ex ante quality of foreign firms is lower (higher) than the quality of exporting firms, a mild minimum quality standard in the home market hinders (supports) exports. The minimum quality standard increases quality in both markets. A welfare maximizing minimum quality standard is always lower under trade than under autarky. A minimum quali...

  19. Soviet energy export prospects

    Energy Technology Data Exchange (ETDEWEB)

    Scanlan, Tony

    1991-05-01

    The Soviet Union produces 20% of world energy but since 1988 this is in decline. Awakening consumerism and a sea-change in the structure of foreign trade and internal investment are placing this key industry into unprecedented uncertainty. The difference between success and failure goes beyond the 1988 peak of six million barrels daily of exports in oil equivalent. The article quantifies the key areas of energy uncertainty as equal in volume to total OPEC output and sees the long-term changes of success more than ever dependent on coordinated planning and investment as well as on market reality. (Author).

  20. Slowed Exports Growth

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The first half of 2010 is showing that the impacts of the financial crisis are still lingering.Zhao Jinping,a researcher at the Development Research Center of the State Council,says that the possible implementation of exit strategies in developed countries may deal a heavy blow to a global rally,and it will certainly result in slowed exports growth for China.Zhao published his opinion in the China Economic Times.The first part was published in issue No.33.Edited excerpts of the second part follow:

  1. Exporting to Russia?

    DEFF Research Database (Denmark)

    Thomsen, Lotte

    2016-01-01

    This article draws on extensive fieldwork conducted in Central Asia to explore food exports to Russia. It takes its theoretical starting point in global value chain theory and pinpoints chain entry barriers relating to financing, transportation and standards. The article also proposes rethinking...... the aspects of territoriality and institutional context, and suggests their integration into one concept, or rather a process of contextualizing territories. In doing so, the article argues for a methodology that not only examines current events, but also captures change as particularly important in what we...

  2. Mozambique. Export perespectives

    Directory of Open Access Journals (Sweden)

    Joanna Sitz-Kuleszo

    2014-09-01

    Full Text Available Destroyed by wars, military and internal conflicts economy of Republic of Mozambique since more than a decade is constantly growing. This 36th biggest country in the world became the object of interest for investment and trade for many developed economies, mostly from Asia. Nowadays investments in Mozambique are focused mostly on rich carbon and gas sources that has been discovered during last decade. Poland is not important trade partner for Mozambique, however could intensify exchange in upcoming years as, if the development will continue, Republic of Mozambique would need for its economy Polish export specialties.

  3. Protein export through the bacterial flagellar type III export pathway.

    Science.gov (United States)

    Minamino, Tohru

    2014-08-01

    For construction of the bacterial flagellum, which is responsible for bacterial motility, the flagellar type III export apparatus utilizes both ATP and proton motive force across the cytoplasmic membrane and exports flagellar proteins from the cytoplasm to the distal end of the nascent structure. The export apparatus consists of a membrane-embedded export gate made of FlhA, FlhB, FliO, FliP, FliQ, and FliR and a water-soluble ATPase ring complex consisting of FliH, FliI, and FliJ. FlgN, FliS, and FliT act as substrate-specific chaperones that do not only protect their cognate substrates from degradation and aggregation in the cytoplasm but also efficiently transfer the substrates to the export apparatus. The ATPase ring complex facilitates the initial entry of the substrates into the narrow pore of the export gate. The export gate by itself is a proton-protein antiporter that uses the two components of proton motive force, the electric potential difference and the proton concentration difference, for different steps of the export process. A specific interaction of FlhA with FliJ located in the center of the ATPase ring complex allows the export gate to efficiently use proton motive force to drive protein export. The ATPase ring complex couples ATP binding and hydrolysis to its assembly-disassembly cycle for rapid and efficient protein export cycle. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. © 2013 Elsevier B.V. All rights reserved.

  4. Aspects of the EOS momentum dependence and of the residual NN cross section on the featuring of nuclear stopping

    CERN Document Server

    Basrak, Z; de la Mota, V

    2016-01-01

    With the semiclassical Landau-Vlasov transport model studied is the stopping observable $R_E$, the energy-based isotropy ratio, for the $^{129}$Xe\\,+\\,$^{120}$Sn reaction at beam energies spanning 12$A$ to 100$A$ MeV. Investigated is the impact of the non-locality of the nuclear mean field, of the in-medium modified nucleon-nucleon ($NN$) cross-section and of the reaction centrality. A fixed set of model parameters yield the $R_E$ values that favourably compares with the experimental ones but only for energies below the Fermi energy $E_F$. Above $E_F$ the agreement is readily possible but by a smooth evolution with energy of the parameter that controls the in-medium modification of $NN$ cross-section. By confronting the simulation correction factor ${\\cal F}$ to be applied to the free $NN$ cross-section with the one which has been deduced from experimental data [Phys.\\ Rev.\\ C\\,{\\bf 90}, 064602 (2014)] one infers that the zero-range mean field almost entirely reproduces it. Also, in accordance with what has b...

  5. Integration of mRNP formation and export.

    Science.gov (United States)

    Björk, Petra; Wieslander, Lars

    2017-08-01

    Expression of protein-coding genes in eukaryotes relies on the coordinated action of many sophisticated molecular machineries. Transcription produces precursor mRNAs (pre-mRNAs) and the active gene provides an environment in which the pre-mRNAs are processed, folded, and assembled into RNA-protein (RNP) complexes. The dynamic pre-mRNPs incorporate the growing transcript, proteins, and the processing machineries, as well as the specific protein marks left after processing that are essential for export and the cytoplasmic fate of the mRNPs. After release from the gene, the mRNPs move by diffusion within the interchromatin compartment, making up pools of mRNPs. Here, splicing and polyadenylation can be completed and the mRNPs recruit the major export receptor NXF1. Export competent mRNPs interact with the nuclear pore complex, leading to export, concomitant with compositional and conformational changes of the mRNPs. We summarize the integrated nuclear processes involved in the formation and export of mRNPs.

  6. 78 FR 37785 - Order Denying Export Privileges

    Science.gov (United States)

    2013-06-24

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Gerardo Domingo... Domingo Rodriguez-Rivera (``Rodriguez-Rivera'') was convicted of violating Section 38 of the ] Arms Export... convicted of knowingly and willfully exporting and causing to be exported and attempting to export...

  7. Export incentives, exchange rate policy and export growth in Turkey

    NARCIS (Netherlands)

    S.J.G. van Wijnbergen; I. Arslan

    1993-01-01

    The driving forces behind the Turkish export miracle, and in fact its very existence, have remained a matter of debate We show there was a boom. As to contributing factors, import growth in the Middle East in excess of import growth elsewhere made a negative contribution. On exports to non-oil count

  8. Export incentives, exchange rate policy and export growth in Turkey

    NARCIS (Netherlands)

    van Wijnbergen, S.J.G.; Arslan, I.

    1993-01-01

    The driving forces behind the Turkish export miracle, and in fact its very existence, have remained a matter of debate We show there was a boom. As to contributing factors, import growth in the Middle East in excess of import growth elsewhere made a negative contribution. On exports to non-oil

  9. Mapping interactions between mRNA export factors in living cells.

    Directory of Open Access Journals (Sweden)

    I-Fang Teng

    Full Text Available The TREX complex couples nuclear mRNA processing events with subsequent export to the cytoplasm. TREX also acts as a binding platform for the mRNA export receptor Nxf1. The sites of mRNA transcription and processing within the nucleus have been studied extensively. However, little is known about where TREX assembly takes place and where Nxf1 is recruited to TREX to form the export competent mRNP. Here we have used sensitized emission Förster resonance energy transfer (FRET and fluorescence lifetime imaging (FLIM-FRET, to produce a spatial map in living cells of the sites for the interaction of two TREX subunits, Alyref and Chtop, with Nxf1. Prominent assembly sites for export factors are found in the vicinity of nuclear speckles in regions known to be involved in transcription, splicing and exon junction complex formation highlighting the close coupling of mRNA export with mRNP biogenesis.

  10. Informal export barriers and poverty

    OpenAIRE

    Porto, Guido G.

    2004-01-01

    The author investigates the poverty impacts of informal export barriers like transport costs, cumbersome customs practices, costly regulations, and bribes. He models these informal barriers as export taxes that distort the efficient allocation of resources. In low-income agricultural economies, this distortion lowers wages and household agricultural income, thereby leading to higher pover...

  11. Tumbling Auto Import and Export

    Institute of Scientific and Technical Information of China (English)

    Yantai Chen

    2009-01-01

    @@ The seemingly rebound global financial crisis has seriously eroded world economy from 2008,of which China's tumbling auto imports and exports business is a good example.At the beginning of 2008 it kicked off as an excellent year for the Chinese automotive market,but ended with the onset of a recession in last quarter both from the perspective of import and export.

  12. Insurability of export credit risks

    NARCIS (Netherlands)

    Alsem, K.J.; Antufjew, J.; Huizingh, K.R.E.; Koning, Ruud H.; Sterken, E.; Woltil, M.

    2003-01-01

    Firms exporting their goods and services abroad face risks that are different from the risks faced by firms who do not engage in international trade. It is common practice to allow the receiving party to pay in instalments. The exporting firm faces credit risk, but as in most countries, Dutch firms

  13. Insurability of export credit risks

    NARCIS (Netherlands)

    Alsem, K.J.; Antufjew, J.; Huizingh, K.R.E.; Koning, Ruud H.; Sterken, E.; Woltil, M.

    2003-01-01

    Firms exporting their goods and services abroad face risks that are different from the risks faced by firms who do not engage in international trade. It is common practice to allow the receiving party to pay in instalments. The exporting firm faces credit risk, but as in most countries, Dutch firms

  14. The south's timer export potential

    Science.gov (United States)

    James E. Granskog

    1986-01-01

    Exports of southern wood products have bccil dcclirling since 1980, following a dramatic rise during the 1970s. The value of these exports rose from near the $50 million level in the early 1970s to almost $500 million in 1980, but has dropped by more than a third since then. Now, however, changing monetary conditions appear to be turning the trend upward again....

  15. Sinosure Helping to Stabilize Exports

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The unfolding international financial crisis is taking its toll on China’s economy, especially China’s exports. On one hand, overseas demand has plummeted, while on the other, with the worsening credit environment and emerging trade protectionism, export enter-prises are suffering from rising credit risks, to the point where some of them dare not even accept orders.

  16. Great Challenge in Steel Export

    Institute of Scientific and Technical Information of China (English)

    Charlsea Liu

    2009-01-01

    @@ In 2008, the export of China steel products experienoeu, a splendid period f fast growing, and then disappointedly followed by fast depression. Until lest December, China in 2008 exported steel products of 59.21 million tons, less than the same term in 2007 by 3.48 million tons, declining about 5.6%.

  17. NEW APPROACHES TO EXPORT COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Alina Petronela NEGREA

    2015-04-01

    Full Text Available The economic literature and the political discourse typically look at international competitiveness mainly by the means of export market shares. However, globalisation, production fragmentation and the growing importance of global value chains (GVCs increasingly challenge traditional approaches of export competitiveness and call for a more accurate and disaggregated level of analysis. Due to the growing fragmentation of production, a country exports now include a significant amount of imports of intermediate goods which are part of the export value. In this case, a simple analysis of the evolution of exports can distort the international competitive position of a country. The article suggests a new approach based on the value-added content of international trade measured by means of global value chain analysis.

  18. Second Thoughts on Exporter Productivity

    DEFF Research Database (Denmark)

    Sørensen, Allan; Schröder, Philipp J.H.

    Empirical literature has established a positive link between firm productivity and export status, yet notable exceptions exist. The present paper shows that the underlying theory (Melitz, 2003) is in fact able to accommodate the rule as well as the exception. The fulcrum of the argument is the te......Empirical literature has established a positive link between firm productivity and export status, yet notable exceptions exist. The present paper shows that the underlying theory (Melitz, 2003) is in fact able to accommodate the rule as well as the exception. The fulcrum of the argument...... is the tension between empirical work measuring productivity based on average cost information, and theoretical work representing productivity by marginal cost. In a heterogeneous firms trade model, we compute productivity based on average cost and find that around the export-indifferent firm, exporters...... will be less productive than non-exporters. Furthermore, we show that this effect may feed through at the industry level....

  19. NEW APPROACHES TO EXPORT COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Alina Petronela NEGREA

    2015-04-01

    Full Text Available The economic literature and the political discourse typically look at international competitiveness mainly by the means of export market shares. However, globalisation, production fragmentation and the growing importance of global value chains (GVCs increasingly challenge traditional approaches of export competitiveness and call for a more accurate and disaggregated level of analysis. Due to the growing fragmentation of production, a country exports now include a significant amount of imports of intermediate goods which are part of the export value. In this case, a simple analysis of the evolution of exports can distort the international competitive position of a country. The article suggests a new approach based on the value-added content of international trade measured by means of global value chain analysis.

  20. Exporting EU Liberalism Eastwards

    Directory of Open Access Journals (Sweden)

    Lynn M. Tesser

    2009-07-01

    Full Text Available There is much more to liberalism in the post communist context than has been acknowledged. A sizeable effort has indeed emerged to transplant a relatively coherent liberal ideology to the region, one exported not merely through the conditionality of international financial institutions, but also through the conditionality and socialization of organizations like the NATO, OSCE, EU, and the Council of Europe. ‘EU liberalism’ includes the ‘standard’ liberal emphasis on individual rights, the rule of law, constitutional democracy, freedom, and market economics as well as support for minority rights, and a seemingly schizophrenic emphasis on economic integration that involves, first bringing down borders for the free movement of people, goods, capital, and services between member states, and second, market regulation to diminish the social downsides of capitalism. This paper outlines EU liberalism’s emergence and its application to Central and East European countries.

  1. On Overinvoicing of Exports in Pakistan

    OpenAIRE

    Zafar Mahmood; Mohammad Azhar

    2001-01-01

    Whereas the policy incentives were designed to promote exports from Pakistan, the incentive system instead led to illicit export practices, i.e., export overinvoicing due to the weaknesses of implementation. Such practices resulted in a significant financial loss to the country and undermined the effectiveness of the export-promoting policy. This paper has determined the presence of overinvoicing of exports in Pakistan and the geographic and product-wise patterns in export overinvoicing. The ...

  2. Exporting calcium from cells.

    Science.gov (United States)

    Guerini, Danilo; Coletto, Luisa; Carafoli, Ernesto

    2005-01-01

    All eukaryotic cells import Ca2+ through a number of variously gated plasma membrane channels. Once inside cells, Ca2+ transmits information to a large number of (enzyme) targets. Eventually, it must be exported again, to prevent the overloading of the cytosol with Ca2+. Two systems export Ca2+ from cells: a high affinity, low capacity Ca2+-ATPase, and a lower affinity, but much larger capacity, Na+/Ca2+ exchanger. The ATPase (commonly called the Ca2+ pump) is the fine-tuner of cell Ca2+, as it functions well even if the concentration of the ion drops below the microM level. It is a large enzyme, with 10 transmembrane domains and a C-terminal cytosolic tail that contains regulatory sites, including a calmodulin-binding domain. Four distinct gene products plus a large number of splice variants have been described. Some are tissue specific, the isoform 2 being specifically expressed in the sensorial cells of the Corti organ in the inner-ear. Its genetic absence causes deafness in mice. Two different families of the Na+/Ca2+ exchanger exist, one of which, originally described in photoreceptors, transports K+ and Ca2+ in exchange for Na+. The exchanger is particularly active in excitable cells, e.g., heart, where the necessity cyclically arises to rapidly eject large amounts of Ca2+. In addition to heart, the exchanger is particularly important to neurons: the cleavage of the most important neuronal isoform (NCX3) by calpains activated by excitotoxic treatments generates Ca2+ overload and eventually cell death.

  3. Examining the role of export competitive advantages on export performance

    Directory of Open Access Journals (Sweden)

    Yeganeh Alimohammadi

    2014-04-01

    Full Text Available This paper investigates the role of export competitive advantage on export performance in food industry. The proposed study designs a questionnaire in Likert scale and distributes it among 280 randomly selected experts in food industry and Cronbach alpha has been calculated as 0.827. The study has applied factor analysis to find important factors influencing export performance. Kaiser-Meyer-Olkin Measure of Sampling Adequacy and Bartlett's Test of Sphericity have been performed to validate the results and they both validated the questionnaire. The results of the survey have determined six effective groups including product development, e-commerce, marketing planning, organizational performance, competitiveness and supply chain management.

  4. Exports and Innovation in Emerging Economies : Firm-Level Evidence from South-Africa

    NARCIS (Netherlands)

    Vannoorenberghe, Gonzague

    2015-01-01

    Using a new dataset on the innovation and exports of 500 South African firms, this paper asks whether exports affect rm innovation in the context of an emerging economy. We use a range of particularly attractive features of the dataset. Firms not only report whether they innovated but describe their

  5. The status and latest issues on KAERI export control implementation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Sook; Park, Ho Jun; Kim, Hyun Jo; Ko, Han Suk; Lee, Byung Doo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2010-10-15

    There are four informal non-proliferation arrangements which seek to control the proliferation of weapons of mass destruction and their missile delivery systems and the transfer of conventional weapons and dual-use technologies. The four arrangements are Wassenaar Arrangement (WA) on export controls for conventional arms and dual use goods and technologies, Nuclear Supplies Group(NSG), Missile Technology Control Regime(MTCR) and Australia Group(AG) on chemical and biological weapons materials. ROK participates in four arrangements to seek to encourage responsible practice in the trade of strategic goods and technologies. It is achieved through the implementation of export control list. MKE Notification (Ministry of Knowledge Economy Notification No. 2009-250) specifies those items and technologies subject to control. In this paper, the status and latest issues on KAERI export control implementation are described

  6. 2006 Rare Earth Export Quota

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ According to correlative stipulations in "Goods Import εt Export Administrating Statute of P.R.C", 2006export quota for important industrial products was issued by the Ministry of Commerce of P.R.C. on December 30th of 2005. Export quota of rare earth products is 45,000 tons. It is said the quota will be distributed in two batches. The first batch of quota will reach 70-80% of the total with 21,700 - 24,800tons for domestic companies and 10,500 - 12,000 tons for foreign invested companies. Quota will be distributed to relevant enterprises directly in recent days.

  7. Learning to export and learning by exporting: The case of Ethiopian manufacturing

    OpenAIRE

    Siba, Eyerusalem; Gebreeyesus, Mulu

    2014-01-01

    In this study, we investigate the relationship between exporting and firm performance using a longer panel dataset of Ethiopian manufacturing firms for the period 1996 - 2009. We test two hypotheses regarding exporting: selection into exporting versus learning by exporting. According to the selection into exporting hypothesis, more productive firms self-select into exporting due to high entry costs. The learning by exporting hypothesis, on the other hand, emphasizes that firms learn after ent...

  8. Selective export of autotaxin from the endoplasmic reticulum.

    Science.gov (United States)

    Lyu, Lin; Wang, Baolu; Xiong, Chaoyang; Zhang, Xiaotian; Zhang, Xiaoyan; Zhang, Junjie

    2017-04-28

    Autotaxin (ATX) or ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) is a secretory glycoprotein and functions as the key enzyme for lysophosphatidic acid generation. The mechanism of ATX protein trafficking is largely unknown. Here, we demonstrated that p23, a member of the p24 protein family, was the protein-sorting receptor required for endoplasmic reticulum (ER) export of ATX. A di-phenylalanine (Phe-838/Phe-839) motif in the human ATX C-terminal region was identified as a transport signal essential for the ATX-p23 interaction. Knockdown of individual Sec24 isoforms by siRNA revealed that ER export of ATX was impaired only if Sec24C was down-regulated. These results suggest that ATX is selectively exported from the ER through a p23, Sec24C-dependent pathway. In addition, it was found that AKT signaling played a role in ATX secretion regulation to facilitate ATX ER export by enhancing the nuclear factor of activated T cell-mediated p23 expression. Furthermore, the di-hydrophobic amino acid motifs (FY) also existed in the C-terminal regions of human ENPP1 and ENPP3. Such a p23, Sec24C-dependent selective ER export mechanism is conserved among these ENPP family members. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Exports reflect "safety of products"

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Most of the made-in-China products are absolutely safe, and the steady increase in exports despite the recent widespread criticism reflects their safety standards, a Ministry of Commerce official said Thursday.

  10. 75 FR 12433 - National Export Initiative

    Science.gov (United States)

    2010-03-16

    ... Enterprises (SMEs). Members of the Export Promotion Cabinet shall develop programs, in consultation with the TPCC, designed to enhance export assistance to SMEs, including programs that improve information and other technical assistance to first-time exporters and assist current exporters in identifying...

  11. 40 CFR 273.40 - Exports.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Exports. 273.40 Section 273.40... UNIVERSAL WASTE MANAGEMENT Standards for Large Quantity Handlers of Universal Waste § 273.40 Exports. A... exporter in 40 CFR 262.53, 262.56(a)(1) through (4), (6), and (b) and 262.57; (b) Export such...

  12. FDI as an Export-Platform

    DEFF Research Database (Denmark)

    Hajderllari, Luljeta; Karantininis, Konstantinos; Lawson, Lartey Godwin

    towards countries with large exports of agri-food, thereby supporting the hypothesis that FDI is used as an export-platform. FDI is coupled with high exports from Denmark, probably of raw or semi-processed food products for further processing and exports. We also find that FDI is higher in countries...

  13. 40 CFR 273.20 - Exports.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Exports. 273.20 Section 273.20... UNIVERSAL WASTE MANAGEMENT Standards for Small Quantity Handlers of Universal Waste § 273.20 Exports. A... exporter in 40 CFR 262.53, 262.56(a) (1) through (4), (6), and (b) and 262.57; (b) Export such...

  14. 27 CFR 28.30 - Export status.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export status. 28.30... Export status. (a) Distilled spirits and wines manufactured, produced, bottled in bottles packed in... such purposes are considered to be exported. Export status is not acquired until application on Form...

  15. E-business and small Ghanaian exporters

    DEFF Research Database (Denmark)

    Hinson, Robert; Sørensen, Olav Jull

    2006-01-01

    The arfticle aims to investigate the relationship between export intensity and e-business adoption in Ghana. No clear relationship is found among exporters of non-traditional items.......The arfticle aims to investigate the relationship between export intensity and e-business adoption in Ghana. No clear relationship is found among exporters of non-traditional items....

  16. 31 CFR 592.304 - Exporting authority.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exporting authority. 592.304 Section... § 592.304 Exporting authority. (a) The term exporting authority means one or more entities designated by a Participant from whose territory a shipment of rough diamonds is being exported as having...

  17. 19 CFR 18.26 - Indirect exportation.

    Science.gov (United States)

    2010-04-01

    ... merchandise to be exported and provide such evidence of exportation as required by the port director under... 19 Customs Duties 1 2010-04-01 2010-04-01 false Indirect exportation. 18.26 Section 18.26 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Exportation from Customs Custody of Merchandise Unentered...

  18. 19 CFR 18.42 - Direct exportation.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Direct exportation. 18.42 Section 18.42 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Merchandise Not Otherwise Subject to Customs Control Exported Under Cover of A Tir Carnet § 18.42 Direct exportation. At the port of exportation, the container...

  19. 19 CFR 18.25 - Direct exportation.

    Science.gov (United States)

    2010-04-01

    ... to be exported and provide such evidence of exportation as required by the port director under § 113... 19 Customs Duties 1 2010-04-01 2010-04-01 false Direct exportation. 18.25 Section 18.25 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Exportation from Customs Custody of Merchandise Unentered...

  20. 14 CFR 1274.942 - Export licenses.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Export licenses. 1274.942 Section 1274.942... FIRMS Other Provisions and Special Conditions § 1274.942 Export licenses. Export Licenses July 2002 (a) The Recipient shall comply with all U.S. export control laws and regulations, including...

  1. 77 FR 40493 - Export Administration Regulations

    Science.gov (United States)

    2012-07-10

    ... Bureau of Industry and Security 15 CFR Parts 740, 742, 748, 750, 752, and 760 Export Administration... heading of paragraph (d) to read ``Shippers Export Declaration or Automated Export System Record''. 0 2...): Once a mass market classification request is accepted in SNAP-R, you may export and reexport...

  2. 77 FR 16768 - Export Sales Reporting Requirements

    Science.gov (United States)

    2012-03-22

    ... Office of the Secretary 7 CFR Part 20 RIN 0551-AA70 Export Sales Reporting Requirements AGENCY: Office of... frozen box/primal cuts) and distillers dried grain (DDG) to the Export Sales Reporting Requirements, is..., Branch Chief, Export Sales Reporting Branch, Import Policies and Export Reporting Division, Office...

  3. 77 FR 72322 - Order Denying Export Privileges

    Science.gov (United States)

    2012-12-05

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Kue Sang Chun... convicted of violating Section 38 of the Arms Export Control Act (22 U.S.C. 2778 (2000)) (``AECA''). Specifically, Chun was convicted of knowingly exporting and causing the export from the United States to...

  4. 78 FR 60248 - Order Denying Export Privileges

    Science.gov (United States)

    2013-10-01

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Volha Dubouskaya... States, that is, to willfully export from the United States to Belarus export-controlled items, including... of $100.00. Section 766.25 of the Export Administration Regulations (``EAR'' or ``Regulations'')...

  5. 78 FR 58995 - Order Denying Export Privileges

    Science.gov (United States)

    2013-09-25

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Iman Kazerani, 153... was convicted of knowingly and willfully exporting and causing the exportation of laptop computers..., a $10,000 criminal fine and an assessment of $100. Section 766.25 of the Export...

  6. Intrinsic and extrinsic negative regulators of nuclear protein transport processes

    OpenAIRE

    Sekimoto, Toshihiro; Yoneda, Yoshihiro

    2012-01-01

    The nuclear–cytoplasmic protein transport is a critical process in cellular events. The identification of transport signals (nuclear localization signal and nuclear export signal) and their receptors has facilitated our understanding of this expanding field. Nuclear transport must be appropriately regulated to deliver proteins through the nuclear pore when their functions are required in the nucleus, and to export them into the cytoplasm when they are not needed in the nucleus. Altered nuclea...

  7. Rising Threshold Shows Export Ambition

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Beginning from March 1 of this year,China only allows authorized manufacturers to engage in automobile exports in an effort to raise auto quality.The licensing system,jointly introduced by Ministry of Commerce,National Development and Reform Commission,General Administration of Customs,State Quality Inspection Administration and Certification and Accreditation Administration of China,aims to ensure that only large and credible auto manufacturers take part in auto exports.

  8. BRAZILIAN EXPORTS OF MANUFACTURED WOOD

    Directory of Open Access Journals (Sweden)

    Rafael de Azevedo Calderon

    2010-08-01

    Full Text Available The present work deals with the Brazilian exports of sawnwood of non-coniferous, veneer sheets and plywood, from 1961 to 2002. The data regarding the three studied products, sawnwood of non-coniferous, veneer sheets and plywood, were joined through the method of Fisher so that an econometric evaluation of the market of the three products could be carried out. Supply and demand models of the Brazilian exports were specified. The results were satisfactory and they match with the literature. The supply of exports presented a positive answer in relation to the exporter's remuneration, to the production, to the use of the installed capacity (cycles of domestic economical activity and to the tendency, and negative in relation to the internal demand. The demand for the Brazilian exports was influenced positively by the world income, participation index and tendency, and negatively for the relative price. The low elasticity-price of the found demand can have implications in the conservation of the Brazilian forest resources because the exporters can increase the prices, reduce the amounts and still increase the incomes.

  9. 76 FR 11756 - Action Affecting Export Privileges; Ali Amirnazmi; Order Denying Export Privileges

    Science.gov (United States)

    2011-03-03

    ... Bureau of Industry and Security Action Affecting Export Privileges; Ali Amirnazmi; Order Denying Export... 766.25 of the Export Administration Regulations (``EAR'' or ``Regulations'') \\1\\ provides, in... the Office of Export Enforcement, may deny the export privileges of any person who has been convicted...

  10. 78 FR 61743 - Revisions to the Export Administration Regulations: Initial Implementation of Export Control...

    Science.gov (United States)

    2013-10-03

    ..., et al. Revisions to the Export Administration Regulations: Initial Implementation of Export Control...-AF65 Revisions to the Export Administration Regulations: Initial Implementation of Export Control... Register of April 16, 2013. As part of the Export Control Reform (ECR) Initiative, the Bureau of...

  11. 78 FR 29700 - President's Export Council; Subcommittee on Export Administration; Notice of Open Meeting

    Science.gov (United States)

    2013-05-21

    ... Bureau of Industry and Security President's Export Council; Subcommittee on Export Administration; Notice of Open Meeting The President's Export Council Subcommittee on Export Administration (PECSEA) will...). The PECSEA provides advice on matters pertinent to those portions of the Export Administration Act,...

  12. 76 FR 10004 - President's Export Council; Subcommittee on Export Administration; Notice of Open Meeting

    Science.gov (United States)

    2011-02-23

    ... Bureau of Industry and Security President's Export Council; Subcommittee on Export Administration; Notice of Open Meeting The President's Export Council Subcommittee on Export Administration (PECSEA) will... provides advice on matters pertinent to those portions of the Export Administration Act, as amended,...

  13. 77 FR 8807 - President's Export Council, Subcommittee on Export Administration; Notice of Open Meeting

    Science.gov (United States)

    2012-02-15

    ... Bureau of Industry and Security President's Export Council, Subcommittee on Export Administration; Notice of Open Meeting The President's Export Council Subcommittee on Export Administration (PECSEA) will... pertinent to those portions of the Export Administration Act, as amended, that deal with United...

  14. 19 CFR 122.78 - Entry or withdrawal for exportation or for transportation and exportation.

    Science.gov (United States)

    2010-04-01

    ... for exportation or for transportation and exportation. If a shipment is exported under an entry or... 19 Customs Duties 1 2010-04-01 2010-04-01 false Entry or withdrawal for exportation or for transportation and exportation. 122.78 Section 122.78 Customs Duties U.S. CUSTOMS AND BORDER...

  15. 15 CFR 732.5 - Steps regarding Shipper's Export Declaration or Automated Export System record, Destination...

    Science.gov (United States)

    2010-01-01

    ... Declaration or Automated Export System record, Destination Control Statements, and recordkeeping. 732.5... THE EAR § 732.5 Steps regarding Shipper's Export Declaration or Automated Export System record... Automated Export System (AES) record. Exporters or agents authorized to complete the Shipper's...

  16. 15 CFR 758.1 - The Shipper's Export Declaration (SED) or Automated Export System (AES) record.

    Science.gov (United States)

    2010-01-01

    ...) or Automated Export System (AES) record. 758.1 Section 758.1 Commerce and Foreign Trade Regulations... (SED) or Automated Export System (AES) record. (a) The Shipper's Export Declaration (SED) or Automated Export System (AES) record. The SED (Form 7525-V, Form 7525-V-Alt, or Automated Export System record)...

  17. Continuity and export performance in Peruvian companies

    Directory of Open Access Journals (Sweden)

    Oscar Malca Guaylupo

    2016-01-01

    Full Text Available This paper studies the relationship between continuity of business in international markets and their export performance. For this, the paper focuses on the Peruvian export companies during the period 2000-2008, stage where Peruvian exports had continued growth. the results achieved in international markets are analyzed and through probabilistic logit model establishes the relationship between continuity in these markets and the export performance measured in export sales.

  18. China will Reduce Aluminium Export in 2005

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    <正>Starting from January 1, 2005, China eliminated the 8 per cent export tax rebate for aluminium, and further more, the exporters will have to pay 5 per cent export tax. This is beyond the expectations of the producers, for most of them thought only the 8 per cent export tax rebate would be eliminated and it was still too early to add the export tax.

  19. Do African Manufacturing Firms Learn from Exporting?

    OpenAIRE

    Paul Collier; Marcel Fafchamps; Francis Teal; Stefan Dercon

    2002-01-01

    In this paper, we use firm-level panel data for the manufacturing sector in four African countries to estimate the effect of exporting on efficiency. Estimating simultaneously a production function and an export regression that control for unobserved firm effects, we find both significant efficiency gains from exporting, supporting the learning-byexporting hypothesis, and evidence for self-selection of more efficient firms into exporting. The evidence of learning-by-exporting suggests that Af...

  20. MOS11: a new component in the mRNA export pathway.

    Directory of Open Access Journals (Sweden)

    Hugo Germain

    2010-12-01

    Full Text Available Nucleocytoplasmic trafficking is emerging as an important aspect of plant immunity. The three related pathways affecting plant immunity include Nuclear Localization Signal (NLS-mediated nuclear protein import, Nuclear Export Signal (NES-dependent nuclear protein export, and mRNA export relying on MOS3, a nucleoporin belonging to the Nup107-160 complex. Here we report the characterization, identification, and detailed analysis of Arabidopsis modifier of snc1, 11 (mos11. Mutations in MOS11 can partially suppress the dwarfism and enhanced disease resistance phenotypes of snc1, which carries a gain-of-function mutation in a TIR-NB-LRR type Resistance gene. MOS11 encodes a conserved eukaryotic protein with homology to the human RNA binding protein CIP29. Further functional analysis shows that MOS11 localizes to the nucleus and that the mos11 mutants accumulate more poly(A mRNAs in the nucleus, likely resulting from reduced mRNA export activity. Epistasis analysis between mos3-1 and mos11-1 revealed that MOS11 probably functions in the same mRNA export pathway as MOS3, in a partially overlapping fashion, before the mRNA molecules pass through the nuclear pores. Taken together, MOS11 is identified as a new protein contributing to the transfer of mature mRNA from the nucleus to the cytosol.

  1. The Impact of Firm’s Export Competencies on Export Performance

    Directory of Open Access Journals (Sweden)

    Mustafa Kaplan

    2014-12-01

    Full Text Available The purpose of this study is to investigate the impacts of employees’ export experience and knowledge, firms’ export experience, firms’ export market information, firms’ export commitment on marketing planning capabilities and export performance and the relationship between marketing planning capabilities and export performance. To test hypotheses the data were collected from a sample of 153 firms operating in the automotive part industry in Turkey via structured questionnaire. Results reveal that employees’ export experience and knowledge, firms’ export experience, firms’ export market information, firms’ export commitment are found to be positively related with the marketing planning capabilities and the export performance. Beside, marketing planning capability is found to be related positively with export performance. 

  2. Measuring the Export Subsidy Equivalents (ESEs) through Price Discrimination Generated by Exporting State Trading Enterprises

    OpenAIRE

    Suzuki, Nobuhiko; Kinoshita, Junko; FUJII, Toshiaki; Kaise, Harry M.

    2005-01-01

    The Doha Round framewoek agreements state that all forms of export sucsides should be eliminated, which includes not only export subsides through food aid and export credits, but also "consumer financed" ones through exporting STEs. Therefore, one needs a theoretical definition and practical measurements of "hidden" export subsides unregulated under the current WTO rules. This paper proposes a basic definition for the "consumer financed" export subsidy equivalent (ESE) created by STEs' price ...

  3. The Effect of Export Tax on Indonesia’s Cocoa Export Competitiveness

    OpenAIRE

    2013-01-01

    The government of Indonesia implemented an export tax policy on cocoa beans since April 2010 in order to develop cocoa processing industry. The objective of this article is to analyze the effect of export tax on Indonesia’s cocoa export competitiveness. The results indicate that with the implementation of export tax, cocoa export product composition shift from cocoa beans to processed cocoa products. On the other hand, Indonesia’s cocoa export growth is lower than the growth of cocoa world de...

  4. The Impact of Firm’s Export Competencies on Export Performance

    OpenAIRE

    Mustafa Kaplan; Selim Said Eren

    2014-01-01

    The purpose of this study is to investigate the impacts of employees’ export experience and knowledge, firms’ export experience, firms’ export market information, firms’ export commitment on marketing planning capabilities and export performance and the relationship between marketing planning capabilities and export performance. To test hypotheses the data were collected from a sample of 153 firms operating in the automotive part industry in Turkey via structured questionnaire. Results reveal...

  5. Managerial and learning skills in exporting SMEs

    Directory of Open Access Journals (Sweden)

    RUBÉN FERNÁNDEZ ORTIZ

    2005-12-01

    Full Text Available The relevance of the perception of exports in the field of business management can have a key impact on the exporting behavior of SMEs. In particular, it can determine the decision to implement an export policy, as well as the policies applied to consolidate exports. This paper covers two main aspects. First, the extent to which managerial perceptions of exports affect the decision to export, and second, for these SMEs which are already exporters, we study the managerial perceptions that can help to consolidate their commitment to exports. To this aim, some scales based on structural equations to measure the perception of the advantages and disadvantages of exporting are developed and validated. Both analyses are carried out considering whether the SMEs involved are family businesses or not, so that the results obtained can also explain the potential impact of this fact.

  6. Export Competitiveness of Textile Commodities: A Panel Data Approach

    OpenAIRE

    Arora, Tarun

    2015-01-01

    The Paper assesses the export competitiveness of top fifteen textile products (different for each export destination) at 6 digit level of HS classification exported by India to top seven textile export destinations by using both price and income export elasticities. The export elasticities are estimated using dynamic panel data approach for each country separately. Commodity specific elasticities are further estimated to forecast the exports of commodities exported to respective export destin...

  7. Determinants of Short-Term Export Performance in Pakistan

    OpenAIRE

    Subhani, Muhammad Imtiaz; Osman, Ms. Amber; Habib, Sukaina

    2010-01-01

    This research investigates the interdependency between independent (Increase of pricing strategy adaptation, Increase of export intensity, Firm's commitment to exporting, Export market development, Export market competition, Past Pricing Strategy Adaptation, Past Export Performance Satisfaction, Past Export Intensity, Export market distance) and dependent variables (i.e. Expected Short-Term Export Performance improvement) of export performance. The framework is tested via a survey through que...

  8. HSF1-TPR interaction facilitates export of stress-induced HSP70 mRNA.

    Science.gov (United States)

    Skaggs, Hollie S; Xing, Hongyan; Wilkerson, Donald C; Murphy, Lynea A; Hong, Yiling; Mayhew, Christopher N; Sarge, Kevin D

    2007-11-23

    Stress conditions inhibit mRNA export, but mRNAs encoding heat shock proteins continue to be efficiently exported from the nucleus during stress. How HSP mRNAs bypass this stress-associated export inhibition was not known. Here, we show that HSF1, the transcription factor that binds HSP promoters after stress to induce their transcription, interacts with the nuclear pore-associating TPR protein in a stress-responsive manner. TPR is brought into proximity of the HSP70 promoter after stress and preferentially associates with mRNAs transcribed from this promoter. Disruption of the HSF1-TPR interaction inhibits the export of mRNAs expressed from the HSP70 promoter, both endogenous HSP70 mRNA and a luciferase reporter mRNA. These results suggest that HSP mRNA export escapes stress inhibition via HSF1-mediated recruitment of the nuclear pore-associating protein TPR to HSP genes, thereby functionally connecting the first and last nuclear steps of the gene expression pathway, transcription and mRNA export.

  9. Export Readiness Assessment of Ten Iranian Pharmaceutical Companies and Comparison with their Export Performance

    Directory of Open Access Journals (Sweden)

    Mehdi Mohammadzadeh, Mohammad Poloee, Tayebeh Ghari

    2016-09-01

    Full Text Available Background: In the area of exporting, in developing countries, including Iran, the concept of export readiness is unknown to many decision makers and field of activity of Iranian pharmaceutical companies have been limited to the domestic market. Therefore, the main objective of this study is to compare the export performance of ten Iranian pharmaceutical companies with their export readiness. Methods: In order to do this, the top ten of Iranian pharmaceutical companies were selected as the sample. The companies' export readiness was measured, and compared with their export volume as well as their export growth (as two factors for determining the export performance in five years, to practically check the model and find the strengths and weaknesses of these Iranian pharmaceutical companies in the export factors. Results: Base on the results of the study, the export readiness of these companies does not have significant correlation with companies' export volume in the current circumstances, but it can predict the export growth in the firm's export rate with 95% certainty. Conclusion: The most important thing is that according to the data collected in our study, most of these ten Iranian pharmaceutical companies are not ready to attend in exporting and international markets and only two companies were ready to export. It seems that making improvement in some variables like obtaining international standards, marketing and exporting education, having a transparent and documented plan and having the responsible person for export could increase export readiness of pharmaceutical companies.

  10. Nuclear power industry

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-04-28

    This press dossier presented in Shanghai (China) in April 1999, describes first the activities of the Framatome group in the people`s republic of China with a short presentation of the Daya Bay power plant and of the future Ling Ao project, and with a description of the technological cooperation with China in the nuclear domain (technology transfers, nuclear fuels) and in other industrial domains (mechanics, oil and gas, connectors, food and agriculture, paper industry etc..). The general activities of the Framatome group in the domain of energy (nuclear realizations in France, EPR project, export activities, nuclear services, nuclear fuels, nuclear equipments, industrial equipments) and of connectors engineering are presented in a second and third part with the 1998 performances. (J.S.)

  11. A study on the nuclear foreign policy

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jae Soo; Lee, H. M.; Jun, E. J.; Lee, D. H.; Lee, B. W.; Won, B. C.; Kim, H. J.

    2011-12-15

    This study addresses four arenas to assist national nuclear foreign policies under international nuclear nonproliferation regimes. Firstly, this study analyzes the trends of the international nuclear non-proliferation regime, which includes the Treaty on the Non-proliferation of Nuclear Weapons (NPT), the international nuclear export control regime, and fissile material cut-off treaty. Secondly, this study analyzes the trends of international nuclear organizations and fora, which include the International Atomic Energy Agency (IAEA) as a central body of international nuclear diplomacy and technical cooperation and International Framework for Nuclear Energy Cooperation (IFNEC) as a forum for international nuclear cooperation. Thirdly, this study analyzes the nuclear foreign policy of the U. S. Administration and reviews bilateral nuclear cooperation agreement between the ROK and the other countries including the U. S. Lastly, this study analyzes the nuclear issues of North Korea and Iran and multilateral nuclear approaches as assurances of nuclear fuel supply.

  12. Technical evaluation of the electrical, instrumentation, and control design aspects of the override of containment purge valve isolation and other engineered safety feature signals for the Fort Calhoun Nuclear Power Plant

    Energy Technology Data Exchange (ETDEWEB)

    Hackett, D.B.

    1980-01-01

    This report documents the technical evaluation of the electrical, instrumentation, and control design aspects of the override of containment purge valve isolation and other engineered safety feature signals for the Fort Calhoun nuclear power plant. The review criteria are based on IEEE Std-279-1971 requirements for the safety signals to all purge and ventilation isolation valves. This report is supplied as part of the Selected Electrical, Instrumentation, and Control Systems Issues Program being conducted for the US Nuclear Regulatory Commission by Lawrence Livermore Laboratory.

  13. RBC nuclear scan

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003835.htm RBC nuclear scan To use the sharing features on this page, please enable JavaScript. An RBC nuclear scan uses small amounts of radioactive material to ...

  14. Quality, Export and Economic Growth

    DEFF Research Database (Denmark)

    Madsen, Erik Strøjer; Pedersen, Kurt

    1998-01-01

    in an international context. The paper, therefore, addresses the complicated interactions between economic growth, export performance and quality. The contribution of the paper, compared to other growth accounting research, is the inclusion of quality data, quality being a significant mirror of technological...... development. The countries covered by the research represent a wide variation in terms of economic development, from poor LDC's to the most developed industrial nations. The empirical results reveal a probable strong relationship between quality/price and export growth as well as economic growth. This new...

  15. Creative destruction and export patterns

    DEFF Research Database (Denmark)

    Hansen, Jørgen Drud; Kvedaras, Virmantas; Nielsen, Jørgen Ulff-Møller

    2014-01-01

    varieties obsolete. For a given technology (variety) production costs decrease after an infant period due to learning. While all firms are assumed to be symmetric in a life-cycle perspective, at a given point in time firms of different ages differ in productivity, firm size, product quality, and export...... behavior. The model highlights a process of creative destruction, which allows firms to produce in a finite span of periods determined by the intensity of product and process innovations. The model predicts a wide range of export behavior of the individual firm during its life cycle depending...

  16. HIV-1 Rev protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment.

    Science.gov (United States)

    Taniguchi, Ichiro; Mabuchi, Naoto; Ohno, Mutsuhito

    2014-06-01

    Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoprotein remodeling activity of Rev may favor viral gene expression.

  17. Home Textile Exports Show Recovery Signs

    Institute of Scientific and Technical Information of China (English)

    Yao Lan; Guoyun

    2010-01-01

    @@ In this article we have analysed the export performance of Chinese main home textile products, including bedding products, carpet, curtain and towel based on official export data during the first eight months of 2010.

  18. 2006 RE Export Enterprises List Announced

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ According to "Requirement for RE Export Enterprises and Application Procedure in 2006", the Ministry of Commerce P.R.C announced "2006 Rare Earth Export Enterprises List "on December 30th of 2005. The enterprises are listed below.

  19. Export Intermediation and the Internet

    DEFF Research Database (Denmark)

    Andersen, Poul Houman

    2005-01-01

    It is claimed that the remarkable growth in numbers of connected firms to the Internet marks a radical shift in current organisation of international business channels. For export intermediaries these new possibilities pose a threat to their current market position. However, virtual market presence...

  20. A Strong Backbone For Export

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    China Export & Credit Insurance Corp., founded in 2001, is the country’s only policy-oriented credit insurance company. In line with the state’s diplomatic, foreign trade and industrial policies, it supports the country’s commodity, technology and servic

  1. On American Cultural Exportation Strategy

    Institute of Scientific and Technical Information of China (English)

    李德俊

    2015-01-01

    American government has been attaching great importance to the role that cultural values plays in international relationships and Culture Exportation has gradually become one of the important parts of American diplomatic strategy.This strategy,which is propelled by a variety of impetuses and conducted by different approaches,is mainly aimed to serve the overall national interests of the United States.

  2. On American Cultural Exportation Strategy

    Institute of Scientific and Technical Information of China (English)

    李德俊

    2015-01-01

    American government has been attaching great importance to the role that cultural values plays in international relationships and Culture Exportation has gradually become one of the important parts of American diplomatic strategy. This strategy,which is propelled by a variety of impetuses and conducted by different approaches,is mainly aimed to serve the overall national interests of the United States.

  3. A Study on the Nuclear Foreign Policy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Wook; Lee, H. M.; Ko, H. S.; Ryu, J. S.; Oh, K. B.; Yang, M. H.; Lee, K. S

    2007-12-15

    This study approaches the international trends related to nuclear non-proliferation in four aspects. First, this study analyzes the trend of the international nuclear non-proliferation regime, which includes the Treaty on the Non-proliferation of Nuclear Weapons (NPT), the international nuclear export control regime and proposals for assurance of nuclear fuel supply. Second, this study analyzes the trend of international nuclear organizations, which includes the International Atomic Energy Agency (IAEA), a central body of development of nuclear technology and international nuclear diplomacy, and the Organization for Economic Co-operation and Development/Nuclear Energy Agency (OECD/NEA), a intergovernmental organization to consist of a group of nuclear advanced countries. Third, this study analyzes the trends of the U.S.'s nuclear foreign policies, particularly nuclear non-proliferation. Fourth, this study analyzes the nuclear issues of North Korea and Iran as they cause serious concerns to a international society.

  4. Export channel pricing management for integrated solutions

    OpenAIRE

    Roine, Henna; Sainio, Liisa-Maija; Saarenketo, Sami

    2012-01-01

    This article studies systems integrators' export channel pricing management for integrated solutions. We find support from our empirical case study for the notion that a systems integrator's export channel pricing strategy is multidimensional and dependent on international pricing environment and partner characteristics and that export partnerships have unique implications on a systems integrator's pricing process. The results show that giving up pricing control in export channel context may ...

  5. Globalisation and Ireland s Export Performance

    OpenAIRE

    Ruane, Frances; Siedschlag, Iulia; Murphy, Gavin

    2013-01-01

    PUBLISHED This paper provides empirical evidence on Ireland?s export performance in the context of increased globalisation over the past ten years. Using insights from recent contributions to international trade and economic growth theories, we first examine patterns and changes of revealed comparative advantages for Ireland?s exports of goods and services. We then investigate whether Irish exports have specialised in fast growing industries and markets in world exports over the period. Th...

  6. Export channel pricing management for integrated solutions

    OpenAIRE

    Roine, Henna; Sainio, Liisa-Maija; Saarenketo, Sami

    2012-01-01

    This article studies systems integrators' export channel pricing management for integrated solutions. We find support from our empirical case study for the notion that a systems integrator's export channel pricing strategy is multidimensional and dependent on international pricing environment and partner characteristics and that export partnerships have unique implications on a systems integrator's pricing process. The results show that giving up pricing control in export channel context may ...

  7. The complete mitochondrial genome of the enigmatic bigheaded turtle (Platysternon: description of unusual genomic features and the reconciliation of phylogenetic hypotheses based on mitochondrial and nuclear DNA

    Directory of Open Access Journals (Sweden)

    Feldman Chris R

    2006-02-01

    Full Text Available Abstract Background The big-headed turtle (Platysternon megacephalum from east Asia is the sole living representative of a poorly-studied turtle lineage (Platysternidae. It has no close living relatives, and its phylogenetic position within turtles is one of the outstanding controversies in turtle systematics. Platysternon was traditionally considered to be close to snapping turtles (Chelydridae based on some studies of its morphology and mitochondrial (mt DNA, however, other studies of morphology and nuclear (nu DNA do not support that hypothesis. Results We sequenced the complete mt genome of Platysternon and the nearly complete mt genomes of two other relevant turtles and compared them to turtle mt genomes from the literature to form the largest molecular dataset used to date to address this issue. The resulting phylogeny robustly rejects the placement of Platysternon with Chelydridae, but instead shows that it is a member of the Testudinoidea, a diverse, nearly globally-distributed group that includes pond turtles and tortoises. We also discovered that Platysternon mtDNA has large-scale gene rearrangements and possesses two, nearly identical, control regions, features that distinguish it from all other studied turtles. Conclusion Our study robustly determines the phylogenetic placement of Platysternon and provides a well-resolved outline of major turtle lineages, while demonstrating the significantly greater resolving power of comparing large amounts of mt sequence over that of short fragments. Earlier phylogenies placing Platysternon with chelydrids required a temporal gap in the fossil record that is now unnecessary. The duplicated control regions and gene rearrangements of the Platysternon mtDNA probably resulted from the duplication of part of the genome and then the subsequent loss of redundant genes. Although it is possible that having two control regions may provide some advantage, explaining why the control regions would be

  8. An Introduction to Export Assistance in the Internet Age

    DEFF Research Database (Denmark)

    Ramanathan, Somasundaram; Rask, Morten

    2004-01-01

    's (2002) model about web marketing strategies for conceptualizing the Internet related developments associated with export assistance. Finally, we highlight the implications of providing export assistance over the Internet. Those interested in export assistance research and those providing export...

  9. An Introduction to Export Assistance in the Internet Age

    DEFF Research Database (Denmark)

    Ramanathan, Somasundaram; Rask, Morten

    's (2002) model about web marketing strategies for conceptualizing the Internet related developments associated with export assistance. Finally, we highlight the implications of providing export assistance over the Internet. Those interested in export assistance research and those providing export...

  10. 76 FR 52935 - President's Export Council, Subcommittee on Export Administration; Notice of Open Meeting

    Science.gov (United States)

    2011-08-24

    ... Bureau of Industry and Security President's Export Council, Subcommittee on Export Administration; Notice of Open Meeting The President's Export Council Subcommittee on Export Administration (PECSEA) will... Administration Act, as amended, that deal with United States policies of encouraging trade with all...

  11. 75 FR 54857 - President's Export Council, Subcommittee on Export Administration; Notice of Recruitment of...

    Science.gov (United States)

    2010-09-09

    ... Bureau of Industry and Security President's Export Council, Subcommittee on Export Administration; Notice of Recruitment of Private-Sector Members; Date Extension Summary: The President's Export Council Subcommittee on Export Administration (PECSEA) advises the U.S. Government on matters and issues pertinent...

  12. 75 FR 47548 - President's Export Council Subcommittee on Export Administration; Notice of Recruitment of...

    Science.gov (United States)

    2010-08-06

    ... Bureau of Industry and Security President's Export Council Subcommittee on Export Administration; Notice of Recruitment of Private-Sector Members SUMMARY: The President's Export Council Subcommittee on Export Administration (PECSEA) advises the U.S. Government on matters and issues pertinent...

  13. 19 CFR 351.414 - Comparison of normal value with export price (constructed export price).

    Science.gov (United States)

    2010-04-01

    ... Price, Fair Value, and Normal Value § 351.414 Comparison of normal value with export price (constructed... 19 Customs Duties 3 2010-04-01 2010-04-01 false Comparison of normal value with export price... value and, in an investigation, prices used as the basis for export price or constructed export price as...

  14. 15 CFR 752.15 - Export clearance.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU... COMPREHENSIVE LICENSE § 752.15 Export clearance. (a) Shipper's Export Declaration (SED) or Automated...

  15. 7 CFR 927.12 - Export market.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export market. 927.12 Section 927.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Definitions § 927.12 Export market. Export market means any destination...

  16. 22 CFR 120.17 - Export.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Export. 120.17 Section 120.17 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.17 Export. (a) Export means: (1) Sending or taking a defense article out of the United States in any manner, except...

  17. 7 CFR 915.12 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 915.12 Section 915.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Regulating Handling Definitions § 915.12 Export. Export means to ship avocados to any destination which...

  18. 7 CFR 948.17 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 948.17 Section 948.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Regulating Handling Definitions § 948.17 Export. Export means the shipment of potatoes to any...

  19. 27 CFR 4.80 - Exports.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exports. 4.80 Section 4.80... TREASURY LIQUORS LABELING AND ADVERTISING OF WINE General Provisions § 4.80 Exports. The regulations in this part shall not apply to wine exported in bond....

  20. Export growth slowdown from January to April

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    January to April this year, the economic operation of China’s textile industry overall in slowdown trend, the growth rate of output of major products fell significantly, exports and profits were greatly affected, the textile industry is facing great operating pressure. The export side, Japan, EU, U.S. textile and garment export growth has slowed down, the market share

  1. 26 CFR 52.4682-5 - Exports.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Exports. 52.4682-5 Section 52.4682-5 Internal... (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-5 Exports. (a) Overview. This section provides rules relating to the tax imposed under section 4681 on ozone-depleting chemicals (ODCs) that are exported. In...

  2. 7 CFR 947.17 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 947.17 Section 947.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Definitions § 947.17 Export. Export means shipment of potatoes beyond the boundaries of continental...

  3. 7 CFR 966.18 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 966.18 Section 966.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Handling Definitions § 966.18 Export. Export means shipment of tomatoes beyond the boundaries of the...

  4. 7 CFR 923.15 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 923.15 Section 923.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... IN WASHINGTON Order Regulating Handling Definitions § 923.15 Export. Export means to ship...

  5. 27 CFR 7.60 - Exports.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exports. 7.60 Section 7.60... TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES General Provisions § 7.60 Exports. This part shall not apply to malt beverages exported in bond....

  6. 7 CFR 51.912 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Export. 51.912 Section 51.912 Agriculture Regulations... Standards for Grades of Table Grapes (European or Vinifera Type) 1 Definitions § 51.912 Export. When designated as Export, grapes shall be packed with any of the customary protective materials such as...

  7. 7 CFR 922.15 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 922.15 Section 922.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... WASHINGTON Order Regulating Handling Definitions § 922.15 Export. Export means to ship apricots beyond...

  8. 27 CFR 16.31 - Exports.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exports. 16.31 Section 16... TREASURY LIQUORS ALCOHOLIC BEVERAGE HEALTH WARNING STATEMENT General Provisions § 16.31 Exports. The..., bottled, or labeled for export from the United States, or for delivery to a vessel or aircraft,...

  9. 7 CFR 946.15 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 946.15 Section 946.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Regulating Handling Definitions § 946.15 Export. Export means shipment of potatoes beyond the boundaries...

  10. 7 CFR 924.15 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 924.15 Section 924.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... WASHINGTON AND IN UMATILLA COUNTY, OREGON Order Regulating Handling Definitions § 924.15 Export. Export...

  11. 7 CFR 959.18 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 959.18 Section 959.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Handling Definitions § 959.18 Export. Export means to ship onions to any destination which is not...

  12. 27 CFR 28.154 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.154..., for Exportation or Transfer to a Foreign-Trade Zone § 28.154 Export marks. In addition to the marks... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

  13. 78 FR 35195 - Acquisition Regulations: Export Control

    Science.gov (United States)

    2013-06-12

    ... Parts 925, 952, and 970 RIN 1991-AB99 Acquisition Regulations: Export Control AGENCY: Department of... amend the Department of Energy Acquisition Regulation (DEAR) to add export control requirements... ``DEAR: Export Control and RIN 1991-AB99,'' by any of the following methods: Federal eRulemaking Portal...

  14. 27 CFR 28.193 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.193... Drawback Filing of Notice and Removal § 28.193 Export marks. In addition to the marks and brands required... chapter, the exporter shall mark the word “Export” on the Government side of each case or Government head...

  15. 27 CFR 28.223 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.223... Export marks. In addition to the marks and brands required to be placed on kegs, barrels, cases, crates... “Export” on each container or case before removal for export, for use on vessels or aircraft, or for...

  16. 78 FR 45168 - Acquisition Regulations: Export Control

    Science.gov (United States)

    2013-07-26

    ... Parts 925, 952 and 970 RIN 1991-AB99 Acquisition Regulations: Export Control AGENCY: Department of... Department of Energy Acquisition Regulation (DEAR) to add export control requirements applicable to the... business August 23, 2013. ADDRESSES: You may submit comments, identified by ``DEAR: Export Control and RIN...

  17. 19 CFR 12.4 - Exportation.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Exportation. 12.4 Section 12.4 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES... Caustic Or Corrosive Substances § 12.4 Exportation. The exportation of merchandise, the subject of §...

  18. 19 CFR 18.43 - Indirect exportation.

    Science.gov (United States)

    2010-04-01

    .... port to another for actual exportation at the second port, any export declarations required to be... 19 Customs Duties 1 2010-04-01 2010-04-01 false Indirect exportation. 18.43 Section 18.43 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Merchandise Not Otherwise Subject to Customs Control...

  19. 78 FR 61953 - Order Denying Export Privileges

    Science.gov (United States)

    2013-10-08

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Timothy Gormley, Inmate... engaging in transactions relating to exporting amplifiers to China and India without obtaining the required... assessment and a $1,000 criminal fine. Section 766.25 of the Export Administration Regulations (``EAR''...

  20. 78 FR 37520 - Order Denying Export Privileges

    Science.gov (United States)

    2013-06-21

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Placido Molina, Jr... convicted of violating Section 38 of the Arms Export Control Act (22 U.S.C. 2778 (2006 & Supp. IV 2010)) (``AECA''). Specifically, Molina was convicted of knowingly and willfully attempting to export and...

  1. 78 FR 60250 - Order Denying Export Privileges

    Science.gov (United States)

    2013-10-01

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Vikramaditya Singh, a.k... attempting to cause the export of digital microwave radios to Iran without the required authorization from... probation, six months of home confinement and a $100,000 fine. Section 766.25 of the Export...

  2. 78 FR 37518 - Order Denying Export Privileges

    Science.gov (United States)

    2013-06-21

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Lee Roy Perez, Inmate... convicted of violating Section 38 of the Arms Export Control Act (22 U.S.C. 2778 (2006 & Supp. IV 2010)) (``AECA''). ] Specifically, Perez was convicted of knowingly and willfully exporting and causing to...

  3. 78 FR 60249 - Order Denying Export Privileges

    Science.gov (United States)

    2013-10-01

    ... Bureau of Industry and Security Order Denying Export Privileges In the Matter of: Andrew Silcox, Inmate... of violating Section 38 of the Arms Export Control Act (22 U.S.C. 2778 (2006 & Supp. IV 2010)) (``AECA''). Specifically, Silcox was convicted of knowingly and willfully exporting from the United...

  4. Isolation and characterization of the Arabidopsis heat-intolerant 2 (hit2) mutant reveal the essential role of the nuclear export receptor EXPORTIN1A (XPO1A) in plant heat tolerance.

    Science.gov (United States)

    Wu, Shin-Jye; Wang, Lian-Chin; Yeh, Ching-Hui; Lu, Chun-An; Wu, Shaw-Jye

    2010-06-01

    *The Arabidopsis heat-intolerant 2 (hit2) mutant was isolated on the basis of its impaired ability to withstand moderate heat stress (37 degrees C). Determination of the genetic mutation that underlies the hit2 thermosensitive phenotype allowed better understanding of the mechanisms by which plants cope with heat stress. *Genetic analysis revealed that hit2 is a single recessive mutation. Map-based cloning was used to identify the hit2 locus. The response of hit2 to other types of heat stress was also investigated to characterize the protective role of HIT2. *hit2 was defective in basal but not in acquired thermotolerance. hit2 was sensitive to methyl viologen-induced oxidative stress, and the survival of hit2 seedlings in response to heat stress was affected by light conditions. The mutated locus was located at the EXPORTIN1A (XPO1A) gene, which encodes a nuclear transport receptor. Two T-DNA insertion lines, xpo1a-1 and xpo1a-3, exhibited the same phenotypes as hit2. *The results provide evidence that Arabidopsis XPO1A is dispensable for normal plant growth and development but is essential for thermotolerance, in part by mediating the protection of plants against heat-induced oxidative stress.

  5. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export.

    Science.gov (United States)

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun

    2014-01-20

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation.

  6. 19 CFR 122.118 - Exportation from port of arrival.

    Science.gov (United States)

    2010-04-01

    ... copy. (2) Exportation copy. The exportation copy shall be filed by the exporting airline when clearance... aircraft's clearance documents. The exportation and clearance copies shall show the exporting airline's... 19 Customs Duties 1 2010-04-01 2010-04-01 false Exportation from port of arrival. 122.118...

  7. 19 CFR 19.38 - Supervision of exportation.

    Science.gov (United States)

    2010-04-01

    ... the sales ticket procedure for exportation shall be exported only under Customs supervision as... exportation transactions, examination of articles being exported, and audits of the proprietor's records. (b) Supervision of ATF bonded exports. Customs officers may conduct general supervision of exportations...

  8. 50 CFR 14.63 - Export declaration requirements.

    Science.gov (United States)

    2010-10-01

    ... PLANTS IMPORTATION, EXPORTATION, AND TRANSPORTATION OF WILDLIFE Wildlife Declarations § 14.63 Export... Declaration for Importation or Exportation of Fish or Wildlife (Form 3-177) signed by the exporter, or the exporter's agent, shall be filed with the Service prior to the export of any wildlife at the port...

  9. The conserved Bud20 zinc finger protein is a new component of the ribosomal 60S subunit export machinery.

    Science.gov (United States)

    Bassler, Jochen; Klein, Isabella; Schmidt, Claudia; Kallas, Martina; Thomson, Emma; Wagner, Maria Anna; Bradatsch, Bettina; Rechberger, Gerald; Strohmaier, Heimo; Hurt, Ed; Bergler, Helmut

    2012-12-01

    The nuclear export of the preribosomal 60S (pre-60S) subunit is coordinated with late steps in ribosome assembly. Here, we show that Bud20, a conserved C(2)H(2)-type zinc finger protein, is an unrecognized shuttling factor required for the efficient export of pre-60S subunits. Bud20 associates with late pre-60S particles in the nucleoplasm and accompanies them into the cytoplasm, where it is released through the action of the Drg1 AAA-ATPase. Cytoplasmic Bud20 is then reimported via a Kap123-dependent pathway. The deletion of Bud20 induces a strong pre-60S export defect and causes synthetic lethality when combined with mutant alleles of known pre-60S subunit export factors. The function of Bud20 in ribosome export depends on a short conserved N-terminal sequence, as we observed that mutations or the deletion of this motif impaired 60S subunit export and generated the genetic link to other pre-60S export factors. We suggest that the shuttling Bud20 is recruited to the nascent 60S subunit via its central zinc finger rRNA binding domain to facilitate the subsequent nuclear export of the preribosome employing its N-terminal extension.

  10. Exporting Variables in a Hierarchically Distributed Control System

    Energy Technology Data Exchange (ETDEWEB)

    Chamizo Llatas, M.

    1995-07-01

    We describe the Remote Variable Access Service (RVAS), a network service developed and used in the distributed control and monitoring system of the TJ-II Heliac, which is under construction at CIEMAT (Madrid, Spain) and devoted to plasma studies in the nuclear fusion field. The architecture of the TJ-II control system consists of one central Sun workstation Sparc 10 and several autonomous subsystems based on VME crates with embedded processors running the OS-9 (V.24) real time operating system. The RVAS service allows state variables in local control processes running in subsystems to be exported to remote processes running in the central control workstation. Thus we extend the concept of exporting of file systems in UNIX machines to variables in processes running in different machines. (Author) 6 refs.

  11. Energy from nuclear fission(*

    Directory of Open Access Journals (Sweden)

    Ripani M.

    2015-01-01

    Full Text Available The main features of nuclear fission as physical phenomenon will be revisited, emphasizing its peculiarities with respect to other nuclear reactions. Some basic concepts underlying the operation of nuclear reactors and the main types of reactors will be illustrated, including fast reactors, showing the most important differences among them. The nuclear cycle and radioactive-nuclear-waste production will be also discussed, along with the perspectives offered by next generation nuclear assemblies being proposed. The current situation of nuclear power in the world, its role in reducing carbon emission and the available resources will be briefly illustrated.

  12. Human Capital and Wages in Exporting Firms

    DEFF Research Database (Denmark)

    Munch, Jakob Roland; Skaksen, Jan Rose

    . Using a very rich matched worker-firm longitudinal dataset we find that firms with high export intensities pay higher wages. However, an interaction term between export intensity and skill intensity has a positive impact on wages and it absorbs the direct effect of the export intensity. That is, we find......This paper studies the link between a firms education level, export performance and wages of its workers. We argue that firms may escape intense competition in international markets by using high skilled workers to differentiate their products. This story is consistent with our empirical results...... an export wage premium, but it accrues to workers in firms with high skill intensities...

  13. Phases definition in marketing export process

    Directory of Open Access Journals (Sweden)

    Rajković Dragan

    2004-01-01

    Full Text Available The result of export marketing process depends on its five phases. The first phase-revision of export capacities, inner view on advantages and defects of company concerning export possibilities. The second phase-identification of export strategy market penetration. The forth phase-preparing for the marketing campaign (action. The fifth phase-carrying out the above mentioned activities. This study shows the structure and contents of the mentioned phases. At the end, export marketing analyzed DPV is given as the example.

  14. Automatic Export of PubMed Citations to EndNote.

    Science.gov (United States)

    London, Sue; Gurdal, Osman; Gall, Carole

    2010-04-01

    The export of MEDLINE references to EndNote can be accomplished in various ways. Unlike Ovid MEDLINE, PubMed does not have a direct export feature to EndNote. Until recently, PubMed references had to be saved as a text file to import into EndNote. Now, the automatic export of PubMed references can be done using Internet Explorer (IE) or Mozilla Firefox Web browsers. The development and teaching of seamless citation management is a value-added service to health professionals.

  15. Improvement of food exports from Serbia

    Directory of Open Access Journals (Sweden)

    Babić Jasna

    2012-01-01

    Full Text Available This paper deals with the analysis of food exports from Serbia and safety food management system. The food is an important export opportunity for Serbia. Food exports recorded robust growth, higher than the growth of total Serbian exports, with positive balance in foreign trade. In order to exploit identified opportunities, it is necessary to improve domestic production, provide basic quality requirements and develop marketing aspects of export supply. This paper presents the necessary standards of a quality related to the food segment and the most important directions for improving marketing export competitiveness factors of agricultural and food products. The purpose of this paper is to highlight the importance of food safety management system certification in the entire food chain and importance of marketing strategies for export development of these products.

  16. Exporting and Productivity: Learning from Vietnam

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn;

    2017-01-01

    different policy stance than typical in Africa. This is especially so in promoting export-oriented industry. If learning by exporting is a key driver of progress, then a fundamental reason for Africa's lack of transformation is likely to be the low policy priority given to export promotion in the past....... To enlarge the body of empirical evidence, we use an extensive 2005–2012 firm-level panel data set from Vietnam and separate out productivity effects of exporting due to self-selection. This allows us to conclude that firms actually learn by exporting. We also examine how this learning takes place. Our...... findings suggest that productivity gains are associated with moving to larger scale for foreign-owned firms with little evidence of subsequent learning on export markets. We find strong evidence to suggest that private domestic firms learn and accumulate knowledge from export markets with learning...

  17. Perceived impediments to export involvement among small and medium sized firms : non-exporters perspective

    Directory of Open Access Journals (Sweden)

    Mercy Mpinganjira

    2011-12-01

    Full Text Available Purpose: The main purpose of this paper is to examine perceived impediments to export involvement among non-exporting small and medium sized firms (SME's in Malawi. The study also examines levels of interest in exporting among the firms. Problem investigated: Many countries have programs aimed at promoting export involvement among SME's. Despite this, most SME's continue to ignore exporting as a viable business strategy. Information on perceived impediments to export involvement especially from the non-exporters' perspective is often lacking hence the need for this study. Methodology: Data was collected from 80 owner managers of non-exporting SME's. A structured questionnaire was the main instrument used to collect data. Personal interviews were also held with managers for the purposes of probing their answers to the questions in the questionnaire. Statistical Package for Social Science (SPSS version 18 was used to analyse the quantitative data obtained from use of the structured questionnaire. Qualitative data obtained through personal interviews was analysed used thematic analysis. Findings: The findings of the study showed significant levels of interest in exporting among the firms. The majority of the owner managers indicated willingness to exploit export opportunities that may be readily available to them. The findings however showed that just over half of the respondents had discussed or investigated the possibility of exporting before. On impediments to exporting, the findings showed that managers perceive many factors as important impediments to their firm's involvement in exporting. The top two most important impediments were internal to the firm and related to human resource issues. They included insufficient knowledge about export opportunities and lack of personnel knowledgeable in exporting. Originality and value of the research: A review of literature shows that most export promotion studies tend to focus more on issues relating to

  18. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: A name change to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features would help prevent overtreatment.

    Science.gov (United States)

    Thompson, Lester Dr

    2016-07-01

    Encapsulated follicular variant of papillary thyroid carcinoma is a common thyroid gland cancer, with a highly indolent behavior. Recently, reclassification as a non-malignant neoplasm has been proposed. There is no comprehensive, community hospital based longitudinal evaluation of encapsulated follicular variant of papillary thyroid carcinoma. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma were identified in a review of all thyroid gland surgeries performed in 2002 within the Southern California Permanente Medical Group. All histology slides were reviewed and follow-up obtained. Seventy-five women and nineteen men, aged 20-80 years (mean 45.6 years), had a single (n=61), multiple (same lobe; n=20), or bilateral (n=13) tumor(s), ranging in size from 0.7 to 9.5 cm in diameter (mean 3.3 cm). Histologically, all cases demonstrated a well-formed tumor capsule, with capsular and/or lymphovascular invasion in 17 and no invasion in 77 cases. Lymph node metastases were not identified. The tumors had a follicular architecture, without necrosis or >3 mitoses/10 high-power fields (HPFs). Classical papillary thyroid carcinoma nuclear features were seen in at least three HPFs per 3 mm of tumor diameter, including enlarged, elongated, crowded, and overlapping nuclei, irregular nuclear contours, nuclear grooves, and nuclear chromatin clearing. Lobectomy alone (n=41), thyroidectomy alone (n=34), or completion thyroidectomy (n=19) was the initial treatment combined with post-op radioablative iodine in 25 patients. All patients were without evidence of disease after a median follow-up of 11.8 years. Encapsulated follicular variant of papillary thyroid carcinoma showed benign behavior, supporting conservative surgery alone and reclassification of these tumors to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).

  19. Export Rebates on Grain Finished

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ According to the State Statistics Bureau, China's consumer price index (CPI) jumped by 6.9 percent year-on-year last November, approaching the high levels seen at the end of 1996, one of the largest areas of increase was the price of grain,which rose by 6.6 percent. There is no doubt the growth in CPI can be mainly attributed to soaring food prices and the diffusion effect of oil price adjustments. Large orders for grain exports have put Chinese grain suppliers under tremendous pressure. In order to solve this problem, the Finance Ministry and State Administration of Taxation together announced that 84 categories of export tax rebates on major types of grain will be eliminated.

  20. Export Rebates on Grain Finished

    Institute of Scientific and Technical Information of China (English)

    Liu; Xinwen

    2008-01-01

      According to the State Statistics Bureau, China's consumer price index (CPI) jumped by 6.9 percent year-on-year last November, approaching the high levels seen at the end of 1996, one of the largest areas of increase was the price of grain,which rose by 6.6 percent. There is no doubt the growth in CPI can be mainly attributed to soaring food prices and the diffusion effect of oil price adjustments. Large orders for grain exports have put Chinese grain suppliers under tremendous pressure. In order to solve this problem, the Finance Ministry and State Administration of Taxation together announced that 84 categories of export tax rebates on major types of grain will be eliminated.……

  1. NAS Panel faults export controls

    Science.gov (United States)

    Katzoff, Judith A.

    A study prepared by a top-level panel says that current export controls on militarily sensitive U.S. technology may be “overcorrecting” previous weaknesses in that system, resulting in “a complex and confusing control system” that makes it more difficult for U.S. businesses to compete in international markets. Moreover, this control system has “an increasingly corrosive effect” on U.S. relations with allies. The panel recommended that the United States concentrate more effort on bringing about uniformity in the export control policies of countries belonging to the Coordinating Committee on Multilateral Export Controls (CoCom), i.e., most of the member nations in NATO (the North Atlantic Treaty Organization) and Japan.The 21-member panel was appointed by the Committee on Science, Engineering, and Public Policy (COSEPUP), a joint unit of the National Academy of Sciences (NAS), the National Academy of Engineering (NAE), and the Institute of Medicine (IOM). The panel, composed of administrators, researchers, and former government officials, was chaired by AGU member Lew Allen, Jr., director of the Jet Propulsion Laboratory (Pasadena, Calif.) and former chief of staff of the U.S. Air Force. Their report was supported by NAS funds, by a number of private organizations (including AGU), by the U.S. Departments of Commerce, Defense, Energy, and State, by the National Science Foundation, and by the National Aeronautics and Space Administration.

  2. Establishing RDCS in CO MESA: Egyptian exporters' perspectives

    Directory of Open Access Journals (Sweden)

    Islam El-Nakib

    2008-03-01

    Full Text Available The role of supply chains has been significant in strengtheningthe competitiveness of interna tiona[ trade among countries.Regional Distribution Centres (RDCs are among the remarkabledrivers of any international trade supply chains. The Egyptianexports face severe competition in the international marketwhich has led the Egyptian government to join regional tradeblocks such as the Common Market for Eastern and SouthernAfrica (COMESA for the aim of establishing export channelsto new markets. Therefore, applying the concept of RDCs wasexamined to enhance the performance of Egyptian exportswhich are facing high competition in the EU, US, and Asianmarkets. Thus, the purpose of this research is to study the associatedaspects to this area of interest based on a survey whichhas targeted the Egyptian exporters who are directly dealingwith the CO MESA to cover several issues regarding the tradebetween Egypt and CO MESA. Moreover, this survey has alsoincluded the analysis of the reasons that make the CO MESAprefer other international products rather than the Egyptianproducts, and the attitudes towards the proposed selection ofEgypt's RDCs in COMESA. In addition, this survey is alsoidentifying the main features of the Egyptian exports comparedwith the foreign exports in COMESA and the recommendedaction to be taken towards the establishment of the EgyptianRDCs in CO MESA.

  3. Natural gas imports and exports. Second quarter report 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    This quarter`s feature report focuses on natural gas exports to Mexico. OFP invites ideas from the public on future topics dealing with North American natural gas import/export trade. Such suggestions should be left on OFP`s electronic bulletin board. Natural Gas exports to Mexico continued to grow and reached an historic high for the month of June (7.8 Bcf). Two new long-term contracts were activated; Pennsylvania Gas & Water Company began importing 14.7 MMcf per day from TransCanada PipeLines Ltd., and Renaissance Energy (U.S.) Inc. began importing 2.8 MMcf per day from Renaissance Energy Ltd. for resale to Delmarva Power & Light Company. Algerian LNG imports remained stagnant with only one tanker being imported by Pan National Gas Sales, Inc. (Pan National). During the first six months of 1995, data indicates gas imports increased by about 10 percent over the 1994 level (1,418 vs. 1,285 Bcf), with Canadian imports increasing by 14 percent and Algerian imports decreasing by 81 percent. During the same time period, exports increased by 18 percent (83 vs. 70.1 Bcf).

  4. Position paper on nuclear proliferation issues preventing nuclear proliferation. A duty for the nuclear community

    Energy Technology Data Exchange (ETDEWEB)

    Goldschmidt, Pierre; Bonin, Bernard [ENS High Scientific Council, Brussels (Belgium)

    2010-06-15

    The production of electricity from nuclear power plants is widely seen today as having an increasing role to play in meeting global energy requirements in a sustainable manner. Conscious of the inherently sensitive nature of nuclear technology and materials the ENS-HSC (European Nuclear Society - High Scientific Council) is well aware that a severe safety, security, environmental or proliferation mishap stemming from nuclear energy anywhere in the world would undermine the potential for nuclear energy to contribute to the global energy supply and the minimization of harmful carbon emissions. While the safety of nuclear power plants has continuously improved over the last three decades, the same degree of success cannot be claimed when it comes to the achievements of the international community in stemming the risk of nuclear weapons proliferation. This unfortunate situation is due to both technical and political reasons. The European nuclear industry is committed to the exclusively peaceful use of nuclear energy and to export nuclear facilities and related materials, equipment and technology solely in accordance with relevant national export laws and regulations, Nuclear Suppliers Group guidelines and pertinent United Nations Security Council Resolutions. The ENS-HSC considers that, as a manifestation of their strong commitment to nonproliferation, it is important for the nuclear industry to pay special attention to and promote proliferation-resistant designs and to take IAEA safeguards requirements into account at the design stage. Preventing nuclear proliferation is primarily the responsibility of states but, as major stakeholders, the nuclear industry and scientific community should actively support nuclear disarmament as foreseen in the Non-Proliferation Treaty and measures necessary to strengthen the non-proliferation regime, particularly the international control of the flux of nuclear material and technology. (orig.)

  5. The interaction of the cellular export adaptor protein Aly/REF with ICP27 contributes to the efficiency of herpes simplex virus 1 mRNA export.

    Science.gov (United States)

    Tian, Xiaochen; Devi-Rao, Gayathri; Golovanov, Alexander P; Sandri-Goldin, Rozanne M

    2013-07-01

    Herpes simplex virus 1 (HSV-1) protein ICP27 enables viral mRNA export by accessing the cellular mRNA export receptor TAP/NXF, which guides mRNA through the nuclear pore complex. ICP27 binds viral mRNAs and interacts with TAP/NXF, providing a link to the cellular mRNA export pathway. ICP27 also interacts with the mRNA export adaptor protein Aly/REF, which binds cellular mRNAs and also interacts with TAP/NXF. Studies using small interfering RNA (siRNA) knockdown indicated that Aly/REF is not required for cellular mRNA export, and similar knockdown studies during HSV-1 infection led us to conclude that Aly/REF may be dispensable for viral RNA export. Recently, the structural basis of the interaction of ICP27 with Aly/REF was elucidated at atomic resolution, and it was shown that three ICP27 residues, W105, R107, and L108, interface with the RNA recognition motif (RRM) domain of Aly/REF. Here, to determine the role the interaction of ICP27 and Aly/REF plays during infection, these residues were mutated to alanine, and a recombinant virus, WRL-A, was constructed. Virus production was reduced about 10-fold during WRL-A infection, and export of ICP27 protein and most viral mRNAs was less efficient. We conclude that interaction of ICP27 with Aly/REF contributes to efficient viral mRNA export.

  6. Export Marketing of Croatian Baby Beef

    Directory of Open Access Journals (Sweden)

    Ante Kolega

    2003-09-01

    Full Text Available Croatia has traditionally been the exporter of livestock and beef. In 1988 Croatia exported a record of 35,7 thousand tons of livestock, worth almost 60 million US $. During the period between 1981 and 1991, the export of beef and processed meat was somewhat smaller, about 12,8 thousand tons, 40 million US $ worth. The most important export destinations were Italy, with almost 90% of all volume and monetary value of export, and Greece. In March 1993 EU has banned the import of livestock and beef from Croatia, due to a scandal with infected cattle. In spite of the subsequent abolition of this ban, Croatian export never really recovered, so today the export of beef amounts to less than a thousand tons. Even though the conditions on the export markets and in the domestic cattle breeding industry have changed, we think that it is possible to achieve the export expansion of Croatian baby beef in the foreign market. This article describes the results of the research conducted on the Italian and Greek market. According to expert opinions and the results of our survey it is evident that, with a certain quality of the product, it would be possible to renew the export of Croatian baby beef to the target markets.

  7. 77 FR 73054 - Application for a License To Export Radioactive Waste

    Science.gov (United States)

    2012-12-07

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Application for a License To Export Radioactive Waste Pursuant to 10 CFR 110.70(b) ``Public Notice.... 2012, October 25, 2012, XW020, radioactive 1178 pounds disposal by the 11006061. waste in the...

  8. 75 FR 74104 - Request for a License To Export Radioactive Waste

    Science.gov (United States)

    2010-11-30

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Request for a License To Export Radioactive Waste Pursuant to 10 CFR 110.70 (b) ``Public Notice of... End use Recipient country application no. docket No. EnergySolutions, August 27, Radioactive waste Not...

  9. 76 FR 56489 - Request for a License To Export Radioactive Waste

    Science.gov (United States)

    2011-09-13

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Request for a License To Export Radioactive Waste Pursuant to 10 CFR 110.70 (b) ``Public Notice of... radioactive Radionuclide Non-conforming Canada. 17, 2011, August 18, 2011, waste in the form reallocation...

  10. 75 FR 27842 - Request for a License to Export Radioactive Waste

    Science.gov (United States)

    2010-05-18

    ... [Federal Register Volume 75, Number 95 (Tuesday, May 18, 2010)] [Notices] [Pages 27842-27843] [FR Doc No: 2010-11822] NUCLEAR REGULATORY COMMISSION Request for a License to Export Radioactive Waste... radioactive pounds (53 cubic disposal by the EnergySolutions), April 19, waste in the feet) of dry original...

  11. 77 FR 14445 - Application for a License To Export Steel Forging

    Science.gov (United States)

    2012-03-09

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Application for a License To Export Steel Forging Pursuant to 10 CFR 110.70(b) ``Public Notice of... Spain. December 15, 2011 head steel head steel February 7, 2012 forging. forging will be XR175...

  12. 77 FR 1956 - Application for a License To Export High-Enriched Uranium

    Science.gov (United States)

    2012-01-12

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Application for a License To Export High-Enriched Uranium Pursuant to 10 CFR 110.70(b) ``Public... Netherlands. Security Complex. Uranium uranium (9.3 targets at December 21, 2011 (93.35%). kilograms U-...

  13. 78 FR 72123 - Request To Amend a License to Export High-Enriched Uranium

    Science.gov (United States)

    2013-12-02

    ... COMMISSION Request To Amend a License to Export High-Enriched Uranium Pursuant to 10 CFR 110.70 (b) ``Public... in Belgium. National Nuclear Security Uranium (HEU) uranium France for irradiation in Administration... contained in 6.2 kg uranium to a new cumulative total of 12.615 kg of U-235 contained in 13.5 kg uranium;...

  14. 78 FR 16303 - Request To Amend a License To Export; High-Enriched Uranium

    Science.gov (United States)

    2013-03-14

    ... From the Federal Register Online via the Government Publishing Office ] NUCLEAR REGULATORY COMMISSION Request To Amend a License To Export; High-Enriched Uranium Pursuant to 10 CFR 110.70 (b) ``Public... of Energy, High-Enriched Uranium 10 kilograms uranium To manufacture HEU targets in France...

  15. 75 FR 6223 - Application For a License To Export High-Enriched Uranium

    Science.gov (United States)

    2010-02-08

    ... From the Federal Register Online via the Government Publishing Office ] NUCLEAR REGULATORY COMMISSION Application For a License To Export High-Enriched Uranium Pursuant to 10 CFR 110.70(c) ``Public... fabricate Canada. Complex December 21, 2009, Uranium (93.35%). uranium (16.3 targets for December 28,...

  16. 75 FR 7525 - Application for a License To Export High-Enriched Uranium

    Science.gov (United States)

    2010-02-19

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Application for a License To Export High-Enriched Uranium Pursuant to 10 CFR 110.70(c) ``Public... fuel France; Belgium. Security Complex, February 2, Uranium (93.35%). uranium (87.3 elements in...

  17. 75 FR 15743 - Application for a License To Export High-Enriched Uranium

    Science.gov (United States)

    2010-03-30

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Application for a License To Export High-Enriched Uranium Pursuant to 10 CFR 110.70(c) ``Public... fabricate fuel France. Complex, March 3, 2010. Uranium (93.35%). uranium (149.36 elements in March 9,...

  18. 78 FR 60928 - Request To Amend a License To Export High-Enriched Uranium

    Science.gov (United States)

    2013-10-02

    ... COMMISSION Request To Amend a License To Export High-Enriched Uranium Pursuant to 10 CFR 110.70 (b) ``Public... Nuclear Security Uranium uranium (17.1 targets in France Administration, September 9, (93.35%). kilograms... 10.1 kg uranium to a new cumulative total of 17.1 kg of U-235 contained in 18.4 kg uranium; and...

  19. Biological feature of radioiodine-131 and use of potassium iodide in nuclear accident%131I的生物学特点和碘化钾在核事故中的应用

    Institute of Scientific and Technical Information of China (English)

    邢家骝; 丁勇; 方毅

    2011-01-01

    Japan 3·11 Fukushima nuclear accident releases a huge amount of radioiodine-131 and attracts public concern with it. This article discusses the feature of radioiodine-131 and the use of potassium iodide in nuclear accident.The potassium iodide has a good role in protecting thyroid.It should pay attention on taking time and dosage based on instruction issued by public health authority.%日本3·11福岛核事故释放出大量 131I,引起公众关注.本文讨论 131I的生物学特点和碘化钾在核事故中的应用.碘化钾有很好的保护甲状腺的作用,但要根据卫生当局的指令,注意服用的时机和剂量.

  20. Nanoscale invaginations of the nuclear envelope: Shedding new light on wormholes with elusive function.

    Science.gov (United States)

    Schoen, Ingmar; Aires, Lina; Ries, Jonas; Vogel, Viola

    2017-07-07

    Recent advances in fluorescence microscopy have opened up new possibilities to investigate chromosomal and nuclear 3D organization on the nanoscale. We here discuss their potential for elucidating topographical details of the nuclear lamina. Single molecule localization microscopy (SMLM) in combination with immunostainings of lamina proteins readily reveals tube-like invaginations with a diameter of 100-500 nm. Although these invaginations have been established as a frequent and general feature of interphase nuclei across different cell types, their formation mechanism and function have remained largely elusive. We critically review the current state of research, propose possible connections to lamina associated domains (LADs), and revisit the discussion about the potential role of these invaginations for accelerating mRNA nuclear export. Illustrative studies using 3D super-resolution imaging are shown and will be instrumental to decipher the physiological role of these nanoscale invaginations.

  1. Price and Income Elasticities of Russian Exports

    Directory of Open Access Journals (Sweden)

    Bernardina Algieri

    2004-12-01

    Full Text Available The paper gauges export demand elasticities for Russia using an Error Correction technique within a cointegration framework. An extended version of the Imperfect Substitutes Model has been implemented to estimate the sensitivity of Russian exports without oil components to price and to Russian and world income. Our results suggest a robust and negative long run cointegration relationship between the real effective exchange rate, defined as the weighted average of the rouble’s exchange rates versus a basket of the three currencies with the largest share in the trade turnover adjusted to incorporate inflation rate differences (the ratio of the domestic price indices to the foreign price indices, and Russian exports. An increase in exports by 24% is caused by a real depreciation by 10%. Furthermore, a 10% growth in world income leads to a 33% rise in exports. Finally, exports drop by 14% whenever a 10% increase in domestic income occurs

  2. Baseline study of US industry solar exports

    Energy Technology Data Exchange (ETDEWEB)

    Jacobius, T M; Levi, R S; Bereny, J A

    1980-10-01

    This study is a detailed aggregate profile of US solar export activity in 1979 based on a survey of all segments of the solar industry. It identifies the dollar volume of exports by technology: (1) solar heating and cooling products; (2) wind products; (3) photovoltaics; (4) solar thermal electric; (5) OTEC and biomass; and (6) support products and services. The study offers to government and industry groups, for the first time, comprehensive information with which to formulate export goals and assistance measures based on the current realities of the solar export marketplace. Specific and aggregate recommendations which can lead to identification of realistic solar export opportunities and development of solar export markets are included.

  3. Tax Exportability in Tourism Market

    Directory of Open Access Journals (Sweden)

    Mohammad Mohebi

    2011-01-01

    Full Text Available Problem statement: Tax incidence is a basic topic in public economics as the tourism industry is an increasingly major contributor to government revenue. Generally, government taxation objectives are for the purpose of financing programs that improve people’s lives and economic prosperity, accelerate economic growth and allow for access to sustainable development. In the first view, tax policy decisions by government are based on their effects on the distribution of economic welfare. Therefore, to provide incentives for governments to select a suitable tax policy, exportability of tax is important. Hotel room tax is one of the main parts of tourism tax. Despite the importance of tax for government, it seems that the exportability of hotel room tax is still not well known. Therefore, understanding the counteraction of foreign visitors with respect to its main factors is important for the Malaysian government and tourism management. To achieve these aims, this study examines tax incidence effects on the tourism market. Approach: We use hotel room as representative of tourism market. Quarterly data from 1995-2009 are used and a dynamic model of simultaneous equation is employed. Results: Our results indicate that in the short run supply is elastic and demand is inelastic.But in the long run both demand and supply are elastic to price. Conclusion: Based the results if the government imposes one ringgit (Malaysian currency tax on hotel room price, the tourist contribution is more than 89 and 74% in the short run and long run respectively. Hence, we conclude that the Malaysian tourism market is exportable. Our results also indicate that tax on hotel has no negative social effects in the short run.

  4. Nonproliferation vs. Industrial Competitiveness: U.S. Export Controls and the Dual-Use Machine Tool Industry

    Science.gov (United States)

    1995-06-01

    Professor Kamil T. Said for his unparalleled insights concerning the situation in Iraq. xiii I. INTRODUCTION A central goal of our national security...French and German technologies. Financially, Iraq was helped by the Gulf Cooperation Council (GCC) members and by the Atlanta office of the Banca ...to common export control policies for nuclear and 52"Meeting On Rocket Technology, Dual-Purpose Knowledge Export," Central Eurasia, January 4, 1993

  5. Exporting by Migrants and Indigenous Entrepreneurs

    DEFF Research Database (Denmark)

    Ashourizadeh, Shayegheh; Schøtt, Thomas; Pişkinsüt Şengüler, Ece

    2016-01-01

    Migrants may become entrepreneurs in their host countries. They may utilize their dual embeddedness in both the home country and the host country, and also use transnational links to gain a competitive advantage in exporting compared to indigenous entrepreneurs. Migrant entrepreneurs’ advantage may...... around the world was surveyed in the Global Entrepreneurship Monitor, which reports on migration and exporting. Hierarchical linear modeling shows that migrant entrepreneurs export more than indigenous entrepreneurs, especially in the first generation, and especially among educated and male migrants...

  6. Human Capital and Wages in Exporting Firms

    DEFF Research Database (Denmark)

    Munch, Jakob Roland; Skaksen, Jan Rose

    2006-01-01

    This paper studies the link between a firms education level, export performance and wages of its workers. We argue that firms may escape intence competition in international markets by using high skilled workers to differentiate their products. This story is consistent with our empirical results....... an export wage premium, but it accrues to workers in firms with high skill intensities.Keywords: Exports, Wages, Human Capital, Rent Sharing, Matched Worker-Firm DataJEL Classification: J30, F10, I20...

  7. Should Australia Export its Native Birds?

    OpenAIRE

    Kingwell, Ross S.

    1994-01-01

    Commercial export from Australia of native birds, wild or captive bred, is prohibited. This paper firstly describes the current legislation and regulations that restrict the export of native birds and discusses why governments have adopted such a regulatory approach to bird species preservation. Secondly, the paper reviews the debate concerning the export ban, pointing out strengths and weaknesses in arguments and indicating the important role of CITES. Lastly, the paper outlines a new case f...

  8. Effective Border Tax Adjustments for Export Promotion

    OpenAIRE

    Glenn P. Jenkins; Chun-Yan Kuo

    2004-01-01

    In this paper, we address the administration issues associated with the most important border tax adjustments for export expansion. These relate to the refund of input tax credits under the VAT and the relief from customs duties on imported inputs used to produce exports. Such refunds in many developing countries are either not paid in a timely fashion or have been fraudulently overstated in the claims made by exporters. These become impediments that have frequently discouraged foreign invest...

  9. Integrated export development under conditions of globalization

    OpenAIRE

    Jatuliavičienė, Gražina

    2010-01-01

    In the dissertation from the holistic point of view are discussed export development peculiarities in the global area. The main aim of the dissertation is the expansion of the export development concept in consideration to the challenges of globalization. Therefore, peculiarities of internationalization and globalization processes and their connections in the context of export development are discussed; alternation of internationalization models under conditions of globalization is evaluated,...

  10. 75 FR 52505 - Fiscal Year 2011 Veterinary Import/Export Services, Veterinary Diagnostic Services, and Export...

    Science.gov (United States)

    2010-08-26

    ... Animal and Plant Health Inspection Service Fiscal Year 2011 Veterinary Import/Export Services, Veterinary... plasm, organisms, and vectors; for certain veterinary diagnostic services; and for export certification... information on Veterinary Diagnostic program operations, contact Dr. Elizabeth Lautner, Director,...

  11. International Marketing Strategies and the relationship with the export performance and export marketing orientation

    Directory of Open Access Journals (Sweden)

    Marlon Dalmoro

    2010-04-01

    Full Text Available This work aims to identify the relationship between marketing strategies of exporting Taquari Valley firms with the export performance and export market orientation. To achieve the goal sought proposed is the development of theoretical benchmark, made up items strategies for international marketing, export performance and export market orientation. In epistemological level was conducted a survey, applying for a questionnaire to a sample of 25 exporting companies that have industrial activities, chosen in a not probabilistic manner. Finally, it was observed that the key decisions on how to act in various markets in terms of strategies for international marketing - satisfaction with the internal market, international consistency, adaptation and localization level of the strategies - have relationship with the export market orientation and the export performance of studied companies.

  12. Prioritization and Ranking Problems Exporting Iranian Saffron

    Directory of Open Access Journals (Sweden)

    Reza Askandari

    2013-10-01

    Full Text Available The main objective of this study is to prioritize and rank problems exporting Iranian saffron. Based on a comprehensive review of the literature on issues related to data and information collected from questionnaires, with 816% reliability is used. In this study, the sample of managers and sales and marketing company is exporting Iranian saffron is the sample size of 231 subjects. The results of this study are positive and significant relationship between the dependent variable and the independent variables of export performance of export barriers exist.

  13. ROMANIAN EXPORT COMPETITIVENESS ON THE EUROPEAN MARKET

    Directory of Open Access Journals (Sweden)

    Paul Clipa

    2011-12-01

    Full Text Available Exports of a nation can form a large part of its commercial card on the international market. Global consumer, according to the quality of exports, may associate a certain image about the country of origin. This article aims at explaining the relationship between exports and competitiveness of a nation, the analysis focuses on the nature and intensity of intra-Community exports of Romania. To this end we considered a number of performance indicators that are able to reveal the positioning of trade from Romania to the EU.

  14. Human Capital and Wages in Exporting Firms

    DEFF Research Database (Denmark)

    Munch, Jakob Roland; Skaksen, Jan Rose

    This paper studies the link between a firms education level, export performance and wages of its workers. We argue that firms may escape intense competition in international markets by using high skilled workers to differentiate their products. This story is consistent with our empirical results....... Using a very rich matched worker-firm longitudinal dataset we find that firms with high export intensities pay higher wages. However, an interaction term between export intensity and skill intensity has a positive impact on wages and it absorbs the direct effect of the export intensity. That is, we find...

  15. Markups and Firm-Level Export Status

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic

    We derive an estimating equation to estimate markups using the insight of Hall (1986) and the control function approach of Olley and Pakes (1996). We rely on our method to explore the relationship between markups and export behavior using plant-level data. We find significantly higher markups when...... we control for unobserved productivity shocks. Furthermore, we find significant higher markups for exporting firms and present new evidence on markup-export status dynamics. More specifically, we find that firms' markups significantly increase (decrease) after entering (exiting) export markets. We...

  16. Essays on China’s Exports to East Africa

    DEFF Research Database (Denmark)

    Yu, Qian

    China’s emergence as the world’s major trading nation has been well documented and discussed in the economics literature. One such trend that has garnered intensive media exposure and political discussion but far less formal economic analysis is the sudden rise of China as Africa’s biggest trading...... partner. The aim of this thesis is to compile a set of empirical economic evidence on the general characteristics of China’s exports to Africa, on the consequences of increasing Chinese exports on African consumers, on explaining why China rose to such prominence on the African market, as well...... as on the economic opportunities and threats placed by China’s expanding role in Africa on the latter’s traditional trading partners. The first three papers contained in this thesis form a sequence to answer the questions proposed above, using Ethiopia as a case study. The first paper describes features of China...

  17. Application Method of Anthropometric Data for Operator Console of Exportable Research Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Goo Hyun; Lee, Jun Hun; Jeng, Ja Won; Lee, Youn Sang; Kim, Min Gyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    This paper studied the method to apply the anthropometric data to operator console and large display that used to control room of the exportable research reactor. It is difficult to provide an appropriate operation environment personally to all operators. Therefore, this paper studied method to provide comfortable operation space common to most operators. In the future, it will be possible to enhance the completeness through conformity assessment of the design based on this paper. Therefore, the results of this paper will be an important basic data to design suitable for body size of the user for exportable products such as large display and operator console. Nuclear-related domestic technology has been exported overseas, starting with the JRTR (Jordan Research and Training Reactor) which is currently on its development scheduled to operate in March 2015. It means that Korean nuclear technology has reached the global level already. Therefore, design standards of Human Factors Engineering (HFE) are needed for good products to make more comfortable and suitable for export products. In addition, U. S. Nuclear Regulatory Commission (NRC) reported that the Three Mile Island (TMI) accident in 1979 has been caused by inappropriate design of control panel, human errors, and incorrect procedures. Accordingly, the importance of HFE was raised. In this paper, we studied the application of anthropometric data for operator console and large display of exportable research reactor. Research for nuclear power has been active around the world with environment friendly image. Therefore, it is also very important to study the HFE as a big part in the field of nuclear safety.

  18. Export Readiness Assessment of Ten Iranian Pharmaceutical Companies and Comparison with their Export Performance

    OpenAIRE

    Mehdi Mohammadzadeh, Mohammad Poloee, Tayebeh Ghari

    2016-01-01

    Background: In the area of exporting, in developing countries, including Iran, the concept of export readiness is unknown to many decision makers and field of activity of Iranian pharmaceutical companies have been limited to the domestic market. Therefore, the main objective of this study is to compare the export performance of ten Iranian pharmaceutical companies with their export readiness. Methods: In order to do this, the top ten of Iranian pharmaceutical companies were selected as the sa...

  19. Foreign Direct Investment and Electronics Exports: Exploratory Empirical Evidence from Malaysia's Top Five Electronics Exports

    OpenAIRE

    Tuck Cheong Tang; Koi Nyen Wong

    2007-01-01

    The foreign direct investment (FDI) has contributed significantly to Malaysia's electronics exports as well as the growth and development of the electronics industry as a result of the export-oriented industrialization initiatives undertaken since 1970s. The aim of this study is to explore the causation between FDI and electronics exports by using Malaysia''s top five electronics exports by SITC (Standard International Trade Classification) product groups. The findings show a bi-directional c...

  20. A short conserved motif in ALYREF directs cap- and EJC-dependent assembly of export complexes on spliced mRNAs.

    Science.gov (United States)

    Gromadzka, Agnieszka M; Steckelberg, Anna-Lena; Singh, Kusum K; Hofmann, Kay; Gehring, Niels H

    2016-03-18

    The export of messenger RNAs (mRNAs) is the final of several nuclear posttranscriptional steps of gene expression. The formation of export-competent mRNPs involves the recruitment of export factors that are assumed to facilitate transport of the mature mRNAs. Using in vitro splicing assays, we show that a core set of export factors, including ALYREF, UAP56 and DDX39, readily associate with the spliced RNAs in an EJC (exon junction complex)- and cap-dependent manner. In order to elucidate how ALYREF and other export adaptors mediate mRNA export, we conducted a computational analysis and discovered four short, conserved, linear motifs present in RNA-binding proteins. We show that mutation in one of the new motifs (WxHD) in an unstructured region of ALYREF reduced RNA binding and abolished the interaction with eIF4A3 and CBP80. Additionally, the mutation impaired proper localization to nuclear speckles and export of a spliced reporter mRNA. Our results reveal important details of the orchestrated recruitment of export factors during the formation of export competent mRNPs.

  1. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function.

    Science.gov (United States)

    Yedavalli, Venkat S R K; Neuveut, Christine; Chi, Ya-Hui; Kleiman, Lawrence; Jeang, Kuan-Teh

    2004-10-29

    A single transcript in its unspliced and spliced forms directs the synthesis of all HIV-1 proteins. Although nuclear export of intron-containing cellular transcripts is restricted in mammalian cells, HIV-1 has evolved the viral Rev protein to overcome this restriction for viral transcripts. Previously, CRM1 was identified as a cellular cofactor for Rev-dependent export of intron-containing HIV-1 RNA. Here, we present evidence that Rev/CRM1 activity utilizes the ATP-dependent DEAD box RNA helicase, DDX3. We show that DDX3 is a nucleo-cytoplasmic shuttling protein, which binds CRM1 and localizes to nuclear membrane pores. Knockdown of DDX3 using either antisense vector or dominant-negative mutants suppressed Rev-RRE-function in the export of incompletely spliced HIV-1 RNAs. Plausibly, DDX3 is the human RNA helicase which functions in the CRM1 RNA export pathway analogously to the postulated role for Dbp5p in yeast mRNA export.

  2. 75 FR 44761 - Export Trade Certificate of Review

    Science.gov (United States)

    2010-07-29

    ... opportunities for sales of canned salmon in the Export Markets, selling strategies for the Export Markets, sales... International Trade Administration Export Trade Certificate of Review ACTION: Notice of Application for an Export Trade Certificate of Review From Canned Wild Salmon Export Council, LLC (``CWSEC''). SUMMARY:...

  3. 77 FR 58809 - Export Trade Certificate of Review

    Science.gov (United States)

    2012-09-24

    ... Operation described below in the following Export Trade and Export Markets. Export Trade COL-RICE plans to... Export Trade Activities and Methods of Operation: 1. Purpose: COL-RICE will manage on an open tender..., incluso pulido o glaseado); 1006.4000--broken rice (arroz partido). Export Market The Republic of...

  4. 10 CFR 590.208 - Small volume exports.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Small volume exports. 590.208 Section 590.208 Energy... WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Applications for Authorization To Import or Export Natural Gas § 590.208 Small volume exports. Any person may export up to 100,000 cubic feet of natural...

  5. 7 CFR 1488.9 - Evidence of export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export. 1488.9 Section 1488.9 Agriculture... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Documents Required for Financing § 1488.9 Evidence of export. (a) If the commodity is exported by rail...

  6. 21 CFR 1312.22 - Application for export permit.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Application for export permit. 1312.22 Section... EXPORTATION OF CONTROLLED SUBSTANCES Exportation of Controlled Substances § 1312.22 Application for export permit. (a) An application for a permit to export controlled substances shall be made on DEA Form 161...

  7. 77 FR 28853 - Export Trade Certificate of Review

    Science.gov (United States)

    2012-05-16

    ... International Trade Administration Export Trade Certificate of Review ACTION: Notice of issuance of an Export....S. Department of Commerce issued an amended Export Trade Certificate of Review Alaska Longline Cod... number) or email at etca@trade.gov . SUPPLEMENTARY INFORMATION: Title III of the Export Trading Company...

  8. 21 CFR 1312.23 - Issuance of export permit.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Issuance of export permit. 1312.23 Section 1312.23... CONTROLLED SUBSTANCES Exportation of Controlled Substances § 1312.23 Issuance of export permit. (a) The... regulation in § 1312.30 of this part be exported only pursuant to the issuance of an export permit. The...

  9. 78 FR 1837 - Export Trade Certificate of Review

    Science.gov (United States)

    2013-01-09

    ... International Trade Administration Export Trade Certificate of Review ACTION: Notice of issuance of an Export.... Department of Commerce issued an amended Export Trade Certificate of Review to Northwest Fruit Exporters on... Export Trading Company Act of 1982 (15 U.S.C. 4001-21) authorizes the Secretary of Commerce to issue...

  10. 78 FR 53727 - Export Trade Certificate of Review

    Science.gov (United States)

    2013-08-30

    ... International Trade Administration Export Trade Certificate of Review ACTION: Notice of Issuance of an Export Trade Certificate of Review to Northwest Fruit Exporters, Application No. 84-24A12. SUMMARY: The U.S. Department of Commerce issued an amended Export Trade Certificate of Review to Northwest Fruit Exporters...

  11. 22 CFR 125.1 - Exports subject to this part.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Exports subject to this part. 125.1 Section 125... EXPORT OF TECHNICAL DATA AND CLASSIFIED DEFENSE ARTICLES § 125.1 Exports subject to this part. (a) The controls of this part apply to the export of technical data and the export of classified defense...

  12. 78 FR 18814 - Amendment to the Export Administration Regulations: List of Items Classified Under Export Control...

    Science.gov (United States)

    2013-03-28

    ... Bureau of Industry and Security 15 CFR Part 774 RIN 0694-AF73 Amendment to the Export Administration Regulations: List of Items Classified Under Export Control Classification 0Y521 Series--Biosensor Systems... specified biosensor systems, ``software'' and ``technology'' under Export Control Classification...

  13. Package power stations for export

    Energy Technology Data Exchange (ETDEWEB)

    1985-01-01

    The cheap and efficient generation of power is an essential requirement for the success and prosperity of any community and is especially important to third world countries. It is therefore logical that the more technologically advanced nations should seek to produce power stations for the developing countries. Power plant can now be designed into a packaged form that may be readily exported and commissioned. This valuable and interesting collection of papers were originally presented at a seminar organised by the Power Industries Division of the Institution of Mechanical Engineers. Topics considered include the developing world market for packaged power stations using indigenous fuels; multi-fuel systems for power generation; packaging, modularisation, and containerisation of equipment for power boilers for export; compact coal-fired industrial plant; rural woodburning power stations; biomass gasification based power generation technology and potential; gas fed reciprocating engine development; packaged heavy duty gas turbines for power generation; and criteria for assessing the appropriateness of package power technologies in developing countries.

  14. Cytoscape tools for the web age: D3.js and Cytoscape.js exporters

    Science.gov (United States)

    Ono, Keiichiro; Demchak, Barry; Ideker, Trey

    2014-01-01

    In this paper we present new data export modules for Cytoscape 3 that can generate network files for Cytoscape.js and D3.js. Cytoscape.js exporter is implemented as a core feature of Cytoscape 3, and D3.js exporter is available as a Cytoscape 3 app. These modules enable users to seamlessly export network and table data sets generated in Cytoscape to popular JavaScript library readable formats. In addition, we implemented template web applications for browser-based interactive network visualization that can be used as basis for complex data visualization applications for bioinformatics research. Example web applications created with these tools demonstrate how Cytoscape works in modern data visualization workflows built with traditional desktop tools and emerging web-based technologies. This interactivity enables researchers more flexibility than with static images, thereby greatly improving the quality of insights researchers can gain from them. PMID:25520778

  15. Cytoscape tools for the web age: D3.js and Cytoscape.js exporters.

    Science.gov (United States)

    Ono, Keiichiro; Demchak, Barry; Ideker, Trey

    2014-01-01

    In this paper we present new data export modules for Cytoscape 3 that can generate network files for Cytoscape.js and D3.js. Cytoscape.js exporter is implemented as a core feature of Cytoscape 3, and D3.js exporter is available as a Cytoscape 3 app. These modules enable users to seamlessly export network and table data sets generated in Cytoscape to popular JavaScript library readable formats. In addition, we implemented template web applications for browser-based interactive network visualization that can be used as basis for complex data visualization applications for bioinformatics research. Example web applications created with these tools demonstrate how Cytoscape works in modern data visualization workflows built with traditional desktop tools and emerging web-based technologies. This interactivity enables researchers more flexibility than with static images, thereby greatly improving the quality of insights researchers can gain from them.

  16. Architecture of the major component of the type III secretion system export apparatus.

    Science.gov (United States)

    Abrusci, Patrizia; Vergara-Irigaray, Marta; Johnson, Steven; Beeby, Morgan D; Hendrixson, David R; Roversi, Pietro; Friede, Miriam E; Deane, Janet E; Jensen, Grant J; Tang, Christoph M; Lea, Susan M

    2013-01-01

    Type III secretion systems (T3SSs) are bacterial membrane-embedded nanomachines designed to export specifically targeted proteins from the bacterial cytoplasm. Secretion through T3SS is governed by a subset of inner membrane proteins termed the 'export apparatus'. We show that a key member of the Shigella flexneri export apparatus, MxiA, assembles into a ring essential for secretion in vivo. The ring-forming interfaces are well-conserved in both nonflagellar and flagellar homologs, implying that the ring is an evolutionarily conserved feature in these systems. Electron cryo-tomography revealed a T3SS-associated cytoplasmic torus of size and shape corresponding to those of the MxiA ring aligned to the secretion channel located between the secretion pore and the ATPase complex. This defines the molecular architecture of the dominant component of the export apparatus and allows us to propose a model for the molecular mechanisms controlling secretion.

  17. 19 CFR 351.402 - Calculation of export price and constructed export price; reimbursement of antidumping and...

    Science.gov (United States)

    2010-04-01

    ... Export Price, Constructed Export Price, Fair Value, and Normal Value § 351.402 Calculation of export... (date of final determination of sales at less than fair value). (3) Presumption. The Secretary may...) Introduction. In order to establish export price, constructed export price, and normal value, the Secretary...

  18. Do Firms Learn by Exporting or Learn to Export? Evidence from Small and Medium-Sized Enterprises (SMEs) in Swedish Manufacturing

    OpenAIRE

    Hansson, Pär; Eliasson, Kent; Lindvert, Markus

    2009-01-01

    Using a matching approach, we compare the productivity trajectories of future exporters and matched and unmatched non-exporters. Future exporters have higher productivity than do unmatched non-exporters before entry into the export market, which indicates self-selection into exports. More interestingly, we also find a productivity increase among future exporters relative to matched non-exporters 1-2 years before export entry. However, the productivity gap between future exporters and matched ...

  19. Entrepreneurship, export orientation, and economic growth

    NARCIS (Netherlands)

    S.J.A. Hessels (Jolanda); A.J. van Stel (André)

    2009-01-01

    textabstractIn this paper the relationship between a country’s prevalence of new ventures and its rate of economic growth is investigated, while taking into account new ventures’ export orientation. It is generally acknowledged that new venture creation as well as export activity may both be importa

  20. 77 FR 73627 - 2012 LNG Export Study

    Science.gov (United States)

    2012-12-11

    ...] [FR Doc No: 2012-29894] DEPARTMENT OF ENERGY 2012 LNG Export Study AGENCY: Office of Fossil Energy, Department of Energy. ACTION: Notice of availability of 2012 LNG Export Study and request for comments. Freeport LNG Expansion, L.P. [FE Docket No. 10-161-LNG] and FLNG Liquefaction, LLC. Lake Charles...

  1. Potentials in Asian Export Credit Cooperation

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    "Mekong River Regional Development Project advocated by Asian Development Bank (ADB) has been implemented. Trans-Asia Railway and Trans-Asia Highway are being discussed. It is a good opportunity for Asian Export Credit Agencies (ECAs) to cooperate and financing these large crossboarder projects."On May 11, at the 10th Annual Meeting of Asian Export Credit Agencies,

  2. 27 CFR 24.292 - Exported wine.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exported wine. 24.292... OF THE TREASURY LIQUORS WINE Removal, Return and Receipt of Wine Removals Without Payment of Tax § 24.292 Exported wine. (a) General. Wine may be removed from a bonded wine premises without payment of tax...

  3. Export Specialisation and Local Economic Growth

    NARCIS (Netherlands)

    Naude, Wim; Bosker, Maarten; Matthee, Marianne

    2010-01-01

    This paper aims to provide empirical evidence on whether export specialization or diversification is better for local economic growth. Using export data from 354 magisterial districts of South Africa for 1996 and 2001 we estimate spatial growth regressions that include measures of the degree of expo

  4. The Export Quotas for Next Year

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    <正>China’s Ministry of Commerce recently announced the 2006 export quotas for some metals commodities. According to the document, China’s export quotas for tungsten and its products will be 15,800 tons. For antimony and its products, the quotas will be

  5. 9 CFR 352.16 - Exports.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Exports. 352.16 Section 352.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION EXOTIC ANIMALS AND HORSES; VOLUNTARY INSPECTION Exotic Animals § 352.16 Exports. This shall...

  6. Risk in A Concentrated Export Market

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The export destination of China’s home textile products are considered to be highly concentrated. This is reflected by the statistical data of the past couple of years when, the top export destination of the following products-bedding products, curtain and towel- is United States.

  7. 7 CFR 945.14 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 945.14 Section 945.14 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Definitions § 945.14 Export....

  8. The Decline in China Textile Exports Narrowed

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This is a crucial moment for China’s textile export industry, which is in the midst of deep economic downturn. In the January-Novem- ber 2009 period, the decline in accumulated textile and apparel exports was being constantly reduced and the tendency of rebound is

  9. 40 CFR 273.56 - Exports.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Exports. 273.56 Section 273.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR UNIVERSAL WASTE MANAGEMENT Standards for Universal Waste Transporters § 273.56 Exports. A universal...

  10. China Not the Only Rare Earth Exporter

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Since China announced it was reducing exports of rare earth,there have been continuous voices in the international community demanding China expand exports or seek alternative resources.The United States has also complained to the WTO that China is hoarding the commodity.

  11. 7 CFR 958.14 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 958.14 Section 958.14 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Definitions § 958.14 Export....

  12. Home Textile Exports Show Recovery Signs

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In this article we have analysed the export performance of Chinese main home textile products, including bedding products, carpet, curtain and towel based on official export data during the first eight months of 2010.Let’s first look at the background. The growth in China’s manufacturing

  13. The Silver Export Quota for 2005

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    <正>China’s Ministry of Commerce recently announced the first lot of silver export quota for 2005. According to report, the first lot of silver export quota amounts to 2,443 tons which is 252 tons more on 2004 basis. There are 37 en-

  14. Exports and firm profitability: Quality matters!

    OpenAIRE

    2014-01-01

    This paper uses a tailor-made newly available data set to investigate for the first time the links between profitability and the quality of exports in enterprises from manufacturing industries in Germany, one of the leading actors on the world market for goods. The paper demonstrates that exporters of high-quality goods tend to be more profitable.

  15. 27 CFR 28.123 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.123..., or Transportation to a Manufacturing Bonded Warehouse § 28.123 Export marks. (a) General. In addition... filled under the provisions of part 24 of this chapter, the proprietor shall mark the word “Export” on...

  16. 27 CFR 28.216 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.216... Export marks. In addition to the marks and brands required to be placed on packages or other bulk... “Export” on the Government side of each case or Government head of each container before removal for...

  17. 27 CFR 28.103 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.103... Manufacturing Bonded Warehouse § 28.103 Export marks. (a) General. In addition to the marks and brands required... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

  18. 27 CFR 28.144 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.144... § 28.144 Export marks. (a) General Requirement. In addition to the marks and brands required to be... brewer shall mark the word “Export” on each container or case of beer, or the words “Beer concentrate for...

  19. Export potential of Brazilian industrial firms

    Directory of Open Access Journals (Sweden)

    Bruno César Pino Oliveira de Araújo

    2010-12-01

    Full Text Available Most of the recent astonishing export growth in Brazil came from firms which already exported. The export base was not able to grow at the same pace. Since expanding the export base may have several positive effects on firms' productivity and size, in this paper we provide a four-level classification of Brazilian industrial firms according to their potential to export, and we identify a subset of non-exporting firms which are potential exporters. The effects of export stimulating policies may be improved by focusing more closely on these firms.O recente crescimento das exportações no Brasil se baseou fortemente naquelas firmas já exportadoras, e a base exportadora não conseguiu acompanhar o mesmo ritmo de crescimento. Considerando que expandir a base exportadora pode ter efeitos positivos sobre a produtividade e tamanho das firmas, neste artigo classificamos as firmas industriais brasileiras em quatro níveis de acordo com o potencial exportador, e especialmente identificamos um subconjunto de firmas que não exportam mas que são potenciais exportadoras. Os efeitos das políticas de promoção às exportações podem ser maximizados se elas forem focalizadas nestas firmas.

  20. Textile Exports to Japan Witnessing a Downturn

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China textile and apparel exports to Japan was witnessing a downturn in all statistics of China Customs and Japan METI in the Jan.-Apr. 2010 period. Exports to Japan this year later will face more pressure as gains in Japan’s consumption could moderate due to a lackluster jobs market and debt crisis.