WorldWideScience

Sample records for er export signals

  1. An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors.

    Science.gov (United States)

    Pan, Yuan; Laird, Joseph G; Yamaguchi, David M; Baker, Sheila A

    2015-06-01

    Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are widely expressed in the retina. In photoreceptors, the hyperpolarization-activated current (Ih) carried by HCN1 is important for shaping the light response. It has been shown in multiple systems that trafficking HCN1 channels to specific compartments is key to their function. The localization of HCN1 in photoreceptors is concentrated in the plasma membrane of the inner segment (IS). The mechanisms controlling this localization are not understood. We previously identified a di-arginine endoplasmic reticulum (ER) retention motif that negatively regulates the surface targeting of HCN1. In this study, we sought to identify a forward trafficking signal that could counter the function of the ER retention signal. We studied trafficking of HCN1 and several mutants by imaging their subcellular localization in transgenic X. laevis photoreceptors. Velocity sedimentation was used to assay the assembly state of HCN1 channels. We found the HCN1 N-terminus can redirect a membrane reporter from outer segments (OS) to the plasma membrane of the IS. The sequence necessary for this behavior was mapped to a 20 amino acid region containing a leucine-based ER export motif. The ER export signal is necessary for forward trafficking but not channel oligomerization. Moreover, this ER export signal alone counteracted the di-arginine ER retention signal. We identified an ER export signal in HCN1 that functions with the ER retention signal to maintain equilibrium of HCN1 between the endomembrane system and the plasma membrane.

  2. Membrane trafficking: ER export encounters dualism.

    Science.gov (United States)

    Barlowe, Charles

    2015-02-16

    Cytoplasmic coat protein complexes perform central roles in sorting protein constituents within the endomembrane system. A new study reveals that the COPII coat operates through dual recognition of signals in a sorting receptor and its bound cargo to promote efficient export from the endoplasmic reticulum. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Effect of the unfolded protein response on ER protein export: a potential new mechanism to relieve ER stress.

    Science.gov (United States)

    Shaheen, Alaa

    2018-05-05

    The unfolded protein response (UPR) is an adaptive cellular response that aims to relieve endoplasmic reticulum (ER) stress via several mechanisms, including inhibition of protein synthesis and enhancement of protein folding and degradation. There is a controversy over the effect of the UPR on ER protein export. While some investigators suggested that ER export is inhibited during ER stress, others suggested the opposite. In this article, their conflicting studies are analyzed and compared in attempt to solve this controversy. The UPR appears indeed to enhance ER export, possibly via multiple mechanisms. However, another factor, which is the integrity of the folding machinery/environment inside ER, determines whether ER export will appear increased or decreased during experimentation. Also, different methods of stress induction appear to have different effects on ER export. Thus, improvement of ER export may represent a new mechanism by which the UPR alleviates ER stress. This may help researchers to understand how the UPR works inside cells and how to manipulate it to alter cell fate during stress, either to promote cell survival or death. This may open up new approaches for the treatment of ER stress-related diseases.

  4. COPII-Dependent ER Export: A Critical Component of Insulin Biogenesis and β-Cell ER Homeostasis.

    Science.gov (United States)

    Fang, Jingye; Liu, Ming; Zhang, Xuebao; Sakamoto, Takeshi; Taatjes, Douglas J; Jena, Bhanu P; Sun, Fei; Woods, James; Bryson, Tim; Kowluru, Anjaneyulu; Zhang, Kezhong; Chen, Xuequn

    2015-08-01

    Pancreatic β-cells possess a highly active protein synthetic and export machinery in the endoplasmic reticulum (ER) to accommodate the massive production of proinsulin. ER homeostasis is vital for β-cell functions and is maintained by the delicate balance between protein synthesis, folding, export, and degradation. Disruption of ER homeostasis by diabetes-causing factors leads to β-cell death. Among the 4 components to maintain ER homeostasis in β-cells, the role of ER export in insulin biogenesis is the least understood. To address this knowledge gap, the present study investigated the molecular mechanism of proinsulin ER export in MIN6 cells and primary islets. Two inhibitory mutants of the secretion-associated RAS-related protein (Sar)1 small GTPase, known to specifically block coat protein complex II (COPII)-dependent ER export, were overexpressed in β-cells using recombinant adenoviruses. Results from this approach, as well as small interfering RNA-mediated Sar1 knockdown, demonstrated that defective Sar1 function blocked proinsulin ER export and abolished its conversion to mature insulin in MIN6 cells, isolated mouse, and human islets. It is further revealed, using an in vitro vesicle formation assay, that proinsulin was packaged into COPII vesicles in a GTP- and Sar1-dependent manner. Blockage of COPII-dependent ER exit by Sar1 mutants strongly induced ER morphology change, ER stress response, and β-cell apoptosis. These responses were mediated by the PKR (double-stranded RNA-dependent kinase)-like ER kinase (PERK)/eukaryotic translation initiation factor 2α (p-eIF2α) and inositol-requiring protein 1 (IRE1)/x-box binding protein 1 (Xbp1) pathways but not via activating transcription factor 6 (ATF6). Collectively, results from the study demonstrate that COPII-dependent ER export plays a vital role in insulin biogenesis, ER homeostasis, and β-cell survival.

  5. 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...

  6. ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology.

    Science.gov (United States)

    Manford, Andrew G; Stefan, Christopher J; Yuan, Helen L; Macgurn, Jason A; Emr, Scott D

    2012-12-11

    Endoplasmic reticulum-plasma membrane (ER-PM) junctions are conserved structures defined as regions of the ER that tightly associate with the plasma membrane. However, little is known about the mechanisms that tether these organelles together and why such connections are maintained. Using a quantitative proteomic approach, we identified three families of ER-PM tethering proteins in yeast: Ist2 (related to mammalian TMEM16 ion channels), the tricalbins (Tcb1/2/3, orthologs of the extended synaptotagmins), and Scs2 and Scs22 (vesicle-associated membrane protein-associated proteins). Loss of all six tethering proteins results in the separation of the ER from the PM and the accumulation of cytoplasmic ER. Importantly, we find that phosphoinositide signaling is misregulated at the PM, and the unfolded protein response is constitutively activated in the ER in cells lacking ER-PM tether proteins. These results reveal critical roles for ER-PM contacts in cell signaling, organelle morphology, and ER function. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. 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. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide

  8. Exports and olympic games: Is there a signal effect?

    OpenAIRE

    Maennig, Wolfgang; Richter, Felix

    2012-01-01

    Rose & Spiegel (2011) find that Olympic Games host countries experience significant positive, lasting effects on exports. They interpret their results as an indication that countries use the hosting of such events to signal openness and competitiveness. We challenge these empirical findings on the grounds that a comparison of structurally different and non-matching groups of countries might suffer from a selection bias. We demonstrate that with an appropriate matching and treatment methodolog...

  9. Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival.

    Directory of Open Access Journals (Sweden)

    Tomohisa Mori

    Full Text Available The membrane of the endoplasmic reticulum (ER of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R in that the Sig-1R chaperones the ER stress sensor IRE1 to facilitate inter-organelle signaling for survival. IRE1 is found in this study to be enriched at the MAM in CHO cells. We found that IRE1 is stabilized at the MAM by Sig-1Rs when cells are under ER stress. Sig-1Rs stabilize IRE1 and thus allow for conformationally correct IRE1 to dimerize into the long-lasting, activated endonuclease. The IRE1 at the MAM also responds to reactive oxygen species derived from mitochondria. Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus.

  10. Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival.

    Science.gov (United States)

    Mori, Tomohisa; Hayashi, Teruo; Hayashi, Eri; Su, Tsung-Ping

    2013-01-01

    The membrane of the endoplasmic reticulum (ER) of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R) in that the Sig-1R chaperones the ER stress sensor IRE1 to facilitate inter-organelle signaling for survival. IRE1 is found in this study to be enriched at the MAM in CHO cells. We found that IRE1 is stabilized at the MAM by Sig-1Rs when cells are under ER stress. Sig-1Rs stabilize IRE1 and thus allow for conformationally correct IRE1 to dimerize into the long-lasting, activated endonuclease. The IRE1 at the MAM also responds to reactive oxygen species derived from mitochondria. Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus.

  11. ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB

    International Nuclear Information System (INIS)

    Mera, Kentaro; Kawahara, Ko-ichi; Tada, Ko-ichi; Kawai, Kazuhiro; Hashiguchi, Teruto; Maruyama, Ikuro; Kanekura, Takuro

    2010-01-01

    Proteins are folded properly in the endoplasmic reticulum (ER). Various stress such as hypoxia, ischemia and starvation interfere with the ER function, causing ER stress, which is defined by the accumulation of unfolded protein (UP) in the ER. ER stress is prevented by the UP response (UPR) and ER-associated degradation (ERAD). These signaling pathways are activated by three major ER molecules, ATF6, IRE-1 and PERK. Using HaCaT cells, we investigated ER signaling in human keratinocytes irradiated by environmental doses of ultraviolet B (UVB). The expression of Ero1-Lα, an upstream signaling molecule of ER stress, decreased at 1-4 h after 10 mJ/cm 2 irradiation, indicating that the environmental dose of UVB-induced ER stress in HaCaT cells, without growth retardation. Furthermore, expression of intact ATF6 was decreased and it was translocated to the nuclei. The expression of XBP-1, a downstream molecule of IRE-1, which is an ER chaperone whose expression is regulated by XBP-1, and UP ubiquitination were induced by 10 mJ/cm 2 UVB at 4 h. PERK, which regulates apoptosis, was not phosphorylated. Our results demonstrate that UVB irradiation generates UP in HaCaT cells and that the UPR and ERAD systems are activated to protect cells from UVB-induced ER stress. This is the first report to show ER signaling in UVB-irradiated keratinocytes.

  12. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

    Science.gov (United States)

    Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

    2010-03-01

    Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.

  13. Temperature signal in suspended sediment export from an Alpine catchment

    Science.gov (United States)

    Costa, Anna; Molnar, Peter; Stutenbecker, Laura; Bakker, Maarten; Silva, Tiago A.; Schlunegger, Fritz; Lane, Stuart N.; Loizeau, Jean-Luc; Girardclos, Stéphanie

    2018-01-01

    Suspended sediment export from large Alpine catchments ( > 1000 km2) over decadal timescales is sensitive to a number of factors, including long-term variations in climate, the activation-deactivation of different sediment sources (proglacial areas, hillslopes, etc.), transport through the fluvial system, and potential anthropogenic impacts on the sediment flux (e.g. through impoundments and flow regulation). Here, we report on a marked increase in suspended sediment concentrations observed near the outlet of the upper Rhône River Basin in the mid-1980s. This increase coincides with a statistically significant step-like increase in basin-wide mean air temperature. We explore the possible explanations of the suspended sediment rise in terms of changes in water discharge (transport capacity), and the activation of different potential sources of fine sediment (sediment supply) in the catchment by hydroclimatic forcing. Time series of precipitation and temperature-driven snowmelt, snow cover, and ice melt simulated with a spatially distributed degree-day model, together with erosive rainfall on snow-free surfaces, are tested to explore possible reasons for the rise in suspended sediment concentration. We show that the abrupt change in air temperature reduced snow cover and the contribution of snowmelt, and enhanced ice melt. The results of statistical tests show that the onset of increased ice melt was likely to play a dominant role in the suspended sediment concentration rise in the mid-1980s. Temperature-driven enhanced melting of glaciers, which cover about 10 % of the catchment surface, can increase suspended sediment yields through an increased contribution of sediment-rich glacial meltwater, increased sediment availability due to glacier recession, and increased runoff from sediment-rich proglacial areas. The reduced extent and duration of snow cover in the catchment are also potential contributors to the rise in suspended sediment concentration through

  14. Identification of a nuclear export signal in the KSHV latent protein LANA2 mediating its export from the nucleus

    International Nuclear Information System (INIS)

    Munoz-Fontela, C.; Collado, M.; Rodriguez, E.; Garcia, M.A.; Alvarez-Barrientos, A.; Arroyo, J.; Nombela, C.; Rivas, C.

    2005-01-01

    LANA2 is a latent protein detected in Kaposi's sarcoma-associated herpesvirus (KSHV)-infected B cells that inhibits p53-dependent transcriptional transactivation and apoptosis and PKR-dependent apoptosis, suggesting an important role in the transforming activity of the virus. It has been reported that LANA2 localizes into the nucleus of both KSHV-infected B cells and transiently transfected HeLa cells. In this study, we show that LANA2 is a nucleocytoplasmic shuttling protein that requires a Rev-type nuclear export signal located in the C-terminus to direct the protein to the cytoplasm, through an association with the export receptor CRM1. In addition, a functional protein kinase B (PKB)/Akt phosphorylation motif partially overlapping with the nuclear export signal was identified. Nuclear exclusion of LANA2 was negatively regulated by the phosphorylation of threonine 564 by Akt. The ability of LANA2 to shuttle between nucleus and cytoplasm has implications for the function of this viral protein

  15. Temperature signal in suspended sediment export from an Alpine catchment

    Directory of Open Access Journals (Sweden)

    A. Costa

    2018-01-01

    Full Text Available Suspended sediment export from large Alpine catchments ( >  1000 km2 over decadal timescales is sensitive to a number of factors, including long-term variations in climate, the activation–deactivation of different sediment sources (proglacial areas, hillslopes, etc., transport through the fluvial system, and potential anthropogenic impacts on the sediment flux (e.g. through impoundments and flow regulation. Here, we report on a marked increase in suspended sediment concentrations observed near the outlet of the upper Rhône River Basin in the mid-1980s. This increase coincides with a statistically significant step-like increase in basin-wide mean air temperature. We explore the possible explanations of the suspended sediment rise in terms of changes in water discharge (transport capacity, and the activation of different potential sources of fine sediment (sediment supply in the catchment by hydroclimatic forcing. Time series of precipitation and temperature-driven snowmelt, snow cover, and ice melt simulated with a spatially distributed degree-day model, together with erosive rainfall on snow-free surfaces, are tested to explore possible reasons for the rise in suspended sediment concentration. We show that the abrupt change in air temperature reduced snow cover and the contribution of snowmelt, and enhanced ice melt. The results of statistical tests show that the onset of increased ice melt was likely to play a dominant role in the suspended sediment concentration rise in the mid-1980s. Temperature-driven enhanced melting of glaciers, which cover about 10 % of the catchment surface, can increase suspended sediment yields through an increased contribution of sediment-rich glacial meltwater, increased sediment availability due to glacier recession, and increased runoff from sediment-rich proglacial areas. The reduced extent and duration of snow cover in the catchment are also potential contributors to the rise in suspended sediment

  16. Morbillivirus nucleoprotein possesses a novel nuclear localization signal and a CRM1-independent nuclear export signal

    International Nuclear Information System (INIS)

    Sato, Hiroki; Masuda, Munemitsu; Miura, Ryuichi; Yoneda, Misako; Kai, Chieko

    2006-01-01

    Morbilliviruses, which belong to the Mononegavirales, replicate its RNA genome in the cytoplasm of the host cell. However, they also form characteristic intranuclear inclusion bodies, consisting of nucleoprotein (N), in infected cells. To analyze the mechanisms of nucleocytoplasmic transport of N protein, we characterized the nuclear localization (NLS) and nuclear export (NES) signals of canine distemper virus (CDV) N protein by deletion mutation and alanine substitution of the protein. The NLS has a novel leucine/isoleucine-rich motif (TGILISIL) at positions 70-77, whereas the NES is composed of a leucine-rich motif (LLRSLTLF) at positions 4-11. The NLS and NES of the N proteins of other morbilliviruses, that is, measles virus (MV) and rinderpest virus (RPV), were also analyzed. The NLS of CDV-N protein is conserved at the same position in MV-N protein, whereas the NES of MV-N protein is located in the C-terminal region. The NES of RPV-N protein is also located at the same position as CDV-N protein, whereas the NLS motif is present not only at the same locus as CDV-N protein but also at other sites. Interestingly, the nuclear export of all these N proteins appears to proceed via a CRM1-independent pathway

  17. NLSdb-major update for database of nuclear localization signals and nuclear export signals.

    Science.gov (United States)

    Bernhofer, Michael; Goldberg, Tatyana; Wolf, Silvana; Ahmed, Mohamed; Zaugg, Julian; Boden, Mikael; Rost, Burkhard

    2018-01-04

    NLSdb is a database collecting nuclear export signals (NES) and nuclear localization signals (NLS) along with experimentally annotated nuclear and non-nuclear proteins. NES and NLS are short sequence motifs related to protein transport out of and into the nucleus. The updated NLSdb now contains 2253 NLS and introduces 398 NES. The potential sets of novel NES and NLS have been generated by a simple 'in silico mutagenesis' protocol. We started with motifs annotated by experiments. In step 1, we increased specificity such that no known non-nuclear protein matched the refined motif. In step 2, we increased the sensitivity trying to match several different families with a motif. We then iterated over steps 1 and 2. The final set of 2253 NLS motifs matched 35% of 8421 experimentally verified nuclear proteins (up from 21% for the previous version) and none of 18 278 non-nuclear proteins. We updated the web interface providing multiple options to search protein sequences for NES and NLS motifs, and to evaluate your own signal sequences. NLSdb can be accessed via Rostlab services at: https://rostlab.org/services/nlsdb/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    International Nuclear Information System (INIS)

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum; Uhm, Sang-Jun; Song, Hyuk; Kim, Nam-Hyung; Kim, Jae-Hwan

    2012-01-01

    Highlights: ► We found the putative nuclear export signal motif within human NANOG homeodomain. ► Leucine-rich residues are important for human NANOG homeodomain nuclear export. ► CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ( 125 MQELSNILNL 134 ) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-ΔNLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  19. The B7-1 cytoplasmic tail enhances intracellular transport and mammalian cell surface display of chimeric proteins in the absence of a linear ER export motif.

    Directory of Open Access Journals (Sweden)

    Yi-Chieh Lin

    Full Text Available Membrane-tethered proteins (mammalian surface display are increasingly being used for novel therapeutic and biotechnology applications. Maximizing surface expression of chimeric proteins on mammalian cells is important for these applications. We show that the cytoplasmic domain from the B7-1 antigen, a commonly used element for mammalian surface display, can enhance the intracellular transport and surface display of chimeric proteins in a Sar1 and Rab1 dependent fashion. However, mutational, alanine scanning and deletion analysis demonstrate the absence of linear ER export motifs in the B7 cytoplasmic domain. Rather, efficient intracellular transport correlated with the presence of predicted secondary structure in the cytoplasmic tail. Examination of the cytoplasmic domains of 984 human and 782 mouse type I transmembrane proteins revealed that many previously identified ER export motifs are rarely found in the cytoplasmic tail of type I transmembrane proteins. Our results suggest that efficient intracellular transport of B7 chimeric proteins is associated with the structure rather than to the presence of a linear ER export motif in the cytoplasmic tail, and indicate that short (less than ~ 10-20 amino acids and unstructured cytoplasmic tails should be avoided to express high levels of chimeric proteins on mammalian cells.

  20. The regulation of ER export and Golgi retention of ST3Gal5 (GM3/GM4 synthase) and B4GalNAcT1 (GM2/GD2/GA2 synthase) by arginine/lysine-based motif adjacent to the transmembrane domain.

    Science.gov (United States)

    Uemura, Satoshi; Shishido, Fumi; Kashimura, Madoka; Inokuchi, Jin-ichi

    2015-12-01

    In the Golgi maturation model, the Golgi cisternae dynamically mature along a secretory pathway. In this dynamic process, glycosyltransferases are transported from the endoplasmic reticulum (ER) to the Golgi apparatus where they remain and function. The precise mechanism behind this maturation process remains unclear. We investigated two glycosyltransferases, ST3Gal5 (ST3G5) and B4GalNAcT1 (B4GN1), involved in ganglioside synthesis and examined their signal sequences for ER export and Golgi retention. Reports have suggested that the [R/K](X)[R/K] motif functions as an ER exporting signal; however, this signal sequence is insufficient in stably expressed, full-length ST3G5. Through further analysis, we have clarified that the (2)R(3)R(X)(5) (9)K(X)(3) (13)K sequence in ST3G5 is essential for ER export. We have named the sequence the R/K-based motif. On the other hand, for ER export of B4GN1, the homodimer formation in addition to the R/K-based motif is required for ER export suggesting the importance of unidentified lumenal side interaction. We found that ST3G5 R2A/R3A and K9A/K13A mutants localized not only in Golgi apparatus but also in endosomes. Furthermore, the amounts of mature type asparagine-linked (N)-glycans in ST3G5 R2A/R3A and K9A/K13A mutants were decreased compared with those in wild-type proteins, and the stability of the mutants was lower. These results suggest that the R/K-based motif is necessary for the Golgi retention of ST3G5 and that the retention is involved in the maturation of N-glycans and in stability. Thus, several basic amino acids located on the cytoplasmic tail of ST3G5 play important roles in both ER export and Golgi retention. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

    Science.gov (United States)

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-09-15

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

  2. 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.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhi [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Liu, Shaoning [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Shandong Institute of Veterinary Drug Quality Inspection, Shandong Key Laboratory for Quality Safety Monitoring and Risk Assessment of Animal Products, Huaicun Street No. 68, Jinan 250722, Shandong Province (China); Sun, Wenbo; Chen, Lei [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Yoo, Dongwan [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Feng [Department of Biology and Microbiology, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007 (United States); Ren, Sufang; Guo, Lihui; Cong, Xiaoyan; Li, Jun [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Zhou, Shun [College of marine science and engineering, Qingdao Agricultural University, Changcheng Road No. 700, Qingdao 266109 (China); Wu, Jiaqiang, E-mail: wujiaqiang2000@sina.com [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); and others

    2016-12-15

    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. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.

  5. Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

    Science.gov (United States)

    Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

    2016-05-23

    The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms

  6. NESmapper: accurate prediction of leucine-rich nuclear export signals using activity-based profiles.

    Directory of Open Access Journals (Sweden)

    Shunichi Kosugi

    2014-09-01

    Full Text Available The nuclear export of proteins is regulated largely through the exportin/CRM1 pathway, which involves the specific recognition of leucine-rich nuclear export signals (NESs in the cargo proteins, and modulates nuclear-cytoplasmic protein shuttling by antagonizing the nuclear import activity mediated by importins and the nuclear import signal (NLS. Although the prediction of NESs can help to define proteins that undergo regulated nuclear export, current methods of predicting NESs, including computational tools and consensus-sequence-based searches, have limited accuracy, especially in terms of their specificity. We found that each residue within an NES largely contributes independently and additively to the entire nuclear export activity. We created activity-based profiles of all classes of NESs with a comprehensive mutational analysis in mammalian cells. The profiles highlight a number of specific activity-affecting residues not only at the conserved hydrophobic positions but also in the linker and flanking regions. We then developed a computational tool, NESmapper, to predict NESs by using profiles that had been further optimized by training and combining the amino acid properties of the NES-flanking regions. This tool successfully reduced the considerable number of false positives, and the overall prediction accuracy was higher than that of other methods, including NESsential and Wregex. This profile-based prediction strategy is a reliable way to identify functional protein motifs. NESmapper is available at http://sourceforge.net/projects/nesmapper.

  7. Dietary gossypol suppressed postprandial TOR signaling and elevated ER stress pathways in turbot (Scophthalmus maximus L.).

    Science.gov (United States)

    Bian, Fuyun; Jiang, Haowen; Man, Mingsan; Mai, Kangsen; Zhou, Huihui; Xu, Wei; He, Gen

    2017-01-01

    Gossypol is known to be a polyphenolic compound toxic to animals. However, its molecular targets are far from fully characterized. To evaluate the physiological and molecular effects of gossypol, we chose turbot (Scophthalmus maximus L.), a carnivorous fish, as our model species. Juvenile turbots (7.83 ± 0.02 g) were fed diets containing gradient levels of gossypol at 0 (G0), 600 (G1), and 1,200 (G2) mg/kg diets for 11 wk. After the feeding trial, fish growth, body protein, and fat contents were significantly reduced in the G2 group compared with those of the G0 group (P TOR) signaling and induced endoplasmic reticulum (ER) stress pathway in both the feeding experiment and cell cultures. Our results demonstrated that gossypol inhibited TOR signaling and elevated ER stress pathways both in vivo and in vitro, thus providing new mechanism of action of gossypol in nutritional physiology. Copyright © 2017 the American Physiological Society.

  8. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.

    Science.gov (United States)

    Hayashi, Teruo; Su, Tsung-Ping

    2007-11-02

    Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca(2+) directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca(2+)-sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca(2+) depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca(2+) signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival.

  9. Nuclear localization signal regulates porcine circovirus type 2 capsid protein nuclear export through phosphorylation.

    Science.gov (United States)

    Hou, Qiang; Hou, Shaohua; Chen, Qing; Jia, Hong; Xin, Ting; Jiang, Yitong; Guo, Xiaoyu; Zhu, Hongfei

    2018-02-15

    The open reading frame 2 (ORF2) of Porcine circovirus type 2 (PCV2) encodes the major Capsid (Cap) protein, which self-assembles into virus-like particle (VLP) of similar morphology to the PCV2 virion and accumulates in the nucleus through the N-terminal arginine-rich nuclear localization signal (NLS). In this study, PCV2 Cap protein and its derivates were expressed via the baculovirus expression system, and the cellular localization of the recombinant proteins were investigated using anti-Cap mAb by imaging flow cytometry. Analysis of subcellular localization of Cap protein and its variants demonstrated that NLS mediated Cap protein nuclear export as well as nuclear import, and a phosphorylation site (S17) was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the NLS domain to regulate Cap protein nuclear export. Phosphorylation of NLS regulating the PCV2 Cap protein nuclear export was also demonstrated in PK15 cells by fluorescence microscopy. Moreover, the influence of Rep and Rep' protein on Cap protein subcellular localization was investigated in PK15 cells. Phosphorylation of NLS regulating Cap protein nuclear export provides more detailed knowledge of the PCV2 viral life cycle. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Optimizing the protein switch: altering nuclear import and export signals, and ligand binding domain

    Science.gov (United States)

    Kakar, Mudit; Davis, James R.; Kern, Steve E.; Lim, Carol S.

    2007-01-01

    Ligand regulated localization controllable protein constructs were optimized in this study. Several constructs were made from a classical nuclear export signal (HIV-rev, MAPKK, or progesterone receptor) in combination with a SV40 T-antigen type nuclear import signal. Different ligand binding domains (LBDs from glucocorticoid receptor or progesterone receptor) were also tested for their ability to impart control over localization of proteins. This study was designed to create constructs which are cytoplasmic in the absence of ligand and nuclear in the presence of ligand, and also to regulate the amount of protein translocating to the nucleus on ligand induction. The balance between the strengths of import and export signals was critical for overall localization of proteins. The amount of protein entering the nucleus was also affected by the dose of ligand (10-100nM). However, the overall import characteristics were determined by the strengths of localization signals and the inherent localization properties of the LBD used. This study established that the amount of protein present in a particular compartment can be regulated by the use of localization signals of various strengths. These optimized localization controllable protein constructs can be used to correct for diseases due to aberrant localization of proteins. PMID:17574289

  11. 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.

  12. 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.

  13. The tight junction protein Z O-2 has several functional nuclear export signals

    International Nuclear Information System (INIS)

    Gonzalez-Mariscal, Lorenza; Ponce, Arturo; Alarcon, Lourdes; Jaramillo, Blanca Estela

    2006-01-01

    The tight junction (TJ) protein ZO-2 changes its subcellular distribution according to the state of confluency of the culture. Thus in confluent monolayers, it localizes at the TJ region whereas in sparse cultures it concentrates at the nucleus. The canine sequence of ZO-2 displays four putative nuclear export signals (NES), two at the second PDZ domain (NES-0 and NES-1) and the rest at the GK region (NES-2 and NES-3). The functionality of NES-0 and NES-3 was unknown, hence here we have explored it with a nuclear export assay, injecting into the nucleus of MDCK cells peptides corresponding to the ZO-2 NES sequences chemically coupled to ovalbumin. We show that both NES-0 and NES-3 are functional and sensitive to leptomycin B. We also demonstrate that NES-1, previously characterized as a non functional NES, is rendered capable of nuclear export upon the acquisition of a negative charge at its Ser369 residue. Experiments performed injecting at the nucleus WT and mutated ZO-2-GST fusion proteins revealed the need of both NES-0 and NES-1, and NES-2 and NES-3 for attaining an efficient nuclear exit of the respective amino and middle segments of ZO-2. Moreover, the transfection of MDCK cells with full-length ZO-2 revealed that the mutation of any of the NES present in the molecule was sufficient to induce nuclear accumulation of the protein

  14. 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.

  15. CD151, a novel host factor of nuclear export signaling in influenza virus infection.

    Science.gov (United States)

    Qiao, Yongkang; Yan, Yan; Tan, Kai Sen; Tan, Sheryl S L; Seet, Ju Ee; Arumugam, Thiruma Valavan; Chow, Vincent T K; Wang, De Yun; Tran, Thai

    2018-05-01

    Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro-differentiated human nasal epithelial cells cultured at air-liquid interface. As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Influence of ER leak on resting cytoplasmic Ca2+ and receptor-mediated Ca2+ signalling in human macrophage.

    Science.gov (United States)

    Layhadi, Janice A; Fountain, Samuel J

    2017-06-03

    Mechanisms controlling endoplasmic reticulum (ER) Ca 2+ homeostasis are important regulators of resting cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyto ) and receptor-mediated Ca 2+ signalling. Here we investigate channels responsible for ER Ca 2+ leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca 2+ we employ ionomycin action at the plasma membrane to stimulate ER Ca 2+ leak. Under these conditions ionomycin elevates [Ca 2+ ] cyto revealing a Ca 2+ leak response which is abolished by thapsigargin. IP 3 receptors (Xestospongin C, 2-APB), ryanodine receptors (dantrolene), and translocon (anisomycin) inhibition facilitated ER Ca 2+ leak in model macrophage, with translocon inhibition also reducing resting [Ca 2+ ] cyto . In primary macrophage, translocon inhibition blocks Ca 2+ leak but does not influence resting [Ca 2+ ] cyto . We identify a role for translocon-mediated ER Ca 2+ leak in receptor-mediated Ca 2+ signalling in both model and primary human macrophage, whereby the Ca 2+ response to ADP (P2Y receptor agonist) is augmented following anisomycin treatment. In conclusion, we demonstrate a role of ER Ca 2+ leak via the translocon in controlling resting cytoplasmic Ca 2+ in model macrophage and receptor-mediated Ca 2+ signalling in model macrophage and primary macrophage. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Identification of a functional nuclear export signal in the green fluorescent protein asFP499

    International Nuclear Information System (INIS)

    Mustafa, Huseyin; Strasser, Bernd; Rauth, Sabine; Irving, Robert A.; Wark, Kim L.

    2006-01-01

    The green fluorescent protein (GFP) asFP499 from Anemonia sulcata is a distant homologue of the GFP from Aequorea victoria. We cloned the asFP499 gene into a mammalian expression vector and showed that this protein was expressed in the human lymphoblast cell line Ramos RA1 and in the embryonic kidney 293T cell line (HEK 293T). In HEK 293T cells, asFP499 was localized mainly in the cytoplasm, suggesting that the protein was excluded from the nucleus. We identified 194 LRMEKLNI 201 as a candidate nuclear export signal in asFP499 and mutated the isoleucine at position 201 to an alanine. Unlike the wildtype form, the mutant protein was distributed throughout the cytoplasm and nucleus. This is First report of a GFP that contains a functional NES

  18. RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

    Science.gov (United States)

    Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

    2011-01-05

    The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

  19. Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Cho Hyunju

    2013-01-01

    Full Text Available Abstract Background Palmitic acid, the most common saturated free fatty acid, has been implicated in ER (endoplasmic reticulum stress-mediated apoptosis. This lipoapotosis is dependent, in part, on the upregulation of the activating transcription factor-4 (ATF4. To better understand the mechanisms by which palmitate upregulates the expression level of ATF4, we integrated literature information on palmitate-induced ER stress signaling into a discrete dynamic model. The model provides an in silico framework that enables simulations and predictions. The model predictions were confirmed through further experiments in human hepatocellular carcinoma (HepG2 cells and the results were used to update the model and our current understanding of the signaling induced by palmitate. Results The three key things from the in silico simulation and experimental results are: 1 palmitate induces different signaling pathways (PKR (double-stranded RNA-activated protein kinase, PERK (PKR-like ER kinase, PKA (cyclic AMP (cAMP-dependent protein kinase A in a time dependent-manner, 2 both ATF4 and CREB1 (cAMP-responsive element-binding protein 1 interact with the Atf4 promoter to contribute to a prolonged accumulation of ATF4, and 3 CREB1 is involved in ER-stress induced apoptosis upon palmitate treatment, by regulating ATF4 expression and possibly Ca2+ dependent-CaM (calmodulin signaling pathway. Conclusion The in silico model helped to delineate the essential signaling pathways in palmitate-mediated apoptosis.

  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

    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. 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.

  2. Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3.

    Science.gov (United States)

    Bedard, James E J; Purnell, Jennifer D; Ware, Stephanie M

    2007-01-15

    Missense, frameshift and nonsense mutations in the zinc finger transcription factor ZIC3 cause heterotaxy as well as isolated congenital heart disease. Previously, we developed transactivation and subcellular localization assays to test the function of ZIC3 point mutations. Aberrant cytoplasmic localization suggested that the pathogenesis of ZIC3 mutations results, at least in part, from failure of appropriate cellular trafficking. To further investigate this hypothesis, the nucleocytoplasmic shuttling properties of ZIC3 have been examined. Subcellular localization assays designed to span the entire open-reading frame of wild-type and mutant ZIC3 proteins identified the presence of nucleocytoplasmic transport signals. ZIC3 domain mapping indicates that a relatively large region containing the zinc finger binding sites and a known GLI interacting domain is required for transport to the nucleus. Site-directed mutagenesis of critical residues within two putative nuclear localization signals (NLSs) leads to loss of nuclear localization. No further decrease was observed when both NLS sites were mutated, suggesting that mutation of either NLS site is sufficient for loss of importin-mediated nuclear localization. Additionally, we identify a cryptic CRM-1-dependent nuclear export signal (NES) within ZIC3, and identify a mutation within this region in a patient with heterotaxy. These results provide the first evidence that control of cellular trafficking of ZIC3 is critical for function and suggest a possible mechanism for transcriptional control during left-right patterning. Identification of mutations in mapped NLS or NES domains in heterotaxy patients demonstrates the functional importance of these domains in cardiac morphogenesis and allows for integration of structural analysis with developmental function.

  3. Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER+ Breast Cancer

    OpenAIRE

    Haricharan, Svasti; Lei, Jonathan; Ellis, Matthew

    2016-01-01

    In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER+ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER+ breast cancer cells and in driving the luminal phenotype of breast cancer.

  4. Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER+ Breast Cancer

    Science.gov (United States)

    Haricharan, Svasti; Lei, Jonathan; Ellis, Matthew

    2016-01-01

    In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER+ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER+ breast cancer cells and in driving the luminal phenotype of breast cancer. PMID:26977876

  5. Functional analysis of the interaction of the human immunodeficiency virus type 1 Rev nuclear export signal with its cofactors

    International Nuclear Information System (INIS)

    Kiss, A.; Li, L.; Gettemeier, T.; Venkatesh, L.K.

    2003-01-01

    Human immunodeficiency virus type 1 (HIV-1) Rev-mediated nuclear export of viral RNAs involves the interaction of its leucine-rich nuclear export sequence (NES) with nuclear cofactors. In yeast two-hybrid screens of a human lymph node derived cDNA expression library, we identified the human nucleoporin Nup98 as a highly specific and potent interactor of the Rev NES. Using an extensive panel of nuclear export positive and negative mutants of the functionally homologous NESs of the HIV-1 Rev, human T cell leukemia virus type 1 (HTLV-1) Rex, and equine infectious anemia virus (EIAV) Rev proteins, physiologically significant interaction of hNup98 with the various NESs was demonstrated. Missense mutations in the yeast nuclear export factor Crm1p that abrogated Rev NES interaction with the XXFG repeat-containing nucleoporin, Rab/hRIP, had minimal effects on the interaction of GLFG repeat-containing hNup98. Functional analysis of Nup98 domains required for nuclear localization demonstrated that the entire ORF was required for efficient incorporation into the nuclear envelope. A putative nuclear localization signal was identified downstream of the GLFG repeat region. Whereas overexpression of both full-length Nup98 and the amino-terminal GLFG repeat region, but not the unique carboxy-terminal region, induced significant suppression of HIV unspliced RNA export, lower levels of exogenous Nup98 expression resulted in a relatively modest increase in unspliced RNA export. These results suggest a physiological role for hNup98 in modulating Rev-dependent RNA export during HIV infection

  6. Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax.

    Science.gov (United States)

    Alefantis, Timothy; Barmak, Kate; Harhaj, Edward W; Grant, Christian; Wigdahl, Brian

    2003-06-13

    Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response element-binding protein and nuclear factor-kappaB, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucine-rich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant TaxDelta214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.

  7. The expression of ER, PR in endometrial cancer and analysis of their correlation with ERK signaling pathway.

    Science.gov (United States)

    Luo, Lan; Xu, Lina; Tang, Liang

    2017-12-12

    Endometrial carcinoma (EC) is a common malignant tumor in gynecology. Its incidence and development are closely associated with the levels of estrogenic and progesterone hormone. Extracellular signal-regulated kinase (ERK) signaling pathway abnormity is associated with a variety of tumors. This study detected estrogen receptor (ER), progesterone receptor (PR), ERK1, and ERK2 expression in EC and analyzed their correlations. A total of 40 EC patients in our hospital were selected as test group, while another 40 healthy volunteers were enrolled as control group. ER, PR, ERK1, and ERK2 expression in EC tissue, para-carcinoma tissue, and normal endometrial tissue were detected by immunohistochemistry and Western blot. The positive rate of ER, PR, ERK1, and ERK2 in the test group was 50%, 40%, 60%, and 65%, respectively, which were significantly higher than those in the control (PPR, ERK1, and ERK2 protein expressions in EC cell were significantly higher than those in the control (PPR (PPR, which were correlated with higher levels of ERK1 and ERK2, suggesting they might be involved in the pathogenesis of EC.

  8. NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

    Science.gov (United States)

    Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

    2010-11-01

    Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

  9. ER stress signaling and neurodegeneration: At the intersection between Alzheimer's disease and Prion-related disorders.

    Science.gov (United States)

    Torres, Mauricio; Matamala, José Manuel; Duran-Aniotz, Claudia; Cornejo, Victor Hugo; Foley, Andrew; Hetz, Claudio

    2015-09-02

    Alzheimer's and Prion diseases are two neurodegenerative conditions sharing different pathophysiological characteristics. Disease symptoms are associated with the abnormal accumulation of protein aggregates, which are generated by the misfolding and oligomerization of specific proteins. Recent functional studies uncovered a key role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in the occurrence of synaptic dysfunction and neurodegeneration in Prion-related disorders and Alzheimer's disease. Here we review common pathological features of both diseases, emphasizing the link between amyloid formation, its pathogenesis and alterations in ER proteostasis. The potential benefits of targeting the UPR as a therapeutic strategy is also discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.

    Science.gov (United States)

    Choi, Hee-Joo; Joo, Hyeong-Seok; Won, Hee-Young; Min, Kyueng-Whan; Kim, Hyung-Yong; Son, Taekwon; Oh, Young-Ha; Lee, Jeong-Yeon; Kong, Gu

    2018-04-01

    resistance (RBP2-overexpressing cells: % cell viability [SD], tamoxifen = 89.0 [3.8]%, vs tamoxifen with BKM120 = 41.3 [5.6]%, P < .001). RBP2 activates ER-IGF1R-ErbB signaling cascade in multiple ways to induce tamoxifen resistance, suggesting that RBP2 is a potential therapeutic target for ER-driven cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  11. Reference hearing threshold levels for chirp signals delivered by an ER-3A insert earphone

    DEFF Research Database (Denmark)

    Gøtsche-Rasmussen, Kristian; Poulsen, Torben; Elberling, Claus

    2012-01-01

    back from a Tucker Davies Technologies System II, and a Matlab program controlled the test setup. The results are specified in dB peak-to-peak equivalent threshold sound pressure levels (dB peETSPL). Study sample: The test group consisted of 25 otologically-normal young adults (age 18–25 years......Objective: To establish reference hearing threshold levels for chirps and frequency-specific chirps. Design: Hearing thresholds were determined monaurally for broad-band chirps and octave-band chirps using the Etymotic Research, ER-3A insert earphone. The chirps were presented using two repetition...

  12. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    LENUS (Irish Health Repository)

    Gupta, Sanjeev

    2010-01-01

    Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha\\/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  13. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    Directory of Open Access Journals (Sweden)

    Sanjeev Gupta

    2010-07-01

    Full Text Available Endoplasmic reticulum (ER stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR. Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  14. ‘WNT-er is coming’: WNT signalling in chronic lung diseases

    Science.gov (United States)

    Baarsma, H A

    2017-01-01

    Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD. While many studies have focused on the canonical WNT/β-catenin signalling pathway, recent reports highlight that non-canonical WNT signalling may also significantly contribute to chronic lung pathologies; these studies will be particularly featured in this review. We further discuss recent advances uncovering the role of WNT signalling early in life, the potential of pharmaceutically modulating WNT signalling pathways and highlight (pre)clinical studies describing promising new therapies for chronic lung diseases. PMID:28416592

  15. A translocator-specific export signal establishes the translocator-effector secretion hierarchy that is important for type III secretion system function

    Science.gov (United States)

    Tomalka, Amanda G.; Stopford, Charles M.; Lee, Pei-Chung; Rietsch, Arne

    2012-01-01

    Summary Type III secretion systems are used by many Gram-negative pathogens to directly deliver effector proteins into the cytoplasm of host cells. To accomplish this, bacteria secrete translocator proteins that form a pore in the host-cell membrane through which the effector proteins are then introduced into the host cell. Evidence from multiple systems indicates that the pore-forming translocator proteins are exported before effectors, but how this secretion hierarchy is established is unclear. Here we used the P. aeruginosa translocator protein PopD as a model to identify its export signals. The amino-terminal secretion signal and chaperone, PcrH, are required for export under all conditions. Two novel signals in PopD, one proximal to the chaperone-binding site and one at the very C-terminus of the protein, are required for export of PopD before effector proteins. These novel export signals establish the translocator-effector secretion hierarchy, which in turn, is critical for the delivery of effectors into host cells. PMID:23121689

  16. ER EXPORT AND SURFACE TARGETING OF THE DOPAMINE TRANSPORTER ARE DEPENDENT ON THE DISTAL C-TERMINUS BUT OCCURS INDEPENDENTLY OF PDZ DOMAIN INTERACTIONS

    DEFF Research Database (Denmark)

    Bjerggaard(Vægter), Christian; Loland, Claus; Hastrup, Hanne

    . Neuron 2001, 30:121-34). As expected, we find that deletion of the PDZ binding sequence (LKV) or substitution with three histidines resulted in retention of hDAT in the ER in both HEK293 and N2A neuroblastoma cells. However, substitution of LKV with the type 2 PDZ binding sequence SLL of the beta2...

  17. ER Alpha Rapid Signaling Is Required for Estrogen Induced Proliferation and Migration of Vascular Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs, which likely underlies its ability to accelerate re-endothelialization and reduce adverse remodeling after vascular injury. In previous studies, we have shown that the protective effects of E2 (the active endogenous form of estrogen in vascular injury require the estrogen receptor alpha (ERα. ERα transduces the effects of estrogen via a classical DNA binding, "genomic" signaling pathway and via a more recently-described "rapid" signaling pathway that is mediated by a subset of ERα localized to the cell membrane. However, which of these pathways mediates the effects of estrogen on endothelial cells is poorly understood. Here we identify a triple point mutant version of ERα (KRR ERα that is specifically defective in rapid signaling, but is competent to regulate transcription through the "genomic" pathway. We find that in ECs expressing wild type ERα, E2 regulates many genes involved in cell migration and proliferation, promotes EC migration and proliferation, and also blocks the adhesion of monocytes to ECs. ECs expressing KRR mutant ERα, however, lack all of these responses. These observations establish KRR ERα as a novel tool that could greatly facilitate future studies into the vascular and non-vascular functions of ERα rapid signaling. Further, they support that rapid signaling through ERα is essential for many of the transcriptional and physiological responses of ECs to E2, and that ERα rapid signaling in ECs, in vivo, may be critical for the vasculoprotective and anti-inflammatory effects of estrogen.

  18. Regulation of traffic and organelle architecture of the ER-Golgi interface by signal transduction.

    Science.gov (United States)

    Tillmann, Kerstin D; Millarte, Valentina; Farhan, Hesso

    2013-09-01

    The components that control trafficking between organelles of the secretory pathway as well as their architecture were uncovered to a reasonable extent in the past decades. However, only recently did we begin to explore the regulation of the secretory pathway by cellular signaling. In the current review, we focus on trafficking between the endoplasmic reticulum and the Golgi apparatus. We highlight recent advances that have been made toward a better understanding of how the secretory pathway is regulated by signaling and discuss how this knowledge is important to obtain an integrative view of secretion in the context of other homeostatic processes such as growth and proliferation.

  19. ER stress stimulates production of the key antimicrobial peptide, cathelicidin, by forming a previously unidentified intracellular S1P signaling complex.

    Science.gov (United States)

    Park, Kyungho; Ikushiro, Hiroko; Seo, Ho Seong; Shin, Kyong-Oh; Kim, Young Il; Kim, Jong Youl; Lee, Yong-Moon; Yano, Takato; Holleran, Walter M; Elias, Peter; Uchida, Yoshikazu

    2016-03-08

    We recently identified a previously unidentified sphingosine-1-phosphate (S1P) signaling mechanism that stimulates production of a key innate immune element, cathelicidin antimicrobial peptide (CAMP), in mammalian cells exposed to external perturbations, such as UVB irradiation and other oxidative stressors that provoke subapoptotic levels of endoplasmic reticulum (ER) stress, independent of the well-known vitamin D receptor-dependent mechanism. ER stress increases cellular ceramide and one of its distal metabolites, S1P, which activates NF-κB followed by C/EBPα activation, leading to CAMP production, but in a S1P receptor-independent fashion. We now show that S1P activates NF-κB through formation of a previously unidentified signaling complex, consisting of S1P, TRAF2, and RIP1 that further associates with three stress-responsive proteins; i.e., heat shock proteins (GRP94 and HSP90α) and IRE1α. S1P specifically interacts with the N-terminal domain of heat shock proteins. Because this ER stress-initiated mechanism is operative in both epithelial cells and macrophages, it appears to be a universal, highly conserved response, broadly protective against diverse external perturbations that lead to increased ER stress. Finally, these studies further illuminate how ER stress and S1P orchestrate critical stress-specific signals that regulate production of one protective response by stimulating production of the key innate immune element, CAMP.

  20. Association of CD147 and Calcium Exporter PMCA4 Uncouples IL-2 Expression from Early TCR Signaling.

    Science.gov (United States)

    Supper, Verena; Schiller, Herbert B; Paster, Wolfgang; Forster, Florian; Boulègue, Cyril; Mitulovic, Goran; Leksa, Vladimir; Ohradanova-Repic, Anna; Machacek, Christian; Schatzlmaier, Philipp; Zlabinger, Gerhard J; Stockinger, Hannes

    2016-02-01

    The Ig superfamily member CD147 is upregulated following T cell activation and was shown to serve as a negative regulator of T cell proliferation. Thus, Abs targeting CD147 are being tested as new treatment strategies for cancer and autoimmune diseases. How CD147 mediates immunosuppression and whether association with other coreceptor complexes is needed have remained unknown. In the current study, we show that silencing of CD147 in human T cells increases IL-2 production without affecting the TCR proximal signaling components. We mapped the immunosuppressive moieties of CD147 to its transmembrane domain and Ig-like domain II. Using affinity purification combined with mass spectrometry, we determined the domain specificity of CD147 interaction partners and identified the calcium exporter plasma membrane calcium ATPase isoform 4 (PMCA4) as the interaction partner of the immunosuppressive moieties of CD147. CD147 does not control the proper membrane localization of PMCA4, but PMCA4 is essential for the CD147-dependent inhibition of IL-2 expression via a calcium-independent mechanism. In summary, our data show that CD147 interacts via its immunomodulatory domains with PMCA4 to bypass TCR proximal signaling and inhibit IL-2 expression. Copyright © 2016 by The American Association of Immunologists, Inc.

  1. Identification of the nuclear export signals that regulate the intracellular localization of the mouse CMP-sialic acid synthetase

    International Nuclear Information System (INIS)

    Fujita, Akiko; Sato, Chihiro; Kitajima, Ken.

    2007-01-01

    The CMP-sialic acid synthetase (CSS) catalyzes the activation of sialic acid (Sia) to CMP-Sia which is a donor substrate of sialyltransferases. The vertebrate CSSs are usually localized in nucleus due to the nuclear localization signal (NLS) on the molecule. In this study, we first point out that a small, but significant population of the mouse CMP-sialic acid synthetase (mCSS) is also present in cytoplasm, though mostly in nucleus. As a mechanism for the localization in cytoplasm, we first identified two nuclear export signals (NESs) in mCSS, based on the localization studies of the potential NES-deleted mCSS mutants as well as the potential NES-tagged eGFP proteins. These two NESs are conserved among mammalian and fish CSSs, but not present in the bacterial or insect CSS. These results suggest that the intracellular localization of vertebrate CSSs is regulated by not only the NLS, but also the NES sequences

  2. Baicalin Ameliorates H2O2 Induced Cytotoxicity in HK-2 Cells through the Inhibition of ER Stress and the Activation of Nrf2 Signaling

    Directory of Open Access Journals (Sweden)

    Miao Lin

    2014-07-01

    Full Text Available Renal ischemia-reperfusion injury plays a key role in renal transplantation and greatly affects the outcome of allograft. Our previous study proved that Baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, protects kidney from ischemia-reperfusion injury. This study aimed to study the underlying mechanism in vitro. Human renal proximal tubular epithelial cell line HK-2 cells were stimulated by H2O2 with and without Baicalin pretreatment. The cell viability, apoptosis and oxidative stress level were measured. The expression of endoplasmic reticulum (ER stress hallmarks, such as binding immunoglobulin protein (BiP and C/EBP homologous protein (CHOP, were analyzed by western blot and real-time PCR. NF-E2-related factor 2 (Nrf2 expression was also measured. In the H2O2 group, cell viability decreased and cell apoptosis increased. Reactive Oxygen Species (ROS and Glutathione/Oxidized Glutathione (GSH/GSSG analysis revealed increased oxidative stress. ER stress and Nrf2 signaling also increased. Baicalin pretreatment ameliorated H2O2-induced cytotoxicity, reduced oxidative stress and ER stress and further activated the anti-oxidative Nrf2 signaling pathway. The inducer of ER stress and the inhibitor of Nrf2 abrogated the protective effects, while the inhibitor of ER stress and the inducer of Nrf2 did not improve the outcome. This study revealed that Baicalin pretreatment serves a protective role against H2O2-induced cytotoxicity in HK-2 cells, where the inhibition of ER stress and the activation of downstream Nrf2 signaling are involved.

  3. A traffic signal for heterodimeric amino acid transporters to transfer from the ER to the Golgi.

    Science.gov (United States)

    Ganapathy, Vadivel

    2009-01-15

    Heterodimeric amino acid transporters represent a unique class of transport systems that consist of a light chain that serves as the 'transporter proper' and a heavy chain that is necessary for targeting the complex to the plasma membrane. The currently prevailing paradigm assigns no role for the light chains in the cellular processing of these transporters. In this issue of the Biochemical Journal, Sakamoto et al. provide evidence contrary to this paradigm. Their studies with the rBAT -b(0,+)AT (related to b(0,+) amino acid transporter-b(0,+)-type amino acid transporter) heterodimeric amino acid transporter show that the C-terminus of the light chain b(0,+)AT contains a sequence motif that serves as the traffic signal for the transfer of the heterodimeric complex from the endoplasmic reticulum to the Golgi. This is a novel function for the light chain in addition to its already established role as the subunit responsible for the transport activity. These new findings also seem to be applicable to other heterodimeric amino acid transporters as well.

  4. ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling.

    Directory of Open Access Journals (Sweden)

    Arindam Banerjee

    Full Text Available The neurotrophic factor ARTEMIN (ARTN has been reported to possess a role in mammary carcinoma progression and metastasis. Herein, we report that ARTN modulates endothelial cell behaviour and promotes angiogenesis in ER-mammary carcinoma (ER-MC. Human microvascular endothelial cells (HMEC-1 do not express ARTN but respond to exogenously added, and paracrine ARTN secreted by ER-MC cells. ARTN promoted endothelial cell proliferation, migration, invasion and 3D matrigel tube formation. Angiogenic behaviour promoted by ARTN secreted by ER-MC cells was mediated by AKT with resultant increased TWIST1 and subsequently VEGF-A expression. In a patient cohort of ER-MC, ARTN positively correlated with VEGF-A expression as measured by Spearman's rank correlation analysis. In xenograft experiments, ER-MC cells with forced expression of ARTN produced tumors with increased VEGF-A expression and increased microvessel density (CD31 and CD34 compared to tumors formed by control cells. Functional inhibition of ARTN by siRNA decreased the angiogenic effects of ER-MC cells. Bevacizumab (a humanized monoclonal anti-VEGF-A antibody partially inhibited the ARTN mediated angiogenic effects of ER-MC cells and combined inhibition of ARTN and VEGF-A by the same resulted in further significant decrease in the angiogenic effects of ER-MC cells. Thus, ARTN stimulates de novo tumor angiogenesis mediated in part by VEGF-A. ARTN therefore co-ordinately regulates multiple aspects of tumor growth and metastasis.

  5. 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

  6. Characterization of nuclear localization and export signals of the major tegument protein VP8 of bovine herpesvirus-1

    International Nuclear Information System (INIS)

    Zheng Chunfu; Brownlie, Robert; Babiuk, Lorne A.; Hurk, Sylvia van Drunen Littel-van den

    2004-01-01

    Bovine herpesvirus-1 (BHV-1) VP8 is found in the nucleus immediately after infection. Transient expression of VP8 fused to yellow fluorescent protein (YFP) in COS-7 cells confirmed the nuclear localization of VP8 in the absence of other viral proteins. VP8 has four putative nuclear localization signals (NLS). Deletion of pat4 ( 51 RRPR 54 ) or pat7 ( 48 PRVRRPR 54 ) NLS2 abrogated nuclear accumulation, whereas deletion of 48 PRV 50 did not, so pat4 NLS2 is critical for nuclear localization of VP8. Furthermore, NLS1 ( 11 RRPRR 15 ), pat4 NLS2, and pat7 NLS2 were all capable of transporting the majority of YFP to the nucleus. Finally, a 12-amino-acid peptide with the sequence RRPRRPRVRRPR directed all of YFP into the nucleus, suggesting that reiteration of the RRPR motif makes the nuclear localization more efficient. Heterokaryon assays demonstrated that VP8 is also capable of shuttling between the nucleus and cytoplasm of the cell. Deletion mutant analysis revealed that this property is attributed to a leucine-rich nuclear export sequence (NES) consisting of amino acids 485 LSAYLTLFVAL 495 . This leucine-rich NES caused transport of YFP to the cytoplasm. These results demonstrate that VP8 shuttles between the nucleus and cytoplasm

  7. Ultraviolet (UV and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Jin Yao

    2013-05-01

    Full Text Available Ultraviolet (UV radiation and reactive oxygen species (ROS impair the physiological functions of retinal pigment epithelium (RPE cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD. The mechanism by which UV/ROS induces RPE cell death is not fully addressed. Here, we observed the activation of a ceramide-endoplasmic reticulum (ER stress-AMP activated protein kinase (AMPK signaling axis in UV and hydrogen peroxide (H2O2-treated RPE cells. UV and H2O2 induced an early ceramide production, profound ER stress and AMPK activation. Pharmacological inhibitors against ER stress (salubrinal, ceramide production (fumonisin B1 and AMPK activation (compound C suppressed UV- and H2O2-induced RPE cell apoptosis. Conversely, cell permeable short-chain C6 ceramide and AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide mimicked UV and H2O2’s effects and promoted RPE cell apoptosis. Together, these results suggest that UV/H2O2 activates the ceramide-ER stress-AMPK signaling axis to promote RPE cell apoptosis.

  8. Excessive signal transduction of gain-of-function variants of the calcium-sensing receptor (CaSR are associated with increased ER to cytosol calcium gradient.

    Directory of Open Access Journals (Sweden)

    Marianna Ranieri

    Full Text Available In humans, gain-of-function mutations of the calcium-sensing receptor (CASR gene are the cause of autosomal dominant hypocalcemia or type 5 Bartter syndrome characterized by an abnormality of calcium metabolism with low parathyroid hormone levels and excessive renal calcium excretion. Functional characterization of CaSR activating variants has been so far limited at demonstrating an increased sensitivity to external calcium leading to lower Ca-EC50. Here we combine high resolution fluorescence based techniques and provide evidence that for the efficiency of calcium signaling system, cells expressing gain-of-function variants of CaSR monitor cytosolic and ER calcium levels increasing the expression of the Sarco-Endoplasmic Reticulum Calcium-ATPase (SERCA and reducing expression of Plasma Membrane Calcium-ATPase (PMCA. Wild-type CaSR (hCaSR-wt and its gain-of-function (hCaSR-R990G; hCaSR-N124K variants were transiently transfected in HEK-293 cells. Basal intracellular calcium concentration was significantly lower in cells expressing hCaSR-wt and its gain of function variants compared to mock. In line, FRET studies using the D1ER probe, which detects [Ca2+]ER directly, demonstrated significantly higher calcium accumulation in cells expressing the gain of function CaSR variants compared to hCaSR-wt. Consistently, cells expressing activating CaSR variants showed a significant increase in SERCA activity and expression and a reduced PMCA expression. This combined parallel regulation in protein expression increases the ER to cytosol calcium gradient explaining the higher sensitivity of CaSR gain-of-function variants to external calcium. This control principle provides a general explanation of how cells reliably connect (and exacerbate receptor inputs to cell function.

  9. Export spillovers

    DEFF Research Database (Denmark)

    Choquette, Eliane; Meinen, Philipp

    2015-01-01

    This paper studies the importance of export spillovers in a firm's decision to enter specific export markets and extends the current state of the literature by assessing different mechanisms through which they may occur, namely (i) labour movement, (ii) intra-industry spillovers and (iii) inter......-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...... the literature on export spillovers by presenting robust evidence of destination-specific export spillovers. The results suggest that labour mobility as well as intra- and inter-industry linkages (backward linkages) are important channels for export spillovers, while presenting heterogeneous effects across firms...

  10. 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....

  11. SEC16 in COPII coat dynamics at ER exit sites

    NARCIS (Netherlands)

    Sprangers, Joep; Rabouille, Catherine

    Protein export from the endoplasmic reticulum (ER), the first step in protein transport through the secretory pathway, is mediated by coatomer protein II (COPII)-coated vesicles at ER exit sites. COPII coat assembly on the ER is well understood and the conserved large hydrophilic protein Sec16

  12. A novel chromosome region maintenance 1-independent nuclear export signal of the large form of hepatitis delta antigen that is required for the viral assembly.

    Science.gov (United States)

    Lee, C H; Chang, S C; Wu, C H; Chang, M F

    2001-03-16

    Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus, as it requires hepatitis B virus for virion production and transmission. We have previously demonstrated that sequences within the C-terminal 19-amino acid domain flanking the isoprenylation motif of the large hepatitis delta antigen (HDAg-L) are important for virion assembly. In this study, site-directed mutagenesis and immunofluorescence staining demonstrated that in the absence of hepatitis B virus surface antigen (HBsAg), the wild-type HDAg-L was localized in the nuclei of transfected COS7 cells. Nevertheless, in the presence of HBsAg, the HDAg-L became both nuclei- and cytoplasm-distributed in about half of the cells. An HDAg-L mutant with a substitution of Pro-205 to alanine could neither form HDV-like particles nor shift the subcellular localization in the presence of HBsAg. In addition, nuclear trafficking of HDAg-L in heterokaryons indicated that HDAg-L is a nucleocytoplasmic shuttling protein. A proline-rich HDAg peptide spanning amino acid residues 198 to 210, designated NES(HDAg-L), can function as a nuclear export signal (NES) in Xenopus oocytes. Pro-205 is critical for the NES function. Furthermore, assembly of HDV is insensitive to leptomycin B, indicating that the NES(HDAg-L) directs nuclear export of HDAg-L to the cytoplasm via a chromosome region maintenance 1-independent pathway.

  13. Organizing export strategies.

    OpenAIRE

    G. Lojacono; M. Venzin

    2014-01-01

    The article unfolds as follows: after a brief introduction on the relevance of international trade and the characteristics of export strategies, we describe four distinct archetypes: export manager, centralistic export developer, export skimmer, integrated export developer.

  14. E2/ER β Enhances Calcineurin Protein Degradation and PI3K/Akt/MDM2 Signal Transduction to Inhibit ISO-Induced Myocardial Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Kuan-Ho Lin

    2017-04-01

    Full Text Available Secretion of multifunctional estrogen and its receptor has been widely considered as the reason for markedly higher frequency of heart disease in men than in women. 17β-Estradiol (E2, for instance, has been reported to prevent development of cardiac apoptosis via activation of estrogen receptors (ERs. In addition, protein phosphatase such as protein phosphatase 1 (PP1 and calcineurin (PP2B are also involved in cardiac hypertrophy and cell apoptosis signaling. However, the mechanism by which E2/ERβ suppresses apoptosis is not fully understood, and the role of protein phosphatase in E2/ERβ action also needs further investigation. In this study, we observed that E2/ERβ inhibited isoproterenol (ISO-induced myocardial cell apoptosis, cytochrome c release and downstream apoptotic markers. Moreover, we found that E2/ERβ blocks ISO-induced apoptosis in H9c2 cells through the enhancement of calcineurin protein degradation through PI3K/Akt/MDM2 signaling pathway. Our results suggest that supplementation with estrogen and/or overexpression of estrogen receptor β gene may prove to be effective means to treat stress-induced myocardial damage.

  15. A disease-associated frameshift mutation in caveolin-1 disrupts caveolae formation and function through introduction of a de novo ER retention signal.

    Science.gov (United States)

    Copeland, Courtney A; Han, Bing; Tiwari, Ajit; Austin, Eric D; Loyd, James E; West, James D; Kenworthy, Anne K

    2017-11-01

    Caveolin-1 (CAV1) is an essential component of caveolae and is implicated in numerous physiological processes. Recent studies have identified heterozygous mutations in the CAV1 gene in patients with pulmonary arterial hypertension (PAH), but the mechanisms by which these mutations impact caveolae assembly and contribute to disease remain unclear. To address this question, we examined the consequences of a familial PAH-associated frameshift mutation in CAV1 , P158PfsX22, on caveolae assembly and function. We show that C-terminus of the CAV1 P158 protein contains a functional ER-retention signal that inhibits ER exit and caveolae formation and accelerates CAV1 turnover in Cav1 -/- MEFs. Moreover, when coexpressed with wild-type (WT) CAV1 in Cav1 -/- MEFs, CAV1-P158 functions as a dominant negative by partially disrupting WT CAV1 trafficking. In patient skin fibroblasts, CAV1 and caveolar accessory protein levels are reduced, fewer caveolae are observed, and CAV1 complexes exhibit biochemical abnormalities. Patient fibroblasts also exhibit decreased resistance to a hypo-osmotic challenge, suggesting the function of caveolae as membrane reservoir is compromised. We conclude that the P158PfsX22 frameshift introduces a gain of function that gives rise to a dominant negative form of CAV1, defining a new mechanism by which disease-associated mutations in CAV1 impair caveolae assembly. © 2017 Copeland, Han, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  16. Nuclear import and export signals of human cohesins SA1/STAG1 and SA2/STAG2 expressed in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Leszek J Tarnowski

    Full Text Available BACKGROUND: Human SA/STAG proteins, homologues of the yeast Irr1/Scc3 cohesin, are the least studied constituents of the sister chromatid cohesion complex crucial for proper chromosome segregation. The two SA paralogues, SA1 and SA2, show some specificity towards the chromosome region they stabilize, and SA2, but not SA1, has been shown to participate in transcriptional regulation as well. The molecular basis of this functional divergence is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In silico analysis indicates numerous putative nuclear localization (NLS and export (NES signals in the SA proteins, suggesting the possibility of their nucleocytoplasmic shuttling. We studied the functionality of those putative signals by expressing fluorescently tagged SA1 and SA2 in the yeast Saccharomyces cerevisiae. Only the N-terminal NLS turned out to be functional in SA1. In contrast, the SA2 protein has at least two functional NLS and also two functional NES. Depending on the balance between these opposing signals, SA2 resides in the nucleus or is distributed throughout the cell. Validation of the above conclusions in HeLa cells confirmed that the same N-terminal NLS of SA1 is functional in those cells. In contrast, in SA2 the principal NLS functioning in HeLa cells is different from that identified in yeast and is localized to the C-terminus. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of the possibility of non-nuclear localization of an SA protein. The reported difference in the organization between the two SA homologues may also be relevant to their partially divergent functions. The mechanisms determining subcellular localization of cohesins are only partially conserved between yeast and human cells.

  17. Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells.

    Science.gov (United States)

    Mao, Zonglei; Zhou, Jin; Luan, Junwei; Sheng, Weihua; Shen, Xiaochun; Dong, Xiaoqiang

    2014-03-01

    Multidrug resistance (MDR), mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem limiting successful chemotherapy of gastric cancer. Tamoxifen (TAM), a triphenylethylene nonsteroidal antiestrogen agent, shows broad-spectrum antitumor properties. Emerging studies demonstrated that TAM could significantly reduce the MDR in a variety of human cancers. Here we investigated the effects and possible underlying mechanisms of action of TAM on the reversion of MDR in ER-negative human gastric cancer cells. Our results demonstrated that in MDR phenotype SGC7901/CDDP gastric cancer cells TAM dramatically lowered the IC50 of CDDP, 5-FU and ADM, increased the intracellular Rhodamine123 accumulation and induced G0/G1 phase arrest, while G2/M phase decreased accordingly. Furthermore, at the molecular level, TAM substantially decreased the expression of P-gp, p-Akt and the Akt-regulated downstream effectors such as p-GSK-3β, p-BAD, Bcl-XL and cyclinD1 proteins without affecting the expression of t-Akt, t-GSK-3β, t-BAD proteins in SGC7901/CDDP cells. Thus, our findings demonstrate that TAM reverses P-gp-mediated gastric cancer cell MDR via inhibiting the PI3K/Akt signaling pathway. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Silencing of BCR/ABL Chimeric Gene in Human Chronic Myelogenous Leukemia Cell Line K562 by siRNA-Nuclear Export Signal Peptide Conjugates.

    Science.gov (United States)

    Shinkai, Yasuhiro; Kashihara, Shinichi; Minematsu, Go; Fujii, Hirofumi; Naemura, Madoka; Kotake, Yojiro; Morita, Yasutaka; Ohnuki, Koichiro; Fokina, Alesya A; Stetsenko, Dmitry A; Filichev, Vyacheslav V; Fujii, Masayuki

    2017-06-01

    Herein we described the synthesis of siRNA-NES (nuclear export signal) peptide conjugates by solid phase fragment coupling and the application of them to silencing of bcr/abl chimeric gene in human chronic myelogenous leukemia cell line K562. Two types of siRNA-NES conjugates were prepared, and both sense strands at 5' ends were covalently linked to a NES peptide derived from TFIIIA and HIV-1 REV, respectively. Significant enhancement of silencing efficiency was observed for both of them. siRNA-TFIIIA NES conjugate suppressed the expression of BCR/ABL gene to 8.3% at 200 nM and 11.6% at 50 nM, and siRNA-HIV-1REV NES conjugate suppressed to 4.0% at 200 nM and 6.3% at 50 nM, whereas native siRNA suppressed to 36.3% at 200 nM and 30.2% at 50 nM. We could also show complex of siRNA-NES conjugate and designed amphiphilic peptide peptideβ7 could be taken up into cells with no cytotoxicity and showed excellent silencing efficiency. We believe that the complex siRNA-NES conjugate and peptideβ7 is a promising candidate for in vivo use and therapeutic applications.

  19. Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy

    Science.gov (United States)

    Giuliano, Mario; Hu, Huizhong; Wang, Yen-Chao; Fu, Xiaoyong; Nardone, Agostina; Herrera, Sabrina; Mao, Sufeng; Contreras, Alejandro; Gutierrez, Carolina; Wang, Tao; Hilsenbeck, Susan G.; De Angelis, Carmine; Wang, Nicholas J.; Heiser, Laura M.; Gray, Joe W.; Lopez-Tarruella, Sara; Pavlick, Anne C.; Trivedi, Meghana V.; Chamness, Gary C.; Chang, Jenny C.; Osborne, C. Kent; Rimawi, Mothaffar F.; Schiff, Rachel

    2015-01-01

    Purpose To investigate the direct effect and therapeutic consequences of epidermal growth factor receptor 2 (HER2)-targeting therapy on expression of estrogen receptor (ER) and Bcl2 in preclinical models and clinical tumor samples. Experimental design Archived xenograft tumors from two preclinical models (UACC812 and MCF7/HER2-18) treated with ER and HER2-targeting therapies, and also HER2+ clinical breast cancer specimens collected in a lapatinib neoadjuvant trial (baseline and week 2 post treatment), were used. Expression levels of ER and Bcl2 were evaluated by immunohistochemistry and western blot. The effects of Bcl2 and ER inhibition, by ABT-737 and fulvestrant respectively, were tested in parental versus lapatinib-resistant UACC812 cells in vitro. Results Expression of ER and Bcl2 was significantly increased in xenograft tumors with acquired resistance to anti-HER2 therapy, compared with untreated tumors, in both preclinical models (UACC812: ER p=0.0014; Bcl2 p<0.001. MCF7/HER2-18: ER p=0.0007; Bcl2 p=0.0306). In the neoadjuvant clinical study, lapatinib treatment for two weeks was associated with parallel upregulation of ER and Bcl2 (Spearman’s coefficient: 0.70; p=0.0002). Importantly, 18% of tumors originally ER-negative (ER−) converted to ER+ upon anti-HER2 therapy. In ER−/HER2+ MCF7/HER2-18 xenografts, ER re-expression was primarily observed in tumors responding to potent combination of anti-HER2 drugs. Estrogen deprivation added to this anti-HER2 regimen significantly delayed tumor progression (p=0.018). In the UACC812 cells, fulvestrant, but not ABT-737, was able to completely inhibit anti-HER2-resistant growth (p<0.0001). Conclusion HER2 inhibition can enhance or restore ER expression with parallel Bcl2 upregulation, representing an ER-dependent survival mechanism potentially leading to anti-HER2 resistance. PMID:26015514

  20. Deubiquitinase inhibitor b-AP15 activates endoplasmic reticulum (ER) stress and inhibits Wnt/Notch1 signaling pathway leading to the reduction of cell survival in hepatocellular carcinoma cells.

    Science.gov (United States)

    Ding, Youming; Chen, Xiaoyan; Wang, Bin; Yu, Bin; Ge, Jianhui

    2018-04-15

    b-AP15, a potent and selective inhibitor of the ubiquitin-specific peptidase 14 (USP14), displays in vitro and in vivo antitumor abilities on some types of cancer cells. However, the mechanism underlying its action is not well elucidated. The purposes of the present study are to observe the potential impacts of b-AP15 on cell survival of hepatocellular carcinoma cells and to investigate whether and how this compound inhibits some survival-promoting signaling pathways. We found that b-AP15 significantly decreased cell viability and increased cell apoptosis in a dose-dependent manner in hepatocellular carcinoma cells, along with the perturbation of cell cycle and the decreased expressions of cell cycle-related proteins. We also demonstrated that the endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were enhanced by b-AP15 supplementation. The inhibition of ER stress/UPR only partly attenuated the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. In addition, b-AP15 treatment inhibited Wnt/β-catenin and Notch1 signaling pathways, and suppressed phosphorylation of STAT3, Akt, and Erk1/2, which were not restored by the inhibition of ER stress/UPR. Furthermore, the expression levels of signaling molecules in Notch1 were reduced by specific inhibitor of Wnt/β-catenin pathway. Notably, either Wnt or Notch1 signaling inhibitor mitigated phosphorylation of STAT3, Akt, and Erk1/2, and mimicked the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. These results clearly indicate that b-AP15 induced cytotoxic response to hepatocellular carcinoma cells by augmenting ER stress/UPR and inhibiting Wnt/Notch1 signaling pathways. This new finding provides a novel mechanism by which b-AP15 produces its antitumor therapeutic effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Export regulation

    International Nuclear Information System (INIS)

    Gates, D.J.

    1978-01-01

    Australia is a major uranium supplier. Uranium is exported under conditions laid down to avoid any nuclear proliferation. On 24 May 1977 the Prime Minister had stated the main elements of Australian policy: the strengthening of the system of international safeguards and the selection of importing countries. (Non-nuclear weapon states must be Contracting Parties to the NPT. Nuclear weapon states must undertake not to use Australian uranium for this purpose). Australia retains property of the uranium up to the UF 6 stage (uranium hexafluoride) in the fuel cycle; it reserves the right to stop any export if the importing country no longer complies with AIEA Safeguards. Any transfer to a third country, any irradiated fuel reprocessing, requires Australia's prior agreement. Finally, importing countries must satisfy physical protection conditions. (NEA) [fr

  2. Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca(2+) regulation in airway smooth muscle (ASM).

    Science.gov (United States)

    Delmotte, Philippe; Sieck, Gary C

    2015-02-01

    Airway inflammation is a key aspect of diseases such as asthma. Several inflammatory cytokines (e.g., TNFα and IL-13) increase cytosolic Ca(2+) ([Ca(2+)]cyt) responses to agonist stimulation and Ca(2+) sensitivity of force generation, thereby enhancing airway smooth muscle (ASM) contractility (hyper-reactive state). Inflammation also induces ASM proliferation and remodeling (synthetic state). In normal ASM, the transient elevation of [Ca(2+)]cyt induced by agonists leads to a transient increase in mitochondrial Ca(2+) ([Ca(2+)]mito) that may be important in matching ATP production with ATP consumption. In human ASM (hASM) exposed to TNFα and IL-13, the transient increase in [Ca(2+)]mito is blunted despite enhanced [Ca(2+)]cyt responses. We also found that TNFα and IL-13 induce reactive oxidant species (ROS) formation and endoplasmic/sarcoplasmic reticulum (ER/SR) stress (unfolded protein response) in hASM. ER/SR stress in hASM is associated with disruption of mitochondrial coupling with the ER/SR membrane, which relates to reduced mitofusin 2 (Mfn2) expression. Thus, in hASM it appears that TNFα and IL-13 result in ROS formation leading to ER/SR stress, reduced Mfn2 expression, disruption of mitochondrion-ER/SR coupling, decreased mitochondrial Ca(2+) buffering, mitochondrial fragmentation, and increased cell proliferation.

  3. US exports

    International Nuclear Information System (INIS)

    Schrage, W.E.

    1991-01-01

    This paper reports on the past, present, and future of US coal exports. It is expected that in the 1990's, the following factors will be evident: Significant increases in coal production and port capacity in Australia and South Africa, but little in Canada; Potentially significant increase in coal production and port capacity in Colombia, Venezuela and Indonesia; Continued movement away from subsidized indigenous coal production in Europe and Japan. A substantial growth in world coal trade; Stronger growth in energy demand in the 1990s than in the 1980s; Significantly fewer additions to nuclear generating capacity in the 1990s than in the 1980s; Reduced coal production in Eastern Europe from that of the 1980s; Greater caution will be exercised in putting in new coal production capacity

  4. Coronavirus infection, ER stress and Apoptosis

    Directory of Open Access Journals (Sweden)

    TO SING eFUNG

    2014-06-01

    Full Text Available The replication of coronavirus, a family of important animal and human pathogens, is closely associated with the cellular membrane compartments, especially the endoplasmic reticulum (ER. Coronavirus infection of cultured cells was previously shown to cause ER stress and induce the unfolded protein response (UPR, a process that aims to restore the ER homeostasis by global translation shutdown and increasing the ER folding capacity. However under prolonged ER stress, UPR can also induce apoptotic cell death. Accumulating evidence from recent studies has shown that induction of ER stress and UPR may constitute a major aspect of coronavirus-host interaction. Activation of the three branches of UPR modulates a wide variety of signaling pathways, such as mitogen-activated protein (MAP kinases activation, autophagy, apoptosis and innate immune response. ER stress and UPR activation may therefore contribute significantly to the viral replication and pathogenesis during coronavirus infection. In this review, we summarize current knowledge on coronavirus-induced ER stress and UPR activation, with emphasis on their cross-talking to apoptotic signaling.

  5. Regulation of G-protein coupled receptor traffic by an evolutionary conserved hydrophobic signal.

    Science.gov (United States)

    Angelotti, Tim; Daunt, David; Shcherbakova, Olga G; Kobilka, Brian; Hurt, Carl M

    2010-04-01

    Plasma membrane (PM) expression of G-protein coupled receptors (GPCRs) is required for activation by extracellular ligands; however, mechanisms that regulate PM expression of GPCRs are poorly understood. For some GPCRs, such as alpha2c-adrenergic receptors (alpha(2c)-ARs), heterologous expression in non-native cells results in limited PM expression and extensive endoplasmic reticulum (ER) retention. Recently, ER export/retentions signals have been proposed to regulate cellular trafficking of several GPCRs. By utilizing a chimeric alpha(2a)/alpha(2c)-AR strategy, we identified an evolutionary conserved hydrophobic sequence (ALAAALAAAAA) in the extracellular amino terminal region that is responsible in part for alpha(2c)-AR subtype-specific trafficking. To our knowledge, this is the first luminal ER retention signal reported for a GPCR. Removal or disruption of the ER retention signal dramatically increased PM expression and decreased ER retention. Conversely, transplantation of this hydrophobic sequence into alpha(2a)-ARs reduced their PM expression and increased ER retention. This evolutionary conserved hydrophobic trafficking signal within alpha(2c)-ARs serves as a regulator of GPCR trafficking.

  6. CTR1 phosphorylates the central regulator EIN2 to control ethylene hormone signaling from the ER membrane to the nucleus in Arabidopsis

    Science.gov (United States)

    The gaseous phytohormone ethylene (C2H4) mediates numerous aspects of growth and development. Genetic analysis has identified a number of critical elements in the ethylene signaling (1), but how these elements interact biochemically to transduce the signal from the ethylene receptor complex at the e...

  7. Politik er ikke lykken

    DEFF Research Database (Denmark)

    Steenbuch, Johannes Aakjær

    2011-01-01

    Der er ikke længere nogen højere sandhed i livet end den, flertallet bestemmer sig for – og dermed ingen del af livet, der ikke er politisk. Højre- og venstrefløjen er i bund og grund enige - enige om, at det er politikernes opgave at forære os det gode liv. Dermed bliver demokratiet totalitært. ...

  8. Man er aldrig alene

    DEFF Research Database (Denmark)

    Hoffmeyer, Jesper

    2013-01-01

    Nu ved vi, at der er mange slags DNA i vores krop, og at samarbejdet mellem de organismer, som bærer alt dette DNA, er essentielt for vores overlevelse" … "Kroppen er en slags økosystem, hvor alle slags samarbejde hen ad vejen bliver afprøvet"...

  9. Exports and Job Training

    OpenAIRE

    Bastos, Paulo; Silva, Joana; Proenca, Rafael

    2016-01-01

    This paper examines whether export participation matters for job training. The paper draws on longitudinal worker-firm data for Brazilian manufacturing, linked with detailed records on training activity from the main provider. The analysis uses industry-specific exchange rate movements to generate exogenous variation in export status at the firm-level. The findings indicate that export par...

  10. Renewable energy export network

    International Nuclear Information System (INIS)

    Anon

    2000-01-01

    A Renewable Energy Exporters Network (REEN) has recently been established, following a meeting of renewable energy exporters and government agencies on 30 October 2000. REEN will assist the Australian renewable energy industry to take advantage of the opportunities offered by the burgeoning global market for renewable energy goods and services. Recent estimates of the significant potential global growth is renewable energy demand have reinforced the industry and Government's view that, in the medium to long-term, growth in the Australian renewable energy industry will largely depend on capturing export market share. Expanding the export market was identified as a crucial component in the Renewable Energy Action Agenda, developed jointly by industry and Government and released in June 2000. It was estimated that, for the industry to achieve its vision of sales of $4 billion per year by 2010, exports would need to comprise approximately 50% of the forecast growth in sales. As such, the need for a specific export strategy for the Australian renewable energy industry was recognised in the Action Agenda, and the establishment of the REEN is one of the first initiatives undertaken as part of the Renewable Energy Export Strategy. The REEN comprises approximately 50 export-ready renewable energy companies, the Department of Industry, Science and Resources, Austrade, and Stage Government agencies such as NSW's Sustainable Energy Development Authority. The Export Network will operate electronically, with face-to-face meetings held as appropriate. The Department of Industry, Science and Resources will facilitate the Export Network and has published a website at www.isr.gov.au/industry/reen. The site includes: a members directory; a discussion forum; information on opportunities to showcase Australian renewable; energy products and services; and Iinks to sites containing information that may be useful to renewable energy exporters. Other actions that are being undertaken as

  11. Ozone (O{sub 3}) elicits neurotoxicity in spinal cord neurons (SCNs) by inducing ER Ca{sup 2+} release and activating the CaMKII/MAPK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yun; Lin, Xiaowen; Zhao, XueJun; Xie, Juntian; JunNan, Wang; Sun, Tao; Fu, Zhijian, E-mail: zhijian_fu@163.com

    2014-11-01

    Ozone (O{sub 3}) is widely used in the treatment of spinal cord related diseases. Excess or accumulation of this photochemical air can however be neurotoxic. In this study, in vitro cultured Wister rat spinal cord neurons (SCNs) were used to investigate the detrimental effects and underlying mechanisms of O{sub 3}. Ozone in a dose-dependent manner inhibited cell viability at a range of 20 to 500 μg/ml, with the dose at 40 μg/ml resulting in a decrease of cell viability to 75%. The cell death after O{sub 3} exposure was related to endoplasmic reticulum (ER) calcium (Ca{sup 2+}) release. Intracellular Ca{sup 2+} chelator, ER stabilizer (inositol 1,4,5-trisphosphate receptor (IP3R) antagonist and ryanodine receptor (RyR) antagonist) and calcium/calmodulin-dependent protein kinase II (CaMKII) antagonist could effectively block Ca{sup 2+} mobilization and inhibit cell death following 40 μg/ml O{sub 3} exposure. In addition, ER Ca{sup 2+} release due to O{sub 3} exposure enhanced phospho-p38 and phospho-JNK levels and apoptosis of SCNs through activating CaMKII. Based on these results, we confirm that ozone elicits neurotoxicity in SCNs via inducing ER Ca{sup 2+} release and activating CaMKII/MAPK signaling pathway. Therefore, physicians should get attention to the selection of treatment concentrations of oxygen/ozone. And, approaches, such as chelating intracellular Ca{sup 2+} and stabilizing neuronal Ca{sup 2+} homeostasis could effectively ameliorate the neurotoxicity of O{sub 3}. - Highlights: • Exposure to O{sub 3} can reduce the viability of SCNs and cause the cell death. • Exposure to O{sub 3} can trigger RyR and IP3R dependent intracellular Ca{sup 2+} release. • Exposure to O{sub 3} can enhance the phospho-CaMKII, phospho-JNK and phospho-p38 levels.

  12. Exporting and Productivity

    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...

  13. Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes

    Science.gov (United States)

    Liu, Ming; Lara-Lemus, Roberto; Shan, Shu-ou; Wright, Jordan; Haataja, Leena; Barbetti, Fabrizio; Guo, Huan; Larkin, Dennis; Arvan, Peter

    2012-01-01

    Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an improper site, producing two subpopulations of molecules. Both show impaired oxidative folding and are retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER exit of coexpressed wild-type proinsulin, accounting for its dominant-negative behavior. Upon increased expression of ER–oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative folding of wild-type proinsulin improves, accelerating its ER export and increasing wild-type insulin production. We conclude that the efficiency of SP cleavage is linked to the oxidation of (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of the mutant as well as that of coexpressed wild-type proinsulin. Improving oxidative folding of wild-type proinsulin may provide a feasible way to rescue insulin production in patients with MIDY. PMID:22357960

  14. Intracellular trafficking of LET-756, a fibroblast growth factor of C. elegans, is controlled by a balance of export and nuclear signals

    International Nuclear Information System (INIS)

    Popovici, Cornel; Fallet, Mathieu; Marguet, Didier; Birnbaum, Daniel; Roubin, Regine

    2006-01-01

    The superfamily of fibroblast growth factors (FGF), which counts 22 members in humans, exerts many functions during animal development and adult life. LET-756 is one of the two FGFs of the nematode C. elegans. Re-introduction of LET-756 in a null mutant strain restores viability, allowing the study of structural requirements for LET-756 trafficking and function. LET-756 protein has several regions and motifs, including a non-classical internal motif required for secretion. We show here that a main difference in the wild-type LET-756 molecule and a truncated molecule that mimics a partial loss-of-function mutant lies on subnuclear expression. Using Cos-1 cells and rescue activity we show that: (i) nuclear localization is due to various redundant NLS, one of them acting as a nucleolar localization signal; (ii) nuclear LET-756 is addressed to the speckles by a stretch of glutamine residues; (iii) nuclear LET-756 is trafficking between speckles and nucleoli; (iv) in the nucleolus, LET-756 is associated with proteins of the rRNA splicing compartment; (v) changing LET-756 secretion signal prevents its nuclear localization. We propose that LET-756 exerts its functions through a balance between secreted and nuclear forms due to two opposite addressing signals (i) synergy of several NLS and (ii) attenuated secretion signal

  15. Vreden er over os

    DEFF Research Database (Denmark)

    Mehlsen, Camilla

    2006-01-01

    Urolige elever, cyklister - der giver fuck-finger, aggressive demonstranter. Samtiden er på vej ind i en æra domineret af vrede, siger rektor Lars-Henrik Schmidt, der er aktuel med bogen 'Om vreden'. Udgivelsesdato: Juni......Urolige elever, cyklister - der giver fuck-finger, aggressive demonstranter. Samtiden er på vej ind i en æra domineret af vrede, siger rektor Lars-Henrik Schmidt, der er aktuel med bogen 'Om vreden'. Udgivelsesdato: Juni...

  16. Exporter Price Premia?

    DEFF Research Database (Denmark)

    Jäkel, Ina Charlotte; Sørensen, Allan

    This paper provides new evidence on manufacturing firms' output prices: in Denmark, on average, exported varieties are sold at a lower price (i.e. a negative exporter price premium) relative to only domestically sold varieties. This finding stands in sharp contrast to previous studies, which have...... found positive exporter price premia. We also document that the exporter price premium varies substantially across products (both in terms of sign and magnitude). We show that in a standard heterogeneous firms model with heterogeneity in quality as well as production efficiency there is indeed no clear......-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...

  17. Characterization of the ER-Targeted Low Affinity Ca2+ Probe D4ER

    Directory of Open Access Journals (Sweden)

    Elisa Greotti

    2016-09-01

    Full Text Available Calcium ion (Ca2+ is a ubiquitous intracellular messenger and changes in its concentration impact on nearly every aspect of cell life. Endoplasmic reticulum (ER represents the major intracellular Ca2+ store and the free Ca2+ concentration ([Ca2+] within its lumen ([Ca2+]ER can reach levels higher than 1 mM. Several genetically-encoded ER-targeted Ca2+ sensors have been developed over the last years. However, most of them are non-ratiometric and, thus, their signal is difficult to calibrate in live cells and is affected by shifts in the focal plane and artifactual movements of the sample. On the other hand, existing ratiometric Ca2+ probes are plagued by different drawbacks, such as a double dissociation constant (Kd for Ca2+, low dynamic range, and an affinity for the cation that is too high for the levels of [Ca2+] in the ER lumen. Here, we report the characterization of a recently generated ER-targeted, Förster resonance energy transfer (FRET-based, Cameleon probe, named D4ER, characterized by suitable Ca2+ affinity and dynamic range for monitoring [Ca2+] variations within the ER. As an example, resting [Ca2+]ER have been evaluated in a known paradigm of altered ER Ca2+ homeostasis, i.e., in cells expressing a mutated form of the familial Alzheimer’s Disease-linked protein Presenilin 2 (PS2. The lower Ca2+ affinity of the D4ER probe, compared to that of the previously generated D1ER, allowed the detection of a conspicuous, more clear-cut, reduction in ER Ca2+ content in cells expressing mutated PS2, compared to controls.

  18. 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...... of firm productivity. This retooling addresses several shortcomings. First, the imperfect correlation of demands reconciles the sales variation observed in and across destinations. Second, since demands for the firm's output are correlated across destinations, a firm can use previously realized demands...... 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...

  19. Hvad f er meningen?

    DEFF Research Database (Denmark)

    Rydén, Pernille; Ringberg, Torsten; Wilke, Ricky

    En forskningsrapport fra CBS om danske lederes opfattelse af sociale medier i detail- og servicebranchen. Rapporten er udarbejdet i regi af Service Platform.......En forskningsrapport fra CBS om danske lederes opfattelse af sociale medier i detail- og servicebranchen. Rapporten er udarbejdet i regi af Service Platform....

  20. Fluxus-øer

    DEFF Research Database (Denmark)

    van der Meijden, Peter Alexander

    2008-01-01

    "Fluxus-øer" er en introduktion til Fluxus med udgangspunkt i den tyske galleri-ejer René Blocks samling, som udstillingen "Food for Thought" i Sukkerfabrikken i Stege (Møn) præsenterede et udvalg af. Artiklen beskriver Fluxus som et heterotopi som beskrevet af Michel Foucault i "Of Other Spaces"...

  1. MIT HJEM ER HVOR MIT HJERTE ER

    DEFF Research Database (Denmark)

    Høst, Jeppe Engset

    2014-01-01

    Ideen om at arbejde med det man kalder de stedbundne ressourcer på en ny måde, er relevant på Bornholm hvor events som blandt andet festivalen ’Wonderfestiwall’, strandfesten ’Vang Pier Beach Party’, karnevallet ’Svaneke Beach Party, kokkekonkurrencen ’Sol over Gudhjem’ og filmfestivalen ’Bornsho...

  2. 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...

  3. 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 traditi...

  4. 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)

  5. Hvor anvendelig er PKI?

    OpenAIRE

    Nielsen, Jon Magne

    2006-01-01

    Denne oppgaven ser på bruken av elektronisk ID i statlige etater i Norge i dag. Det ses spesielt på om bruken av tekologien PKI er en god løsning på etatenes behov på dette området. Som utgangspunkt for analysen er det sett spesielt på to statlige etater. Disse etatenes behov og bruk av elektronisk ID generelt og PKI spesielt blir undersøkt. Det er videre gjort rede for hvilke lover, forskrifter og andre førende dokumenter som danner de formelle rammebetingelsene for etaters bruk av PKI. ...

  6. Iran, a gas exporter?

    International Nuclear Information System (INIS)

    Therme, C.

    2008-01-01

    The development of the gas sector has not allowed, up to now, Iran to become one of the main gas actors, whether it is on the regional or international market. This under-development of the gas sector finds expression, each winter, through the Iranian incapability to satisfy its domestic demand as well as its exportation commitments to Turkey or Armenia. In this study, the author tries to examine the origins of Iranian difficulties to increase its gas production and to abide by its commitments to export gas to other countries. The possibility of gas exportation from Iran to the European Union is also discussed

  7. Markups and Exporting Behavior

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic Michel Patrick

    2012-01-01

    In this paper, we develop a method to estimate markups using plant-level production data. Our approach relies on cost minimizing producers and the existence of at least one variable input of production. The suggested empirical framework relies on the estimation of a production function and provides...... 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......, on average, higher markups and that markups increase upon export entry....

  8. 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

  9. Innovation er brugerdreven!

    DEFF Research Database (Denmark)

    Helms, Niels Henrik

    2008-01-01

    Brugerdreven innovation er blevet svaret på mange af de udfordringer, som vores moderne samfund står overfor.Det er skrevet ind i såvel regeringsgrundlaget som i de forskellige tiltag, som skal ruste Danmark i forhold til globaliseringen. Vi har ifølge argumentationen her enrække særlige forudsæt....... Udgivelsesdato: marts 2008...

  10. Metabolomics er fremtiden

    DEFF Research Database (Denmark)

    Pedersern, Birger

    2010-01-01

    Forskningen i fødevarer har fået et potent redskab i hånden. Metabolomics er vejen frem, mener professor Søren Balling Engelsen fra Københavns Universitet......Forskningen i fødevarer har fået et potent redskab i hånden. Metabolomics er vejen frem, mener professor Søren Balling Engelsen fra Københavns Universitet...

  11. Er KU et mobbeuniversitet?

    DEFF Research Database (Denmark)

    Olden-Jørgensen, Sebastian

    2009-01-01

    Ansatte på KU mobber hverken mere eller mindre end på andre danske arbejdspladser. Mediernes dækning af APV-undersøgelsens resultater mht. mobning er sensationalistisk og delvis vildledende.......Ansatte på KU mobber hverken mere eller mindre end på andre danske arbejdspladser. Mediernes dækning af APV-undersøgelsens resultater mht. mobning er sensationalistisk og delvis vildledende....

  12. Er jeres ledere 'likeable'?

    DEFF Research Database (Denmark)

    Nielsen, Rikke Kristine

    2013-01-01

    Færdigheder: Oftest er lederne langtfra de første til at kaste sig over ny teknologi. It-kundskaberne på chefgangen trænger til en opgradering.......Færdigheder: Oftest er lederne langtfra de første til at kaste sig over ny teknologi. It-kundskaberne på chefgangen trænger til en opgradering....

  13. er 1999

    DEFF Research Database (Denmark)

    Jensen, J. P.; Søndergaard, M.; Jeppesen, E.

    små cladoceer og hjuldyr, og især er maksimumsforekom-sterne af calanoide vandlopper og de små og store cladoceer og daf-nier gået tilbage. Den gennemsnitlige biomasse af dafnier er derimod øget især p.g.a. stigning i de 25 % af søerne med størst forekomster. Dyreplanktons græsning Betragtet under et...

  14. er 2000

    DEFF Research Database (Denmark)

    Jensen, J. P.; Søndergaard, M.; Jeppesen, E.

    styrke det fagli-ge grundlag for de mil-jøpolitiske prioriteringer og beslut-ninger. En væsentlig del af denne opgave er overvågning af miljø og natur. Det er derfor et naturligt led i Danmarks Miljø-undersø-gelsers opgave at forestå den landsdækkende rapportering af overvågnings-program-met inden...

  15. Arctigenin alleviates ER stress via activating AMPK

    Science.gov (United States)

    Gu, Yuan; Sun, Xiao-xiao; Ye, Ji-ming; He, Li; Yan, Shou-sheng; Zhang, Hao-hao; Hu, Li-hong; Yuan, Jun-ying; Yu, Qiang

    2012-01-01

    Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5 and 10 μmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 μmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 μmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 μmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 μmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 β cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. PMID:22705729

  16. Coal exports still growing

    International Nuclear Information System (INIS)

    Blain, M.

    1998-01-01

    It is shown that the swings and roundabouts of the Asian economic shake out and Australian dollar devaluation are starting to work their way through the Australian export coal market. Perhaps somewhat surprisingly, at this stage the results are not proving to be as bad as were at first predicted by some market watchers. Export revenue and tonnages are up 12% for the year to July 98. Coal exports totaling $9.5 billion left Australia's shores in the 12 months confirming coal as Australia's single largest export revenue earner. Sales volumes in the present financial year are still increasing, the market being driven by steadily increasing Asian demand for steaming coal from places like Korea, Malaysia, Thailand and the Philippines

  17. 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 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......, it is predominantly the marketing-related investment decisions associated with starting to export that lead to increases in firm productivity. We conclude that learning-by-exporting might be more properly characterized as ?learning about and exploiting new markets? rather than ?learning about new technologies...

  18. Quebec's electricity exports

    International Nuclear Information System (INIS)

    Averyt, W.F.

    1992-01-01

    In 1987 Hydro-Quebec exported over 16 TWh to New England and New York and it plans to export 3,500 MW of firm power, not interruptible, by the early 2000s. It estimates that the northeast US market has an additional potential of 9,000 MW. The export market has become more difficult than anticipated. The federal/state regulatory framework for electricity generation was changing - it encouraged small scale generation, cogeneration and conservation which decreased demand. Demand for power imports has also been influenced by pricing judgements and avoided costs. Environmental concerns and Native protest have become increasingly important factors affecting future export sales and hence the proposed James Bay developments. Regulatory changes affecting supply and pricing, concerns about continental impacts, about further development of electrical sources together with Native requirements will further complicate the Quebec-US electricity trade. (author)

  19. Nuclear export controls

    International Nuclear Information System (INIS)

    Thorne, C.E.

    1999-01-01

    One approach to describing the multilateral nuclear export controls is to do it according to time. This led to an interesting discovery, i.e. multilateral export controls have been defined by four distinct periods, the forst two of abut five years each, the second two about twice as long. These time periods have another interesting property. The two suppliers groups, which we will discuss in detail, have alternated in dominance over nearly thirty years. After describing the historical developments, the status of the present situation in multilateral nuclear export controls is examined, with the strengths and weaknesses. The future of multilateral nuclear export controls and possible ways that might be taken are considered

  20. 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

  1. 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)

  2. IMPACTS OF OLYMPICS ON EXPORTS AND TOURISM

    OpenAIRE

    Wonho Song

    2010-01-01

    There have been debates on the effects of Olympics on economy. Previous studies estimated the direct benefits and costs of Olympic Games, and concluded that the net effects were positive or negative depending on specific assumptions used for evaluations. Recent studies turn attentions to indirect benefits. For example, signaling model by Rose and Spiegel (2010) argues that mega events are the signals of liberalization the country sends, and that the hosting of mega events spurs exports. This ...

  3. Canada's reactor exports

    International Nuclear Information System (INIS)

    Morrison, R.W.

    1981-01-01

    A brief sketch of the development of Canada's nuclear exports is presented and some of the factors which influence the ability to export reactors have been identified. The potential market for CANDUs is small and will develop slowly. The competition will be tough. There are few good prospects for immediate export orders in the next two or three years. Nonetheless there are reasonable opportunities for CANDU exports, especially in the mid-to-late 1980s. Such sales could be of great benefit to Canada and could do much to sustain the domestic nuclear industry. Apart from its excellent economic and technical performance, the main attraction of the CANDU seems to be the autonomy it confers on purchasing countries, the effectiveness with which the associated technology can be transferred, and the diversification it offers to countries which wish to reduce their dependence on the major industrial suppliers. Each sales opportunity is unique, and marketing strategy will have to be tailored to the customer's needs. Over the next decade, the factors susceptible to Canadian government action which are most likely to influence CANDU exports will be the political commitment of the government to those reactor exports, the performance established by the four 600 MWe CANDUs now nearing completion, the continuing successful operation of the nuclear program in Ontario, and the co-ordination of the different components of Canada's nuclear program (AECL, nuclear industry, utilities, and government) in putting forth a coherent marketing effort and following through with effective project management

  4. An exporter's checklist

    International Nuclear Information System (INIS)

    Englot, P.

    1995-01-01

    The benefits of exporting goods and services was discussed. The article listed a summary of issues which could be referred to to assist with the development of an effective plan to export. Some issues to consider were: (1) analysis of the export market, such as political and cultural issues, local legislation, competition, infrastructure, transportation and logistics, (2) internal issues, such as people, equipment, capital, time, understanding of the risks, relocation and identification of all costs, (3) sources of support such as banks, government and transporters, (4) development of a solid payment plan. It was concluded that exporting was not for the faint-hearted. It can be expensive, and time consuming, however, if approached in the right spirit it could be highly rewarding. As a rule of thumb, the probability of success was said to be directly related to the amount of effort put into the preparatory phase. Potential exporters were reminded of the very strong infrastructure that exists in Canada to promote and support export initiatives, including all levels of government, financial institutions, freight forwarders and innumerable consultant/specialists

  5. Indonesian coal export potential

    International Nuclear Information System (INIS)

    Millsteed, Ch.; Jolly, L.; Stuart, R.

    1993-01-01

    Indonesia's coal mining sector is expanding rapidly. Much of the increase in coal production since the mid-1980s has been exported. Indonesian coal mining companies have large expansion programs and continuing strong export growth is projected for the remainder of the 1990s. The low mining costs of indonesian coal, together with proximity to Asian markets, mean that Indonesia is well placed to compete strongly with other thermal coal exporters and win market share in the large and expanding thermal coal market in Asia. However, there is significant uncertainty about the likely future level of Indonesia's exportable surplus of coal. The government's planned expansion in coal fired power generation could constrain export growth, while the ability of producers to meet projected output levels is uncertain. The purpose in this article is to review coal supply and demand developments in Indonesia and, taking account of the key determining factors, to estimate the level of coal exports from Indonesia to the year 2000. This time frame has been chosen because all currently committed mine developments are expected to be on stream by 2000 and because it is difficult to project domestic demand for coal beyond that year. 29 refs., 8 tabs., 7 figs

  6. Export Taxes under Bertrand Duopoly

    OpenAIRE

    David Collie; Roger Clarke

    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...

  7. Rab7a modulates ER stress and ER morphology.

    Science.gov (United States)

    Mateus, Duarte; Marini, Elettra Sara; Progida, Cinzia; Bakke, Oddmund

    2018-05-01

    The Endoplasmic Reticulum (ER) is a membranous organelle with diverse structural and functional domains. Peripheral ER includes interconnected tubules, and dense tubular arrays called "ER matrices" together with bona fide flat cisternae. Transitions between these states are regulated by membrane-associated proteins and cytosolic factors. Recently, the small GTPases Rab10 and Rab18 were reported to control ER shape by regulating ER dynamics and fusion. Here, we present evidence that another Rab protein, Rab7a, modulates the ER morphology by controlling the ER homeostasis and ER stress. Indeed, inhibition of Rab7a expression by siRNA or expression of the dominant negative mutant Rab7aT22 N, leads to enlargement of sheet-like ER structures and spreading towards the cell periphery. Notably, such alterations are ascribable neither to a direct modulation of the ER shaping proteins Reticulon-4b and CLIMP63, nor to interactions with Protrudin, a Rab7a-binding protein known to affect the ER organization. Conversely, depletion of Rab7a leads to basal ER stress, in turn causing ER membrane expansion. Both ER enlargement and basal ER stress are reverted in rescue experiments by Rab7a re-expression, as well as by the ER chemical chaperone tauroursodeoxycholic acid (TUDCA). Collectively, these findings reveal a new role of Rab7a in ER homeostasis, and indicate that genetic and pharmacological ER stress manipulation may restore ER morphology in Rab7a silenced cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. GR and ER co-activation alters the expression of differentiation genes and associates with improved ER+ breast cancer outcome

    Science.gov (United States)

    West, Diana C.; Pan, Deng; Tonsing-Carter, Eva Y.; Hernandez, Kyle M.; Pierce, Charles F.; Styke, Sarah C.; Bowie, Kathleen R.; Garcia, Tzintzuni I.; Kocherginsky, Masha; Conzen, Suzanne D.

    2016-01-01

    In estrogen receptor (ER)-negative breast cancer (BC), high tumor glucocorticoid receptor (GR) expression has been associated with a relatively poor outcome. In contrast, using a meta-analysis of several genomic datasets, here we find that tumor GR mRNA expression is associated with improved ER+ relapse-free survival (RFS) (independently of progesterone receptor (PR) expression). To understand the mechanism by which GR expression is associated with a better ER+ BC outcome, the global effect of GR-mediated transcriptional activation in ER+ BC cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in ER+/GR+ MCF-7 cells revealed that upon co-activation of GR and ER, GR chromatin association became enriched at proximal promoter regions. Furthermore, following ER activation, increased GR chromatin association was observed at ER, FOXO, and AP1 response elements. In addition, ER associated with GR response elements, suggesting that ER and GR interact in a complex. Co-activation of GR and ER resulted in increased expression (relative to ER activation alone) of transcripts that encode proteins promoting cellular differentiation (e.g. KDM4B, VDR) and inhibiting the Wnt-signaling pathway (IGFBP4). Finally, expression of these individual pro-differentiation genes was associated with significantly improved RFS in ER+ BC patients. Together, these data suggest that the co-expression and subsequent activity of tumor cell GR and ER contribute to the less aggressive natural history of early-stage BC by coordinating the altered expression of genes favoring differentiation. Implications The interaction between estrogen and glucocorticoid receptor activity highlights the importance of context-dependent nuclear receptor function in cancer. PMID:27141101

  9. Jeg Er blevet FRANKofil

    DEFF Research Database (Denmark)

    Andersson, Lasse

    2014-01-01

    afhængig af Frank Underwood fra serien House of Cards på den fremadstormende TV-streamingstjenesten Netflix. Jeg har opdaget et nyt internetbaseret datingforhold. Et surrealt, fedt miks af det kyniske og joviale personificeret i karakteren Frank Underwood, som er helt igennem ubehagelig, men fantastisk...... spillet af Kevin Spacey. Og tak til Spacey der for en tid har forladt teateret ’The Old Vic’ i London for at begejstre mig. Der er generelt to årsager til mine FRANKofile tilbøjeligheder. For det første er Netflix’s remake af den tyve år gamle BBC serie House of Cards efter min menig et stykke tv...... anden grund, til at jeg er blevet Frankofil, er, at jeg ikke skal sidde og vente på næste søndag efter søndag efter søndag for at få lov at se næste afsnit. Netflix lagde alle tretten timer af sæson 2 ud på nettet. Jeg afgør selv, hvornår jeg skal have mere Frank! Men på trods af mit narkomanlignende...

  10. International marketing and export management

    DEFF Research Database (Denmark)

    Strandskov, Jesper; Albaum, Gerald; Duerr, Edwin C.

    Fremstillingen er en lærebog inden for international markedsføring. Bogen består af ialt 14 kapitler og er en 2. revideret udgave af 1989-bogen. Revisionen er gennemgribende idet den omfatter en række nye cases (også danske), der er tilføjet to nye kapitler om henholdsvis 'Eksportsamarbejde og st...

  11. Ondskaben er fortryllende

    DEFF Research Database (Denmark)

    Schubart, Rikke

    2013-01-01

    Indlæg om tv-serien Once Upon a Time (2011-), der hører til genren fairytale fantasy, der blander eventyr og fantasy. Her bliver alle eventyr brugt i en fortælling om alle beboere i en lille by, der ikke ved, at de i virkeligheden er eventyr-karakterer.......Indlæg om tv-serien Once Upon a Time (2011-), der hører til genren fairytale fantasy, der blander eventyr og fantasy. Her bliver alle eventyr brugt i en fortælling om alle beboere i en lille by, der ikke ved, at de i virkeligheden er eventyr-karakterer....

  12. Coal export facilitation

    International Nuclear Information System (INIS)

    Eeles, L.

    1998-01-01

    There is a wide range of trade barriers, particularly tariffs, in current and potential coal market. Commonwealth departments in Australia play a crucial role in supporting government industry policies. This article summarises some of more recent activities of the Department of Primary Industries and Energy (DPIE) in facilitating the export of Australian Coals. Coal export facilitation activities are designed to assist the Australian coal industry by directing Commonwealth Government resources towards issues which would be inappropriate or difficult for the industry to address itself

  13. Canada's nuclear export policy

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, R W; Wonder, E F [Carleton Univ., Ottawa, Ontario (Canada)

    1978-01-01

    The factors influencing the evolution of Canada's nuclear export policy are examined. Initially, nuclear technology was exported to establish an industry in Canada and to share the technology with other countries. After 1974 an increasingly broad range of political and social factors were taken into account and safeguards became the dominant factor. The indirect impacts of the new policy fall into two groups. One consists of the effects of Canada's leadership in taking a tough stand on safeguards. The second group of effects involve the concern of other countries about access to secure energy supplies and advanced technology.

  14. Canada's nuclear export policy

    International Nuclear Information System (INIS)

    Morrison, R.W.; Wonder, E.F.

    1978-01-01

    The factors influencing the evolution of Canada's nuclear export policy are examined. Initially, nuclear technology was exported to establish an industry in Canada and to share the technology with other countries. After 1974 an increasingly broad range of political and social factors were taken into account and safeguards became the dominant factor. The indirect impacts of the new policy fall into two groups. One consists of the effects of Canada's leadership in taking a tough stand on safeguards. The second group of effects involve the concern of other countries about access to secure energy supplies and advanced technology. (O.T.)

  15. Scenen er blevet din

    DEFF Research Database (Denmark)

    Helms, Niels Henrik

    2008-01-01

    Verden kan betragtes som en skueplads med mange forskellige scener. I bidrgaet vil læseren kunne stifte bekendtskab med forskellige refleksioner over netop denne metaforik som analyseoptik i forhold til begrebet innovation. Afsættet er ønsket om at finde en måde at analysere og begrebsliggøre inn...

  16. Er tang fremtidens superfood?

    DEFF Research Database (Denmark)

    Holdt, Susan Løvstad

    seneste år fået øjnene op for tang indenfor områderne: biokemikalier og bioaktive stoffer, ekstraktion, gastronomi, produktudvikling, foder, bioraffinaderier, dyrkning osv. Men hvad er det tang kan? Dette foredrag vil vise at vi med tangdyrkning kan rykke mere bæredygtig fødevareproduktion ud på havet...

  17. Ideologi er noget bras

    DEFF Research Database (Denmark)

    Hansen, Brian Benjamin; Bjerre, Henrik Jøker

    fra den slovenske filosof Slavoj Zizek stilles imidlertid det spørgsmål i bogen, om ideologien idag ikke blot har taget en anden form. Vi lever i dag ikke i post-ideologiske tider. Snarere er braset selv – X Factor, forbrugsobjekter, underholdning, følelser og balloner – blevet den næsten usynlige...

  18. Riget - alt er tilladt

    DEFF Research Database (Denmark)

    2017-01-01

    Riget indtager en nøglestilling, når overgangen mellem faser i Triers produktion skal karakteriseres. Riget danner bro mellem den billedfascination og de radikale stileksperimenter, der præger Triers tidlige produktion, og den genre- og plotbevidsthed, der er typisk for film som Breaking the Waves...

  19. Hvad er tidligt sprog

    DEFF Research Database (Denmark)

    Skriver Jensen, Anders

    2009-01-01

    Forfatteren argumenterer for at "early literacy" kan oversættes til "tidligt sprog"; særligt når der er tale om en helhedsorienteret tilgang med vægt på sprog som et alsidigt medie for kommunikation- og betydningsskabelse. Med inspiration fra Jerome Bruners kulturpsykologi diskuteres mulige...

  20. Er danskerne racister

    DEFF Research Database (Denmark)

    Bech, Henning; Necef, Mehmet Ümit

    Igennem de seneste årtier er det blevet almindeligt at tale om, at der er en udbredt racisme i Danmark. Påstande om danskernes racisme, fremmedhad og diskrimination optræder dagligt i offentligheden og i medierne, og der henvises ofte til, hvad ’forskerne’ og de ’videnskabelige undersøgelser’ siger...... om emnet. Der kan da næppe heller være tvivl om, at der forekommer racistiske holdninger hos nogle danskere. Men er problemet så stort, som det gøres til i den offentlige debat? Bogen ønsker at afklare, hvorvidt der er videnskabelig dokumentation for påstandene om danskernes racisme. Den går i dybden...... med en række forskeres og eksperters udtalelser på området og præsenterer en grundig analyse af deres fremstilling af dansk racisme i forhold til emner som kultur, seksualitet, kriminalitet og arbejdsmarked....

  1. Herp enhances ER-associated protein degradation by recruiting ubiquilins

    International Nuclear Information System (INIS)

    Kim, Tae-Yeon; Kim, Eunmin; Yoon, Sungjoo Kim; Yoon, Jong-Bok

    2008-01-01

    ER-associated protein degradation (ERAD) is a protein quality control system of ER, which eliminates misfolded proteins by proteasome-dependent degradation and ensures export of only properly folded proteins from ER. Herp, an ER membrane protein upregulated by ER stress, is implicated in regulation of ERAD. In the present study, we show that Herp interacts with members of the ubiquilin family, which function as a shuttle factor to deliver ubiquitinated substrates to the proteasome for degradation. Knockdown of ubiquilin expression by small interfering RNA stabilized the ERAD substrate CD3δ, whereas it did not alter or increased degradation of non-ERAD substrates tested. CD3δ was stabilized by overexpressed Herp mutants which were capable of binding to ubiquilins but were impaired in ER membrane targeting by deletion of the transmembrane domain. Our data suggest that Herp binding to ubiquilin proteins plays an important role in the ERAD pathway and that ubiquilins are specifically involved in degradation of only a subset of ubiquitinated targets, including Herp-dependent ERAD substrates

  2. Correlations-Adjusted Export Market Diversification

    OpenAIRE

    Jung Joo La

    2011-01-01

    This paper introduces new export market diversification indices incorporated with correlations of business cycles among export partners to identify the actual effects of export market diversification on export instability. Three existing export market diversification indices reflect the dispersion level in terms of the number of export partners and their export shares, without a clear control for correlations among export earnings from export partners. In addition, they are underestimated or ...

  3. Composition of Exports and Export Performance of Eurozone Countries

    NARCIS (Netherlands)

    Wierts, P.J.; Kerkhoff, H.; de Haan, J.

    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

  4. Er HR ude i tovene?

    DEFF Research Database (Denmark)

    Poulfelt, Flemming

    2015-01-01

    HR: Er der behov for nytænkning i HR-land? Artikler i Harvard Business Review - bakket op af en dansk undersøgelse - konkluderer, at HR stadig mangler gennemslagskraft i virksomhederne. Er HR ude i tovene? ... For i undersøgelsen "Ny Dansk Ledelse" (maj 2015), som er baseret på danske lederes...

  5. Facebook er internettet nu

    DEFF Research Database (Denmark)

    Tække, Jesper

    2014-01-01

    Den store vision for world wide web var, at alle kunne få ubegrænset adgang til alverdens information. www var mangfoldigt og anarkistisk. I dag er der rigtig mange, der kun bruger nettet til at være på Facebook. Hvad bruger Facebook det til? Og hvad gør det ved vores udsyn?......Den store vision for world wide web var, at alle kunne få ubegrænset adgang til alverdens information. www var mangfoldigt og anarkistisk. I dag er der rigtig mange, der kun bruger nettet til at være på Facebook. Hvad bruger Facebook det til? Og hvad gør det ved vores udsyn?...

  6. Hvad er en by?

    DEFF Research Database (Denmark)

    Parby, Jakob; Thelle, Mikkel

    2011-01-01

    Nytænkning. Med de moderne megabyer er det slut med at forestille sig byen som noget, man planlægger og giver form. Vi skal lære at se dem som vildtvoksende urbane landskaber. Artikel om megabyer, byudvikling og forestillingen om byen gennem tiderne. Skrevet delvist i anledning af åbningen af...... udstillingen Citambulos på Københavns Museum, der handlede om Mexico City....

  7. Exporting Humanist Architecture

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2016-01-01

    The article is a chapter in the catalogue for the Danish exhibition at the 2016 Architecture Biennale in Venice. The catalogue is conceived at an independent book exploring the theme Art of Many - The Right to Space. The chapter is an essay in this anthology tracing and discussing the different...... 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...

  8. Nuclear exporters cartel

    International Nuclear Information System (INIS)

    Mandelbaum, M.

    1977-01-01

    Events that have transpired in the past few years that have caused renewed concern about the spread of nuclear weapons are reviewed. Many proposals have been made recently for keeping the bomb from spreading. The author feels that the most novel and intriguing of them is the one advanced by Senator Abraham Ribicoff and Steven J. Baker; in their proposal, the world market for nuclear reactors would be divided into precisely defined shares among the industrial nations that now manufacture them for export; each exporter would be guaranteed a certain number of sales annually; and each would pledge not to sell uranium enrichment or plutonium reprocessing technology, as Germany did to Brazil. This might not halt proliferation, but it would give the world a few more years to find a solution

  9. Export development financing

    International Nuclear Information System (INIS)

    Balint, J.

    1995-01-01

    The main activities of the Export Development Corporation (EDC) were described, as well as some of the changes currently being implemented. EDC is Canada's official export credit agency, providing risk management services such as insurance, loans, guarantees, equity and leasing. EDC's project finance initiative started in 1991, and focused mainly on the up-front process. It has established itself as a recognized leader in project financing. It has over 15 years experience in a variety of sectors and countries. Energy projects financed to date include hydro projects in India, Argentina and Pakistan, and thermal projects in Thailand, China, Indonesia and Egypt. Lending criteria used to select projects were outlined, along with the risks endemic to project financing

  10. Are Competitors' Free Trade Agreements Putting U.S. Agricultural Exporters at a Disadvantage?

    OpenAIRE

    Wainio, John; Dyck, John H.; Gehlhar, Mark J.; Vollrath, Thomas L.

    2011-01-01

    The growing number of free trade agreements among U.S. competitors has prompted questions about whether U.S. agricultural exporters may lose a share of the global market. ERS research shows that the recently created ASEAN-China and ASEANAustralia/ New Zealand free trade agreements are likely to have modest adverse impacts on U.S. agricultural exports. The Mercosur-Colombia free trade agreement has reduced U.S. agricultural exports to Colombia; U.S. grain sellers face increasingly stiff compet...

  11. Gas Exports in Turkmenistan

    International Nuclear Information System (INIS)

    Vasanczki, Luca Zs.

    2011-01-01

    The Caspian region has been at the center of attention since Europe began seeking alternative routes to natural-gas resources. Turkmenistan has the potential to become an important gas exporter to Europe. As a landlocked country, Turkmenistan until recently has relied on post-Soviet pipeline infrastructures. The Central Asian republic has been at the mercy of Moscow's energy policy, which overlaps its foreign policy. At the same time, the revenue from gas exports is an essential part of the Turkmen national budget. This prompted Ashgabat to look for energy partners bypassing Russian territories. It started to convey natural gas first to Iran and then to China. This gave Turkmenistan strong leverage vis-a-vis Moscow. Ashgabat has not decided to export every gas molecule eastward, but, in jeopardizing its relations with Moscow, it expects more than empty pledges from Europe. On the other hand, a simple question emerges: Does Europe really need alternative sources? The answer is in the hands of Gazprom and Russian policy-makers

  12. Exports of petroleum products, 1987

    International Nuclear Information System (INIS)

    1988-04-01

    A summary is presented of exports of motor gasoline, middle distillate, aviation turbine fuel, heavy fuel oil, and partially processed oil from Canada for the 1987 calendar year. A discussion of petroleum product imports is included in order to put exports in the context of the overall trade. Exports of the above petroleum products averaged 22,200 m 3 /d in 1987, up 15% from 1986 levels. Exports of middle distillates and aviation fuel had the largest gains in 1987. Export prices for light petroleum products stayed relatively close to USA spot prices. The heavy fuel oil price was below the New York spot price in the beginning of 1987 but remained close for the rest of the year. Canada's petroleum products exports were made to 5 countries while imports came from at least 13 countries. The USA remained Canada's largest trading partner in petroleum products. Exports to Japan and the Far East rose ca 60% over 1986. Product outturns for export were 9% of total Canadian refinery throughput. Exports of aviation turbine fuel from Ontario began in April 1987. The top single exporter in Canada was Irving Oil Ltd. with 2,485,000 m 3 . Irving was also the top exporter in 1986. 11 figs., 4 tabs

  13. The future of Russian gas exports

    International Nuclear Information System (INIS)

    Rodiononv, Alexander; Krasheninnikov, Yuri; Panin, Sergei

    1999-12-01

    Contains Executive Summary and Chapters on: Introduction; The structure of Russian gas exports; Exports to Europe; Exports to Turkey/Middle East; Exports to Asia/Pacific Rim; FSU gas exports; Regulations for exporting gas from Russia; Equipment and services. (Author)

  14. Managing export success – An empirical picture of German wineries’ performance

    Directory of Open Access Journals (Sweden)

    Dressler Marc

    2015-01-01

    Full Text Available Export represents an important strategic lever for enterprises to reach new clients, to diversify, and to participate in regional economic growth. An online based survey invited more than 800 wine experts to assess wine export success factors as well as the performance of German producers. The questionnaire tested a literature based success factor framework with the four success factors. The experts assessed the relevance of the levers for the wine industry and the performance of German produc- ers. Respondents judged all four success factors as well as all underlying 27 criteria to be relevant in the wine industry. Export strategy receives highest value of the success factor rating. The survey depicts a heterogeneous performance of German produc- ers comparing the success factors but a homogeneous performance for all the underlying criteria within each success factor. The responses reveal a performance gap for the success factors export commitment and export strategy. For the success factor export knowledge German producers apparently overperform. Export programs are of importance and in the case of Germany appar- ently meet the needed level of support and activity. The results thereby support empiric findings in the context of cultural differ- ences of different nations. The study provides orientation for German wine producers but also small and medium enterprises of other industries.

  15. Hvad er tekstfiktion?

    DEFF Research Database (Denmark)

    Widell, Peter

    2012-01-01

    artiklen er et bidrag til belysningen af genteori og bygger på ideen om at karakterisere skønlitteratur som et restringeret sæt af universelle tekstparametre. Artiklen fokuserer især på parametren tekstfiktion, hvor jeg forsvarer den position, at en fiktiv tekst hverken kan karakteriseres som en ...... intentioner. Det betyder dog ikke, at sandhed og mening ikke spiller noget rolle ved identifikationen af fiktion, sådan som det hævdes af Walsh og andre....

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

    OpenAIRE

    Yeganeh Alimohammadi; Reza Aghamousa; Fataneh Alizadeh Meshkani

    2014-01-01

    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 th...

  17. Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

    International Nuclear Information System (INIS)

    Roy, S.S.; Vadlamudi, R.K.

    2012-01-01

    Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis

  18. Exporting to Russia?

    DEFF Research Database (Denmark)

    Thomsen, Lotte

    2016-01-01

    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......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...

  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. Export Variety and Country Productivity

    OpenAIRE

    Feenstra, Robert; Looi Kee, Hiau

    2004-01-01

    The authors study the link between export product variety and country productivity based on data from 34 industrial and developing countries, from 1982 to 1997. They measure export product variety by the share of U.S. imports on the set of goods exported by each sampled country relative to the world. It is a theoretically sound index which is consistent with within-country GDP maximization...

  1. Import-Export Business Plan

    OpenAIRE

    Asad, Muhammad

    2014-01-01

    Import export businesses, also known as international trading, are one of the hottest commercial trends of this decade. Since the owner of an import export enterprise, can work as a distributor by focusing on exporting and importing goods and services that cannot be obtained on national soil. With a rapidly growing population of about 150 million, Pakistan is a major country, recognized by the international community, and is one of the most important actors in the Islamic world. Based on its ...

  2. Rouw mag er zijn

    Directory of Open Access Journals (Sweden)

    Marlieke Moors

    2015-12-01

    Full Text Available ABSTRACTGrieving is allowedGrief is a human experience. Every form of loss shapes you into the human being you are today. Contrary to what earlier, unproven grief models postulate, grief does not have an end point. That is, bereavement does not have to be completely processed, but it should be integrated into someone’s life. The outdated grief models were often interpreted and used in a normative way, which led to a normative standard model. This portraits the belief that every mourner would experience similar symptoms and would go through a fixed pattern of phases. However, the updated vision emphasizes the individual and unique process of coping with loss: norms concerning grief should be banned. By means of literature research, interviews with professionals and personal experiences, it became clear that finding an equilibrium between restoration-orientated and loss-orientated coping styles is most beneficial. An important aspect in finding this balance is meaningfulness. Furthermore, the ability to bear a loss and to adapt accordingly are important components. Lastly, attaching significance to a loss is a constructive way of integrating the loss into one’s life. The death of a loved one should therefore not be forgotten or tucked away. After all, grief is the price we pay for love. SAMENVATTINGRouw mag er zijnRouw is een menselijke ervaring en elk verlies vormt je als mens. Rouw heeft, in tegenstelling tot wat de verouderde, niet bewezen rouwmodellen beweren, geen eindpunt. Verlies hoeft namelijk niet verwerkt te worden, maar moet juist geïntegreerd worden in iemands leven. De verouderde rouwmodellen zijn vaak normatief opgevat en toegepast, waaruit een normatief standaardmodel is ontstaan. Daarbij werd gedacht dat elke rouwende dezelfde symptomen zou vertonen en het rouwproces volgens vaste fasen zou verlopen. Binnen de vernieuwde visie wordt er juist van uitgegaan dat elk individu een unieke manier van reageren op rouw heeft. Er zou

  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. Russian nuclear industry exports

    International Nuclear Information System (INIS)

    Gorbatchev, A.

    2016-01-01

    Rosatom is the world leader for the export of nuclear technologies. 34 reactors of Russian technology are being built or planned worldwide. Most reactors proposed by Rosatom are third generation VVER-1200 units with an electric power output of 1200 MWe. Although the nuclear island is always built by Rosatom, the remain of the plant can be subcontracted to other enterprises and European companies are sought because they would bring a european quality touch to Russian works. One of the main assets of Rosatom is to propose an integrated offer from supplying nuclear fuel to managing nuclear waste via the turnkey building of nuclear power plants. Another important asset is the financial assistance of the Russian state through state credit or the support from Russian national banks that appears to be a decisive advantage in the international competition to win markets. We have to temper the Russian export perspectives by noting that most projects are set in countries that are prone to instabilities and that the economic crisis affecting Russia has a negative impact on its financial means. (A.C.)

  5. Exports of petroleum products, 1988

    International Nuclear Information System (INIS)

    1989-04-01

    A summary is presented of exports of motor gasoline, middle distillate, aviation turbine fuel, heavy fuel oil, and partially processed oil from Canada for the 1988 calendar year. A discussion of petroleum product imports is included in order to put exports in the context of the overall trade. Exports of the above petroleum products averaged 32,000 m 3 /d in 1988, up 44% from 1987 levels. Each product except aviation fuel registered increases in export volumes, which reached the highest total volume of the decade. The main reason for the large increase was the first full year of production from the export-directed refinery at Come By Chance, Newfoundland. Export prices for light petroleum products stayed relatively close to USA spot prices. The heavy fuel oil price was mostly above the USA east coast spot price during 1988. Attractive prices on the USA east coast resulted in a few cargoes of middle distillate and motor gasoline shipped from British Columbia. Petroleum products imports came from 12 countries; Quebec had the largest volume of imports in 1988. The USA remained Canada's largest trading partner in petroleum products. Western exporters view the Far East as an ongoing important market. The top single exporter in Canada was Newfoundland Processing, with 32% of the total export volume. 12 figs., 3 tabs

  6. Han er her endnu

    DEFF Research Database (Denmark)

    Bonde, Lisbeth

    2012-01-01

    Interview med den kinesiske aktivist og billedkunstner Ai Weiwei, der sad fængslet i 81 dage i 2011. Hans pas er stadig (i februar 2014) inddraget af myndighederne, så han kan ikke forlade landet, selv om han har betalt en bøde på 13 mio. kr. for ”skatteunddragelse”. Både i sin kunst og i sine...... mange aktioner retter han en hård kritik af det korrupte kinesiske styre, som træder menneskerettighederne under fode. Men uretfærdighedsfølelsen har sin pris i et totalitært og topstyret samfund. Ligegyldigt, hvor mange vigtige udstillinger han har i udlandet, må han blive hjemme og styre aktiviteterne...... via cyberspace. I interviewet fortæller Ai Weiwei om de personlige omkostninger, som hans kamp mod systemet indebærer....

  7. 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

  8. De 9 P’er

    DEFF Research Database (Denmark)

    Rennison, Betina Wolfgang

    2017-01-01

    Ledere skal i dag selv skabe deres eget rum til ledelse, men hvad er med til at sætte det, hvilke betingelser og udfordringer er der, og hvordan kan lederne skabe sig selv i et hav af forventninger? Dette katalog inviterer til refleksion herom....

  9. Fremtidens undervisningsmiljøer

    DEFF Research Database (Denmark)

    2013-01-01

    Som oplægget til dette temanummer af LOM også indikerede, så sætter vi fokus på fremtidens undervisningsmiljøer på universiteter og UCer. Fremtidens undervisningsmiljøer har mange facetter, hvilket samlingen af artikler også illustrerer. “Fremtidens Undervisningsmiljø” handler om eksisterende erf...

  10. Den rige personlighed er livsduelig

    DEFF Research Database (Denmark)

    Holm, Claus

    2015-01-01

    For omtrent 160 år siden formulerede Karl Marx forestillingen om en rig individualitet som det kommunistiske samfunds individideal. I dag får forestillingen relevans. Lyder det lidt besynderligt, er det ikke mærkeligt. For de fleste af os går næppe rundt og tror, at vi er lige på trapperne til...

  11. Humor er en alvorlig sag

    DEFF Research Database (Denmark)

    Søltoft, Pia

    2016-01-01

    I modsætning til ironi er humor for Kierkegaard fællesskabsgivende – ironikeren hævder sig selv, men humoristen har sympati med den, man ler med. Humor er hos Kierkegaard udtryk for, at humoristen forliger sig med tilværelsen og dens luner, og dermed grænser humoren hos Kierkegaard op til det...

  12. Brandulykker er et socialt problem

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    1999-01-01

    Det er de gamle, de syge, de handicappede og alkoholikerne, der brænder inde. Typisk har de tabt en cigaret eller tændstik på tøjet. En del af disse brandulykker opstår på plejehjem og andre institutioner, hvor det ofte er plejepersonalet, der opdager og slukker branden....

  13. 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.

  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. 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

  16. Exports of crude oil, 1988

    International Nuclear Information System (INIS)

    1989-06-01

    Effective June 1, 1985, licensing and charging of oil exports ended. The Board now issues export orders specifying neither volumes nor prices and covering an exportation period of up to 1 year for light crude oil and up to 2 years for heavy crude oil, available on request to both Canadian and foreign companies. The Board has assumed a monitoring role, and export prices and volumes are reported monthly by exporters. This annual report provides a review of the volumes and prices associated with the supply and disposition of Canadian crude oil during 1988. Highlights are given with detailed information on prices, both internationally, in Canada, and the Chicago posted price by light or heavy crude, and on volumes including capacity and disposition in both domestic and export markets. A short description of the import market is included. Comparisons are made with the previous year. Export volumes of light crude oil in 1988 increased by 13% to average 50,200 m 3 /d. Export volumes of heavy crude also increased by ca 13% to 62,600 m 3 /d. 15 figs., 2 tabs

  17. Mexico: Imports or exports?

    International Nuclear Information System (INIS)

    Estrada, J.

    2002-01-01

    This presentation provides an overview of Mexico's energy sector. Proven oil reserves place Mexico in ninth position in the world and fourth largest in natural gas reserves. Energy is one of the most important economic activities of the country, representing 3 per cent of Gross Domestic Product (GDP). Oil exports represent 8.4 per cent of total exports. Approximately 40 per cent of total public investment is earmarked for energy projects. The author discusses energy resources and energy sector limitations. The energy sector plan for the period 2001-2006 is discussed. Its goals are to ensure energy supply, to develop the energy sector, to stimulate participation of Mexican enterprises, to promote renewable energy sources, and to strengthen international energy cooperation. The regulatory framework is being adapted to increase private investment. Some graphs are presented, displaying the primary energy production and primary energy consumption. Energy sector reforms are reviewed, as are electricity and natural gas reforms. The energy sector demand for 2000-2010 and investment requirements are reviewed, as well as fuel consumption for power generation. The author discusses the National Pipeline System (SNG) and the bottlenecks caused by pressure efficiency in the northeast, flow restriction on several pipeline segments, variability of the Petroleos Mexicanos (PEMEX) own use, and pressure drop on central regions. The entire prospect for natural gas in the country is reviewed, along with the Strategic Gas Program (PEG) consisting of 20 projects, including 4 non-associated natural gas, 9 exploration and 7 optimization. A section dealing with multiple service contracts is included in the presentation. The authors conclude by stating that the priority is a national energy policy to address Mexico's energy security requirements, to increase natural gas production while promoting the diversification of imports, and a regulatory framework to be updated in light of current

  18. 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.

  19. 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....

  20. ER stress, autophagy, and RNA viruses

    Directory of Open Access Journals (Sweden)

    Jia-Rong eJheng

    2014-08-01

    Full Text Available Endoplasmic reticulum (ER stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR, which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell’s response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host’s defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment.

  1. 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.

  2. IRE1: ER stress sensor and cell fate executor.

    Science.gov (United States)

    Chen, Yani; Brandizzi, Federica

    2013-11-01

    Cells operate a signaling network termed the unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) is an ER transmembrane sensor that activates the UPR to maintain the ER and cellular function. Although mammalian IRE1 promotes cell survival, it can initiate apoptosis via decay of antiapoptotic miRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of the IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Canadian solar export market study. Export policy recommendations

    Energy Technology Data Exchange (ETDEWEB)

    1983-11-01

    This report outlines policies and recommendations on the export of Canadian solar equipment and technology, with a view toward stimulating the domestic solar industry. The current picture is of an industry which is relatively small, operates in a competitive domestic market with low profit margins, and needs assistance in order to break into the world market. A number of recommendations are therefore made on the main thrust of industry and government solar export development activities. An export development program is described which includes a strategy of concentrating on a limited number of product lines, namely: low-temperature solar heating systems for recreational applications, integrated residential water heating systems, prepackaged commercial water heating systems, and industrial pre-heat systems. It is also recommended that this strategy be directed only at a limited number of target countries where the market justifies such activity. Market research, international cooperation agreements, promotional services, and proper export organization are also needed.

  4. 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. © 2015 The Authors. Genes to Cells published by Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  5. Min mentor er min voksenven

    DEFF Research Database (Denmark)

    Kaiser, Birte

    2009-01-01

    En artikel i bogen: 6 belysninger af vejledning, brydninger, forståelser & praksis. Artiklen er et sammendrag af en diskursanalyse fra 2008 fra projetrapporten: Ind under huden, www.vejledning.net...

  6. Forenklingens fire F'er

    DEFF Research Database (Denmark)

    Bentzen, Tina Øllgaard

    2017-01-01

    At fjerne styring er det, man ofte forbinder med afbureaukratisering, men det er ikke tilstrækkeligt, når man vil gå fra flotte ambitioner til en styring, som reelt opleves enklere. For at forenkle må man også forandre, forankre og fastholde styring, og det må ske i et samspil mellem de aktører, ...

  7. The implications of uranium export

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    It is argued that Australia should not enter the business of uranium mining enrichment and export because of the hazards of nuclear power and because there are practical alternatives to the development of nuclear power. (R.L.)

  8. Export controls on high technology

    Energy Technology Data Exchange (ETDEWEB)

    Frank, N.K.

    1987-01-01

    A overview of the Export Administration Act of 1979 and subsequent regulations and amendments focuses on how licensing requirements and restrictions against boycott affect high technology exports. The purpose of these controls is to limit the export of technology with possible military applications, as well as to advance US foreign policy and protect the economy without imposing too great a restriction on the principles of free trade. Thus, the act encompasses political, economic, and security goals. Problems of predictability arise when embargoes or other controls are imposed for political or foreign policy reasons without regard to economic impacts. Amendments have attempted to streamline the exporting process, particularly in the area of computer and software licensing.

  9. Australia's uranium export potential

    International Nuclear Information System (INIS)

    Mosher, D.V.

    1981-01-01

    During the period 1954-71 in Australia approximately 9000 MT of U 3 O 8 was produced from five separate localities. Of this, 7000 MT was exported to the United Kingdom and United States and the balance stockpiled by the Australian Atomic Energy Commission (AAEC). Australia's uranium ore reserves occur in eight deposits in three states and the Northern Territory. However, 83% of Australia's reserves are contained in four deposits in lower Proterozoic rocks in the East Alligator River region of the Northern Territory. The AAEC has calculated Australia's recoverable uranium reserves by eliminating estimated losses during the mining and milling of the ores. AAEC has estimated reasonably assured resources of 289,000 MT of uranium at a recovery cost of less than US$80 per kilogram uranium. The companies have collectively announced a larger ore reserve than the Australian Atomic Energy Commission. This difference is a result of the companies adopting different ore reserve categories. On August 25, 1977, the federal government announced that Australia would develop its uranium resources subject to stringent environmental controls, recognition of Aboriginal Land Rights, and international safeguards. Australian uranium production should gradually increase from 1981 onward, growing to 10,000 to 15,000 MT by 1985-86. Further increases in capacity may emerge during the second half of the 1980s when expansion plans are implemented. Exploration for uranium has not been intensive due to delays in developing the existing deposits. It is likely that present reserves can be substantially upgraded if more exploration is carried out. 6 figures, 3 tables

  10. Pre-emptive Quality Control Protects the ER from Protein Overload via the Proximity of ERAD Components and SRP

    Directory of Open Access Journals (Sweden)

    Hisae Kadowaki

    2015-11-01

    Full Text Available Cells possess ER quality control systems to adapt to ER stress and maintain their function. ER-stress-induced pre-emptive quality control (ER pQC selectively degrades ER proteins via translocational attenuation during ER stress. However, the molecular mechanism underlying this process remains unclear. Here, we find that most newly synthesized endogenous transthyretin proteins are rerouted to the cytosol without cleavage of the signal peptide, resulting in proteasomal degradation in hepatocytes during ER stress. Derlin family proteins (Derlins, which are ER-associated degradation components, reroute specific ER proteins, but not ER chaperones, from the translocon to the proteasome through interactions with the signal recognition particle (SRP. Moreover, the cytosolic chaperone Bag6 and the AAA-ATPase p97 contribute to the degradation of ER pQC substrates. These findings demonstrate that Derlins-mediated substrate-specific rerouting and Bag6- and p97-mediated effective degradation contribute to the maintenance of ER homeostasis without the need for translocation.

  11. ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells.

    Science.gov (United States)

    Arduino, Daniela M; Esteves, A Raquel; Domingues, A Filipa; Pereira, Claudia M F; Cardoso, Sandra M; Oliveira, Catarina R

    2009-11-30

    Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

  12. 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.

  13. Exports of petroleum products, 1990

    International Nuclear Information System (INIS)

    1991-04-01

    A summary is presented of exports of motor gasoline, middle distillate, aviation turbine fuel, heavy fuel oil, and partially processed oil from Canada for the 1990 calendar year. Exports of the above petroleum products averaged 34,000 m 3 /d in 1990, up 12% from 1989 levels. The increase reflects increased output from the Come By Chance refinery in Newfoundland. Motor gasoline exports increased 35% to 10,500 m 3 /d, reflecting refinery upgrading in eastern Canada. Export prices were generally in line with spot product prices in the USA. Spot prices rose sharply following the Kuwait crisis in August 1990 but fell again in November. The spot price for jet fuel rose more dramatically in that period than for other products, reflecting increased military demand. In winter 1989/90 and during the Kuwait conflict, the export price of heating oil tended to track the USA spot price. Petroleum products imports in 1990 were 18,500 m 3 /d, compared to 21,900 m 3 /d in 1988. Imports were lower partially as a result of higher crude runs in Quebec and a Quebec refinery expansion. Imports of heavy fuel oil in eastern Canada continued to be strong in comparison to the mid-1980s. The top single exporter in 1990, as in 1989, was Newfoundland Processing, with a volume of 4,506,400 m 3 . 13 figs., 5 tabs

  14. Exports of petroleum products, 1989

    International Nuclear Information System (INIS)

    1990-04-01

    A summary is presented of exports of motor gasoline, middle distillate, aviation turbine fuel, heavy fuel oil, and partially processed oil from Canada for the 1989 calendar year. A discussion of petroleum product imports is included in order to put exports in the context of the overall trade. Exports of the above petroleum products averaged 30,400 m 3 /d in 1989, down 5% from 1988 levels. Motor gasoline shipments showed the largest decrease, down 1,500 m 3 to 7,700 m 3 /d. Export prices for light petroleum products stayed relatively close to USA spot prices except in June and July 1989, when attractive prices were obtained for shipments from the prairie provinces. The heavy fuel oil export price was similar to the USA east coast spot price in 1989, except in December. Canada's petroleum products imports in 1989 were 21,600 m 3 /d, compared to 18,400 m 3 /d in 1988. Imports of heavy fuel oil in eastern Canada rose 36% in 1989 because of industries switching from electricity and the high demand for thermal power generation. The USA remained Canada's largest trading partner in petroleum products. The top single exporter in 1989, as in 1988, was Newfoundland Processing, with a volume of 3,484,500 m 3 . 24 figs., 4 tabs

  15. The anatomy of China's export growth

    OpenAIRE

    Amiti, Mary; Freund, Caroline

    2008-01-01

    Decomposing China's real export growth, of over 500 percent since 1992, reveals a number of interesting findings. First, China's export structure changed dramatically, with growing export shares in electronics and machinery and a decline in agriculture and apparel. Second, despite the shift into these more sophisticated products, the skill content of China's manufacturing exports remained ...

  16. 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....

  17. 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...

  18. Phases definition in marketing export process

    OpenAIRE

    Rajković Dragan; Kokić Miljko

    2004-01-01

    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 ...

  19. Markups and Firm-Level Export Status

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic

    and export behavior using plant-level data. We find that i) markups are estimated significantly higher when controlling for unobserved productivity, ii) exporters charge on average higher markups and iii) firms' markups increase (decrease) upon export entry (exit).We see these findings as a first step...... in opening up the productivity-export black box, and provide a potential explanation for the big measured productivity premia for firms entering export markets....

  20. Topics in Productivity, Exporting and Outsourced Services

    OpenAIRE

    Kidder, Matthew Benjamin

    2016-01-01

    This dissertation is a collection of three empirical studies using the a survey of Chilean Manufactures. The first two chapters of this dissertation evaluates the productivity impact of exporting and service outsourcing. The last chapter evaluates selection mechanisms into exporting.The first chapter examines productivity and exporting. I find that asymmetric responses, between exporters and non-exporters, to changes in the domestic lending rate can cause propensity-score-matching-differen...

  1. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    International Nuclear Information System (INIS)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-01-01

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  2. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

    2015-10-15

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  3. China's coal export and inspection

    International Nuclear Information System (INIS)

    Xiaodong Li

    1993-01-01

    With the development of world's business and trade, coal has become a large part of the import and export goods in the international market. The total amount of coal trade has risen a lot. China is rich in coal resources. According to the estimate made by some experts, the reserve which has been explored recently could be exploited hundreds of years. China's output of raw coal has risen a lot during the past forty years. China coal industry has developed rapidly since the 1980s. It is possible for China to become a big coal export country since it has rich resources and increasing output. The paper suggests four steps which must be taken to expand coal exports in China: improve the level of management and administration of coal mines so as to raise the economic benefit; the follow-up production capacity of the present mines must be enhanced rapidly; step up construction of new large-scale mines; and China's coal washing capacity must be improved speedily since the low capacity has seriously influenced the improvement of coal quality. The paper describes the inspection bureaus and companies that have developed to perform inspection of exports in order to guarantee the quality of export coal

  4. The Export Administration Act of 1979 and Computer Exports to China

    National Research Council Canada - National Science Library

    Perez, Elizabeth

    2002-01-01

    .... The statute that regulates computer exports, the Export Administration Act of 1979 (EAA79), has been interpreted both strictly and loosely by policymakers, executive agencies, and export control regimes...

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

    OpenAIRE

    Rifin, Amzul; Nauly, Dahlia

    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...

  6. Potential mechanisms underlying estrogen-induced expression of the molluscan estrogen receptor (ER) gene

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Thi Kim Anh [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia); Department of Agriculture, Forestry and Fisheries, Vinh University, 182 Le Duan St., Vinh City, Nghe An (Viet Nam); MacFarlane, Geoff R. [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia); Kong, Richard Yuen Chong [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong Special Administrative Region (China); O’Connor, Wayne A. [New South Wales Department of Primary Industries, Port Stephens Fisheries Institute, Taylors Beach, NSW 2316 (Australia); Yu, Richard Man Kit, E-mail: Richard.Yu@newcastle.edu.au [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia)

    2016-10-15

    Highlights: • This is the first report on the putative promoter sequence of a molluscan ER gene. • The gene promoter contains putative binding sites for direct and indirect interaction with ER. • E2 upregulates ER gene expression in the ovary in vitro and in vivo. • E2-induced gene expression may require a novel ligand-dependent receptor. • The ER proximal promoter is hypomethylated regardless of gene expression levels. - Abstract: In vertebrates, estrogens and estrogen mimicking chemicals modulate gene expression mainly through a genomic pathway mediated by the estrogen receptors (ERs). Although the existence of an ER orthologue in the mollusc genome has been known for some time, its role in estrogen signalling has yet to be deciphered. This is largely due to its constitutive (ligand-independent) activation and a limited mechanistic understanding of its regulation. To fill this knowledge gap, we cloned and characterised an ER cDNA (sgER) and the 5′-flanking region of the gene from the Sydney rock oyster Saccostrea glomerata. The sgER cDNA is predicted to encode a 477-amino acid protein that contains a DNA-binding domain (DBD) and a ligand-binding domain (LBD) typically conserved among both vertebrate and invertebrate ERs. A comparison of the sgER LBD sequence with those of other ligand-dependent ERs revealed that the sgER LBD is variable at several conserved residues known to be critical for ligand binding and receptor activation. Ligand binding assays using fluorescent-labelled E2 and purified sgER protein confirmed that sgER is devoid of estrogen binding. In silico analysis of the sgER 5′-flanking sequence indicated the presence of three putative estrogen responsive element (ERE) half-sites and several putative sites for ER-interacting transcription factors, suggesting that the sgER promoter may be autoregulated by its own gene product. sgER mRNA is ubiquitously expressed in adult oyster tissues, with the highest expression found in the ovary

  7. Hvis en kartoffel er forkert, hvad er en Mars-bar så?

    DEFF Research Database (Denmark)

    Lichtenstein, Mia Beck; Thomsen, Freja; Hinze, Cecilie

    2016-01-01

    Danske unge er de slankeste af 41 europæiske unge, men de føler sig ofte tykke og går på slankekur. Hvad er årsagen, og hvorfor er det et problem?......Danske unge er de slankeste af 41 europæiske unge, men de føler sig ofte tykke og går på slankekur. Hvad er årsagen, og hvorfor er det et problem?...

  8. ER phospholipid composition modulates lipogenesis during feeding and in obesity.

    Science.gov (United States)

    Rong, Xin; Wang, Bo; Palladino, Elisa Nd; de Aguiar Vallim, Thomas Q; Ford, David A; Tontonoz, Peter

    2017-10-02

    Sterol regulatory element-binding protein 1c (SREBP-1c) is a central regulator of lipogenesis whose activity is controlled by proteolytic cleavage. The metabolic factors that affect its processing are incompletely understood. Here, we show that dynamic changes in the acyl chain composition of ER phospholipids affect SREBP-1c maturation in physiology and disease. The abundance of polyunsaturated phosphatidylcholine in liver ER is selectively increased in response to feeding and in the setting of obesity-linked insulin resistance. Exogenous delivery of polyunsaturated phosphatidylcholine to ER accelerated SREBP-1c processing through a mechanism that required an intact SREBP cleavage-activating protein (SCAP) pathway. Furthermore, induction of the phospholipid-remodeling enzyme LPCAT3 in response to liver X receptor (LXR) activation promoted SREBP-1c processing by driving the incorporation of polyunsaturated fatty acids into ER. Conversely, LPCAT3 deficiency increased membrane saturation, reduced nuclear SREBP-1c abundance, and blunted the lipogenic response to feeding, LXR agonist treatment, or obesity-linked insulin resistance. Desaturation of the ER membrane may serve as an auxiliary signal of the fed state that promotes lipid synthesis in response to nutrient availability.

  9. Aging induced ER stress alters sleep and sleep homeostasis

    Science.gov (United States)

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2014-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

  10. 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...

  11. 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...

  12. 75 FR 44761 - Export Trade Certificate of Review

    Science.gov (United States)

    2010-07-29

    ... sales prices and/or minimum target sales prices, and other terms of sales in the Export Markets... canned salmon in the Export Markets, selling strategies for the Export Markets, sales for the Export... described below for the following Export Trade and Export Markets: Export Trade Products Shelf stable non...

  13. Export-Led Growth Hypothesis: Evidence from Agricultural Exports ...

    African Journals Online (AJOL)

    This study examines the nature and direction of causality in Tanzania between economic growth and agricultural exports along with some selected variables such as labour force and domestic investment. The analysis for this study was carried out using time series data for the period of 1980 to 2013. The data series were ...

  14. Export of radiopharmaceuticals and establishment of export base of cyclotron

    International Nuclear Information System (INIS)

    Jung, Kyungil; Kim, Youngsik

    2006-01-01

    Sam young Unit ech has seized an opportunity to advance into the radiopharmaceuticals market through successful transfer of radiopharmaceuticals manufacturing technology and medical cyclotron, an original technology in nuclear medicine that is the core of less developed areas in nuclear-related fields. The company has continued to push for research development and establishment of market base through industry-academia-research center cooperation with an aim to complement relatively less developed domestic technology and market than in advanced countries, and is making efforts to establish export base in the overseas market based on stabilized supply in the domestic market. As for radiopharmaceuticals, the company is exporting Tc-99m generator to Vietnam, Thailand and the Philippines and preparing itself to export manufacture facilities for Tc-99m generator to Syria and Kazakhstan. In addition, it plans to export 13Mev Cyclotron that has been commercialized after being developed in the domestic market to the U. S. The company plans to grow up to play a pivotal role in the domestic RT area by conducting proactive business activities with an aim to revitalize the domestic market and further domestic original technologies and products in the global market

  15. Den sproglige leg er super fly

    DEFF Research Database (Denmark)

    Just, Sine Nørholm

    2013-01-01

    Man kan rappe om alt. I hvert fald hvis man er Marvelous Mosell. I spændingsfeltet mellem fiktion og virkelighed skaber Mosell sin persona i et forjættende 80' er-univers der på en og samme tid er vildt overdrevet og helt autentisk.......Man kan rappe om alt. I hvert fald hvis man er Marvelous Mosell. I spændingsfeltet mellem fiktion og virkelighed skaber Mosell sin persona i et forjættende 80' er-univers der på en og samme tid er vildt overdrevet og helt autentisk....

  16. N-ov-emb-er

    Indian Academy of Sciences (India)

    " to. Andrew Z Fire - Stanford University School of Medicine Stanford, CA, USA. Craig C Mello - University of Massachusetts Medical School Worcester, MA, USA. -96----------------------------~~--------R-ES-O-N-A-N-C-E--1 -N-ov-e-m-b-er--2-oo-6.

  17. Hvad er ledelse af brugerinddragelse?

    DEFF Research Database (Denmark)

    Holm-Petersen, Christina; Navne, Laura Emdal

    2015-01-01

    Brugerinddragelse i det danske sundhedsvæsen står højt på den politiske dagsorden, men det er stadig en udfordring at implementere visionen i klinisk praksis. Ledelse af brugerinddragelse bliver aktuelt udpeget som en central nøgle til at føre visionen ud i livet. Samtidig er der kun relativt lidt......, at brugerinddragelse skal implementeres i en verden, hvor der allerede er en række andre mål tilstede. En central ledelsesudfordring er derfor, at nogle af målene med brugerinddragelse forudsætter nye måder at organisere ikke bare arbejdet og kompetencer på, men også relationer til patienter og pårørende. En væsentlig...... that organize relations Patient involvement in the health services in Denmark is high on the political agenda, though continues to be a challenge to implement. It is increasingly said that leadership is crucial to the implementation process. However, research into the role of leaders in patient involvement...

  18. 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...

  19. Changes of MODY signal pathway genes in the endoplasmic reticulum stress in INS-1-3 cells.

    Directory of Open Access Journals (Sweden)

    Yanan Dong

    Full Text Available Metabolic disturbances induce endoplasmic reticulum stress (ERS in pancreatic beta cells. This study aims to investigate whether a common pathway exists in the ERS induced by various chemicals, including high levels of glucose and palmitate in INS-1-3 cells.ERS in INS-1-3 cells was induced by exposure cells to thapsigargin (TG, tunicamycin (TM or palmitic acid (PA +high glucose (HG. Digital gene expression (DGE profiling technique was used to detect differentially expressed genes. The profile of gene expression was detected by gene oncology (GO function and pathway enrichment analysis. Nkx6.1 over-expression was established in INS-1-3 cell lines by lentivirus infection to revert the inhibition of Nkx6.1 expression found in the situation of ERS. Real time reverse transcription polymerase chain reaction (RT-PCR was used to verify the expression changes of key genes. Cell viability was measured by 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT assay. The apoptosis was determined by flow cytometry. INS-1-3 cell function was measured by glucose stimulated insulin secretion test(GSIS.As compared to control, DGE demonstrated that there were 135, 57 and 74 differentially expressed genes in TM, TG and HG+PA groups, respectively. Those differentially expressed genes were enriched to ERS, antigen processing and presentation, protein export pathways, and interestingly, the maturity onset diabetes of the young (MODY pathway. Nkx6.1 is one of common down-regulated gene in MODY signaling pathway among TM, TG and HG+PA groups. Over-expression of Nkx6.1 ameliorated glucolipotoxicity induced apoptosis rate by 45.4%, and increased proliferation by 40.9%. At the same time, GSIS increased by 1.82 folds.MODY pathway genes expression was changed in the state of ERS. Over-expression of Nkx6.1 protected the INS-1-3 cells from glucolipotoxicity.

  20. 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.

  1. Nuclear Export of Messenger RNA

    Directory of Open Access Journals (Sweden)

    Jun Katahira

    2015-03-01

    Full Text Available 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.

  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. 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.

  4. 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

  5. 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...

  6. ER2OWL: Generating OWL Ontology from ER Diagram

    Science.gov (United States)

    Fahad, Muhammad

    Ontology is the fundamental part of Semantic Web. The goal of W3C is to bring the web into (its full potential) a semantic web with reusing previous systems and artifacts. Most legacy systems have been documented in structural analysis and structured design (SASD), especially in simple or Extended ER Diagram (ERD). Such systems need up-gradation to become the part of semantic web. In this paper, we present ERD to OWL-DL ontology transformation rules at concrete level. These rules facilitate an easy and understandable transformation from ERD to OWL. The set of rules for transformation is tested on a structured analysis and design example. The framework provides OWL ontology for semantic web fundamental. This framework helps software engineers in upgrading the structured analysis and design artifact ERD, to components of semantic web. Moreover our transformation tool, ER2OWL, reduces the cost and time for building OWL ontologies with the reuse of existing entity relationship models.

  7. Endoplasmic Reticulum (ER Stress and Endocrine Disorders

    Directory of Open Access Journals (Sweden)

    Daisuke Ariyasu

    2017-02-01

    Full Text Available The endoplasmic reticulum (ER is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR, which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI, Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2 are discussed in this article.

  8. Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

    Science.gov (United States)

    Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

    2017-01-01

    The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI), Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2) are discussed in this article. PMID:28208663

  9. Export markets for nuclear technology

    International Nuclear Information System (INIS)

    Huettl, A.J.

    1985-01-01

    By late 1984, nuclear power plants were in operation or under construction in 32 countries of the globe. An additional six countries had concrete plans for building nuclear power plants. Of these 38 countries, ten have shown that they posses the necessary know-how and the technical facilities to plan and build nuclear power plants practically on their own. Seven of these ten countries have already acted as exporters of nuclear power plants, albeit with very different degrees of market penetration. In addition, there have been a number of countries for quite some time whose industries have managed to manufacture many important nuclear power plant components. Their high level of technical development and the problems frequently encountered in export financing have made them very attractive partners of the true exporters of nuclear power plants. For the future, it must be expected that some of the countries which have so far limited their efforts to the construction of nuclear power plants at home will also develop into exporters of nuclear technology. The report contains a survey of the range of nuclear products available, a list of reactor vendors, reactor lines, and data on the economics of electricity generation in nuclear plants. It then goes on to offer detailed descriptions of the market and the demand situation. Interesting chapters are devoted to the selection criteria applied by importing countries, to financing problems, and to the influences exerted by the political environment. A realistic forecast is attempted in order to make a quantitative analysis of possible export contracts up until the year 2000. (orig.) [de

  10. Hvornår er man ung?

    DEFF Research Database (Denmark)

    Gundelach, Peter; Nørregård-Nielsen, Esther C.

    2002-01-01

    Hvornår er man ung, og hvornår er man voksen? Er der forskelle i befolkningens værdier i forhold til arbejde og politik, når det undersøges ud fra henholdsvis et alders- eller generationsperspektiv? Baseret på data fra den danske del af den internationale værdiundersøgelse vises at der er så store...

  11. Australian coal exports - threat to market share

    Energy Technology Data Exchange (ETDEWEB)

    James, P

    1989-10-01

    Australian coal exports fell 3% for the fiscal year ending June 1989, but at just under 100mt, they make Australia the world's leading coal exporter. Figures for production, consumption and exports are given. Industrial and structural changes within the industry are discussed. It is concluded that the industry and unions must improve structures and communication if potential production and exports are to be achieved. 2 figs.

  12. Chinese Competition and Brazilian Exports of Manufactures

    OpenAIRE

    Jenkins, Rhys

    2014-01-01

    In recent years concerns have been raised over the impact of Chinese competition on Latin American exports, particularly those from Mexico. This article shows that Brazilian manufactured exports too have been negatively affected, and that this has been reflected in the “primarization” of Brazilian exports and a declining share in the import markets of its major customers. A variety of different indicators were used to analyse the extent to which Brazilian exports have faced competition from C...

  13. 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 ...

  14. Hvorfor er sygeplejersker usynlige i offentlige medier?

    DEFF Research Database (Denmark)

    Joensen, Annemi Lund; Hall, Elisabeth

    2015-01-01

    Når der er sygeplejerelevante emner til debat i de offentlige medier på Færøerne, bærer debatten præg af sygeplejerskers manglende deltagelse. Sygeplejerskerne er usynlige. Et eksempel på dette er en debat om besparelser inden for ældreomsorgen. Til trods for at besparelsen fik omfattende konsekv...

  15. Exporting nuclear engineering and the government's viewpoint

    International Nuclear Information System (INIS)

    Schill, H.

    1986-01-01

    The reasons for the government's positive attitude to nuclear engineering exports are explained, especially with regard to them being a compensation of the decreasing domestic demand. The federal government considers such exports to be necessary and correct for economical and energy-political reasons. Their contribution reaches from accompanying measures to the provision of state guarantees of export financing activities. (UA) [de

  16. Firm-level volatility and exports

    NARCIS (Netherlands)

    Vannoorenberghe, G.C.L.

    2012-01-01

    This paper shows that the share of exports in the total sales of a firm has a positive and substantial impact on the volatility of its sales. Decomposing the volatility of sales of exporters between their domestic and export markets, I show using an identification strategy based on a firm-specific

  17. 75 FR 12433 - National Export Initiative

    Science.gov (United States)

    2010-03-16

    ... Order 13534 of March 11, 2010 National Export Initiative By the authority vested in me as President by... performance will, in turn, create good high-paying jobs. The National Export Initiative (NEI) shall be an Administration initiative to improve conditions that directly affect the private sector's ability to export. The...

  18. 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 Section 28.216 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Exportation of Wine With Benefit of Drawback § 28.216...

  19. 77 FR 16768 - Export Sales Reporting Requirements

    Science.gov (United States)

    2012-03-22

    ... DEPARTMENT OF AGRICULTURE Office of the Secretary 7 CFR Part 20 RIN 0551-AA70 Export Sales... Sales Reporting Requirements, is being withdrawn. The Foreign Agricultural Service (FAS) is currently...: Contact Peter W. Burr, Branch Chief, Export Sales Reporting Branch, Import Policies and Export Reporting...

  20. 78 FR 35195 - Acquisition Regulations: Export Control

    Science.gov (United States)

    2013-06-12

    ... DEPARTMENT OF ENERGY 48 CFR Parts 925, 952, and 970 RIN 1991-AB99 Acquisition Regulations: Export... Energy (DOE) is proposing to amend the Department of Energy Acquisition Regulation (DEAR) to add export... comments, identified by ``DEAR: Export Control and RIN 1991-AB99,'' by any of the following methods...

  1. 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 cherries...

  2. 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...

  3. 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. Export...

  4. 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. Export...

  5. 77 FR 73627 - 2012 LNG Export Study

    Science.gov (United States)

    2012-12-11

    ... 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 Exports, LLC.... [FE Docket...

  6. 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 destination...

  7. 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 within...

  8. 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 is...

  9. 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 the...

  10. 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 of...

  11. 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 48...

  12. 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 cushions...

  13. 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 which...

  14. 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 by...

  15. 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 means...

  16. 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...

  17. 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 United...

  18. 78 FR 45168 - Acquisition Regulations: Export Control

    Science.gov (United States)

    2013-07-26

    ... DEPARTMENT OF ENERGY 48 CFR Parts 925, 952 and 970 RIN 1991-AB99 Acquisition Regulations: Export... (78 FR 35195) to amend the Department of Energy Acquisition Regulation (DEAR) to add export control... ``DEAR: Export Control and RIN 1991-AB99,'' by any of the following methods: Federal eRulemaking Portal...

  19. 75 FR 69573 - Export Enforcement Coordination Center

    Science.gov (United States)

    2010-11-15

    ... Export Enforcement Coordination Center By the authority vested in me as President by the Constitution and... enforcement of United States export control laws and enhanced intelligence exchange in support of such enforcement efforts, it is hereby ordered as follows: Section 1. Policy. Export controls are critical to...

  20. 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...

  1. 76 FR 66693 - President's Export Council: Meeting of the President's Export Council

    Science.gov (United States)

    2011-10-27

    .... ACTION: Notice of an open meeting. SUMMARY: The President's Export Council will hold a meeting to discuss.... exports, jobs, and growth. DATES: November 16, 2011 at 9:30 a.m. (ET) ADDRESSES: The President's Export... on December 20, 1973 to advise the President on matters relating to U.S. export trade and report to...

  2. 76 FR 9550 - President's Export Council: Meeting of the President's Export Council

    Science.gov (United States)

    2011-02-18

    .... ACTION: Notice of an open meeting. SUMMARY: The President's Export Council will hold a meeting to discuss.... exports, jobs, and growth. DATES: March 11, 2011 at 9:30 a.m. (ET). ADDRESSES: The President's Export... on December 20, 1973 to advise the President on matters relating to U.S. export trade and report to...

  3. 75 FR 47548 - President's Export Council Subcommittee on Export Administration; Notice of Recruitment of...

    Science.gov (United States)

    2010-08-06

    ... DEPARTMENT OF COMMERCE 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... their services. The PECSEA is seeking private-sector members with senior export control expertise and...

  4. Aging induced ER stress alters sleep and sleep homeostasis

    OpenAIRE

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2013-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical ...

  5. Jordkvalitetskriterier for PAH'er

    DEFF Research Database (Denmark)

    Carlsen, Lars

    2009-01-01

    For to år siden forhøjede Miljøstyrelsen den administrativt fastsatte grænseværdi for polycycliske hydrocarboner (PAH’er) i jord med en faktor 3, hvilket i praksis betød at en række grunde, der tidligere var klassifi ceret som forurenede, nu ikke klassifi ceres sådan. Den hidtidige og den nye met...

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

    Energy Technology Data Exchange (ETDEWEB)

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka [Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kondoh, Yasumitsu; Osada, Hiroyuki [Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori [Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2017-07-15

    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. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.

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

    International Nuclear Information System (INIS)

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

    2017-01-01

    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. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.

  8. 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...... an export wage premium, but it accrues to workers in firms with high skill intensities...

  9. 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.

  10. Core labour standards and exports

    OpenAIRE

    Siroën, Jean-Marc

    2017-01-01

    (english) Core labour standards defined by the ILO in 1998 are universal, but applied very differently across countries. Compliance is much higher in high income countries. However, the causality between improved labour standards and economic growth remains a controversial issue. Export-led growth strategies might encourage developing countries to curb the process of standards improvement. In this way, they can raise the volume of their unskilled labour endowments (child and/or forced labour)...

  11. Immigrant Entrepreneurs, Diasporas and Exports

    OpenAIRE

    Bratti, Massimiliano; De Benedictis, Luca; Santoni, Gianluca

    2018-01-01

    In this paper we highlight a new complementary channel to the business and social network effect à la Rauch (2001) through which immigrants generate increased export flows from the regions in which they settle to their countries of origin: they can become entrepreneurs. Using very small-scale (NUTS-3) administrative data on immigrants’ location in Italy, the local presence of immigrant entrepreneurs (i.e. firms owned by foreign-born entrepreneurs) in the manufacturing sector, and on trade ...

  12. The Chinese Export Displacement Effect Revisited

    DEFF Research Database (Denmark)

    Elleby, Christian; Yu, Wusheng; Yu, Qian

    China’s global export share has increased dramatically over the past decades. This development has prompted an empirical literature on whether Chinese exports displace those originated from elsewhere in various destination markets. In this paper we focus on the growth of China’s exports to the East...... African Community (EAC) countries and show how it has affected exports from the European Union (EU) to the EAC. Our main contribution to the literature on the displacement effect of Chinese exports is a set of total and relative displacement estimates based on different specifications of the gravity model...... where we control for country-year fixed effects so as to avoid the “gold medal mistake” of not accounting for time varying “multilateral resistance”. Our findings do not support the hypothesis that Chinese exports have displaced exports from other countries in general. Nor do they support the hypothesis...

  13. Expression profiling on soybean leaves reveals integration of ER- and osmotic-stress pathways

    Directory of Open Access Journals (Sweden)

    Dewey Ralph E

    2007-11-01

    Full Text Available Abstract Background Despite the potential of the endoplasmic reticulum (ER stress response to accommodate adaptive pathways, its integration with other environmental-induced responses is poorly understood in plants. We have previously demonstrated that the ER-stress sensor binding protein (BiP from soybean exhibits an unusual response to drought. The members of the soybean BiP gene family are differentially regulated by osmotic stress and soybean BiP confers tolerance to drought. While these results may reflect crosstalk between the osmotic and ER-stress signaling pathways, the lack of mutants, transcriptional response profiles to stresses and genome sequence information of this relevant crop has limited our attempts to identify integrated networks between osmotic and ER stress-induced adaptive responses. As a fundamental step towards this goal, we performed global expression profiling on soybean leaves exposed to polyethylene glycol treatment (osmotic stress or to ER stress inducers. Results The up-regulated stress-specific changes unmasked the major branches of the ER-stress response, which include enhancing protein folding and degradation in the ER, as well as specific osmotically regulated changes linked to cellular responses induced by dehydration. However, a small proportion (5.5% of total up-regulated genes represented a shared response that seemed to integrate the two signaling pathways. These co-regulated genes were considered downstream targets based on similar induction kinetics and a synergistic response to the combination of osmotic- and ER-stress-inducing treatments. Genes in this integrated pathway with the strongest synergistic induction encoded proteins with diverse roles, such as plant-specific development and cell death (DCD domain-containing proteins, an ubiquitin-associated (UBA protein homolog and NAC domain-containing proteins. This integrated pathway diverged further from characterized specific branches of ER-stress as

  14. 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

  15. Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma

    International Nuclear Information System (INIS)

    Ma, Ji; Zhang, Jian; Liu, Wenchao; Guo, Yan; Chen, Suning; Zhong, Cuiping; Xue, Yan; Zhang, Yuan; Lai, Xiaofeng; Wei, Yifang; Yu, Shentong

    2014-01-01

    Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). However, many ER-positive patients are low reactive or resistant to tamoxifen. Metformin is a widely used anti-diabetic drug with noteworthy anti-cancer effects. We investigated whether metformin has the additive effects with tamoxifen in ER-positive breast cancer therapy. The efficacy of metformin alone and in combination with tamoxifen against ER-positive breast cancer was analyzed by cell survival, DNA replication activity, plate colony formation, soft-agar, flow cytometry, immunohistochemistry, and nude mice model assays. The involved signaling pathways were detected by western blot assay. When metformin was combined with tamoxifen, the concentration of tamoxifen required for growth inhibition was substantially reduced. Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells. In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Finally, two-drug combination therapy significantly inhibited tumor growth in vivo. The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer

  16. Endoplasmic reticulum (ER Chaperones and Oxidoreductases: Critical Regulators of Tumor Cell Survival and Immunorecognition

    Directory of Open Access Journals (Sweden)

    Thomas eSimmen

    2014-10-01

    Full Text Available Endoplasmic reticulum (ER chaperones and oxidoreductases are abundant enzymes that mediate the production of fully folded secretory and transmembrane proteins. Resisting the Golgi and plasma membrane-directed bulk flow, ER chaperones and oxidoreductases enter retrograde trafficking whenever they are pulled outside of the ER. However, solid tumors are characterized by the increased production of reactive oxygen species (ROS, combined with reduced blood flow that leads to low oxygen supply and ER stress. Under these conditions, hypoxia and the unfolded protein response (UPR upregulate ER chaperones and oxidoreductases. When this occurs, ER oxidoreductases and chaperones become important regulators of tumor growth. However, under these conditions, these proteins not only promote the production of proteins, but also alter the properties of the plasma membrane and hence modulate tumor immune recognition. For instance, high levels of calreticulin serve as an eat-me signal on the surface of tumor cells. Conversely, both intracellular and surface BiP/GRP78 promotes tumor growth. Other ER folding assistants able to modulate the properties of tumor tissue include protein disulfide isomerase (PDI, Ero1α and GRP94. Understanding the roles and mechanisms of ER chaperones in regulating tumor cell functions and immunorecognition will lead to important insight for the development of novel cancer therapies.

  17. ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

    Science.gov (United States)

    Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

    2011-01-01

    The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult ApoER2 was expressed by A-II amacrine cells. ApoER2 knockout (KO) mice had rod bipolar morphogenic defects, altered A-II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding disabled-1 (Dab1) and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway while the alternatively-spliced exon19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID:21976526

  18. ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.

    Science.gov (United States)

    Costello, Joseph L; Castro, Inês G; Hacker, Christian; Schrader, Tina A; Metz, Jeremy; Zeuschner, Dagmar; Azadi, Afsoon S; Godinho, Luis F; Costina, Victor; Findeisen, Peter; Manner, Andreas; Islinger, Markus; Schrader, Michael

    2017-02-01

    Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO-ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A-binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5-VAPB interaction regulates PO-ER associations. Moreover, we demonstrate that loss of PO-ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO-ER associations in mammalian cells and report a new function for ACBD5 in PO-ER tethering. © 2017 Costello et al.

  19. Nuclear export controls - Closing the gaps

    International Nuclear Information System (INIS)

    Schmidt, Fritz W.

    2005-01-01

    Concerns over a nuclear 'black market' have focused international attention on the effectiveness of nuclear export controls. IAEA Director General Mohamed ElBaradei has stated that the emergence of a multinational illicit network demonstrated the inadequacy of the present export control system, that international cooperation on export controls lay on informal arrangements that were not only not binding but also limited in membership, and that export control information was not systematically shared with the IAEA. This criticism, often heard on the political level, does not really do justice to the work of export control groups. The emergence of a multinational illicit network does not necessarily prove failures in export control systems. Criminal activities, by definition, try to circumvent existing rules and regulations, or they exploit the absence of such rules on State level. To fight such individual cases is not so much a task of regular export control systems, whose function lies primarily in establishing standards and procedures for export controls on State level, but rather the task for intelligence services and their international cooperation. The basis of the export control regime is the Nuclear Non-Proliferation Treaty (NPT). Export controls can - and do - play an important role in fostering this universality goal by demanding the implementation of internationally agreed security standards in recipient countries before export licenses are granted. Drawn from the deliberations in the NPT conferences, the current standards to be demanded as conditions of supply are the following: Safeguards, Physical Protection, National export control provisions. According to the NPT system, export controls require IAEA verification in the recipient country. In addition, export controls enable States to provide information to the IAEA on exports and imports as required by the Additional Protocol. The 2005 NPT Review Conference will be an opportunity to review developments

  20. Understanding China's renewable energy technology exports

    International Nuclear Information System (INIS)

    Liu, Jialu; Goldstein, Don

    2013-01-01

    China became a major player in renewable energy (RE) technology during the 2000s. Chinese solar PV cell and module makers quickly dominated global sales in that industry, while the country's wind turbine producers became poised for significant exports after capturing their rapidly growing home market. In countries like the US, Chinese RE technology strength has been met with claims of excessive governmental support of exports. This study examines to what extent Chinese firms' solar PV and wind technology successes have been enabled by policy supports, and whether those policies appear to have been driven by broader goals versus RE export promotion per se. The evidence suggests that governmental policy toward both wind and solar originated in a push for export-competitive Chinese companies. But the specifics differed substantially due to the particular requirements of building technological capabilities in each: export readiness necessitated substantial support for domestic installation of wind but not solar PV power. The findings also suggest that as the decade of the 2000s progressed, environmental goals played an increasing role alongside export promotion in motivating and shaping Chinese RE technology policies. - Highlights: ► Export policy in the rise of Chinese renewable energy technologies is studied. ► Policy supported wind turbine firms' capabilities via domestic uptake, not exports. ► Pre-2009 solar module exports enjoyed, but did not depend on, export subsidies. ► Renewables development also fit wider technology and environmental policy goals.

  1. ER Stress and Lipid Metabolism in Adipocytes

    Directory of Open Access Journals (Sweden)

    Beth S. Zha

    2012-01-01

    Full Text Available The role of endoplasmic reticulum (ER stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

  2. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

    Science.gov (United States)

    Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

    2014-01-01

    Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

  3. Will Exports Prevail over Austerity?

    OpenAIRE

    Vasily Astrov; Vladimir Gligorov; Peter Havlik; Mario Holzner; Gabor Hunya; Kazimierz Laski; Sebastian Leitner; Zdenek Lukas; Anton Mihailov; Olga Pindyuk; Leon Podkaminer; Josef Pöschl; Sandor Richter; Waltraut Urban; Hermine Vidovic

    2010-01-01

    The Central, East and Southeast European (CESEE) economies will experience on average a minor rebound of economic growth to 1% in 2010 which will speed up to 2.5% in 2011 and 3.5% in 2012. GDP growth will be higher in the CIS countries and in Turkey, about average in the Central European NMS and lower in the SEE countries and the Baltics. Growth is currently driven mostly by exports which should outweigh the dampening effects of the austerity measures. Whether the countries will actually bene...

  4. A perspective on energy exports

    International Nuclear Information System (INIS)

    O'Connor, A.J.

    1983-06-01

    Based on New Brunswick Power's energy export experience over the past two decades, it appears that Canada could have a very special and unique opportunity to input into the US energy market over the coming decades. The CANDU reactor can offer one of these opportunities. Such business opportunities can be of very real benefit to both countries and to the particular regions involved. Like any other form of business, this one must be carefully planned and must be conducted in an environment conducive to the achievement of the objectives of the business

  5. Optimal fodring af goldkøer

    DEFF Research Database (Denmark)

    Bjerre-Harpøth, Vibeke; Damgaard, Birthe Marie

    2013-01-01

    Et forsøg har vist, at køer på lavt energiniveau i goldperioden var fysiologisk sundere og havde mindre risiko for at udvikle stofskiftesygdomme end køer på et højt energiniveau. Forsøget viste også, at køer på et normalt energiniveau i senlaktationen gav mere mælk i den efterfølgende laktation e...

  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....... Osing 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...... 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. Promoting exports in the energy technology area

    International Nuclear Information System (INIS)

    Iten, R.; Oettli, B.; Jochem, E.; Mannsbart, W.

    2001-01-01

    This report for the Swiss Federal Office of Energy (SFOE) examines the position of Switzerland as a leader in the investment goods markets for energy-efficiency products and for technologies for using renewable forms of energy. The report quotes figures for exports in these areas and discusses the difficulty of extracting useful data on these products from normal statistical data. Analyses made by a group of experts from the export-oriented technology field, energy service providers and representatives of export promotion institutions are presented and figures are quoted for various product categories. Factors promoting the competitiveness of Swiss products are discussed as well as those impeding it. An analysis of export potential is presented and measures to promote export are discussed. The report also discusses the aids and promotion activities that are considered necessary by companies in the field and the macro-economic perspectives of increased export promotion

  8. 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

  9. 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...... see these results as a first step in opening up the productivity-export black box, and provide a potential explanation for the big measured productivity premia for firms entering export markets....

  10. Export Failure and its Consequences: Theory and Evidence

    OpenAIRE

    Mora, Jesse

    2015-01-01

    The purpose of this dissertation is to argue that exporting is a risky endeavor and that there are consequences to export failure. Exporters pay high fixed costs to enter foreign markets, yet the majority will not export beyond one year. What happens to these exporters after they fail abroad? For these firms, exporting likely resulted in heavy profit losses. Despite this, trade literature often views exporting as a harmless exercise based on a simple cost-benefit analysis of foreign profits. ...

  11. Er moral bare noget vi leger?

    DEFF Research Database (Denmark)

    Thomsen, Frej Klem

    2014-01-01

    Hvis man er skeptiker, så er moral nemlig altid kun et udtryk for psykologi og kultur, også når det handler om for eksempel misbrug af børn i Tønder-sagen eller terror-angreb i Madrid, London og Mumbai .......Hvis man er skeptiker, så er moral nemlig altid kun et udtryk for psykologi og kultur, også når det handler om for eksempel misbrug af børn i Tønder-sagen eller terror-angreb i Madrid, London og Mumbai ....

  12. Export dynamics and sales at home

    OpenAIRE

    Nicolas Berman; Antoine Berthou; Jérôme Héricourt

    2012-01-01

    How do firms’ sales interact across markets? Are foreign and domestic sales complements or substitutes? Using a large French firm-level database that combines balance-sheet and product-destination specific export information over the period 1995-2001, we study the interconnections between exports and domestic sales. We identify exogenous shocks that affect the firms’ demand on foreign markets to instrument yearly variations in exports. We use alternatively as instruments product-destination s...

  13. Uranium enrichment export control guide: Gaseous diffusion

    Energy Technology Data Exchange (ETDEWEB)

    1989-09-01

    This document was prepared to serve as a guide for export control officials in their interpretation, understanding, and implementation of export laws that relate to the Zangger International Trigger List for gaseous diffusion uranium enrichment process components, equipment, and materials. Particular emphasis is focused on items that are especially designed or prepared since export controls are required for these by States that are party to the International Nuclear Nonproliferation Treaty.

  14. Vertical integration, disintegration and ability to export

    OpenAIRE

    Rossini, Giampaolo; Vici, Laura

    2007-01-01

    Recent literature on trade has emphasized the role of firms' heterogeneities in export performance and trade specialization of countries (Melitz, 2003; Melitz and Ottaviano, 2005). Exporting seems to be a strategy available only to most efficient and productive firms even in a framework with transport costs and no reciprocal dumping. We do not know much about the internal organization of these smarter companies which are exporting part of their production. However, from related theoretical (H...

  15. Nuclear exportation and importation - the Brazilian situation

    International Nuclear Information System (INIS)

    Lavos Coimbra, G.

    1986-01-01

    The author proposes to set up a working group which should be responsible for the compilation of laws, procedures, and national policies for the nuclear importation and exportation in the supplying and receiving countries. Shared international views would simplify the flow of imports and exports between the countries. The author describes the different phases of exportation and importation of nuclear material are processed in her country, Brazil. (CW) [de

  16. Import-push or Export-pull?

    DEFF Research Database (Denmark)

    Jäkel, Ina Charlotte

    2014-01-01

    predictions regarding the export market and the role of product differentiation. Empirical results for a sample of Danish manufacturing industries confirm the import- "push" hypothesis as well as the export- "pull" hypothesis, but also reveal differences across industries. The selection effect of trade...... is mainly driven by the "import-push" if product differentiation is high, whereas it is driven by the "export-pull" if goods are homogeneous....

  17. Import-push or Export-pull?

    DEFF Research Database (Denmark)

    Jäkel, Ina Charlotte

    predictions regarding the export market and the role of product differentiation. Empirical results for a sample of Danish manufacturing industries confirm the import-"push" hypothesis as well as the export-"pull" hypothesis, but also reveal differences across industries. The selection effect of trade...... is mainly driven by the "import-push" if product differentiation is high, whereas it is driven by the "export-pull" if goods are homogeneous....

  18. Export opportunities in developing countries

    International Nuclear Information System (INIS)

    Sullivan, J.

    1992-01-01

    Developing countries will offer major opportunities to US exporters of energy and related environmental equipment in the next ten years. These opportunities arise because the markets in developing countries will be growing much faster than those in the developed countries during this period, and because these countries will not in most cases have strong domestic manufacturers to compete against. US technologies will help these countries solve their energy, environmental, and economic development problems, and help the US solve its serious trade balance problems. This market will represent over $200 billion between now and 2000. There are, however, many potential problems. These include a lack of focus and coordination among US government trade assistance organizations, a lack of interest on the part of US firms in exporting and an unwillingness to make the needed investments, barriers put up by the governments of potential foreign customers, and strong international competition. This paper describes how the United States Agency for International Development's (A.I.D.) Office of Energy and other US agencies are helping US firms resolve these problems with a comprehensive program of information, trade promotion assistance, and co-funding of feasibility studies. In addition, there are monies available to match unfair concessionary financing offered by our major competitors

  19. Nuclear exports and international cooperation

    International Nuclear Information System (INIS)

    McCardle, J.J.

    1981-06-01

    Canada's nuclear export policy together with its non-proliferation and safeguards policy embrace both the country's desire to promote international cooperation in the peaceful uses of nuclear energy and its effort to minimize the risk of further proliferation of nuclear weapons. This policy reflects the belief that only if Canadian parliamentary and public opinion can be convinced that Canada's nuclear exports will not contribute to nuclear proliferation will the long-term health of the country's nuclear industry be assured. Canada requires a political commitment to non-proliferation from its nuclear partners, and looks to the IAEA to administer safeguards on nuclear material of Canadian origin to guarantee that commitment. Agreements reached with its nuclear partners are in accordance with provisions of the non-proliferation treaty and include a contingency provision for fall-back safeguards if the other state should withdraw from the NPT. Provision is made for mutual agreement on reprocessing and enrichment of nuclear material. Agreements have been reached with some twenty nuclear partners, and efforts are continuing to come to new international understanding on reprocessing, enrichment, and plutonium storage

  20. Thermodynamic assessments of the Ag-Er and Er-Y systems

    International Nuclear Information System (INIS)

    Wang, S.L.; Wang, C.P.; Liu, X.J.; Tang, A.T.; Pan, F.S.; Ishida, K.

    2010-01-01

    The phase diagrams and thermodynamic properties in the Ag-Er and Er-Y binary systems have been assessed by using the CALPHAD (Calculation of Phase Diagrams) method on the basis of the experimental data including the thermodynamic properties and phase equilibria. The Gibbs free energies of the liquid, bcc, fcc, and hcp phases were described by the subregular solution model with the Redlich-Kister equation, and those of intermetallic compounds (Ag 2 Er and AgEr phases) were treated as stoichiometric compounds, and Ag 51 Er 14 phase was modeled by the sublattice model in the Ag-Er binary system. The thermodynamic parameters of the Ag-Er and Er-Y binary systems were obtained, and an agreement between the calculated results and experimental data was obtained for each binary system.

  1. The Puzzle of the Missing Greek Exports

    OpenAIRE

    Uwe Boewer; Vasiliki Michou; Christoph Ungerer

    2014-01-01

    Why is Greece such a surprisingly closed economy? We employ a gravity model of trade to explain the appallingly poor export performance of Greece and argue that weak institutional quality accounts for a large part of this shortfall. Using a rich dataset of bilateral value-added exports of goods and services of 39 exporters and 56 importers for 18 sectors, we first estimate that Greece exports ? less than what regular international trade patterns would predict on basis of Greek GDP, the size o...

  2. Export Controls: Controls Over the Export Licensing Process for Chemical and Biological Items

    National Research Council Canada - National Science Library

    2005-01-01

    .... foreign policy should read this report. The report discusses the effectiveness of the DoD review process for export license applications and updates to Federal export regulations to prevent the proliferation of items that could pose...

  3. 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.

  4. 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...

  5. Export Margins, Price and Quantity of Belarus’s Export Growth

    Directory of Open Access Journals (Sweden)

    Otamurodov Shavkat

    2017-03-01

    Full Text Available This paper examines the sources of Belarus’s export growth and decomposes export growth into extensive and intensive margins. This study also aims to determine export margins for intermediate and final goods and to determine the price and quantity components of the intensive export margin. In order to achieve the desired objectives, we use two methods for decomposing export growth, the count method and the export shares method. We analyse Belarus's export growth using export data at the HS-6 digit level for the 2004-2014 period. Our results show that Belarus's exports grew mainly due to growth in the price margin during the studied period 2004-2014. However, the extensive margin was important in export growth to some extent. Comparing the growth rate across final and intermediate goods reveals that although the share of final products in Belarus’s exports is not very big (18.9% in 2014, the average annual growth in exports of final products is higher than that of intermediate goods. Our investigation also shows that Belarus produces a wide range of commodities, but the share of the most of these commodities is not large; its exports depend on a restricted range of commodities. Moreover, most of the commodities are exported to Russia and Ukraine. Our results give us reason to assume that finding new markets for their new products is one of the main challenges for developing countries wishing to increase their exports by an extensive margin. This has important implications for how policy makers promote the trade and diversification of exports.

  6. Neoclassical transport in ERS regime

    International Nuclear Information System (INIS)

    Lin, Z.; Tang, W.; Lee, W.W.

    1996-01-01

    The core ion thermal conductivity has been observed to fall below the standard neoclassical level in recent TFTR reversed magnetic shear discharges. Due to the combination of high central q and small local inverse aspect ratio, the ion poloidal gyroradius can be larger than the minor radius and comparable to the pressure gradient scale length in this ERS regime. It is then expected that finite orbit width effects play a key role in modifying the standard picture of neoclassical transport. Specifically, both the trapped particle fraction and the banana orbit width axe reduced by the finite minor radius and possibly by the pressure-gradient-driven radial electric field. In addition, the steep pressure gradient can generate neoclassical poloidal flows which, in turn, could reduce the particle and heat transports. Results from analytic estimates as well as those from full toroidal gyrokinetic neoclassical simulations will be presented

  7. Ungdomslitteratur former(er) sig

    DEFF Research Database (Denmark)

    Henkel, Ayoe Qvist

    2016-01-01

    Igennem en 'mediesensitiv' analyse af romanen "Akavet" af Ronnie Andersen (2014) og perspektivering til andre aktuelle romaner for og med unge undersøger artiklen, hvordan ungdomslitteratur udvikler sig i dialog med digitale og mediebaserede impulser, og hvilke konsekvenser for udsigelserne om...... ungdomsliv og ungdomslitteraturens æstetik og mulige egenart, denne udvikling har. Artiklen baserer sig på en materialitetstilgang særligt inspireret af N. Katherine Hayles, som ikke tidligere har fået opmærksomhed i læsninger af ungdomslitteratur eller i diskussioner af ungdomslitteraturens mulige egenart......, at ungdomslitteratur drejer sig om unges udviklingsproces fra barndom og til voksenhed og dermed skildrer en overgang præget af linearitet, modning og vækst. Artiklen konkluderer, at der er ungdomslitteratur, der realiseres på andre præmisser, og Akavet kan ses som eksponent for en bevægelse fra ungdomslitteratur som...

  8. Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

    Science.gov (United States)

    Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

    2018-05-08

    Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

  9. 75 FR 70905 - President's Export Council: Meeting of the President's Export Council

    Science.gov (United States)

    2010-11-19

    .... ACTION: Notice of an open meeting. SUMMARY: The President's Export Council will hold a meeting to discuss.... exports, jobs, and growth. DATES: December 9, 2010 at 9 a.m. (EST). ADDRESSES: The President's Export... trade and report to the President on its activities and on its recommendations for expanding U.S...

  10. 76 FR 54193 - Fiscal Year 2012 Veterinary Import/Export, Diagnostic Services, and Export Certification for...

    Science.gov (United States)

    2011-08-31

    ...] Fiscal Year 2012 Veterinary Import/Export, Diagnostic Services, and Export Certification for Plants and.... SUMMARY: This notice pertains to user fees charged for Veterinary Services animal quarantine and other..., organisms, and vectors; for certain veterinary diagnostic services; and for export certification of plants...

  11. 76 FR 11756 - Action Affecting Export Privileges; Ali Amirnazmi; Order Denying Export Privileges

    Science.gov (United States)

    2011-03-03

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Action Affecting Export Privileges; Ali Amirnazmi; Order Denying Export Privileges In the Matter of: Ali Amirnazmi, Register 63302-066, FCI... release and forfeit $81,277.37. Section 766.25 of the Export Administration Regulations (``EAR'' or...

  12. Development of microstructured large area magnetic calorimeters with Au:Er- and Ag:Er-sensors for the detection of x-ray quanta and high energetic particles

    International Nuclear Information System (INIS)

    Burck, Andreas

    2008-01-01

    This thesis describes the development of large-area magnetic calorimeters which could for example be used for the investigation of the dissociative recombination or the measurement of the Lamb-shift for hydrogenlike heavy ions. The detectors consist of two meandershaped niobium thin film pickup coils and a paramagnetic sensor. The deposition of energy in the sensor results in a temperature change and therefore in a change of magnetisation of the sensor, which can be measured by a SQUID-magnetometer with high precision. As sensormaterials a dilute alloy of gold-erbium (Au:Er) as well as silver-erbium (Ag:Er) were used. Whereas the Ag:Er-sensor was glued on the pickup coil the Au:Er-sensor was for the first time microstructured by a novel microstructuring process established in this thesis. For the characterisation of the detectors and the sensormaterials a fluorescence source and a 55 Fe source were used. The thermodynamic properties of the Au:Er-sensors thereby show promising results, as the magnetisation shows bulk properties down to 20 mK. The measurements of the signalize and the magnetisation with the detector which was equipped with a Ag:Er-sensor showed that the thermodynamic properties of the Ag:Eralloy could be fully described. Furthermore the shape of the pulses, the noise and the energy resolution of both detectors will be discussed. (orig.)

  13. Scheme to reward microgenerators exporting excess electricity

    International Nuclear Information System (INIS)

    2007-01-01

    Many suppliers are offering tariffs for export. However, many of the tariffs on offer deliver a value that is higher than the underlying commercial value of the electricity to the supplier. In most cases suppliers do not currently register the export within the industry's settlement arrangements and so gain no value from the export they have purchased. It is clear from this that the current situation is unlikely to be sustainable and suppliers will not be able to offer significant payment for a product that has little commercial value to them when the numbers of exporting microgenerators increases. Initiatives to simplify and streamline the existing trading arrangements should be progressed; this should include simplification of processes for registering new export customers and improvements in the provision of new export meters. Suppliers should initiate the change management procedures required to progress Option 1 (allowing suppliers to register a customer's export and import under a single registration (a single MPAN)) through the industry's normal change management procedures. Ofgem should ensure that its review of the Structure of Distribution charges includes the treatment of DUoS charges for customers with microgeneration and ensure that they properly reflect the benefits of microgeneration. Any changes that are progressed should not prevent the subsequent introduction of 'smart meters' that could process both import and export electricity data. Ofgem should ensure that the cost effectiveness of including both an import and export capability in all new metering systems is assessed as part of the metering innovation agenda. Suppliers should make the prices they are offering for export more widely available in a simple and easy to understand form. Government should consider whether additional intervention is required to yield a higher value for exported electricity (or total generation) via mechanisms such as those contemplated under Option 3 (The supplier

  14. Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the nanoparticle [Gd@C82(OH)22]n: A systems biology study.

    Science.gov (United States)

    Wang, Lin; Meng, Jie; Cao, Weipeng; Li, Qizhai; Qiu, Yuqing; Sun, Baoyun; Li, Lei M

    2014-06-01

    The nanoparticle gadolinium endohedral metallofullerenol [Gd@C82(OH)22]n is a new candidate for cancer treatment with low toxicity. However, its anti-cancer mechanisms remain mostly unknown. In this study, we took a systems biology view of the gene expression profiles of human breast cancer cells (MCF-7) and human umbilical vein endothelial cells (ECV304) treated with and without [Gd@C82(OH)22]n, respectively, measured by the Agilent Gene Chip G4112F. To properly analyze these data, we modified a suit of statistical methods we developed. For the first time we applied the sub-sub normalization to Agilent two-color microarrays. Instead of a simple linear regression, we proposed to use a one-knot SPLINE model in the sub-sub normalization to account for nonlinear spatial effects. The parameters estimated by least trimmed squares- and S-estimators show similar normalization results. We made several kinds of inferences by integrating the expression profiles with the bioinformatic knowledge in KEGG pathways, Gene Ontology, JASPAR, and TRANSFAC. In the transcriptional inference, we proposed the BASE2.0 method to infer a transcription factor's up-regulation and down-regulation activities separately. Overall, [Gd@C82(OH)22]n induces more differentiation in MCF-7 cells than in ECV304 cells, particularly in the reduction of protein processing such as protein glucosylation, folding, targeting, exporting, and transporting. Among the KEGG pathways, the ErbB signaling pathway is up-regulated, whereas protein processing in endoplasmic reticulum (ER) is down-regulated. CHOP, a key pro-apoptotic gene downstream of the ER stress pathway, increases to nine folds in MCF-7 cells after treatment. These findings indicate that ER stress may be one important factor that induces apoptosis in MCF-7 cells after [Gd@C82(OH)22]n treatment. The expression profiles of genes associated with ER stress and apoptosis are statistically consistent with other profiles reported in the literature, such as

  15. Determinants of export demand and their stability in Ghana | Osei ...

    African Journals Online (AJOL)

    Therefore, the study examines the factors that determine export demand in Ghana for the period 1970 to 2011. Using Johansen cointegration methodology, export demand is cointegrated with real effective exchange rate, domestic export prices, world export prices and real world income. The export demand function exhibits ...

  16. 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...

  17. 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 or...

  18. 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...

  19. Multiple band structure in 156Er

    International Nuclear Information System (INIS)

    Sunyar, A.W.; Der Mateosian, E.; Kistner, O.C.; Johnson, A.; Lumpkin, A.H.; Thieberger, P.

    1976-01-01

    The 142 Nd( 18 O,4n) 156 Er reaction at 90-95 MeV was used to study 156 Er high-spin states to spin 24. In addition to the background ground-state band, two well developed off-spin side bands, one of each parity, were observed. (Auth.)

  20. Er der en underviser til stede?

    DEFF Research Database (Denmark)

    Christiansen, René Boyer; Nortvig, Anne-Mette; Rosenlund, Lea Tilde

    2015-01-01

    I de senere år er MOOC (Massive Open Online Courses) blevet en faktor på uddannelsesområdet. MOOC-forskning er et forholdsvist nyt felt, men har inden for de seneste 2-3 år udviklet sig med hastige skridt (Liyanagunawardena et al. 2013, Bayne & Ross 2014). En stor del af denne forskning har haft...

  1. Led strategisk med 3 F'er

    DEFF Research Database (Denmark)

    Klausen, Kurt Klaudi

    2017-01-01

    Artiklen gennemgår kort de tre F'er: at fremskrive, forudse og forestille som strategiske værktøjer til strategic forecast......Artiklen gennemgår kort de tre F'er: at fremskrive, forudse og forestille som strategiske værktøjer til strategic forecast...

  2. Et kors er ikke bare et kors

    DEFF Research Database (Denmark)

    Bach-Nielsen, Carsten

    2015-01-01

    Om et kors, der er rejst uden for den danske kirke i Bruxelles; formodentlig en afledning af det såkaldte Brabanterkors.......Om et kors, der er rejst uden for den danske kirke i Bruxelles; formodentlig en afledning af det såkaldte Brabanterkors....

  3. Er formen blevet vigtigst i politik?

    DEFF Research Database (Denmark)

    Etemadi, Maziar Haghpaidar

    2005-01-01

    RETORIK: Retorikken er kunsten at tage ordet - skriftligt eller mundtligt - og udtrykke sig smukt og velformuleret. Gorgias (ca. 490-ca. 390 f. Kr.) fra Leontinoi på Sicilien betragtes som ophavsmanden til den første endelige formulering af retorikkens virke og muligheder: "Talen er en mægtig...

  4. En isoleret verden er en bedre verden

    DEFF Research Database (Denmark)

    Enrum, Nils

    2014-01-01

    Man skal ikke kaste med sten, hvis man bor i et hus med energimærke D ... Men problemet med varmetab fra danske boliger er til at løse......Man skal ikke kaste med sten, hvis man bor i et hus med energimærke D ... Men problemet med varmetab fra danske boliger er til at løse...

  5. "Det man siger er man selv..."

    DEFF Research Database (Denmark)

    Næsby, Torben; Nørgaard, Britta; Uddholm, Mats

    forhold, der er hermeneutisk, strukturelt og relationelt bestemt. Praksisviden kan ikke være objektiv i gængs forstand, men det behøver ikke at diskvalificere denne viden. Forståelse er altid knyttet til den sag og bundet til den situation man står overfor og i som professionel og som menneske....

  6. Er3+ phosphate glass optical waveguide amplifiers at 1.5 μm on silicon

    Science.gov (United States)

    Yan, Yingchao; Faber, Anne J.; de Waal, Henk

    1996-01-01

    RF-sputtering techniques were employed to produce Er-doped phosphate glass films on thermally oxidized silicon wafers. Film compositions were characterized by X-ray photoelectron spectroscopy. As-deposited films showed very low Er luminescence lifetimes. By postannealing of deposited films in pure oxygen, Er photoluminescence emission lifetime of the 4I13/2 - 4I15/2 transition could be increased from 1 - 2 ms to 8 - 9 ms. The long Er lifetime of the deposited films is very promising for achieving an optical gain. A dependence of measured lifetimes on pump power was observed which are related to a up-conversion quenching process. After postannealing, the sputtered waveguides showed relatively low attenuation loss at the potential pumping and signaling wavelengths. The loss spectrum from 700 nm to 1600 nm was measured by two-prism coupling. The films were easy to be patterned by lithography and ridge channel waveguides were developed by argon plasma etching.

  7. Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, Stephan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Boyd, Stephen [Univ. of New Mexico, Albuquerque, NM (United States); Cantor, Robin [STAR Cryoelectronics, Santa Fe, NM (United States)

    2015-11-25

    This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

  8. Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, Stephan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Boyd, Stephen [Univ. of New Mexico, Albuquerque, NM (United States); Cantor, Robin [STAR Cryoelectronics, Santa Fe, NM (United States)

    2016-05-06

    This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

  9. Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

    International Nuclear Information System (INIS)

    Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

    2016-01-01

    This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

  10. Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

    International Nuclear Information System (INIS)

    Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

    2015-01-01

    This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

  11. Determinants Of Vertical And Horizontal Export Diversification ...

    African Journals Online (AJOL)

    The study also reveals domestic investment plays an important role to enhance vertical as well as horizontal export diversification for East Asia, while it only ... resource-based industries and gradually shift production and exports from customary products to more dynamic ones by developing competitive advantage in the ...

  12. Export Specialisation and Local Economic Growth

    NARCIS (Netherlands)

    Naude, Wim; Bosker, Maarten; Matthee, Marianne

    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

  13. 14 CFR 1274.942 - Export licenses.

    Science.gov (United States)

    2010-01-01

    ... writing, that the Agreement Officer authorize it to export ITAR-controlled technical data (including... appropriate licenses or other approvals, if required, for exports of hardware, technical data, and software, or for the provision of technical assistance. (b) The Recipient shall be responsible for obtaining...

  14. 19 CFR 351.520 - Export insurance.

    Science.gov (United States)

    2010-04-01

    ... Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Identification and Measurement of Countervailable Subsidies § 351.520 Export insurance. (a) Benefit—(1) In general. In the case of export insurance, a benefit exists if the premium rates charged are inadequate to...

  15. 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,

  16. 77 FR 34342 - Order Denying Export Privileges

    Science.gov (United States)

    2012-06-11

    ..., Luohu District, Shenzhen, 518001, China. On January 26, 2011, in the U.S. District Court, District of... Economic Powers Act (50 U.S.C. 1701 et seq. (2000)) (``IEEPA'') and violating Section 38 of the Arms Export Control Act (22 U.S.C. 2778 (2000)) (``AECA''). Specifically, Wu was convicted of illegally exporting...

  17. 77 FR 34340 - Order Denying Export Privileges

    Science.gov (United States)

    2012-06-11

    ... Economic Powers Act (50 U.S.C. 1701 et seq. (2000)) (``IEEPA'') and Section 38 of the Arms Export Control Act (22 U.S.C. 2778 (2000)) (``AECA''). Specifically, Chitron- US was convicted of illegally exporting... components designated on the U.S. Munitions List to China through Hong Kong between 2004 and 2007. In...

  18. 78 FR 37785 - Order Denying Export Privileges

    Science.gov (United States)

    2013-06-24

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the... Order with the Under Secretary of Commerce for Industry and Security. The appeal must be filed within 45... the Internal Security Act of 1950 (50 U.S.C. 783(b)), or section 38 of the Arms Export Control Act (22...

  19. 78 FR 61953 - Order Denying Export Privileges

    Science.gov (United States)

    2013-10-08

    ... counsel, Gormley has indicated that he does not intend to contest BIS's decision to deny his export..., selling, delivering, storing, disposing of, forwarding, transporting, financing, or otherwise servicing in... Regulations that has been or will be exported from the United States, including financing or other support...

  20. 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...

  1. 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...

  2. Fixed export cost heterogeneity, trade and welfare

    DEFF Research Database (Denmark)

    Jørgensen, Jan Guldager; Schröder, Philipp J.H.

    2008-01-01

    -country intra-industry trade model where firms are of two different marginal costs types and where fixed export costs are heterogeneous across firms. This model traces many of the stylized facts of international trade. However, we find that with heterogeneous fixed export costs there exists a positive bilateral...

  3. 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...

  4. 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 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE General Provisions § 4.80 Exports. The regulations in...

  5. 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...

  6. Export versus domestic market opportunities

    International Nuclear Information System (INIS)

    Melin, S.

    2006-01-01

    This presentation analyzed the current global wood pellet market and evaluated some of the forces currently driving market expansion. Global wood pellet production statistics were also presented. Large forest companies are now expanding into the energy sector and seeking to produce processing heat from biomass in addition to creating value-added products such as wood pellets, ethanol and electricity. The European biomass action plan has promised to increase production of energy from biomass from 4 per cent to 8 per cent by 2010. Various biomass boiler eco-directives have been established internationally, and some countries in Europe are now aggressively promoting the use of combined heat and power (CHP) systems. Biofuels mixing quotas have been established in various countries as well as tax relief plans for users of bio-fuels. As a result of these developments, along with various new directives, wood pellet consumption in Europe has increased from approximately 1 million tonnes in 2000 to 5 million tonnes in 2005. Consumption of wood pellets in Canada has increased only marginally in the same time period. While Canada currently exported 330,000 tonnes of wood pellets to Europe in 2006, it is expected that exports will increase to 800,000 tonnes by 2010. Other potential markets for Canadian wood pellets include South America, South Africa, Japan, and China. Production of wood pellets in China is expected to increase from current negligible production figures to approximately 50 million tonnes by 2020. Biomass research and development activities in Europe and North America are continuing to improve the calorific value of wood pellets and improve their mechanical strength. Researchers are also investigating methods of lowering wood pellet production costs. refs., tabs., figs

  7. Decoherence and absorption of Er3+:KTiOPO4 (KTP) at 1.5 μm

    International Nuclear Information System (INIS)

    Böttger, Thomas; Thiel, C.W.; Sun, Y.; Macfarlane, R.M.; Cone, R.L.

    2016-01-01

    We present results of laser absorption spectroscopy and two-pulse photon echo decoherence measurements on the lowest 4 I 15/2 to lowest 4 I 13/2 transition in Er 3+ : KTiOPO 4 (KTP—potassium titanyl phosphate) for the optical transition located at 1537.238 nm. This transition was found to have an inhomogeneous absorption linewidth of 950 MHz and pronounced polarization dependence. Two-pulse photon echo decay measurements as a function of applied magnetic field strength at 1.9 K revealed a narrow homogeneous linewidth of 2.5 kHz at 0.2 T that increased to 5.8 kHz at 1.2 T and then decreased to 1.6 kHz at 4.5 T. This behavior was successfully described by decoherence due to Er 3+ –Er 3+ magnetic dipole interactions. Significant superhyperfine coupling of Er 3+ spins to the nuclear moments of ions in the host lattice was observed, modulating the photon echo decay at low magnetic fields and limiting the effective homogenous linewidth at high fields. Combined with the well-established potential of KTP for fabrication of high-quality optical waveguides and integrated non-linear frequency conversion, our results suggest that Er 3+ :KTP is a promising material system for practical spectral hole burning, signal processing, and quantum information applications. - Highlights: • Bulk Er 3+ :KTP has dominant Er 3+ site at 1537.238 nm with Γ inh of 950 MHz and T 1 of 16.9 ms. • Two-pulse photon echoes revealed magnetic field dependent kHz-wide homogeneous linewidth. • Decoherence modeled using direct-phonon driven Er 3+ –Er 3+ magnetic dipole-dipole interactions. • Evidence of superhyperfine coupling of Er 3+ spins to nuclear moments of host ions. • Er 3+ :KTP is a promising material system for quantum memory and signal processing applications.

  8. 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...

  9. Macroeconomic Effects of Export Demand in Nigeria

    Directory of Open Access Journals (Sweden)

    Bolaji Adesola Adesoye

    2017-05-01

    Full Text Available This study examines the macroeconomic effects of aggregate export demand in Nigeria using annual time series data between 1970 and 2013. The paper made use of the ordinary least square method to analyse the long-run relationship for the period under study. The empirical results confirm that there exists a unique and significant long-run equilibrium relationship among export volume, world income, crude oil price, domestic output, exchange rate and cost of doing business. The estimated results show that domestic income has the highest elasticity, followed by world’s output and cost of doing business, which all report positive relations. Other macroeconomic factors reported negative relationship with aggregate export volume. Thus, an important policy implication of our findings is that stabilizing Nigeria’s export earnings potential by counteracting the external factors that influence adversely the Nigerian exports such as crude oil price and cost of doing business.

  10. Exports and economic growth in Nigeria

    Directory of Open Access Journals (Sweden)

    Goodly Otto

    2016-09-01

    Full Text Available Nigeria is an oil dependent economy, over 90 per cent of its exports receipts in recent years flow from petroleum but this sector is currently affected by local challenges, which include insecurity, oil thefts, sabotage and an unfriendly operational environment. These challenges are generating loses for the major producers and encouraging capital flight but amidst this situation, the economy is said to be having an impressive growth. This paradox informed this research. The study was designed to see the nexus between exports and economic growth in Nigeria. Using data from the Central Bank of Nigeria spanning 1980-2011, the study with the aid of OLS regression analysis found a strong relationship between Exports and economic growth in Nigeria. Nigeria will be better served if it diversifies its export base. It must also create structures that lead to better redistribution of export incomes within the local economy.

  11. Exporting nuclear engineering and the industry's viewpoint

    International Nuclear Information System (INIS)

    Barthelt, K.

    1986-01-01

    Nuclear energy offers all possibilities to reduce the energy problems in the world which arise with the world-wide increasing population and the energy demand connected with it. The Federal Republic of Germany lives on the exports of refined technical methods which also include nuclear engineering. The exports of nuclear engineering should lead to a technology transfer with guidance and training on an equal basis between the industrial and developing countries. The preconditions of exporting nuclear-technical systems are a well-functioning domestic market and a certain support by the government, especially with regard to giving guarantees for the special exports risks of these big projects. On the other hand, exports are also needed in order to be able to continue providing high-level technology for the domestic market. (UA) [de

  12. The Export Promoting Effect of Emigration

    DEFF Research Database (Denmark)

    Hiller, Sanne

    The theoretical claim that ethnic networks encourage trade has found broad empirical support in the literature on migration, business networks and international trade. Ethnic networks matter for the exporting firm, as they exhibit the potential to lower fixed and variable cost of exporting....... This paper provides a first attempt to identify the export-promoting effect of emigration on the firm level. Using detailed Danish firm-level data, we can parsimoniously control for export determinants other than emigration, unobserved heterogeneity at the firm level, as well as for self-selection of firms...... into exporting. Additionally accounting for taste similarity between Denmark and its trade partners, our findings suggest a positive effect of emigration on Danish manufacturing trade within Europe, thereby corroborating preceding studies on aggregate data. Nevertheless, as a novel insight, our analysis reveals...

  13. Nuclear exports. Parliamentary control and confidentiality

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2015-01-01

    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.

  14. Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis.

    Science.gov (United States)

    Song, Yu-Feng; Hogstrand, Christer; Wei, Chuan-Chuan; Wu, Kun; Pan, Ya-Xiong; Luo, Zhi

    2017-09-01

    The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway. Zn also induced an increase in intracellular Ca 2+ level, which could be partially prevented by dantrolene (RyR receptor inhibitor) and 2-APB (IP3 receptor inhibitor), demonstrating that the disturbed Ca 2+ homeostasis in ER contributed to ER stress and dysregulation of lipolysis. Inhibition of ER stress by PBA attenuated UPR, inhibited the activation of cAMP/PKA pathway and resulted in down-regulation of lipolysis. Inhibition of protein kinase RNA-activated-like ER kinase (PERK) by GSK2656157 and inositol-requiring enzyme (IRE) by STF-083010 differentially influenced Zn-induced changes of lipid metabolism, indicating that PERK and IRE pathways played different regulatory roles in Zn-induced lipolysis. Inhibition of PKA by H89 blocked the Zn-induced activation of cAMP/PKA pathway with a concomitant inhibition of ER stress-mediated lipolysis. Taken together, our findings highlight the importance of the ER stress-cAMP/PKA axis in Zn-induced lipolysis, which provides new insights into Zn toxicology in fish and probably in other vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 77 FR 72324 - Export Trade Certificate of Review

    Science.gov (United States)

    2012-12-05

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 85-17A18] Export Trade Certificate of Review ACTION: Notice of Application to Amend the Export Trade Certificate of Review Issued to... to amend an Export [[Page 72325

  16. GABAB receptor cell surface export is controlled by an endoplasmic reticulum gatekeeper

    Science.gov (United States)

    Doly, Stéphane; Shirvani, Hamasseh; Gäta, Gabriel; Meye, Frank; Emerit, Michel-Boris; Enslen, Hervé; Achour, Lamia; Pardo-Lopez, Liliana; Kwon, Yang Seung; Armand, Vincent; Gardette, Robert; Giros, Bruno; Gassmann, Martin; Bettler, Bernhard; Mameli, Manuel; Darmon, Michèle; Marullo, Stefano

    2016-01-01

    Summary Endoplasmic reticulum (ER) release and cell surface export of many G protein-coupled receptors (GPCRs), are tightly regulated. For GABAB receptors of GABA, the major mammalian inhibitory neurotransmitter, the ligand-binding GB1 subunit is maintained in the ER by unknown mechanisms in the absence of hetero-dimerization with the GB2 subunit. We report that GB1 retention is regulated by a specific gatekeeper, PRAF2. This ER resident transmembrane protein binds to GB1, preventing its progression in the biosynthetic pathway. GB1 release occurs upon competitive displacement from PRAF2 by GB2. PRAF2 concentration, relative to that of GB1 and GB2, tightly controls cell surface receptor density and controls GABAB function in neurons. Experimental perturbation of PRAF2 levels in vivo caused marked hyperactivity disorders in mice. These data reveal an unanticipated major impact of specific ER gate-keepers on GPCR function and identify PRAF2 as a new molecular target with therapeutic potential for psychiatric and neurological diseases involving GABAB function. PMID:26033241

  17. Supervision og de tre k´er

    DEFF Research Database (Denmark)

    Schilling, Benedicte; Jacobsen, Claus Haugaard; Nielsen, Jan

    2010-01-01

    Kontrol, kontrakt og kontekst er supervisionens tre k'er. Men hvad er supervision i det hele taget for en størrelse, der spillerså central en rolle for den psykologfaglige profession?......Kontrol, kontrakt og kontekst er supervisionens tre k'er. Men hvad er supervision i det hele taget for en størrelse, der spillerså central en rolle for den psykologfaglige profession?...

  18. The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs

    Directory of Open Access Journals (Sweden)

    Chunman Li

    2017-10-01

    Full Text Available G-protein-coupled receptors (GPCRs constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.

  19. En hat er vel en hat ... eller?

    DEFF Research Database (Denmark)

    Bøilerehauge, Dorrit

    2007-01-01

    Mens vi kører i høj fart på "the information highway" - i den helt store bus midt på vejen - glemmer vi ofte noget meget vigtigt i vores glæde over, at verden tilsyneladende åbner sig for os, og vi kan kommunikere med hele verden med ét klik. Vi glemmer, at selvom trafikskilte som oftest er ens -...... - så er selve trafikken og forventningerne blandt medtrafikanterne helt forskellige fra det, vi er vant til. Udgivelsesdato: Februar...

  20. Ytringsfriheden er ikke nødvendig

    DEFF Research Database (Denmark)

    Lauritzen, Pia

    2008-01-01

    nemlig godt konstatere, at ytringsfriheden ikke er nødvendig uden dermed at give afkald på frihed og demokrati.Vi kan oven i købet mene, at ytringsfriheden ophører med at være frihed, når vi betragter den som nødvendig. Og det er lige nøjagtig det, jeg efterlyser: at vi bruger filosoffer som Immanuel...... Kant og Luigi Pareyson til at forstå, at friheden er betydelig mere kompleks, end vi gør den til i øjeblikket....

  1. Hvordan er det å leve med CRPS?

    OpenAIRE

    Hovind, Thomas

    2014-01-01

    Hensikten med denne studien er å se på hvordan pasienter med komplekst regionalt smertesyndrom (CRPS) opplever å leve med tilstanden og hvordan disse pasientene har opplevd å bli møtt i helsevesenet. CRPS er en langvarig tilstand med sterke smerter som kan medføre økt smerterespons, redusert funksjon og nedsatt livskvalitet hos pasientene. Studien er en kvalitativ undersøkelse basert på dybdeintervju av fire pasienter med CRPS. Pasientene ble rekruttert fra en smerteavdeling i Nord-Norge og u...

  2. Branding er ikke til at komme udenom

    DEFF Research Database (Denmark)

    Hermansen, Judy

    2008-01-01

    Søren Askegaard definerer branding som "et iscenesat og afkodet symbolunivers". Det vil sige, at vi på den ene side har virksomhedens strategiske profilering, hvor den forsøger at skabe sig en særlig differentieret og positioneret profil, som adskiller den fra andre virksomheder. "Og det er denne...... strategiske kommunikation, der gør at branding er et ledelsesbegreb og ikke kun et markedsføringsbegreb. Det er ikke staffage, men værdier, som skal gennemsyre alle organisationens aktiviteter." Udgivelsesdato: maj...

  3. Protein Export by the Mycobacterial SecA2 System Is Determined by the Preprotein Mature Domain

    Science.gov (United States)

    Feltcher, Meghan E.; Gibbons, Henry S.; Ligon, Lauren S.

    2013-01-01

    At the core of the bacterial general secretion (Sec) pathway is the SecA ATPase, which powers translocation of unfolded preproteins containing Sec signal sequences through the SecYEG membrane channel. Mycobacteria have two nonredundant SecA homologs: SecA1 and SecA2. While the essential SecA1 handles “housekeeping” export, the nonessential SecA2 exports a subset of proteins and is required for Mycobacterium tuberculosis virulence. Currently, it is not understood how SecA2 contributes to Sec export in mycobacteria. In this study, we focused on identifying the features of two SecA2 substrates that target them to SecA2 for export, the Ms1704 and Ms1712 lipoproteins of the model organism Mycobacterium smegmatis. We found that the mature domains of Ms1704 and Ms1712, not the N-terminal signal sequences, confer SecA2-dependent export. We also demonstrated that the lipid modification and the extreme N terminus of the mature protein do not impart the requirement for SecA2 in export. We further showed that the Ms1704 mature domain can be efficiently exported by the twin-arginine translocation (Tat) pathway. Because the Tat system exports only folded proteins, this result implies that SecA2 substrates can fold in the cytoplasm and suggests a putative role of SecA2 in enabling export of such proteins. Thus, the mycobacterial SecA2 system may represent another way that bacteria solve the problem of exporting proteins that can fold in the cytoplasm. PMID:23204463

  4. Exporting Rambutan to United States: One Reality?

    International Nuclear Information System (INIS)

    Ahmad Zainuri Mohd Dzomir; Zainon Othman; Mohd Sidek Othman

    2011-01-01

    Rambutan is a one of commodity that are passed by United States of America authority to be market in that states. The main condition for the approval is the exporter must use irradiation technology as quarantine treatment to monitor the insects in there. United States of America's Agriculture Department (USDA-APHIS) has make early survey to the facilities involved in exporting process chain to overview Malaysia preparedness for this purpose. This paper work will discussed the possibility of this exporting implemented based on conditions rule by the USDA. (author)

  5. Oil exporting countries need nuclear power

    International Nuclear Information System (INIS)

    Stauffer, T.R.

    1982-01-01

    The economic rationale for nuclear power in the oil exporting countries is analysed, with the collateral objective of defining the size of the potential market in terms of the exporting countries' economic opportunities and energy needs. The need for appropriate new institutions for licensing reactors, training personnel, and starting up plants follows directly from the size of the market and the economic incentives for the oil exporters to husband gas and oil. Gas and oil resources of the Middle Eastern countries are discussed, and future electricity needs estimated. (author)

  6. How Important is Export-Platform FDI?

    DEFF Research Database (Denmark)

    Geishecker, Ingo; Nielsen, Jørgen Ulff-Møller; Pawlik, Konrad

    This paper investigates the link between export performance and multinational enterprise presence utilizing trade and industry data for Polish manufacturing industries for the years 1994-2002. Decomposing trade into final and intermediate goods and assessing the impact of foreign-owned capital...... on the respective export performance of Polish industries, we suggest a significant role of export-platform FDI into Poland, while the importance of FDI for vertical integration is limited suggesting that the sourcing of intermediate goods from Poland primarily occurs through arm's-length contractual outsourcing...

  7. Exporting licensing regulations affecting US geothermal firms

    Energy Technology Data Exchange (ETDEWEB)

    1988-08-01

    This document presents a brief introduction and overview of the Department of Commerce's Export Administration Regulations which might affect potential US geothermal goods exporters. It is intended to make US geothermal firms officials aware of the existence of such regulations and to provide them with references, contacts and phone numbers where they can obtain specific and detailed information and assistance. It must be stressed however, that the ultimate responsibility for complying with the above mentioned regulations lies with the exporter who must consult the complete version of the regulations.

  8. The export of China nuclear power

    International Nuclear Information System (INIS)

    Zhang Jian

    2012-01-01

    The article first introduces the meaning of nuclear power export, and then analyses the advantages of China nuclear industry based on the status and development of this industry. At the same time. the collection of nuclear development for the next 30 years of several nations in south-east Asia, south Asia, Middle East, Africa and South America is compiled, which could be a valuable reference for foreseeing nuclear power export market. Finally, as the situation throughout the world is considered, some suggestions are made that what else could be done for future development and export. (author)

  9. Photovoltaic systems for export application. Informal report

    Energy Technology Data Exchange (ETDEWEB)

    Duffy, J.; Campbell, H.; Sajo, A.; Sanz, E. [Univ. of Lowell, MA (United States)

    1988-01-31

    One approach to improving the competitiveness of photovoltaic systems is the development of designs specifically for export applications. In other words, where is it appropriate in a system design to incorporate components manufactured and/or assembled in the receiving country in order to improve the photovoltaic exports from the US? What appears to be needed is a systematic method of evaluating the potential for export from the US of PV systems for various application in different countries. Development of such a method was the goal of this project.

  10. The Competitiveness of Romanian Services Exports

    Directory of Open Access Journals (Sweden)

    Corina Grigorovici

    2008-02-01

    Full Text Available Romania carried on significant progresses in its intercession to fetch up the gaps towards the European Union concerning the services compartment, the balance of those being of almost 10% from the total Romanian export, during the first semester of 2007. In 2006, the export of services increased with 45% comparatively to the year before, consolidating the status of our country as a services exporter. The IT left its mark on the structure and organizing method of the tertiary compartment and ameliorated the form in which the services were performed in the context of enhanced electronic transfers.

  11. German radionuclide exports and imports 1990

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    The statistics compiled by the German Federal Office for Trade and Industry (Bundesamt fuer Wirtschaft) for the Federal Ministry for the Environment, Conservation of Nature, and Reactor Protection of imports and exports of radionuclides, irradiation samples and sealed emitters above 1850 GBq show a slight decline by 11.8%, on the basis of activity, in imports and a somewhat higher rise by 21.6% in exports in 1990. Imports returned to the level of 1988 after having experienced an extraordinary rise in 1989. Exports were slightly better than in the previous year, but still considerably below the average of the past five years. (orig.) [de

  12. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells

    International Nuclear Information System (INIS)

    Sun, Qing; Liang, Ying; Zhang, Tianli; Wang, Kun; Yang, Xingsheng

    2017-01-01

    Objective: Estrogen receptor alpha 36 (ER-α36), a truncated variant of ER-α, is different from other nuclear receptors of the ER-α family. Previous findings indicate that ER-α36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-α36 and cervical cancer are rare. This study aimed to detect the expression of ER-α36 in cervical cancer; the role of ER-α36 in 17-β-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms. Methods: Immunohistochemistry and immunofluorescence were used to determine the location of ER-α36 in cervical cancer tissues and cervical cell lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish stable cell lines with knockdown and overexpression of ER-α36. Wound healing assay, transwell invasion assay, and EdU incorporation proliferation assay were performed to evaluate the migration, invasion, and proliferation ability. The phosphorylation levels of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling molecules were examined with western blot analysis. Results: ER-α36 expression was detected in both cervical cell lines and cervical cancer tissues. Downregulation of ER-α36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-α36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation. Conclusion: ER-α36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells. - Highlights: • ER-α36 is expressed on both cervical cell lines and cervical cancer tissues. • ER-α36 mediates estrogen

  13. Nuclear safeguards and export controls

    International Nuclear Information System (INIS)

    Mueller, H.

    1994-01-01

    Precisely from the perspective of the two most important nonnuclear weapons states, Japan and Germany, the safeguards and arms control agendas have not been finally dealt with. Because of their central position in the nonproliferation regime as nuclear suppliers and states with large nuclear energy industries, both countries are compelled to take a leading role in pursuing future reforms. In the dialogue with the nonaligned, this leadership position is helped by their nonnuclear status. In fact, Japan and Germany have some interests in common with the nonaligned states, such as the expansion of safeguards in the nuclear weapons states. To be sure, both Japan and Germany will pursue such interests with due regard to the interests of their friends and allies. For Japan, maintaining a close relationship with the United States is as important as shaping viable relations with China. Initiatives and controversies on nuclear policy must be weighed against this interest. By the same token, Germany must take into account the dense network of relations with its allies and with Russia, in addition to the German-French friendship. This will always set limits to Germany's readiness to confront the nuclear weapons states on nuclear issues. This, however, does not mean that both countries must shut up when the P 5 speak. The nuclear weapons register and the extension of the ''erga omnes'' rule in export controls, for example, should not be relegated to the dustbin of history, just because some friendly nuclear powers don't like these ideas. (orig.)

  14. Inhibition of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase by thapsigargin analogs induces cell death via ER Ca2+ depletion and the unfolded protein response

    DEFF Research Database (Denmark)

    Sehgal, Pankaj; Szalai, Paula; Olesen, Claus

    2017-01-01

    Calcium (Ca2+) is a fundamental regulator of cell signaling and function. Thapsigargin (Tg) blocks the sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA), disrupts Ca2+ homeostasis, and causes cell death. However, the exact mechanisms whereby SERCA-inhibition induces cell death are incompletely...... extensive drainage of the ER Ca2+ stores. This Ca2+ depletion was followed by markedly reduced cell proliferation rates and morphological changes that developed over 2–4 days and culminated in cell death. Interestingly, these changes were not accompanied by bulk increases in cytosolic Ca2+ levels. Moreover...... and their detrimental effects on cell viability. Furthermore, caspase activation and cell death were associated with a sustained unfolded protein response (UPR). We conclude that ER Ca2+ drainage and sustained UPR activation are key for initiation of apoptosis at low concentrations of Tg and Tg analogs, whereas high...

  15. CHITINASE-B FROM SERRATIA-MARCESCENS-BJL200 IS EXPORTED TO THE PERIPLASM WITHOUT PROCESSING

    NARCIS (Netherlands)

    BRURBERG, MB; EIJSINK, VGH; HAANDRIKMAN, AJ; VENEMA, G; NES, IF

    A gene encoding a chitinase from Serratia marcescens BJL200 was cloned and expressed in Escherichia coli and S. marcescens. Nucleotide sequencing revealed an open reading frame encoding a 55.5 kDa protein of 499 amino acids without a typical signal peptide for export. The cellular localization of

  16. ER Consolidated Quarterly Report October 2014

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-10-01

    This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective actions and related Long- Term Stewardship (LTS) activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) ER for the April, May, and June 2014 quarterly reporting period. Section 2.0 provides the status of ER Operations activities including closure activities for the Mixed Waste Landfill (MWL), project management and site closure, and hydrogeologic characterizations. Section 3.0 provides the status of LTS activities that relate to the Chemical Waste Landfill (CWL) and the associated Corrective Action Management Unit (CAMU). Section 4.0 provides the references noted in Section I of this report.

  17. Quantifying export production in the Southern Ocean: Implications for the Baxs proxy

    Science.gov (United States)

    Hernandez-Sanchez, Maria T.; Mills, Rachel A.; Planquette, HéLèNe; Pancost, Richard D.; Hepburn, Laura; Salter, Ian; Fitzgeorge-Balfour, Tania

    2011-12-01

    The water column and sedimentary Baxs distribution around the Crozet Plateau is used to decipher the controls and timing of barite formation and to evaluate how export production signals are recorded in sediments underlying a region of natural Fe fertilization within the Fe limited Southern Ocean. Export production estimated from preserved, vertical sedimentary Baxs accumulation rates are compared with published export fluxes assessed from an integrated study of the biological carbon pump to determine the validity of Baxs as a quantitative proxy under different Fe supply conditions typical of the Southern Ocean. Detailed assessment of the geochemical partitioning of Ba in sediments and the lithogenic end-member allows appropriate correction of the bulk Ba content and determination of the Baxs content of sediments and suspended particles. The upper water column distribution of Baxs is extremely heterogeneous spatially and temporally. Organic carbon/Baxs ratios in deep traps from the Fe fertilized region are similar to other oceanic settings allowing quantification of the inferred carbon export based on established algorithms. There appears to be some decoupling of POC and Ba export in the Fe limited region south of the Plateau. The export production across the Crozet Plateau inferred from the Baxs sedimentary proxy indicates that the Fe fertilized area to the north of the Plateau experiences enhanced export relative to equivalent Southern Ocean settings throughout the Holocene and that this influence may also have impacted the site to the south for significant periods. This interpretation is corroborated by alternative productivity proxies (opal accumulation, 231Paxs/230Thxs). Baxs can be used to quantify export production in complex settings such as naturally Fe-fertilized (volcanoclastic) areas, providing appropriate lithogenic correction is undertaken, and sediment focusing is corrected for along with evaluation of barite preservation.

  18. Modeling of Yb3+-sensitized Er3+-doped silica waveguide amplifiers

    DEFF Research Database (Denmark)

    Lester, Christian; Bjarklev, Anders Overgaard; Rasmussen, Thomas

    1995-01-01

    A model for Yb3+-sensitized Er3+-doped silica waveguide amplifiers is described and numerically investigated in the small-signal regime. The amplified spontaneous emission in the ytterbium-band and the quenching process between excited erbium ions are included in the model. For pump wavelengths...

  19. Development of microstructured large area magnetic calorimeters with Au:Er- and Ag:Er-sensors for the detection of x-ray quanta and high energetic particles; Entwicklung grossflaechiger mikrostrukturierter magnetischer Kalorimeter mit Au:Er- und Ag:Er-Sensoren fuer den energieaufgeloesten Nachweis von Roentgenquanten und hochenergetischen Teilchen

    Energy Technology Data Exchange (ETDEWEB)

    Burck, Andreas

    2008-11-04

    This thesis describes the development of large-area magnetic calorimeters which could for example be used for the investigation of the dissociative recombination or the measurement of the Lamb-shift for hydrogenlike heavy ions. The detectors consist of two meandershaped niobium thin film pickup coils and a paramagnetic sensor. The deposition of energy in the sensor results in a temperature change and therefore in a change of magnetisation of the sensor, which can be measured by a SQUID-magnetometer with high precision. As sensormaterials a dilute alloy of gold-erbium (Au:Er) as well as silver-erbium (Ag:Er) were used. Whereas the Ag:Er-sensor was glued on the pickup coil the Au:Er-sensor was for the first time microstructured by a novel microstructuring process established in this thesis. For the characterisation of the detectors and the sensormaterials a fluorescence source and a {sup 55}Fe source were used. The thermodynamic properties of the Au:Er-sensors thereby show promising results, as the magnetisation shows bulk properties down to 20 mK. The measurements of the signalize and the magnetisation with the detector which was equipped with a Ag:Er-sensor showed that the thermodynamic properties of the Ag:Eralloy could be fully described. Furthermore the shape of the pulses, the noise and the energy resolution of both detectors will be discussed. (orig.)

  20. Er iPad digital udeskole?

    DEFF Research Database (Denmark)

    Schilhab, Theresa

    2014-01-01

    Hvor ’konkret’ skal en oplevelse være, for at intuitionen om, at det selvoplevede styrker læringen, holder? Er brug af tablets (e.g. iPads) et ligebyrdigt alternativ til den konkrete oplevelse?......Hvor ’konkret’ skal en oplevelse være, for at intuitionen om, at det selvoplevede styrker læringen, holder? Er brug af tablets (e.g. iPads) et ligebyrdigt alternativ til den konkrete oplevelse?...

  1. Snip snap snude - dobbelthagerne er ude

    DEFF Research Database (Denmark)

    Larsen, Malene Charlotte; Kofoed, Jette

    2015-01-01

    Det handler om at være grim. Det står i skarp kontrast til det pæne og polerede på Instagram. Det er flygtigt, useriøst og ligegyldigt. Og så forsvinder det heldigvis igen, så man behøver kun at forholde sig til det i de få sekunder, det foregår. Snapchat vokser i popularitet og er nu det...

  2. Håndbold er en praksis!

    DEFF Research Database (Denmark)

    Olsen, Poul Bitsch

    2008-01-01

    Dansk håndbold er en kæmpemæssig succeshistorie. Ser man snævert på den udvikling, elitedelen af sporten har gennemlevet de seneste 15 år, viser stort set alle tænkelige parametre fremgang. De internationale resultater for lands og klubhold er med få udfald blevet stadigt bedre, omsætningen i klu...

  3. Bæredygtighed hos SMV'er

    DEFF Research Database (Denmark)

    2016-01-01

    Valg af materiale/medie/form: YouTube Valg af arbejdsform: Videoerne kan bruges som caseundervisning Begrundelse for valg af materiale/medie/form/arbejdsform: Caseundervisning er velegnet til at lære om praksis......Valg af materiale/medie/form: YouTube Valg af arbejdsform: Videoerne kan bruges som caseundervisning Begrundelse for valg af materiale/medie/form/arbejdsform: Caseundervisning er velegnet til at lære om praksis...

  4. Hvad litteraturen kan, er ofte det rigtige ..

    DEFF Research Database (Denmark)

    Bundsgaard, Jeppe; Kühn, Lisbet

    2010-01-01

    Læsning i dansk handler i første omgang om at blive god til at læse, men på mellemtrinnet er det ved at være tiden til også at bruge skønlitteraturen til det, den er god til, nemlig til at få indsigt i menneskelivets kompleksitet. I dette kapitel anbefales det at gøre noget med litteraturen, fx f...

  5. Hvilke Dødehavstekster er "sekteriske"?

    DEFF Research Database (Denmark)

    Holst, Søren

    2003-01-01

    Skønt Dødehavsrullerne antageligt tilhørte en gruppering, der boede i Qumran, tyder alt på, at mange af teksterne er forfattet andre steder. Artiklen undersøger den særlige sprogbrug, som antageligt er typisk for Qumran-samfundet, og som præger forbavsende få af tekserne. En meget stor del af...

  6. Trump er godt nyt for verdensfreden

    DEFF Research Database (Denmark)

    Jakobsen, Peter Viggo

    2017-01-01

    Trumps uberegnelighed øger ikke risikoen for krig. Den mindsker den ved at få de allierede til at gøre mere og modstanderne til at forhandle. Det er godt for verdensfreden......Trumps uberegnelighed øger ikke risikoen for krig. Den mindsker den ved at få de allierede til at gøre mere og modstanderne til at forhandle. Det er godt for verdensfreden...

  7. Nuclear Import and Export of the Thyroid Hormone Receptor.

    Science.gov (United States)

    Zhang, Jibo; Roggero, Vincent R; Allison, Lizabeth A

    2018-01-01

    The thyroid hormone receptors, TRα1 and TRβ1, are members of the nuclear receptor superfamily that forms one of the most abundant classes of transcription factors in multicellular organisms. Although primarily localized to the nucleus, TRα1 and TRβ1 shuttle rapidly between the nucleus and cytoplasm. The fine balance between nuclear import and export of TRs has emerged as a critical control point for modulating thyroid hormone-responsive gene expression. Mutagenesis studies have defined two nuclear localization signal (NLS) motifs that direct nuclear import of TRα1: NLS-1 in the hinge domain and NLS-2 in the N-terminal A/B domain. Three nuclear export signal (NES) motifs reside in the ligand-binding domain. A combined approach of shRNA-mediated knockdown and coimmunoprecipitation assays revealed that nuclear entry of TRα1 is facilitated by importin 7, likely through interactions with NLS-2, and importin β1 and the adapter importin α1 interacting with both NLS-1 and NLS-2. Interestingly, TRβ1 lacks NLS-2 and nuclear import depends solely on the importin α1/β1 heterodimer. Heterokaryon and fluorescence recovery after photobleaching shuttling assays identified multiple exportins that play a role in nuclear export of TRα1, including CRM1 (exportin 1), and exportins 4, 5, and 7. Even single amino acid changes in TRs dramatically alter their intracellular distribution patterns. We conclude that mutations within NLS and NES motifs affect nuclear shuttling activity, and propose that TR mislocalization contributes to the development of some types of cancer and Resistance to Thyroid Hormone syndrome. © 2018 Elsevier Inc. All rights reserved.

  8. Promoting exports in the energy technology area; Foerderung des Exports im Bereich der Energietechnologien

    Energy Technology Data Exchange (ETDEWEB)

    Iten, R.; Oettli, B. [Infras, Zuerich (Switzerland); Jochem, E.; Mannsbart, W. [Fraunhofer Institut Systemtechnik und Innovationsforschung, Karlsruhe (Germany)

    2001-07-01

    This report for the Swiss Federal Office of Energy (SFOE) examines the position of Switzerland as a leader in the investment goods markets for energy-efficiency products and for technologies for using renewable forms of energy. The report quotes figures for exports in these areas and discusses the difficulty of extracting useful data on these products from normal statistical data. Analyses made by a group of experts from the export-oriented technology field, energy service providers and representatives of export promotion institutions are presented and figures are quoted for various product categories. Factors promoting the competitiveness of Swiss products are discussed as well as those impeding it. An analysis of export potential is presented and measures to promote export are discussed. The report also discusses the aids and promotion activities that are considered necessary by companies in the field and the macro-economic perspectives of increased export promotion.

  9. Arabidopsis ETR1 and ERS1 Differentially Repress the Ethylene Response in Combination with Other Ethylene Receptor Genes1[W

    Science.gov (United States)

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The ethylene response is negatively regulated by a family of five ethylene receptor genes in Arabidopsis (Arabidopsis thaliana). The five members of the ethylene receptor family can physically interact and form complexes, which implies that cooperativity for signaling may exist among the receptors. The ethylene receptor gene mutations etr1-1(C65Y)(for ethylene response1-1), ers1-1(I62P) (for ethylene response sensor1-1), and ers1C65Y are dominant, and each confers ethylene insensitivity. In this study, the repression of the ethylene response by these dominant mutant receptor genes was examined in receptor-defective mutants to investigate the functional significance of receptor cooperativity in ethylene signaling. We showed that etr1-1(C65Y), but not ers1-1(I62P), substantially repressed various ethylene responses independent of other receptor genes. In contrast, wild-type receptor genes differentially supported the repression of ethylene responses by ers1-1(I62P); ETR1 and ETHYLENE INSENSITIVE4 (EIN4) supported ers1-1(I62P) functions to a greater extent than did ERS2, ETR2, and ERS1. The lack of both ETR1 and EIN4 almost abolished the repression of ethylene responses by ers1C65Y, which implied that ETR1 and EIN4 have synergistic effects on ers1C65Y functions. Our data indicated that a dominant ethylene-insensitive receptor differentially repressed ethylene responses when coupled with a wild-type ethylene receptor, which supported the hypothesis that the formation of a variety of receptor complexes may facilitate differential receptor signal output, by which ethylene responses can be repressed to different extents. We hypothesize that plants can respond to a broad ethylene concentration range and exhibit tissue-specific ethylene responsiveness with differential cooperation of the multiple ethylene receptors. PMID:22227969

  10. Corporate Managers' International Orientation and the Export ...

    African Journals Online (AJOL)

    Corporate Managers' International Orientation and the Export Performance of Firms in ... and for determining influence between interval level variables, respectively. ... Enhancing product adaptation and use of foreign strategic partnerships by ...

  11. Private hydropower projects: exporting the american experience

    International Nuclear Information System (INIS)

    Rogers, W.L.; Bourgeacq, J.P.

    1991-01-01

    This paper addresses different aspects of exporting the American knowledge and experience in the private development of small-scale hydropower projects. It details the 'export' and 'adaptation/translation' of American PURPA philosophy to other countries. The major stumbling blocks on the road to exportation are listed. The subject countries'market evaluation is explained, as well as methods for researching and gathering the necessary information on a specific country. Methods of choosing a target country are discussed, and the criteria necessary for making a choice are detailed. The subject of legal framework and privatization of power generation issues overseas and the ways and means to help the 'export of U.S. expertise' through U.S. Government programs are described. The subjects of financing and joint ventures with local entities are also included in this paper. Various scenarios for private development overseas are presented

  12. 78 FR 54238 - President's Export Council; Meeting

    Science.gov (United States)

    2013-09-03

    ... DEPARTMENT OF COMMERCE International Trade Administration President's Export Council; Meeting AGENCY: International Trade Administration, U.S. Department of Commerce. ACTION: Notice of an open...; understanding best value in government procurement; de minimis reform; intellectual property protections in the...

  13. The NPT and nuclear export controls

    International Nuclear Information System (INIS)

    Berkhout, F.

    1992-01-01

    Controls on the export of nuclear materials and technology were originally imposed in wartime and under the United States Atomic Energy Act of 1946 to restrict the supply of uranium. But there was no international agreement until the mid 1960s; before that the United States, Canada, France and the Soviet Union imposed export controls on a national basis. The Non-Proliferation Treaty, especially Articles I-IV, set out the first world wide controls on the nuclear trade. These articles are explained in the context of the relevant Committees (the Zangger Committee, the Committee on the Assurance of Supply, the National Export Committee and the Coordinating Committee for Multilateral Export Control) and Guidelines (the Nuclear Suppliers Guidelines and the International Nuclear Fuel Cycle Evaluation). Recent developments which have a bearing on nuclear trade, such as the single European market, the emergence of new supplies and the break-up of the Soviet Union, are considered. (UK)

  14. Safety and exportation of nuclear power stations

    International Nuclear Information System (INIS)

    Coudray, M.; Perrais, J.P.

    1976-01-01

    Safety problems arising from exportation are especially handled through the French exportation of PWR stations. Regulations differ widely from one country to another. However, very large use of American regulations is made and frequently there is a tendency to harden such or such clause in the quotation. Industry must be ready to give satisfaction to such demands of customers. Sometimes also, it is a mere duplication of French stations which is above all looked for. In that case, it is the problem of using French regulations abroad which arises. Desirable changes in examination proceedings are analyzed together with a French regulation effort aiming to make easier the promotion of their use abroad. Finally, safety may be a factor of success for exportation attempts. It is shown how useless some outbiddings may be, but also how, on the contrary, speeding up of research and development effort towards specific safety problems in case of exportation, is to be promoted [fr

  15. 1986 imports and exports of radionuclides

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    The statistics compiled by the German Federal Office for Industry (Bundesamt fuer Wirtschaft), on behalf of the Federal Ministry for the Environment, Protection of Nature, and Reactor Safety, of the imports and exports of radionuclides, irradiation samples, and sealed emitters of more than 1850 GBq show an enormous increase by 152.7% of imports (on the basis of activity) and a decline by 19.5% of exports. In the category of imports, some 98% of the total activity were made up of the H-3, Co-60, Mo-99, and Ir-192 nuclides. In the category of sealed emitters, the imports of Co-60 have trebled. In the exports category, more than 95% of the total activity were made up of the H-3, Mo-99, and Ir-192 nuclides. In the category of sealed emitters, exports of Cs-137 experienced a fourfold increase over the level of the previous year. (orig.) [de

  16. An Export Promotion Policy after Financial Crisis

    Directory of Open Access Journals (Sweden)

    Ingyo Cheong

    1998-09-01

    Full Text Available Although the Korean government puts in place various export support policies after the financial crisis, Korean export is still in stagnation because the foreign-oriented economic conditions, such as the continual ripple effect of the Eastern Asia financial crisis and the American economy which is slowing down, are deteriorating. After the financial crisis, Korean trading circle considered the difficulties in financing and the buying of raw material to be the most important factors which blocked the export. This thesis first analyzed the change of the actual export results, then analyzed the policy the government brought forward as the solution of the difficulties in financing and raw material buying. Meanwhile, this thesis brought forward alternative policies like taking auto-rediscount and signing Free Trade Agreement with major trade states.

  17. How the Eximbank helps US nuclear exporters

    International Nuclear Information System (INIS)

    Moore, J.L. Jr.

    1981-01-01

    The way in which the Export-Import Bank operates in support of the United States nuclear industry noting particularly its flexibility in responding to changing needs and budget constraints is described. (author)

  18. Migrant entrepreneurship, economic activity and export performance:

    DEFF Research Database (Denmark)

    Vang, Jan; Baklanov, Nikita; Rezaei, Shahamak

    Recent studies on transnational entrepreneurship) suggest that migrant entrepreneur play an increasingly significant role as sources of economic activities and especially export revenue. The literature is, however, biased on the US experience, lacks a comparative perspective between migrants...... and non-migrants and is primarily anecdotal in nature (Saxenian, 2002; 2006, Ruzzlier et al, 2007; Honig and Drori, 2010, Drodi et al, 2010)). This paper aims at reducing this gap by mapping the recent changes in the role of migrant entrepreneurs as a source of increased economic activity and export...... in across ethic categories. Export revenue is proxied by the number of firms in the different ethnic categories that exports. The Danish context provides unique data allowing for a comparison across migrants and non-migrants, across sectors and across time. The paper reveals that migrants play a decreasing...

  19. Australia: A Growing Market for Asean Exports?

    OpenAIRE

    Tongzon, J.L.

    1988-01-01

    Much has been written regarding South East Asian countries as growing markets for Australian exports particularly in the past decade. But nothing so far has been done to examine whether ASEAN exports have also experienced some redirection towards the Australian market. The findings confirm our a priori expectations: no significant general reorientation was observed for the ASEAN group of countries, and ASEAN’s country bias declined over the period under study. This is in contrast to the Austr...

  20. Sudanese live sheep and mutton exports competitiveness

    OpenAIRE

    Babiker Idris Babiker; Abdul-Jabbar Mohammed Abdullah; Mohamed Ahmed Al-Feel

    2011-01-01

    The livestock sector of Sudan provides livelihood for about 17% of the population. Sudanese livestock products meet the domestic demand for meat in addition to a substantial excess for export amounting to about 22% of total country exports. It contributes about 19% of GDP. Sheep marketing in Sudan is characterised by traditional operations and is informally organised, although, recently there are great efforts by the formal livestock authorities to organise some secondary and terminal livesto...

  1. Export of electric power through industrial products

    International Nuclear Information System (INIS)

    Azevedo, J.B.L. de; David, J.M.S.; Campos, J.M.; Perecmanis, J.; Carneiro, N.S.

    1990-01-01

    We forecast the electrical energy incorporated to the exports of products of the industrial sectors of steel, aluminium, ferro-alloys, chlorine and caustic soda, pulp and paper and petrochemistry, accordingly to scenarios for these sectors consistent with a macro economic reference scenario, for the period 1990/2000. We also compare the electrical energy exported through those industrial products with the forecasted industrial and total markets of electrical energy. (author)

  2. Oil exports under GATT and the WTO

    International Nuclear Information System (INIS)

    Abdallah, H.

    2005-01-01

    This paper will try to focus on two aspects of oil production policy under the General Agreement on Tariffs and Trade (GATT) and the World Trade Organization. The first is how freely an oil producer can regulate the quantity of oil production and exports without violating GATT rules and the second is how an oil exporter could benefit from GATT rules to overstep barriers to market access imposed by oil-importing countries. (author)

  3. Exporter Price Response to Exchange Rate Changes

    DEFF Research Database (Denmark)

    Fosse, Henrik Barslund

    Firms exporting to foreign markets face a particular challenge: to price their exports in a foreign market when the exchange rate changes. This paper takes on pricing- to-market using a unique data set that covers rm level monthly trade at great detail. As opposed to annual trade ows, monthly trade...... theoretical contributions to the litterature on pricing-to-market and exchange rate pass-through....

  4. Export Control in the AREVA Group

    International Nuclear Information System (INIS)

    Zero, S.

    2013-01-01

    After the Second World War the nuclear technology was mostly considered inappropriate for the export. It remains strictly regulated today, but the development of the civil applications urged states to facilitate the peaceful uses while establishing a strict control in the domains of the internal security and the nuclear proliferation. AREVA decided to set up an Export Control program applied to all the products and in all the countries where the group operates. AREVA can export products or make transfer of technology considered as sensitive for the non-proliferation and the risks linked to the terrorism. This sensitiveness results from the nature of the products or from the country of destination and in certain cases both of them. AREVA has set up an Export Control program and an interactive e-learning training within the Group to make exports of sensitive products, raw materials and technologies more secure. The subject is rather complex, the regulations are constantly evolving, and becoming familiar with them is necessarily a gradual process, but it must be made in-depth, hence the idea of regular training sessions. The implementation of the Export Control in the AREVA Group declines in four fundamental stages: -) Policy and procedure; -) Appointment of Export Control Officers (ECO); -) Training; and -) Audit and Self Assessment. The training program is composed by the following elements: Ethics (Value Charter) of the Group, Non-proliferation, international regulations and more particularly those that are applicable in Europe (Germany and France) and in the United States. Particular attention is devoted to the Export Control practice in China, Japan and India. (A.C.)

  5. Purple perilla extracts allay ER stress in lipid-laden macrophages.

    Directory of Open Access Journals (Sweden)

    Sin-Hye Park

    Full Text Available There is a growing body of evidence that excess lipids, hypoxic stress and other inflammatory signals can stimulate endoplasmic reticulum (ER stress in metabolic diseases. However, the pathophysiological importance and the underlying mechanisms of this phenomenon remain unknown. The current study investigated that 50 ng/ml oxidized LDL promoted unfolded protein response (UPR and ER stress in J774A1 murine macrophages, which was blocked by extracts (PPE of purple Perilla frutescens, a plant of the mint family Lamiaceae. The ER stressor tunicamycin was employed as a positive control. Treating 1-10 µg/ml oxidized LDL for 24 h elicited lipotoxic apoptosis in macrophages with obvious nuclear condensation and DNA fragmentation, which was inhibited by PPE. Tunicamycin and oxidized LDL activated and induced the UPR components of activating transcription factor 6 and ER resident chaperone BiP/Grp78 in temporal manners and such effects were blocked by ≥5 µg/ml PPE. In addition, PPE suppressed the enhanced mRNA transcription and splicing of X-box binding protein 1 (XBP1 by tunicamycin and oxidized LDL. The protein induction and nuclear translocation of XBP1 were deterred in PPE-treated macrophages under ER stress. The induction of ATP-binding cassette transporter A1 (ABCA1, scavenger receptor-B1 (SR-B1 and intracellular adhesion molecule-1 (ICAM-1 was abolished by the ER stressor in activated macrophages. The protein induction of ABCA1 and ICAM1 but not SR-B1 was retrieved by adding 10 µg/ml PPE to cells. These results demonstrate that PPE inhibited lipotoxic apoptosis and demoted the induction and activation of UPR components in macrophages. PPE restored normal proteostasis in activated macrophages oxidized LDL. Therefore, PPE was a potent agent antagonizing macrophage ER stress due to lipotoxic signals associated with atherosclerosis.

  6. New insights on the functional role of URG7 in the cellular response to ER stress.

    Science.gov (United States)

    Armentano, Maria Francesca; Caterino, Marianna; Miglionico, Rocchina; Ostuni, Angela; Pace, Maria Carmela; Cozzolino, Flora; Monti, Maria; Milella, Luigi; Carmosino, Monica; Pucci, Piero; Bisaccia, Faustino

    2018-04-28

    Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is up-regulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signalling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown. To shed light on URG7 activity, we first analysed its interactome in HepG2 transfected cells: this analysis suggests that URG7 could have a role in affecting protein synthesis, folding and promoting proteins degradation. Moreover, keeping into account its subcellular localisation in the ER and that several viral infections give rise to ER stress, a panel of experiments was performed to evaluate a putative role of URG7 in ER stress. Our main results demonstrate that in ER-stressed cells URG7 is able to modulate the expression of Unfolded Protein Response (UPR) markers towards survival outcomes, up-regulating GRP78 protein and down-regulating the pro-apoptotic protein CHOP. Furthermore, URG7 reduces the ER stress by decreasing the amount of unfolded proteins, by increasing both the total protein ubiquitination and the AKT activation and reducing Caspase 3 activation. All together these data suggest that URG7 plays a pivotal role as a reliever of ER stress-induced apoptosis. This is the first characterisation of URG7 activity under ER stress conditions. The results presented here will help to hypothesise new strategies to counteract the antiapoptotic activity of URG7 in the context of the viral infection. © 2018 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  7. ZmbZIP60 mRNA is spliced in maize in response to ER stress

    Directory of Open Access Journals (Sweden)

    Li Yanjie

    2012-03-01

    Full Text Available Abstract Background Adverse environmental conditions produce ER stress and elicit the unfolded protein response (UPR in plants. Plants are reported to have two "arms" of the ER stress signaling pathway-one arm involving membrane-bound transcription factors and the other involving a membrane-associated RNA splicing factor, IRE1. IRE1 in yeast to mammals recognizes a conserved twin loop structure in the target RNA. Results A segment of the mRNA encoding ZmbZIP60 in maize can be folded into a twin loop structure, and in response to ER stress this mRNA is spliced, excising a 20b intron. Splicing converts the predicted protein from a membrane-associated transcription factor to one that is targeted to the nucleus. Splicing of ZmbZIP60 can be elicited in maize seedlings by ER stress agents such as dithiothreitol (DTT or tunicamycin (TM or by heat treatment. Younger, rather than older seedlings display a more robust splicing response as do younger parts of leaf, along a developmental gradient in a leaf. The molecular signature of an ER stress response in plants includes the upregulation of Binding Protein (BIP genes. Maize has numerous BIP-like genes, and ER stress was found to upregulate one of these, ZmBIPb. Conclusions The splicing of ZmbZIP60 mRNA is an indicator of ER stress in maize seedlings resulting from adverse environmental conditions such as heat stress. ZmbZIP60 mRNA splicing in maize leads predictively to the formation of active bZIP transcription factor targeted to the nucleus to upregulate stress response genes. Among the genes upregulated by ER stress in maize is one of 22 BIP-like genes, ZmBIPb.

  8. Competitiveness, export control and export promotion of dual-use goods. European and German balancing exercises

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2014-01-01

    The EU Commission Communication of 24 April 2014 to the Council and the European Parliament ''The review of export control policy: Ensuring Security and Competitiveness in a changing world'' as well as the increasingly number of inquiries and applications to the German Federal Government (e.g. the rejection of Hermes guarantees and state funding of nuclear export and termination of bilateral cooperation in the field of nuclear technologies) once again reason to discuss the current tension between the principle of free movement of goods, competitiveness and export promotion on the one hand and the export control on the other.

  9. 77 FR 69591 - President's Export Council: Meeting of the President's Export Council

    Science.gov (United States)

    2012-11-20

    ... meeting to deliberate on recommendations related to export expansion through streamlined consideration of.../peccomments.asp ) without change, including any business or personal information provided such as names...

  10. Renewables and exports: how Export Credit Agencies could help develop markets

    International Nuclear Information System (INIS)

    Volpi, G.; Salter, L.

    2002-01-01

    Future export markets for renewable energies have enormous potential, yet business-as-usual investment trends will not achieve that potential, write Giulio Volpi and Liam Salter. They examine the role that Export Credit Agencies - which have provided essential support for exports in the conventional energy business - could play in aiding the renewables sector, characterized as it is by small- and medium-sized enterprises. This new role will require certain reforms - but without those reforms the Export Credit Agencies will simply not be providing relevant services to new technologies and new market players. (author)

  11. Diagnostics of the Enterprise Export Potential

    Directory of Open Access Journals (Sweden)

    Skrynkovskyy Ruslan M.

    2016-11-01

    Full Text Available The aim of the article is to form and develop theoretical and methodological foundations for diagnostics of the enterprise export potential, which should be understood as a process of identification, analysis and assessment of the level of potential possibility and readiness of the enterprise to implement export activities taking into account the impact of interrelated internal variables (goals, technology, structure, tasks, educational and professional potential of the staff and factors of the enterprise external environment (customers, competitors, suppliers, intermediaries, contact audience, etc. in order to ensure a qualitatively new level of its development and formation of its prospects. It is determined that the key business indicators of the system for diagnostics of enterprise export potential are: the level of enterprises competitiveness in the international (global market; the level of competitiveness of enterprise products; the level of competitiveness of enterprise export products; the level of enterprise resource opportunities; the level of enterprise export performance. Prospects for further research in this direction are to develop a classification (specifically detailed list of objectives of the enterprise diagnostics by the level of detail (element, partial, complex, taking into account diagnostics of export potential of the enterprise as part of diagnostic objective.

  12. Sudanese live sheep and mutton exports competitiveness

    Directory of Open Access Journals (Sweden)

    Babiker Idris Babiker

    2011-01-01

    Full Text Available The livestock sector of Sudan provides livelihood for about 17% of the population. Sudanese livestock products meet the domestic demand for meat in addition to a substantial excess for export amounting to about 22% of total country exports. It contributes about 19% of GDP. Sheep marketing in Sudan is characterised by traditional operations and is informally organised, although, recently there are great efforts by the formal livestock authorities to organise some secondary and terminal livestock markets. These markets are deficient in basic infrastructures and systematic marketing research. The system as a whole is faced by various complex obstacles and constraints, which decrease the contribution of livestock in general, and sheep in particular, to the national economy, and suppress the optimum exploitation of this resource. These obstacles are represented in the lack of transportation networks that connect the production and consumption centres to break the seasonality of supply that creates shortages and high prices at the consumption centres. This paper employs the policy analysis matrix (PAM technique to examine the Sudanese live sheep and mutton competitiveness in the international market. The results indicated that the market price was greater than the border price implying a positive incentive as an implicit subsidy to the live sheep exporter. The mutton exporters were found subsidised as well. The international value added (IVA indicted a positive foreign exchange earnings or savings. Exported live sheep and mutton coefficient of competitiveness (CIC implied that sheep and mutton exports are profitable and internationally competitive.

  13. Nuclear export controls and nuclear safeguards

    International Nuclear Information System (INIS)

    Sevini, F.

    2013-01-01

    The export control of dual use goods has developed since the early seventies to counter nuclear proliferation. The paper provides an overview of dual-use export control issues also in relation with the Additional Protocol to the Comprehensive Safeguards Agreement, which requires States to provide declarations of the export of the controlled items listed in its Annex II, derived from the Nuclear Suppliers Group Trigger list. Recommendations for improvement are proposed. On the EU level, the paper summarises the framework set by the European Council Regulation 428/2009, requiring Member States to impose control on exports, brokering and transit of dual use goods. The Regulation includes the so-called 'EU dual-use control list' integrating the lists of dual-use items defined by the international regimes and requires also the control on intangible technology transfers as foreseen by U.N. Security Council Resolution 1540. ESARDA has recently launched a new sub-Working Group on export control, which raised large interest and may evolve to a full-fledged working group. Export control may provide an opportunity of technical collaboration between ESARDA and INMM. The paper is followed by the slides of the presentation. (author)

  14. ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress

    OpenAIRE

    Zhang, Chunbin; Wang, Guohui; Zheng, Ze; Maddipati, Krishna Rao; Zhang, Xuebao; Dyson, Gregory; Williams, Paul; Duncan, Stephen A.; Kaufman, Randal J.; Zhang, Kezhong

    2012-01-01

    CREBH is a liver-specific transcription factor that is localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the li...

  15. 75 FR 29514 - Export Trade Certificate of Review

    Science.gov (United States)

    2010-05-26

    ... new Export Markets, such as advertising and trade shows. 6. ALCC may, for itself and on behalf of its...: a. Sales and marketing efforts, and activities and opportunities for sales of Export Product in Export Markets, including but not limited to selling strategies and pricing, projected demand for Export...

  16. Are there regional differences in US hardwood product exports?

    Science.gov (United States)

    Matt Bumgardner; Scott Bowe; William Luppold

    2016-01-01

    Exporting is a critical component of the product mix for many domestic hardwood firms. Previous research has identified factors associated with hardwood lumber exporting behavior, but less is known about the advantages and disadvantages to exporting associated with the region within which a firm is located, or about exporting of secondary hardwood products. A procedure...

  17. Firm-Level Determinants of Exporting Behaviour: Evidence from ...

    African Journals Online (AJOL)

    This paper uses firm-level panel data to investigate the exporting behaviour of the Kenyan manufacturing firms. Using probit and tobit regression models, the results obtained show that factors determining the decision to export are different from those affecting the share exported. Likewise, factors determining exporting ...

  18. 22 CFR 120.30 - The Automated Export System (AES).

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false The Automated Export System (AES). 120.30... DEFINITIONS § 120.30 The Automated Export System (AES). The Automated Export System (AES) is the Department of... system for collection of export data for the Department of State. In accordance with this subchapter U.S...

  19. 7 CFR 1493.470 - Evidence of export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export. 1493.470 Section 1493.470... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.470 Evidence of export. (a) Report of export. The...

  20. 9 CFR 322.3 - Transferring products for export.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Transferring products for export. 322... INSPECTION AND CERTIFICATION EXPORTS 1 § 322.3 Transferring products for export. When inspected and passed products for export are transferred from tank cars to other containers on vessels, such transfer shall be...

  1. 7 CFR 35.8 - Date of export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Date of export. 35.8 Section 35.8 Agriculture... Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Definitions § 35.8 Date of export. Date of export means the date of loading on board the...

  2. 78 FR 53727 - Export Trade Certificate of Review

    Science.gov (United States)

    2013-08-30

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 84-24A12] 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...

  3. 19 CFR 113.55 - Cancellation of export bonds.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Cancellation of export bonds. 113.55 Section 113... export bonds. (a) Manner of cancellation. A bond to assure exportation as defined in § 101.1 of this... shall be signed by a revenue officer of the foreign country to which the merchandise is exported, unless...

  4. 78 FR 1837 - Export Trade Certificate of Review

    Science.gov (United States)

    2013-01-09

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 84-23A12] Export Trade Certificate of Review ACTION: Notice of issuance of an Export Trade Certificate of Review to Northwest Fruit Exporters, Application No. 84-23A12. SUMMARY: The U.S. Department of Commerce issued an amended Export Trade...

  5. 48 CFR 1825.1103-70 - Export control.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Export control. 1825.1103...-70 Export control. (a) Background. (1) NASA contractors and subcontractors are subject to U.S. export... 120 through 130, and the Export Administration Regulations (EAR), 15 CFR parts 730 through 799. The...

  6. 7 CFR 1493.280 - Evidence of export report.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export report. 1493.280 Section 1493.280... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.280 Evidence of export report. (a) Report of export. The...

  7. 7 CFR 1493.80 - Evidence of export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export. 1493.80 Section 1493.80... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103...

  8. INTERNATIONALIZATION STRATEGIES: A CASE STUDY AT SMALL EXPORT COMPANIES

    Directory of Open Access Journals (Sweden)

    Elaine Di Diego Antunes

    2009-04-01

    Full Text Available The purpose of this study is to identify the main internationalization strategies used by small manufacturers of hammocks. Our findings show that these export companies have up to 20 employees and their main internationalization strategy is exportation. This plan is carried out in 3 ways: indirect exportation, through trading companies; direct exportation, through sales performed in the companies and cooperative exportation, through a network of dealers in greater companies. Its was also verified that some organizations export up to 60% of their products while the vast majority does not even export 5% of it, turning primarily to the domestic market.

  9. Political risk and export promotion: evidence from Germany

    OpenAIRE

    Moser, Christoph; Nestmann, Thorsten; Wedow, Michael

    2006-01-01

    Political risk represents an important hidden transaction cost that reduces international trade. This paper investigates the claim that German public export credit guarantees (Hermes guarantees) mitigate this friction to trade flows and hence promote exports. We employ an empirical trade gravity model, where we explicitly control for political risk in the importing country in order to evaluate the effect of export guarantees. The idea behind export promotion through public export credit agenc...

  10. International Comparison of the Export Competitiveness of Chinese Honey

    OpenAIRE

    Ma, Lunjiao

    2009-01-01

    Honey production and trade in the world are introduced. Total output of honey shows an increasing trend while the output of Chinese honey always ranks the first in the world. China, Argentina, Mexico are the major exporters of honey. In the year 2006, honey exports of China, Argentina and Mexico occupy 49.9% of the world's total export volume. International competitiveness of the three honey export countries are calculated, compared and analyzed by adopting the indices such as export price, i...

  11. An Introduction to Export Assistance in the Internet Age

    DEFF Research Database (Denmark)

    Ramanathan, Somasundaram; Rask, Morten

    2003-01-01

    '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......Governments and other non-profit organizations have been providing information-oriented services for long to encourage exports. The primary targeted recipient of such services is Small and Medium sized Enterprises (SME's). The effectiveness of such activities has been researched extensively until...

  12. 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......Governments and other non-profit organizations have been providing information-oriented services for long to encourage exports. The primary targeted recipient of such services is Small and Medium sized Enterprises (SME's). The effectiveness of such activities has been researched extensively until...

  13. INTERNATIONALIZATION STRATEGIES: A CASE STUDY AT SMALL EXPORT COMPANIES

    OpenAIRE

    Elaine Di Diego Antunes; Joysinett Moraes Silva

    2009-01-01

    The purpose of this study is to identify the main internationalization strategies used by small manufacturers of hammocks. Our findings show that these export companies have up to 20 employees and their main internationalization strategy is exportation. This plan is carried out in 3 ways: indirect exportation, through trading companies; direct exportation, through sales performed in the companies and cooperative exportation, through a network of dealers in greater companies. Its was also veri...

  14. Synthesis of Er and Er : Yb doped sol–gel derived silica glass and ...

    Indian Academy of Sciences (India)

    Unknown

    Materials Science Centre, †Central Research Facility, Optical Fibre Unit, Indian Institute of Technology,. Kharagpur 721 302, India. MS received 1 March 2004; revised 4 July 2004. Abstract. Er3+ and Er3+ : Yb3+ doped optical quality, crack and bubble free glasses for possible use in mak- ing laser material have been ...

  15. Export diversification in Uganda : developments in non-traditional agricultural exports

    NARCIS (Netherlands)

    Dijkstra, T.

    2001-01-01

    Over the last two decades agricultural export diversification has been pushed as an economic development strategy for sub-Saharan Africa. This paper looks at Uganda, where nontraditional agricultural export commodities have been (re)-introduced since Museveni came to power in 1986. The most

  16. 75 FR 52929 - President's Export Council: Meeting of the President's Export Council

    Science.gov (United States)

    2010-08-30

    .... ACTION: Notice of an open meeting. SUMMARY: The President's Export Council will hold a meeting to discuss... how to promote U.S. exports, jobs, and growth. DATES: September 16, 2010 at 9:30 a.m. (EDT). ADDRESSES... trade and report to the President on its activities and on its recommendations for expanding U.S...

  17. 78 FR 12719 - President's Export Council: Meeting of the President's Export Council

    Science.gov (United States)

    2013-02-25

    ... deliberate on recommendations related to promoting the expansion of U.S. exports. Topics may include the Administration's ``Doing Business in Africa'' campaign, the need for nominations to the U.S. Export- Import Bank.../pec ) without change, including any business or personal information provided such as names, addresses...

  18. 75 FR 54857 - President's Export Council, Subcommittee on Export Administration; Notice of Recruitment of...

    Science.gov (United States)

    2010-09-09

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security President's Export Council, Subcommittee on Export Administration; Notice of Recruitment of Private-Sector Members; Date Extension Summary: The... Subcommittee will not be compensated for their services. The PECSEA is seeking private-sector members with...

  19. Site of Er ions in silica layers codoped with Si nanoclusters and Er

    International Nuclear Information System (INIS)

    Pellegrino, P.; Garrido, B.; Arbiol, J.; Garcia, C.; Lebour, Y.; Morante, J.R.

    2006-01-01

    Silica layers implanted with Si and Er ions to various doses and annealed at 950 deg. C have been investigated by means of energy-filtered transmission electron microscopy (EFTEM) and high annular angle dark field (HAADF). EFTEM analysis reveals Si nanoclusters (Si-nc) with an average size around 3 nm for high Si content (15 at. %) whereas no clusters can be imaged for the lowest Si excess (5 at. %). Raman scattering supports that amorphous Si precipitates are present in all the samples. Moreover, the filtered images show that Er ions appear preferentially located outside the Si-nc. HAADF analysis confirms that the Er atoms form agglomerations of 5-10 nm size when the Er concentration exceeds 1x10 20 cm -3 . This observation correlates well with the reduction of the Er population excitable by Si nanoclusters, in the best case corresponding to 10% of the total. A suitable tuning of the annealing drastically reduces this deleterious effect

  20. Identification of ER Proteins Involved in the Functional Organisation of the Early Secretory Pathway in Drosophila Cells by a Targeted RNAi Screen

    Science.gov (United States)

    Kondylis, Vangelis; Tang, Yang; Fuchs, Florian; Boutros, Michael; Rabouille, Catherine

    2011-01-01

    Background In Drosophila, the early secretory apparatus comprises discrete paired Golgi stacks in close proximity to exit sites from the endoplasmic reticulum (tER sites), thus forming tER-Golgi units. Although many components involved in secretion have been identified, the structural components sustaining its organisation are less known. Here we set out to identify novel ER resident proteins involved in the of tER-Golgi unit organisation. Results To do so, we designed a novel screening strategy combining a bioinformatics pre-selection with an RNAi screen. We first selected 156 proteins exhibiting known or related ER retention/retrieval signals from a list of proteins predicted to have a signal sequence. We then performed a microscopy-based primary and confirmation RNAi screen in Drosophila S2 cells directly scoring the organisation of the tER-Golgi units. We identified 49 hits, most of which leading to an increased number of smaller tER-Golgi units (MG for “more and smaller Golgi”) upon depletion. 16 of them were validated and characterised, showing that this phenotype was not due to an inhibition in secretion, a block in G2, or ER stress. Interestingly, the MG phenotype was often accompanied by an increase in the cell volume. Out of 6 proteins, 4 were localised to the ER. Conclusions This work has identified novel proteins involved in the organisation of the Drosophila early secretory pathway. It contributes to the effort of assigning protein functions to gene annotation in the secretory pathway, and analysis of the MG hits revealed an enrichment of ER proteins. These results suggest a link between ER localisation, aspects of cell metabolism and tER-Golgi structural organisation. PMID:21383842

  1. Notice to exporters on products prohibited from export (nuclear material, equipment and large nuclear units)

    International Nuclear Information System (INIS)

    1988-01-01

    In order to ensure that the policy to avoid the proliferation of nuclear weapons is complied with, the French Administration applies stricter controls over the export of certain sensitive products, materials and equipment. To this effect, lists of such products, materials and equipment are published in the form of Notices to exporters and periodically revised. This Notice repeals and replaces the previous Notice published in the Official Gazette of 21 January 1986. Annex I contains the list of materials whose export is subject to nuclear non-proliferation controls. Annex II lists the equipment whose export is subject to the same controls. Annex III includes the list of large nuclear units for which an application for prior approval of export must be submitted to the Administrations concerned. (NEA) [fr

  2. Superstar Exporters: An Empirical Investigation of Strategic Interactions in Danish Export Markets

    DEFF Research Database (Denmark)

    Ciliberto, Federico; Jäkel, Ina Charlotte

    , product and destination. We also obtain detailed information on applied, preferential tariff protection from the MAcMap-HS6 database. We find evidence of strong negative competitive effects of entry: in the absence of strategic competitive effects, firms would be 54.3 percentage points more likely...... to export to a given market. Next, we run two counterfactual exercises. We show that failing to account for the strategic interaction among superstar exporters leads to: (i) overstating the probability that firms would start exporting to a market following tariff elimination by 8 percentage points; and, (ii......) overstating the probability that firms would stop exporting to a market if tariffs were imposed by 7.5 percentage points. We also show that competitive effects vary across export markets and competitors. This heterogeneity in the competitive effects implies that there exist multiple equilibria, both...

  3. Quebec-USA electricity export contracts

    International Nuclear Information System (INIS)

    Labbe, J.-F.

    1993-06-01

    Electricity exports from Hydro-Quebec to utilities in the USA significantly affects the economy and environment of Quebec. These exports may be arranged under interconnection agreements to sell excess capacity and production during off-peak periods or under firm sales contracts. Hydro-Quebec exports could also replace power plants that would otherwise be needed in the USA. The economic environment for Hydro-Quebec exports to the USA is reviewed along with the regulatory environment applicable to international trade (General Agreement on Tariffs and Trade, Canada-USA Free Trade Agreement, North American Free Trade Agreement), Quebec (Canadian federal and provincial law), and the USA (federal and state law). A jurisdictional analysis of power export contracts is then presented, citing examples of contracts already signed by Hydro-Quebec with utilities in New York and New England. Contract law and contract provisions are discussed, including common clauses and particular clauses. Suggestions are made for new clauses that would improve the electricity trade. 215 refs., 13 figs., 3 tabs

  4. Final argument on regulation of electricity exports

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    Ontario Hydro addresses the request of the National Energy Board review that parties comment on the broader question of the need for federal regulation in electricity exports and the objectives which underlie the view expressed. Electricity exports benefit Canadian sellers and U.S. purchasers as well the Canadian economy in general. There is a clear consensus that these benefits exist and should be realized, but the evidence indicates that there is no consensus on how the benefits can best be distributed within Canada. The divergent views expressed by interested parties from across Canada clearly demonstrate the complexity associated with determining the overall Canadian interest and that there is a need for a balancing of these interests by a federal body. The regulation of electricity exports is clearly a matter of international commerce and Ontario Hydro submitted that the Constitution Act deems the province incompetent to regulate the export of electricity from Canada. Ontario Hydro submitted that a federal body is required in the regulation of electricity exports to protect the broader Canadian interest.

  5. Synaptotagmin SYTA forms ER-plasma membrane junctions that are recruited to plasmodesmata for plant virus movement.

    Science.gov (United States)

    Levy, Amit; Zheng, Judy Y; Lazarowitz, Sondra G

    2015-08-03

    Metazoan synaptotagmins are Ca(2+) sensors that regulate exocytosis and endocytosis in various cell types, notably in nerve and neuroendocrine cells [1, 2]. Recently, the structurally related extended synaptotagmins were shown to tether the cortical ER to the plasma membrane in human and yeast cells to maintain ER morphology and stabilize ER-plasma membrane (ER-PM) contact sites for intracellular lipid and Ca(2+) signaling [3, 4]. The Arabidopsis synaptotagmin SYTA regulates endocytosis and the ability of plant virus movement proteins (MPs) to alter plasmodesmata to promote virus cell-to-cell transport [5, 6]. Yet how MPs modify plasmodesmata, the cellular functions of SYTA and how these aid MP activity, and the proteins essential to form plant cell ER-PM contact sites remain unknown. We addressed these questions using an Arabidopsis SYTA knockdown line syta-1 and a Tobamovirus movement protein MP(TVCV) [5, 7]. We report here that SYTA localized to ER-PM contact sites. These sites were depleted and the ER network collapsed in syta-1, and both reformed upon rescue with SYTA. MP(TVCV) accumulation in plasmodesmata, but not secretory trafficking, was also inhibited in syta-1. During infection, MP(TVCV) recruited SYTA to plasmodesmata, and SYTA and the cortical ER were subsequently remodeled to form viral replication sites adjacent to plasmodesmata in which MP(TVCV) and SYTA directly interacted caged within ER membrane. SYTA also accumulated in plasmodesmata active in MP(TVCV) transport. Our findings show that SYTA is essential to form ER-PM contact sites and suggest that MPs interact with SYTA to recruit these sites to alter plasmodesmata for virus cell-to-cell movement. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. DNA as a component of ER materials

    International Nuclear Information System (INIS)

    Minagawa, K; Aoki, Y; Berber, M R; Mori, T; Tanaka, M

    2009-01-01

    Deoxyribonucleic acid (DNA), which is known as a typical biopolymer, has been utilized for a few types of ER materials. Suspensions were prepared with the particles of DNA, DNA/lipid complexes, and LDH (layered double hydroxide)/DNA composites. The purified DNA showed larger ER effect than the others, but this particle tended to absorb water, which caused less stability. Preliminary experiments of preparing composite with LDH indicated that this inorganic material would be useful for hydrophobic modification of DNA particles, although further optimization of composite preparation is needed. In addition, the LDH/DNA suspensions showed interesting behaviours under some conditions, which indicated possibility for controlling ER property in a wide range.

  7. DNA as a component of ER materials

    Energy Technology Data Exchange (ETDEWEB)

    Minagawa, K; Aoki, Y; Berber, M R [Institute of Technology and Science, University of Tokushima, Tokushima 770-8506 (Japan); Mori, T [Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka 819-0395 (Japan); Tanaka, M [Faculty of Pharmaceutical Science, Tokushima Bunri University, Tokushima 770-8514 (Japan)], E-mail: minagawa@chem.tokushima-u.ac.jp

    2009-02-01

    Deoxyribonucleic acid (DNA), which is known as a typical biopolymer, has been utilized for a few types of ER materials. Suspensions were prepared with the particles of DNA, DNA/lipid complexes, and LDH (layered double hydroxide)/DNA composites. The purified DNA showed larger ER effect than the others, but this particle tended to absorb water, which caused less stability. Preliminary experiments of preparing composite with LDH indicated that this inorganic material would be useful for hydrophobic modification of DNA particles, although further optimization of composite preparation is needed. In addition, the LDH/DNA suspensions showed interesting behaviours under some conditions, which indicated possibility for controlling ER property in a wide range.

  8. A stabilized optical frequency comb based on an Er-doped fiber femtosecond laser

    Science.gov (United States)

    Xia, Chuanqing; Wu, Tengfei; Zhao, Chunbo; Xing, Shuai

    2018-03-01

    An optical frequency comb based on a 250 MHz home-made Er-doped fiber femtosecond laser is presented in this paper. The Er-doped fiber laser has a ring cavity and operates mode-locked in femtosecond regime with the technique of nonlinear polarization rotation. The pulse duration is 118 fs and the spectral width is 30 nm. A part of the femtosecond laser is amplified in Er-doped fiber amplifier before propagating through a piece of highly nonlinear fiber for expanding the spectrum. The carrier-envelope offset frequency of the comb which has a signal-to-noise ratio more than 35 dB is extracted by means of f-2f beating. It demonstrates that both carrier-envelope offset frequency and repetition frequency keep phase locked to a Rubidium atomic clock simultaneously for 2 hours. The frequency stabilized fiber combs will be increasingly applied in optical metrology, attosecond pulse generation, and absolute distance measurement.

  9. ARM CLASIC ER2 CRS/EDOP

    Energy Technology Data Exchange (ETDEWEB)

    Gerald Heymsfield

    2010-12-20

    Data was taken with the NASA ER-2 aircraft with the Cloud Radar System and other instruments in conjunction with the DOE ARM CLASIC field campaign. The flights were near the SGP site in north Central Oklahoma and targeted small developing convection. The CRS is a 94 GHz nadir pointing Doppler radar. Also on board the ER-2 was the Cloud Physics Lidar (CPL). Seven science flights were conducted but the weather conditions did not cooperate in that there was neither developing convection, or there was heavy rain.

  10. Psyken er en grænseflade

    DEFF Research Database (Denmark)

    Hoffmeyer, Jesper

    2011-01-01

    En computer er i sig selv blot et stykke mekanik. Det afgørende sker i mødet mellem maskinen, mennesker og fællesskaber: på grænsefladen. Præcis som hos levende væsner......En computer er i sig selv blot et stykke mekanik. Det afgørende sker i mødet mellem maskinen, mennesker og fællesskaber: på grænsefladen. Præcis som hos levende væsner...

  11. Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors

    Directory of Open Access Journals (Sweden)

    Hui eHan

    2013-10-01

    Full Text Available Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER stress response in liver cancer development was investigated using an animal model with a liver knockout of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet (HFD feeding resulted in higher levels of serum alanine aminotransferase (ALT, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months knockout females than in either middle-aged (6 months knockouts or older (aged 16 months wild type females. In the older knockout females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER associated degradation (ERAD were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2, Herpud1 (ubiquitin-like domain member, Wfs1 (wolfram syndrome gene, and Yod1 (deubiquinating enzyme 1 was co-present with decreased proteasome activities, increased estrogen receptor alpha variant (ERa36, and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2 and STAT3 (the signal transducers and activators of transcription in the older knockout female fed alcohol. Our results suggest that long-term alcohol consumption and ageing may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ER associated degradation.

  12. Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.

    Directory of Open Access Journals (Sweden)

    Caroline Kulangara

    Full Text Available In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1. In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.

  13. Export competitiveness of pakistani horticultural products

    International Nuclear Information System (INIS)

    Akhtar, W.; Akmal, N.; Shah, H.; Tahir, A.; Niazi, M.A.

    2013-01-01

    This paper examines Pakistan's competitiveness in export of selected horticulture commodities by employing set of revealed comparative advantage (RCA) and revealed competitive advantage indices with respect to global trade. Results demonstrate that Pakistan has comparative and competitive advantage over the period under analysis and indicates a transition from comparative and competitive disadvantage to comparative and competitive advantage during the period under analysis. Tangerines, mandarins, clem have maintained relatively higher revealed comparative advantage as compared to other categories for the whole period under analysis. Onion export has revealed comparative advantage with some fluctuations over time. The research indicates that Pakistan's comparative and competitive advantages have been increasing in all the selected commodities during period under analysis which indicates the potential of horticulture exports for foreign exchange earnings. There is need to strengthen comparative and competitive advantage in horticulture sector by policy support and facilitating role by all stakeholders. (author)

  14. 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......, however, be contingent on attributes such as gender and education, especially among the first generation of migrants, in that being male and educated is more advantageous for migrants than for indigenous entrepreneurs. A representative sample of 50,371 entrepreneurs establishing or operating enterprises...... 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...

  15. Export and import. Conformity with regulations

    International Nuclear Information System (INIS)

    Shapar, M.

    1976-01-01

    Since the division of the former US Atomic Energy Commission's tasks, the regulation and control of import and export of nuclear materials and equipment has become the responsability of the Nuclear Regulatory Commission (NRC). The import and export of nuclear fuels, equipment and reactors are therefore subject to prior licensing by the Commission. This requirement aims to guarantee that such activities will not create serious hazards for defense and national safety, and that the exported products will not be diverted from their peaceful uses. The relevant applicable legal provisions are based on the Atomic Energy Act of 1954 and on the detailed regulations issued by the Commission. Under the pressure of public opinion, there is a current tendency to restrict these activities because of the hazards they present, in particular during transport, until the Commission has completed all the necessary studies. (NEA) [fr

  16. German nuclear fuel exports and imports 1991

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The statistics compiled by the German Federal Office for Trade and Industry (Bundesamt fuer Wirtschaft) for the Federal Ministry for the Environment, Conservation of Nature, and Reactor Safety of imports and exports of nuclear fuels and source materials in 1991 show a major drop by 33.8% in imports and a pronounced rise by 191.5% in exports, compared to the levels in the previous year. Source material for the purposes of these statistics refers only to uranium concentrate. Quantitatively, the biggest import items are source materials, depleted uranium, and uranium enriched up to 3%. Exports of unirradiated material quantitatively comprise mainly depleted uranium, source material, and uranium enriched up to 10%. (orig.) [de

  17. New U.S. nuclear export legislation

    International Nuclear Information System (INIS)

    Patermann, C.

    1978-01-01

    The new 1978 Export Control Act of the United States of America introduces a comprehensive arrangement of the criteria, responsibilities and procedures associated with nuclear exports, especially under the nonproliferation aspect. After a detailed analysis of the multitude of provisions it must be feared that, merely as a result of the high degree of formalization, bureaucratization and politicalization of these procedures, the U.S. can henceforth no longer be regarded as a reliable source of nuclear materials and facilities. An aspect received abroad with particular anguish is the fact that this unilateral aggravation of export controls was initiated after the start of the two-year INFCE program for international fuel cycle evaluation and that the new legislation forces the American government to renegotiate existing agreements on cooperation with the receiver countries under the threat of a delivery stop. (orig.) [de

  18. Should Australia mine and export uranium?

    International Nuclear Information System (INIS)

    Cobb, M.; Broadbent, Steve.

    1989-01-01

    In this chapter, the case for and against the mining and export of Australian uranium is discussed. For those in favour of uranium export, the nuclear energy, a source of energy which could bring a much needed boost to Australian export and employment, is being stifled by specious 'scare tactics' about the danger and misuse of uranium. It is also shown that uranium is the only feasible energy source, being cheaper, safer and cleaner when compared with other energy sources. Meanwhile, the opponents of nuclear energy, argue that uranium mining is environmentally destructive, is a danger to workers and residents health, it is bad for economy and it provides raw materials for nuclear weapons. 2 tabs

  19. Direct Evidence on Learning by Exporting

    DEFF Research Database (Denmark)

    Grimpe, Christoph; Belderbos, Rene

    2014-01-01

    learning and export learning – an issue that has been ignored in prior studies. Learning from foreign customers is more prevalent than learning from foreign competitors. Firms’ underlying innovation strategy appears as an important moderator of the propensity to learn and of the relationship between......We examine first direct evidence on the occurrence of learning by exporting, using unique survey data for German innovating firms on the role of (foreign) customers and competitors as sources of ideas and impetus for innovation. Export intensive firms frequently benefit simultaneously from domestic...... learning and innovativeness. Firms adopting a strategy of technology leadership more often exhibit effective learning from diverse foreign customers and this learning is strongly associated with innovative sales – but mostly so if combined with domestic customer learning. In contrast, firms that have...

  20. British Columbia's untapped wind export potential

    International Nuclear Information System (INIS)

    Kaplan, M.

    2008-01-01

    This presentation discussed wind energy developments in British Columbia (BC). There are currently more than 5000 MW of wind power development activities in British Columbia, but only 325 MW of wind power purchase agreements (PPAs). Various renewable portfolio standards and greenhouse gas (GHG) initiatives are now being use to create demand for additional renewable energy development in the northwestern United States. Studies have demonstrated that BC wind export initiatives have the potential to deliver wind power to markets in the Pacific northwest. Canadian transmission export proposals are now examining methods of bringing renewable energy to areas with high load demands. However, the United States has more than 240,000 MW of proposed wind projects for key markets in the northwestern region. It was concluded that activities in United States wind development are now posing a challenge to Canadian wind energy exporters. Various transmission projects in the United States are now looking at developing renewable energy sources close to BC. tabs., figs

  1. 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

  2. Migrant entrepreneurship, economic activity and export performance

    DEFF Research Database (Denmark)

    Baklanov, Nikita; Rezaei, Shahamak; Vang, Jan

    2014-01-01

    Recent studies on transnational entrepreneurship suggest that migrant entrepreneur plays an increasingly significant role as sources of economic activities and especially export revenue. The literature is, however, biased on the US experience, lacks a comparative perspective between migrants...... and non-migrants and is primarily anecdotal in nature. This paper aims to reduce this gap by mapping the recent changes in the role of migrant entrepreneurs as a source of increased economic activity and export revenue in the Danish context and thereby linking the challenges stemming from...... the transnational entrepreneurship literature to the immigration and internationalisation of entrepreneurship literature. Entrepreneurial economic activity in this paper is proxied by the changing share of self-owned firms across ethic categories. Export revenue is proxied by the number of firms in the different...

  3. Energy efficiency and exporting: Evidence from firm-level data

    International Nuclear Information System (INIS)

    Roy, Jayjit; Yasar, Mahmut

    2015-01-01

    While exporting firms and non-exporters have been compared across several dimensions, empirical comparisons on the basis of environmental performance are relatively few. Moreover, analyzing the environmental implications of firm-level exports is not trivial due to non-random selection into exporting. In this light, we examine the impact of exporting on firms' energy efficiency by resorting to an instrumental variables strategy based on a differencing approach (Pitt and Rosenzweig, 1990). Utilizing data from Indonesia, we find (i) exporting to reduce the use of fuels (relative to electricity) and (ii) concerns over endogeneity of exporting status to be relevant. - Highlights: • We examine the impact of exporting on firms' energy efficiency. • We employ cost share equations, firm-level data from Indonesia, and an instrumental variables strategy. • Exporting is found to reduce the use of fuels (relative to electricity).

  4. Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig, E-mail: blackstc@ninds.nih.gov

    2016-11-15

    Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells also

  5. Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

    International Nuclear Information System (INIS)

    Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig

    2016-01-01

    Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells also

  6. ER Stress: A Therapeutic Target in Rheumatoid Arthritis?

    Science.gov (United States)

    Rahmati, Marveh; Moosavi, Mohammad Amin; McDermott, Michael F

    2018-04-22

    Diverse physiological and pathological conditions that impact on protein folding of the endoplasmic reticulum (ER) cause ER stress. The unfolded protein response (UPR) and the ER-associated degradation (ERAD) pathway are activated to cope with ER stress. In rheumatoid arthritis (RA), inflammation and ER stress work in parallel by driving inflammatory cells to release cytokines that induce chronic ER stress pathways. This chronic ER stress may contribute to the pathogenesis of RA through synoviocyte proliferation and proinflammatory cytokine production. Therefore, ER stress pathways and their constituent elements are attractive targets for RA drug development. In this review, we integrate current knowledge of the contribution of ER stress to the overall pathogenesis of RA, and suggest some therapeutic implications of these discoveries. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. PLOT3D Export Tool for Tecplot

    Science.gov (United States)

    Alter, Stephen

    2010-01-01

    The PLOT3D export tool for Tecplot solves the problem of modified data being impossible to output for use by another computational science solver. The PLOT3D Exporter add-on enables the use of the most commonly available visualization tools to engineers for output of a standard format. The exportation of PLOT3D data from Tecplot has far reaching effects because it allows for grid and solution manipulation within a graphical user interface (GUI) that is easily customized with macro language-based and user-developed GUIs. The add-on also enables the use of Tecplot as an interpolation tool for solution conversion between different grids of different types. This one add-on enhances the functionality of Tecplot so significantly, it offers the ability to incorporate Tecplot into a general suite of tools for computational science applications as a 3D graphics engine for visualization of all data. Within the PLOT3D Export Add-on are several functions that enhance the operations and effectiveness of the add-on. Unlike Tecplot output functions, the PLOT3D Export Add-on enables the use of the zone selection dialog in Tecplot to choose which zones are to be written by offering three distinct options - output of active, inactive, or all zones (grid blocks). As the user modifies the zones to output with the zone selection dialog, the zones to be written are similarly updated. This enables the use of Tecplot to create multiple configurations of a geometry being analyzed. For example, if an aircraft is loaded with multiple deflections of flaps, by activating and deactivating different zones for a specific flap setting, new specific configurations of that aircraft can be easily generated by only writing out specific zones. Thus, if ten flap settings are loaded into Tecplot, the PLOT3D Export software can output ten different configurations, one for each flap setting.

  8. Adducin family proteins possess different nuclear export potentials.

    Science.gov (United States)

    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

  9. US coal industry seeks export markets

    Energy Technology Data Exchange (ETDEWEB)

    1981-07-01

    Problems encountered in the expansion of the USA export market for coal are discussed, including: lack of port facilities to handle bulk coal shipments; inadequate rail facilities and the already high costs; and delays caused by complex legislation. Solutions to the problem of ports are suggested, and also the advantages of coal export expansion with respect to industry as a whole and unemployment. Details of projects on the Canton Railroad and the terminal in Baltimore are given. Views of the American Association of Port Authorities on navigation are expressed.

  10. ANALYSIS OF CHINESE GARMENT EXPORT SECTOR

    OpenAIRE

    Zhang, Mina

    2009-01-01

    This paper analyzes the Chinese garment export sector. The Chinese garment industry has been an economic pillar ever since the open-door policy and economic reforms of the country took effect in 1979. Earnings from apparel exports have been a major source of foreign revenue. The industry has thus developed and played a vital role in the growth of China?s foreign trade and economic development although some signs of slackened vigour have been revealed recently. To assess the threats and opport...

  11. Multinational retailers and home country food exports

    OpenAIRE

    Cheptea, Angela; Latouche, Karine; Emlinger, Charlotte

    2015-01-01

    This article questions whether food exports to a given national market are impacted by a domestic retailer opening in that market. To answer this question, we considered an empirical gravity-type trade model. We tested our model with data on bilateral exports of food products sold in supermarkets (groceries) on a large panel of countries, as well as the foreign grocery sales of the world’s 100 largest retail companies from 2001–2010. We found a strong positive effect of the overseas presence ...

  12. Export policy and non-proliferation

    International Nuclear Information System (INIS)

    Fischer, D.A.V.

    1978-01-01

    Developing countries with a nuclear programme are about a dozen according to information obtained by IAEA. They are a group hostile to any restriction imposed on nuclear technology export and consider that such restriction is contrary to the global concept of North/South co-operation which provides for transfer of advanced technology. In particular, they object to the fact that nuclear weapon states make use of Article 4 of the NPT. Industrialised countries are required to keep a balance between a regular and stable supply system and the assurance that exported nuclear installations and materials are placed under international control according to the IAEA Safeguards. (NEA) [fr

  13. NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis.

    Science.gov (United States)

    Widenmaier, Scott B; Snyder, Nicole A; Nguyen, Truc B; Arduini, Alessandro; Lee, Grace Y; Arruda, Ana Paula; Saksi, Jani; Bartelt, Alexander; Hotamisligil, Gökhan S

    2017-11-16

    Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While the mechanisms by which the ER defends against cholesterol insufficiency are well described, it remains unclear how the ER senses and effectively defends against cholesterol excess. Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process. We show that Nrf1 directly binds to and specifically senses cholesterol in the ER through a defined domain and that cholesterol regulates Nrf1 turnover, processing, localization, and activity. In Nrf1 deficiency, in vivo cholesterol challenges induce massive hepatic cholesterol accumulation and damage, which is rescued by replacing Nrf1 exogenously. This Nrf1-mediated mechanism involves the suppression of CD36-driven inflammatory signaling and derepression of liver X receptor activity. These findings reveal Nrf1 as a guardian of cholesterol homeostasis and a core component of adaptive responses to excess cellular cholesterol. Copyright © 2017. Published by Elsevier Inc.

  14. ER-associated degradation is required for vasopressin prohormone processing and systemic water homeostasis

    Science.gov (United States)

    Somlo, Diane R.M.; Kim, Geun Hyang; Prescianotto-Baschong, Cristina; Sun, Shengyi; Beuret, Nicole; Long, Qiaoming; Rutishauser, Jonas

    2017-01-01

    Peptide hormones are crucial regulators of many aspects of human physiology. Mutations that alter these signaling peptides are associated with physiological imbalances that underlie diseases. However, the conformational maturation of peptide hormone precursors (prohormones) in the ER remains largely unexplored. Here, we report that conformational maturation of proAVP, the precursor for the antidiuretic hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex. Serum hyperosmolality induces expression of both ERAD components and proAVP in AVP-producing neurons. Mice with global or AVP neuron–specific ablation of Se1L-Hrd1 ERAD progressively developed polyuria and polydipsia, characteristics of diabetes insipidus. Mechanistically, we found that ERAD deficiency causes marked ER retention and aggregation of a large proportion of all proAVP protein. Further, we show that proAVP is an endogenous substrate of Sel1L-Hrd1 ERAD. The inability to clear misfolded proAVP with highly reactive cysteine thiols in the absence of Sel1L-Hrd1 ERAD causes proAVP to accumulate and participate in inappropriate intermolecular disulfide–bonded aggregates, promoted by the enzymatic activity of protein disulfide isomerase (PDI). This study highlights a pathway linking ERAD to prohormone conformational maturation in neuroendocrine cells, expanding the role of ERAD in providing a conducive ER environment for nascent proteins to reach proper conformation. PMID:28920920

  15. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

    Science.gov (United States)

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-06-08

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.

  16. Ledelse af samskabelse er en ny ledelsesdisciplin

    DEFF Research Database (Denmark)

    Ulrich, Jens; Martin Nielsen, Kim; Bartram, Jan

    2018-01-01

    Samskabelse er blevet det nye orienteringspunkt for rigtig mange offentlige organisationer. Det skyldes en udbredt konsensus om, at velfærdsopgaverne ikke kan løses inden for de vante organisatoriske rammer, men må løses i tæt kontakt med de parter, som opgaverne vedrører. Denne nye tilgang til...

  17. Der er fuld religionsfrihed i Danmark, men..

    DEFF Research Database (Denmark)

    Christoffersen, Lisbet

    2018-01-01

    Artiklen analyserer en rapport, udgivet af FN's special rapporteur on Freedom of Religion and Belief, Heiner Bielefeldt. Rapporten vedrører Danmark. Analysen tilslutter sig rapporten på de fleste punkter, men kritiserer begrebet 'blød diskrimination'; kritiserer at rapporten ikke er gået tættere på...

  18. Hvad er kildekritik?

    DEFF Research Database (Denmark)

    Olden-Jørgensen, Sebastian

    2009-01-01

    Hvad er Kildekritik? I stedet for at forstå kildekritik som et stringent system, grundlagt af Leopold von Ranke og i Danmark kanoniseret af Kristian Erslev, kunne man med større historiografisk ret og faglig frugtbarhed opfatte kildekritikken som en faglig tradition med tre lag afsat (sedimentere...

  19. Hvad er PET og fMRI?

    DEFF Research Database (Denmark)

    B. Paulson, Olaf; Balslev, Daniela; Gerlach, Christian

    2007-01-01

    Hvilken rolle spiller følelserne for vores tankeliv, og hvorfor har vi overhovedet følelser? I kraft af avancerede hjerneskanningsteknikker er den moderne hjernevidenskab blevet i stand til at besvare disse spørgsmål. Gennem artiklerne i denne antologi, skrevet af ledende danske forskere, bliver ...

  20. Creating Smart-er Cities: An Overview

    Science.gov (United States)

    Allwinkle, Sam; Cruickshank, Peter

    2011-01-01

    The following offers an overview of what it means for cities to be "smart." It draws the supporting definitions and critical insights into smart cities from a series of papers presented at the 2009 Trans-national Conference on Creating Smart(er) Cities. What the papers all have in common is their desire to overcome the all too often…

  1. Geometric calibration of ERS satellite SAR images

    DEFF Research Database (Denmark)

    Mohr, Johan Jacob; Madsen, Søren Nørvang

    2001-01-01

    Geometric calibration of the European Remote Sensing (ERS) Satellite synthetic aperture radar (SAR) slant range images is important in relation to mapping areas without ground reference points and also in relation to automated processing. The relevant SAR system parameters are discussed...

  2. Er nogen mere lige end andre?

    DEFF Research Database (Denmark)

    Møberg, Rasmus Juul

    normativ fordring. Kohlis (2007) formulering af normalbiografien er en tredeling af livsforløbet (uddannelse – arbejdsliv - pension). En tredeling der bliver kritiseret for at være køns- og familieblind, hvorfor linked lives-begrebet bliver introduceret. Begrebet har den teoretiske implikation...... analyser tager højde for afhængighed over tid i den afhængige variabel. Overordnet set er det tre aspekter af datas karakteristika, der fordrer specielle metoder. Det er censurering af data, tidsmæssig variation i de uafhængige variable samt potentiel korrelation mellem målingerne af den afhængige variabel...... for disse ændringer, hvorved risikoen for en given transition beregnes mere præcist. Afhandlingens empiriske grundlag er registerdata for alle personer i Danmark, der tilhører fødselskohorterne 1968, 1972 og 1976. Data dækker over personlige, familiære forhold og oplysninger på arbejdspladsniveau, hvor den...

  3. Hvad nu hvis sommerfuglen er ekshibitionist?

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2008-01-01

    Groft sagt vil denne artikel, ved at aflæse hvad hhv. Inger Christensen, Sigmund Freud og Jacques Lacan har at sige om sommerfugle, argumentere for at der er et afgørende skel mellem naturvidenskab og litteraturvidenskab; mellem naturen, dyret, sommerfuglen på den ene side og bevidstheden...

  4. Hvad er hjemkundskabslæreren?

    DEFF Research Database (Denmark)

    Benn, Jette

    2009-01-01

        En appetizer: De praktisk-musiske fag på dagsordenen Temaet for denne artikel er hjemkundskabsfaget, -professionen og dens praktisering belyst gennem et interviewstudie fra 2008 af lærerstuderende og deres lærere. Dette studie relateres til forfatterens tidligere studie af fag og profession i...

  5. Er Storm P. en hardcore vagabond?

    DEFF Research Database (Denmark)

    Sortkær, Allan

    2002-01-01

    Den vagabond, som vi kender som Storm P.s, er ikke en figur, der kom fra en guddommelig inspiration eller deslige. Den var en allerede velkendt figur, før Storm P. tog den til sig, og figuren gennemgik radikale forandringer gennem Storm P.s liv: Krads social satire, hypervoldelig eller hyggelig...

  6. Er Frank rationel demokrat eller naiv fetichist?

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2014-01-01

    Artiklen er en diskussion af demokrati-begrebet i Rune Lykkebergs Alle har ret. Over for Lykkebregs demokrati-begreb sætter den Rancières og Zizeks forståelse af demokratiet som en åbning for det, den sociale orden ikke kan rumme. Det fører til en kritik af Lykkebergs anvendelse af begreberne om...

  7. Hvad er militær ledelse?

    DEFF Research Database (Denmark)

    Barfod, Jakob Rømer

    militær ledelse unik og derved muliggøre en opdeling, således at Forsvarets skoler kun underviser i den del af ledelse, som andre civile uddannelsesinstitutioner ikke menes at kunne undervise i. Men er det muligt at adskille begreber og praksis på den måde? Dette brief undersøger nogle betydninger af...

  8. Finanskrisen - er den markedsorienterede regulering skurken?

    DEFF Research Database (Denmark)

    Grosen, Anders

    2009-01-01

    markedsorienterede opgørelse tilsyneladende skyld i bankernes dårlige resultater. I hvert fald er standardsætteren inden for international regnskabsregulering, IASB, i efteråret 2008 på rekordtid kommet de betrængte virksomheder - herunder bankerne - til undsætning med en regnskabsmæssig hjælpepakke som supplement...

  9. Effects of material growth technique and Mg doping on Er3+ photoluminescence in Er-implanted GaN

    International Nuclear Information System (INIS)

    Kim, S.; Henry, R. L.; Wickenden, A. E.; Koleske, D. D.; Rhee, S. J.; White, J. O.; Myoung, J. M.; Kim, K.; Li, X.; Coleman, J. J.

    2001-01-01

    Photoluminescence (PL) and photoluminescence excitation (PLE) spectroscopies have been carried out at 6 K on the ∼1540 nm 4 I 13/2 - 4 I 15/2 emissions of Er 3+ in Er-implanted and annealed GaN. These studies revealed the existence of multiple Er 3+ centers and associated PL spectra in Er-implanted GaN films grown by metalorganic chemical vapor deposition, hydride vapor phase epitaxy, and molecular beam epitaxy. The results demonstrate that the multiple Er 3+ PL centers and below-gap defect-related absorption bands by which they are selectively excited are universal features of Er-implanted GaN grown by different techniques. It is suggested that implantation-induced defects common to all the GaN samples are responsible for the Er site distortions that give rise to the distinctive, selectively excited Er 3+ PL spectra. The investigations of selectively excited Er 3+ PL and PLE spectra have also been extended to Er-implanted samples of Mg-doped GaN grown by various techniques. In each of these samples, the so-called violet-pumped Er 3+ PL band and its associated broad violet PLE band are significantly enhanced relative to the PL and PLE of the other selectively excited Er 3+ PL centers. More importantly, the violet-pumped Er 3+ PL spectrum dominates the above-gap excited Er 3+ PL spectrum of Er-implanted Mg-doped GaN, whereas it was unobservable under above-gap excitation in Er-implanted undoped GaN. These results confirm the hypothesis that appropriate codopants can increase the efficiency of trap-mediated above-gap excitation of Er 3+ emission in Er-implanted GaN. [copyright] 2001 American Institute of Physics

  10. Optical signal inverter of erbium-doped yttrium aluminum garnet with red shift of laser diodes.

    Science.gov (United States)

    Maeda, Y

    1994-08-10

    An optical signal inverter was demonstrated in a simple structure that combined a laser diode with Er-doped YAG crystal. The optical signal inversion occurred at a response time of 7 ns and was caused by the decrease of transmission of Er:YAG against the red shift of the wavelength of the laser diode.

  11. Regulation of p53 tetramerization and nuclear export by ARC.

    Science.gov (United States)

    Foo, Roger S-Y; Nam, Young-Jae; Ostreicher, Marc Jason; Metzl, Mark D; Whelan, Russell S; Peng, Chang-Fu; Ashton, Anthony W; Fu, Weimin; Mani, Kartik; Chin, Suet-Feung; Provenzano, Elena; Ellis, Ian; Figg, Nichola; Pinder, Sarah; Bennett, Martin R; Caldas, Carlos; Kitsis, Richard N

    2007-12-26

    Inactivation of the transcription factor p53 is central to carcinogenesis. Yet only approximately one-half of cancers have p53 loss-of-function mutations. Here, we demonstrate a mechanism for p53 inactivation by apoptosis repressor with caspase recruitment domain (ARC), a protein induced in multiple cancer cells. The direct binding in the nucleus of ARC to the p53 tetramerization domain inhibits p53 tetramerization. This exposes a nuclear export signal in p53, triggering Crm1-dependent relocation of p53 to the cytoplasm. Knockdown of endogenous ARC in breast cancer cells results in spontaneous tetramerization of endogenous p53, accumulation of p53 in the nucleus, and activation of endogenous p53 target genes. In primary human breast cancers with nuclear ARC, p53 is almost always WT. Conversely, nearly all breast cancers with mutant p53 lack nuclear ARC. We conclude that nuclear ARC is induced in cancer cells and negatively regulates p53.

  12. Virtual water exported from Californian agriculture

    Science.gov (United States)

    Nicholas, K. A.; Johansson, E. L.

    2015-12-01

    In an increasingly teleconnected world, international trade drives the exchange of virtual land and water as crops produced in one region are consumed in another. In theory, this can be an optimal use of scarce resources if crops are grown where they can most efficiently be produced. Several recent analyses examine the export of land and water from food production in developing countries where these resources may be more abundant. Here we focus on a developed region and examine the virtual export of land and water from California, the leading agricultural state in the US and the leading global producer of a wide range of fruit, nut, and other specialty crops. As the region faces a serious, ongoing drought, water use is being questioned, and water policy governance re-examined, particularly in the agricultural sector which uses over three-quarters of water appropriations in the state. We look at the blue water embodied in the most widely grown crops in California and use network analysis to examine the trading patterns for flows of virtual land and water. We identify the main crops and export partners representing the majority of water exports. Considered in the context of tradeoffs for land and water resources, we highlight the challenges and opportunities for food production systems to play a sustainable role in meeting human needs while protecting the life-support systems of the planet.

  13. 78 FR 58995 - Order Denying Export Privileges

    Science.gov (United States)

    2013-09-25

    ... computers from the United States to Iran in violation of the embargo imposed upon that country by the United... submission from Kazerani. Based upon my review and consultations with BIS's Office of Export Enforcement... at the time of his conviction. Accordingly, it is hereby Ordered I. Until January 30, 2018, Iman...

  14. Human capital and wages in exporting firms

    DEFF Research Database (Denmark)

    Munch, Jakob Roland; Skaksen, Jan Rose

    2008-01-01

    This paper studies the link between the education level of workers, export performance and wages. 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...

  15. Know-how and nuclear exports

    International Nuclear Information System (INIS)

    Luxo, A.

    1978-01-01

    The concrete content of nuclear know-how is defined, and the present position as to the exchange of know-how is discussed. The new forms which may be taken by this know-how are considered and the results which may be expected from a know-how transfer (both for the exporting and the importing countries) are related [fr

  16. France intends to raise electricity exports

    International Nuclear Information System (INIS)

    Grotelueschen, M.; Boiteux.

    1986-01-01

    In this interview with the Chairman of the Supervisory Board of Electricite de France (EdF), the promotion of nuclear power in France, the chances on the export sector, and the structure of electric power supply are discussed and compared with the situation in West Germany. (UA) [de

  17. Subcellular sites for bacterial protein export

    NARCIS (Netherlands)

    Campo, Nathalie; Tjalsma, Harold; Buist, Girbe; Stepniak, Dariusz; Meijer, Michel; Veenhuis, Marten; Westermann, Martin; Müller, Jörg P.; Bron, Sierd; Kok, Jan; Kuipers, Oscar P.; Jongbloed, Jan D.H.

    2004-01-01

    Most bacterial proteins destined to leave the cytoplasm are exported to extracellular compartments or imported into the cytoplasmic membrane via the highly conserved SecA-YEG pathway. In the present studies, the subcellular distributions of core components of this pathway, SecA and SecY, and of the

  18. Subcellular sites for bacterial protein export.

    NARCIS (Netherlands)

    Campo, N.; Tjalsma, H.; Buist, G.; Stepniak, D.; Meijer, M.; Veenhuis, M.; Westermann, M.; Muller, J.P.; Bron, S.; Kok, J.; Kuipers, O.P.; Jongbloed, J.D.

    2004-01-01

    Most bacterial proteins destined to leave the cytoplasm are exported to extracellular compartments or imported into the cytoplasmic membrane via the highly conserved SecA-YEG pathway. In the present studies, the subcellular distributions of core components of this pathway, SecA and SecY, and of the

  19. Exporting vector muscles for facial animation

    NARCIS (Netherlands)

    Bui, T.D.; Butz, Andreas; Kruger, Antonio; Heylen, Dirk K.J.; Olivier, Patrick; Nijholt, Antinus; Poel, Mannes

    2003-01-01

    In this paper we introduce a method of exporting vector muscles from one 3D face to another for facial animation. Starting from a 3D face with an extended version of Waters’ linear muscle system, we transfer the linear muscles to a target 3D face.We also transfer the region division, which is used

  20. Extensive Margins of Offshoring and Exporting

    DEFF Research Database (Denmark)

    Laugesen, Anders Rosenstand

    This paper derives new comparative statics within a two-country version of the recent offshoring model by Antràs, Fort, and Tintelnot (2014) with nonprohibitive costs of exporting final goods. One key finding is that an asymmetric trade liberalisation might very well imply that the fractions of o...