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Sample records for requirements regulate cortactin

  1. PTP1B Regulates Cortactin Tyrosine Phosphorylation by Targeting Tyr446*S⃞

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    Stuible, Matthew; Dubé, Nadia; Tremblay, Michel L.

    2008-01-01

    The emergence of protein-tyrosine phosphatase 1B (PTP1B) as a potential drug target for treatment of diabetes, obesity, and cancer underlies the importance of understanding its full range of cellular functions. Here, we have identified cortactin, a central regulator of actin cytoskeletal dynamics, as a substrate of PTP1B. A trapping mutant of PTP1B binds cortactin at the phosphorylation site Tyr446, the regulation and function of which have not previously been characterized. We show that phosphorylation of cortactin Tyr446 is induced by hyperosmolarity and potentiates apoptotic signaling during prolonged hyperosmotic stress. This study advances the importance of Tyr446 in the regulation of cortactin and provides a potential mechanism to explain the effects of PTP1B on processes including cell adhesion, migration, and tumorigenesis. PMID:18387954

  2. Src binds cortactin through an SH2 domain cystine-mediated linkage

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    Evans, Jason V.; Ammer, Amanda G.; Jett, John E.; Bolcato, Chris A.; Breaux, Jason C.; Martin, Karen H.; Culp, Mark V.; Gannett, Peter M.; Weed, Scott A.

    2012-01-01

    Summary Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions. PMID:23097045

  3. Src binds cortactin through an SH2 domain cystine-mediated linkage.

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    Evans, Jason V; Ammer, Amanda G; Jett, John E; Bolcato, Chris A; Breaux, Jason C; Martin, Karen H; Culp, Mark V; Gannett, Peter M; Weed, Scott A

    2012-12-15

    Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions.

  4. The F-Actin Binding Protein Cortactin Regulates the Dynamics of the Exocytotic Fusion Pore through its SH3 Domain

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    González-Jamett, Arlek M.; Guerra, María J.; Olivares, María J.; Haro-Acuña, Valentina; Baéz-Matus, Ximena; Vásquez-Navarrete, Jacqueline; Momboisse, Fanny; Martinez-Quiles, Narcisa; Cárdenas, Ana M.

    2017-01-01

    Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate the neurosecretory process. This actin rearrangement includes both disruption of the preexisting actin network and de novo actin polymerization. However, the mechanism by which a Ca2+ signal elicits the formation of new actin filaments remains uncertain. Cortactin, an actin-binding protein that promotes actin polymerization in synergy with the nucleation promoting factor N-WASP, could play a key role in this mechanism. We addressed this hypothesis by analyzing de novo actin polymerization and exocytosis in bovine adrenal chromaffin cells expressing different cortactin or N-WASP domains, or cortactin mutants that fail to interact with proline-rich domain (PRD)-containing proteins, including N-WASP, or to be phosphorylated by Ca2+-dependent kinases, such as ERK1/2 and Src. Our results show that the activation of nicotinic receptors in chromaffin cells promotes cortactin translocation to the cell cortex, where it colocalizes with actin filaments. We further found that, in association with PRD-containing proteins, cortactin contributes to the Ca2+-dependent formation of F-actin, and regulates fusion pore dynamics and the number of exocytotic events induced by activation of nicotinic receptors. However, whereas the actions of cortactin on the fusion pore dynamics seems to depend on the availability of monomeric actin and its phosphorylation by ERK1/2 and Src kinases, cortactin regulates the extent of exocytosis by a mechanism independent of actin polymerization. Together our findings point out a role for cortactin as a critical modulator of actin filament formation and exocytosis in neuroendocrine cells. PMID:28522963

  5. Cortactin Tyrosine Phosphorylation Promotes Its Deacetylation and Inhibits Cell Spreading

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    Meiler, Eugenia; Nieto-Pelegrín, Elvira; Martinez-Quiles, Narcisa

    2012-01-01

    Background Cortactin is a classical Src kinase substrate that participates in actin cytoskeletal dynamics by activating the Arp2/3 complex and interacting with other regulatory proteins, including FAK. Cortactin has various domains that may contribute to the assembly of different protein platforms to achieve process specificity. Though the protein is known to be regulated by post-translational modifications such as phosphorylation and acetylation, how tyrosine phosphorylation regulates cortactin activity is poorly understood. Since the basal level of tyrosine phosphorylation is low, this question must be studied using stimulated cell cultures, which are physiologically relevant but unreliable and difficult to work with. In fact, their unreliability may be the cause of some contradictory findings about the dynamics of tyrosine phosphorylation of cortactin in different processes. Methodology/Principal Findings In the present study, we try to overcome these problems by using a Functional Interaction Trap (FIT) system, which involves cotransfecting cells with a kinase (Src) and a target protein (cortactin), both of which are fused to complementary leucine-zipper domains. The FIT system allowed us to control precisely the tyrosine phosphorylation of cortactin and explore its relationship with cortactin acetylation. Conclusions/Significance Using this system, we provide definitive evidence that a competition exists between acetylation and tyrosine phosphorylation of cortactin and that phosphorylation inhibits cell spreading. We confirmed the results from the FIT system by examining endogenous cortactin in different cell types. Furthermore, we demonstrate that cell spreading promotes the association of cortactin and FAK and that tyrosine phosphorylation of cortactin disrupts this interaction, which may explain how it inhibits cell spreading. PMID:22479425

  6. The C-terminus SH3-binding domain of Kv1.3 is required for the actin-mediated immobilization of the channel via cortactin

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    Hajdu, Peter; Martin, Geoffrey V.; Chimote, Ameet A.; Szilagyi, Orsolya; Takimoto, Koichi; Conforti, Laura

    2015-01-01

    Kv1.3 channels play a pivotal role in the activation and migration of T-lymphocytes. These functions are accompanied by the channels' polarization, which is essential for associated downstream events. However, the mechanisms that govern the membrane movement of Kv1.3 channels remain unclear. F-actin polymerization occurs concomitantly to channel polarization, implicating the actin cytoskeleton in this process. Here we show that cortactin, a factor initiating the actin network, controls the membrane mobilization of Kv1.3 channels. FRAP with EGFP-tagged Kv1.3 channels demonstrates that knocking down cortactin decreases the actin-based immobilization of the channels. Using various deletion and mutation constructs, we show that the SH3 motif of Kv1.3 mediates the channel immobilization. Proximity ligation assays indicate that deletion or mutation of the SH3 motif also disrupts interaction of the channel with cortactin. In T-lymphocytes, the interaction between HS1 (the cortactin homologue) and Kv1.3 occurs at the immune synapse and requires the channel's C-terminal domain. These results show that actin dynamics regulates the membrane motility of Kv1.3 channels. They also provide evidence that the SH3 motif of the channel and cortactin plays key roles in this process. PMID:25739456

  7. Vascular endothelial growth factor C promotes cervical cancer cell invasiveness via regulation of microRNA-326/cortactin expression.

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    Cheng, Yang; Jiang, Shuyi; Yuan, Jin; Liu, Junxiu; Simoncini, Tommaso

    2018-04-16

    Vascular endothelial growth factor C (VEGF-C) accelerates cervical cancer metastasis, while the detailed mechanism remains largely unknown. Recent evidence indicates that microRNA play a crucial role in controlling cancer cell invasiveness. In the present study, we investigated the role of miR-326 in VEGF-C-induced cervical cancer cell invasion. VEGF-C expression was higher and miR-326 was much lower in primary cervical cancer specimens than that in non-cancerous specimens, and a negative correlation between VEGF-C and miR-326 was found. On cervical carcinoma cell line SiHa cells, treatment with VEGF-C downregulated miR-326 level and increased cortactin protein expression. Transfection with miR-326 mimic reversed cortactin expression induced by VEGF-C, suggesting that VEGF-C increased cortactin via downregulation of miR-326. VEGF-C activated c-Src and c-Src inhibitor PP2 abolished VEGF-C effect on miR-326 and cortactin expression, implying that VEGF-C regulated miR-326/cortactin via c-Src signaling. VEGF-C promoted SiHa cell invasion index, which was largely inhibited by transfection with miR-326 antagonist or by siRNA against cortactin. In conclusion, our findings implied that VEGF-C reduced miR-326 expression and increased cortactin expression through c-Src signaling, leading to enhanced cervical cancer invasiveness. This may shed light on potential therapeutic strategies for cervical cancer therapy.

  8. Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.

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    Schnoor, Michael; Lai, Frank P L; Zarbock, Alexander; Kläver, Ruth; Polaschegg, Christian; Schulte, Dörte; Weich, Herbert A; Oelkers, J Margit; Rottner, Klemens; Vestweber, Dietmar

    2011-08-01

    Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β(2)-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.

  9. Cortactin and phagocytosis in isolated Sertoli cells

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    Wolski Katja M

    2005-12-01

    Full Text Available Abstract Background Cortactin, an actin binding protein, has been associated with Sertoli cell ectoplasmic specializations in vivo, based on its immunolocalization around the heads of elongated spermatids, but not previously identified in isolated Sertoli cells. In an in vitro model of Sertoli cell-spermatid binding, cortactin was identified around debris and dead germ cells. Based on this observation, we hypothesized that this actin binding protein may be associated with a non-junction-related physiological function, such as phagocytosis. The purpose of this study was to identify the presence and distribution of cortactin in isolated rat Sertoli cells active in phagocytic activity following the addition of 0.8 μm latex beads. Results Sertoli cell monocultures were incubated with or without follicle stimulating hormone (FSH; 0.1 μg/ml in the presence or absence of cytochalasin D (2 μM, as an actin disrupter. Cortactin was identified by standard immunostaining with anti-cortactin, clone 4F11 (Upstate after incubation times of 15 min, 2 hr, and 24 hr with or without beads. Cells exposed to no hormone and no beads appeared to have a ubiquitous distribution of cortactin throughout the cytoplasm. In the presence of cytochalasin D, cortactin immunostaining was punctate and distributed in a pattern similar to that reported for actin in cells exposed to cytochalasin D. Sertoli cells not exposed to FSH, but activated with beads, did not show cortactin immunostaining around the phagocytized beads at any of the time periods. FSH exposure did not alter the distribution of cortactin within Sertoli cells, even when phagocytic activity was upregulated by the presence of beads. Conclusion Results of this study suggest cortactin is not associated with peripheralized actin at junctional or phagocytic sites. Further studies are necessary to clarify the role of cortactin in Sertoli cells.

  10. High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin.

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    Wang, Zhi-Na; Liu, Dan; Yin, Bin; Ju, Wen-Yi; Qiu, Hui-Zhong; Xiao, Yi; Chen, Yuan-Jia; Peng, Xiao-Zhong; Lu, Chong-Mei

    2017-05-30

    Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC) patients with stages II and III CRC, which widely different in prognosis and treatment, by immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation and invasion in vitro. Denovirus shRNA knockdown of PTBP1 inhibited colorectal cancer growth in vivo. Furthermore, PTBP1 regulates alternative splicing of many target genes involving in tumorgenesis in colon cancer cells. We confirmed that the splicing of cortactin exon 11 which was only contained in cortactin isoform-a, as a PTBP1 target. Knockdown of PTBP1 decreased the expression of cortactin isoform-a by exclusion of exon 11. Also the mRNA levels of PTBP1 and cortactin isoform-a were cooperatively expressed in colorectal cancer tissues. Knocking down cortactin isoform-a significantly decreased cell migration and invasion in colorectal cancer cells. Overexpression of cortactin isoform-a could rescue PTBP1-knockdown effect of cell motility. In summary the study revealed that PTBP1 facilitates colorectal cancer migration and invasion activities by inclusion of cortactin exon 11.

  11. Cortactin is involved in the entry of Coxiella burnetii into non-phagocytic cells.

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    Eliana M Rosales

    Full Text Available BACKGROUND: Cortactin is a key regulator of the actin cytoskeleton and is involved in pathogen-host cell interactions. Numerous pathogens exploit the phagocytic process and actin cytoskeleton to infect host cells. Coxiella burnetii, the etiologic agent of Q fever, is internalized by host cells through a molecular mechanism that is poorly understood. METHODOLOGY/PRINCIPAL FINDING: Here we analyzed the role of different cortactin motifs in the internalization of C. burnetii by non-phagocytic cells. C. burnetii internalization into HeLa cells was significantly reduced when the cells expressed GFP-cortactin W525K, which carries a mutation in the SH3 domain that renders the protein unable to bind targets such as N-WASP. However, internalization was unaffected when the cells expressed the W22A mutant, which has a mutation in the N-terminal acidic region that destroys the protein's ability to bind and activate Arp2/3. We also determined whether the phosphorylation status of cortactin is important for internalization. Expression of GFP-cortactin 3F, which lacks phosphorylatable tyrosines, significantly increased internalization of C. burnetii, while expression of GFP-cortactin 3D, a phosphotyrosine mimic, did not affect it. In contrast, expression of GFP-cortactin 2A, which lacks phosphorylatable serines, inhibited C. burnetii internalization, while expression of GFP-cortactin SD, a phosphoserine mimic, did not affect it. Interestingly, inhibitors of Src kinase and the MEK-ERK kinase pathway blocked internalization. In fact, both kinases reached maximal activity at 15 min of C. burnetii infection, after which activity decreased to basal levels. Despite the decrease in kinase activity, cortactin phosphorylation at Tyr421 reached a peak at 1 h of infection. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the SH3 domain of cortactin is implicated in C. burnetii entry into HeLa cells. Furthermore, cortactin phosphorylation at serine and dephosphorylation

  12. Characterization of cortactin as an in vivo protein kinase D substrate: interdependence of sites and potentiation by Src.

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    De Kimpe, Line; Janssens, Katrien; Derua, Rita; Armacki, Milena; Goicoechea, Silvia; Otey, Carol; Waelkens, Etienne; Vandoninck, Sandy; Vandenheede, Jackie R; Seufferlein, Thomas; Van Lint, Johan

    2009-02-01

    Protein Kinase D (PKD) has been implicated in the regulation of actin turnover at the leading edge, invasion and migration. In particular, a complex between cortactin, paxillin and PKD in the invadopodia of invasive breast cancer cells has been described earlier, but so far this complex remained ill defined. Here we have investigated the possible role of PKD as a cortactin kinase. Using a mass spectrometric approach, we found that PKD phosphorylates cortactin on Ser 298 in the 6th cortactin repeat region and on Ser 348, right before the helical-proline rich domain of cortactin. We developed phosphospecific antibodies against these phosphorylated sequences, and used them as tools to follow the in vivo phosphorylation of cortactin by PKD. Examination of cortactin phosphorylation kinetics revealed that Ser 298 serves as a priming site for subsequent phosphorylation of Ser 348. Src, a well-known cortactin kinase, strongly potentiated the in vivo PKD mediated cortactin phosphorylation. This Src effect is neither mediated by pre-phosphorylation of cortactin nor by activation of PKD by Src. Phosphorylation of cortactin by PKD does not affect its subcellular localization, nor does it affect its translocation to podosomes or membrane ruffles. Moreover, there was no effect of PKD mediated cortactin phosphorylation on EGF receptor degradation and LPA induced migration. Taken together, these data establish cortactin as a novel PKD substrate and reveal a novel connection between Src and PKD.

  13. Sirtuin1 Maintains Actin Cytoskeleton by Deacetylation of Cortactin in Injured Podocytes

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    Motonishi, Shuta; Wada, Takehiko; Ishimoto, Yu; Ohse, Takamoto; Matsusaka, Taiji; Kubota, Naoto; Shimizu, Akira; Kadowaki, Takashi; Tobe, Kazuyuki

    2015-01-01

    Recent studies have highlighted the renoprotective effect of sirtuin1 (SIRT1), a deacetylase that contributes to cellular regulation. However, the pathophysiologic role of SIRT1 in podocytes remains unclear. Here, we investigated the function of SIRT1 in podocytes. We first established podocyte-specific Sirt1 knockout (SIRT1pod−/−) mice. We then induced glomerular disease by nephrotoxic serum injection. The increase in urinary albumin excretion and BUN and the severity of glomerular injury were all significantly greater in SIRT1pod−/− mice than in wild-type mice. Western blot analysis and immunofluorescence showed a significant decrease in podocyte-specific proteins in SIRT1pod−/− mice, and electron microscopy showed marked exacerbation of podocyte injury, including actin cytoskeleton derangement in SIRT1pod−/− mice compared with wild-type mice. Protamine sulfate-induced podocyte injury was also exacerbated by podocyte-specific SIRT1 deficiency. In vitro, actin cytoskeleton derangement in H2O2-treated podocytes became prominent when the cells were pretreated with SIRT1 inhibitors. Conversely, this H2O2-induced derangement was ameliorated by SIRT1 activation. Furthermore, SIRT1 activation deacetylated the actin-binding and -polymerizing protein cortactin in the nucleus and facilitated deacetylated cortactin localization in the cytoplasm. Cortactin knockdown or inhibition of the nuclear export of cortactin induced actin cytoskeleton derangement and dissociation of cortactin from F-actin, suggesting the necessity of cytoplasmic cortactin for maintenance of the actin cytoskeleton. Taken together, these findings indicate that SIRT1 protects podocytes and prevents glomerular injury by deacetylating cortactin and thereby, maintaining actin cytoskeleton integrity. PMID:25424328

  14. Cortactin overexpression results in sustained epidermal growth factor receptor signaling by preventing ligand-induced receptor degradation in human carcinoma cells

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    van Rossum, AGSH; Gibcus, J; van der Wal, J; Schuuring, E

    2005-01-01

    The chromosome 11q13 region is frequently amplified in human carcinomas and results in an increased expression of various genes including cortactin, and is also associated with an increased invasive potential. Cortactin acts as an important regulator of the actin cytoskeleton. It is therefore very

  15. Identification of a novel myositis-associated antibody directed against cortactin.

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    Labrador-Horrillo, Moisés; Martínez, Maria Angeles; Selva-O'Callaghan, Albert; Trallero-Araguás, Ernesto; Grau-Junyent, Josep M; Vilardell-Tarrés, Miquel; Juarez, Candido

    2014-10-01

    The aim of this study is to describe a novel myositis-associated autoantibody (anti-cortactin antibody) and assess related clinical and immunological manifestations and its clinical significance. Adult patients with myositis (dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and inclusion body myositis), as well as patients with other autoimmune diseases and non-inflammatory myopathies were analyzed for the presence of anti-cortactin antibody using in-house developed ELISA and immunoblotting techniques with a commercial source of purified cortactin. The cut-off for positive status was determined in a group of healthy volunteers. Antibody against cortactin was positive in 7/34 (20%) polymyositis patients, 9/117 (7.6%) dermatomyositis, 2/7 (26%) immune-mediated necrotizing myopathy, and none of the 4 patients with inclusion body myositis. The antibody also tested positive in 3/101 patients with other autoimmune diseases (2 systemic sclerosis and 1 systemic lupus erythematosus), and in 1/29 patients with non-inflammatory myopathy. No relevant association with specific clinical features was found in patients with these antibodies. Anti-cortactin antibody was more frequently positive in patients with polymyositis and immune-mediated necrotizing myopathy than in the remaining myositis patients, and was the only myositis autoantibody found in sera of 3 patients from these groups. Our data indicate that cortactin is a novel target antigen in patients with autoimmune diseases, especially patients with polymyositis or immune-mediated necrotizing myopathy. Anti-cortactin can be considered a new myositis-associated antibody. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation.

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    Lee, Mi-Sook; Kim, Sudong; Kim, Baek Gil; Won, Cheolhee; Nam, Seo Hee; Kang, Suki; Kim, Hye-Jin; Kang, Minkyung; Ryu, Jihye; Song, Haeng Eun; Lee, Doohyung; Ye, Sang-Kyu; Jeon, Noo Li; Kim, Tai Young; Cho, Nam Hoon; Lee, Jung Weon

    2014-09-01

    Although an in vitro 3D environment cannot completely mimic the in vivo tumor site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the study of cancer cell behaviors and the screening of anti-metastatic reagents with a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions (including cell density, extracellular acidity, or hypoxia as mimics for a continuous tumor growth) reduced JNKs, enhanced TGFβ1/Smad signaling activity, induced Snail1, and reduced cortactin expression. The reduced JNKs activity blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1-MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1 expression. Snail1 then repressed cortactin expression, causing reduced invadopodia formation and prominent localization of MT1-MMP at perinuclear regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation and invasion in 3D collagen I upon JNKs inhibition. These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Hippocampal Cortactin Levels are Reduced Following Spatial Working Memory Formation, an Effect Blocked by Chronic Calpain Inhibition.

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    Olson, Mikel L; Ingebretson, Anna E; Harmelink, Katherine M

    2015-06-19

    The mechanism by which the hippocampus facilitates declarative memory formation appears to involve, among other things, restructuring of the actin cytoskeleton within neuronal dendrites. One protein involved in this process is cortactin, which is an important link between extracellular signaling and cytoskeletal reorganization. In this paper, we demonstrate that total hippocampal cortactin, as well as Y421-phosphorylated cortactin are transiently reduced following spatial working memory formation in the radial arm maze (RAM). Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression. Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training. These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

  18. Hippocampal Cortactin Levels are Reduced Following Spatial Working Memory Formation, an Effect Blocked by Chronic Calpain Inhibition

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    Mikel L. Olson

    2015-06-01

    Full Text Available The mechanism by which the hippocampus facilitates declarative memory formation appears to involve, among other things, restructuring of the actin cytoskeleton within neuronal dendrites. One protein involved in this process is cortactin, which is an important link between extracellular signaling and cytoskeletal reorganization. In this paper, we demonstrate that total hippocampal cortactin, as well as Y421-phosphorylated cortactin are transiently reduced following spatial working memory formation in the radial arm maze (RAM. Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression. Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training. These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

  19. Cortactin is a prognostic marker for oral squamous cell carcinoma and its overexpression is involved in oral carcinogenesis.

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    Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Yeh, Chung-Min; Tseng, Hsien-Chang; Lin, Yung-Chang; Chung, Jing-Gung

    2017-03-01

    EMS1 (chromosome eleven, band q13, mammary tumor and squamous cell carcinoma-associated gene 1) gene amplification and the concomitant cortactin overexpression have been reported to associate with poor prognosis and tumor metastasis. In this study, we examined cortactin expression by immunohistochemistry in human oral tumors and murine tongue tumors which were induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO). The immunostaining results show over- to moderate expression of cortactin in 85% (104/122) of oral squamous cell carcinoma (OSCC) tissues and in all 15 leukoplakia tissues examined. Further, statistical analysis indicates that cortactin overexpression appears to be a predictor for shorter survival and poorer prognosis in OSCC patients. In an animal model, cortactin is shown to upregulate in infiltrating squamous cell carcinoma, papilloma, and epithelia with squamous hyperplasia, indicating that cortactin induction is an early event during oral carcinogenesis. It is suggested that cortactin expression is mediated in the progression of pre-malignancy to papilloma, based on earlier cortactin induction in pre-malignancy preceding cyclin D1 in papilloma. In conclusion, cortactin overexpression is frequently observed in human OSCC and mouse tongue tumors. Thus, cortactin may have an important role in the development of oral tumors in human and mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 799-812, 2017. © 2016 Wiley Periodicals, Inc.

  20. Cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes

    International Nuclear Information System (INIS)

    Ceccarelli, Simona; Cardinali, Giorgia; Aspite, Nicaela; Picardo, Mauro; Marchese, Cinzia; Torrisi, Maria Rosaria; Mancini, Patrizia

    2007-01-01

    Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte migration is not clearly established. Here we analyzed the motogenic activity of FGF10 and KGF on human keratinocytes. Migration assays and immunofluorescence of actin cytoskeleton revealed that FGF10 is less efficient than KGF in promoting migration and exerts a delayed effect in inducing lamellipodia and ruffles formation. Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration; however, FGF10-induced cortactin phosphorylation was reduced, more transient and delayed with respect to that promoted by KGF. Cortactin phosphorylation induced by both growth factors was Src-dependent, while its membrane translocation and cell migration were blocked by either Src and PI3K inhibitors, suggesting that both pathways are involved in KGF- and FGF10-dependent motility. Furthermore, siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. These results indicate that cortactin is involved in keratinocyte migration promoted by both KGF and FGF10

  1. Characterization of cortactin as an in vivo protein kinase D substrate: interdependence of sites and potentiation by Src

    NARCIS (Netherlands)

    de Kimpe, Line; Janssens, Katrien; Derua, Rita; Armacki, Milena; Goicoechea, Silvia; Otey, Carol; Waelkens, Etienne; Vandoninck, Sandy; Vandenheede, Jackie R.; Seufferlein, Thomas; van Lint, Johan

    2009-01-01

    Protein Kinase D (PKD) has been implicated in the regulation of actin turnover at the leading edge, invasion and migration. In particular, a complex between cortactin, paxillin and PKD in the invadopodia of invasive breast cancer cells has been described earlier, but so far this complex remained ill

  2. Analysis of the Role of Cortactin in Tumor Cell Invasion

    National Research Council Canada - National Science Library

    Zhan, Xi

    1999-01-01

    .... Studies have demonstrated that cortactin (also EMS1), a filamentous actin (F-actin) associated protein and a substrate of protein tyrosine kinase Src, plays an important role in the amplification...

  3. Analysis of the Role of Cortactin in Tumor Cell Invasion

    National Research Council Canada - National Science Library

    Zhan, Xi

    2001-01-01

    Cortactin is an actin cytoskeleton associated protein, frequently amplified and overexpressed along with the chromosome 11q13 in breast cancer, and acts as a prominent substrate of protein tyrosine kinase Src...

  4. Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells.

    Science.gov (United States)

    Lin, Yuan-Na; Izbicki, Jakob R; König, Alexandra; Habermann, Jens K; Blechner, Christine; Lange, Tobias; Schumacher, Udo; Windhorst, Sabine

    2014-04-01

    In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably down-regulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy. © 2013 UICC.

  5. Two amino acid residues confer different binding affinities of Abelson family kinase SRC homology 2 domains for phosphorylated cortactin.

    Science.gov (United States)

    Gifford, Stacey M; Liu, Weizhi; Mader, Christopher C; Halo, Tiffany L; Machida, Kazuya; Boggon, Titus J; Koleske, Anthony J

    2014-07-11

    The closely related Abl family kinases, Arg and Abl, play important non-redundant roles in the regulation of cell morphogenesis and motility. Despite similar N-terminal sequences, Arg and Abl interact with different substrates and binding partners with varying affinities. This selectivity may be due to slight differences in amino acid sequence leading to differential interactions with target proteins. We report that the Arg Src homology (SH) 2 domain binds two specific phosphotyrosines on cortactin, a known Abl/Arg substrate, with over 10-fold higher affinity than the Abl SH2 domain. We show that this significant affinity difference is due to the substitution of arginine 161 and serine 187 in Abl to leucine 207 and threonine 233 in Arg, respectively. We constructed Abl SH2 domains with R161L and S187T mutations alone and in combination and find that these substitutions are sufficient to convert the low affinity Abl SH2 domain to a higher affinity "Arg-like" SH2 domain in binding to a phospho-cortactin peptide. We crystallized the Arg SH2 domain for structural comparison to existing crystal structures of the Abl SH2 domain. We show that these two residues are important determinants of Arg and Abl SH2 domain binding specificity. Finally, we expressed Arg containing an "Abl-like" low affinity mutant Arg SH2 domain (L207R/T233S) and find that this mutant, although properly localized to the cell periphery, does not support wild type levels of cell edge protrusion. Together, these observations indicate that these two amino acid positions confer different binding affinities and cellular functions on the distinct Abl family kinases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

    Science.gov (United States)

    Lysko, Daniel E.; Putt, Mary

    2014-01-01

    Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process. PMID:24695713

  7. SDF1 reduces interneuron leading process branching through dual regulation of actin and microtubules.

    Science.gov (United States)

    Lysko, Daniel E; Putt, Mary; Golden, Jeffrey A

    2014-04-02

    Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process.

  8. Disruption of microtubule network rescues aberrant actin comets in dynamin2-depleted cells.

    Directory of Open Access Journals (Sweden)

    Yuji Henmi

    Full Text Available A large GTPase dynamin, which is required for endocytic vesicle formation, regulates the actin cytoskeleton through its interaction with cortactin. Dynamin2 mutants impair the formation of actin comets, which are induced by Listeria monocytogenes or phosphatidylinositol-4-phosphate 5-kinase. However, the role of dynamin2 in the regulation of the actin comet is still unclear. Here we show that aberrant actin comets in dynamin2-depleted cells were rescued by disrupting of microtubule networks. Depletion of dynamin2, but not cortactin, significantly reduced the length and the speed of actin comets induced by Listeria. This implies that dynamin2 may regulate the actin comet in a cortactin-independent manner. As dynamin regulates microtubules, we investigated whether perturbation of microtubules would rescue actin comet formation in dynamin2-depleted cells. Treatment with taxol or colchicine created a microtubule-free space in the cytoplasm, and made no difference between control and dynamin2 siRNA cells. This suggests that the alteration of microtubules by dynamin2 depletion reduced the length and the speed of the actin comet.

  9. 40 CFR 63.312 - Existing regulations and requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Existing regulations and requirements. 63.312 Section 63.312 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... National Emission Standards for Coke Oven Batteries § 63.312 Existing regulations and requirements. (a) The...

  10. MIIP, a cytoskeleton regulator that blocks cell migration and invasion, delays mitosis, and suppresses tumorogenesis.

    Science.gov (United States)

    Wang, Yingmei; Wen, Jing; Zhang, Wei

    2011-02-01

    The migration and invasion inhibitory protein (MIIP) was initially discovered in a yeast two-hybrid screen for proteins that interact and inhibit the migration and invasion-promoting protein insulin-like growth factor binding protein 2 (IGFBP2). Recent studies have shown that MIIP not only modulates IGFBP2 but also regulates microtubule by binding to and inhibiting HDAC6, a class 2 histone deacetylase that deacetylates α-tubulin, heat-shock protein 90 (HSP90), and cortactin. In addition, MIIP also regulates the mitosis checkpoint, another microtubule-associated process. The location of the MIIP gene in chromosomal region 1p36, a commonly deleted region in a broad spectrum of human cancers, and the observation that MIIP attenuates tumorigenesis in a mouse model suggest that it functions as a tumor-suppressor gene. This review summarizes the recent progress in characterizing this novel protein, which regulates cell migration and mitosis, two processes that rely on the highly coordinated dynamics of the microtubule and cytoskeleton systems.

  11. New HCFA regulations clarify PSO requirements.

    Science.gov (United States)

    Brock, T H

    1998-06-01

    In March and April of 1998, HCFA promulgated regulations regarding various requirements for provider-sponsored organizations (PSOs). These regulations define what constitutes an affiliated provider to a PSO, identify what percentage of services must be provided directly to beneficiaries by PSO affiliated providers, define what constitutes provider ownership in a PSO, and set minimum capitalization and liquidity standards for PSOs.

  12. Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity

    CSIR Research Space (South Africa)

    Rolando, M

    2010-07-01

    Full Text Available . They show that knock-down of cortactin and rhophilin-2 under conditions of calponin-1 expression defines the minimal set of genes regulated by LT for actin cable formation. Together their data establish that the modulation of the cell transcriptome by LT...

  13. 77 FR 12754 - Contractor Legal Management Requirements; Acquisition Regulations

    Science.gov (United States)

    2012-03-02

    ... DEPARTMENT OF ENERGY 10 CFR Part 719 48 Parts 931, 952 and 970 RIN 1990-AA37 Contractor Legal... rulemaking (NOPR) to revise existing regulations covering contractor legal management requirements and make... relating to the DOE notice of proposed rulemaking to revise existing regulations covering contractor legal...

  14. Review of orders and regulations requiring environmental protection

    International Nuclear Information System (INIS)

    Kelly, E.; Cunningham, R.; Michael, D.

    1996-01-01

    With the increased awareness of and interest in potential ecological risks associated with past, current, and future Department of Energy (DOE) activities, DOE's Defense Programs (DP) Office of Technical and Environmental Support sponsored a study to (1) evaluate the effectiveness of the current compliance-driven environmental protection and assessment efforts relative to ecological concerns; (2) explore the need for a more focused, integrated approach to address ecological impacts; and (3) identify the requirements for an integrated approach. The study explored four questions. (a) Which federal regulations and DOE orders either explicitly require ecological assessments or implicitly require them through environmental protection language? (b) What currently is being done at selected DOE facilities to implement these regulations and orders? (c) What are private sector industries doing in terms of ecological risk assessments and how do industry approaches and issues compare with those of DOE? (d) What, if anything, in addition to current efforts is needed to ensure the protection of ecological resources associated with DOE facilities, to support defensible decision making, and to improve efficiency? The results of this study are presented in a report titled open-quotes Integrated, Comprehensive Ecological Impact Assessments In Support of Department of Energy Decision Makingclose quotes. This report is a companion document to that report. This report provides a more detailed discussion of the document reviews of the relevant environmental protection regulations and current and pending DOE orders. The main goal of the document reviews was to understand existing requirements for ecological data collection and impact assessments

  15. Part I---Evaluating Effects of Oligomer Formation on Cytochrome P450 2C9 Electron Transfer and Drug Metabolism, Part II---Utilizing Molecular Modeling Techniques to Study the Src-Interacting Proteins Actin Filament Associated Protein of 110 kDa (AFAP-110) and Cortactin

    Science.gov (United States)

    Jett, John Edward, Jr.

    nanopillars, the immobilization of CYP2C9 enzymes to those nanopillars, and the utilization of the array to perform conductive probe atomic force microscopy experiments examining the electron transfer process of CYP2C9 in the absence and presence of substrate molecules. Part II. The Src protein has been known to play a role in cancer cell progression for over 30 years. The function of a non-receptor tyrosine kinase such as Src is to relay extracellular signals through intracellular tyrosine phosphorylation. As a tyrosine kinase, Src and the cellular signaling pathways it is involved in play many functional roles in the cell, both in cellular proliferation and in cytoskeletal dynamics, cell adhesion, motility and invasion. Two of the many proteins comprising Src cellular signaling pathways are actin filament associated protein of 110 kDa (AFAP-110) and cortactin. AFAP-110 is a known activator of Src; one mechanism to abrogate the AFAP-110-induced activation of Src is to inhibit their colocalization within the cell. This colocalization is expected to occur when the pleckstrin homology (PH1 and PH2) domains of AFAP-110 are allowed to interact with membrane-bound phospholipids. Cortactin, on the other hand, is a cytosolic protein capable of being phosphorylated on various tyrosine residues, activating it and allowing it to interact with actin. The Src homology 2 (SH2) domain of Src has been shown to be capable of interacting with cortactin, an association which will be probed here. This section of the dissertation will discuss the use of molecular modeling techniques to develop structural models of the AFAP-110 PH1 and PH2 domains and use them to make predictions about how the protein interacts with phospholipids in the plasma membrane and how they might be stabilized to interact with other proteins. Structural models were designed using homology modeling methods, docking programs were used to predict key residues of AFAP-110 involved in binding to phospholipids and mutational

  16. NEW INTERNATIONAL FINANCIAL REGULATION: NECESSITY OR REQUIRED BY CRISIS

    Directory of Open Access Journals (Sweden)

    Cojocari Anatol

    2010-07-01

    Full Text Available The global economic and financial crisis showed the limits faced by the international financial system. International financial regulations in general, and especially the banking sector regulations, should be refined and adapted to build a stronger and stable international financial system. We analyze the main trends in international regulations: the proposed amendments on capital requirements, the introduction of a global standard for liquidity and indebtedness, the winding-up directive, as well as their impact on the Romanian financial system.

  17. Regulation E 69-14. Monitoring requirements for medical devices

    International Nuclear Information System (INIS)

    2015-01-01

    In the 'Regulations for the State Evaluation and Registration of Medical Equipment' force (Hereinafter Rules) set forth in Chapter VII, Articles 79 and 86, the monitoring activity as one of the programs necessary for evaluating the safety and effectiveness of medical monitoring equipment. In the years 2008 and 2011 were approved and implemented by the Center for State Control of Medical Equipment (CCEEM) Regulations and -1.1 ER and ER-1 that support and regulatory requirements 'Control and monitoring of pacemakers and implantable defibrillators' and 'Assessment, recording and control after market surgical silicone implants,' which are specific to these products and have provided a useful result for the performance of the activity. Given the number and diversity of high-risk medical devices as implantable or sustain human life that are brought into our National Health System (SNS), a regulation establishing control over the behavior becomes necessary safety and effectiveness of this equipment during use, which provide inputs to risk management. The objective of this regulation is to establish the regulatory requirements for tracking medical equipment introduced in the NHS. The provisions of this Regulation is aimed at health institutions, to CECMED as manufacturers, suppliers, distributors and importers of medical equipment.

  18. Regulations for the Safe Transport of Radioactive Material, 2009 ed. Safety Requirements

    International Nuclear Information System (INIS)

    2009-01-01

    This publication establishes the regulations that are applied to the transport of radioactive material by all modes of transport on land, water or in the air, including transport that is incidental to the use of the radioactive material. The objective and scope of the regulations are described in detail as well as the range of their application. The publication provides requirements useful to governments, regulators, operators of nuclear and radiation facilities, carriers, users of radiation sources and cargo handling personnel. Contents: 1. Introduction; 2. Definitions; 3. General provisions; 4. Activity limits and classification; 5. Requirements and controls for transport; 6. Requirements for radioactive materials and for packagings and packages; 7. Test procedures; 8. Approval and administrative requirements; Annex I: Summary of approval and prior notification requirements; Annex II: Conversion factors and prefixes.

  19. 78 FR 29247 - Contractor Legal Management Requirements; Acquisition Regulations; Correction

    Science.gov (United States)

    2013-05-20

    ... DEPARTMENT OF ENERGY 48 CFR Part 952 RIN 1990-AA37 Contractor Legal Management Requirements; Acquisition Regulations; Correction AGENCY: Department of Energy. ACTION: Final rule; correction. SUMMARY: The... (78 FR 25795). In this document, DOE revised existing regulations covering contractor legal management...

  20. 78 FR 60898 - Regulation on Definition and Requirements for a Nationally Recognized Testing Laboratory...

    Science.gov (United States)

    2013-10-02

    ...] Regulation on Definition and Requirements for a Nationally Recognized Testing Laboratory; Revision of the Office of Management and Budget's (OMB) Approval of Information Collection (Paperwork) Requirements... collection requirements specified by its Regulation at 29 CFR 1910.7, ``definition and requirements for a...

  1. Greater-than-Class C low-level radioactive waste transportation regulations and requirements study

    International Nuclear Information System (INIS)

    Tyacke, M.; Schmitt, R.

    1993-07-01

    The purpose of this report is to identify the regulations and requirements for transporting greater-than-Class C (GTCC) low-level radioactive waste (LLW) and to identify planning activities that need to be accomplished in preparation for transporting GTCC LLW. The regulations and requirements for transporting hazardous materials, of which GTCC LLW is included, are complex and include several Federal agencies, state and local governments, and Indian tribes. This report is divided into five sections and three appendices. Section 1 introduces the report. Section 2 identifies and discusses the transportation regulations and requirements. The regulations and requirements are divided into Federal, state, local government, and Indian tribes subsections. This report does not identify the regulations or requirements of specific state, local government, and Indian tribes, since the storage, treatment, and disposal facility locations and transportation routes have not been specifically identified. Section 3 identifies the planning needed to ensure that all transportation activities are in compliance with the regulations and requirements. It is divided into (a) transportation packaging; (b) transportation operations; (c) system safety and risk analysis, (d) route selection; (e) emergency preparedness and response; and (f) safeguards and security. This section does not provide actual planning since the details of the Department of Energy (DOE) GTCC LLW Program have not been finalized, e.g., waste characterization and quantity, storage, treatment and disposal facility locations, and acceptance criteria. Sections 4 and 5 provide conclusions and referenced documents, respectively

  2. Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro.

    Science.gov (United States)

    Chellaiah, Meenakshi A; Schaller, Michael D

    2009-08-01

    PTP-PEST is involved in the regulation of sealing ring formation in osteoclasts. In this article, we have shown a regulatory role for PTP-PEST on dephosphorylation of c-Src at Y527 and phosphorylation at Y418 in the catalytic site. Activation of Src in osteoclasts by over-expression of PTP-PEST resulted in the phosphorylation of cortactin at Y421 and WASP at Y294. Also enhanced as a result, is the interaction of Src, cortactin, and Arp2 with WASP. Moreover, the number of osteoclasts displaying sealing ring and bone resorbing activity was increased in response to PTP-PEST over-expression as compared with control osteoclasts. Cells expressing constitutively active-Src (527YDeltaF) simulate the effects mediated by PTP-PEST. Treatment of osteoclasts with a bisphosphonate alendronate or a potent PTP inhibitor PAO decreased the activity and phosphorylation of Src at Y418 due to reduced dephosphorylation state at Y527. Therefore, Src-mediated phosphorylation of cortactin and WASP as well as the formation of WASP.cortactin.Arp2 complex and sealing ring were reduced in these osteoclasts. Similar effects were observed in osteoclasts treated with an Src inhibitor PP2. We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP-PEST/Src, in addition to its effect on the inhibition of the post-translational modification of small GTP-binding proteins such as Rab, Rho, and Rac as shown by others. The promising effects of the inhibitors PP2 and PAO on osteoclast function suggest a therapeutic approach for patients with bone metastases and osteoporosis as an alternative to bisphosphonates.

  3. 7 CFR 330.200 - Movement of plant pests regulated; permits required.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Movement of plant pests regulated; permits required... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FEDERAL PLANT PEST REGULATIONS; GENERAL; PLANT PESTS; SOIL, STONE, AND QUARRY PRODUCTS; GARBAGE Movement of Plant Pests § 330.200 Movement of...

  4. GENERAL CONSIDERATIONS ON REGULATIONS AND SAFETY REQUIREMENTS FOR QUADRICYCLES

    Directory of Open Access Journals (Sweden)

    Ana Pavlovic

    2015-12-01

    Full Text Available In recent years, a new class of compact vehicles has been emerging and wide-spreading all around Europe: the quadricycle. These four-wheeled motor vehicles, originally derived from motorcycles, are a small and fuel-efficient mean of transportation used in rural or urban areas as an alternative to motorbikes or city cars. In some countries, they are also endorsed by local authorities and institutions which support small and environmentally-friendly vehicles. In this paper, several general considerations on quadricycles will be provided including the vehicle classification, evolution of regulations (as homologation, driver licence, emissions, etc, technical characteristics, safety requirements, most relevant investigations, and other additional useful information (e.g. references, links. It represents an important and actual topic of investigation for designers and manufacturers considering that the new EU regulation on the approval and market surveillance of quadricycles will soon enter in force providing conclusive requirements for functional safety environmental protection of these promising vehicles.

  5. 76 FR 35218 - Federal Acquisition Regulation; Information Collection; Cost or Pricing Data Requirements and...

    Science.gov (United States)

    2011-06-16

    ... Pricing Data, by any of the following methods: Regulations.gov : http://www.regulations.gov . Submit...; Information Collection; Cost or Pricing Data Requirements and Information Other Than Cost or Pricing Data... concerning cost or pricing data requirements and information other than cost or pricing data. Public comments...

  6. Present state of nuclear regulation organizations of main countries in the world. Importance of regulation staffs and requirements

    International Nuclear Information System (INIS)

    Nishida, Naoki

    2013-01-01

    After Fukushima accident, NRA (Nuclear Regulation Authority) was established in Japan as an independent organization from promotion. In order to perform effective and reliable nuclear regulation, it was important management organization such as nuclear regulation commission worked efficiently, and also requirements for nuclear regulation staffs engaged in actual regulatory works were of importance so as for appropriate decision making or judgments of management organization. Since regulation staffs needed professional expertise and technical judgment capabilities in wide areas including other than nuclear energy, various efforts had been done to get able regulation staffs in US, France and UK nuclear regulation organizations concerned, which became clarified after overseas investigation for this article. Since knowledge in nuclear industry could be used for effective regulation, mid-career recruitment had been employed in regulation organization of each country so as to take such knowledge and so it was important how to utilize industrial knowledge under appropriate conditions compatible with independence of regulation organization. (T. Tanaka)

  7. New requirements, rules and regulations, and vested rights of nuclear power plants

    International Nuclear Information System (INIS)

    Raetzke, C.

    2006-01-01

    The article deals with the question whether new requirements can be imposed on existing nuclear power plants. It was promoted by the fact that the German Federal Ministry for the Environment currently is working on a thorough revision of German nuclear regulations. When looking at backfitting requirements, the all-important question is whether new findings show that the provisions taken in the license to guarantee the 'necessary precautions' (as defined in the German Atomic Energy Act) contain errors or omissions; only in this case can the authority demand that remedial measures, including backfitting, be taken. Beyond that, German nuclear law contains no obligation for operators to improve and develop safety still further. This applies regardless of whether new requirements are justified by new technical possibilities or new scientific analyses or whether they are prompted by a mere abstract re-evaluation of the safety level to be achieved. In the former case, if there are good technical or scientific reasons, the operators, as a rule, will perform backfitting voluntarily. Pursuant to these criteria, the article covers three categories of backfitting requirements and illustrates them by examples. These general principles are also valid when a new set of regulations - as planned by the BMU - are put into effect and applied. They may lead to existing plants not having to comply fully with the requirements contained in new regulations. (orig.)

  8. Cellular growth in plants requires regulation of cell wall biochemistry.

    Science.gov (United States)

    Chebli, Youssef; Geitmann, Anja

    2017-02-01

    Cell and organ morphogenesis in plants are regulated by the chemical structure and mechanical properties of the extracellular matrix, the cell wall. The two primary load bearing components in the plant cell wall, the pectin matrix and the cellulose/xyloglucan network, are constantly remodelled to generate the morphological changes required during plant development. This remodelling is regulated by a plethora of loosening and stiffening agents such as pectin methyl-esterases, calcium ions, expansins, and glucanases. The tight spatio-temporal regulation of the activities of these agents is a sine qua non condition for proper morphogenesis at cell and tissue levels. The pectin matrix and the cellulose-xyloglucan network operate in concert and their behaviour is mutually dependent on their chemical, structural and mechanical modifications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Radioactive materials and nuclear fuel transport requirements in Poland in the light of international regulations

    International Nuclear Information System (INIS)

    Musialowicz, T.

    1977-01-01

    National regulations for the transport of radioactive materials and nuclear fuel in Poland are discussed. Basic transport requirements and regulations, transport experience including transport accidents and emergency service are described. The comparison with international regulations is given

  10. 78 FR 63462 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Science.gov (United States)

    2013-10-24

    ... Relating to Organizational Conflict of Interest-Major Defense Acquisition Program; OMB Control Number 0704...] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Organizational Conflict... submit comments, identified by OMB Control Number 0704-0477, using any of the following methods: [cir...

  11. Methods of Cell Propulsion through the Local Stroma in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Kerry J. Davies

    2014-01-01

    Full Text Available In the normal breast, cellular structures change cyclically in response to ovarian hormones. Cell proliferation, apoptosis, invasion, and differentiation are integral processes that are precisely regulated. Normal epithelial cells depend on the formation of intercellular adhesion contacts to form a continuous sheet of stratifying cell layers that are attached to one and other horizontally and vertically. Cells migrate by extending membrane protrusions to explore the extracellular space locating their targets in a chemotactic manner. The formation of cell protrusions is driven by the assembly of actin filaments at the leading edge. Reorganisation is regulated by a highly integrated signalling cascade that transduces extracellular stimuli to the actin filaments. This signalling cascade is governed by GTPases which act as molecular switches leading to actin polymerisation and the formation of filopodia and lamellipodia. This process is linked to downstream molecules known collectively as WASP proteins, which, in the presence of cortactin, form a complex leading to nucleation and formation of branched filaments. In breast cancer, the cortactin is over expressed leading to increased cellular motility and invasiveness. This hugely complex and integrated signalling cascade transduces extracellular stimuli. There are multiple genes related to cell motility which are dysregulated in human breast cancers.

  12. Methods for ensuring compliance with regulatory requirements: regulators and operators

    International Nuclear Information System (INIS)

    Fleischmann, A.W.

    1989-01-01

    Some of the methods of ensuring compliance with regulatory requirements contained in various radiation protection documents such as Regulations, ICRP Recommendations etc. are considered. These include radiation safety officers and radiation safety committees, personnel monitoring services, dissemination of information, inspection services and legislative power of enforcement. Difficulties in ensuring compliance include outmoded legislation, financial and personnel constraints

  13. Requirement of a novel splicing variant of human histone deacetylase 6 for TGF-{beta}1-mediated gene activation

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Yan [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States); Nguyen, Hong T. [Graduate Program in Biomedical Sciences, Tulane School of Medicine, New Orleans, LA 70112 (United States); Lasky, Joseph A. [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States); Cao, Subing [Graduate Program in Biomedical Sciences, Tulane School of Medicine, New Orleans, LA 70112 (United States); Li, Cui [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States); Xiangya Hospital, Central South University, Hunan 41008 (China); Hu, Jiyao; Guo, Xinyue; Burow, Matthew E. [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States); Shan, Bin, E-mail: bshan@tulane.edu [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States)

    2010-02-19

    Histone deacetylase 6 (HDAC6) belongs to the family of class IIb HDACs and predominantly deacetylates non-histone proteins in the cytoplasm via the C-terminal deacetylase domain of its two tandem deacetylase domains. HDAC6 modulates fundamental cellular processes via deacetylation of {alpha}-tubulin, cortactin, molecular chaperones, and other peptides. Our previous study indicates that HDAC6 mediates TGF-{beta}1-induced epithelial-mesenchymal transition (EMT) in A549 cells. In the current study, we identify a novel splicing variant of human HDAC6, hHDAC6p114. The hHDAC6p114 mRNA arises from incomplete splicing and encodes a truncated isoform of the hHDAC6p114 protein of 114 kDa when compared to the major isoform hHDAC6p131. The hHDAC6p114 protein lacks the first 152 amino acids from N-terminus in the hHDAC6p131 protein, which harbors a nuclear export signal peptide and 76 amino acids of the N-terminal deacetylase domain. hHDAC6p114 is intact in its deacetylase activity against {alpha}-tubulin. The expression hHDAC6p114 is elevated in a MCF-7 derivative that exhibits an EMT-like phenotype. Moreover, hHDAC6p114 is required for TGF-{beta}1-activated gene expression associated with EMT in A549 cells. Taken together, our results implicate that expression and function of hHDAC6p114 is differentially regulated when compared to hHDAC6p131.

  14. 76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2011-12-20

    ..., electronic record requirements, and investigator initiated research. Topics for discussion include the...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Clinical Research Associates (SoCRA), is announcing a public workshop. The public workshop on FDA's...

  15. Meeting the International Health Regulations (2005) surveillance core capacity requirements at the subnational level in Europe

    DEFF Research Database (Denmark)

    Ziemann, Alexandra; Rosenkötter, Nicole; Riesgo, Luis Garcia-Castrillo

    2015-01-01

    BACKGROUND: The revised World Health Organization's International Health Regulations (2005) request a timely and all-hazard approach towards surveillance, especially at the subnational level. We discuss three questions of syndromic surveillance application in the European context for assessing...... public health emergencies of international concern: (i) can syndromic surveillance support countries, especially the subnational level, to meet the International Health Regulations (2005) core surveillance capacity requirements, (ii) are European syndromic surveillance systems comparable to enable cross...... effect of different types of public health emergencies in a timely manner as required by the International Health Regulations (2005)....

  16. 75 FR 14448 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2010-03-25

    ... requirements, and investigator initiated research. Topics for discussion include the following: (1) What FDA...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Society of Clinical Research Associates, Inc. (SoCRA) is announcing a public workshop entitled ``FDA...

  17. 77 FR 8886 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2012-02-15

    ..., electronic record requirements, and investigator initiated research. Topics for discussion include the...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Research Associates (SoCRA) is announcing a public workshop. The public workshop on FDA's clinical trial...

  18. Liberalization, Moral Hazard in Banking, and Prudential Regulation: Are Capital Requirements Enough?

    OpenAIRE

    Kevin C. Murdock; Thomas F. Hellmann; Joseph E. Stiglitz

    2000-01-01

    In a dynamic model of moral hazard, competition can undermine prudent bank behavior. While capital-requirement regulation can induce prudent behavior, the policy yields Pareto-inefficient outcomes. Capital requirements reduce gambling incentives by putting bank equity at risk. However, they also have a perverse effect of harming banks' franchise values, thus encouraging gambling. Pareto-efficient outcomes can be achieved by adding deposit-rate controls as a regulatory instrument, since they f...

  19. 76 FR 51040 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2011-08-17

    ... requirements, and investigator initiated research. Topics for discussion include the following: (1) What FDA...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Clinical Research Associates (SoCRA) is announcing a public workshop. The public workshop on FDA's clinical...

  20. Establishing Reusable Requirements Derived from Laws and Regulations for Medical Device Development

    DEFF Research Database (Denmark)

    Hauksdóttir, Dagný; Mortensen, Niels Henrik; Ritsing, Brian

    2016-01-01

    skills and consumes significant effort in product development. Therefore initiating reuse from the analysis and elicitation of requirements from standards and regulations may provide promising potential for gaining efficiency in development and also for assuring sufficient quality of the work...

  1. Experiences in certification of packages for transportation of fresh nuclear fuel in the context of new safety requirements established by IAEA regulations (IAEA-96 regulations, ST-1) for air transportation of nuclear materials (requirements to C-type packages)

    Energy Technology Data Exchange (ETDEWEB)

    Dudai, V.I.; Kovtun, A.D.; Matveev, V.Z.; Morenko, A.I.; Nilulin, V.M.; Shapovalov, V.I.; Yakushev, V.A.; Bobrovsky, V.S.; Rozhkov, V.V.; Agapov, A.M.; Kolesnikov, A.S. [Russian Federal Nuclear Centre - All-Russian Research Inst. of Experimental Physics, Sarov (Russian Federation)]|[JSC ' ' MSZ' ' , Electrostal (Russian Federation)]|[JSC ' ' NPCC' ' , Novosibirsk (Russian Federation)]|[Minatom of Russia, Moscow (Russian Federation)]|[Gosatomnadzor of Russia, Moscow (Russian Federation)

    2004-07-01

    Every year in Russia, a large amount of domestic and international transportation of fresh nuclear fuel (FNF) used in Russian and foreign energy and research atomic reactors and referred to fissile materials based on IAEA Regulations is performed. Here, bulk transportation is performed by air, and it concerns international transportation in particular. According to national ''Main Regulations for Safe Transport and physical Protection of Nuclear Materials (OPBZ- 83)'' and ''Regulations for the Safe Transport of Radioactive Materials'' of the International Atomic Energy Agency (IAEA Regulations), nuclear and radiation security under normal (accident free) and accident conditions of transport must be completely provided by the package design. In this context, high requirements to fissile packages exposed to heat and mechanical loads in transport accidents are imposed. A long-standing experience in accident free transportation of FM has shown that such approach to provide nuclear and radiation security pays for itself completely. Nevertheless, once in 10 years the International Atomic Energy Agency on every revision of the ''Regulations for the Safe Transport of Radioactive Materials'' places more stringent requirements upon the FM and transportation thereof, resulting from the objectively increasing risk associated with constant rise in volume and density of transportation, and also strained social and economical situation in a number of regions in the world. In the new edition of the IAEA Regulations (ST-1), published in 1996 and brought into force in 2001 (IAEA-96 Regulations), the requirements to FM packages conveyed by aircraft were radically changed. These requirements are completely presented in new Russian ''Regulations for the Safe Transport of Radioactive Materials'' (PBTRM- 2004) which will be brought into force in the time ahead.

  2. The regulation and deregulation requirements for the decommissioning of nuclear installations

    International Nuclear Information System (INIS)

    Wagner, H.

    1993-01-01

    On the basis of a brief outline of the starting point in terms of technical conditions and status, and of the main aspects of application and interpretation of the law, the regulation and deregulation requirements are elaborated in the light of suggestions for change and with regard to their possible concretization in laws and subordinate laws; the strongest need for change undoubtedly is in the field of the technical codes and regulations, which hitherto have been established primarily for the construction and operation of nuclear installations and hence are not necessarily applicable to the activities to be performed for decommissioning. Practice so far has shown, however, that these regulations are applied not analogously, as would be adequate, but in direct manner. The required review and modification of the existing regulatory codes for the purpose of decommissioning will have to concentrate on the following aspects: - Scope and level of specification of application documents; - definition of important, safety-related events (as e.g. accidents); - scope and level of specification of expert opinions, taking into account the reduced risk level. As a long-term objective, it would be desirable to harmonize existing German regulatory provisions for the decommissioning of industrial plants with an environmental impact (as e.g, the Waste Management Act, Atomic Energy Act, mining law, Federal Emission Control Act), and to seek an approach of national regulatory systems and technical codes in this field under the roof of the EC. (orig./HSCH) [de

  3. Casein kinase 1-Like 3 is required for abscisic acid regulation of ...

    African Journals Online (AJOL)

    Casein kinase 1-Like 3 is required for abscisic acid regulation of seed germination, root growth, and gene expression in Arabidopsis. M Wang, D Yu, X Guo, X Li, J Zhang, L Zhao, H Chang, S Hu, C Zhang, J Shi, X Liu ...

  4. 25 CFR 518.7 - If a tribe holds a certificate of self-regulation, is it required to report information to the...

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false If a tribe holds a certificate of self-regulation, is it... REGULATION OF CLASS II GAMING § 518.7 If a tribe holds a certificate of self-regulation, is it required to... certificate of self-regulation shall be required to submit a self-regulation report annually to the Commission...

  5. Eph receptor interclass cooperation is required for the regulation of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Jurek, Aleksandra; Genander, Maria [Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Kundu, Parag [Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Catchpole, Timothy [Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390 (United States); He, Xiao; Strååt, Klas; Sabelström, Hanna [Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Xu, Nan-Jie [Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390 (United States); Pettersson, Sven [Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); The National Cancer Centre, Singapore General Hospital (Singapore); Henkemeyer, Mark [Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390 (United States); Frisén, Jonas, E-mail: jonas.frisen@ki.se [Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden)

    2016-10-15

    Cancer often arises by the constitutive activation of mitogenic pathways by mutations in stem cells. Eph receptors are unusual in that although they regulate the proliferation of stem/progenitor cells in many adult organs, they typically fail to transform cells. Multiple ephrins and Eph receptors are often co-expressed and are thought to be redundant, but we here describe an unexpected dichotomy with two homologous ligands, ephrin-B1 and ephrin-B2, regulating specifically migration or proliferation in the intestinal stem cell niche. We demonstrate that the combined activity of two different coexpressed Eph receptors of the A and B class assembled into common signaling clusters in response to ephrin-B2 is required for mitogenic signaling. The requirement of two different Eph receptors to convey mitogenic signals identifies a new type of cooperation within this receptor family and helps explain why constitutive activation of a single receptor fails to transform cells. - Highlights: • We demonstrate that ephrin-B1 and ephrin-B2 have largely non-overlapping functions in the intestinal stem cell niche. • Ephrin-B1 regulates cell positioning and ephrin-B2 regulates cell proliferation in the intestinal stem cell niche. • EphA4/B2 receptor cooperation in response to ephrin-B2 binding is obligatory to convey mitogenic signals in the intestine. • EphA4 facilitates EphB2 phosphorylation in response to ephrin-B2 in SW480 adenocarcinoma cells. • Ephrin-B1 and ephrin-B2 induce phosphorylation and degradation of the EphB2 receptor with different kinetics.

  6. Eph receptor interclass cooperation is required for the regulation of cell proliferation

    International Nuclear Information System (INIS)

    Jurek, Aleksandra; Genander, Maria; Kundu, Parag; Catchpole, Timothy; He, Xiao; Strååt, Klas; Sabelström, Hanna; Xu, Nan-Jie; Pettersson, Sven; Henkemeyer, Mark; Frisén, Jonas

    2016-01-01

    Cancer often arises by the constitutive activation of mitogenic pathways by mutations in stem cells. Eph receptors are unusual in that although they regulate the proliferation of stem/progenitor cells in many adult organs, they typically fail to transform cells. Multiple ephrins and Eph receptors are often co-expressed and are thought to be redundant, but we here describe an unexpected dichotomy with two homologous ligands, ephrin-B1 and ephrin-B2, regulating specifically migration or proliferation in the intestinal stem cell niche. We demonstrate that the combined activity of two different coexpressed Eph receptors of the A and B class assembled into common signaling clusters in response to ephrin-B2 is required for mitogenic signaling. The requirement of two different Eph receptors to convey mitogenic signals identifies a new type of cooperation within this receptor family and helps explain why constitutive activation of a single receptor fails to transform cells. - Highlights: • We demonstrate that ephrin-B1 and ephrin-B2 have largely non-overlapping functions in the intestinal stem cell niche. • Ephrin-B1 regulates cell positioning and ephrin-B2 regulates cell proliferation in the intestinal stem cell niche. • EphA4/B2 receptor cooperation in response to ephrin-B2 binding is obligatory to convey mitogenic signals in the intestine. • EphA4 facilitates EphB2 phosphorylation in response to ephrin-B2 in SW480 adenocarcinoma cells. • Ephrin-B1 and ephrin-B2 induce phosphorylation and degradation of the EphB2 receptor with different kinetics.

  7. Capital Regulation, Liquidity Requirements and Taxation in a Dynamic Model of Banking

    NARCIS (Netherlands)

    Di Nicolo, G.; Gamba, A.; Lucchetta, M.

    2011-01-01

    This paper formulates a dynamic model of a bank exposed to both credit and liquidity risk, which can resolve financial distress in three costly forms: fire sales, bond issuance ad equity issuance. We use the model to analyze the impact of capital regulation, liquidity requirements and taxation on

  8. Capital Regulation, Liquidity Requirements and Taxation in a Dynamic Model of Banking

    NARCIS (Netherlands)

    Di Nicolo, G.; Gamba, A.; Lucchetta, M.

    2011-01-01

    This paper formulates a dynamic model of a bank exposed to both credit and liquidity risk, which can resolve financial distress in three costly forms: fire sales, bond issuance and equity issuance. We use the model to analyze the impact of capital regulation, liquidity requirements and taxation on

  9. Dimerization in the Grb7 Protein

    OpenAIRE

    Peterson, Tabitha A.; Benallie, Renee L.; Bradford, Andrew M.; Pias, Sally C.; Yazzie, Jaron.; Lor, Siamee N.; Haulsee, Zachary M.; Park, Chad K.; Johnson, Dennis L.; Rohrschneider, Larry R.; Spuches, Anne.; Lyons, Barbara A.

    2012-01-01

    In previous studies, we showed that the tyrosine phosphorylation state of growth factor receptor–bound protein 7 (Grb7) affects its ability to bind to the transcription regulator FHL2 and the cortactin-interacting protein, human HS-1-associated protein-1. Here, we present results describing the importance of dimerization in the Grb7–Src homology 2 (SH2) domain in terms of its structural integrity and the ability to bind phosphorylated tyrosine peptide ligands. A tyrosine phosphorylation-mimic...

  10. ER-16 regulation. Requirements for granting the permit exceptional use of medical devices in humans

    International Nuclear Information System (INIS)

    2015-01-01

    The purpose of this regulation is to establish requirements for applying for a permit exceptional use of medical equipment in Human Beings, the procedures for the evaluation process and bestowal. This regulation is aimed at researchers and designers of medical equipment, related to or associated with National Health Service's priority programs of interest to health.

  11. The Role of HDAC6 in Cancer

    Directory of Open Access Journals (Sweden)

    Grace I. Aldana-Masangkay

    2011-01-01

    Full Text Available Histone deacetylase 6 (HDAC6, a member of the HDAC family whose major substrate is α-tubulin, has become a target for drug development to treat cancer due to its major contribution in oncogenic cell transformation. Overexpression of HDAC6 correlates with tumorigenesis and improved survival; therefore, HDAC6 may be used as a marker for prognosis. Previous work demonstrated that in multiple myeloma cells, inhibition of HDAC6 results in apoptosis. Furthermore, HDAC6 is required for the activation of heat-shock factor 1 (HSF1, an activator of heat-shock protein encoding genes (HSPs and CYLD, a cylindromatosis tumor suppressor gene. HDAC6 contributes to cancer metastasis since its upregulation increases cell motility in breast cancer MCF-7 cells and its interaction with cortactin regulates motility. HDAC6 also affects transcription and translation by regulating the heat-shock protein 90 (Hsp90 and stress granules (SGs, respectively. This review will discuss the role of HDAC6 in the pathogenesis and treatment of cancer.

  12. Guide to NRC reporting and recordkeeping requirements. Compiled from requirements in Title 10 of the U.S. Code of Federal Regulations as codified on December 31, 1993; Revision 1

    International Nuclear Information System (INIS)

    Collins, M.; Shelton, B.

    1994-07-01

    This compilation includes in the first two sections the reporting and recordkeeping requirements applicable to US Nuclear Regulatory Commission (NRC) licensees and applicants and to members of the public. It includes those requirements codified in Title 10 of the code of Federal Regulations, Chapter 1, on December 31, 1993. It also includes, in a separate section, any of those requirements that were superseded or discontinued between January 1992 and December 1993. Finally, the appendix lists mailing and delivery addresses for NRC Headquarters and Regional Offices mentioned in the compilation. The Office of Information Resources Management staff compiled this listing of reporting and recordkeeping requirements to briefly describe each in a single document primarily to help licensees readily identify the requirements. The compilation is not a substitute for the regulations, and is not intended to impose any new requirements or technical positions. It is part of NRC's continuing efforts to comply with the Paperwork Reduction Act of 1980 and the Office of Management and Budget regulations that mandate effective and efficient Federal information resources management programs

  13. 78 FR 65218 - Defense Federal Acquisition Regulation Supplement: Private Sector Notification Requirements of In...

    Science.gov (United States)

    2013-10-31

    ... Federal Acquisition Regulation Supplement: Private Sector Notification Requirements of In-Sourcing Actions... Supplement (DFARS) to implement a section of the National Defense Authorization Act regarding private sector... section 938 of the National Defense Authorization Act (NDAA) for Fiscal Year 2012 regarding private sector...

  14. Extracellular Matrix-Regulated Gene Expression RequiresCooperation of SWI/SNF and Transcription Factors

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ren; Spencer, Virginia A.; Bissell, Mina J.

    2006-05-25

    Extracellular cues play crucial roles in the transcriptional regulation of tissue-specific genes, but whether and how these signals lead to chromatin remodeling is not understood and subject to debate. Using chromatin immunoprecipitation (ChIP) assays and mammary-specific genes as models, we show here that extracellular matrix (ECM) molecules and prolactin cooperate to induce histone acetylation and binding of transcription factors and the SWI/SNF complex to the {beta}- and ?-casein promoters. Introduction of a dominant negative Brg1, an ATPase subunit of SWI/SNF complex, significantly reduced both {beta}- and ?-casein expression, suggesting that SWI/SNF-dependent chromatin remodeling is required for transcription of mammary-specific genes. ChIP analyses demonstrated that the ATPase activity of SWI/SNF is necessary for recruitment of RNA transcriptional machinery, but not for binding of transcription factors or for histone acetylation. Coimmunoprecipitation analyses showed that the SWI/SNF complex is associated with STAT5, C/EBP{beta}, and glucocorticoid receptor (GR). Thus, ECM- and prolactin-regulated transcription of the mammary-specific casein genes requires the concerted action of chromatin remodeling enzymes and transcription factors.

  15. Five Conditions Commonly Used to Down-regulate Tor Complex 1 Generate Different Physiological Situations Exhibiting Distinct Requirements and Outcomes*

    Science.gov (United States)

    Tate, Jennifer J.; Cooper, Terrance G.

    2013-01-01

    Five different physiological conditions have been used interchangeably to establish the sequence of molecular events needed to achieve nitrogen-responsive down-regulation of TorC1 and its subsequent regulation of downstream reporters: nitrogen starvation, methionine sulfoximine (Msx) addition, nitrogen limitation, rapamycin addition, and leucine starvation. Therefore, we tested a specific underlying assumption upon which the interpretation of data generated by these five experimental perturbations is premised. It is that they generate physiologically equivalent outcomes with respect to TorC1, i.e. its down-regulation as reflected by TorC1 reporter responses. We tested this assumption by performing head-to-head comparisons of the requirements for each condition to achieve a common outcome for a downstream proxy of TorC1 inactivation, nuclear Gln3 localization. We demonstrate that the five conditions for down-regulating TorC1 do not elicit physiologically equivalent outcomes. Four of the methods exhibit hierarchical Sit4 and PP2A phosphatase requirements to elicit nuclear Gln3-Myc13 localization. Rapamycin treatment required Sit4 and PP2A. Nitrogen limitation and short-term nitrogen starvation required only Sit4. G1 arrest-correlated, long-term nitrogen starvation and Msx treatment required neither PP2A nor Sit4. Starving cells of leucine or treating them with leucyl-tRNA synthetase inhibitors did not elicit nuclear Gln3-Myc13 localization. These data indicate that the five commonly used nitrogen-related conditions of down-regulating TorC1 are not physiologically equivalent and minimally involve partially differing regulatory mechanisms. Further, identical requirements for Msx treatment and long-term nitrogen starvation raise the possibility that their effects are achieved through a common regulatory pathway with glutamine, a glutamate or glutamine metabolite level as the sensed metabolic signal. PMID:23935103

  16. 14 CFR 11.61 - May I ask FAA to adopt, amend, or repeal a regulation, or grant relief from the requirements of a...

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false May I ask FAA to adopt, amend, or repeal a regulation, or grant relief from the requirements of a current regulation? 11.61 Section 11.61 Aeronautics... to adopt, amend, or repeal a regulation, or grant relief from the requirements of a current...

  17. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4

    Science.gov (United States)

    Foresti, Ombretta; Ruggiano, Annamaria; Hannibal-Bach, Hans K; Ejsing, Christer S; Carvalho, Pedro

    2013-01-01

    Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together to control sterol biosynthesis at different levels and thereby allowing independent regulation of multiple products of the mevalonate pathway. DOI: http://dx.doi.org/10.7554/eLife.00953.001 PMID:23898401

  18. VEGF-A/Notch-Induced Podosomes Proteolyse Basement Membrane Collagen-IV during Retinal Sprouting Angiogenesis

    Directory of Open Access Journals (Sweden)

    Pirjo Spuul

    2016-10-01

    Full Text Available During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch inhibition exacerbates podosome formation and collagen-IV loss. We propose that the localized proteolytic action of podosomes on basement membrane collagen-IV facilitates endothelial cell sprouting and anastomosis within the developing vasculature. The identification of podosomes as key components of the sprouting machinery provides another opportunity to target angiogenesis therapeutically.

  19. 75 FR 26165 - Regulation of Fuels and Fuel Additives: Alternative Affirmative Defense Requirements for Ultra...

    Science.gov (United States)

    2010-05-11

    ... Regulation of Fuels and Fuel Additives: Alternative Affirmative Defense Requirements for Ultra-Low Sulfur... refiners, importers, distributors, and retailers of highway diesel fuel the option to use an alternative affirmative defense if the Agency finds highway diesel fuel samples above the specified sulfur standard at...

  20. Effect of increased regulation on capital costs and manual labor requirements of nuclear power plants

    International Nuclear Information System (INIS)

    Paik, S.; Schriver, W.R.

    1981-01-01

    An attempt is made to explain the impact of increasing governmental regulation on capital costs and labor requirements for constructing light water reactor (LWR) electric power plants. The principal factors contributing to these increases are: (1) market conditions and (2) increased regulation. General market conditions include additional costs attributable to price inflation of equipment, material, labor, and the increased cost of money. The central objective of this work is to estimate the impact of increasing regulation on plant costs and, conversely, on output. To do this it is necessary to isolate two opposing sets of forces which have been in operation during the period of major regulatory expansion: learning based upon plant design experience and economies of scale with increasing size (generating capacity) of newer plants. Conceptual models are specified to capture the independent effects of increasing regulation, learning, and economies of scale. Empirical results were obtained by estimating the models on data collected from industry experience during the 1967-1980 period. 23 refs

  1. A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons.

    Science.gov (United States)

    Vidaki, Marina; Drees, Frauke; Saxena, Tanvi; Lanslots, Erwin; Taliaferro, Matthew J; Tatarakis, Antonios; Burge, Christopher B; Wang, Eric T; Gertler, Frank B

    2017-08-02

    During neuronal development, local mRNA translation is required for axon guidance and synaptogenesis, and dysregulation of this process contributes to multiple neurodevelopmental and cognitive disorders. However, regulation of local protein synthesis in developing axons remains poorly understood. Here, we uncover a novel role for the actin-regulatory protein Mena in the formation of a ribonucleoprotein complex that involves the RNA-binding proteins HnrnpK and PCBP1 and regulates local translation of specific mRNAs in developing axons. We find that translation of dyrk1a, a Down syndrome- and autism spectrum disorders-related gene, is dependent on Mena, both in steady-state conditions and upon BDNF stimulation. We identify hundreds of additional mRNAs that associate with the Mena complex, suggesting that it plays broader role(s) in post-transcriptional gene regulation. Our work establishes a dual role for Mena in neurons, providing a potential link between regulation of actin dynamics and local translation. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Cost-optimal levels of minimum energy performance requirements in the Danish Building Regulations

    Energy Technology Data Exchange (ETDEWEB)

    Aggerholm, S.

    2013-09-15

    The purpose of the report is to analyse the cost optimality of the energy requirements in the Danish Building Regulations 2010, BR10 to new building and to existing buildings undergoing major renovation. The energy requirements in the Danish Building Regulations have by tradition always been based on the cost and benefits related to the private economical or financial perspective. Macro economical calculations have in the past only been made in addition. The cost optimum used in this report is thus based on the financial perspective. Due to the high energy taxes in Denmark there is a significant difference between the consumer price and the macro economical for energy. Energy taxes are also paid by commercial consumers when the energy is used for building operation e.g. heating, lighting, ventilation etc. In relation to the new housing examples the present minimum energy requirements in BR 10 all shows gaps that are negative with a deviation of up till 16 % from the point of cost optimality. With the planned tightening of the requirements to new houses in 2015 and in 2020, the energy requirements can be expected to be tighter than the cost optimal point, if the costs for the needed improvements don't decrease correspondingly. In relation to the new office building there is a gap of 31 % to the point of cost optimality in relation to the 2010 requirement. In relation to the 2015 and 2020 requirements there are negative gaps to the point of cost optimality based on today's prices. If the gaps for all the new buildings are weighted to an average based on mix of building types and heat supply for new buildings in Denmark there is a gap of 3 % in average for the new building. The excessive tightness with today's prices is 34 % in relation to the 2015 requirement and 49 % in relation to the 2020 requirement. The component requirement to elements in the building envelope and to installations in existing buildings adds up to significant energy efficiency

  3. 13 CFR 120.1511 - Certification and other reporting and notification requirements for Other Regulated SBLCs.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Certification and other reporting and notification requirements for Other Regulated SBLCs. 120.1511 Section 120.1511 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based Lender Oversight Enforcement Actions § 120...

  4. Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles.

    Science.gov (United States)

    Kong, Dong; Farmer, Veronica; Shukla, Anil; James, Jana; Gruskin, Richard; Kiriyama, Shigeo; Loncarek, Jadranka

    2014-09-29

    Newly formed centrioles in cycling cells undergo a maturation process that is almost two cell cycles long before they become competent to function as microtubule-organizing centers and basal bodies. As a result, each cell contains three generations of centrioles, only one of which is able to form cilia. It is not known how this long and complex process is regulated. We show that controlled Plk1 activity is required for gradual biochemical and structural maturation of the centrioles and timely appendage assembly. Inhibition of Plk1 impeded accumulation of appendage proteins and appendage formation. Unscheduled Plk1 activity, either in cycling or interphase-arrested cells, accelerated centriole maturation and appendage and cilia formation on the nascent centrioles, erasing the age difference between centrioles in one cell. These findings provide a new understanding of how the centriole cycle is regulated and how proper cilia and centrosome numbers are maintained in the cells.

  5. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4

    DEFF Research Database (Denmark)

    Foresti, Ombretta; Ruggiano, Annamaria; Hannibal-Bach, Hans K

    2013-01-01

    Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate......-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin...... ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together...

  6. Historical background of the development of various requirements in the international regulations for the safe packaging and transport of radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Pope, R.B.

    2004-07-01

    Questions are frequently asked regarding the source of some of the package test requirements in the Transport Regulations, the philosophy behind them and the basis for selecting them. This paper summarizes the results of a review of early historical documents and elaborates on the early philosophy behind the regulatory requirements. To the extent possible, the paper compares the early philosophy with the current structure of the Transport Regulations in key topic areas with a focus on the test requirements for packages that are designed to withstand accident conditions of transport.

  7. Historical background of the development of various requirements in the international regulations for the safe packaging and transport of radioactive material

    International Nuclear Information System (INIS)

    Pope, R.B.

    2004-01-01

    Questions are frequently asked regarding the source of some of the package test requirements in the Transport Regulations, the philosophy behind them and the basis for selecting them. This paper summarizes the results of a review of early historical documents and elaborates on the early philosophy behind the regulatory requirements. To the extent possible, the paper compares the early philosophy with the current structure of the Transport Regulations in key topic areas with a focus on the test requirements for packages that are designed to withstand accident conditions of transport

  8. Sweden's radiation protection regulations for spent fuel and nuclear waste: Requirements and compliance

    International Nuclear Information System (INIS)

    Norden, M.; Jensen, M.; Larsson, C.M.; Avila, R.; Bergman, S.S.; Wiebert, A.; Wiklund, A.

    2000-01-01

    The Swedish regulations on radiation protection in connection with spent fuel and nuclear waste disposal concern protection of human health and the environment. The reasoning behind the regulations is in observance with the Rio declaration, in the sense that they take into consideration sustainable development also in continued presence of multiple sources of radioactive effluents. Optimisation and best available technique are used as methods for risk reduction. For human health, a risk concept is used, whereas for environmental protection, focus is set on protection of biological resources and diversity. Compliance with the health and environmental goals is discussed using generic definition of the environment. The hypothetical outflow from a repository takes place in the different compartments and the resulting spread in doses are discussed and compared to the requirements of the individual dose standard, and other environmental effects are assessed. (author)

  9. Regulation EM-ER-6. Requirements for the realization of clinical essays to the medical equipments

    International Nuclear Information System (INIS)

    2015-01-01

    This regulation applies to the medical equipment that become incorporated to the stage of clinical trial required for its evaluation and record, for which they are subdued to clinical investigation for the sake of verifying, in conditions specified of use, its functioning, identifying besides any undesirable defect. It extends to manufacturers of medical equipments, Public Health's units where the clinical investigations with those equipments take place and to the rest of the entities of the MINSAP . Its objective is to protect the participating subjects in the clinical investigations; Assuring the conduction of the clinical investigation and specifying the requirements for the conduction of the clinical investigations and the documentation required for it.

  10. Development of guidance on applications of regulatory requirements for regulating large, contaminated equipment and large decommissioning and decontamination (D and D) components

    International Nuclear Information System (INIS)

    Pope, R.B.; Easton, E.P.; Cook, J.R.; Boyle, R.W.

    1997-01-01

    In 1985, the International Atomic Energy Agency issued revised regulations for the safe transport of radioactive material. Significant were major changes to requirements for Low Specific Activity (LSA) material and Surface Contaminated Objects (SCOs). As these requirements were adopted into regulations in the United States, it was recognised that guidance on how to apply these requirements to large, contaminated/activated pieces of equipment and decommissioning and decontamination (D and D) objects would be needed both by the regulators and those regulated to clarify technical uncertainties and ensure implementation. Thus, the US Department of Transportation and the US Nuclear Regulatory Commission, with assistance of staff from Oak Ridge National Laboratory, are preparing regulatory guidance which will present examples of acceptable methods for demonstrating compliance with the revised rules for large items. Concepts being investigated for inclusion in the pending guidance are discussed in this paper. Under current plans, the guidance will be issued for public comment before final issuance in 1997. (Author)

  11. Development of guidance on applications of regulatory requirements for regulating large, contaminated equipment and large decommissioning and decontamination (D and D) components

    International Nuclear Information System (INIS)

    Pope, R.B.; Easton, E.P.; Cook, J.R.; Boyle, R.W.

    1997-01-01

    In 1985, the International Atomic Energy Agency issued revised regulations for the safe transport of radioactive material. Significant were major changes to requirements for Low Specific Activity material and Surface Contaminated Objects. As these requirements were adopted into regulations in the US, it was recognized that guidance on how to apply these requirements to large, contaminated/activated pieces of equipment and decommissioning and decontamination objects would be needed both by the regulators and those regulated to clarify technical uncertainties and ensure implementation. Thus, the US Department of Transportation and the US Nuclear Regulatory Commission, with assistance of staff from Oak Ridge National Laboratory, are preparing regulatory guidance which will present examples of acceptable methods for demonstrating compliance with the revised rules for large items. Concepts being investigated for inclusion in the pending guidance are discussed in this paper. Under current plans, the guidance will be issued for public comment before final issuance in 1997

  12. Profiles of Motivated Self-Regulation in College Computer Science Courses: Differences in Major versus Required Non-Major Courses

    Science.gov (United States)

    Shell, Duane F.; Soh, Leen-Kiat

    2013-12-01

    The goal of the present study was to utilize a profiling approach to understand differences in motivation and strategic self-regulation among post-secondary STEM students in major versus required non-major computer science courses. Participants were 233 students from required introductory computer science courses (194 men; 35 women; 4 unknown) at a large Midwestern state university. Cluster analysis identified five profiles: (1) a strategic profile of a highly motivated by-any-means good strategy user; (2) a knowledge-building profile of an intrinsically motivated autonomous, mastery-oriented student; (3) a surface learning profile of a utility motivated minimally engaged student; (4) an apathetic profile of an amotivational disengaged student; and (5) a learned helpless profile of a motivated but unable to effectively self-regulate student. Among CS majors and students in courses in their major field, the strategic and knowledge-building profiles were the most prevalent. Among non-CS majors and students in required non-major courses, the learned helpless, surface learning, and apathetic profiles were the most prevalent. Students in the strategic and knowledge-building profiles had significantly higher retention of computational thinking knowledge than students in other profiles. Students in the apathetic and surface learning profiles saw little instrumentality of the course for their future academic and career objectives. Findings show that students in STEM fields taking required computer science courses exhibit the same constellation of motivated strategic self-regulation profiles found in other post-secondary and K-12 settings.

  13. Candida albicans: The Ability to Invade Epithelial Cells and Survive under Oxidative Stress Is Unlinked to Hyphal Length

    Directory of Open Access Journals (Sweden)

    Paloma K. Maza

    2017-07-01

    Full Text Available In its hyphal form, Candida albicans invades epithelial and endothelial cells by two distinct mechanisms: active penetration and induced endocytosis. The latter is dependent on a reorganization of the host cytoskeleton (actin/cortactin recruitment, whilst active penetration does not rely on the host's cellular machinery. The first obstacle for the fungus to reach deep tissues is the epithelial barrier and this interaction is crucial for commensal growth, fungal pathogenicity and host defense. This study aimed to characterize in vitro epithelial HeLa cell invasion by four different isolates of C. albicans with distinct clinical backgrounds, including a C. albicans SC5314 reference strain. All isolates invaded HeLa cells, recruited actin and cortactin, and induced the phosphorylation of both Src-family kinases (SFK and cortactin. Curiously, L3881 isolated from blood culture of a patient exhibited the highest resistance to oxidative stress, although this isolate showed reduced hyphal length and displayed the lowest cell damage and invasion rates. Collectively, these data suggest that the ability of C. albicans to invade HeLa cells, and to reach and adapt to the host's blood, including resistance to oxidative stress, may be independent of hyphal length.

  14. Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis.

    Science.gov (United States)

    Gray, Lawrence R; Sultana, Mst Rasheda; Rauckhorst, Adam J; Oonthonpan, Lalita; Tompkins, Sean C; Sharma, Arpit; Fu, Xiaorong; Miao, Ren; Pewa, Alvin D; Brown, Kathryn S; Lane, Erin E; Dohlman, Ashley; Zepeda-Orozco, Diana; Xie, Jianxin; Rutter, Jared; Norris, Andrew W; Cox, James E; Burgess, Shawn C; Potthoff, Matthew J; Taylor, Eric B

    2015-10-06

    Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. translin Is Required for Metabolic Regulation of Sleep.

    Science.gov (United States)

    Murakami, Kazuma; Yurgel, Maria E; Stahl, Bethany A; Masek, Pavel; Mehta, Aradhana; Heidker, Rebecca; Bollinger, Wesley; Gingras, Robert M; Kim, Young-Joon; Ja, William W; Suter, Beat; DiAngelo, Justin R; Keene, Alex C

    2016-04-04

    Dysregulation of sleep or feeding has enormous health consequences. In humans, acute sleep loss is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely, metabolic state potently modulates sleep and circadian behavior; yet, the molecular basis for sleep-metabolism interactions remains poorly understood. Here, we describe the identification of translin (trsn), a highly conserved RNA/DNA binding protein, as essential for starvation-induced sleep suppression. Strikingly, trsn does not appear to regulate energy stores, free glucose levels, or feeding behavior suggesting the sleep phenotype of trsn mutant flies is not a consequence of general metabolic dysfunction or blunted response to starvation. While broadly expressed in all neurons, trsn is transcriptionally upregulated in the heads of flies in response to starvation. Spatially restricted rescue or targeted knockdown localizes trsn function to neurons that produce the tachykinin family neuropeptide Leucokinin. Manipulation of neural activity in Leucokinin neurons revealed these neurons to be required for starvation-induced sleep suppression. Taken together, these findings establish trsn as an essential integrator of sleep and metabolic state, with implications for understanding the neural mechanism underlying sleep disruption in response to environmental perturbation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Regulation amending the mandatory reporting requirements for emissions of certain contaminants into the atmosphere : economic impact study

    International Nuclear Information System (INIS)

    Menard, R.; Turgeon, M.L.; Dumais, M.; Bernier, A.G.; Leblond, V.; Benoit, J.Y.

    2010-01-01

    Quebec's proposal to amend regulations regarding pollutants responsible for the increase in greenhouse gases, acid rain, smog and toxic pollution will ensure improved monitoring of the state of the environment. The proposed amendments are designed to harmonize with the Western Climate Initiative (WCI) to lower greenhouse gas (GHG) emissions and determine certain methods of calculation. The WCI includes seven U.S. states, including California, and 4 Canadian provinces including Quebec, Ontario, British Columbia and Manitoba. By joining WCI in 2008, Quebec agreed to a cap and trade of GHG emissions. One of the first steps of the process leading to the creation of a common carbon market is to ensure the thoroughness of the information collected on these emissions. Once established, the system of cap and trade will become an important instrument of the provincial strategy to address climate change. The current regulations require Quebec businesses to report GHG emissions that equal or exceed 50,000 tonnes of carbon dioxide (CO 2 ) equivalent. According to the rules of the WCI, the new threshold for reporting will be 10,000 tonnes of CO 2 equivalent. To date, companies did not have any requirements as to how to quantify their emissions. With the amended regulation, calculation methods for GHG emissions will be required for most emission sources. These methods have been adapted for Quebec businesses and were first developed by WCI partners from existing techniques used by international organizations such as the Intergovernmental Panel on Climate Change (IPCC) and the United States Environmental Protection Agency (EPA). They will standardize how issuers calculate their GHG emissions. In addition, the reporting of 25,000 tonnes of CO 2 equivalent or more, will have to be verified by an accredited organization to ensure that the prescribed methods of calculation have been followed and that the statements contain all required data. 1 tab.

  17. 77 FR 33635 - Amendment to the Bank Secrecy Act Regulations-Requirement That Clerks of Court Report Certain...

    Science.gov (United States)

    2012-06-07

    ... business rule reflects that the definition of currency used therein is slightly different from the... Amendment to the Bank Secrecy Act Regulations--Requirement That Clerks of Court Report Certain Currency...: FinCEN is amending the rules relating to the reporting of certain currency transactions consistent...

  18. Adjustment of Energy requirements in TEK; TEK= Technical Regulations under the Norwegian Planning and Building Act; Justering av energikrav i TEK

    Energy Technology Data Exchange (ETDEWEB)

    Thyholt, Marit; Dokka, Tor Helge; Schild, Peter; Grini, Catherine; Mysen, Mads; Sartori, Igor

    2008-07-01

    The National Office of Building Technology and Administration (BE) desired to review the consequences of different levels of ambition for requirements for heat gaining from vent air, as well as a possible requirement for energy efficient design of building fronts. In addition the energy scope in the regulation (TEK2007) should be adjusted according to the final establishment of a new calculation standard (Norwegian Standard - NS 3031:2007). A statement on these subjects has been carried out at SINTEF Byggforsk, and is described in this report. Adjustments of framework regulations.There are only minor differences between adjusted calculations according to NS 3031 and the original energy framework calculations, i.e. the difference for net energy need amounts to the size of 0 to 6 percent. Heat gain.The report shows that it is possible - both from techical and financial considerations - to increase the requirement level for heat gain from vent air for most categories of buildings. This implies a sharpening of the annual median temperature efficiency from 70 % to 80 %, for all building categories, except from hospitals, institutions and light industry/workshops. A possible sharpening of regulations for heat gain in houses has not been evaluated. Depending on building category a sharpening of regulations for heat gain from vent air will imply that net energy need will be reduced on a scale of 20 to 30 kWh/m2 per annum. The report demonstrates that despite a possible sharpening of the requirements on energy efficiency for heat recovery devices does not prevent the use of large areas of windows and window panes. Vulnerability analyses show that deviations from the prerequisites in the basis for the energy framework concerning air quantities and air temperatures give the possibility of weakening the building's heating characteristics. Building fronts. Different methods for added requirements for building fronts have been examined. The aim has been to find methods and

  19. Regulation No. 56/2006 Coll. of the Nuclear Regulatory Authority of the Slovak Republic dated as of January 12, 2006 on details concerning requirements for quality system documentation of authorisation holder, as well as details concerning quality requirements for nuclear installations, details concerning quality requirements for classified equipment and details concerning the scope of their approval

    International Nuclear Information System (INIS)

    2006-01-01

    This Regulation provides details of the requirements for quality system documentation holder, details of the quality requirements for nuclear installations, details concerning quality requirements for classified equipment and details of the scope of their approval. This Regulation came into force on March 1, 2006.

  20. 48 CFR 30.202 - Disclosure requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Disclosure requirements. 30.202 Section 30.202 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.202 Disclosure...

  1. Good for your health? An analysis of the requirements for scientific substantiation in European health claims regulation

    Directory of Open Access Journals (Sweden)

    Oliver Todt

    2016-05-01

    Full Text Available Objective. To identify the various types of evidence, as well as their relative importance in European health claims regulation, in order to analyze the consequences for consumer protection of the requirements for scientific substantiation in this regulation. Materials and methods. Qualitative analysis of various documents relevant to the regulatory process, particularly as to the implications of the standards of proof for the functional food market, as well as consumer behavior. Results. European regulation defines a hierarchy of evidence that turns randomized controlled trials into a necessary and sufficient condition for health claim autho- rizations. Conclusions. Consumer protection can be interpreted in different manners. High standards of proof protect consumers from false information about the health outcomes of functional foods, while lower standards lead to more, albeit less accurate information about such outcomes being available to consumers.

  2. New requirements embodied in expert knowledge regulations for industrial radiation protection officers

    International Nuclear Information System (INIS)

    Vogt, H.G.

    2001-01-01

    Expert knowledge standards and certification requirements of health physics responsible persons or radiation safety officers in industry or in health care are laid down in Germany in administrative regulations. Now the new Radiation Protection Ordinance (StrlSchV) contains a specific section exclusively devoted to all aspects of expert knowledge in industrial radiation protection, which inter alia demonstrates the special significance of education and further training of radiation protection specialists. It is expected that the forthcoming new X-ray Ordinance (RoeV) will contain a similar amendment. The article explains the implications of the new Radiation Protection Ordinance for the education and further training of industrial radiation protection officers, but does not address specific aspects of nuclear engineering. (orig./CB) [de

  3. Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation

    DEFF Research Database (Denmark)

    Shebelut, Conrad W.; Jensen, Rasmus Bugge; Gitai, Zemer

    2009-01-01

    Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation...... determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated....

  4. Fps/Fes and Fer non-receptor protein-tyrosine kinases regulate collagen- and ADP-induced platelet aggregation.

    Science.gov (United States)

    Senis, Y A; Sangrar, W; Zirngibl, R A; Craig, A W B; Lee, D H; Greer, P A

    2003-05-01

    Fps/Fes and Fer proto-oncoproteins are structurally related non-receptor protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. We show that Fps/Fes and Fer are expressed in human and mouse platelets, and are activated following stimulation with collagen and collagen-related peptide (CRP), suggesting a role in GPVI receptor signaling. Fer was also activated following stimulation with thrombin and a protease-activated receptor4 (PAR4)-activating peptide, suggesting a role in signaling downstream from the G protein-coupled PAR4. There were no detectable perturbations in CRP-induced activation of Syk, PLCgamma2, cortactin, Erk, Jnk, Akt or p38 in platelets from mice lacking Fps/Fes, Fer, or both kinases. Platelets lacking Fps/Fes, from a targeted fps/fes null strain of mice, showed increased rates and amplitudes of collagen-induced aggregation, relative to wild-type platelets. P-Selectin expression was also elevated on the surface of Fps/Fes-null platelets in response to CRP. Fer-deficient platelets, from mice targeted with a kinase-inactivating mutation, disaggregated more rapidly than wild-type platelets in response to ADP. This report provides the first evidence that Fps/Fes and Fer are expressed in platelets and become activated downstream from the GPVI collagen receptor, and that Fer is activated downstream from a G-protein coupled receptor. Furthermore, using targeted mouse models we show that deficiency in Fps/Fes or Fer resulted in disregulated platelet aggregation and disaggregation, demonstrating a role for these kinases in regulating platelet functions.

  5. Frontiers of environmental regulation: environmental management systems: a regulator`s perspective

    Energy Technology Data Exchange (ETDEWEB)

    Stone, M.J. [South Australian Dept. of Mines and Energy, Adelaide, SA (Australia)

    1996-12-31

    Leading edge companies throughout the world have embraced management systems to achieve optimal sustainable performance in the ever changing business environment of the 1990s. Given that the natural environment and environmental performance have become major issues affecting organizations, the need for integrating environmental management with all the other components of an organization`s overall management approach is now widely recognized. This paper is organized in five parts. The first explores recently released environmental standards, the interim environmental management systems (EMS) general guidelines standard AS/NZS ISO 14004 (Int) and identifies how this has dealt with the regulator/community/company interface. The second identifies company requirements for addressing environmental issues. The third, considers regulatory theory to identify current requirements for an effective regulatory system and how this can interface with a company`s EMS. These form the basis in the fourth section for identifying some opportunities which occur at the company/ regulator interface. The fifth and final section draws a number of conclusions about the current frontiers of environmental regulation. The coincidence of the requirements of a regulatory framework with the areas of interface between what is referred to in the draft International Standard for EMS as `Interested Parties`, the regulators and community, are identified. (author). 1 tab., 2 figs., 20 refs.

  6. Successful emotion regulation requires both conviction and skill: beliefs about the controllability of emotions, reappraisal, and regulation success.

    Science.gov (United States)

    Gutentag, Tony; Halperin, Eran; Porat, Roni; Bigman, Yochanan E; Tamir, Maya

    2017-09-01

    To succeed in self-regulation, people need to believe that it is possible to change behaviour and they also need to use effective means to enable such a change. We propose that this also applies to emotion regulation. In two studies, we found that people were most successful in emotion regulation, the more they believed emotions can be controlled and the more they used an effective emotion regulation strategy - namely, cognitive reappraisal. Cognitive reappraisal moderated the link between beliefs about the controllability of emotion and success in emotion regulation, when reappraisal was measured as a trait (Study 1) or manipulated (Study 2). Such moderation was found when examining the regulation of disgust elicited by emotion-inducing films (Study 1), and the regulation of anger elicited by real political events (Study 2). We discuss the implications of our findings for research and practice in emotion regulation.

  7. Unique C-terminal region of Hap3 is required for methanol-regulated gene expression in the methylotrophic yeast Candida boidinii.

    Science.gov (United States)

    Oda, Saori; Yurimoto, Hiroya; Nitta, Nobuhisa; Sakai, Yasuyoshi

    2016-05-01

    The Hap complex of the methylotrophic yeast Candida boidinii was found to be required for methanol-regulated gene expression. In this study, we performed functional characterization of CbHap3p, one of the Hap complex components in C. boidinii. Sequence alignment of Hap3 proteins revealed the presence of a unique extended C-terminal region, which is not present in Hap3p from Saccharomyces cerevisiae (ScHap3p), but is found in Hap3p proteins of methylotrophic yeasts. Deletion of the C-terminal region of CbHap3p (Δ256-292 or Δ107-237) diminished activation of methanol-regulated genes and abolished the ability to grow on methanol, but did not affect nuclear localization or DNA-binding ability. However, deletion of the N-terminal region of CbHap3p (Δ1-20) led to not only a growth defect on methanol and a decreased level of methanol-regulated gene expression, but also impaired nuclear localization and binding to methanol-regulated gene promoters. We also revealed that CbHap3p could complement the growth defect of the Schap3Δ strain on glycerol, although ScHap3p could not complement the growth defect of a Cbhap3Δ strain on methanol. We conclude that the unique C-terminal region of CbHap3p contributes to maximum activation of methanol-regulated genes, whilst the N-terminal region is required for nuclear localization and binding to DNA.

  8. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Cheng Cui

    2013-11-01

    Full Text Available Planar cell polarity (PCP regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin

  9. An assessment of the fire protection requirements throughout a NPP life related to current IAEA regulations and American, Canadian and UE regulations

    International Nuclear Information System (INIS)

    Branzeu, N.; Necula, D.; Badea, M.; Teodorescu, D.; Peteu, M.

    2006-01-01

    Statistics on fires has surprisingly shown that the frequency of fires in a nuclear power plant are as high as in the conventional industrial units. The analyses on fires occurred in a NPP need to consider both their well-known severe damages and the nuclear consequences. In 1975 a severe fire occurred in BROWNS FERRY NPP due to the ignition of the polyurethane foam used in the electric cable penetration sealings. The fire propagated to the cable channels and damaged over 1600 cables. The fire event revealed important shortcomings in the fire protection design and procedures. The fire represented a crucial event that changed fundamentally the fire protection regulation in the United States nuclear industry. The fire protection programs, standards and guides currently applied, have been developed on basis of this fire analysis and gained conclusions/experience. The purpose of the article is to be a short presentation of the fire protection requirements for all NPP life stages (i.e. design, construction, commissioning, operation and decommissioning), including the most recent issues of the standards, codes, guides and regulations in US, Canada, IAEA and some European countries. Such documentation represented the main technical support in establishing the national fire protection standard design regarding all the stages of a CANDU-6 NPP life, all the types of operational NPPs, particularly for Cernavoda NPP Unit 1 and Unit 2 (now in an advanced stage of construction). In order to satisfy the requirements provided by this documentation, as practically as possible, a list of analyses and fire protection improvement measures for Cernavoda NPP is presented. (authors)

  10. The rgg0182 gene encodes a transcriptional regulator required for the full Streptococcus thermophilus LMG18311 thermal adaptation.

    Science.gov (United States)

    Henry, Romain; Bruneau, Emmanuelle; Gardan, Rozenn; Bertin, Stéphane; Fleuchot, Betty; Decaris, Bernard; Leblond-Bourget, Nathalie

    2011-10-07

    Streptococcus thermophilus is an important starter strain for the production of yogurt and cheeses. The analysis of sequenced genomes of four strains of S. thermophilus indicates that they contain several genes of the rgg familly potentially encoding transcriptional regulators. Some of the Rgg proteins are known to be involved in bacterial stress adaptation. In this study, we demonstrated that Streptococcus thermophilus thermal stress adaptation required the rgg0182 gene which transcription depends on the culture medium and the growth temperature. This gene encoded a protein showing similarity with members of the Rgg family transcriptional regulator. Our data confirmed that Rgg0182 is a transcriptional regulator controlling the expression of its neighboring genes as well as chaperones and proteases encoding genes. Therefore, analysis of a Δrgg0182 mutant revealed that this protein played a role in the heat shock adaptation of Streptococcus thermophilus LMG18311. These data showed the importance of the Rgg0182 transcriptional regulator on the survival of S. thermophilus during dairy processes and more specifically during changes in temperature.

  11. The rgg0182 gene encodes a transcriptional regulator required for the full Streptococcus thermophilus LMG18311 thermal adaptation

    Directory of Open Access Journals (Sweden)

    Bertin Stéphane

    2011-10-01

    Full Text Available Abstract Background Streptococcus thermophilus is an important starter strain for the production of yogurt and cheeses. The analysis of sequenced genomes of four strains of S. thermophilus indicates that they contain several genes of the rgg familly potentially encoding transcriptional regulators. Some of the Rgg proteins are known to be involved in bacterial stress adaptation. Results In this study, we demonstrated that Streptococcus thermophilus thermal stress adaptation required the rgg0182 gene which transcription depends on the culture medium and the growth temperature. This gene encoded a protein showing similarity with members of the Rgg family transcriptional regulator. Our data confirmed that Rgg0182 is a transcriptional regulator controlling the expression of its neighboring genes as well as chaperones and proteases encoding genes. Therefore, analysis of a Δrgg0182 mutant revealed that this protein played a role in the heat shock adaptation of Streptococcus thermophilus LMG18311. Conclusions These data showed the importance of the Rgg0182 transcriptional regulator on the survival of S. thermophilus during dairy processes and more specifically during changes in temperature.

  12. ENVIRONMENTAL SPECIFICATION REQUIREMENTS

    International Nuclear Information System (INIS)

    TIFFT, S.R.

    2003-01-01

    Through regulations, permitting or binding negotiations, Regulators establish requirements, limits, permit conditions and Notice of Construction (NOC) conditions with which the Office of River Protection (ORP) and the Tank Farm Contractor (TFC) must comply. Operating Specifications are technical limits which are set on a process to prevent injury to personnel, or damage to the facility or environment. The main purpose of this document is to provide specification limits and recovery actions for the TFC Environmental Surveillance Program at the Hanford Site. Specification limits are given for monitoring frequencies and permissible variation of readings from an established baseline or previous reading. The requirements in this document are driven by environmental considerations and data analysis issues, rather than facility design or personnel safety issues. This document is applicable to all SST and DST waste tanks, and the associated catch tanks and receiver tanks, and transfer systems. This Tank Farm ESD implements environmental-regulatory limits on the configuration and operation of the Hanford Tank Farms facility that have been established by Regulators. This ESD contains specific field operational limits and recovery actions for compliance with airborne effluent regulations and agreements, liquid effluents regulations and agreements, and environmental tank system requirements. The scope of this ESD is limited to conditions that have direct impact on Operations/Projects or that Operations/Projects have direct impact upon. This document does not supercede or replace any DOE Orders, regulatory permits, notices of construction, or Regulatory agency agreements binding on the ORP or the TFC. Refer to the appropriate regulation, permit, or NOC for an inclusive listing of requirements

  13. WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria.

    KAUST Repository

    Abdallah, Abdallah

    2018-04-09

    The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.

  14. WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria.

    KAUST Repository

    Abdallah, Abdallah; Weerdenburg, Eveline; Guan, Qingtian; Ummels, Roy; Borggreve, S; Adroub, Sabir; Malas, Tareq; Naeem, Raeece; Zhang, Huoming; Otto, Thomas; Bitter, Wilbert; Pain, Arnab

    2018-01-01

    The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.

  15. Learned stressor resistance requires extracellular signal-regulated kinase in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    John Paul Christianson

    2014-10-01

    Full Text Available Behaviorally controllable stressors confer protection from the neurochemical and behavioral consequences of future uncontrollable stressors, a phenomenon termed behavioral immunization. Recent data implicate neuroplasticity within the ventromedial prefrontal cortex (mPFC as critical to behavioral immunization. Adult, male Sprague-Dawley rats were exposed to a series of controllable tailshocks and one week later to uncontrollable tailshocks, followed 24h later by social exploration and shuttlebox escape tests. To test the involvement of N-methyl-D-aspartate receptors (NMDAR and the extracellular signal-regulated kinase (ERK cascade in behavioral immunization, either D-AP5 or the MEK inhibitor U0126 was injected to the prelimbic (PL or infralimbic (IL mPFC prior to controllable stress exposure. Phosphorylated ERK and P70S6K, regulators of transcription and translation, were quantified by Western blot or immunohistochemistry after controllable or uncontrollable tailshocks. Prior controllable stress prevented the social exploration and shuttlebox performance deficits caused by the later uncontrollable stressor, and this effect was blocked by injections of D-AP5 into mPFC. A significant increase in phosphorylated ERK1 and ERK2, but not P70S6K, occurred within the PL and IL in rats exposed to controllable stress, but not to uncontrollable stress. However, U0126 only prevented behavioral immunization when injected to the PL. We provide evidence that NMDAR and ERK dependent plasticity within the PL region is required for behavioral immunization, a learned form of stressor resistance.

  16. 40 CFR 141.70 - General requirements.

    Science.gov (United States)

    2010-07-01

    ...) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.70 General requirements. (a... regulations establish criteria under which filtration is required as a treatment technique for public water... filtration requirements in § 141.73 and the disinfection requirements in § 141.72(b). (c) Each public water...

  17. 48 CFR 9903.202 - Disclosure requirements.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.202 Disclosure requirements. ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Disclosure requirements. 9903.202 Section 9903.202 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  18. EU Regulation of Nanobiocides: Challenges in Implementing the Biocidal Product Regulation (BPR)

    DEFF Research Database (Denmark)

    Brinch, Anna; Hansen, Steffen Foss; Hartmann, Nanna B.

    2016-01-01

    The Biocidal Products Regulation (BPR) contains several provisions for nanomaterials (NMs) and is the first regulation in the European Union to require specific testing and risk assessment for the NM form of a biocidal substance as a part of the information requirements. Ecotoxicological data...

  19. 48 CFR 1430.202 - Disclosure requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Disclosure requirements. 1430.202 Section 1430.202 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 1430.202 Disclosure...

  20. 48 CFR 430.202 - Disclosure requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Disclosure requirements. 430.202 Section 430.202 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 430.202 Disclosure...

  1. 48 CFR 1330.202 - Disclosure requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Disclosure requirements. 1330.202 Section 1330.202 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 1330.202 Disclosure...

  2. Identification of two gene clusters and a transcriptional regulator required for Pseudomonas aeruginosa glycine betaine catabolism.

    Science.gov (United States)

    Wargo, Matthew J; Szwergold, Benjamin S; Hogan, Deborah A

    2008-04-01

    Glycine betaine (GB), which occurs freely in the environment and is an intermediate in the catabolism of choline and carnitine, can serve as a sole source of carbon or nitrogen in Pseudomonas aeruginosa. Twelve mutants defective in growth on GB as the sole carbon source were identified through a genetic screen of a nonredundant PA14 transposon mutant library. Further growth experiments showed that strains with mutations in two genes, gbcA (PA5410) and gbcB (PA5411), were capable of growth on dimethylglycine (DMG), a catabolic product of GB, but not on GB itself. Subsequent nuclear magnetic resonance (NMR) experiments with 1,2-(13)C-labeled choline indicated that these genes are necessary for conversion of GB to DMG. Similar experiments showed that strains with mutations in the dgcAB (PA5398-PA5399) genes, which exhibit homology to genes that encode other enzymes with demethylase activity, are required for the conversion of DMG to sarcosine. Mutant analyses and (13)C NMR studies also confirmed that the soxBDAG genes, predicted to encode a sarcosine oxidase, are required for sarcosine catabolism. Our screen also identified a predicted AraC family transcriptional regulator, encoded by gbdR (PA5380), that is required for growth on GB and DMG and for the induction of gbcA, gbcB, and dgcAB in response to GB or DMG. Mutants defective in the previously described gbt gene (PA3082) grew on GB with kinetics similar to those of the wild type in both the PAO1 and PA14 strain backgrounds. These studies provided important insight into both the mechanism and the regulation of the catabolism of GB in P. aeruginosa.

  3. ENVIRONMENTAL SPECIFICATION REQUIREMENTS

    International Nuclear Information System (INIS)

    TIFFT, S.R.

    2003-01-01

    Through regulations, permitting or binding negotiations, Regulators establish requirements, limits, permit conditions and Notice of Construction (NOC) conditions with which the Office of River Protection (ORP) and the Tank Farm Contractor (TFC) must comply. Operating Specifications are technical limits which are set on a process to prevent injury to personnel, or damage to the facility or environment. The main purpose of this document is to provide specification limits and recovery actions for the TFC Environmental Surveillance Program at the Hanford Site. Specification limits are given for monitoring frequencies and permissible variation of readings from an established baseline or previous reading. The requirements in this document are driven by environmental considerations and data analysis issues, rather than facility design or personnel safety issues. This document is applicable to all single-shell tank (SST) and double-shell tank (DST) waste tanks, and the associated catch tanks and receiver tanks, and transfer systems. This Tank Farm Environmental Specifications Document (ESD) implements environmental-regulatory limits on the configuration and operation of the Hanford Tank Farms facility that have been established by Regulators. This ESD contains specific field operational limits and recovery actions for compliance with airborne effluent regulations and agreements, liquid effluents regulations and agreements, and environmental tank system requirements. The scope of this ESD is limited to conditions that have direct impact on Operations Projects or that Operations/Projects have direct impact upon. This document does not supercede or replace any DOE Orders, regulatory permits, notices of construction, or Regulatory agency agreements binding on the ORP or the TFC. Refer to the appropriate regulation, permit, or NOC for an inclusive listing of requirements

  4. Molecular analysis of mxbD and mxbM, a putative sensor-regulator pair required for oxidation of methanol in Methylobacterium extorquens AM1.

    Science.gov (United States)

    Springer, A L; Morris, C J; Lidstrom, M E

    1997-05-01

    Five genes are thought to be required for transcription of methanol oxidation genes in Methylobacterium strains. These putative regulatory genes include mxcQE, which encode a putative sensor-regulator pair, and mxbDM and mxaB, whose functions are less well-understood. In this study, mxbDM in Methylobacterium extorquens AM1 were shown to be required for expression of a xylE transcriptional fusion to the structural gene for the large subunit of methanol dehydrogenase (mxaF), confirming the role of these genes in transcriptional regulation of mxaF. The nucleotide sequence suggests that mxbD encodes a histidine protein kinase with two transmembrane domains and that mxbM encodes a DNA-binding response regulator. A xylE transcriptional fusion to the putative mxbD promoter showed low-level expression in wild-type cells grown on one-carbon (C1) compounds and no detectable expression in cells grown on succinate. Deletion analysis of this promoter construct showed that the region 229-129 bp upstream of the start of mxbD is required for expression. The expression of the mxbD-xylE fusion was examined in each of the five known regulatory mutant classes. xylE expression was reduced to non-detectable levels in MxcQ and MxcE mutants, but was not affected in the other regulatory mutants or in non-regulatory mutants defective in methanol oxidation. These results suggest a regulatory hierarchy in which the sensor-regulator pair MxcQE control expression of the sensor-regulator pair MxbDM, and MxbDM in turn control expression of a number of genes involved in methanol oxidation.

  5. Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells.

    Directory of Open Access Journals (Sweden)

    Yo-Chuen Lin

    Full Text Available Metastasis is a major cause of mortality in cancer patients. Invadopodia are considered to be crucial structures that allow cancer cells to penetrate across the extracellular matrix (ECM by using matrix metalloproteinases (MMPs. Previously, we isolated a highly invasive A431-III subline from parental A431 cells by Boyden chamber assay. The A431-III cells possess higher invasive and migratory abilities, elevated levels of MMP-9 and an enhanced epithelial-mesenchymal transition (EMT phenotype. In this study, we discovered that A431-III cells had an increased potential to form invadopodia and an improved capacity to degrade ECM compared with the original A431 cells. We also observed enhanced phosphorylation levels of cortactin and Src in A431-III cells; these phosphorylated proteins have been reported to be the main regulators of invadopodia formation. Flavonoids, almost ubiquitously distributed in food plants and plant food products, have been documented to exhibit anti-tumor properties. Therefore, it was of much interest to explore the effects of flavonoid antioxidants on the metastatic activity of A431-III cells. Exposure of A431-III cells to two potent dietary flavonoids, namely luteolin (Lu and quercetin (Qu, caused inhibition of invadopodia formation and decrement in ECM degradation. We conclude that Lu and Qu attenuate the phosphorylation of cortactin and Src in A431-III cells. As a consequence, there ensues a disruption of invadopodia generation and the suppression of MMP secretion. These changes, in concert, bring about a reduction in metastasis.

  6. Towards trust in regulation. Moving to a public value regulation

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Catherine; Woodman, Bridget [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom)

    2010-06-15

    The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR). (author)

  7. Towards trust in regulation-moving to a public value regulation

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Catherine, E-mail: catherine.mitchell@exeter.ac.u [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom); Woodman, Bridget [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom)

    2010-06-15

    The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR).

  8. Towards trust in regulation-moving to a public value regulation

    International Nuclear Information System (INIS)

    Mitchell, Catherine; Woodman, Bridget

    2010-01-01

    The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR).

  9. 78 FR 31551 - Federal Acquisition Regulation; Submission for OMB Review; Commerce Patent Regulations

    Science.gov (United States)

    2013-05-24

    ...; Submission for OMB Review; Commerce Patent Regulations AGENCIES: Department of Defense (DOD), General... collection requirement concerning Department of Commerce patent regulations. A notice was published in...- 0095, Commerce Patent Regulations, by any of the following methods: Regulations.gov : http://www...

  10. Nevada Nuclear Waste Storage Investigations: A review of requirements for biological information in federal, state, and local environmental laws and regulations

    International Nuclear Information System (INIS)

    Collins, E.; O'Farrell, T.P.

    1987-01-01

    Biological information concerning Yucca Mountain collected since 1980 is evaluated to determine if it is sufficient to satisfy the requirements of the various federal, state, and local laws and regulations that pertain to environmental protection or to development of waste repositories. The pertinent requirements of each law are summarized, missing information is identified, and recommendations are made for studies to fill these gaps. 11 refs., 2 figs., 1 tab

  11. Interdomain allosteric regulation of Polo kinase by Aurora B and Map205 is required for cytokinesis

    Science.gov (United States)

    Kachaner, David; Pinson, Xavier; El Kadhi, Khaled Ben; Normandin, Karine; Talje, Lama; Lavoie, Hugo; Lépine, Guillaume; Carréno, Sébastien; Kwok, Benjamin H.; Hickson, Gilles R.

    2014-01-01

    Drosophila melanogaster Polo and its human orthologue Polo-like kinase 1 fulfill essential roles during cell division. Members of the Polo-like kinase (Plk) family contain an N-terminal kinase domain (KD) and a C-terminal Polo-Box domain (PBD), which mediates protein interactions. How Plks are regulated in cytokinesis is poorly understood. Here we show that phosphorylation of Polo by Aurora B is required for cytokinesis. This phosphorylation in the activation loop of the KD promotes the dissociation of Polo from the PBD-bound microtubule-associated protein Map205, which acts as an allosteric inhibitor of Polo kinase activity. This mechanism allows the release of active Polo from microtubules of the central spindle and its recruitment to the site of cytokinesis. Failure in Polo phosphorylation results in both early and late cytokinesis defects. Importantly, the antagonistic regulation of Polo by Aurora B and Map205 in cytokinesis reveals that interdomain allosteric mechanisms can play important roles in controlling the cellular functions of Plks. PMID:25332165

  12. A distal ABA responsive element in AtNCED3 promoter is required for positive feedback regulation of ABA biosynthesis in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Yan-Zhuo Yang

    Full Text Available The plant hormone abscisic acid (ABA plays a crucial role in plant development and responses to abiotic stresses. Recent studies indicate that a positive feedback regulation by ABA exists in ABA biosynthesis in plants under dehydration stress. To understand the molecular basis of this regulation, we analyzed the cis-elements of the AtNCED3 promoter in Arabidopsis. AtNCED3 encodes the first committed and highly regulated dioxygenase in the ABA biosynthetic pathway. Through delineated and mutagenesis analyses in stable-transformed Arabidopsis, we revealed that a distal ABA responsive element (ABRE: GGCACGTG, -2372 to -2364 bp is required for ABA-induced AtNCED3 expression. By analyzing the AtNCED3 expression in ABRE binding protein ABF3 over-expression transgenic plants and knock-out mutants, we provide evidence that the ABA feedback regulation of AtNCED3 expression is not mediated by ABF3.

  13. A distal ABA responsive element in AtNCED3 promoter is required for positive feedback regulation of ABA biosynthesis in Arabidopsis.

    Science.gov (United States)

    Yang, Yan-Zhuo; Tan, Bao-Cai

    2014-01-01

    The plant hormone abscisic acid (ABA) plays a crucial role in plant development and responses to abiotic stresses. Recent studies indicate that a positive feedback regulation by ABA exists in ABA biosynthesis in plants under dehydration stress. To understand the molecular basis of this regulation, we analyzed the cis-elements of the AtNCED3 promoter in Arabidopsis. AtNCED3 encodes the first committed and highly regulated dioxygenase in the ABA biosynthetic pathway. Through delineated and mutagenesis analyses in stable-transformed Arabidopsis, we revealed that a distal ABA responsive element (ABRE: GGCACGTG, -2372 to -2364 bp) is required for ABA-induced AtNCED3 expression. By analyzing the AtNCED3 expression in ABRE binding protein ABF3 over-expression transgenic plants and knock-out mutants, we provide evidence that the ABA feedback regulation of AtNCED3 expression is not mediated by ABF3.

  14. A novel splice variant of supervillin, SV5, promotes carcinoma cell proliferation and cell migration

    International Nuclear Information System (INIS)

    Chen, Xueran; Yang, Haoran; Zhang, Shangrong; Wang, Zhen; Ye, Fang; Liang, Chaozhao; Wang, Hongzhi; Fang, Zhiyou

    2017-01-01

    Supervillin is an actin-associated protein that regulates actin dynamics by interacting with Myosin II, F-actin, and Cortactin to promote cell contractility and cell motility. Two splicing variants of human Supervillin (SV1 and SV4) have been reported in non-muscle cells; SV1 lacks 3 exons present in the larger isoform SV4. SV2, also called archvillin, is present in striated muscle; SV3, also called smooth muscle archvillin or SmAV, was cloned from smooth muscle. In the present study, we identify a novel splicing variant of Supervillin (SV5). SV5 contains a new splicing pattern. In the mouse tissues and cell lines examined, SV5 was predominantly expressed in skeletal and cardiac muscles and in proliferating cells, but was virtually undetectable in most normal tissues. Using RNAi and rescue experiments, we show here that SV5 displays altered functional properties in cancer cells, and regulates cell proliferation and cell migration.

  15. TANK FARM ENVIRONMENTAL REQUIREMENTS

    International Nuclear Information System (INIS)

    TIFFT, S.R.

    2003-01-01

    Through regulations, permitting or binding negotiations, Regulators establish requirements, limits, permit conditions and Notice of Construction (NOC) conditions with which the Office of River Protection (ORP) and the Tank Farm Contractor (TFC) must comply. Operating Specifications are technical limits which are set on a process to prevent injury to personnel, or damage to the facility or environment, The main purpose of this document is to provide specification limits and recovery actions for the TFC Environmental Surveillance Program at the Hanford Site. Specification limits are given for monitoring frequencies and permissible variation of readings from an established baseline or previous reading. The requirements in this document are driven by environmental considerations and data analysis issues, rather than facility design or personnel safety issues. This document is applicable to all single-shell tank (SST) and double-shell tank (DST) waste tanks, and the associated catch tanks and receiver tanks, and transfer systems. This Tank Farm Environmental Specifications Document (ESD) implements environmental-regulatory limits on the configuration and operation of the Hanford Tank Farms facility that have been established by Regulators. This ESD contains specific field operational limits and recovery actions for compliance with airborne effluent regulations and agreements, liquid effluents regulations and agreements, and environmental tank system requirements. The scope of this ESD is limited to conditions that have direct impact on Operations/Projects or that Operations Projects have direct impact upon. This document does not supercede or replace any Department of Energy (DOE) Orders, regulatory permits, notices of construction, or Regulatory agency agreements binding on the ORP or the TFC. Refer to the appropriate regulation, permit, or Notice of Construction for an inclusive listing of requirements

  16. Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells.

    Directory of Open Access Journals (Sweden)

    Mehmet Yabas

    Full Text Available Natural killer T (NKT cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo and mature (NK1.1(hi cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder, that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.

  17. 7 CFR 981.51 - Requirements for reserve.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Requirements for reserve. 981.51 Section 981.51... Regulating Handling Volume Regulation § 981.51 Requirements for reserve. Each handler may satisfy his reserve... include grade requirements for reserve almonds delivered to human consumption outlets. [41 FR 26853, June...

  18. EU Regulation of Nanobiocides: Challenges in Implementing the Biocidal Product Regulation (BPR

    Directory of Open Access Journals (Sweden)

    Anna Brinch

    2016-02-01

    Full Text Available The Biocidal Products Regulation (BPR contains several provisions for nanomaterials (NMs and is the first regulation in the European Union to require specific testing and risk assessment for the NM form of a biocidal substance as a part of the information requirements. Ecotoxicological data are one of the pillars of the information requirements in the BPR, but there are currently no standard test guidelines for the ecotoxicity testing of NMs. The overall objective of this work was to investigate the implications of the introduction of nano-specific testing requirements in the BPR and to explore how these might be fulfilled in the case of copper oxide nanoparticles. While there is information and data available in the open literature that could be used to fulfill the BPR information requirements, most of the studies do not take the Organisation for Economic Co-operation and Development’s nanospecific test guidelines into consideration. This makes it difficult for companies as well as regulators to fulfill the BPR information requirements for nanomaterials. In order to enable a nanospecific risk assessment, best practices need to be developed regarding stock suspension preparation and characterization, exposure suspensions preparation, and for conducting ecotoxicological test.

  19. EU Regulation of Nanobiocides: Challenges in Implementing the Biocidal Product Regulation (BPR).

    Science.gov (United States)

    Brinch, Anna; Hansen, Steffen Foss; Hartmann, Nanna B; Baun, Anders

    2016-02-16

    The Biocidal Products Regulation (BPR) contains several provisions for nanomaterials (NMs) and is the first regulation in the European Union to require specific testing and risk assessment for the NM form of a biocidal substance as a part of the information requirements. Ecotoxicological data are one of the pillars of the information requirements in the BPR, but there are currently no standard test guidelines for the ecotoxicity testing of NMs. The overall objective of this work was to investigate the implications of the introduction of nano-specific testing requirements in the BPR and to explore how these might be fulfilled in the case of copper oxide nanoparticles. While there is information and data available in the open literature that could be used to fulfill the BPR information requirements, most of the studies do not take the Organisation for Economic Co-operation and Development's nanospecific test guidelines into consideration. This makes it difficult for companies as well as regulators to fulfill the BPR information requirements for nanomaterials. In order to enable a nanospecific risk assessment, best practices need to be developed regarding stock suspension preparation and characterization, exposure suspensions preparation, and for conducting ecotoxicological test.

  20. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes

    Science.gov (United States)

    Caviston, Juliane P.; Zajac, Allison L.; Tokito, Mariko; Holzbaur, Erika L.F.

    2011-01-01

    Huntingtin (Htt) is a membrane-associated scaffolding protein that interacts with microtubule motors as well as actin-associated adaptor molecules. We examined a role for Htt in the dynein-mediated intracellular trafficking of endosomes and lysosomes. In HeLa cells depleted of either Htt or dynein, early, recycling, and late endosomes (LE)/lysosomes all become dispersed. Despite altered organelle localization, kinetic assays indicate only minor defects in intracellular trafficking. Expression of full-length Htt is required to restore organelle localization in Htt-depleted cells, supporting a role for Htt as a scaffold that promotes functional interactions along its length. In dynein-depleted cells, LE/lysosomes accumulate in tight patches near the cortex, apparently enmeshed by cortactin-positive actin filaments; Latrunculin B-treatment disperses these patches. Peripheral LE/lysosomes in dynein-depleted cells no longer colocalize with microtubules. Htt may be required for this off-loading, as the loss of microtubule association is not seen in Htt-depleted cells or in cells depleted of both dynein and Htt. Inhibition of kinesin-1 relocalizes peripheral LE/lysosomes induced by Htt depletion but not by dynein depletion, consistent with their detachment from microtubules upon dynein knockdown. Together, these data support a model of Htt as a facilitator of dynein-mediated trafficking that may regulate the cytoskeletal association of dynamic organelles. PMID:21169558

  1. Identification of Two Gene Clusters and a Transcriptional Regulator Required for Pseudomonas aeruginosa Glycine Betaine Catabolism▿ †

    Science.gov (United States)

    Wargo, Matthew J.; Szwergold, Benjamin S.; Hogan, Deborah A.

    2008-01-01

    Glycine betaine (GB), which occurs freely in the environment and is an intermediate in the catabolism of choline and carnitine, can serve as a sole source of carbon or nitrogen in Pseudomonas aeruginosa. Twelve mutants defective in growth on GB as the sole carbon source were identified through a genetic screen of a nonredundant PA14 transposon mutant library. Further growth experiments showed that strains with mutations in two genes, gbcA (PA5410) and gbcB (PA5411), were capable of growth on dimethylglycine (DMG), a catabolic product of GB, but not on GB itself. Subsequent nuclear magnetic resonance (NMR) experiments with 1,2-13C-labeled choline indicated that these genes are necessary for conversion of GB to DMG. Similar experiments showed that strains with mutations in the dgcAB (PA5398-PA5399) genes, which exhibit homology to genes that encode other enzymes with demethylase activity, are required for the conversion of DMG to sarcosine. Mutant analyses and 13C NMR studies also confirmed that the soxBDAG genes, predicted to encode a sarcosine oxidase, are required for sarcosine catabolism. Our screen also identified a predicted AraC family transcriptional regulator, encoded by gbdR (PA5380), that is required for growth on GB and DMG and for the induction of gbcA, gbcB, and dgcAB in response to GB or DMG. Mutants defective in the previously described gbt gene (PA3082) grew on GB with kinetics similar to those of the wild type in both the PAO1 and PA14 strain backgrounds. These studies provided important insight into both the mechanism and the regulation of the catabolism of GB in P. aeruginosa. PMID:17951379

  2. 16 CFR 307.2 - Required warnings.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Required warnings. 307.2 Section 307.2 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS REGULATIONS UNDER... Comprehensive Smokeless Tobacco Health Education Act of 1986 is the law that requires the enactment of these...

  3. Rhetoric and Realities: What Independence of the Bar Requires of Lawyer Regulation

    Directory of Open Access Journals (Sweden)

    Alice Woolley

    2011-06-01

    Full Text Available The Canadian legal profession is largely self-regulating. Provincial law societies governed by lawyers elected by their peers set the standards for admission to the profession and for ethical conduct, and investigate, prosecute and adjudicate allegations of professional misconduct by lawyers. Advocates for this regulatory structure rely on the concept of “independence of the bar”, the idea that lawyers must be free from any external interference with their representation of clients. Critics of the regulatory structure, meanwhile, argue that independence has a broader meaning than the advocates suppose and that, in any event, the self-regulatory structure of the Canadian profession is not necessary to ensure independence. This paper presents the varying interpretations of independence of the bar and suggests that while the advocates for self-regulation have a more justifiable understanding of independence than do critics, the concept of independence of the bar is not itself central to assessing the validity of any particular regulatory scheme. Rather, the things that independence should protect – the ability of lawyers to be zealous advocates for clients within the bounds of legality – should be used to assess the adequacies of any regulatory scheme. Does regulation ensure that lawyers fulfill their duty of zealous advocacy? Does regulation ensure that lawyers remain within the bounds of legality? Does regulation ensure access to justice? With these criteria in mind, and using recent changes to the regulation of lawyers in England and Wales as a comparator, the paper then analyzes the adequacy of regulation of Canadian lawyers with respect to competence, the general structure of professional regulation and access to justice. Based on this analysis, the author proposes changes to improve lawyer regulation in Canada. These changes do not abandon self-regulation. However, they include separating the adjudicative function of the law societies

  4. Pressure transmitters: Addressing post-Fukushima regulations and requirements with Bibloc technology by Rolls-Royce

    International Nuclear Information System (INIS)

    Fabbro, Herve; Desgeorge, Romain; Chowanek, Michel

    2013-06-01

    Nuclear power stations are designed to withstand substantial seismic activity and as such represent some of the most robust buildings in the world. However The Fukushima nuclear incident highlighted the potential vulnerability of nuclear power plants when multiple natural events of historic proportions happen simultaneously. Following the incident, the worldwide nuclear industry quite rightly called for an immediate review and a targeted reassessment of the safety margins of nuclear reactors. Several recommendations have been given by international safety authorities, including a significant toughening of the already stringent regulations and requirements, with respect to earthquakes, extreme temperatures, pressure and radiation resistance. In the event of an accident, a quick response is imperative and to act efficiently, a correct knowledge of the situation as well as an accurate estimation of its severity are required. Thus, it is essential to be able to rely on the most reliable sensors possible, in particular for the 50 to 100 classified pressure transmitters. Equipment used in nuclear plants all over the world, such pressure transmitters, are implemented following one of two different types of design: - The Monobloc design where almost all the equipment or system is installed very close to the reactor, within the reactor building. - The Bibloc design where the most sensitive parts (in particular the electronics) are removed from the harsh environment present in the vicinity of the reactor to be placed outside of the reactor building. The paper will present the advantages of the Bibloc technology and will show how this technology meets the 'Post Fukushima' requirements. (authors)

  5. Tyrosine kinase signalling in breast cancer: Modulation of tyrosine kinase signalling in human breast cancer through altered expression of signalling intermediates

    International Nuclear Information System (INIS)

    Kairouz, Rania; Daly, Roger J

    2000-01-01

    The past decade has seen the definition of key signalling pathways downstream of receptor tyrosine kinases (RTKs) in terms of their components and the protein-protein interactions that facilitate signal transduction. Given the strong evidence that links signalling by certain families of RTKs to the progression of breast cancer, it is not surprising that the expression profile of key downstream signalling intermediates in this disease has also come under scrutiny, particularly because some exhibit transforming potential or amplify mitogenic signalling pathways when they are overexpressed. Reflecting the diverse cellular processes regulated by RTKs, it is now clear that altered expression of such signalling proteins in breast cancer may influence not only cellular proliferation (eg Grb2) but also the invasive properties of the cancer cells (eg EMS1/cortactin)

  6. 76 FR 81408 - Contractor Legal Management Requirements; Acquisition Regulations

    Science.gov (United States)

    2011-12-28

    ... DEPARTMENT OF ENERGY 10 CFR Part 719 48 CFR Parts 931, 952 and 970 RIN 1990-AA37 Contractor Legal... Energy (DOE or Department) is proposing to revise existing regulations covering contractor legal... costs by certain contractors whose contracts exceed $100,000,000 as well as legal counsel retained...

  7. 78 FR 25795 - Contractor Legal Management Requirements; Acquisition Regulations

    Science.gov (United States)

    2013-05-03

    ... DEPARTMENT OF ENERGY 10 CFR Part 719 48 CFR Parts 931, 952, and 970 RIN 1990-AA37 Contractor Legal.... ACTION: Final rule. SUMMARY: The Department of Energy revises existing regulations covering contractor... costs by certain contractors whose contracts exceed $100,000,000 as well as legal counsel retained...

  8. 78 FR 68829 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

    Science.gov (United States)

    2013-11-15

    ... DFARS 252.232-7007, Limitation of Government's Obligation. DFARS subpart 232.7, Contract [[Page 68830...; Defense Federal Acquisition Regulation Supplement; Contract Financing AGENCY: Defense Acquisition... and OMB Number: Defense Federal Acquisition Regulation Supplement (DFARS) Part 232, Contract Financing...

  9. The international radioactive transportation regulations: A model for national regulations

    International Nuclear Information System (INIS)

    Pope, R.B.; Rawl, R.R.

    1990-06-01

    The International Atomic Energy Agency's (IAEA) Regulations for the Safe Transport of Radioactive Material, Safety Series No. 6 (herein after denoted as the ''International Regulations'') serve as the model for the regulations for individual countries and international modal organizations controlling the packaging and transportation of radioactive materials. The purpose of this paper is to outline the background and history of the International Regulations, the general principles behind the requirements of the International Regulations, the structure and general contents of the latest edition of the International Regulations, and the roles of various international bodies in the development and implementation of the International Regulations and the current status of regulatory and supportive document development at both the international and domestic level. This review will provide a basis for users and potential users to better understand the source and application of the International Regulations. 1 tab

  10. Proteolytic cleavage and PKA phosphorylation of α1C subunit are not required for adrenergic regulation of CaV1.2 in the heart.

    Science.gov (United States)

    Katchman, Alexander; Yang, Lin; Zakharov, Sergey I; Kushner, Jared; Abrams, Jeffrey; Chen, Bi-Xing; Liu, Guoxia; Pitt, Geoffrey S; Colecraft, Henry M; Marx, Steven O

    2017-08-22

    Calcium influx through the voltage-dependent L-type calcium channel (Ca V 1.2) rapidly increases in the heart during "fight or flight" through activation of the β-adrenergic and protein kinase A (PKA) signaling pathway. The precise molecular mechanisms of β-adrenergic activation of cardiac Ca V 1.2, however, are incompletely known, but are presumed to require phosphorylation of residues in α 1C and C-terminal proteolytic cleavage of the α 1C subunit. We generated transgenic mice expressing an α 1C with alanine substitutions of all conserved serine or threonine, which is predicted to be a potential PKA phosphorylation site by at least one prediction tool, while sparing the residues previously shown to be phosphorylated but shown individually not to be required for β-adrenergic regulation of Ca V 1.2 current (17-mutant). A second line included these 17 putative sites plus the five previously identified phosphoregulatory sites (22-mutant), thus allowing us to query whether regulation requires their contribution in combination. We determined that acute β-adrenergic regulation does not require any combination of potential PKA phosphorylation sites conserved in human, guinea pig, rabbit, rat, and mouse α 1C subunits. We separately generated transgenic mice with inducible expression of proteolytic-resistant α 1C Prevention of C-terminal cleavage did not alter β-adrenergic stimulation of Ca V 1.2 in the heart. These studies definitively rule out a role for all conserved consensus PKA phosphorylation sites in α 1C in β-adrenergic stimulation of Ca V 1.2, and show that phosphoregulatory sites on α 1C are not redundant and do not each fractionally contribute to the net stimulatory effect of β-adrenergic stimulation. Further, proteolytic cleavage of α 1C is not required for β-adrenergic stimulation of Ca V 1.2.

  11. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

    LENUS (Irish Health Repository)

    Liu, Jinghua

    2010-05-15

    Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll\\/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.

  12. Financial Market Regulation in Germany - Capital Requirements of Financial Institutions

    Directory of Open Access Journals (Sweden)

    Daniel Karl Detzer

    2015-03-01

    Full Text Available This paper examines capital adequacy regulation in Germany. The first part reviews capital adequacy regulation from the 1930s up to the financial crisis and identifies two main trends: a gradual softening of the eligibility criteria for equity and increasing reliance on internal risk models. While the first trend has been reversed following the financial crisis, internal risk models still play a central role. Therefore, the second part discusses the problems with the use of internal risk models and discusses the potentials of Basel 2.5 and Basel III to alleviate the identified problems. It is concluded that the relevant problems are not resolved. Therefore, in the final part some suggestions of how the problems could be addressed properly are given.

  13. 48 CFR 9904.411-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.411-40 Fundamental requirement. (a) The contractor shall... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9904.411-40 Section 9904.411-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  14. 48 CFR 9904.402-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.402-40 Fundamental requirement. All costs incurred for... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9904.402-40 Section 9904.402-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  15. 48 CFR 9904.418-40 - Fundamental requirements.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.418-40 Fundamental requirements. (a) A business unit... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirements. 9904.418-40 Section 9904.418-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  16. 48 CFR 1437.7001 - Contractor qualification requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contractor qualification requirements. 1437.7001 Section 1437.7001 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... Contractor qualification requirements. (a) Prior to award of a contract for real property appraisal services...

  17. Supplement to the approved requirements for the packaging, labelling and carriage of radioactive material by rail. Packaging, Labelling and Carriage of Radioactive Material by Rail Regulations 1996

    International Nuclear Information System (INIS)

    1999-01-01

    The ADR and RID Framework Directives require EC member states' arrangements for the carriage of dangerous goods on domestic road and rail journeys to align with the existing ADR and RID agreements which cover international journeys by road and rail. Because ADR and RID are updated every two years in line with technical and scientific developments, the ADR/RID Framework Directives are also revised on a two-year cycle, to require member states to amend their implementing legislation accordingly. In Great Britain, these two Directives were initially implemented on 1 September 1996 via regulations (usually referred to as the 'carriage regulations'), containing the general legal duties, supported by approved documents, and an Approved Code of Practice containing the detailed technical requirements. The following approved documents have been updated: (a) Approved Vehicle Requirements (AVR) - L89; (b) Approved Requirements and test methods for the classification and packaging of dangerous goods for carriage (ARTM) - L88; (c) Approved Requirements for the packaging, labelling and carriage of radioactive material by rail (ARCRR) - L94; (d) Approved Requirements for the construction of vehicles intended for the carriage of explosives by road (AEVR) - L92; and (e) Approved Carriage List (ACL) - L90

  18. Industrial sources in Norway -- Regulations and requirements

    International Nuclear Information System (INIS)

    Saxeboel, G.

    2001-01-01

    On 12 May 2000, a new Act on radiation protection passed the Norwegian parliament. The report explains the requirements for the licensing process of sealed industrial sources and provides information, in particular, on the national inventory of industrial gauges, industrial radiography and logging sources. (author)

  19. 48 CFR 1646.301 - Contractor inspection requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contractor inspection requirements. 1646.301 Section 1646.301 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT... Clauses 1646.301 Contractor inspection requirements. The clause set forth at 1652.246-70 shall be inserted...

  20. 24 CFR 200.36 - Financial reporting requirements.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Financial reporting requirements. 200.36 Section 200.36 Housing and Urban Development Regulations Relating to Housing and Urban... Regulations § 200.36 Financial reporting requirements. The mortgagor must comply with the financial reporting...

  1. Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development.

    Science.gov (United States)

    Siegel, Rachael; Kim, Unkyu; Patke, Alina; Yu, Xin; Ren, Xiaodi; Tarakhovsky, Alexander; Roeder, Robert G

    2006-05-19

    OCA-B was originally identified as a nuclear transcriptional coactivator that is essential for antigen-driven immune responses. The later identification of a membrane bound, myristoylated form of OCA-B suggested additional, unique functions in B cell signaling pathways. This study has shown that OCA-B also functions in the pre-B1-to-pre-B2 cell transition and, most surprisingly, that it directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction-a transcriptional coactivator with a signaling kinase-occurs in the cytoplasm and directly regulates SYK stability. This study indicates that OCA-B is required for pre-BCR and BCR signaling at multiple stages of B cell development through its nontranscriptional regulation of SYK. Combined with the deregulation of OCA-B target genes, this may help explain the multitude of defects observed in B cell development and immune responses of Oca-b-/- mice.

  2. Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling.

    Science.gov (United States)

    Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G; Bezprozvanny, Ilya; Huber, Kimberly M; Wu, Jiang I

    2016-01-01

    Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Nanomaterials: Regulation and Risk Assessment

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Grieger, Khara Deanne; Baun, Anders

    2013-01-01

    , the Water Framework Directive, pharmaceuticals regulation, and the Novel Foods Regulation. Current regulation of nanomaterials entail three overall challenges: 1) limitations in regard to terminology and definitions of key terms such as a “substance,” “novel food,” etc.; 2) safety assessment requirements...

  4. Vernalization and the Chilling Requirement to Exit Bud Dormancy: Shared or Separate Regulation?

    Directory of Open Access Journals (Sweden)

    Amy M Brunner

    2014-12-01

    Full Text Available Similarities have long been recognized between vernalization, the prolonged exposure to cold temperatures that promotes the floral transition in many plants, and the chilling requirement to release bud dormancy in woody plants of temperate climates. In both cases the extended chilling period occurring during winter is used to coordinate developmental events to the appropriate seasonal time. However, whether or not these processes share common regulatory components and molecular mechanisms remain largely unknown. Both gene function and association genetics studies in Populus are beginning to answer this question. In Populus, studies have revealed that orthologs of the antagonistic flowering time genes FT and CEN/TFL1 might have central roles in both processes. We review Populus seasonal shoot development related to dormancy release and the floral transition and evidence for FT/TFL1-mediated regulation of these processes to consider the question of regulatory overlap. In addition, we discuss the potential for and challenges to integrating functional and population genomics studies to uncover the regulatory mechanisms underpinning these processes in woody plant systems.

  5. Intracellular pH regulation in unstimulated Calliphora salivary glands is Na+ dependent and requires V-ATPase activity.

    Science.gov (United States)

    Schewe, Bettina; Blenau, Wolfgang; Walz, Bernd

    2012-04-15

    Salivary gland cells of the blowfly Calliphora vicina have a vacuolar-type H(+)-ATPase (V-ATPase) that lies in their apical membrane and energizes the secretion of a KCl-rich primary saliva upon stimulation with serotonin (5-hydroxytryptamine). Whether and to what extent V-ATPase contributes to intracellular pH (pH(i)) regulation in unstimulated gland cells is unknown. We used the fluorescent dye BCECF to study intracellular pH(i) regulation microfluorometrically and show that: (1) under resting conditions, the application of Na(+)-free physiological saline induces an intracellular alkalinization attributable to the inhibition of the activity of a Na(+)-dependent glutamate transporter; (2) the maintenance of resting pH(i) is Na(+), Cl(-), concanamycin A and DIDS sensitive; (3) recovery from an intracellular acid load is Na(+) sensitive and requires V-ATPase activity; (4) the Na(+)/H(+) antiporter is not involved in pH(i) recovery after a NH(4)Cl prepulse; and (5) at least one Na(+)-dependent transporter and the V-ATPase maintain recovery from an intracellular acid load. Thus, under resting conditions, the V-ATPase and at least one Na(+)-dependent transporter maintain normal pH(i) values of pH 7.5. We have also detected the presence of a Na(+)-dependent glutamate transporter, which seems to act as an acid loader. Despite this not being a common pH(i)-regulating transporter, its activity affects steady-state pH(i) in C. vicina salivary gland cells.

  6. The French Space Operation Act: Technical Regulations

    Science.gov (United States)

    Trinchero, J. P.; Lazare, B.

    2010-09-01

    The French Space Operation Act(FSOA) stipulates that a prime objective of the National technical regulations is to protect people, property, public health and the environment. Compliance with these technical regulations is mandatory as of 10 December 2010 for space operations by French space operators and for space operations from French territory. The space safety requirements and regulations governing procedures are based on national and international best practices and experience. A critical design review of the space system and procedures shall be carried out by the applicant, in order to verify compliance with the Technical Regulations. An independent technical assessment of the operation is delegated to CNES. The principles applied when drafting technical regulations are as follows: requirements must as far as possible establish the rules according to the objective to be obtained, rather than how it is to be achieved; requirements must give preference to international standards recognised as being the state of the art; requirements must take previous experience into account. Technical regulations are divided into three sections covering common requirements for the launch, control and return of a space object. A dedicated section will cover specific rules to be applied at the Guiana Space Centre. The main topics addressed by the technical regulations are: operator safety management system; study of risks to people, property, public health and the Earth’s environment; impact study on the outer space environment: space debris generated by the operation; planetary protection.

  7. 16 CFR 301.3 - English language requirements.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false English language requirements. 301.3 Section... AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.3 English language requirements. All..., shall be set out in the English language. If labels, invoices or advertising matter contain any of the...

  8. 48 CFR 801.602-71 - Basic review requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Basic review requirements... GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.602-71 Basic review requirements. Contracting officers must obtain...

  9. Model Regulations for Decommissioning of Facilities

    International Nuclear Information System (INIS)

    2017-07-01

    The IAEA has systematic programmes to provide Member States with the guidance, services and training necessary for establishing a legal and regulatory framework, including the planning and implementation of decommissioning. The model regulations provided in this publication cover all aspects of the planning, conduct and termination of the decommissioning of facilities and management of the associated waste, in accordance with the relevant requirements of the IAEA safety standards. They provide a framework for establishing regulatory requirements and conditions of authorization to be incorporated into individual authorizations for the decommissioning of specific facilities. The model regulations also establish criteria to be used for assessing compliance with regulatory requirements. The publication will be of assistance to Member States in appraising the adequacy of their existing regulations and regulatory guides, and serves as a reference for those Member States developing regulations for the first time.

  10. New storm water regulations impact industry

    International Nuclear Information System (INIS)

    Gemar, C.

    1991-01-01

    In November 1990, new Environmental Protection Agency (EPA) regulations aimed at governing the discharge of storm water from industrial facilities became effective. Because some industrial runoff contains toxics and other pollutants, the EPA considers storm water a major source of water contamination. The new regulations will have a profound impact on the National Pollutant Discharge Elimination System (NPDES) permit requirements for industry. This paper summarizes the new storm water regulations, focusing on the requirements for industrial facilities. It also presents suggestions for compliance

  11. Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions

    NARCIS (Netherlands)

    Mittag, J.; Lyons, D.J.; Sällström, J.; Vujoviv, M.; Dudazy-Gralla, S.; Warner, A.; Wallis, K.; Alkemade, A.; Nordström, K.; Monyer, H.; Broberger, C.; Arner, A.; Vennström, B.

    2013-01-01

    Thyroid hormone is well known for its profound direct effects on cardiovascular function and metabolism. Recent evidence, however, suggests that the hormone also regulates these systems indirectly through the central nervous system. While some of the molecular mechanisms underlying the hormone’s

  12. Economic impact of potential NORM regulations

    International Nuclear Information System (INIS)

    Smith, G.E.; Fitzgibbon, T.; Karp, S.

    1995-01-01

    Oil and gas field wastes and sites contaminated with naturally occurring radioactive materials (NORM) have quickly become a focus of substantial attention by regulators both at the state and federal level. Although currently regulated in a number of states, the Environmental Protection Agency (EPA) has indicated a desire to develop federal regulations to address management and disposal of NORM-contaminated wastes. This paper provides a brief overview of current state NORM regulations, currently available technologies for managing and disposing NORM wastes, and the cost of employing these techniques. Based on these characterizations and alternative assumptions about the volume of NORM wastes, four alternative scenarios have been developed to bracket potential future NORM requirements. These scenarios have been used is the basis for an analysis of the potential economic and supply impacts of NORM requirements on the U.S. oil and gas industry. The results illustrate that a reasonable approach to regulation that focuses only on those NORM wastes that pose a risk and allows producers to use safe, low cost disposal methods (downhole or other) would have minimal economic impacts on the oil and gas industry. A very stringent regulatory approach that covered large volumes of wastes, required the use of higher cost disposal techniques, and required extensive site clean-up activities could have a substantial economic impact, resulting in a loss of up to 20 percent of U.S. oil production and 8 percent of U.S. gas production by 2000. The costs of compliance with these alternative approaches could range from $71 million to over $14 billion annually. Between these two cases lies the opportunity for regulators to develop requirements for management and disposal of NORM wastes that will address any environmental and human health risks posed at industry sites without imposing unnecessarily costly regulations on the U.S. oil and gas E ampersand P industry

  13. Two new pollution regulations introduced

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    A newly proposed regulation in Ontario will require the mandatory tracking of 358 airborne pollutants by the electricity sector as well as by other large industrial facilities such as iron and steel manufacturers and petroleum refiners. If passed, the regulation would make Ontario the first jurisdiction in the world to require monitoring and reporting of a full suite of major greenhouse gases, including smog and acid-rain causing emissions. The proposed regulation also provides for immediate public access to any reported information. Ontario residents can comment on the proposed regulation through the Environmental Bill of Rights registry. A new, more severe hazardous waste regulation will also take effect on March 31, 2001, whereby testing for 88 contaminants will be done according to a new standard called the Toxicity Characteristic Leaching Procedure (TCLP). This new regulation also introduces a new 'derived from' rule which requires that a listed hazardous waste keep its classification until it can be demonstrated otherwise. Ontario's list of hazardous wastes has been updated to include 129 new chemicals and industrial processes. The Ontario Ministry has also adopted the Canada-wide Standards for Particulate Matter and Ozone, as well as the Canada-wide Standards for mercury emissions from base metal smelters as well as from incineration of sewage sludge and municipal, medical, hazardous waste

  14. Up-regulation of insulin-like growth factor 2 by ketamine requires glycogen synthase kinase-3 inhibition

    Science.gov (United States)

    Grieco, Steven F.; Cheng, Yuyan; Eldar-Finkelman, Hagit; Jope, Richard S.; Beurel, Eléonore

    2016-01-01

    An antidepressant dose of the rapidly-acting ketamine inhibits glycogen synthase kinase-3 (GSK3) in mouse hippocampus, and this inhibition is required for the antidepressant effect of ketamine in learned helplessness depression-like behavior. Here we report that treatment with an antidepressant dose of ketamine (10 mg/kg) increased expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect that required ketamine-induced inhibition of GSK3. Ketamine also inhibited hippocampal GSK3 and increased expression of hippocampal IGF2 in mice when administered after the induction of learned helplessness. Treatment with the specific GSK3 inhibitor L803-mts was sufficient to up-regulate hippocampal IGF2 expression. Administration of IGF2 siRNA reduced ketamine's antidepressant effect in the learned helplessness paradigm. Mice subjected to the learned helplessness paradigm were separated into two groups, those that were resilient (non-depressed) and those that were susceptible (depressed). Non-depressed resilient mice displayed higher expression of IGF2 than susceptible mice. These results indicate that IGF2 contributes to ketamine's antidepressant effect and that IGF2 may confer resilience to depression-like behavior. PMID:27542584

  15. Discovery of a Splicing Regulator Required for Cell Cycle Progression

    Energy Technology Data Exchange (ETDEWEB)

    Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

    2013-02-01

    In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

  16. Cost regulation on the inspection of plants requiring supervision

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    According to annexes I to VI of this regulation, TUeVs (technical control authorities) (2nd sentence of para. 1 of sect. 24 c of the trade law) collect fees for inspections ordered by the authorities for the following plants and installations: 1. steam boiler plants, 2. pressure vessels, high-pressure gas vessels, feeders, 3. lifts, 4. acetylene plants, 5. plants for the storage, racking and transport of combustile liquids, 6. electrical installations on hazardous location. (orig.) [de

  17. 7 CFR 46.3 - License required.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE MARKETING OF PERISHABLE AGRICULTURAL COMMODITIES REGULATIONS (OTHER... considered to result in separate firms and, therefore, do not require separate licenses. ...

  18. Self-regulation through Goal Setting

    DEFF Research Database (Denmark)

    Koch, Alexander; Nafziger, Julia

    self-control problems. We show how goals permit self-regulation, but also that they are painful self-disciplining devices. Greater self-control problems therefore lead to stronger self-regulation through goals only up to a certain point. For severely present-biased preferences, the required goal...... for self-regulation is too painful and the individual rather gives up....

  19. Regulating chemicals: law, science, and the unbearable burdens of regulation.

    Science.gov (United States)

    Silbergeld, Ellen K; Mandrioli, Daniele; Cranor, Carl F

    2015-03-18

    The challenges of regulating industrial chemicals remain unresolved in the United States. The Toxic Substances Control Act (TSCA) of 1976 was the first legislation to extend coverage to the regulation of industrial chemicals, both existing and newly registered. However, decisions related to both law and science that were made in passing this law inevitably rendered it ineffectual. Attempts to fix these shortcomings have not been successful. In light of the European Union's passage of innovative principles and requirements for chemical regulation, it is no longer possible to deny the opportunity and need for reform in US law and practice.

  20. 48 CFR 311.7000 - Defining electronic information technology requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Defining electronic information technology requirements. 311.7000 Section 311.7000 Federal Acquisition Regulations System HEALTH... Accessibility Standards 311.7000 Defining electronic information technology requirements. HHS staff that define...

  1. The ionising radiation (medical exposure) regulations - IR (ME) R, Malta

    International Nuclear Information System (INIS)

    Desai, R.; Brejza, P.; Cremona, J.

    2004-01-01

    Full text: The regulations in Malta at present are in draft stage. These regulations partially implement European Council Directive 97/43/Euratom. This Directive lays down the basic measurements for the health and protection of individuals against dangers of ionising radiation in relation to medical exposure. The regulations impose duties on persons administering radiations, to protect people from unnecessary exposure whether as part of their own medical diagnosis, treatment or as part of occupational health worker for health screening, medico-legal procedures, voluntary participation in research etc. These regulations also apply to individuals who help other individuals undergoing medical exposure. Main provisions 1. Regulation 2 contains the definitions of 28 terms used in these regulations. 2. Regulation 3.1 and 3.2 sets out the medical exposures to which the regulations apply. 3. Regulation 4 requires approval of medical exposures due to medical research, from radiation protection board of Malta. 4. Regulation 5 prohibits new procedures involving medical exposure unless it has been justified in advance. 5. Regulation 6 provides conditions justifying medical exposures. It prohibits any medical exposure from being carried out which has not been justified and authorized and sets out matters to be taken into account for justification. 6. Regulation 7 requires that practitioner justifies the exposure, shall pay special attention towards (a) exposure from medical research procedures where there is no direct health benefit to the individual undergoing exposure, (b) exposures for medico-legal purposes; (c) exposures to pregnant or possible pregnant women and (d) exposures to breast-feeding women. 7. Regulation 8.1 to 8.3 prohibit any medical exposure from being carried out which has not been justified and sets out matters to be taken for justification 8. Regulation 8.4 prohibits an exposure if it cannot be justified. 9. Regulation 9 requires the employer to provide a

  2. Impacts and Compliance Implementation Plans and Required Deviations for Toxic Substance Control Act (TSCA) Regulation of Double Shell Tanks (DST)

    International Nuclear Information System (INIS)

    MULKEY, C.H.

    2000-01-01

    In May 2000, the U.S. Department of Energy, Office of River Protection (DOE-ORP) and the U.S. Environmental Protection Agency (EPA) held meetings regarding the management of polychlorinated biphenyls (PCBs) in the Hanford tank waste. It was decided that the radioactive waste currently stored in the double-shell tanks (DSTs) contain waste which will become subject to the Toxic Substance Control Act (TSCA) (40 CFR 761). As a result, DOE-ORP directed the River Protection Project tank farm contractor (TFC) to prepare plans for managing the PCB inventory in the DSTs. Two components of the PCB management plans are this assessment of the operational impacts of TSCA regulation and the identifications of deviations from TSCA that are required to accommodate tank farm unique limitations. This plan provides ORP and CH2M HILL Hanford Group, Inc. (CHG) with an outline of TSCA PCB requirements and their applicability to tank farm activities, and recommends a compliance/implementation approach. Where strict compliance is not possible, the need for deviations from TSCA PCB requirements is identified. The purpose of assembling this information is to enhance the understanding of PCB management requirements, identify operational impacts and select impact mitigation strategies. This information should be useful in developing formal agreements with EPA where required

  3. Requirements to be met by the operation manual

    International Nuclear Information System (INIS)

    1981-03-01

    The rule applies to the contents and the lay-out of the operating manual for stationary nuclear power plants. The draft contains: 1. General requirement to be met by the contents of the operating manual. The operating manual to be arranged in 4 parts (part 1: internal rules and regulations; part 2: operation overall plant; part 3: incidents; part 4: operation systems). Safety specifications to be included in the manual, the exemption being the system of technical documentation. 2. General requirements to be met by the lay-out of the operating manual. Comprehensibility; legibility; structure and subdivisions; arrangement of the instructions and design of the manuals cover. 3. Requirements to be met by part 1. Defining the various internal rules and regulations (personnel management); rules and regulations concerning inspections and shift work; maintenance and repair; radiation protection; guard duty and admission; alarm; fire protection; first aid. 4. Requirements to be met by part 2. Provisions and operational limitations; limit values important from the point of view of safety; normal operation; anomalous operation; in-service inspections. 6. Requirements to be met by part 3. 7. Annex: Rules, regulations and stipulations mentioned in the rule draft. (orig.)

  4. Pdlim7 Regulates Arf6-Dependent Actin Dynamics and Is Required for Platelet-Mediated Thrombosis in Mice.

    Directory of Open Access Journals (Sweden)

    Alexander E Urban

    Full Text Available Upon vessel injury, platelets become activated and rapidly reorganize their actin cytoskeleton to adhere to the site of endothelial damage, triggering the formation of a fibrin-rich plug to prevent further blood loss. Inactivation of Pdlim7 provides the new perspective that regulation of actin cytoskeletal changes in platelets is dependent on the encoded PDZ-LIM protein. Loss-of-function of Pdlim7 triggers hypercoagulopathy and causes significant perinatal lethality in mice. Our in vivo and in vitro studies reveal that Pdlim7 is dynamically distributed along actin fibers, and lack of Pdlim7 leads to a marked inability to rearrange the actin cytoskeleton. Specifically, the absence of Pdlim7 prevents platelets from bundling actin fibers into a concentric ring that defines the round spread shape of activated platelets. Similarly, in mouse embryonic fibroblasts, loss of Pdlim7 abolishes the formation of stress fibers needed to adopt the typical elongated fibroblast shape. In addition to revealing a fundamental cell biological role in actin cytoskeletal organization, we also demonstrate a function of Pdlim7 in regulating the cycling between the GTP/GDP-bound states of Arf6. The small GTPase Arf6 is an essential factor required for actin dynamics, cytoskeletal rearrangements, and platelet activation. Consistent with our findings of significantly elevated initial F-actin ratios and subsequent morphological aberrations, loss of Pdlim7 causes a shift in balance towards an increased Arf6-GTP level in resting platelets. These findings identify a new Pdlim7-Arf6 axis controlling actin dynamics and implicate Pdlim7 as a primary endogenous regulator of platelet-dependent hemostasis.

  5. 20 CFR 302.6 - Publication requirements.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Publication requirements. 302.6 Section 302.6 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT QUALIFIED EMPLOYEE § 302.6 Publication requirements. (a) Publication of base year compensation requirement...

  6. Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth

    Science.gov (United States)

    Low, Malcolm J.; Otero-Corchon, Veronica; Parlow, Albert F.; Ramirez, Jose L.; Kumar, Ujendra; Patel, Yogesh C.; Rubinstein, Marcelo

    2001-01-01

    Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst–/–) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst–/– compared with Smst+/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst–/– mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst-/- mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth. PMID:11413165

  7. Future directions in water quality regulations

    International Nuclear Information System (INIS)

    Pontius, F.W.

    1997-01-01

    The Safe Drinking Water Act amendments of 1996 have imposed new requirements on the US Environmental Protection Agency (USEPA) to establish drinking water regulations. The regulatory process has been revised and now requires the use of sound science. Costs, benefits, and competing risks may also be considered. Current regulations for fluoride, volatile organic chemicals, total coliforms, surface water treatment, Phase 2 and Phase 5 synthetic organic and inorganic contaminants, and lead and copper remain basically unchanged. New deadlines are established for the regulation of arsenic, sulfate, radon, disinfectants and disinfection by-products, enhanced surface water treatment, and groundwater disinfection

  8. Cost-optimal levels for energy performance requirements

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Aggerholm, Søren; Kluttig-Erhorn, Heike

    2011-01-01

    The CA conducted a study on experiences and challenges for setting cost optimal levels for energy performance requirements. The results were used as input by the EU Commission in their work of establishing the Regulation on a comparative methodology framework for calculating cost optimal levels...... of minimum energy performance requirements. In addition to the summary report released in August 2011, the full detailed report on this study is now also made available, just as the EC is about to publish its proposed Regulation for MS to apply in their process to update national building requirements....

  9. Transcription factor VdCmr1 is required for pigment production, protection from UV irradiation, and regulates expression of melanin biosynthetic genes in Verticillium dahliae.

    Science.gov (United States)

    Wang, Yonglin; Hu, Xiaoping; Fang, Yulin; Anchieta, Amy; Goldman, Polly H; Hernandez, Gustavo; Klosterman, Steven J

    2018-04-01

    Verticillium dahliae is a soilborne fungus that causes vascular wilt diseases on numerous plant species worldwide. The production of darkly melanized microsclerotia is crucial in the disease cycle of V. dahliae, as these structures allow for long-term survival in soil. Previously, transcriptomic and genomic analysis identified a cluster of genes in V. dahliae that encodes some dihydroxynaphthalene (DHN) melanin biosynthetic pathway homologues found in related fungi. In this study, we explored the roles of cluster-specific transcription factor VdCmr1, as well as two other genes within the cluster encoding a polyketide synthase (VdPKS1) and a laccase (VdLac1), enzymes at initial and endpoint steps in DHN melanin production. The results revealed that VdCmr1 and VdPKS1 are required for melanin production, but neither is required for microsclerotia production. None of the three genes were required for pathogenesis on tobacco and lettuce. Exposure of ΔVdCmr1 and wild-type strains to UV irradiation, or to high temperature (40 °C), revealed an approx. 50 % reduction of survival in the ΔVdCmr1 strain, relative to the wild-type strain, in response to either condition. Expression profiles revealed that expression of some melanin biosynthetic genes are in part dependent on VdCmr1. Combined data indicate VdCmr1 is a key regulator of melanin biosynthesis, and that via regulation of melanogenesis, VdCmr1 affects survival of V. dahliae in response to abiotic threats. We conclude with a model showing regulation of VdCmr1 by a high osmolarity glycerol response (Hog)-type MAP kinase pathway.

  10. The Regulation of Food Science and Technology Professions in Europe

    Directory of Open Access Journals (Sweden)

    Rui Costa

    2014-04-01

    Full Text Available The regulation of a profession is justified when it improves consumer protection and public health. Higher education food science and technology (FST degrees, widely offered in many universities in Europe open to a wide range of jobs in the food sectors where the employees could cover different positions, roles and carry out diverse activities dealing with the food production and the quality and safety of the food products. This work reviews the state of the art of the FST regulated professions requiring higher education qualifications in the European countries. The research was carried out by collecting specific information on regulated professions by contacting unions, professional associations, public servant categories/professions, and by visiting national and EU websites.  The data collected for each regulated profession were: country, training/education required, date of implementation of regulation, professional training (if required, capability test (if required and acts required by law to be signed by a regulated professional. Only professions that required a higher education diploma were included in this search. Few countries were found to have a regulated profession in FST, in particular: Food Engineering (Turkey, Food Technologist (Greece, Iceland, Italy and Slovenia, and Oenologist (Italy, Portugal and Spain. FST regulated professions in Europe are thus scarce and have a rather limited history. The Food Technologist in Italy and the Food Engineer in Turkey were found to be the only completely regulated professions found in Europe. Food and professional regulation have been evolved over the years and raised the debate on the regulation of FST professions. Academia as well as other policymakers has to further contribute to this discussion to keep high the standards for quality of education and training of the qualified workforce and professionals in the food sector.

  11. 7 CFR 1942.117 - General requirements.

    Science.gov (United States)

    2010-01-01

    ... § 1942.117 General requirements. (a) Reserve requirements. Loans under this subpart are subject to the... 7 Agriculture 13 2010-01-01 2009-01-01 true General requirements. 1942.117 Section 1942.117 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...

  12. 7 CFR 800.25 - Required elevator and merchandising records.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Required elevator and merchandising records. 800.25 Section 800.25 Agriculture Regulations of the Department of Agriculture (Continued) GRAIN INSPECTION... REGULATIONS Recordkeeping and Access to Facilities § 800.25 Required elevator and merchandising records. (a...

  13. Ionising radiation: a guide to the Regulations

    International Nuclear Information System (INIS)

    Hughes, Donald.

    1986-01-01

    The author explains the basic requirements on health and safety personnel in relation to the Ionising Radiations Regulations 1985. The outline paper is presented under the following headings: Dose assessment, Interpretation and general regulations 1-5, Dose limitation regulations 6 and 7, Regulation of work - regulations 8-12, Dosimetry and medical surveillance - regulations 13-17, summary of records to be kept, entry to controlled areas, Control of radioactive substances -regulations 18-23, Monitoring of radiation regulation 24, Assessments and notifications - regulations 25-31, Safety of articles and equipment - regulations 32-34, Other guidance. (U.K.)

  14. Radiation Safety (General) Regulations 1983 (Western Australia)

    International Nuclear Information System (INIS)

    1983-01-01

    The provisions of the Regulations cover, inter alia, the general precautions and requirements relating to radiation safety of the public and radiation workers and registration of irradiating apparatus or premises on which such apparatus is operated. In addition, the Regulations set forth requirements for the operation of such apparatus and for the premises involved. (NEA) [fr

  15. 16 CFR 303.4 - English language requirement.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false English language requirement. 303.4 Section... AND REGULATIONS UNDER THE TEXTILE FIBER PRODUCTS IDENTIFICATION ACT § 303.4 English language requirement. All required information shall be set out in the English language. If the required information...

  16. 12 CFR 204.7 - Supplemental reserve requirement.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Supplemental reserve requirement. 204.7 Section... RESERVE REQUIREMENTS OF DEPOSITORY INSTITUTIONS (REGULATION D) § 204.7 Supplemental reserve requirement... reserve requirement on every depository institution of not more than 4 percent of its total transaction...

  17. Franchise Values, Regulatory Monitoring, and Capital Requirements in Optimal Bank Regulation

    DEFF Research Database (Denmark)

    Andersen, Thomas Barnebeck; Harr, Thomas

    2008-01-01

    This paper demonstrates that financial deregulation is likely to make standard prudential regulatory instruments less effective in curbing excessive risk-taking incentives among banks. This has interesting implications for optimal bank regulation. When there is an increase in competition, the opt...

  18. 29 CFR 1620.32 - Recordkeeping requirements.

    Science.gov (United States)

    2010-07-01

    ... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.32 Recordkeeping requirements. (a) Employers having employees subject to the Act are required to keep records in... subject to the equal pay provisions of the Act shall maintain and preserve all records required by the...

  19. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    Within hunting, wildlife populations are estimated to be too high in many countries which is assumed to be due to the market failure, that each hunter harvests too little compared to what the regulator wants. This may be due to the existing regulation which, among other things, requires knowledge...... by an individual, variable tax rate. The variable tax rate is, among other things, based on the difference in marginal value of the population between the hunter and the regulator. The paper shows that the population tax/subsidy secures a first-best optimum. Thus, the population tax is a good alternative...... to the existing regulation....

  20. 12 CFR 204.9 - Emergency reserve requirement.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Emergency reserve requirement. 204.9 Section... RESERVE REQUIREMENTS OF DEPOSITORY INSTITUTIONS (REGULATION D) § 204.9 Emergency reserve requirement. (a..., additional reserve requirements on depository institutions at any ratio on any liability upon a finding by at...

  1. Melanocortin 4 receptor is not required for estrogenic regulations on energy homeostasis and reproduction

    Science.gov (United States)

    Brain estrogen receptor-a (ERa) is essential for estrogenic regulation of energy homeostasis and reproduction. We previously showed that ERa expressed by pro-opiomelanocortin (POMC) neurons mediates estrogen's effects on food intake, body weight, negative regulation of hypothalamic–pituitary–gonadal...

  2. 78 FR 70025 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Science.gov (United States)

    2013-11-22

    ... and Procedures AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION... proposed information collection; (c) ways to enhance the quality, utility, and clarity of the information..., withhold, or withdraw purchasing system approval at the conclusion of a purchasing system review...

  3. Waste management system requirements document

    International Nuclear Information System (INIS)

    1991-02-01

    This volume defines the top level requirements for the Mined Geologic Disposal System (MGDS). It is designed to be used in conjunction with Volume 1 of the WMSR, General System Requirements. It provides a functional description expanding the requirements allocated to the MGDS in Volume 1 and elaborates on each requirement by providing associated performance criteria as appropriate. Volumes 1 and 4 of the WMSR provide a minimum set of requirements that must be satisfied by the final MGDS design. This document sets forth specific requirements that must be fulfilled. It is not the intent or purpose of this top level document to describe how each requirement is to be satisfied in the final MGDS design. Each subsequent level of the technical document hierarchy must provide further guidance and definition as to how each of these requirements is to be implemented in the design. It is expected that each subsequent level of requirements will be significantly more detailed. Section 2 of this volume provides a functional description of the MGDS. Each function is addressed in terms of requirements, and performance criteria. Section 3 provides a list of controlling documents. Each document cited in a requirement of Chapter 2 is included in this list and is incorporated into this document as a requirement on the final system. The WMSR addresses only federal requirements (i.e., laws, regulations and DOE orders). State and local requirements are not addressed. However, it will be specifically noted at the potentially affected WMSR requirements that there could be additional or more stringent regulations imposed by a state or local requirements or administering agency over the cited federal requirements

  4. 76 FR 79529 - Community Reinvestment Act Regulations

    Science.gov (United States)

    2011-12-22

    ... ``agencies'') are amending their Community Reinvestment Act (CRA) regulations to adjust the asset-size... ``intermediate small savings association.'' As required by the CRA regulations, the adjustment to the threshold... Description of the Joint Final Rule The agencies' CRA regulations establish CRA performance standards for...

  5. Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Midori [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Yamamoto, Ayumu [Department of Chemistry, Shizuoka University, 836 Ohya, Suruga-ku, Sizuoka 422-8529 (Japan); Murakami-Tonami, Yuko; Nakanishi, Makoto; Yoshida, Takashi [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aiba, Hirofumi [Laboratory of Molecular Microbiology, School of Agriculture, Nagoya University, Chikusa-ku, Nagoya 464-8601 (Japan); Murakami, Hiroshi, E-mail: hmura@med.nagoya-cu.ac.jp [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2009-10-23

    The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2{sup +}. The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint by regulating Mad2p.

  6. Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

    International Nuclear Information System (INIS)

    Shimada, Midori; Yamamoto, Ayumu; Murakami-Tonami, Yuko; Nakanishi, Makoto; Yoshida, Takashi; Aiba, Hirofumi; Murakami, Hiroshi

    2009-01-01

    The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2 + . The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint by regulating Mad2p.

  7. 27 CFR 70.411 - Imposition of taxes, qualification requirements, and regulations.

    Science.gov (United States)

    2010-04-01

    ... (including activities incident thereto) of distilled spirits plants for the production and/or warehousing... use in making the necessary computation from gauge data. (5) Rules of practice in permit proceedings... regulations relating to the production, bonded warehousing, and withdrawal of distilled spirits, and denatured...

  8. 76 FR 65411 - Specialty Crops; Import Regulations; Proposed Pistachio Import Requirements

    Science.gov (United States)

    2011-10-21

    ..., or E-mail: [email protected] or [email protected] . Small businesses may request... the proposed regulations, ``pistachio'' would mean the nut of the pistachio tree, Pistachia vera.... Pages 326-359. \\5\\ Eaton, David L.; Jennifer E. Hobden; and Bruce J. Kelman. 2002. Aflatoxin in...

  9. 77 FR 43076 - Federal Acquisition Regulation; Information Collection; Value Engineering Requirements

    Science.gov (United States)

    2012-07-23

    ... respond, through the use of appropriate technological collection techniques or other forms of information... collection. All comments received will be posted without change to http://www.regulations.gov , including any personal and/or business confidential information provided. FOR FURTHER INFORMATION CONTACT: Mr. Curtis E...

  10. 48 CFR 301.606-73 - Requirements for continuous learning maintenance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Requirements for continuous learning maintenance. 301.606-73 Section 301.606-73 Federal Acquisition Regulations System HEALTH..., and Responsibilities 301.606-73 Requirements for continuous learning maintenance. Designated Project...

  11. Human regulator of telomere elongation helicase 1 (RTEL1) is required for the nuclear and cytoplasmic trafficking of pre-U2 RNA

    OpenAIRE

    Schertzer , Michael; Jouravleva , Karina; Perderiset , Mylène; Dingli , Florent; Loew , Damarys; Le Guen , Tangui; Bardoni , Barbara; De Villartay , Jean-Pierre; Revy , Patrick; Londono-Vallejo , Arturo

    2015-01-01

    International audience; Hoyeraal-Hreidarsson syndrome (HHS) is a severe form of Dyskeratosis congenita characterized by developmental defects, bone marrow failure and im-munodeficiency and has been associated with telom-ere dysfunction. Recently, mutations in Regulator of Telomere ELongation helicase 1 (RTEL1), a helicase first identified in Mus musculus as being responsible for the maintenance of long telomeres, have been identified in several HHS patients. Here we show that RTEL1 is require...

  12. 7 CFR 33.10 - Minimum requirements.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Regulations § 33.10 Minimum requirements. No person shall... shipment of apples to any foreign destination unless: (a) Apples grade at least U.S. No. 1 or U.S. No. 1...

  13. [Consideration of Mobile Medical Device Regulation].

    Science.gov (United States)

    Peng, Liang; Yang, Pengfei; He, Weigang

    2015-07-01

    The regulation of mobile medical devices is one of the hot topics in the industry now. The definition, regulation scope and requirements, potential risks of mobile medical devices were analyzed and discussed based on mobile computing techniques and the FDA guidance of mobile medical applications. The regulation work of mobile medical devices in China needs to adopt the risk-based method.

  14. 75 FR 78160 - Requirement of a Statement Disclosing Uncertain Tax Positions

    Science.gov (United States)

    2010-12-15

    ... amendments to the Income Tax Regulations (26 CFR part 1) under section 6012 relating to the returns of income... every person liable for income tax to make the returns required by regulation. Section 6012 requires... corporations to file a schedule disclosing uncertain tax positions related to the tax return as required by the...

  15. 78 FR 18795 - Truth in Lending (Regulation Z)

    Science.gov (United States)

    2013-03-28

    ... of credit at account opening. The consumer is also required to pay a cash advance fee that is equal... amount equal to any fees the consumer was required to pay with respect to the account that exceed 25... Regulation Z, which implements the Truth in Lending Act, and the Official Interpretations of the regulation...

  16. Constructions complying with tightened Danish sound insulation requirements for new housing

    OpenAIRE

    Rasmussen, Birgit; Hoffmeyer, Dan

    2010-01-01

    New sound insulation requirements in Denmark in 2008 New Danish Building Regulations with tightened sound insulation requirements were introduced in 2008 (and in 2010 with unchanged acoustic requirements). Compared to the Building Regulations from 1995, the airborne sound insulation requirements were 2 –3 dB stricter and the impact sound insulation requirements 5 dB stricter. The limit values are given using the descriptors R’w and L’n,w as before. For the first time, acoustic requirements fo...

  17. SOR/83-77, Physical Security Regulations

    International Nuclear Information System (INIS)

    1983-01-01

    These Regulations establish and require the maintenance of security systems, equipment and procedures to implement Canada's international obligations regarding security at those nuclear facilities. The Regulations, which determine the different areas in a nuclear facility, provide for the establishment of security barriers around the ''protected areas'' occupied by facilities and prescribe that the licensees (operators) are required to keep the facilities for which they hold a licence under constant surveillance. They must also make arrangements for a response force - a local, provincial or federal police force detachment or similar force - to provide assistance where necessary. No person may enter a protected area without written authorization from the licensee concerned. Inspectors appointed under the Atomic Energy Control Regulations or designated under an agreement between Canada and the IAEA may be granted an authorization to enter such areas to discharge their duties. The Regulations have been amended by SOR/84-81 of 12 January 1988 to add certain requirements concerning documentary evidence and the duties of the board; by SOR/85-1016 of 25 October 1985 to revise the definition of response force and provide other clarifications; by SOR/91-585 of 10 October 1991 to clarify wording in French. (NEA)

  18. 40 CFR 233.31 - Coordination requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Coordination requirements. 233.31 Section 233.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING 404 STATE PROGRAM REGULATIONS Program Operation § 233.31 Coordination requirements. (a) If a proposed...

  19. Novel insights into iron regulation and requirement in marine medaka Oryzias melastigma.

    Science.gov (United States)

    Wang, Jian; Wang, Wen-Xiong

    2016-05-24

    Iron (Fe) is an essential trace element for marine fish. However, our knowledge of Fe requirements at different development stages of marine fish is still limited. Here, we reported the efficient Fe absorption strategies adopted by larval fish under different dietary Fe supplementary levels (i.e., 0-640 mg/kg). Biokinetically, the larval fish controlled their dietary Fe assimilation efficiency (AE, 1.6-18.5%), and enhanced their waterborne Fe uptake (ca. 2.5 fold change of uptake rate constant) once the dietary Fe was deficient (i.e., 27.4 mg Fe/kg feed). Transcriptionally, the expression of hepcidin1 (hep1; Fe regulator; i.e., 2.3-15.7 fold change) in larval fish was positively correlated with the Fe supplementary levels. Comparatively, the female adult fish were poor in assimilating the added Fe source (i.e., ferric form) with similar life-sustainable levels of Fe (i.e., 0.046-0.12 μg/g/d assimilated for Fe supplementary levels of 27.4, 162 and 657 mg Fe/kg feed). The overall feeding experiments suggested that dietary net Fe flux sufficient for the normal growth of larval medaka was 0.71-1.75 μg/g/d (i.e., 83.9 mg Fe/kg feed), consistent with the modeled value (i.e., 1.09-2.16 μg/g/d). In female adults, the estimated essential net Fe flux was 0.88-0.90 μg/g/d.

  20. 48 CFR 849.111-70 - Required review.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Required review. 849.111... MANAGEMENT TERMINATION OF CONTRACTS General Principles 849.111-70 Required review. (a) FAR 49.111 requires each agency to establish procedures, when necessary, for the administrative review of proposed...

  1. 48 CFR 9905.501-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.501-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.501-40 Section 9905.501-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  2. 48 CFR 9905.502-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.502-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.502-40 Section 9905.502-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  3. 48 CFR 9905.506-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.506-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.506-40 Section 9905.506-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  4. 12 CFR 204.4 - Computation of required reserves.

    Science.gov (United States)

    2010-01-01

    ... RESERVE REQUIREMENTS OF DEPOSITORY INSTITUTIONS (REGULATION D) § 204.4 Computation of required reserves. (a) In determining the reserve requirement under this part, the amount of cash items in process of... reserves are computed by applying the reserve requirement ratios below to net transaction accounts...

  5. 77 FR 51686 - Specialty Crops; Import Regulations; New Pistachio Import Requirements

    Science.gov (United States)

    2012-08-27

    ... the new regulation, ``pistachio'' means the nut of the pistachio tree, Pistachia vera, whether inshell... Order No. 983. 2002. Pages 326-359. \\5\\ Eaton, David L.; Jennifer E. Hobden; and Bruce J. Kelman. 2002..., and New Mexico. AMS is committed to complying with the E-Government Act, to promote the use of the...

  6. SOR/89-426, Transport Packaging of Radioactive Materials Regulations, amendment

    International Nuclear Information System (INIS)

    1989-01-01

    These Regulations of 24 August 1989 amend the Transport Packaging of Radioactive Materials Regulations by clarifying the text and specifying certain requirements. In particular certain definitions have been replaced, namely those of ''Fissile Class III package'' and ''Special form radioactive material''. Also, this latter material may not be carried without a certificate attesting that it meets the requirements of the Regulations. (NEA)

  7. 7 CFR 926.17 - Reporting requirements.

    Science.gov (United States)

    2010-01-01

    ... Federal cranberry marketing order (7 CFR Part 926) shall be required to submit four times annually, for... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... RECORDKEEPING REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.17...

  8. 15 CFR 971.418 - Diligence requirements.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Diligence requirements. 971.418 Section 971.418 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued...: Terms, Conditions and Restrictions Terms, Conditions and Restrictions § 971.418 Diligence requirements...

  9. 49 CFR 601.45 - Required information.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Required information. 601.45 Section 601.45 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ORGANIZATION, FUNCTIONS, AND PROCEDURES Emergency Procedures for Public Transportation Systems § 601.45 Required...

  10. Regulation of the Osem gene by abscisic acid and the transcriptional activator VP1: analysis of cis-acting promoter elements required for regulation by abscisic acid and VP1.

    Science.gov (United States)

    Hattori, T; Terada, T; Hamasuna, S

    1995-06-01

    Osem, a rice gene homologous to the wheat Em gene, which encodes one of the late-embryogenesis abundant proteins was isolated. The gene was characterized with respect to control of transcription by abscisic acid (ABA) and the transcriptional activator VP1, which is involved in the ABA-regulated gene expression during late embryo-genesis. A fusion gene (Osem-GUS) consisting of the Osem promoter and the bacterial beta-glucuronidase (GUS) gene was constructed and tested in a transient expression system, using protoplasts derived from a suspension-cultured line of rice cells, for activation by ABA and by co-transfection with an expression vector (35S-Osvp1) for the rice VP1 (OSVP1) cDNA. The expression of Osem-GUS was strongly (40- to 150-fold) activated by externally applied ABA and by over-expression of (OS)VP1. The Osem promoter has three ACGTG-containing sequences, motif A, motif B and motif A', which resemble the abscisic acid-responsive element (ABRE) that was previously identified in the wheat Em and the rice Rab16. There is also a CATGCATG sequence, which is known as the Sph box and is shown to be essential for the regulation by VP1 of the maize anthocyanin regulatory gene C1. Focusing on these sequence elements, various mutant derivatives of the Osem promoter in the transient expression system were assayed. The analysis revealed that motif A functions not only as an ABRE but also as a sequence element required for the regulation by (OS)VP1.

  11. Investigation on regulatory requirements for radiation safety management

    International Nuclear Information System (INIS)

    Han, Eun Ok; Choi, Yoon Seok; Cho, Dae Hyung

    2013-01-01

    NRC recognizes that efficient management of radiation safety plan is an important factor to achieve radiation safety service. In case of Korea, the contents to perform the actual radiation safety management are legally contained in radiation safety management reports based on the Nuclear Safety Act. It is to prioritize the importance of safety regulations in each sector in accordance with the current situation of radiation and radioactive isotopes-used industry and to provide a basis for deriving safety requirements and safety regulations system maintenance by the priority of radiation safety management regulations. It would be helpful to achieve regulations to conform to reality based on international standards if consistent safety requirements is developed for domestic users, national standards and international standards on the basis of the results of questions answered by radiation safety managers, who lead on-site radiation safety management, about the priority of important factors in radioactive sources use, sales, production, moving user companies, to check whether derived configuration requirements for radiation safety management are suitable for domestic status

  12. 47 CFR 76.925 - Costs of franchise requirements.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Costs of franchise requirements. 76.925 Section... MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.925 Costs of franchise requirements. (a) Franchise requirement costs may include cost increases required by the franchising authority in...

  13. The ciliogenic transcription factor RFX3 regulates early midline distribution of guidepost neurons required for corpus callosum development.

    Directory of Open Access Journals (Sweden)

    Carine Benadiba

    Full Text Available The corpus callosum (CC is the major commissure that bridges the cerebral hemispheres. Agenesis of the CC is associated with human ciliopathies, but the origin of this default is unclear. Regulatory Factor X3 (RFX3 is a transcription factor involved in the control of ciliogenesis, and Rfx3-deficient mice show several hallmarks of ciliopathies including left-right asymmetry defects and hydrocephalus. Here we show that Rfx3-deficient mice suffer from CC agenesis associated with a marked disorganisation of guidepost neurons required for axon pathfinding across the midline. Using transplantation assays, we demonstrate that abnormalities of the mutant midline region are primarily responsible for the CC malformation. Conditional genetic inactivation shows that RFX3 is not required in guidepost cells for proper CC formation, but is required before E12.5 for proper patterning of the cortical septal boundary and hence accurate distribution of guidepost neurons at later stages. We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8 at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene family zinc finger 3 (GLI3 repressor to activator forms. We demonstrate on brain explant cultures that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3 mutants. This study unravels a crucial role of RFX3 during early brain development by indirectly regulating GLI3 activity, which leads to FGF8 upregulation and ultimately to disturbed distribution of guidepost neurons required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel understandings of the mechanisms that underlie CC agenesis in ciliopathies.

  14. [Revision of the drinking water regulations].

    Science.gov (United States)

    Hauswirth, S

    2011-11-01

    The revision the Drinking Water Regulations will come into effect on 01.11.2011. Surveillance authorities and owners of drinking water supply systems had hoped for simplifications and reductions because of the new arrangements. According to the official statement for the revision the legislature intended to create more clarity, consider new scientific findings, to change regulations that have not been proved to close regulatory gaps, to deregulate and to increase the high quality standards. A detailed examination of the regulation text, however, raises doubts. The new classification of water supply systems requires different modalities of registration, water analyses and official observation, which will complicate the work of the authorities. In particular, the implementation of requirements of registration and examination for the owners of commercial and publicly-operated large hot-water systems in accordance with DVGW Worksheet W 551 requires more effort. According to the estimated 30 000 cases of legionellosis in Germany the need for a check of such systems for Legionella, however, is not called into question. Furthermore, the development of sampling plans and the monitoring of mobile water supply systems requires more work for the health authorities. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Benchmarking and Regulation

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    . The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  16. Constructions complying with tightened Danish sound insulation requirements for new housing

    DEFF Research Database (Denmark)

    Rasmussen, Birgit; Hoffmeyer, Dan

    New sound insulation requirements in Denmark in 2008 New Danish Building Regulations with tightened sound insulation requirements were introduced in 2008 (and in 2010 with unchanged acoustic requirements). Compared to the Building Regulations from 1995, the airborne sound insulation requirements...... were 2 –3 dB stricter and the impact sound insulation requirements 5 dB stricter. The limit values are given using the descriptors R’w and L’n,w as before. For the first time, acoustic requirements for dwellings are not found as figures in the Building Regulations. Instead, it is stated......), Denmark. [2] "Lydisolering mellem boliger – Nybyggeri" (Sound insulation between dwellings – Newbuild)". Publication expected in April 2011. The guideline is a part of a series of seven new SBi acoustic guidelines. Project leader Birgit Rasmussen. The series shall replace the existing guidelines 1984...

  17. 5 CFR 5.1 - Civil Service regulations.

    Science.gov (United States)

    2010-01-01

    ... if such a variation is within the spirit of the regulations, and the efficiency of the Government and... hardship involved, (b) what is permitted in place of what is required by regulations, (c) the circumstances...

  18. 75 FR 10567 - Commerce Acquisition Regulation (CAR)

    Science.gov (United States)

    2010-03-08

    ... regulations, Federal acquisition regulations, Government procurement, Government contracts, Procurement, Reporting and recordkeeping requirements. 48 CFR Part 1302 Definitions, Government procurement, Terms. 48 CFR Part 1303 Antitrust, Conflict of interests, Ethical conduct, Government procurement, Reporting and...

  19. 15 CFR 970.517 - Diligence requirements.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Diligence requirements. 970.517 Section 970.517 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued..., Conditions and Restrictions Terms, Conditions, and Restrictions § 970.517 Diligence requirements. The terms...

  20. 7 CFR 97.8 - Specimen requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Specimen requirements. 97.8 Section 97.8 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... required by the examiner to furnish representative specimens of the variety, or its flower, fruit, or seeds...

  1. 12 CFR 370.9 - Recordkeeping requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Recordkeeping requirements. 370.9 Section 370.9 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY TEMPORARY LIQUIDITY GUARANTEE PROGRAM § 370.9 Recordkeeping requirements. The FDIC will establish procedures...

  2. 48 CFR 509.306 - Solicitation requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Solicitation requirements... COMPETITION AND ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS First Article Testing and Approval 509.306... contracting officer must address the requirements in FAR 9.306(d) and (f) through (j) in the solicitation's...

  3. The Porphyromonas gingivalis ferric uptake regulator orthologue does not regulate iron homeostasis

    Directory of Open Access Journals (Sweden)

    Catherine Butler

    2015-09-01

    Full Text Available Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that has an absolute requirement for iron which it transports from the host as heme and/or Fe2+. Iron transport must be regulated to prevent toxic effects from excess metal in the cell. P. gingivalis has one ferric uptake regulator (Fur orthologue encoded in its genome called Har, which would be expected to regulate the transport and usage of iron within this bacterium. As a gene regulator, inactivation of Har should result in changes in gene expression of several genes compared to the wild-type. This dataset (GEO accession number GSE37099 provides information on expression levels of genes in P. gingivalis in the absence of Har. Surprisingly, these genes do not relate to iron homeostasis.

  4. 48 CFR 11.303 - Special requirements for printing and writing paper.

    Science.gov (United States)

    2010-10-01

    ... ACQUISITION REGULATION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Acceptable Material 11.303 Special... material is not reasonably available, does not meet reasonable performance requirements, or is only... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Special requirements for...

  5. Status of mixed-waste regulation

    International Nuclear Information System (INIS)

    Bahadur, S.

    1988-01-01

    Mixed waste is waste containing radionuclides regulated by the US Nuclear Regulatory Commission (NRC) under the Atomic Energy Act, as well as hazardous waste materials regulated by the Environmental Protection Agency (EPA) under the Resource Conservation and Recovery Act (RCRA). This has led to a situation of dual regulation in which both NRC and EPA regulate the same waste under requirements that at times appear conflicting. The NRC has been working with the EPA to resolve the issues associated with the dual regulation of mixed waste. Discussions between the two agencies indicate that dual regulation of mixed wastes appears technically achievable, although the procedures may be complex and burdensome to the regulated community. The staffs of both agencies have been coordinating their efforts to minimize the burden of dual regulation on state agencies and the industry. Three major issues were identified as sources of potential regulatory conflict: (a) definition and identification of mixed waste, (b) siting guidelines for disposal facilities, and (c) design concepts for disposal units

  6. 15 CFR 745.2 - End-Use Certificate reporting requirements under the Chemical Weapons Convention.

    Science.gov (United States)

    2010-01-01

    ... requirements under the Chemical Weapons Convention. 745.2 Section 745.2 Commerce and Foreign Trade Regulations... EXPORT ADMINISTRATION REGULATIONS CHEMICAL WEAPONS CONVENTION REQUIREMENTS § 745.2 End-Use Certificate reporting requirements under the Chemical Weapons Convention. Note: The End-Use Certificate requirement of...

  7. Requirement for the eIF4E binding proteins for the synergistic down-regulation of protein synthesis by hypertonic conditions and mTOR inhibition.

    Science.gov (United States)

    Clemens, Michael J; Elia, Androulla; Morley, Simon J

    2013-01-01

    The protein kinase mammalian target of rapamycin (mTOR) regulates the phosphorylation and activity of several proteins that have the potential to control translation, including p70S6 kinase and the eIF4E binding proteins 4E-BP1 and 4E-BP2. In spite of this, in exponentially growing cells overall protein synthesis is often resistant to mTOR inhibitors. We report here that sensitivity of wild-type mouse embryonic fibroblasts (MEFs) to mTOR inhibitors can be greatly increased when the cells are subjected to the physiological stress imposed by hypertonic conditions. In contrast, protein synthesis in MEFs with a double knockout of 4E-BP1 and 4E-BP2 remains resistant to mTOR inhibitors under these conditions. Phosphorylation of p70S6 kinase and protein kinase B (Akt) is blocked by the mTOR inhibitor Ku0063794 equally well in both wild-type and 4E-BP knockout cells, under both normal and hypertonic conditions. The response of protein synthesis to hypertonic stress itself does not require the 4E-BPs. These data suggest that under certain stress conditions: (i) translation has a greater requirement for mTOR activity and (ii) there is an absolute requirement for the 4E-BPs for regulation by mTOR. Importantly, dephosphorylation of p70S6 kinase and Akt is not sufficient to affect protein synthesis acutely.

  8. Digital Convergence and Content Regulation

    Directory of Open Access Journals (Sweden)

    Michael John Starks

    2014-12-01

    Full Text Available Broadcasting, Press and Internet journalism systems of distribution are converging: the same infrastructure can deliver all three historically separate services. Reception devices mirror this: the Connected TV, the tablet and the smart phone overlap in their functionality. Service overlaps are evident too, with broadcasters providing online and on-demand services and newspapers developing electronic versions. Does this mean that media regulation policies must converge too?My argument is that they should, though only where historically different communications are now fulfilling a similar function, e.g. broadcaster online services and electronic versions of newspapers. Convergence requires a degree of harmonisation and, to this end, I advocate a review of UK broadcasting's 'due impartiality' requirement and of the UK's application of the public service concept. I also argue for independent self-regulation (rather than state-based regulation of non-public-service broadcasting journalism.

  9. Radiation Safety (Qualifications) Regulations 1980

    International Nuclear Information System (INIS)

    1980-01-01

    These Regulations, promulgated pursuant to the provisions of the Radiation Safety Act, 1975-1979, require persons engaged in activities involving radiation to pass a radiation safety examination or to possess an approved qualification in radiation. The National Health and Medical Research Council is authorised to exempt persons from compliance with these requirements or, conversely, to impose such requirements on persons other than those designated. (NEA) [fr

  10. Technical guideline technology according to the X-ray regulations

    International Nuclear Information System (INIS)

    2011-01-01

    The guideline covers the required technical knowledge concerning radiation protection and knowledge concerning for the operation of X-ray devices for technical purposes and stray radiation sources requiring licensing, and requirements for the qualification of officially authorized inspectors. The guidelines includes the following chapters: (1) introductory regulations; (2) Volume of the required technical knowledge; (3) Acquirement and certification of the technical knowledge; (4) Actualization of the technical knowledge; (5)Approval of courses and other training measures; (6) Combination of courses and training measures according to the guideline; (7) Requirements for qualification of officially authorized inspectors; (8) Interim regulations.

  11. 40 CFR 59.105 - Reporting requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Reporting requirements. 59.105 Section... Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.105 Reporting requirements. (a) Each regulated entity must submit an initial report no later than January 11, 1999 or within...

  12. 76 FR 3485 - Required Scale Tests

    Science.gov (United States)

    2011-01-20

    ...-AB10 Required Scale Tests AGENCY: Grain Inspection, Packers and Stockyards Administration, USDA. ACTION... their scales tested at least twice each calendar year at intervals of approximately 6 months. This final rule requires that regulated entities complete the first of the two scale tests between January 1 and...

  13. Federal Gasoline Regulations

    Science.gov (United States)

    The Clean Air Act requires EPA to regulate fuels and fuel additives for use in mobile sources if such fuel, fuel additive or any emission products causes or contributes to air or water pollution that may endanger the public health or welfare.

  14. DIII-D ICRF high voltage power supply regulator upgrade

    International Nuclear Information System (INIS)

    Cary, W.P.; Burley, B.L.; Grosnickle, W.H.

    1997-11-01

    For reliable operation and component protection, of the 2 MW 30--120 MHz ICRF Amplifier System on DIII-D, it is desirable for the amplifier to respond to high VSWR conditions as rapidly as possible. This requires a rapid change in power which also means a rapid change in the high voltage power supply current demands. An analysis of the power supply's regulator dynamics was needed to verify its expected operation during such conditions. Based on this information it was found that a new regulator with a larger dynamic range and some anticipation capability would be required. This paper will discuss the system requirements, the as-delivered regulator performance, and the improved performance after installation of the new regulator system. It will also be shown how this improvement has made the amplifier perform at higher power levels more reliably

  15. The actual development of European aviation safety requirements in aviation medicine: prospects of future EASA requirements.

    Science.gov (United States)

    Siedenburg, J

    2009-04-01

    Common Rules for Aviation Safety had been developed under the aegis of the Joint Aviation Authorities in the 1990s. In 2002 the Basic Regulation 1592/2002 was the founding document of a new entity, the European Aviation Safety Agency. Areas of activity were Certification and Maintenance of aircraft. On 18 March the new Basic Regulation 216/2008, repealing the original Basic Regulation was published and applicable from 08 April on. The included Essential Requirements extended the competencies of EASA inter alia to Pilot Licensing and Flight Operations. The future aeromedical requirements will be included as Annex II in another Implementing Regulation on Personnel Licensing. The detailed provisions will be published as guidance material. The proposals for these provisions have been published on 05 June 2008 as NPA 2008- 17c. After public consultation, processing of comments and final adoption the new proposals may be applicable form the second half of 2009 on. A transition period of four year will apply. Whereas the provisions are based on Joint Aviation Requirement-Flight Crew Licensing (JAR-FCL) 3, a new Light Aircraft Pilot Licence (LAPL) project and the details of the associated medical certification regarding general practitioners will be something new in aviation medicine. This paper consists of 6 sections. The introduction outlines the idea of international aviation safety. The second section describes the development of the Joint Aviation Authorities (JAA), the first step to common rules for aviation safety in Europe. The third section encompasses a major change as next step: the foundation of the European Aviation Safety Agency (EASA) and the development of its rules. In the following section provides an outline of the new medical requirements. Section five emphasizes the new concept of a Leisure Pilot Licence. The last section gives an outlook on ongoing rulemaking activities and the opportunities of the public to participate in them.

  16. The regulator's perspective

    International Nuclear Information System (INIS)

    Norrby, S.

    1997-01-01

    Recommendations on general safety objectives and good practices related to radioactive waste management are given by international organisations such as the OECD/NEA and the IAEA. Moreover, international conventions and other supranational legal instruments, such as EU directives, lay down requirements on the safe management of radioactive waste. The implementer of the system for waste management and disposal and the regulator will have different roles. The responsibility for the management and disposal of radioactive waste is with the implementer, who has taken over that responsibility from the generator of the waste. The regulator's responsibility is to define safety and radiation protection requirements, to issue guidance on safety assessment methodology and documentation, to review the implementer's safety assessments as a basis for licensing of waste management and disposal activities and facilities and to inspect and review construction and operation of nuclear facilities to ensure compliance with licensing conditions. (R.P.)

  17. ROS signalling – Specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian Max; Sweetlove, Lee J

    2011-01-01

    The production of reactive oxygen species (ROS) increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 may induce a general stress response, but it does...... messengers and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. (This is a new project funded by FNU) References: Møller, I.M. & Sweetlove, L.J. 2010. ROS signalling – Specificity is required. Trends Plant Sci. 15: 370-374...... not have the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g., in chloroplasts or mitochondria. We here argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS...

  18. A Trio-Rac1-PAK1 signaling axis drives invadopodia disassembly

    Science.gov (United States)

    Moshfegh, Yasmin; Bravo-Cordero, Jose Javier; Miskolci, Veronika; Condeelis, John; Hodgson, Louis

    2014-01-01

    Rho family GTPases control cell migration and participate in the regulation of cancer metastasis. Invadopodia, associated with invasive tumor cells, are crucial for cellular invasion and metastasis. To study Rac1 GTPase in invadopodia dynamics, we developed a genetically-encoded, single-chain Rac1 Fluorescence Resonance Energy Transfer (FRET) biosensor. The biosensor shows Rac1 activity exclusion from the core of invadopodia, and higher activity when invadopodia disappear, suggesting that reduced Rac1 activity is necessary for their stability, and Rac1 activation is involved in disassembly. Photoactivating Rac1 at invadopodia confirmed this previously-unknown Rac1 function. We built an invadopodia disassembly model, where a signaling axis involving TrioGEF, Rac1, PAK1, and phosphorylation of cortactin, causing invadopodia dissolution. This mechanism is critical for the proper turnover of invasive structures during tumor cell invasion, where a balance of proteolytic activity and locomotory protrusions must be carefully coordinated to achieve a maximally invasive phenotype. PMID:24859002

  19. Regulation of Development and Nitrogen Fixation in Anabaena

    Energy Technology Data Exchange (ETDEWEB)

    James W. Golden

    2008-10-17

    The regulation of development and cellular differentiation is important for all multicellular organisms. The nitrogen-fixing filamentous cyanobacterium Anabaena (also Nostoc) sp. PCC 7120 (hereafter Anabaena) provides a model of multicellular microbial development and pattern formation. Anabaena reduces N2 to ammonia in specialized terminally differentiated cells called heterocysts. A one-dimensional developmental pattern of single heterocysts regularly spaced along filaments of photosynthetic vegetative cells is established to form a multicellular organism composed of these two interdependent cell types. This multicellular growth pattern, the distinct phylogeny of cyanobacteria, and the suspected antiquity of heterocyst development make this an important model system. Our long-term goal is to understand the regulatory network required for heterocyst development and nitrogen fixation. This project is focused on two key aspects of heterocyst regulation: one, the mechanism by which HetR controls the initiation of differentiation, and two, the cis and trans acting factors required for expression of the nitrogen-fixation (nif) genes. HetR is thought to be a central regulator of heterocyst development but the partners and mechanisms involved in this regulation are unknown. Our recent results indicate that PatS and other signals that regulate heterocyst pattern cannot interact, directly or indirectly, with a R223W mutant of HetR. We plan to use biochemical and genetic approaches to identify proteins that interact with the HetR protein, which will help reveal the mechanisms underlying its regulation of development. Our second goal is to determine how the nif genes are expressed. It is important to understand the mechanisms controlling nif genes since they represent the culmination of the differentiation process and the essence of heterocyst function. The Anabaena genome lacks the genes required for expression of nif genes present in other organisms such as rpoN (sigma 54

  20. 48 CFR 801.602-70 - General review requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false General review... AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.602-70 General review requirements. (a) Contracting officers...

  1. 7 CFR 57.200 - Records and related requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Records and related requirements. 57.200 Section 57.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS...

  2. Towards spatially differentiated regulation of nitrogen

    DEFF Research Database (Denmark)

    Lajer Højberg, Anker; Refsgaard, Jens Christian; Jørgensen, Lisbeth Flindt

    EU member states are challenged by nitrogen loads to estuaries and inland freshwater systems impeding the achievement of good ecological status as required by the Water Framework Directive (WFD). In Denmark nitrate leaching from the root zone has been reduced by 50% since 1987, but additional...... reductions of 30-50% are required to meet the objectives of the WFD. Achieving such abatements by uniform restrictions for all areas, would be very costly and inefficient as studies have shown that reduction varies spatially depending on the local hydrogeological conditions, the presence and dynamics...... of drains and hydro-biogeochemical conditions in associated riparian lowlands. Hence, a shift of paradigm in regulation practice is needed, whit a cost-effective regulation accounting for this variability and differentiate the regulations/restrictions between resilient and vulnerable areas. However...

  3. 78 FR 12623 - Insurer Reporting Requirements

    Science.gov (United States)

    2013-02-25

    ... NHTSA's regulation requiring motor vehicle insurers to submit information on the number of thefts and recoveries of insured vehicles and actions taken by the insurer to deter or reduce motor vehicle theft. NHTSA..., which requires insurers to submit information about the make, model, and year of all vehicle thefts, the...

  4. 24 CFR 700.175 - Other Federal requirements.

    Science.gov (United States)

    2010-04-01

    ... requirements described in 24 CFR part 44 (OMB Circular A-128). (b) Conflict of interest. In addition to the conflict of interest requirements in OMB Circular A-87 and 24 CFR part 85, no person who is an employee..., and the implementing regulations at 24 CFR part 108; and (3) Racial and ethnic collection requirements...

  5. Recent changes in federal PCB regulations

    International Nuclear Information System (INIS)

    Ewing, H.

    1995-01-01

    An overview of the federal regulations dealing with PCBs, the draft PCB Transformer Decontamination Standards and Protocols, and the Practice of Ballast Splitting was given. Answers were provided to practical questions concerning the regulations, specifically, responsibility for storage, labelling requirements, waste export regulations, treatment and destruction standards, transformer decontamination, decontamination standards, and the practice of ballast splitting into PCB and non-PCB materials. Details of sampling procedures and sample handling were also described

  6. 40 CFR 141.174 - Filtration sampling requirements.

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Filtration and Disinfection... water system subject to the requirements of this subpart that provides conventional filtration treatment... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Filtration sampling requirements. 141...

  7. 75 FR 33271 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Foreign...

    Science.gov (United States)

    2010-06-11

    ... Certain Contracts with Foreign Entities for the Conduct of Ballistic Missile Defense Research, Development..., development, test, or evaluation in connection with the Ballistic Missile Defense Program. The provision... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0229...

  8. Economic regulation of TSOs in the Nordic countries

    Energy Technology Data Exchange (ETDEWEB)

    Syvertsen, S. C.; Steinnes, S. H. [Norwegian Water Resources and Energy Directorate, Oslo (Norway); Robles, H. B.; Ek, G. [Energy Markets Inspectorate, Eskilstuna (Sweden); Ilonen, M; Nurmi, S. [Energy Market Authority, Helsinki (Finland); Thomsen, H. [Sekretariatet for Energitilsynet, Valby (Denmark)

    2012-12-15

    The main topic of this report is the economic regulation of the transmission system operators (To) in the Nordic countries (Denmark, Finland, Norway and Sweden). The purpose of this report is to give an overview of the design of the economic regulation and compare the main elements of the regulation between the countries. There is one To in each country. For all countries, the revenues of the Tos are regulated by yearly decisions. In Finland, Norway and Sweden the regulators set an annual revenue cap. In Denmark, the To sets the tariffs according to budget, while the regulator approves the annual report and thereby also approves the tariffs ex post. The economic regulation of TSOs includes both regulation of system operations and the regulation of network operations. Chapter 3 describes in brief the main responsibilities of the system operator in each country and how the costs related to these tasks are regulated. Norway regulates the system operation costs, where 60 percent of the costs are based on a cost-norm which is evaluated periodically. In Finland and Sweden these costs are considered as non-controllable and are passed through directly in the revenue cap. In Denmark only costs considered as necessary at efficient operation shall be included in the tariffs, and the regulators have the opportunity to exclude costs based on this. There are no benchmark or efficiency requirements in the Danish regulation. In chapter 4 the main elements of the economic regulation of network operations are described and compared in tables. All countries regulate the network operations of the TSO. In Denmark there are no explicit efficiency requirements, and the regulation is based on a non-profit principle. The TSO only gets a return based on a price adjustment on its capital base as of 2005. In Finland, Norway and Sweden the regulation include efficiency requirements or benchmarking of costs. In Norway this regards 60 percent of total costs related to the network operations

  9. Capital Requirements and Banks' Leniency

    DEFF Research Database (Denmark)

    Dietrich, J. Kimball; Wihlborg, Clas

    2003-01-01

    We investigate the effect of changes in capital regulation on the strictness(leniency) of loan terms using a simple model of bank capital requirements andasset quality examinations. Banks offer different levels of `leniency' in the senseof willingness to offer automatic extensions of loans...... rates. As capital requirements increase thedifference between initial capital levels and between interest rates of strict andlenient banks decrease. Thus, higher capital requirements in recessions tend toreduce the interest rate premium paid for leniency. If a recession is interpreted asan increase...... in the required return, the interest rate premium paid for leniency isincreased in recession at a given level of required capital....

  10. A voltage-gated calcium channel regulates lysosomal fusion with endosomes and autophagosomes and is required for neuronal homeostasis.

    Directory of Open Access Journals (Sweden)

    Xuejun Tian

    2015-03-01

    Full Text Available Autophagy helps deliver sequestered intracellular cargo to lysosomes for proteolytic degradation and thereby maintains cellular homeostasis by preventing accumulation of toxic substances in cells. In a forward mosaic screen in Drosophila designed to identify genes required for neuronal function and maintenance, we identified multiple cacophony (cac mutant alleles. They exhibit an age-dependent accumulation of autophagic vacuoles (AVs in photoreceptor terminals and eventually a degeneration of the terminals and surrounding glia. cac encodes an α1 subunit of a Drosophila voltage-gated calcium channel (VGCC that is required for synaptic vesicle fusion with the plasma membrane and neurotransmitter release. Here, we show that cac mutant photoreceptor terminals accumulate AV-lysosomal fusion intermediates, suggesting that Cac is necessary for the fusion of AVs with lysosomes, a poorly defined process. Loss of another subunit of the VGCC, α2δ or straightjacket (stj, causes phenotypes very similar to those caused by the loss of cac, indicating that the VGCC is required for AV-lysosomal fusion. The role of VGCC in AV-lysosomal fusion is evolutionarily conserved, as the loss of the mouse homologues, Cacna1a and Cacna2d2, also leads to autophagic defects in mice. Moreover, we find that CACNA1A is localized to the lysosomes and that loss of lysosomal Cacna1a in cerebellar cultured neurons leads to a failure of lysosomes to fuse with endosomes and autophagosomes. Finally, we show that the lysosomal CACNA1A but not the plasma-membrane resident CACNA1A is required for lysosomal fusion. In summary, we present a model in which the VGCC plays a role in autophagy by regulating the fusion of AVs with lysosomes through its calcium channel activity and hence functions in maintaining neuronal homeostasis.

  11. 76 FR 68064 - Reserve Requirements of Depository Institutions

    Science.gov (United States)

    2011-11-03

    ... Reserve Requirements of Depository Institutions AGENCY: Board of Governors of the Federal Reserve System. ACTION: Final rule. SUMMARY: The Board is amending Regulation D, Reserve Requirements of Depository Institutions, to reflect the annual indexing of the reserve requirement exemption amount and the low reserve...

  12. 75 FR 65563 - Reserve Requirements of Depository Institutions

    Science.gov (United States)

    2010-10-26

    ... Requirements of Depository Institutions AGENCY: Board of Governors of the Federal Reserve System. ACTION: Final rule. SUMMARY: The Board is amending Regulation D, Reserve Requirements of Depository Institutions, to reflect the annual indexing of the reserve requirement exemption amount and the low reserve tranche for...

  13. 78 FR 66249 - Reserve Requirements of Depository Institutions

    Science.gov (United States)

    2013-11-05

    ... Requirements of Depository Institutions AGENCY: Board of Governors of the Federal Reserve System. ACTION: Final rule. SUMMARY: The Board is amending Regulation D, Reserve Requirements of Depository Institutions, to reflect the annual indexing of the reserve requirement exemption amount and the low reserve tranche for...

  14. 77 FR 65773 - Reserve Requirements of Depository Institutions

    Science.gov (United States)

    2012-10-31

    ... Requirements of Depository Institutions AGENCY: Board of Governors of the Federal Reserve System. ACTION: Final rule. SUMMARY: The Board is amending Regulation D, Reserve Requirements of Depository Institutions, to reflect the annual indexing of the reserve requirement exemption amount and the low reserve tranche for...

  15. 48 CFR 801.602-75 - Review requirements-OGC.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Review requirements-OGC... GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.602-75 Review requirements—OGC. (a) Contracting officers must obtain...

  16. 34 CFR 350.4 - What regulations apply?

    Science.gov (United States)

    2010-07-01

    ... (IRB) reviews research that purposefully requires inclusion of children with disabilities or... REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND REHABILITATION RESEARCH PROJECTS AND CENTERS PROGRAM General § 350.4 What regulations apply? The following regulations apply to the Disability and...

  17. Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival.

    Science.gov (United States)

    Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa

    2010-12-28

    Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.

  18. Required warnings for cigarette packages and advertisements. Final rule.

    Science.gov (United States)

    2011-06-22

    The Food and Drug Administration (FDA) is amending its regulations to add a new requirement for the display of health warnings on cigarette packages and in cigarette advertisements. This rule implements a provision of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) that requires FDA to issue regulations requiring color graphics, depicting the negative health consequences of smoking, to accompany the nine new textual warning statements required under the Tobacco Control Act. The Tobacco Control Act amends the Federal Cigarette Labeling and Advertising Act (FCLAA) to require each cigarette package and advertisement to bear one of nine new textual warning statements. This final rule specifies the color graphic images that must accompany each of the nine new textual warning statements.

  19. 78 FR 20624 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Science.gov (United States)

    2013-04-05

    ... Identification Advance Shipment Notices AGENCY: Defense Acquisition Regulations System, Department of Defense (Do...) Whether the proposed collection of information is necessary for the proper performance of the functions of... at 252.211; Radio Frequency Identification Advance Shipment Notices, OMB Control Number 0704-0434...

  20. 78 FR 15935 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Science.gov (United States)

    2013-03-13

    ... automated collection techniques or other forms of information technology. The Office of Management and... construction contract in Spain has adequate insurance coverage. Affected Public: Businesses or other for profit... construction contract in Spain. Kortnee Stewart, Editor, Defense Acquisition Regulations System. [FR Doc. 2013...

  1. 15 CFR 30.17 - Customs and Border Protection regulations.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Customs and Border Protection regulations. 30.17 Section 30.17 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade... Requirements § 30.17 Customs and Border Protection regulations. Refer to the DHS's CBP regulations, 19 CFR 192...

  2. 76 FR 72916 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Science.gov (United States)

    2011-11-28

    ... information collection requires contractors to comply with the notification process at DFARS clause 252.204... purposes. The U.S.-IAEA Additional Protocol permits the United States unilaterally to declare exclusions from inspection requirements for activities with direct national security significance. The clause at...

  3. 10 CFR 603.695 - Requirements for supplies.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Requirements for supplies. 603.695 Section 603.695 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Award Terms Affecting Participants' Financial, Property, and Purchasing Systems Property § 603.695 Requirements for...

  4. 48 CFR 9904.416-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement..., OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.416-40 Fundamental requirement. (a) The amount of...

  5. 48 CFR 9904.413-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement..., OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.413-40 Fundamental requirement. (a) Assignment of...

  6. 48 CFR 9904.417-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.417-40 Fundamental requirement. The cost of money applicable to the investment in tangible and intangible capital assets being constructed, fabricated, or...

  7. 48 CFR 46.301 - Contractor inspection requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contractor inspection... CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Clauses 46.301 Contractor inspection requirements. The contracting officer shall insert the clause at 52.246-1, Contractor Inspection Requirements, in solicitations...

  8. 8 CFR 333.1 - Description of required photographs.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Description of required photographs. 333.1 Section 333.1 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS PHOTOGRAPHS § 333.1 Description of required photographs. (a) Every applicant required to furnish photographs of...

  9. 42 CFR 421.310 - Conflict of interest requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Conflict of interest requirements. 421.310 Section... Conflict of interest requirements. Offerors for MIP contracts and MIP contractors are subject to the following: (a) The conflict of interest standards and requirements of the Federal Acquisition Regulation...

  10. ROS signalling - specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian M; Sweetlove, Lee J

    2010-01-01

    Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression...

  11. Regulation on control systems tests

    International Nuclear Information System (INIS)

    Grau, J.; Navarro, J.M.

    1978-01-01

    Requirements under regulation applicable to the testing of control systems and controlled equipments in the case of USA nuclear projects are examined. They are reviewed, in particular, the following standards and criteria: 10 Code of Federal Regulations 50, Appendix A, General Design Criteria 20 and 21; IEEE Standards 279 and 308; IEEE Standard 338; US Regulatory Guides 1.22 and 1.118.(J.E.de C.)

  12. Interpreting the SARA and RCRA training requirements

    International Nuclear Information System (INIS)

    Moreland, W.M.; Wells, S.M.

    1987-01-01

    The Resource Conservation and Recovery Act (RCRA) and the Superfund Amendments and Reauthorization Act (SARA) promulgated by the EPA (RCRA) and the OSHA (SARA) require hazardous materials training for all individuals working with hazardous materials. Facilities that are involved in the generation, storage, treatment, transportation, or disposal/removal of hazardous materials/waste must comply with all relevant training regulations. Using the guidelines contained in the RCRA and SARA regulations, decisions must be made to determine: the type of regulatory requirement based on facility function (i.e., whether the facility is a RCRA or CERCLA facility). The type of training required for specific categories of workers (e.g. managers, supervisors, or general site workers). The level of training needed for each category of worker. This presentation outlines how the Environmental Compliance and Health Protection Technical Resources and Training Group, working with waste operations personnel, establishes specific training requirements

  13. 48 CFR 1804.470 - Security requirements for unclassified information technology (IT) resources.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Security requirements for unclassified information technology (IT) resources. 1804.470 Section 1804.470 Federal Acquisition Regulations... Classified Information Within Industry 1804.470 Security requirements for unclassified information technology...

  14. 40 CFR 52.2382 - Rules and regulations.

    Science.gov (United States)

    2010-07-01

    ... pollution notification requirements. (5) Conflict of interest requirements. (b) Regulation for visibility monitoring and new source review. The provisions of §§ 52.26 and 52.27 are hereby incorporated and made a...

  15. 9 CFR 201.4 - Bylaws, rules and regulations, and requirements of exchanges, associations, or other...

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Bylaws, rules and regulations, and... 201.4 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS ADMINISTRATION (PACKERS AND... of any exchange, association, or other organization, or any other valid law, rule or regulation, or...

  16. A review of tritium licensing requirements

    International Nuclear Information System (INIS)

    Meikle, A.B.

    1982-12-01

    Present Canadian regulations and anticipated changes to these regulations relevant to the utilization of tritium in fusion facilities and in commercial applications have been reviewed. It is concluded that there are no serious licensing obstacles, but there are a number of requirements which must be met. A license will be required from Atomic Energy Control Board if Ontario Hydro tritium is to be applied by other users. A license is required from the Federal Government to export or import tritium. A licensed container will be required for the storage and shipping of tritium. The containers being designed by AECL and Ontario Hydro and which are currently being tested will adequately store and ship all of the Ontario Hydro tritium but are unnecessarily large for the small quantities required by the commercial tritium users. Also, some users may prefer to receive tritium in gaseous form. An additional, smaller container should be considered. The licensing of overseas fusion facilities for the use of tritium is seen as a major undertaking offering opportunities to Canadian Fusion Fuels Technology Project to undertake health, safety and environmental analysis on behalf of these facilities

  17. Regulations for the safe transport of radioactive material. 1996 ed.

    International Nuclear Information System (INIS)

    1996-01-01

    This publication is the revised version of the IAEA's Regulations for the Safe Transport of Radioactive Materials as approved by the Board of Governors in September 1996. It establishes standards of safety which provide an acceptable level of control of the radiation, criticality and thermal hazards to persons, property and the environment that are associated with the transport of radioactive material. After an introductory section, the publication is structured as follows: Section 2 defines the terms that are required for the purposes of the Regulations; Section 3 provides general provisions; Section 4 gives the activity limits and material restrictions used throughout these Regulations; Section 5 provides requirements and controls for transport; Section 6 provides requirements for radioactive materials and for packagings and packages; Section 7 provides requirements for test procedures; Section 8 provides approval and administrative requirements. The requirements for the transport of specified types of consignments are included in an abbreviated form as Schedules. Refs, figs, tabs

  18. The effect of business regulations on nascent to young business entrepreneurship

    NARCIS (Netherlands)

    A.J. van Stel (André); D. Storey (David); A.R. Thurik (Roy)

    2007-01-01

    textabstractWe examine the relationship, across 39 countries, between regulation and entrepreneurship using a new two-equation model. We find the minimum capital requirement required to start a business lowers entrepreneurship rates across countries, as do labour market regulations. However the

  19. Bulletin 2005-12 : revised Alberta pipeline regulation issued

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-05-31

    A revised Pipeline Regulation has been issued and is currently available on the Alberta Energy and Utilities Board (EUB) website. Changes to the regulation reflect bothchanges in EUB regulatory policy and processes and technological improvements. Goals of the revision include improvements in overall pipeline performance, and the implementation of recommendations derived from the Public Safety and Sour Gas Committee concerning sour gas pipeline safety. The regulation was re-organized for greater clarity, and structured into 11 parts. Issues concerning the transition to the revised regulation were presented. The summary of notable administrative changes included clarifications of when a pipeline application is not required; when ABSA approval is required for steam lines; situations for which low-pressure natural gas lines must be licensed; and emergency response requirements. Technical clarifications include requirements for pipeline operations and maintenance manuals; composite materials; limitations on amounts of H{sub 2}S in polymeric pipe; pressure mismatches; approval for testing with gaseous media; venting of small volumes of raw gas; right-of-way surveillance; inspection of surface construction activities; annual corrosion evaluations; registering of pipelines and excavators in controlled areas with Alberta One-Call; ground disturbance training; restoration and signage maintenance on abandoned pipelines; sour service steel pipelines; unused pipelines and abandoned pipelines; and remediation of stub ends in operating pipelines.

  20. 48 CFR 9904.420-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement..., OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.420-40 Fundamental requirement. (a) The basic unit for...

  1. 7 CFR 1948.62 - Environmental impact requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Environmental impact requirements. 1948.62 Section... Development Assistance Program § 1948.62 Environmental impact requirements. (a) The policies and regulations... studied for environmental impacts. (c) Boundaries shall define the area within which the environmental...

  2. Regulatory capital requirements and bail in mechanisms

    NARCIS (Netherlands)

    Joosen, B.P.M.; Haentjens, M.; Wessels, B.

    2015-01-01

    With the introduction of the Capital Requirements Regulation (CRR) in the European Union, the qualitative requirements for bank regulatory capital have changed. These changes aim at implementing in Europe the Basel III principles for better bank capital that is able to absorb losses of banks,

  3. Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Joseph L. Regan

    2017-12-01

    Full Text Available Summary: Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs. To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non-canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT, we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival. : Colon cancer is a heterogeneous tumor driven by a subpopulation(s of therapy-resistant cancer stem cells (CSCs. Regan et al. use 3D culture models to demonstrate that CSC survival is regulated by non-canonical, SHH-dependent, PTCH1-dependent Hedgehog signaling, which acts as a positive regulator of WNT signaling to block CSC differentiation. Keywords: WNT pathway, non-canonical Hedgehog signaling, cancer stem cell, colon cancer, cancer organoid, PTCH1, HHAT, SHH

  4. 24 CFR 884.225 - PHA reporting requirements. [Reserved

    Science.gov (United States)

    2010-04-01

    ... reporting requirements. [Reserved] ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false PHA reporting requirements. [Reserved] 884.225 Section 884.225 Housing and Urban Development Regulations Relating to Housing and Urban...

  5. 19 CFR 12.73 - Motor vehicle and engine compliance with Federal antipollution emission requirements.

    Science.gov (United States)

    2010-04-01

    ... requirements. This section is ancillary to the regulations of the U.S. Environmental Protection Agency (EPA.... Those regulations should be consulted for more detailed information concerning EPA emission requirements... and exclusions from emission requirements based on age of vehicle. The following motor vehicles...

  6. Classification of low energy houses in Danish Building Regulations

    DEFF Research Database (Denmark)

    Rose, Jørgen; Svendsen, Svend

    2005-01-01

    The new Danish Building Regulations (Building Regulations, 2005) introduces the total energy consumption, i.e. energy use for heating, ventilation, cooling and domestic hot water, for buildings as a measure for the energy efficiency of new buildings, i.e. moving away from the former U-value demands....... In addition to the minimum requirements for new buildings, the new Building Regulations also specify requirements for characterizing a building as either low energy building class 1 or low energy building class 2. This paper describes a type-house that is presently being built in Denmark. The type......-house easily meets the requirements for being categorized as a low energy building class 1, and the paper investigates how much U-values can be increased if the type-house were to fulfil the requirements for a low energy building class 2 or a building that just fulfils the minimum demands....

  7. Calcium-regulation of mitochondrial respiration maintains ATP homeostasis and requires ARALAR/AGC1-malate aspartate shuttle in intact cortical neurons.

    Science.gov (United States)

    Llorente-Folch, Irene; Rueda, Carlos B; Amigo, Ignacio; del Arco, Araceli; Saheki, Takeyori; Pardo, Beatriz; Satrústegui, Jorgina

    2013-08-28

    Neuronal respiration is controlled by ATP demand and Ca2+ but the roles played by each are unknown, as any Ca2+ signal also impacts on ATP demand. Ca2+ can control mitochondrial function through Ca2+-regulated mitochondrial carriers, the aspartate-glutamate and ATP-Mg/Pi carriers, ARALAR/AGC1 and SCaMC-3, respectively, or in the matrix after Ca2+ transport through the Ca2+ uniporter. We have studied the role of Ca2+ signaling in the regulation of mitochondrial respiration in intact mouse cortical neurons in basal conditions and in response to increased workload caused by increases in [Na+]cyt (veratridine, high-K+ depolarization) and/or [Ca2+]cyt (carbachol). Respiration in nonstimulated neurons on 2.5-5 mm glucose depends on ARALAR-malate aspartate shuttle (MAS), with a 46% drop in aralar KO neurons. All stimulation conditions induced increased OCR (oxygen consumption rate) in the presence of Ca2+, which was prevented by BAPTA-AM loading (to preserve the workload), or in Ca2+-free medium (which also lowers cell workload). SCaMC-3 limits respiration only in response to high workloads and robust Ca2+ signals. In every condition tested Ca2+ activation of ARALAR-MAS was required to fully stimulate coupled respiration by promoting pyruvate entry into mitochondria. In aralar KO neurons, respiration was stimulated by veratridine, but not by KCl or carbachol, indicating that the Ca2+ uniporter pathway played a role in the first, but not in the second condition, even though KCl caused an increase in [Ca2+]mit. The results suggest a requirement for ARALAR-MAS in priming pyruvate entry in mitochondria as a step needed to activate respiration by Ca2+ in response to moderate workloads.

  8. Medical devices regulations, standards and practices

    CERN Document Server

    Ramakrishna, Seeram; Wang, Charlene

    2015-01-01

    Medical Devices and Regulations: Standards and Practices will shed light on the importance of regulations and standards among all stakeholders, bioengineering designers, biomaterial scientists and researchers to enable development of future medical devices. Based on the authors' practical experience, this book provides a concise, practical guide on key issues and processes in developing new medical devices to meet international regulatory requirements and standards. Provides readers with a global perspective on medical device regulationsConcise and comprehensive information on how to desig

  9. Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP Binding: Requirement for Establishing Chronic Persistent Infection

    Energy Technology Data Exchange (ETDEWEB)

    Drumm, J.; Mi, K; Bilder, P; Sun, M; Lim, J; Bielefeldt-Ohmann, H; Basaraba, R; So, M; Zhu, G; et. al.

    2009-01-01

    Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

  10. 48 CFR 52.204-2 - Security Requirements.

    Science.gov (United States)

    2010-10-01

    ... Agreement (DD Form 441), including the National Industrial Security Program Operating Manual (DOD 5220.22-M... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Security Requirements. 52....204-2 Security Requirements. As prescribed in 4.404(a), insert the following clauses: Security...

  11. 40 CFR 80.92 - Baseline auditor requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Baseline auditor requirements. 80.92... (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Anti-Dumping § 80.92 Baseline auditor requirements. (a... determination methodology, resulting baseline fuel parameter, volume and emissions values verified by an auditor...

  12. 41 CFR 101-26.607-3 - Emergency requirements.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Emergency requirements. 101-26.607-3 Section 101-26.607-3 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 26-PROCUREMENT SOURCES AND...

  13. Nuclear Safety Regulations

    International Nuclear Information System (INIS)

    Novosel, N.; Prah, M.

    2008-01-01

    Beside new Ordinance on the control of nuclear material and special equipment ('Official Gazette' No. 15/08), from 2006 State Office for Nuclear Safety (SONS) adopted Ordinance on performing nuclear activities ('Official Gazette' No. 74/06) and Ordinance on special requirements which expert organizations must fulfil in order to perform certain activities in the field of nuclear safety ('Official Gazette' No. 74/06), based on Nuclear Safety Act ('Official Gazette' No. 173/03). The Ordinance on performing nuclear activities regulates the procedure of notification of the intent to perform nuclear activities, submitting the application for the issue of a licence to perform nuclear activities, and the procedure for issuing decisions on granting a licence to perform a nuclear activity. The Ordinance also regulates the content of the forms for notification of the intent to perform nuclear activities, as well as of the application for the issue of a licence to perform the nuclear activity and the method of keeping the register of nuclear activities. According to the Nuclear Safety Act, nuclear activities are the production, processing, use, storage, disposal, transport, import, export, possession or other handling of nuclear material or specified equipment. The Ordinance on special requirements which expert organizations must fulfil in order to perform certain activities in the field of nuclear safety regulates these mentioned conditions, whereas compliance is established by a decision passed by the SONS. Special requirements which expert organizations must fulfil in order to perform certain activities in the field of nuclear safety are organizational, technical, technological conditions and established system of quality assurance. In 2007, State Office for Nuclear Safety finalized the text of new Ordinance on conditions for nuclear safety and protection with regard to the siting, design, construction, use and decommissioning of a facility in which a nuclear activity is

  14. 7 CFR 801.12 - Design requirements incorporated by reference.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Design requirements incorporated by reference. 801.12 Section 801.12 Agriculture Regulations of the Department of Agriculture (Continued) GRAIN INSPECTION... OFFICIAL PERFORMANCE REQUIREMENTS FOR GRAIN INSPECTION EQUIPMENT § 801.12 Design requirements incorporated...

  15. The regulations concerning the reprocessing business of spent fuels

    International Nuclear Information System (INIS)

    1978-01-01

    In compliance with ''The law for the regulations of nuclear source material, nuclear fuel material and reactors'' these regulations prescribe concerning reprocessing facilities: The procedures to apply for the approval of the design and method of construction and the approval of the change thereof; as well as the procedure to apply for the inspection of the facilities, and details of the inspection (in sections 2-6). After that, the regulations require the enterpriser of reprocessing business to keep necessary records and take necessary measures for safety concerning the facilities, operation of reprocessing equipments, and transportation, storage on disposal of used fuel, materials separated therefrom or materials contaminated by either of them (in sections 8-16). Further, the regulations prescribe the procedure to apply for the approval of the safety rule required to the enterpriser of reprocessing business by above mentioned law and specifies items which should be included into the rule (section 17). Moreover, the regulations require the enterpriser to submit reports of each use of the internationally controllled material and specifies the items which should be included into these reports (section 19). (Matsushima, A.)

  16. 5 CFR 831.642 - Marriage duration requirements.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Marriage duration requirements. 831.642... REGULATIONS (CONTINUED) RETIREMENT Survivor Annuities Eligibility § 831.642 Marriage duration requirements. (a... in paragraph (b) of this section; or (2) A child was born of the marriage, as explained in paragraph...

  17. The bifunctional abiotic stress signalling regulator and endogenous RNA silencing suppressor FIERY1 is required for lateral root formation

    KAUST Repository

    Chen, Hao

    2010-09-28

    The Arabidopsis FIERY1 (FRY1) locus was originally identified as a negative regulator of stress-responsive gene expression and later shown to be required for suppression of RNA silencing. In this study we discovered that the FRY1 locus also regulates lateral root formation. Compared with the wild type, fry1 mutant seedlings generated significantly fewer lateral roots under normal growth conditions and also exhibited a dramatically reduced sensitivity to auxin in inducing lateral root initiation. Using transgenic plants that overexpress a yeast homolog of FRY1 that possesses only the 3\\', 5\\'-bisphosphate nucleotidase activity but not the inositol 1-phosphatase activity, we demonstrated that the lateral root phenotypes in fry1 result from loss of the nucleotidase activity. Furthermore, a T-DNA insertion mutant of another RNA silencing suppressor, XRN4 (but not XRN2 or XRN3), which is an exoribonuclease that is inhibited by the substrate of the FRY1 3\\', 5\\'-bisphosphate nucleotidase, exhibits similar lateral root defects. Although fry1 and xrn4 exhibited reduced sensitivity to ethylene, our experiments demonstrated that restoration of ethylene sensitivity in the fry1 mutant is not sufficient to rescue the lateral root phenotypes of fry1. Our results indicate that RNA silencing modulated by FRY1 and XRN4 plays an important role in shaping root architecture. © 2010 Blackwell Publishing Ltd.

  18. 7 CFR 301.86-2 - Regulated articles.

    Science.gov (United States)

    2010-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Pale Cyst Nematode § 301.86-2 Regulated articles. The following are regulated articles: (a) Pale cyst nematodes.2 2 Permit and other requirements for the interstate movement of pale cyst nematodes are contained in part 330 of this chapter. (b) The...

  19. Purpose of Engagement in Academic Self-Regulation

    Science.gov (United States)

    Lichtinger, Einat; Kaplan, Avi

    2011-01-01

    "Academic self-regulation" refers to the self-generated, reflective, and strategic engagement in academic tasks (Zimmerman, 2000). Self-regulation is crucial for academic success, particularly in higher education, where students are required to take increased responsibility for their learning and where the diversity of courses and activities may…

  20. Risk based regulation: a convenient concept for legislation and regulation in the field of technical risks?

    International Nuclear Information System (INIS)

    Seiler, J.H.

    1998-01-01

    Legislation and regulation concerning risk activities are traditionally based on deterministic safety measures. This may lead to inefficient results: sometimes the law requires safety measures which are - from an economic viewpoint - not justified because of their poor cost-effectiveness; sometimes it does not require safety measures although they would be very efficient. The risk based regulation approach wants to make the law more efficient and to get more safety at less costs. Legislation and regulation should be based on terms of risk rather than on deterministic rules. Risk should be expressed in quantitative terms and risk regulation should be based on the cost-effectiveness of safety measures. Thus a most efficient (in the sense of the economic analysis of the law) strategy for safety and environmental law could be established. The approach is economically reasonable and theoretically convincing. Its practical implementation however raises a lot of technical and legal questions. The project 'Risk Based Regulation' (1996-1999), sponsored by the Swiss National Fund for Scientific Research, intends to evaluate the practical feasibility of the approach from a technical and a legal view. It contains a general part which describes the risk based regulation approach and its legal and technical questions, case studies which try to practically implement the risk based regulation approach; the case studies are: storage and management of explosives in the army, storage and management of explosives for non-military purposes, safety at work, accident prevention in the non-professional field (mainly road accidents), fire protection, transportation of dangerous goods, waste disposal: traditional waste, waste disposal: radioactive waste, nuclear energy (reactor safety), a synthesis with recommendations for the future legislation and regulation in the field of technical risks. The paper presents the project and its preliminary results. (author)

  1. 12 CFR 219.23 - Recordkeeping and reporting requirements.

    Science.gov (United States)

    2010-01-01

    ... Funds § 219.23 Recordkeeping and reporting requirements. (a) Domestic and international funds transfers... recordkeeping and reporting requirements for domestic and international funds transfers by insured depository... usefulness in criminal, tax, or regulatory investigations or proceedings. These regulations are codified at...

  2. 76 FR 36627 - Required Warnings for Cigarette Packages and Advertisements

    Science.gov (United States)

    2011-06-22

    ...The Food and Drug Administration (FDA) is amending its regulations to add a new requirement for the display of health warnings on cigarette packages and in cigarette advertisements. This rule implements a provision of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) that requires FDA to issue regulations requiring color graphics, depicting the negative health consequences of smoking, to accompany the nine new textual warning statements required under the Tobacco Control Act. The Tobacco Control Act amends the Federal Cigarette Labeling and Advertising Act (FCLAA) to require each cigarette package and advertisement to bear one of nine new textual warning statements. This final rule specifies the color graphic images that must accompany each of the nine new textual warning statements.

  3. EUROPEAN REQUIREMENTS REGARDING THE AUDIT REPORTING

    Directory of Open Access Journals (Sweden)

    Daniel Botez

    2017-07-01

    Full Text Available In recent years, reporting requirements on the statutory audit have been revised and amended to increase the audit report’s communication value. In addition to the stipulations of the International Auditing Standards Package on reporting, revised and enforceable on 15 December 2016, the European Union issued the Directive 2014/56 / EU amending Directive 2006/43 / EC on statutory audits of annual financial statements and consolidated financial statements and EU Regulation no. 537/2014 on specific requirements for the statutory audit of public interest entities, both of which were published on the same date, June 17, 2014 and with the same application deadline, June 17, 2016. These normative acts foresee increased requirements for the reporting procedure in the statutory audit. Thus, the Directive provides for additional content requirements for the audit report, and the regulation requires additional information in the report but also the issuance and provision of other reports by the auditor: report to the audit committee of the public interest entity; In some cases, a report to the public-interest entity's supervisory authority or to the auditor's supervisory authority, and a transparency report published annually on the auditor's website. Our article details this information with direct reference to the content of these European official documents.

  4. Quebec petroleum regulations to be amended this spring

    International Nuclear Information System (INIS)

    Dubois, Y.A.; Meighen, M.

    1996-01-01

    Amendments proposed by the Government of Quebec with respect to petroleum products regulations were described. The amending regulation provides a list of works which will no longer require ministerial authorization such as the removal of petroleum equipment, the installation of spill prevention systems, electrical works and repair of fueling areas, loading and unloading zones. An owner will not be required to remove an unused underground petroleum storage tank if it can be shown that it is impervious according to prescribed pressure tests, and that the period during which the equipment has been unused does not exceed five years. The draft regulations also provide precautionary measures that have to be taken prior to abandoning a tank

  5. Study on the risk-informed regulation of NPP

    International Nuclear Information System (INIS)

    Wang Chaogui

    2007-01-01

    The risk-informed regulation is a modern type of NPP safety management mode using both deterministic and probabilistic approaches. It is necessary to entirely and systematically study the associated regulations, standards and practices in order to promote the developments of risk-informed regulations in China. This paper introduces the risk-informed regulation, gives out the basic principles, method and acceptance risk criteria of risk-informed decision,making, discusses the PSA requirements for risk-informed decision-making and makes some suggestions about the application of risk-informed regulations in Chinese NPP. (authors)

  6. Phytophthora capsici homologue of the cell cycle regulator SDA1 is required for sporangial morphology, mycelial growth and plant infection.

    Science.gov (United States)

    Zhu, Chunyuan; Yang, Xiaoyan; Lv, Rongfei; Li, Zhuang; Ding, Xiaomeng; Tyler, Brett M; Zhang, Xiuguo

    2016-04-01

    SDA1 encodes a highly conserved protein that is widely distributed in eukaryotic organisms. SDA1 is essential for cell cycle progression and organization of the actin cytoskeleton in yeasts and humans. In this study, we identified a Phytophthora capsici orthologue of yeast SDA1, named PcSDA1. In P. capsici, PcSDA1 is strongly expressed in three asexual developmental states (mycelium, sporangia and germinating cysts), as well as late in infection. Silencing or overexpression of PcSDA1 in P. capsici transformants affected the growth of hyphae and sporangiophores, sporangial development, cyst germination and zoospore release. Phalloidin staining confirmed that PcSDA1 is required for organization of the actin cytoskeleton. Moreover, 4',6-diamidino-2-phenylindole (DAPI) staining and PcSDA1-green fluorescent protein (GFP) fusions revealed that PcSDA1 is involved in the regulation of nuclear distribution in hyphae and sporangia. Both silenced and overexpression transformants showed severely diminished virulence. Thus, our results suggest that PcSDA1 plays a similar role in the regulation of the actin cytoskeleton and nuclear division in this filamentous organism as in non-filamentous yeasts and human cells. © 2015 BSPP and John Wiley & Sons Ltd.

  7. Recent and proposed changes in criticality alarm system requirements

    International Nuclear Information System (INIS)

    Putman, V.L.

    1998-01-01

    Various changes in criticality alarm system (CAS) requirements of American Nuclear Society (ANS) standards, US Department of Energy (DOE) orders, US Nuclear Regulatory Commission (NRC) regulations and guidance, and Occupational Safety and Health Administration (OSHA) standards or regulations were approved or proposed in the last 5 yr. Many changes interpreted or clarified existing requirements or accommodated technological or organizational developments. However, some changes could substantively affect CAS programs, including several changes originally thought to be editorial. These changes are discussed here

  8. Casein kinase II is required for proper cell division and acts as a negative regulator of centrosome duplication in Caenorhabditis elegans embryos

    Directory of Open Access Journals (Sweden)

    Jeffrey C. Medley

    2017-01-01

    Full Text Available Centrosomes are the primary microtubule-organizing centers that orchestrate microtubule dynamics during the cell cycle. The correct number of centrosomes is pivotal for establishing bipolar mitotic spindles that ensure accurate segregation of chromosomes. Thus, centrioles must duplicate once per cell cycle, one daughter per mother centriole, the process of which requires highly coordinated actions among core factors and modulators. Protein phosphorylation is shown to regulate the stability, localization and activity of centrosome proteins. Here, we report the function of Casein kinase II (CK2 in early Caenorhabditis elegans embryos. The catalytic subunit (KIN-3/CK2α of CK2 localizes to nuclei, centrosomes and midbodies. Inactivating CK2 leads to cell division defects, including chromosome missegregation, cytokinesis failure and aberrant centrosome behavior. Furthermore, depletion or inhibiting kinase activity of CK2 results in elevated ZYG-1 levels at centrosomes, restoring centrosome duplication and embryonic viability to zyg-1 mutants. Our data suggest that CK2 functions in cell division and negatively regulates centrosome duplication in a kinase-dependent manner.

  9. 16 CFR 1510.3 - Requirements.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Requirements. 1510.3 Section 1510.3 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS... purposes, the English measurements shall be used. Metric equivalents are included for convenience.) Rattles...

  10. Environmental requirements for oil and gas operations in Saskatchewan

    International Nuclear Information System (INIS)

    Nystuen, L.J.

    1997-01-01

    The administration and regulation of environmental issues regarding the oil and gas industry in Saskatchewan were discussed. The political and cultural differences in Saskatchewan that make environmental processes distinct from its neighbouring jurisdictions were described. The following Saskatchewan legislation deals with environmental requirements: Environmental Management and Protection Act, Environmental Assessment Act, Oil and Gas Conservation Act, Wildlife Habitat Protection Act, Clean Air Act, Planning and Development Act, Forest Act, Water Corporation Act, Heritage Property Act, and Parks Act. The Saskatchewan Department of Energy and Mines (SEM) is the primary regulator of the upstream oil and gas industry. It regulates the construction, operation, reporting and abandonment requirements for oilfield operations. SEM also manages crude oil prior to refining and manages the wastes contaminated with crude oil. Provisions of the relevant Acts regarding drilling in environmentally sensitive areas, flaring requirements, transporting and disposing of oilfield wastes, road-building, operating restrictions, emergency response plans, spill clean-up responsibilities, well abandonment and site reclamation responsibilities were discussed. 8 refs., 2 tabs

  11. The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth Arrest.

    Science.gov (United States)

    Gascoyne, Duncan M; Spearman, Hayley; Lyne, Linden; Puliyadi, Rathi; Perez-Alcantara, Marta; Coulton, Les; Fisher, Simon E; Croucher, Peter I; Banham, Alison H

    2015-01-01

    Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21WAF1/CIP1. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21WAF1/CIP1 activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology.

  12. The 2010 amendments to the environmental emergency regulations

    International Nuclear Information System (INIS)

    Dowdall, E.; Ketcheson, K.; Shrives, J.; Hradecky, K.

    2009-01-01

    This presentation gave notice of amendments to the Environmental Emergency Regulations, pursuant to section 200 of the 1999 Canadian Environmental Protection Act. At the time of publication, the Regulations required the development and implementation of environmental emergency plans for 174 substances with associated thresholds that, if released to the environment, could harm human health or environmental quality. Substances of concern, including CEPA toxic substances are reviewed regularly by the Environmental Emergencies Division of Environment Canada to determine whether they should be added to the Regulations. An evaluation of substances has been completed and, as a result, 33 new substances have been proposed to be added to the Regulations. Thirty are known CEPA toxics and the other 3 are substances of concern, notably acetic acid, ammonium nitrate and styrene. These substances of concern are considered to pose an unacceptable level of risk from their release and would require environmental emergency planning. This paper also identified the substances from the Chemicals Management Plan that have been evaluated using environmental criteria and have been found to be candidates for possible future addition to the Regulations. The process used to determine regulated threshold quantities was also described. 5 refs., 5 tabs.

  13. 49 CFR 1510.15 - Accounting and auditing requirements.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Accounting and auditing requirements. 1510.15 Section 1510.15 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION... CIVIL AVIATION SECURITY SERVICE FEES § 1510.15 Accounting and auditing requirements. (a) Direct air...

  14. 48 CFR 52.246-1 - Contractor Inspection Requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Contractor Inspection....246-1 Contractor Inspection Requirements. As prescribed in 46.301, insert the following clause: Contractor Inspection Requirements (APR 1984) The Contractor is responsible for performing or having...

  15. 19 CFR 122.4 - English language required.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false English language required. 122.4 Section 122.4... TREASURY AIR COMMERCE REGULATIONS General Definitions and Provisions § 122.4 English language required. A translation in the English language shall be attached to the original and each copy of any form or document...

  16. 15 CFR 762.4 - Original records required.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Original records required. 762.4... § 762.4 Original records required. The regulated person must maintain the original records in the form....5 of this part relating to reproduction of records. If the original record does not meet the...

  17. CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.

    Science.gov (United States)

    Převorovský, Martin; Oravcová, Martina; Zach, Róbert; Jordáková, Anna; Bähler, Jürg; Půta, František; Folk, Petr

    2016-11-16

    For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals.

  18. Incentive regulation of nuclear power plants by state regulators

    International Nuclear Information System (INIS)

    Martin, R.L.; Baker, K.; Olson, J.

    1991-02-01

    The Nuclear Regulatory Commission (NRC) monitors incentive programs established by state regulators in order to obtain current information and to consider the potential safety effects of the incentive programs as applied to nuclear units. The current report is an update of NUREG/CR-5509, Incentive Regulation of Nuclear Power Plants by State Public Utility Commissions, published in December 1989. The information in this report was obtained from interviews conducted with each state regulator and each utility with a minimum entitlement of 10%. The agreements, orders, and settlements from which each incentive program was implemented were reviewed as required. The interviews and supporting documentation form the basis for the individual state reports describing the structure and financial impact of each incentive program. The programs currently in effect represent the adoption of an existing nuclear performance incentive program proposal and one new program. In addition, since 1989 a number of nuclear units have been included in one existing program; while one program was discontinued and another one concluded. 6 refs., 27 tabs

  19. NFAT5 regulates the canonical Wnt pathway and is required for cardiomyogenic differentiation

    International Nuclear Information System (INIS)

    Adachi, Atsuo; Takahashi, Tomosaburo; Ogata, Takehiro; Imoto-Tsubakimoto, Hiroko; Nakanishi, Naohiko; Ueyama, Tomomi; Matsubara, Hiroaki

    2012-01-01

    Highlights: ► NFAT5 protein expression is downregulated during cardiomyogenesis. ► Inhibition of NFAT5 function suppresses canonical Wnt signaling. ► Inhibition of NFAT5 function attenuates mesodermal induction. ► NFAT5 function is required for cardiomyogenesis. -- Abstract: While nuclear factor of activated T cells 5 (NFAT5), a transcription factor implicated in osmotic stress response, is suggested to be involved in other processes such as migration and proliferation, its role in cardiomyogenesis is largely unknown. Here, we examined the role of NFAT5 in cardiac differentiation of P19CL6 cells, and observed that it was abundantly expressed in undifferentiated P19CL6 cells, and its protein expression was significantly downregulated by enhanced proteasomal degradation during DMSO-induced cardiomyogenesis. Expression of a dominant negative mutant of NFAT5 markedly attenuated cardiomyogenesis, which was associated with the inhibition of mesodermal differentiation. TOPflash reporter assay revealed that the transcriptional activity of canonical Wnt signaling was activated prior to mesodermal differentiation, and this activation was markedly attenuated by NFAT5 inhibition. Pharmacological activation of canonical Wnt signaling by [2′Z, 3′E]-6-bromoindirubin-3′-oxime (BIO) restored Brachyury expression in NFAT5DN-expressing cells. Inhibition of NFAT5 markedly attenuated Wnt3 and Wnt3a induction. Expression of Dkk1 and Cerberus1, which are secreted Wnt antagonists, was also inhibited by NFAT5 inhibition. Thus, endogenous NFAT5 regulates the coordinated expression of Wnt ligands and antagonists, which are essential for cardiomyogenesis through the canonical Wnt pathway. These results demonstrated a novel role of NFAT5 in cardiac differentiation of stem cells.

  20. The Arabidopsis mediator complex subunits MED16, MED14, and MED2 regulate mediator and RNA polymerase II recruitment to CBF-responsive cold-regulated genes.

    Science.gov (United States)

    Hemsley, Piers A; Hurst, Charlotte H; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R; De Cothi, Elizabeth A; Steele, John F; Knight, Heather

    2014-01-01

    The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation-induced freezing tolerance. In addition, these three subunits are required for low temperature-induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced.

  1. Capital regulation: Less really can be more when incentives are socially aligned. Comments on Richard J. Herring "The Evolving Complexity of Capital Regulation". "The Interplay of Financial Regulations, Resilience, and Growth", Federal Reserve Bank of Philadelphia June 16-17, 2016

    OpenAIRE

    Hughes, Joseph P.

    2017-01-01

    Capital regulation has become increasingly complex as the largest financial institutions arbitrage differences in requirements across financial products to increase expected return for any given amount of regulatory capital, as financial regulators amend regulations to reduce arbitrage opportunities, and as financial institutions innovate to escape revised regulations - a regulatory dialectic. This increasing complexity makes monitoring bank risk-taking by markets and regulators more difficul...

  2. 9 CFR 2.35 - Recordkeeping requirements.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.35 Recordkeeping requirements. (a) The research... include: (i) The species and breed or type of animal; (ii) The sex; (iii) The date of birth or approximate...

  3. Nutrition-labeling regulation impacts on restaurant environments.

    Science.gov (United States)

    Saelens, Brian E; Chan, Nadine L; Krieger, James; Nelson, Young; Boles, Myde; Colburn, Trina A; Glanz, Karen; Ta, Myduc L; Bruemmer, Barbara

    2012-11-01

    Recent attempts to improve the healthfulness of away-from-home eating include regulations requiring restaurants to post nutrition information. The impact of such regulations on restaurant environments is unknown. To examine changes in restaurant environments from before to after nutrition-labeling regulation in a newly regulated county versus a nonregulated county. Using the Nutrition Environment Measures Survey-Restaurant version audit, environments within the same quick-service chain restaurants were evaluated in King County (regulated) before and 6 and 18 months after regulation enforcement and in Multnomah County (nonregulated) restaurants over a 6-month period. Data were collected in 2008-2010 and analyses conducted in 2011. Overall availability of healthy options and facilitation of healthy eating did not increase differentially in King County versus Multnomah County restaurants aside from the substantial increase in onsite nutrition information posting in King County restaurants required by the new regulation. Barriers to healthful eating decreased in King County relative to Multnomah County restaurants, particularly in food-oriented establishments. King County restaurants demonstrated modest increases in signage that promotes healthy eating, although the frequency of such promotion remained low, and the availability of reduced portions decreased in these restaurants. The healthfulness of children's menus improved modestly over time, but not differentially by county. A restaurant nutrition-labeling regulation was accompanied by some, but not uniform, improvements in other aspects of restaurant environments in the regulated compared to the nonregulated county. Additional opportunities exist for improving the healthfulness of away-from-home eating beyond menu labeling. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  4. The chemotaxis regulator pilG of Xylella fastidiosa is required for virulence in Vitis vinifera grapevines

    Science.gov (United States)

    Type IV pili of X. fastidiosa are regulated by pilG, a response regulator protein putatively involved in chemotaxis-like operon sensing stimuli through signal transduction pathways. To elucidate roles of pilG in pathogenicity of X. fastidiosa, the pilG-deletion mutant and complementary strain contai...

  5. 76 FR 69329 - Proposed Collection; Comment Request for Regulation Project

    Science.gov (United States)

    2011-11-08

    ... collection requirements related to Tax Shelter Regulations. DATES: Written comments should be received on or before January 9, 2012 to be assured of consideration. ADDRESSES: Direct all written comments to Yvette B... . SUPPLEMENTARY INFORMATION: Title: Tax Shelter Disclosure Regulations. OMB Number: 1545-1685. Regulation Project...

  6. Global approaches to regulating electronic cigarettes

    Science.gov (United States)

    Kennedy, Ryan David; Awopegba, Ayodeji; De León, Elaine; Cohen, Joanna E

    2017-01-01

    Objectives Classify and describe the policy approaches used by countries to regulate e-cigarettes. Methods National policies regulating e-cigarettes were identified by (1) conducting web searches on Ministry of Health websites, and (2) broad web searches. The mechanisms used to regulate e-cigarettes were classified as new/amended laws, or existing laws. The policy domains identified include restrictions or prohibitions on product: sale, manufacturing, importation, distribution, use, product design including e-liquid ingredients, advertising/promotion/sponsorship, trademarks, and regulation requiring: taxation, health warning labels and child-safety standards. The classification of the policy was reviewed by a country expert. Results The search identified 68 countries that regulate e-cigarettes: 22 countries regulate e-cigarettes using existing regulations; 25 countries enacted new policies to regulate e-cigarettes; 7 countries made amendments to existing legislation; 14 countries use a combination of new/amended and existing regulation. Common policies include a minimum-age-of-purchase, indoor-use (vape-free public places) bans and marketing restrictions. Few countries are applying a tax to e-cigarettes. Conclusions A range of regulatory approaches are being applied to e-cigarettes globally; many countries regulate e-cigarettes using legislation not written for e-cigarettes. PMID:27903958

  7. Regulation and drive system for high rep-rate magnetic-pulse compressors

    International Nuclear Information System (INIS)

    Birx, D.L.; Cook, E.G.; Hawkins, S.; Meyers, A.; Reginato, L.L.; Schmidt, J.A.; Smith, M.W.

    1982-01-01

    The essentially unlimited rep-rate capability of non-linear magnetic systems has imposed strict requirements on the drive system which initiates the pulse compression. An order of magnitude increase in the rep-rates achieved by the Advanced Test Accelerator (ATA) gas blown system is not difficult to achieve in the magnetic compressor. The added requirement of having a high degree of regulation at the higher rep-rates places strict requirements on the triggerable switch for charging and de-Queing. A novel feedback technique which applies the proper bias to a magnetic core by comparing a reference voltage to the charging voltage eases considerably the regulation required to achieve low jitter in magnetic compression. The performance of the high rep-rate charging and regulation systems will be described in the following pages

  8. Regulations for the safe transport of radioactive material, 2005 edition. Safety requirements

    International Nuclear Information System (INIS)

    2005-01-01

    This publication includes amendments to the 1996 Edition (As Amended 2003) arising from the second cycle of the biennial review and revision process, as agreed by the Transport Safety Standards Committee (TRANSSC) at its ninth meeting in March 2004, as endorsed by the Commission on Safety Standards at its meeting in June 2004 and as approved by the IAEA Board of Governors in November 2004. Although this publication is identified as a new edition, there are no changes that affect the administrative and approval requirements in Section VIII. The fields covered are General Provisions (radiation protection; emergency response; quality assurance; compliance assurance; non-compliance; special arrangement and training); Activity Limits and Materials Restrictions, Requirement and Controls for Transport , Requirements for Radioactive Materials and for Packagings and Packages, Test Procedures, Approval and Administrative Requirements

  9. 49 CFR 577.9 - Conformity to statutory requirements.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Conformity to statutory requirements. 577.9 Section 577.9 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY... NOTIFICATION § 577.9 Conformity to statutory requirements. A notification that does not conform to the...

  10. Regulation of abiotic stress signalling by Arabidopsis C-terminal domain phosphatase-like 1 requires interaction with a k-homology domain-containing protein.

    Directory of Open Access Journals (Sweden)

    In Sil Jeong

    Full Text Available Arabidopsis thaliana CARBOXYL-TERMINAL DOMAIN (CTD PHOSPHATASE-LIKE 1 (CPL1 regulates plant transcriptional responses to diverse stress signals. Unlike typical CTD phosphatases, CPL1 contains two double-stranded (ds RNA binding motifs (dsRBMs at its C-terminus. Some dsRBMs can bind to dsRNA and/or other proteins, but the function of the CPL1 dsRBMs has remained obscure. Here, we report identification of REGULATOR OF CBF GENE EXPRESSION 3 (RCF3 as a CPL1-interacting protein. RCF3 co-purified with tandem-affinity-tagged CPL1 from cultured Arabidopsis cells and contains multiple K-homology (KH domains, which were predicted to be important for binding to single-stranded DNA/RNA. Yeast two-hybrid, luciferase complementation imaging, and bimolecular fluorescence complementation analyses established that CPL1 and RCF3 strongly associate in vivo, an interaction mediated by the dsRBM1 of CPL1 and the KH3/KH4 domains of RCF3. Mapping of functional regions of CPL1 indicated that CPL1 in vivo function requires the dsRBM1, catalytic activity, and nuclear targeting of CPL1. Gene expression profiles of rcf3 and cpl1 mutants were similar during iron deficiency, but were distinct during the cold response. These results suggest that tethering CPL1 to RCF3 via dsRBM1 is part of the mechanism that confers specificity to CPL1-mediated transcriptional regulation.

  11. 48 CFR 652.219-73 - Mentor Requirements and Evaluation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Mentor Requirements and... Mentor Requirements and Evaluation. As prescribed in 619.202-70(o)(2), insert the following clause: Mentor Requirements and Evaluation (APR 2004) (a) Mentor and protégé firms shall submit an evaluation to...

  12. 48 CFR 1852.219-79 - Mentor requirements and evaluation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Mentor requirements and... and Clauses 1852.219-79 Mentor requirements and evaluation. As prescribed in 1819.7215, insert the following clause: Mentor Requirements and Evaluation (MAY 2009) (a) The purpose of the NASA Mentor-Protégé...

  13. 48 CFR 1052.219-75 - Mentor Requirements and Evaluation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Mentor Requirements and... Mentor Requirements and Evaluation. As prescribed in DTAR 1019.202-70, insert the following clause: Mentor Requirements and Evaluation (JAN 2000) (a) Mentor and protégé firms shall submit an evaluation to...

  14. Regulatory requirements important to Hanford single-shell tank waste management decisions

    International Nuclear Information System (INIS)

    Keller, J.F.; Woodruff, M.G.

    1989-06-01

    This report provides an initial analysis of the regulations that may be pertinent to SST management activities (e.g., characterization, disposal, retrieval, processing, etc.) and the interrelationships among those regulations. Waste disposal decisions regarding SST waste must consider the regulatory requirements against which technical solutions will be evaluated. Regulatory requirements can also be used as guidelines for management and disposal of waste in a manner that protects human health and safety and the environment. Also, in cases where waste management regulations do not specifically address a waste form, such as radioactive mixed waste, the SST waste may come under the purview of a number of regulations related to radioactive waste management, hazardous waste management, and water and air quality protection. This report provides a comprehensive review of the environmental pollution control and radioactive waste management statutes and regulations that are relevant to SST waste characterization and management. Also, other statutes and regulations that contain technical standards that may be used in the absence of directly applicable regulations are analyzed. 8 refs., 4 figs

  15. 75 FR 26739 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 244...

    Science.gov (United States)

    2010-05-12

    ... Control Number 0704-0253) AGENCY: Defense Acquisition Regulations System, Department of Defense. ACTION... proposed information collection; (c) ways to enhance the quality, utility, and clarity of the information..., withhold, or withdraw purchasing system approval at the conclusion of a purchasing system review...

  16. 15 CFR 762.3 - Records exempt from recordkeeping requirements.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Records exempt from recordkeeping requirements. 762.3 Section 762.3 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

  17. 7 CFR 1290.10 - Audit requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Audit requirements. 1290.10 Section 1290.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... audit, a copy of the audit results. ...

  18. Panel presentation: Should some type of incentive regulation replace traditional methods for regulating LDCs?

    International Nuclear Information System (INIS)

    Costello, K.W.

    1992-01-01

    State regulators should consider new approaches to regulating LDCs. They should seriously look at different incentive systems, even if only as an experiment, to address the major inefficiencies they see plaguing LDCs. Regulators have become more receptive in recent years to applying different incentive systems for historically heavily regulated industries such as the telecommunications and electric industries. In view of prevailing conditions in the natural gas industry, there is no good reason why regulators should not be as receptive to applying incentive systems for LDCs. For gas services offered in competitive markets, regulators should ask themselves whether regulation is necessary any longer. For services still requiring regulation, regulators should explore whether changes in traditional regulation are needed. While some PUCs have undertaken new regulatory practices, the question before them today is whether they should do more; whether, for example, states should accelerate their efforts toward adopting more flexible pricing and other incentive-based regulations or toward considering deregulating selected services. PUCs have different options. They can choose from among a large number of incentive systems. Their choices should hinge upon what they view as major sources of inefficiencies. For example, if uneconomical bypass is perceived as a problem then different price rules might constitute the cornerstone of an incentive-based policy. On the other hand, if excessive purchased-gas costs seem to be a major problem, a PUC may want to consider abolishing the PGA or modifying it in a form that would eliminate the cost-plus component

  19. 29 CFR 1926.704 - Requirements for precast concrete.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Requirements for precast concrete. 1926.704 Section 1926..., DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Concrete and Masonry Construction § 1926.704 Requirements for precast concrete. (a) Precast concrete wall units, structural framing...

  20. 40 CFR 465.03 - Monitoring and reporting requirements.

    Science.gov (United States)

    2010-07-01

    ... less than 30 days in advance of the scheduled production and shall provide the chemical analysis of the... this regulation. (a) Periodic analyses for cyanide are not required when both of the following... method required for determination of petroleum hydrocarbons (non-polar material) is given under the...

  1. Gas distribution regulations (Nova Scotia)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-11-03

    A consolidation of Nova Scotia`s gas distribution regulations made under subsection 42(1) of the Gas Distribution Act S.N.S. 1997, c4 - O.I.C. 1998-576 (November 10, 1998), N.S. Reg. 86/98 are presented. The consolidation is issued for reference purposes only, and while it has no official sanction, it is considered useful in providing an interpretation of the regulation, explaining franchise evaluation, the granting of franchises, and exemptions from application requirements. 1 tab.

  2. 77 FR 21846 - Reserve Requirements of Depository Institutions: Reserves Simplification

    Science.gov (United States)

    2012-04-12

    ... Requirements of Depository Institutions: Reserves Simplification AGENCY: Board of Governors of the Federal Reserve System. ACTION: Final rule. SUMMARY: The Board is amending Regulation D, Reserve Requirements of Depository Institutions, to simplify the administration of reserve requirements. The final rule creates a...

  3. Regulations for marine microalgal toxins: Towards harmonization of ...

    African Journals Online (AJOL)

    The World Trade Organization and the General Agreements on Tariffs and Trade encourage the harmonization of regulations on food safety requirements. The current policy on trade liberalization of seafood is presented, together with a review of the regulations for marine microalgal toxins. Activities on harmonization of ...

  4. 77 FR 5454 - Modifications to Minimum Present Value Requirements for Partial Annuity Distribution Options...

    Science.gov (United States)

    2012-02-03

    ... Modifications to Minimum Present Value Requirements for Partial Annuity Distribution Options Under Defined... guidance relating to the minimum present value requirements applicable to certain defined benefit pension plans. These proposed regulations would change the regulations regarding the minimum present value...

  5. 48 CFR 215.403-3 - Requiring information other than cost or pricing data.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Requiring information other than cost or pricing data. 215.403-3 Section 215.403-3 Federal Acquisition Regulations System... CONTRACTING BY NEGOTIATION Contract Pricing 215.403-3 Requiring information other than cost or pricing data...

  6. Enhancing socially shared regulation in collaborative learning groups: designing for CSCL regulation tools

    NARCIS (Netherlands)

    Järvelä, Sanna; Kirschner, Paul A.; Panadero, Ernesto; Malmberg, Jonna; Phielix, Chris; Jaspers, Jos; Koivuniemi, Marieke; Järvenoja, Hanna

    2016-01-01

    For effective computer supported collaborative learning (CSCL), socially shared regulation of learning (SSRL) is necessary. To this end, this article extends the idea first posited by Ja¨rvela¨ and Hadwin (Educ Psychol 48(1):25–39, 2013) that successful collaboration in CSCL contexts requires

  7. 48 CFR 552.219-76 - Mentor Requirements and Evaluation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Mentor Requirements and....219-76 Mentor Requirements and Evaluation. As prescribed in 519.7017(b), insert the following clause: Mentor Requirements and Evaluation (SEP 2009) (a) The purpose of the GSA Mentor-Protégé Program is for a...

  8. 48 CFR 752.219-71 - Mentor requirements and evaluation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Mentor requirements and....219-71 Mentor requirements and evaluation. As prescribed in AIDAR 719.273-11(b), insert the following clause: Mentor Requirements and Evaluation (July 13, 2007) (a) Mentor and Protégé firms shall submit an...

  9. Regulation and Control of Hazardous Wastes

    OpenAIRE

    Hans W. Gottinger

    1994-01-01

    Hazardous waste regulations require disposal in approved dumpsites, where environmental consequences are minimal but entry may be privately very costly. Imperfect policing of regulations makes the socially more costly option illicit disposal preferable form the perspective of the private decision maker. The existence of the waste disposal decision, its economic nature, production independence, and the control over environmental damage are key issues in the economics of hazardous waste managem...

  10. 75 FR 71344 - Uniform Compliance Date for Food Labeling Regulations

    Science.gov (United States)

    2010-11-23

    .... FSIS-2010-0031] RIN 0583-AD Uniform Compliance Date for Food Labeling Regulations AGENCY: Food Safety... regulations that require changes in the labeling of meat and poultry food products. Many meat and poultry... for new food labeling regulations is consistent with FDA's approach in this regard. FDA is also...

  11. Ex Post Regulation as the Method of Sectoral Regulation in Electricity Sector

    Directory of Open Access Journals (Sweden)

    Rafał Nagaj

    2017-10-01

    Full Text Available Aim/purpose - The aim of the article is to present the essence of ex post approach to sectoral regulation, to show the advantages and disadvantages of ex post regulation and to answer the question whether it is worth using in the electricity sector. Design/methodology/approach - For this purpose, a critical analysis of expert literature was made and an empirical analysis of countries that have applied ex post regulation in the electricity sector in the European Union. Two research methods were used: a case study and a comparison of changes in price and quality of services. The research period covered the period 2000-2016. Findings - It was found that ex post regulation reduces regulatory costs, does not adversely affect the quality of service and long-term rates, gives businesses the freedom of decision-making and the ability to react quickly to changes in the economy. The main disadvantages of ex post regulation are the tendency for companies to over-estimate bills for consumers, the difficulty of pursuing claims by consumers and the need to shift regulatory risk to consumers. Research implications/limitations - In the paper there was identified a research gap, i.e. the effects of ex post regulation in the electricity sector in European Union countries where such regulation was applied. Identifying the research gap will help us understand what are the advantages and disadvantages of ex post regulation and will create a model for when it is good moment to implement this in the economy. Besides identifying the research gap, further studies will be required over ex post regulation. Originality/value/contribution - The additional value of the paper is the study of ex post regulation, its essence and types. The article analyzed the effects of ex post regulation in the electricity sector and provided valuable insights into the potential risks associated with this approach to economic regulation.

  12. 48 CFR 1336.270 - Special requirements for ship construction

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Special requirements for ship construction 1336.270 Section 1336.270 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 1336.270 Special...

  13. HIF- and Non-HIF-Regulated Hypoxic Responses Require the Estrogen-Related Receptor in Drosophila melanogaster

    Science.gov (United States)

    Li, Yan; Padmanabha, Divya; Gentile, Luciana B.; Dumur, Catherine I.; Beckstead, Robert B.; Baker, Keith D.

    2013-01-01

    Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been determined. Here, we investigate how HIF influences hypoxic adaptation throughout Drosophila melanogaster development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in sima mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIFa and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIFa in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs. PMID:23382692

  14. Environmental Requirements Management

    Energy Technology Data Exchange (ETDEWEB)

    Cusack, Laura J.; Bramson, Jeffrey E.; Archuleta, Jose A.; Frey, Jeffrey A.

    2015-01-08

    CH2M HILL Plateau Remediation Company (CH2M HILL) is the U.S. Department of Energy (DOE) prime contractor responsible for the environmental cleanup of the Hanford Site Central Plateau. As part of this responsibility, the CH2M HILL is faced with the task of complying with thousands of environmental requirements which originate from over 200 federal, state, and local laws and regulations, DOE Orders, waste management and effluent discharge permits, Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) response and Resource Conservation and Recovery Act (RCRA) corrective action documents, and official regulatory agency correspondence. The challenge is to manage this vast number of requirements to ensure they are appropriately and effectively integrated into CH2M HILL operations. Ensuring compliance with a large number of environmental requirements relies on an organization’s ability to identify, evaluate, communicate, and verify those requirements. To ensure that compliance is maintained, all changes need to be tracked. The CH2M HILL identified that the existing system used to manage environmental requirements was difficult to maintain and that improvements should be made to increase functionality. CH2M HILL established an environmental requirements management procedure and tools to assure that all environmental requirements are effectively and efficiently managed. Having a complete and accurate set of environmental requirements applicable to CH2M HILL operations will promote a more efficient approach to: • Communicating requirements • Planning work • Maintaining work controls • Maintaining compliance

  15. 7 CFR 58.647 - Composition requirements for ice cream.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Composition requirements for ice cream. 58.647 Section 58.647 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... requirements for ice cream. See § 58.605(a). ...

  16. Regulations for the Safe Transport of Radioactive Materials. Vietnam Standard (TCVN 4985-89)

    International Nuclear Information System (INIS)

    1989-01-01

    The regulations were prepared in line with the Safety Regulation for Ionizing Radiations 1988 of Vietnam. Its purpose is to provide requirements in transport of radioactive materials. The exposure levels of transport personnel are determined. The package for different types of materials is regulated. The orders and procedures in transport are defined. In addition, specific requirements for each mean of transport are given. (N.H.A)

  17. 77 FR 4632 - Defense Federal Acquisition Regulation Supplement; Independent Research and Development Technical...

    Science.gov (United States)

    2012-01-30

    ... Federal Acquisition Regulation Supplement; Independent Research and Development Technical Descriptions... Regulation Supplement (DFARS) to require major contractors to report independent research and development (IR... 11414 on March 2, 2011, to revise requirements for reporting IR&D projects to the Defense Technical...

  18. 49 CFR 176.99 - Permit requirements for certain hazardous materials.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Permit requirements for certain hazardous materials. 176.99 Section 176.99 Transportation Other Regulations Relating to Transportation PIPELINE AND... CARRIAGE BY VESSEL Special Requirements for Barges § 176.99 Permit requirements for certain hazardous...

  19. 24 CFR 570.610 - Uniform administrative requirements and cost principles.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Uniform administrative requirements and cost principles. 570.610 Section 570.610 Housing and Urban Development Regulations Relating to... GRANTS Other Program Requirements § 570.610 Uniform administrative requirements and cost principles. The...

  20. 47 CFR 61.41 - Price cap requirements generally.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Price cap requirements generally. 61.41 Section... (CONTINUED) TARIFFS General Rules for Dominant Carriers § 61.41 Price cap requirements generally. (a... companies shall not bar a carrier from electing price cap regulation provided the carrier is otherwise...

  1. Environmentally acceptable thread compounds: Requirements defined

    International Nuclear Information System (INIS)

    Stringfellow, W.D.; Hendriks, R.V.; Jacobs, N.L.

    1993-01-01

    New environmental regulations on thread compounds are now being enforced in several areas with strong maritime tradition and a sensitive environment. These areas include Indonesia, Alaska and portions of Norway. The industry generally recognizes the environmental concerns but, with wider enforcement of regulations imminent, has not been able to define clearly the requirements for environmental compliance. This paper, written in collaboration with The Netherlands State Supervision of Mines, is based on the National Policy on Thread Compounds of The Netherlands. This national policy is representative of policies being followed by other North Sea governments. Similar policies might well be adopted by other governments worldwide. These policies will affect the operator, drilling contractor, and supplier. This paper provides a specific and detailed definition of thread compound requirements by addressing four relevant categories. The categories of interest are regulatory approval, environmental, health, and performance

  2. Situation selection is a particularly effective emotion regulation strategy for people who need help regulating their emotions.

    Science.gov (United States)

    Webb, Thomas L; Lindquist, Kristen A; Jones, Katelyn; Avishai, Aya; Sheeran, Paschal

    2018-03-01

    Situation selection involves choosing situations based on their likely emotional impact and may be less cognitively taxing or challenging to implement compared to other strategies for regulating emotion, which require people to regulate their emotions "in the moment"; we thus predicted that individuals who chronically experience intense emotions or who are not particularly competent at employing other emotion regulation strategies would be especially likely to benefit from situation selection. Consistent with this idea, we found that the use of situation selection interacted with individual differences in emotional reactivity and competence at emotion regulation to predict emotional outcomes in both a correlational (Study 1; N = 301) and an experimental field study (Study 2; N = 125). Taken together, the findings suggest that situation selection is an effective strategy for regulating emotions, especially for individuals who otherwise struggle to do so.

  3. 49 CFR 397.73 - Public information and reporting requirements.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Public information and reporting requirements. 397.73 Section 397.73 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL... Hazardous Materials § 397.73 Public information and reporting requirements. (a) Public information...

  4. 16 CFR 1500.125 - Labeling requirements for accompanying literature.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Labeling requirements for accompanying literature. 1500.125 Section 1500.125 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL... REGULATIONS § 1500.125 Labeling requirements for accompanying literature. When any accompanying literature...

  5. Emotion regulation choice : A conceptual framework and supporting evidence

    NARCIS (Netherlands)

    Sheppes, Gal; Scheibe, Susanne; Suri, Gaurav; Radu, Peter; Blechert, Jens; Gross, James J.

    Choice behavior is considered the fundamental means by which individuals exert control over their environments. One important choice domain that remains virtually unexplored is that of emotion regulation. This is surprising given that healthy adaptation requires flexibly choosing between regulation

  6. Safety Regulations for Ionizing Radiations. Vietnam Standard (TCVN 4397-87)

    International Nuclear Information System (INIS)

    1987-01-01

    The regulations were prepared for purpose of providing basic requirements of ionizing radiation protection and giving guide for design criteria of radiation installations in Vietnam. The allowable maximum levels for personnel categories are established. Regulated are methods for handling sealed and unsealed sources of radiation, transfer and transport of radioactive materials. Defined requirements and operating conditions that must be met. Determined are procedures and actions of decontamination. (N.H.A)

  7. 75 FR 51824 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2010-08-23

    ... discussion include the following: (1) What FDA expects in a pharmaceutical clinical trial; (2) adverse event reporting--science, regulation, error, and safety; (3) Part 11 Compliance--Electronic signatures; (4...

  8. Development of full sweet, umami, and bitter taste responsiveness requires Regulator of G protein Signaling-21 (RGS21).

    Science.gov (United States)

    Schroer, Adam B; Gross, Joshua D; Kaski, Shane W; Wix, Kim; Siderovski, David P; Vandenbeuch, Aurelie; Setola, Vincent

    2018-04-26

    The mammalian tastes of sweet, umami, and bitter are initiated by activation of G protein-coupled receptors (GPCRs) of the T1R and T2R families on taste receptor cells. GPCRs signal via nucleotide exchange and hydrolysis, the latter hastened by GTPase-accelerating proteins (GAPs) that include the Regulators of G protein Signaling (RGS) protein family. We previously reported that RGS21, uniquely expressed in Type II taste receptor cells, decreases the potency of bitter-stimulated T2R signaling in cultured cells, consistent with its in vitro GAP activity. However, the role of RGS21 in organismal responses to GPCR-mediated tastants was not established. Here, we characterized mice lacking the Rgs21 fifth exon. Eliminating Rgs21 expression had no effect on body mass accumulation (a measure of alimentation), fungiform papillae number and morphology, circumvallate papillae morphology, and taste bud number. Two-bottle preference tests, however, revealed that Rgs21-null mice have blunted aversion to quinine and denatonium, and blunted preference for monosodium glutamate, the sweeteners sucrose and SC45647, and (surprisingly) NaCl. Observed reductions in GPCR-mediated tastant responses upon Rgs21 loss are opposite to original expectations, given that loss of RGS21 -- a GPCR signaling negative regulator -- should lead to increased responsiveness to tastant-mediated GPCR signaling (all else being equal). Yet, reduced organismal tastant responses are consistent with observations of reduced chorda tympani nerve recordings in Rgs21-null mice. Reduced tastant-mediated responses and behaviors exhibited by adult mice lacking Rgs21 expression since birth have thus revealed an underappreciated requirement for a GPCR GAP to establish the full character of tastant signaling.

  9. Requirements for Ion and Solute Transport, and pH Regulation During Enamel Maturation

    Science.gov (United States)

    LACRUZ, RODRIGO S.; SMITH, CHARLES E.; MOFFATT, PIERRE; CHANG, EUGENE H.; BROMAGE, TIMOTHY G.; BRINGAS, PABLO; NANCI, ANTONIO; BANIWAL, SANJEEV K.; ZABNER, JOSEPH; WELSH, MICHAEL J.; KURTZ, IRA; PAINE, MICHAEL L.

    2012-01-01

    Transcellular bicarbonate transport is suspected to be an important pathway used by ameloblasts to regulate extracellular pH and support crystal growth during enamel maturation. Proteins that play a role in amelogenesis include members of the ABC transporters (SLC gene family and CFTR). A number of carbonic anhydrases (CAs) have also been identified. The defined functions of these genes are likely interlinked during enamel mineralization. The purpose of this study is to quantify relative mRNA levels of individual SLC, Cftr, and CAs in enamel cells obtained from secretory and maturation stages on rat incisors. We also present novel data on the enamel phenotypes for two animal models, amutant porcine(CFTR-ΔF508) and the NBCe1-null mouse.Our data show that two SLCs(AE2 and NBCe1),Cftr,and Car2, Car3,Car6,and Car12 are all significantly up-regulated at the onset of the maturation stage of amelogenesis when compared to the secretory stage. The remaining SLCs and CA gene transcripts showed negligible expression or no significant change in expression from secretory to maturation stages. The enamel of Cftr-ΔF508 adult pigs was hypomineralized and showed abnormal crystal growth. NBCe1-null mice enamel was structurally defective and had a marked decrease in mineral content relative to wild-type. These data demonstrate the importance of many non-matrix proteins to amelogenesis and that the expression levels of multiple genes regulating extracellular pH are modulated during enamel maturation in response to an increased need for pH buffering during hydroxyapatite crystal growth. PMID:21732355

  10. Concerning major items in government ordinance requiring modification of part of enforcement regulation for law relating to control of nuclear material, nuclear fuel and nuclear reactor

    International Nuclear Information System (INIS)

    1989-01-01

    The report describes major items planned to be incorporated into the enforcement regulations for laws relating to control of nuclear material, nuclear fuel and nuclear reactor. The modifications have become necessary for the nation to conclude a nuclear material protection treaty with other countries. The modification include the definitions of 'special nuclear fuel substances' and 'special nuclear fuel substances' and 'special nuclear fuel substances subject to protection'. The modifications require that protective measures be taken when handling and transporting special nuclear fuel substances subject to protection. Transport of special nuclear fuel substances requires approval from the Prime Minister or Transport Minister. Transport of special nuclear fuel substances subject to protection should be conducted after notifying the prefectural Public Safety Commission. Transport of special nuclear fuel substances subject to protection requires the conclusion of arrangements among responsible persons and approval of them from the Prime Minister. (N.K.)

  11. Regulations and classification advice: transport safety

    International Nuclear Information System (INIS)

    Davies, M.; Owen, K.

    1990-01-01

    The packaging of radioactive material for transport must conform with the regulations of the International Atomic Energy Agency (IAEA). These regulations are extensive and complex and require specialist interpretation. Packaging must be designed to contain the material, to limit radiation to safe levels, and to maintain the material in a safe state under both normal and accident conditions. British Nuclear Fuels Ltd. (BNFL) developed the TRANAID expert system to provide automated expert advice on the subject. It is used at BNFL and by other users internationally. The system was produced to meet an internal BNFL emphasis on accurate consistent and reliable interpretation of the complex IAEA regulations; and to provide a commercial product which would meet an external need. TRANAID provides reliable and consistent advice on safe transport procedures which reduce the workload on scarce skilled personnel, and allows them to concentrate on their primary task of packaging design. TRANAID also avoids overclassifying radioactive shipments, which would lead to the use of more expensive packaging than strictly is required. The IAEA regulations are applied internationally, and so there is a large potential worldwide market. The indications from the initial response are that future sales and use are expected to more than cover the investment. Other non-quantifiable benefits include the provision of consistent advice within a uniform approach, the safe-guarding of knowledge of the IAEA regulations, training and improvement in the expertise of users, improved management control, and enhancement of the professional image of BNFL. (author)

  12. 78 FR 80369 - Federal Acquisition Regulation; Service Contracts Reporting Requirements

    Science.gov (United States)

    2013-12-31

    ... (e.g., cost-reimbursement, time-and- materials, and labor-hour contracts), which already require... contract costs and labor can significantly fluctuate each year or how this type of labor can be comingled... of direct labor hours expended on the services performed is extremely concerning, particularly in a...

  13. Regulation Plans on Severe Accidents developed by KINS Severe Accident Regulation Preparation TFT

    International Nuclear Information System (INIS)

    Kim, Kyun Tae; Chung, Ku Young; Na, Han Bee

    2016-01-01

    Some nuclear power plants in Fukushima Daiichi site had lost their emergency reactor cooling function for long-time so the fuels inside the reactors were molten, and the integrity of containment was damaged. Therefore, large amount of radioactive material was released to environment. Because the social and economic effects of severe accidents are enormous, Korean Government already issued 'Severe Accident Policy' in 2001 which requires nuclear power plant operators to set up 'Quantitative Safety Goal', to do 'Probabilistic Safety Analysis', to install 'Severe Accident Countermeasures' and to make 'Severe Accident Management Plan'. After the Fukushima disaster, a Special Safety Inspection was performed for all operating nuclear power plants of Korea. The inspection team from industry, academia, and research institutes assessed Korean NPPs capabilities to cope with or respond to severe accidents and emergency situation caused by natural disasters such as a large earthquake or tsunami. As a result of the special inspection, about 50 action items were identified to increase the capability to cope with natural disaster and severe accidents. Nuclear Safety Act has been amended to require NPP operators to submit Accident Management Plant as part of operating license application. The KINS Severe Accident Regulation Preparation TFT had first investigated oversea severe accident regulation trend before and after the Fukushima accident. Then, the TFT has developed regulation draft for severe accidents such as Severe accident Management Plans, the required design features for new NPPs to prevent severe accident against multiple failures and beyond-design external events, countermeasures to mitigate severe accident and to keep the integrity of containment, and assessment methodology on safety assessment plan and probabilistic safety assessment

  14. Improved temperature regulation of APS linac RF components

    International Nuclear Information System (INIS)

    Dortwegt, R.

    1998-01-01

    The temperature of the APS S-Band linac's high-power rf components is regulated by water from individual closed-loop deionized (DI) water systems. The rf components are all made of oxygen-free high-conductivity copper and respond quickly to temperature changes. The SLED cavities are especially temperature-sensitive and cause beam energy instabilities when the temperature is not well regulated. Temperature regulation better than ± 0.1 F is required to achieve good energy stability. Improvements in the closed-loop water systems have enabled them to achieve a regulation of ± 0.05 F over long periods. Regulation philosophy and equipment are discussed and numerical results are presented

  15. 76 FR 17138 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2011-03-28

    ... initiated research. Topics for discussion include the following: (1) What FDA Expects in a Pharmaceutical Clinical Trial; (2) Adverse Event Reporting--Science, Regulation, Error, and Safety; (3) Part 11 Compliance...

  16. Overview of hazardous-waste regulation at federal facilities

    International Nuclear Information System (INIS)

    Tanzman, E.; LaBrie, B.; Lerner, K.

    1982-05-01

    This report is organized in a fashion that is intended to explain the legal duties imposed on officials responsible for hazardous waste at each stage of its existence. Section 2 describes federal hazardous waste laws, explaining the legal meaning of hazardous waste and the protective measures that are required to be taken by its generators, transporters, and storers. In addition, penalties for violation of the standards are summarized, and a special discussion is presented of so-called imminent hazard provisions for handling hazardous waste that immediately threatens public health and safety. Although the focus of Sec. 2 is on RCRA, which is the principal federal law regulating hazardous waste, other federal statutes are discussed as appropriate. Section 3 covers state regulation of hazardous waste. First, Sec. 3 explains the system of state enforcement of the federal RCRA requirements on hazardous waste within their borders. Second, Sec. 3 discusses two peculiar provisions of RCRA that appear to permit states to regulate federal facilities more strictly than RCRA otherwise would require

  17. Overview of hazardous-waste regulation at federal facilities

    Energy Technology Data Exchange (ETDEWEB)

    Tanzman, E.; LaBrie, B.; Lerner, K.

    1982-05-01

    This report is organized in a fashion that is intended to explain the legal duties imposed on officials responsible for hazardous waste at each stage of its existence. Section 2 describes federal hazardous waste laws, explaining the legal meaning of hazardous waste and the protective measures that are required to be taken by its generators, transporters, and storers. In addition, penalties for violation of the standards are summarized, and a special discussion is presented of so-called imminent hazard provisions for handling hazardous waste that immediately threatens public health and safety. Although the focus of Sec. 2 is on RCRA, which is the principal federal law regulating hazardous waste, other federal statutes are discussed as appropriate. Section 3 covers state regulation of hazardous waste. First, Sec. 3 explains the system of state enforcement of the federal RCRA requirements on hazardous waste within their borders. Second, Sec. 3 discusses two peculiar provisions of RCRA that appear to permit states to regulate federal facilities more strictly than RCRA otherwise would require.

  18. 78 FR 67084 - Drawbridge Operation Regulation; Broad Creek, Laurel, DE

    Science.gov (United States)

    2013-11-08

    ...-AA09 Drawbridge Operation Regulation; Broad Creek, Laurel, DE AGENCY: Coast Guard, DHS. ACTION: Notice....25, both at Laurel, DE. The proposed new rule would change the current regulation by requiring a..., mile 8.2, all at Laurel, shall open on signal if at least 48 hours notice is given. Previous regulation...

  19. Procedure manual: protocol for regulation of petroleum hydrocarbons in water under the special waste and contaminated sites regulation

    International Nuclear Information System (INIS)

    Evans, P.; Partridge, E.

    2002-05-01

    This document details the regulation governing numerical standards for petroleum hydrocarbons in water under the special waste and contaminated sites regulations of British Columbia. Groundwater containing benzene, toluene, ethylbenzene or xylenes in excess of the leachate standards is exempted from the regulatory regime of the Special Waste Regulation. The document contains a description of the conditions that apply to the management of petroleum hydrocarbons in water at contaminated sites. Some definitions are included, followed by an overview of the regulation. The third section deals with authorization and mandatory conditions, while additional requirements that might apply are enumerated in section four. This protocol directly affects the Environmental Management, and the Environmental Protection Regional Operations organizations. 1 tab

  20. 7 CFR 3430.906 - Matching requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Matching requirements. 3430.906 Section 3430.906 Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE COMPETITIVE AND NONCOMPETITIVE NON-FORMULA FEDERAL...

  1. Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis

    Energy Technology Data Exchange (ETDEWEB)

    MULKEY, C.H.

    1999-07-06

    This document describes the results of the data quality objective (DQO) process undertaken to define data needs for state and federal requirements associated with toxic, hazardous, and/or radiological air emissions under the jurisdiction of the River Protection Project (RPP). Hereafter, this document is referred to as the Air DQO. The primary drivers for characterization under this DQO are the regulatory requirements pursuant to Washington State regulations, that may require sampling and analysis. The federal regulations concerning air emissions are incorporated into the Washington State regulations. Data needs exist for nonradioactive and radioactive waste constituents and characteristics as identified through the DQO process described in this document. The purpose is to identify current data needs for complying with regulatory drivers for the measurement of air emissions from RPP facilities in support of air permitting. These drivers include best management practices; similar analyses may have more than one regulatory driver. This document should not be used for determining overall compliance with regulations because the regulations are in constant change, and this document may not reflect the latest regulatory requirements. Regulatory requirements are also expected to change as various permits are issued. Data needs require samples for both radionuclides and nonradionuclide analytes of air emissions from tanks and stored waste containers. The collection of data is to support environmental permitting and compliance, not for health and safety issues. This document does not address health or safety regulations or requirements (those of the Occupational Safety and Health Administration or the National Institute of Occupational Safety and Health) or continuous emission monitoring systems. This DQO is applicable to all equipment, facilities, and operations under the jurisdiction of RPP that emit or have the potential to emit regulated air pollutants.

  2. Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis

    International Nuclear Information System (INIS)

    MULKEY, C.H.

    1999-01-01

    This document describes the results of the data quality objective (DQO) process undertaken to define data needs for state and federal requirements associated with toxic, hazardous, and/or radiological air emissions under the jurisdiction of the River Protection Project (RPP). Hereafter, this document is referred to as the Air DQO. The primary drivers for characterization under this DQO are the regulatory requirements pursuant to Washington State regulations, that may require sampling and analysis. The federal regulations concerning air emissions are incorporated into the Washington State regulations. Data needs exist for nonradioactive and radioactive waste constituents and characteristics as identified through the DQO process described in this document. The purpose is to identify current data needs for complying with regulatory drivers for the measurement of air emissions from RPP facilities in support of air permitting. These drivers include best management practices; similar analyses may have more than one regulatory driver. This document should not be used for determining overall compliance with regulations because the regulations are in constant change, and this document may not reflect the latest regulatory requirements. Regulatory requirements are also expected to change as various permits are issued. Data needs require samples for both radionuclides and nonradionuclide analytes of air emissions from tanks and stored waste containers. The collection of data is to support environmental permitting and compliance, not for health and safety issues. This document does not address health or safety regulations or requirements (those of the Occupational Safety and Health Administration or the National Institute of Occupational Safety and Health) or continuous emission monitoring systems. This DQO is applicable to all equipment, facilities, and operations under the jurisdiction of RPP that emit or have the potential to emit regulated air pollutants

  3. Targeted genome regulation via synthetic programmable transcriptional regulators

    KAUST Repository

    Piatek, Agnieszka Anna

    2016-04-19

    Regulation of gene transcription controls cellular functions and coordinates responses to developmental, physiological and environmental cues. Precise and efficient molecular tools are needed to characterize the functions of single and multiple genes in linear and interacting pathways in a native context. Modular DNA-binding domains from zinc fingers (ZFs) and transcriptional activator-like proteins (TALE) are amenable to bioengineering to bind DNA target sequences of interest. As a result, ZF and TALE proteins were used to develop synthetic programmable transcription factors. However, these systems are limited by the requirement to re-engineer proteins for each new target sequence. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) genome editing tool was recently repurposed for targeted transcriptional regulation by inactivation of the nuclease activity of Cas9. Due to the facile engineering, simplicity, precision and amenability to library construction, the CRISPR/Cas9 system is poised to revolutionize the functional genomics field across diverse eukaryotic species. In this review, we discuss the development of synthetic customizable transcriptional regulators and provide insights into their current and potential applications, with special emphasis on plant systems, in characterization of gene functions, elucidation of molecular mechanisms and their biotechnological applications. © 2016 Informa UK Limited, trading as Taylor & Francis Group

  4. 17 CFR 242.301 - Requirements for alternative trading systems.

    Science.gov (United States)

    2010-04-01

    ... trading systems. 242.301 Section 242.301 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... FUTURES Regulation Ats-Alternative Trading Systems § 242.301 Requirements for alternative trading systems. (a) Scope of section. An alternative trading system shall comply with the requirements in paragraph...

  5. Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development

    DEFF Research Database (Denmark)

    Elias, Bertha C; Das, Amrita; Parekh, Diptiben V

    2015-01-01

    The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development and main......The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development...

  6. 29 CFR 1926.703 - Requirements for cast-in-place concrete.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Requirements for cast-in-place concrete. 1926.703 Section..., DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Concrete and Masonry Construction § 1926.703 Requirements for cast-in-place concrete. (a) General requirements for formwork. (1...

  7. Developing Young Children's Self-Regulation through Everyday Experiences

    Science.gov (United States)

    Florez, Ida Rose

    2011-01-01

    Every child is different. Some have difficulty expressing their ideas verbally. Some struggle to get along with peers or follow classroom routines. In each case, however, one thing is the same: improved learning and behavior requires strong self-regulation skills. Children develop foundational skills for self-regulation in the first five years of…

  8. Implementation of the new regulation on radiological safety in Peru

    International Nuclear Information System (INIS)

    Medina Gironzini, E.

    1997-01-01

    Since its creation in 1975, the Peruvian Institute of Nuclear Energy (IPEN) has enacted three regulations of national importance on the norms of protection against ionizing radiation. The first regulation, which is called regulation of radiological protection (1980) approved by a resolution of IPEN, is the result of the work of a committee constituted by IPEN and the Ministry of Health. Its implementation caused some problems as result of which, in 1989, a new regulation on radiological protection was enacted through a supreme decree. Taking into account the new recommendation of the International Commission on Radiological Protection and the International Basic Safety Standard for Protection against Ionizing Radiation and for the Safety of Radiation Sources, approved in May 1997, the regulation of radiological safety also considers evolving aspects in the Project ARCAL XVII/IAEA. This regulation includes various topics such as exclusions, requirements of protection (medical exposure, occupational exposure, public exposure, chronic exposure), requirements of source safety, interventions and emergencies, control of sources and practices (exemptions, authorizations, inspections) etc. The implementation of this regulation at the national level falls to IPEN, the unique authority commissioned to control nuclear installations, radioactivity and x ray facilities in medicine, industry and research

  9. 49 CFR 178.801 - General requirements.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR PACKAGINGS... transportation and are considered minimum requirements. Each packaging must be manufactured and assembled so as... design type refers to an IBC that does not differ in structural design, size, material of construction...

  10. Oligomerization of Bacillus subtilis DesR is required for fine tuning regulation of membrane fluidity.

    Science.gov (United States)

    Najle, Sebastián R; Inda, María E; de Mendoza, Diego; Cybulski, Larisa E

    2009-10-01

    The DesK-DesR two-component system regulates the order of membrane lipids in the bacterium Bacillus subtilis by controlling the expression of the des gene coding for the delta 5-acyl-lipid desaturase. To activate des transcription, the membrane-bound histidine kinase DesK phosphorylates the response regulator DesR. This covalent modification of the regulatory domain of dimeric DesR promotes, in a cooperative fashion, the hierarchical occupation of two adjacent, non-identical, DesR-P binding sites, so that there is a shift in the equilibrium toward the tetrameric active form of the response regulator. However, the mechanism of regulation of DesR activity by phosphorylation and oligomerization is not well understood. We employed deletion analysis and reporter fusions to study the role of the N-terminal domain on DesR activity. In addition, electromobility shift assays were used to analyze the binding capacity of the transcription factor to deletion mutants of the des promoter. We show that DesR lacking the N-terminal domain is still able to bind to the des promoter. We also demonstrate that if the RA site is moved closer to the -35 region of Pdes, the adjacent site RB is dispensable for activation. Our results indicate that the unphosphorylated regulatory domain of DesR obstructs the access of the recognition helix of DesR to its DNA target. In addition, we present evidence showing that RB is physiologically relevant to control the activation of the des gene when the levels of DesR-P reach a critical threshold.

  11. 77 FR 55475 - Federal Acquisition Regulation; Information Collection; Permits, Authorities, or Franchises

    Science.gov (United States)

    2012-09-10

    ...; Information Collection; Permits, Authorities, or Franchises AGENCY: Department of Defense (DOD), General... approved information collection requirement concerning permits, authorities, or franchises for regulated..., Authorities, or Franchises, by any of the following methods: Regulations.gov : http://www.regulations.gov...

  12. Certification of School Librarians: A Compilation of State Requirements, 1958. Bulletin, 1958, No. 12

    Science.gov (United States)

    Mahar, Mary Helen

    1958-01-01

    This bulletin on requirements by States and Territories for the certification of school librarians was prepared to provide a compilation of current certification regulations for school librarians and a summary of practices in formulating these regulations. The requirements for each State were obtained from either the State school library…

  13. 49 CFR 192.513 - Test requirements for plastic pipelines.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Test requirements for plastic pipelines. 192.513 Section 192.513 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... Test requirements for plastic pipelines. (a) Each segment of a plastic pipeline must be tested in...

  14. Regulation of ROCK Activity in Cancer

    DEFF Research Database (Denmark)

    Morgan-Fisher, Marie; Wewer, Ulla M; Yoneda, Atsuko

    2013-01-01

    , these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.......Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key...... regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active...

  15. Dealing with duplicate regulations and conflicting jurisdictions

    International Nuclear Information System (INIS)

    Aamodt, P.L.

    1991-01-01

    There are a number of situations where mixed wastes are regulated by dual regulations and regulators. This presentation attempts to show where such duplication exists and how it evolved historically through legislative actions. The presentation includes a discussion of strategies that have been used to deal with the problems that result from duplicate regulations and jurisdictional conflicts. The RCRA and AEA regulations are really more similar than dissimilar. There are significant issues that must be worked through with the regulators. It is most important to work with your regulators early in process. The following are suggestions for dealing with the regulators. (1) Know the regulations in advance of discussions. (2) Begin dialogue with the regulator(s) as early as possible and get to know the people you will be dealing with -- and let them know you. (3) Explain the technical/regulatory issues/problems that you face at your facility in sufficient detail that they are clearly understood, and work with the regulator(s) to reasonably address them in the language/requirements of the permit. (4) Always attempt to comply with the regulations first before going in with a variance request -- document your efforts, and be honest with your assessment of issues. (5) Don't be adversarial -- remember that the regulator has the same objectives as you do. 1 tab

  16. International laser-safety regulations: a status update

    Science.gov (United States)

    Weiner, Robert M.

    1990-07-01

    There is an increase in international laser safety requirements as part of the emphasis on world-wide standardization of products and regulations. In particular the documents which will evolve from the 1992 consolidation efforts of the European Community (EC) will impact both laser manufacturers and users. This paper provides a discussion of the current status of the various laser radiation standards. NORTH AMERICAN REQUIREMENTS United States Requirements on manufacturers from the Food and Drug Administration (FDA) have been in effect since 1975. The Center for Devices and Radiological Health (CDRH) within that agency ensures that these mandatory requirements [1] are satisfied. The CDRH regulations include the division of products into classes depending on their potential for hazard criteria for power measurement and requirements for product features labels and manuals and records and reports. Manufacturers must test products and certify that they comply with the CDRH requirements. User requirements are found in a standard published by the American National Standards Institute (ANSI) and in requirements from several individual states. Specific ANSI standards have also been published for fiber communications systems [34] and for lasers in medical applications [35]. Please note that the Appendix includes additional information on the standards discussed in this paper including sources for obtaining the documents. Canada In the past Canada has had requirements for two specified product categories (bar code scanners and educational lasers) [26 These will be replaced

  17. 49 CFR 383.123 - Requirements for a school bus endorsement.

    Science.gov (United States)

    2010-10-01

    ... devices required for school buses by State or Federal law or regulation. (ii) Emergency exits and... 49 Transportation 5 2010-10-01 2010-10-01 false Requirements for a school bus endorsement. 383.123... Requirements for a school bus endorsement. (a) An applicant for a school bus endorsement must satisfy the...

  18. Grid code requirements for wind power generation

    International Nuclear Information System (INIS)

    Djagarov, N.; Filchev, S.; Grozdev, Z.; Bonev, M.

    2011-01-01

    In this paper production data of wind power in Europe and Bulgaria and plans for their development within 2030 are reviewed. The main characteristics of wind generators used in Bulgaria are listed. A review of the grid code in different European countries, which regulate the requirements for renewable sources, is made. European recommendations for requirements harmonization are analyzed. Suggestions for the Bulgarian gird code are made

  19. 77 FR 13046 - Customer Due Diligence Requirements for Financial Institutions

    Science.gov (United States)

    2012-03-05

    ... industries that have anti-money laundering (AML) program requirements under FinCEN's regulations. At this... effective anti-money laundering program.\\1\\ \\1\\ See, e.g., ``Anti-Money Laundering Programs for Insurance... BSA and FinCEN's implementing regulations or guard against money laundering.\\6\\ \\2\\ The BSA is...

  20. 48 CFR 752.245-70 - Government property-USAID reporting requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Government property-USAID reporting requirements. 752.245-70 Section 752.245-70 Federal Acquisition Regulations System AGENCY FOR... recommendation, USAID contracts, except for those for commercial items, must contain the following preface and...

  1. 15 CFR 738.4 - Determining whether a license is required.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Determining whether a license is required. 738.4 Section 738.4 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

  2. 78 FR 4307 - Current Good Manufacturing Practice Requirements for Combination Products

    Science.gov (United States)

    2013-01-22

    ...-2009-N-0435] Current Good Manufacturing Practice Requirements for Combination Products AGENCY: Food and...) is issuing this regulation on the current good manufacturing practice (CGMP) requirements applicable... this subpart? (Sec. 4.2) D. What current good manufacturing practice requirements apply to my...

  3. 10 CFR 51.94 - Requirement to consider final environmental impact statement.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Requirement to consider final environmental impact...-Regulations Implementing Section 102(2) Final Environmental Impact Statements-General Requirements § 51.94 Requirement to consider final environmental impact statement. The final environmental impact statement...

  4. The Arabidopsis Mediator Complex Subunits MED16, MED14, and MED2 Regulate Mediator and RNA Polymerase II Recruitment to CBF-Responsive Cold-Regulated Genes[C][W][OPEN

    Science.gov (United States)

    Hemsley, Piers A.; Hurst, Charlotte H.; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R.; De Cothi, Elizabeth A.; Steele, John F.; Knight, Heather

    2014-01-01

    The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation–induced freezing tolerance. In addition, these three subunits are required for low temperature–induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced. PMID:24415770

  5. Down-regulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on.

    Science.gov (United States)

    Bergö, Martin; Wu, Gengshu; Ruge, Toralph; Olivecrona, Thomas

    2002-04-05

    During short term fasting, lipoprotein lipase (LPL) activity in rat adipose tissue is rapidly down-regulated. This down-regulation occurs on a posttranslational level; it is not accompanied by changes in LPL mRNA or protein levels. The LPL activity can be restored within 4 h by refeeding. Previously, we showed that during fasting there is a shift in the distribution of lipase protein toward an inactive form with low heparin affinity. To study the nature of the regulatory mechanism, we determined the in vivo turnover of LPL activity, protein mass, and mRNA in rat adipose tissue. When protein synthesis was inhibited with cycloheximide, LPL activity and protein mass decreased rapidly and in parallel with half-lives of around 2 h, and the effect of refeeding was blocked. This indicates that maintaining high levels of LPL activity requires continuous synthesis of new enzyme protein. When transcription was inhibited by actinomycin, LPL mRNA decreased with half-lives of 13.3 and 16.8 h in the fed and fasted states, respectively, demonstrating slow turnover of the LPL transcript. Surprisingly, when actinomycin was given to fed rats, LPL activity was not down-regulated during fasting, indicating that actinomycin interferes with the transcription of a gene that blocks the activation of newly synthesized LPL protein. When actinomycin was given to fasted rats, LPL activity increased 4-fold within 6 h, even in the absence of refeeding. The same effect was seen with alpha-amanitin, another inhibitor of transcription. The response to actinomycin was much less pronounced in aging rats, which are obese and insulin-resistant. These data suggest a default state where LPL protein is synthesized on a relatively stable mRNA and is processed into its active form. During fasting, a gene is switched on whose product prevents the enzyme from becoming active even though synthesis of LPL protein continues unabated.

  6. Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis

    International Nuclear Information System (INIS)

    MULKEY, C.H.

    1999-01-01

    This document describes the results of the data quality objective (DQO) process undertaken to define data needs for state and federal requirements associated with toxic, hazardous, and/or radiological air emissions under the jurisdiction of the River Protection Project (RPP). Hereafter, this document is referred to as the Air DQO. The primary drivers for characterization under this DQO are the regulatory requirements pursuant to Washington State regulations, that may require sampling and analysis. The federal regulations concerning air emissions are incorporated into the Washington State regulations. Data needs exist for nonradioactive and radioactive waste constituents and characteristics as identified through the DQO process described in this document. The purpose is to identify current data needs for complying with regulatory drivers for the measurement of air emissions from RPP facilities in support of air permitting. These drivers include best management practices; similar analyses may have more than one regulatory driver. This document should not be used for determining overall compliance with regulations because the regulations are in constant change, and this document may not reflect the latest regulatory requirements. Regulatory requirements are also expected to change as various permits are issued. Data needs require samples for both radionuclides and nonradionuclide analytes of air emissions from tanks and stored waste containers. The collection of data is to support environmental permitting and compliance, not for health and safety issues

  7. The Drosophila nerfin-1 mRNA requires multiple microRNAs to regulate its spatial and temporal translation dynamics in the developing nervous system.

    Science.gov (United States)

    Kuzin, Alexander; Kundu, Mukta; Brody, Thomas; Odenwald, Ward F

    2007-10-01

    The mRNA encoding the Drosophila Zn-finger transcription factor Nerfin-1, required for CNS axon pathfinding events, is subject to post-transcriptional silencing. Although nerfin-1 mRNA is expressed in many neural precursor cells including all early delaminating CNS neuroblasts, the encoded Nerfin-1 protein is detected only in the nuclei of neural precursors that divide just once to generate neurons and then only transiently in nascent neurons. Using a nerfin-1 promoter-controlled reporter transgene, replacement of the nerfin-1 3' UTR with the viral SV-40 3' UTR releases the neuroblast translational block and prolongs reporter protein expression in neurons. Comparative genomics analysis reveals that the nerfin-1 mRNA 3' UTR contains multiple highly conserved sequence blocks that either harbor and/or overlap 21 predicted binding sites for 18 different microRNAs. To determine the functional significance of these microRNA-binding sites and less conserved microRNA target sites, we have studied their ability to block or limit the expression of reporter protein in nerfin-1-expressing cells during embryonic development. Our results indicate that no single microRNA is sufficient to fully inhibit protein expression but rather multiple microRNAs that target different binding sites are required to block ectopic protein expression in neural precursor cells and temporally restrict expression in neurons. Taken together, these results suggest that multiple microRNAs play a cooperative role in the post-transcriptional regulation of nerfin-1 mRNA, and the high degree of microRNA-binding site evolutionary conservation indicates that all members of the Drosophila genus employ a similar strategy to regulate the onset and extinction dynamics of Nerfin-1 expression.

  8. 7 CFR 35.11 - Minimum requirements.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... applicable to the variety and destination specified: (a) Any such variety for export to destinations in Japan... requirements. (b) Any such variety for export to any foreign destination, other than destinations in Japan...

  9. 12 CFR 701.31 - Nondiscrimination requirements.

    Science.gov (United States)

    2010-01-01

    ... ORGANIZATION AND OPERATION OF FEDERAL CREDIT UNIONS § 701.31 Nondiscrimination requirements. (a) Definitions... words, symbols, models or other forms of communication that suggest a discriminatory preference or... in § 110.25(a) of the United States Department of Housing and Urban Development's (HUD) regulations...

  10. 16 CFR 1512.17 - Other requirements.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Other requirements. 1512.17 Section 1512.17 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS... the ground plane. (d) Toe clearance. Bicycles not equipped with positive foot-retaining devices (such...

  11. 20 CFR 633.309 - Recordkeeping requirements.

    Science.gov (United States)

    2010-04-01

    ... data components provide federally-required records and reports that are accurate, uniform in definition... accordance with established program definitions contained in the Act and these regulations; (2) Follow..., consistent, and accurate; (5) Meet generally accepted accounting principles as prescribed in 41 CFR part 29...

  12. Combinatorial Cis-regulation in Saccharomyces Species

    Directory of Open Access Journals (Sweden)

    Aaron T. Spivak

    2016-03-01

    Full Text Available Transcriptional control of gene expression requires interactions between the cis-regulatory elements (CREs controlling gene promoters. We developed a sensitive computational method to identify CRE combinations with conserved spacing that does not require genome alignments. When applied to seven sensu stricto and sensu lato Saccharomyces species, 80% of the predicted interactions displayed some evidence of combinatorial transcriptional behavior in several existing datasets including: (1 chromatin immunoprecipitation data for colocalization of transcription factors, (2 gene expression data for coexpression of predicted regulatory targets, and (3 gene ontology databases for common pathway membership of predicted regulatory targets. We tested several predicted CRE interactions with chromatin immunoprecipitation experiments in a wild-type strain and strains in which a predicted cofactor was deleted. Our experiments confirmed that transcription factor (TF occupancy at the promoters of the CRE combination target genes depends on the predicted cofactor while occupancy of other promoters is independent of the predicted cofactor. Our method has the additional advantage of identifying regulatory differences between species. By analyzing the S. cerevisiae and S. bayanus genomes, we identified differences in combinatorial cis-regulation between the species and showed that the predicted changes in gene regulation explain several of the species-specific differences seen in gene expression datasets. In some instances, the same CRE combinations appear to regulate genes involved in distinct biological processes in the two different species. The results of this research demonstrate that (1 combinatorial cis-regulation can be inferred by multi-genome analysis and (2 combinatorial cis-regulation can explain differences in gene expression between species.

  13. Regulation Plans on Severe Accidents developed by KINS Severe Accident Regulation Preparation TFT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyun Tae; Chung, Ku Young; Na, Han Bee [KINS, Daejeon (Korea, Republic of)

    2016-05-15

    Some nuclear power plants in Fukushima Daiichi site had lost their emergency reactor cooling function for long-time so the fuels inside the reactors were molten, and the integrity of containment was damaged. Therefore, large amount of radioactive material was released to environment. Because the social and economic effects of severe accidents are enormous, Korean Government already issued 'Severe Accident Policy' in 2001 which requires nuclear power plant operators to set up 'Quantitative Safety Goal', to do 'Probabilistic Safety Analysis', to install 'Severe Accident Countermeasures' and to make 'Severe Accident Management Plan'. After the Fukushima disaster, a Special Safety Inspection was performed for all operating nuclear power plants of Korea. The inspection team from industry, academia, and research institutes assessed Korean NPPs capabilities to cope with or respond to severe accidents and emergency situation caused by natural disasters such as a large earthquake or tsunami. As a result of the special inspection, about 50 action items were identified to increase the capability to cope with natural disaster and severe accidents. Nuclear Safety Act has been amended to require NPP operators to submit Accident Management Plant as part of operating license application. The KINS Severe Accident Regulation Preparation TFT had first investigated oversea severe accident regulation trend before and after the Fukushima accident. Then, the TFT has developed regulation draft for severe accidents such as Severe accident Management Plans, the required design features for new NPPs to prevent severe accident against multiple failures and beyond-design external events, countermeasures to mitigate severe accident and to keep the integrity of containment, and assessment methodology on safety assessment plan and probabilistic safety assessment.

  14. Regulation on Radiation Safety of Guatemala

    International Nuclear Information System (INIS)

    2001-03-01

    This regulation includes all the requirements administrative, radiation protection, that licensees must meet in order to obtain authorization from the competent authority to apply and use radiation sources, equipment emiting ionizing radiation in different practices authorized

  15. Regulation requirements for the protection of workers against electromagnetic fields occurring in the work environment

    International Nuclear Information System (INIS)

    Aniolczyk, H.; Zmyslony, M.

    2006-01-01

    In Poland, electromagnetic fields (EMF), one of potentially hazardous physical factors occurring in the work environment, are subjected to compulsory surveillance. In 2001, the Directive issued by the Minister of Labor and Social Policy substantially changed the approach towards the protection of workers against EMF. The Directive regulates the whole range of EMF frequencies and electromagnetic radiation, namely from 0 Hz to 300 GHz, which means the possibility of assessing workers EMF exposure, determined by exposure index, along with the hygiene assessment of EMF sources, defined by protection zones. In 2003 - 2005, a number of amended executive and supplementary regulations were issued. However, it should be emphasized that in the process of their elaboration, striving after perfection, numerous incoherent and ambiguous provisions were adopted, which finally created difficulties in the interpretation of individual regulations. This is also linked with doubts and discussions on their practical application by services responsible for control, measurements and monitoring of working conditions under the exposure to EMF. In this work an attempt was made to clarify all issues and arrange them according to the faced problems. The authors also present proposals how to solve all these problems. (author)

  16. Guidance and methods for satisfying low specific activity material and surface contaminated object regulatory requirements

    International Nuclear Information System (INIS)

    Pope, R.B.; Shappert, L.B.; Michelhaugh, R.D.; Boyle, R.W.; Easton, E.P.; Coodk, J.R.

    1998-01-01

    The U.S. Department of Transportation (DOT) and the U.S. Nuclear Regulatory Commission (NRC) have prepared a comprehensive set of draft guidance for shippers and inspectors to use when applying the newly imposed regulatory requirements for low specific activity (LSA) material and surface contaminated objects (SCOs). These requirements represent significant departures in some areas from the manner in which these materials and objects were regulated by the earlier versions of the regulations. The proper interpretation and application of the regulatory criteria can require a fairly complex set of decisions be made. To assist those trying these regulatory requirements, a detailed set of logic-flow diagrams representing decisions related to multiple factors were prepared and included in the draft report for comment on Categorizing and Transporting Low Specific Activity Materials and Surface Contaminated Objects, (DOT/NRC, 1997). These logic-flow diagrams, as developed, are specific to the U.S. regulations, but were readily adaptable to the IAEA regulations. The diagrams have been modified accordingly and tied directly to specific paragraphs in IAEA Safety Series No. 6. This paper provides the logic-flow diagrams adapted in the IAEA regulations, and demonstrated how these diagrams can be used to assist consignors and inspectors in assessing compliance of shipments with the LSA material and SCO regulatory requirements. (authors)

  17. Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis; FINAL

    International Nuclear Information System (INIS)

    MULKEY, C.H.

    1999-01-01

    This document describes the results of the data quality objective (DQO) process undertaken to define data needs for state and federal requirements associated with toxic, hazardous, and/or radiological air emissions under the jurisdiction of the River Protection Project (RPP). Hereafter, this document is referred to as the Air DQO. The primary drivers for characterization under this DQO are the regulatory requirements pursuant to Washington State regulations, that may require sampling and analysis. The federal regulations concerning air emissions are incorporated into the Washington State regulations. Data needs exist for nonradioactive and radioactive waste constituents and characteristics as identified through the DQO process described in this document. The purpose is to identify current data needs for complying with regulatory drivers for the measurement of air emissions from RPP facilities in support of air permitting. These drivers include best management practices; similar analyses may have more than one regulatory driver. This document should not be used for determining overall compliance with regulations because the regulations are in constant change, and this document may not reflect the latest regulatory requirements. Regulatory requirements are also expected to change as various permits are issued. Data needs require samples for both radionuclides and nonradionuclide analytes of air emissions from tanks and stored waste containers. The collection of data is to support environmental permitting and compliance, not for health and safety issues. This document does not address health or safety regulations or requirements (those of the Occupational Safety and Health Administration or the National Institute of Occupational Safety and Health) or continuous emission monitoring systems. This DQO is applicable to all equipment, facilities, and operations under the jurisdiction of RPP that emit or have the potential to emit regulated air pollutants

  18. Waste classification - history, standards, and requirements for disposal

    International Nuclear Information System (INIS)

    Kocher, D.C.

    1989-01-01

    This document contains an outline of a presentation on the historical development in US of different classes (categories) or radioactive waste, on laws and regulations in US regarding classification of radioactive wastes; and requirements for disposal of different waste classes; and on the application of laws and regulations for hazardous chemical wastes to classification and disposal of naturally occurring and accelerator-produced radioactive materials; and mixed radioactive and hazardous chemical wastes

  19. IEE wiring regulations explained and illustrated

    CERN Document Server

    Scaddan, Brian

    2013-01-01

    The IEE Wiring Regulations Explained and Illustrated, Second Edition discusses the recommendations of the IEE Regulations for the Electrical Equipment of Buildings for the safe selection or erection of wiring installations. The book emphasizes earthing, bonding, protection, and circuit design of electrical wirings. The text reviews the fundamental requirements for safety, earthing systems, the earth fault loop impedance, and supplementary bonding. The book also describes the different types of protection, such as protection against mechanical damage, overcurrent, under voltage (which prevents

  20. Regulation of radiation sources in Canada

    International Nuclear Information System (INIS)

    Brown, W.R.

    1989-04-01

    This paper describes in general the Canadian program for the regulation of radiation sources, with particular emphasis on radioisotope licences. The Atomic Energy Control Board is described, as are the most significant parts of the Regulations. Licensing, which is the method chosen for control, is explained by describing the assessment of an application through the enforcement of the requirements, and the overall effectiveness of the program is measured by analyzing the incidents and overexposures that have occurred in recent years

  1. Developmentally regulated GTP-binding protein 2 is required for stabilization of Rac1-positive membrane tubules.

    Science.gov (United States)

    Mani, Muralidharan; Lee, Unn Hwa; Yoon, Nal Ae; Yoon, Eun Hye; Lee, Byung Ju; Cho, Wha Ja; Park, Jeong Woo

    2017-11-04

    Previously we have reported that developmentally regulated GTP-binding protein 2 (DRG2) localizes on Rab5 endosomes and plays an important role in transferrin (Tfn) recycling. We here identified DRG2 as a key regulator of membrane tubule stability. At 30 min after Tfn treatment, DRG2 localized to membrane tubules which were enriched with phosphatidylinositol 4-monophosphate [PI(4)P] and did not contain Rab5. DRG2 interacted with Rac1 more strongly with GTP-bound Rac1 and tubular localization of DRG2 depended on Rac1 activity. DRG2 depletion led to destabilization of membrane tubules, while ectopic expression of DRG2 rescued the stability of the membrane tubules in DRG2-depleted cells. Our results reveal a novel mechanism for regulation of membrane tubule stability mediated by DRG2. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 45 CFR 2553.73 - What are grants management requirements?

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false What are grants management requirements? 2553.73 Section 2553.73 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL... § 2553.73 What are grants management requirements? What rules govern a sponsor's management of grants? (a...

  3. 7 CFR 58.648 - Microbiological requirements for ice cream.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Microbiological requirements for ice cream. 58.648 Section 58.648 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... requirements for ice cream. The finished product shall contain not more than 50,000 bacteria per gram as...

  4. 22 CFR 161.11 - Environmental review and consultation requirements.

    Science.gov (United States)

    2010-04-01

    ... requirements. 161.11 Section 161.11 Foreign Relations DEPARTMENT OF STATE ENVIRONMENTAL PROTECTION REGULATIONS FOR IMPLEMENTATION OF THE NATIONAL ENVIRONMENTAL POLICY ACT (NEPA) Coordination of Other Requirements... comments. (d) Fish and Wildlife Coordination Act, 16 U.S.C. 661 et seq. (e) Section 309 of the Clean Air...

  5. The application of dangerous goods regulations to the transport of radioactive wastes

    International Nuclear Information System (INIS)

    Blenkin, J.J.; Darby, W.P.; Heywood, J.D.; Wikinson, H.L.; Carrington, C.K.; Murray, M.A.

    1998-01-01

    Some radioactive materials to be transported, including certain radioactive wastes, contain materials that qualify as dangerous goods as defined by the United Nations Recommendations on the Transport of Dangerous Goods (United Nations 1997). The regulations governing the transport of radioactive and dangerous goods in the UK are largely based on the IAEA Regulations for the Safe Transport of Radioactive Material (IAEA 1990) and the UN Recommendations (United Nations 1993). Additional legislation will also apply including the Carriage of Dangerous Goods by Road (Driver Training) Regulations 1996 (UK 1996). The IAEA Transport Regulations are clear that where radioactive materials have other dangerous properties the requirements of other relevant transport regulations for dangerous goods must also be met. They require that consignments are appropriately segregated from other dangerous goods, in accordance with relevant legislation, and that dangerous properties such as explosiveness, flammability etc. are taken into account in packing, labelling, marking, placarding, storage and transport. In practice, however, it requires a clear understanding of the relationship between the IAEA Transport Regulations and other dangerous goods legislation in order to avoid a number of problems in the approval of package design. This paper discusses the regulations applying to the transport of dangerous goods and explores practical problems associated with implementing them. It highlights a number of opportunities for developing the regulations, to make them easier to apply to radioactive materials that also have other potentially dangerous properties. (authors)

  6. Underground storage tanks: State regulations and compliance strategies

    International Nuclear Information System (INIS)

    Robinson, J.E.

    1988-01-01

    In an effort to resolve underground storage tank (UST) management problems, several states and localities have moved ahead of EPA in the promulgation of UST regulations. Developed independently, these regulations represent different strategies for ensuring compliance: from an extensive set of permitting requirements that allow for the implementation of site-specific control measures to a uniform set of technical and operational requirements that vary according to installation date. For the tank owner, complying with these regulations can be a time-consuming and frustrating endeavor. However, during the course of several environmental audits of similar facilities in different states, useful strategies were observed or developed that enabled facilities to respond more effectively to requirements: these included computerization of files, designation of tank custodians, installation of low-maintenance equipment, and increased use of above-ground tanks. Of special additional interest was the wide variation in costs for similar tank services quoted by both private and government sources. These strategies are coupled with general observations on the efficacy of the various regulatory approaches to provide a field view that may be useful to tank owners and others involved in underground tank management and evaluation

  7. 16 CFR 1203.12 - Test requirements.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Test requirements. 1203.12 Section 1203.12 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY... midsagittal plane when measured in accordance with § 1203.14 of this standard. (b) Positional stability. No...

  8. 7 CFR 3052.200 - Audit requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Audit requirements. 3052.200 Section 3052.200 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE AUDITS OF STATES, LOCAL GOVERNMENTS, AND NON-PROFIT ORGANIZATIONS Audits § 3052.200...

  9. 15 CFR 806.2 - Recordkeeping requirements.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Recordkeeping requirements. 806.2 Section 806.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF ECONOMIC ANALYSIS, DEPARTMENT OF COMMERCE DIRECT INVESTMENT SURVEYS § 806.2 Recordkeeping...

  10. CYB5D2 requires heme-binding to regulate HeLa cell growth and confer survival from chemotherapeutic agents.

    Directory of Open Access Journals (Sweden)

    Anthony Bruce

    Full Text Available The cytochrome b5 domain containing 2 (CYB5D2; Neuferricin protein has been reported to bind heme, however, the critical residues responsible for heme-binding are undefined. Furthermore, the relationship between heme-binding and CYB5D2-mediated intracellular functions remains unknown. Previous studies examining heme-binding in two cytochrome b5 heme-binding domain-containing proteins, damage-associated protein 1 (Dap1; Saccharomyces cerevisiae and human progesterone receptor membrane component 1 (PGRMC1, have revealed that conserved tyrosine (Y 73, Y79, aspartic acid (D 86, and Y127 residues present in human CYB5D2 may be involved in heme-binding. CYB5D2 binds to type b heme, however, only the substitution of glycine (G at D86 (D86G within its cytochrome b5 heme-binding (cyt-b5 domain abolished its heme-binding ability. Both CYB5D2 and CYB5D2(D86G localize to the endoplasmic reticulum. Ectopic CYB5D2 expression inhibited cell proliferation and anchorage-independent colony growth of HeLa cells. Conversely, CYB5D2 knockdown and ectopic CYB5D2(D86G expression increased cell proliferation and colony growth. As PGRMC1 has been reported to regulate the expression and activities of cytochrome P450 proteins (CYPs, we examined the role of CYB5D2 in regulating the activities of CYPs involved in sterol synthesis (CYP51A1 and drug metabolism (CYP3A4. CYB5D2 co-localizes with cytochrome P450 reductase (CYPOR, while CYB5D2 knockdown reduced lanosterol demethylase (CYP51A1 levels and rendered HeLa cells sensitive to mevalonate. Additionally, knockdown of CYB5D2 reduced CYP3A4 activity. Lastly, CYB5D2 expression conferred HeLa cell survival from chemotherapeutic agents (paclitaxel, cisplatin and doxorubicin, with its ability to promote survival being dependent on its heme-binding ability. Taken together, this study provides evidence that heme-binding is critical for CYB5D2 in regulating HeLa cell growth and survival, with endogenous CYB5D2 being required to

  11. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation.

    Science.gov (United States)

    Moreira, Ricardo N; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M

    2017-09-19

    The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. IMPORTANCE Bacterial cells have evolved several

  12. 17 CFR 242.303 - Record preservation requirements for alternative trading systems.

    Science.gov (United States)

    2010-04-01

    ... requirements for alternative trading systems. 242.303 Section 242.303 Commodity and Securities Exchanges... REQUIREMENTS FOR SECURITY FUTURES Regulation Ats-Alternative Trading Systems § 242.303 Record preservation requirements for alternative trading systems. (a) To comply with the condition set forth in paragraph (b)(9) of...

  13. 20 CFR 219.42 - When evidence of child's dependency is required.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When evidence of child's dependency is required. 219.42 Section 219.42 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... child's dependency is required. Evidence of a child's dependency on the employee is required when— (a...

  14. Quality assurance requirements for packaging and transportation of radioactive materials

    International Nuclear Information System (INIS)

    Barker, R.F.; MacDonald, C.E.; Doda, R.J.

    1978-01-01

    This paper discusses the new quality assurance regulations of the Nuclear Regulatory Commission (NRC) for packaging and transportation of radioactive materials. These regulations became effective on October 18, 1977. Background information concerning these regulations and packaging and transportation history is included. The quality assurance program is described with indications of how it is composed of general (administrative) provisions which must meet the 18 quality assurance criteria and be approved by the NRC; specific provisions which appear in the DOT and NRC regulations and in the individual package design approval; and other specific procedures which are not required by regulations but which are necessary for the proper control of quality. The quality assurance program is to be developed using a graded approach for the application of pertinent criteria and optimizing the required degree of safety and control efforts involved in achieving this level of safety. The licensee-user is responsible for all phases of quality assurance for packaging activities including: design, manufacture, test, use, maintenance and repair. The package design phase is considered to be particularly important in producing adequate safety in operational activities concerning packaging and transportation of radioactive materials

  15. Risk-based regulation - an NRC perspective and status

    International Nuclear Information System (INIS)

    King, T.L.; Murphy, J.A.

    1993-01-01

    The consideration of risk in regulatory decision making has traditionally been part of the US Nuclear Regulatory Commission's (NRC's) policy and practice. In the early days of regulation, this consideration was more qualitative in nature and was reflected in prescriptive/deterministic regulatory requirements. However, with the development of quantitative risk assessment methods, more detailed and comprehensive (although not complete) risk information on nuclear power plants is available to the designer, operator, and regulator. The availability of such information provides an opportunity to assess the need for change in the current regulatory structure and to develop future regulatory requirements in a less prescriptive, more performance-oriented fashion

  16. Regulation of Stem Cell Differentiation by Histone Methyltransferases and Demethylases

    DEFF Research Database (Denmark)

    Pasini, D; Bracken, A P; Agger, K

    2008-01-01

    The generation of different cell types from stem cells containing identical genetic information and their organization into tissues and organs during development is a highly complex process that requires defined transcriptional programs. Maintenance of such programs is epigenetically regulated...... and the factors involved in these processes are often essential for development. The activities required for cell-fate decisions are frequently deregulated in human tumors, and the elucidation of the molecular mechanisms that regulate these processes is therefore important for understanding both developmental...

  17. Mining in the Northern Territory: evolution of regulation

    International Nuclear Information System (INIS)

    McGill, T.

    2002-01-01

    The Northern Territory Government is shifting away from the traditional command and control prescriptive style regulation, to self-regulation with its increased emphasis on company responsibility. Benchmarking in the areas of environment, health and safety are key steps in this shift. It is widely recognised that heavy-handed regulatory systems are not a particularly effective way to achieve best practice outcomes, a more holistic approach to regulation is required. The ideal situation is to have Government and industry jointly setting goals and reviewing progress towards those goals

  18. System certification progress in concept recognition in IAEA regulation

    International Nuclear Information System (INIS)

    Luna, R.E.; Pollog, T.

    1995-01-01

    System Certification is a regulatory concept which is intended to expand the scope of radioactive material transport regulations by allowing alternative means for proving compliance with the requisite standards of safety set out in transport regulations. In practice it may allow more stringent requirements in one aspect of the regulations to be substituted for less stringent application in other areas so long as the safety standard provided by regulation is preserved. The concept is widely perceived as the imposition of operational controls in exchange for relaxation of packaging standards, but that is only one possibility in the spectrum of potential actions under a System Certification provision in IAEA or national regulations

  19. Regulation No. 100/2006 Coll. of the Ministry of Health of the Slovak Republic dated as of February 6, 2006 laying down the requirements for natural healing water and natural mineral water, Balneology details of the report, distribution, extent of monitoring and content analysis of natural healing waters and natural mineral waters and their products and requirements for entry to the list of accredited laboratories maintained by the State Commission bathroom

    International Nuclear Information System (INIS)

    2006-01-01

    This Regulation provides: (a) requirements for natural healing water and natural mineral water; (b) requirements for the recognition of natural mineral water; (c) details of balneology report; (d) distribution of natural healing waters and natural mineral water; (e) the extent of tracking of natural healing waters and natural mineral waters and their products; (f) content analysis of natural healing waters and natural mineral waters and their products; (g) registration requirements for accredited laboratories in the list maintained by the State Commission bathroom. This Regulation came into force on March 1, 2006.

  20. Regulation of Autophagy by Kinases

    International Nuclear Information System (INIS)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

    2011-01-01

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets

  1. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-06-09

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  2. Regulation of Autophagy by Kinases

    Science.gov (United States)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

    2011-01-01

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets. PMID:24212825

  3. Regulation of Autophagy by Kinases

    Directory of Open Access Journals (Sweden)

    Savitha Sridharan

    2011-06-01

    Full Text Available Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  4. Cosmetic Regulations: A Comparative Study.

    Science.gov (United States)

    Suhag, Jyoti; Dureja, Harish

    2015-01-01

    The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations.

  5. 31 CFR 223.6 - Requirements applicable to surety companies.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Requirements applicable to surety companies. 223.6 Section 223.6 Money and Finance: Treasury Regulations Relating to Money and Finance... BUSINESS WITH THE UNITED STATES § 223.6 Requirements applicable to surety companies. Every company now or...

  6. 48 CFR 301.603-73 - Additional HHS training requirements.

    Science.gov (United States)

    2010-10-01

    ... Contract Specialist is not required to take the class as long as the Contract Specialist is working under... requirements. 301.603-73 Section 301.603-73 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES... each be 8 hours or more in length. (b) Performance based acquisition training. Effective January 1...

  7. 77 FR 67366 - Federal Acquisition Regulation; Information Collection; Travel Costs

    Science.gov (United States)

    2012-11-09

    ...; Information Collection; Travel Costs AGENCY: Department of Defense (DOD), General Services Administration (GSA... requirement concerning Travel Costs. Public comments are particularly invited on: Whether this collection of...- 0088, Travel Costs by any of the following methods: Regulations.gov : http://www.regulations.gov...

  8. 77 FR 3840 - Proposed Collection; Comment Request for Regulation Project

    Science.gov (United States)

    2012-01-25

    ... consideration. ADDRESSES: Direct all written comments to Yvette Lawrence, Internal Revenue Service, room 6129...-1353. Regulation Project Number: FI-189-84. Abstract: These regulations provide definitions, reporting requirements, elections, and general rules relating to the tax treatment of debt instruments with original...

  9. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    Jackson, M.

    2002-01-01

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  10. 40 CFR 80.840 - What requirements apply to transmix processors?

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Toxics Gasoline Toxics Performance Requirements § 80.840 What requirements apply to transmix processors? Any transmix processor who produces gasoline or gasoline blendstock from transmix, or recovers gasoline or gasoline blendstock from transmix...

  11. 40 CFR 80.1236 - What requirements apply to California gasoline?

    Science.gov (United States)

    2010-07-01

    ... gasoline? 80.1236 Section 80.1236 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Gasoline Benzene Requirements § 80.1236 What requirements apply to California gasoline? (a) Definition. For purposes of this subpart...

  12. 40 CFR 80.845 - What requirements apply to California gasoline?

    Science.gov (United States)

    2010-07-01

    ... gasoline? 80.845 Section 80.845 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Toxics Gasoline Toxics Performance Requirements § 80.845 What requirements apply to California gasoline? (a) Definition. For purposes of this...

  13. 76 FR 78126 - Disclosure Requirements for Depository Institutions Lacking Federal Deposit Insurance (Regulation I)

    Science.gov (United States)

    2011-12-16

    ..., Office of Regulations, at (202) 435-7700. SUPPLEMENTARY INFORMATION: I. Background The Federal Deposit... products or services or information otherwise promoting the institution; and (2) Small utilitarian items.... SUMMARY: Title X of the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act...

  14. Regulation of chemical safety at fuel cycle facilities by the United States Nuclear Regulatory Commission

    International Nuclear Information System (INIS)

    Ramsey, Kevin M.

    2013-01-01

    When the U.S. Nuclear Regulatory Commission (NRC) was established in 1975, its regulations were based on radiation dose limits. Chemical hazards rarely influenced NRC regulations. After the Three Mile Island reactor accident in 1979, the NRC staff was directed to address emergency planning at non-reactor facilities. Several fuel cycle facilities were ordered to submit emergency plans consistent with reactor emergency plans because no other guidance was available. NRC published a notice that it was writing regulations to codify the requirements in the Orders and upgrade the emergency plans to address all hazards, including chemical hazards. The legal authority of NRC to regulate chemical safety was questioned. In 1986, an overfilled uranium hexafluoride cylinder ruptured and killed a worker. The NRC staff was directed to address emergency planning for hazardous chemicals in its regulations. The final rule included a requirement for fuel cycle facilities to certify compliance with legislation requiring local authorities to establish emergency plans for hazardous chemicals. As with emergency planning, NRC's authority to regulate chemical safety during routine operations was limited. NRC established memoranda of understanding (MOUs) with other regulatory agencies to encourage exchange of information between the agencies regarding occupational hazards. In 2000, NRC published new, performance-based, regulations for fuel cycle facilities. The new regulations required an integrated safety analysis (ISA) which used quantitative standards to assess chemical exposures. Some unique chemical exposure cases were addressed while implementing the new regulations. In addition, some gaps remain in the regulation of hazardous chemicals at fuel cycle facilities. The status of ongoing efforts to improve regulation of chemical safety at fuel cycle facilities is discussed. (authors)

  15. 16 CFR 1750.5 - Detailed requirements.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Detailed requirements. 1750.5 Section 1750.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION REFRIGERATOR SAFETY ACT REGULATIONS STANDARD FOR... directed perpendicularly to the plane of the door and applied anywhere along the latch edge of the inside...

  16. 33 CFR 26.03 - Radiotelephone required.

    Science.gov (United States)

    2010-07-01

    ... BRIDGE-TO-BRIDGE RADIOTELEPHONE REGULATIONS § 26.03 Radiotelephone required. (a) Unless an exemption is... 26 feet or over in length while navigating; and (4) Every dredge and floating plant engaged in or... for an unmanned or intermittently manned floating plant under the control of a dredge. (b) Every...

  17. Incentive regulation of electricity distribution networks: Lessons of experience from Britain

    International Nuclear Information System (INIS)

    Jamasb, Tooraj; Pollitt, Michael

    2007-01-01

    This paper reviews the recent experience of the UK electricity distribution sector under incentive regulation. The UK has a significant and transparent history in implementing incentive regulation in the period since 1990. We demonstrate the successes of this period in reducing costs, prices, and energy losses while maintaining quality of service. We also draw out the lessons for other countries in implementing distribution sector reform. We conclude by discussing the place of incentive regulation of networks within the wider reform context, the required legislative framework, the need for appropriate unbundling, the importance of quality of service incentives, the regulatory information requirements, and the role of sector rationalisation. (author)

  18. German rules and regulations eith special reference to application documents

    International Nuclear Information System (INIS)

    Kraut, A.

    1979-01-01

    Regulations and standards play an essential role in achieving a safe and economic technology and in making the licensing procedure systematic, effective and clear. German rules and regulations applicable to the nuclear field are presented in this paper together with references to the rulemaking organizations. Detailed information is given on those rules and regulations, which prescribe the requirements concerning necessary documents for the nuclear licensing procedure. (author)

  19. Regulation of mtl operon promoter of Bacillus subtilis: requirements of its use in expression vectors

    Directory of Open Access Journals (Sweden)

    Altenbuchner Josef

    2011-10-01

    Full Text Available Abstract Background Several vector systems have been developed to express any gene desired to be studied in Bacillus subtilis. Among them, the transcriptionally regulated promoters involved in carbohydrate utilization are a research priority. Expression systems based on Bacillus promoters for xylose, maltose, and mannose utilization, as well as on the heterologous E. coli lactose promoter, have been successfully constructed. The promoter of the mtlAFD operon for utilization of mannitol is another promising candidate for its use in expression vectors. In this study, we investigated the regulation of the mtl genes in order to identify the elements needed to construct a strong mannitol inducible expression system in B. subtilis. Results Regulation of the promoters of mtlAFD operon (PmtlA and mtlR (PmtlR encoding the activator were investigated by fusion to lacZ. Identification of the PmtlA and PmtlR transcription start sites revealed the σA like promoter structures. Also, the operator of PmtlA was determined by shortening, nucleotide exchange, and alignment of PmtlA and PmtlR operator regions. Deletion of the mannitol-specific PTS genes (mtlAF resulted in PmtlA constitutive expression demonstrating the inhibitory effect of EIICBMtl and EIIAMtl on MtlR in the absence of mannitol. Disruption of mtlD made the cells sensitive to mannitol and glucitol. Both PmtlA and PmtlR were influenced by carbon catabolite repression (CCR. However, a CcpA deficient mutant showed only a slight reduction in PmtlR catabolite repression. Similarly, using PgroE as a constitutive promoter, putative cre sites of PmtlA and PmtlR slightly reduced the promoter activity in the presence of glucose. In contrast, glucose repression of PmtlA and PmtlR was completely abolished in a ΔptsG mutant and significantly reduced in a MtlR (H342D mutant. Conclusions The mtl operon promoter (PmtlA is a strong promoter that reached a maximum of 13,000 Miller units with lacZ as a reporter on

  20. An approach to regulatory compliance with radioactive mixed waste regulations

    International Nuclear Information System (INIS)

    Baker, G.G.; Mihalovich, G.S.; Provencher, R.B.

    1991-01-01

    On May 7, 1990, radioactive mixed waste (RMW) at the West Valley Demonstration Project (WVDP) became subject to the State Of New York hazardous waste regulations. The facility was required to be in full compliance by June 6, 1990. Achievement of this goal was difficult because of the short implementation time frame. Compliance with the hazardous waste regulations also presented some potential conflicts between the hazardous waste requirements and other regulatory requirements specifically applicable to nuclear facilities. The potential conflicts involved construction, operation, and control measures. However, the facility had been working extensively with EPA Region 2 and the New York State Department of Environmental Conservation (NYSDEC) on the application of the hazardous waste regulations to the facility. During these preliminary contacts, WVDP identified three issues that related to the potential conflicts: 1. Equivalency of Design and Equipment, 2. Land Disposal Restrictions (LDR), and 3. The Principle of As Low As Reasonable Achievable (ALARA) Radiation Exposure. The equivalency of nuclear facility design and equipment to the hazardous waste requirements is based in part on the increased construction criteria for nuclear facilities, the use of remote radiological monitoring for leak detection, and testing of system components that are not accessible to personnel due to high levels of radiation. This paper discusses in detail: 1. The implementation and results of the WVDP's interaction with its regulators, 2. How the regulators were helped to understand the different situations and conditions of nuclear and chemical facilities, and 3. How, by working together, the result was not only mutually advantageous to the NWDP and the agencies, but it also assured that the health and safety of workers, the public, and the environment were protected

  1. 78 FR 69267 - Defense Federal Acquisition Regulation Supplement: Requirements Relating to Supply Chain Risk...

    Science.gov (United States)

    2013-11-18

    ... payroll, finance, logistics, and personnel management applications; or (2) Is protected at all times by... recommendation from the Under Secretary of Defense for Acquisition, Technology, and Logistics (USD(AT&L)) and the... assess all costs and benefits of available regulatory alternatives and, if regulation is necessary, to...

  2. Legal requirements governing proxy voting in Denmark

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2008-01-01

    The requirements in Danish company law concerning proxy voting in companies whose shares have been accepted for listing on a regulated market have been successively tightened in recent years, and corporate governance principles have also led to the introduction of several requirements concerning...... proxy holders. A thorough knowledge of these requirements is important not only for the listed companies but also for their advisers and investors in Denmark and abroad. This article considers these requirements as well as the additional requirements which will derive from Directive 2007....../36 on the exercise of shareholders' rights in listed companies, which must be implemented by 3 August 2009. It is pointed out that companies may provide with advantage in their articles of association for both the existing and the forthcoming requirements at this early stage....

  3. OSHA regulations: how they relate to ophthalmic practice.

    Science.gov (United States)

    Garber, N

    1992-01-01

    The OSHA regulations, which took effect March 6, 1992, require that all employees be trained in infection control practices when they are hired, their job description changes, or the standards for universal precautions are revised. An explanation, provided to inform employees where a copy of the OSHA standard can be reviewed should be available at each clinical and surgical site, and OSHA regulation definitions must also be posted. The OSHA regulation applies to any clinical, housekeeping, or administrative staff that has any potential risk of exposure to blood or other potentially infectious substances.

  4. Regulatory requirements for the transport of radioactive materials in Canada

    Energy Technology Data Exchange (ETDEWEB)

    Garg, R. [Canadian Nuclear Safety Commission, Ottawa (Canada)

    2004-07-01

    Canada is a major producer and shipper of radioactive material. Each year more than a million packages are transported in Canada. The safety record with the transport of RAM in Canada has historically been excellent. There have never been any serious injuries, overexposure or fatality or environmental consequences attributable to the radioactive nature of such material being transported or being involved in a transport accident. In Canada, the Canadian Nuclear Safety Commission (CNSC) is the prime agency of the federal government entrusted with regulating all activities related to the use of nuclear energy and nuclear substances including the packaging and transport of nuclear substances. The mission of the CNSC is to regulate the use of nuclear energy and materials to protect health, safety, security of the person and the environment and to respect Canada's international commitments on the peaceful use of nuclear energy. The division of responsibility for the regulation of transport of radioactive material has been split between Transport Canada and the CNSC. The governing Transport Canada's regulations are Transport of Dangerous Goods (TDG) Regulations and the CNSC regulations are Packaging and Transport of Nuclear Substances Regulations (PTNSR). Canada has actively participated in the development of the IAEA regulations for the safe transport of radioactive material since 1960. As an IAEA member state, Canada generally follows the requirements of IAEA regulations with few deviations. The Nuclear Safety and Control Act (NSCA) strongly supports Canada's international obligations to ensure safe packaging, transport, storage and disposal of nuclear substances, prescribed equipment and prescribed information. Prescribed equipment and prescribed information are defined in the CNSC General Nuclear Safety and Control Regulations. This paper presents the current CNSC regulatory requirements and initiatives taken by the CNSC to improve its effectiveness and

  5. Regulatory requirements for the transport of radioactive materials in Canada

    International Nuclear Information System (INIS)

    Garg, R.

    2004-01-01

    Canada is a major producer and shipper of radioactive material. Each year more than a million packages are transported in Canada. The safety record with the transport of RAM in Canada has historically been excellent. There have never been any serious injuries, overexposure or fatality or environmental consequences attributable to the radioactive nature of such material being transported or being involved in a transport accident. In Canada, the Canadian Nuclear Safety Commission (CNSC) is the prime agency of the federal government entrusted with regulating all activities related to the use of nuclear energy and nuclear substances including the packaging and transport of nuclear substances. The mission of the CNSC is to regulate the use of nuclear energy and materials to protect health, safety, security of the person and the environment and to respect Canada's international commitments on the peaceful use of nuclear energy. The division of responsibility for the regulation of transport of radioactive material has been split between Transport Canada and the CNSC. The governing Transport Canada's regulations are Transport of Dangerous Goods (TDG) Regulations and the CNSC regulations are Packaging and Transport of Nuclear Substances Regulations (PTNSR). Canada has actively participated in the development of the IAEA regulations for the safe transport of radioactive material since 1960. As an IAEA member state, Canada generally follows the requirements of IAEA regulations with few deviations. The Nuclear Safety and Control Act (NSCA) strongly supports Canada's international obligations to ensure safe packaging, transport, storage and disposal of nuclear substances, prescribed equipment and prescribed information. Prescribed equipment and prescribed information are defined in the CNSC General Nuclear Safety and Control Regulations. This paper presents the current CNSC regulatory requirements and initiatives taken by the CNSC to improve its effectiveness and efficiency

  6. Cyclic di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation in Staphylococcus aureus but dispensable for viability in anaerobic conditions.

    Science.gov (United States)

    Zeden, Merve S; Schuster, Christopher F; Bowman, Lisa; Zhong, Qiyun; Williams, Huw D; Gründling, Angelika

    2018-03-02

    Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered signaling molecule important for the survival of Firmicutes, a large bacterial group that includes notable pathogens such as Staphylococcus aureus However, the exact role of this molecule has not been identified. dacA , the S. aureus gene encoding the diadenylate cyclase enzyme required for c-di-AMP production, cannot be deleted when bacterial cells are grown in rich medium, indicating that c-di-AMP is required for growth in this condition. Here, we report that an S. aureus dacA mutant can be generated in chemically defined medium. Consistent with previous findings, this mutant had a severe growth defect when cultured in rich medium. Using this growth defect in rich medium, we selected for suppressor strains with improved growth to identify c-di-AMP-requiring pathways. Mutations bypassing the essentiality of dacA were identified in alsT and opuD, encoding a predicted amino acid and osmolyte transporter, the latter of which we show here to be the main glycine betaine-uptake system in S. aureus. Inactivation of these transporters likely prevents the excessive osmolyte and amino acid accumulation in the cell, providing further evidence for a key role of c-di-AMP in osmotic regulation. Suppressor mutations were also obtained in hepS, hemB, ctaA, and qoxB, coding proteins required for respiration. Furthermore, we show that dacA is dispensable for growth in anaerobic conditions. Together, these findings reveal an essential role for the c-di-AMP signaling network in aerobic, but not anaerobic, respiration in S. aureus . © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Using geospatial solutions to meet distribution integrity management requirements

    Energy Technology Data Exchange (ETDEWEB)

    McElroy, Robert A. [New Century Software, Inc., Fort Collins, CO (United States)

    2010-07-01

    In the United States, incidents on gas distribution pipelines kill on average 10 persons per year in addition to causing 40 serious injuries and millions of dollars of property damage. In order to remedy to this situation, the US Department of Transportation/Pipeline Hazardous Materials Safety Administration enacted new regulations requiring operators to develop distribution integrity management programs (DIMP) which must include: knowledge and identification of threats, evaluation of risk, identification and implementation of measures to address risks, performance measuring, periodic evaluation and improvement and results reporting. The aim of this paper is to show how geographic information systems (GIS) can help operators meet each requirement of the DIMP regulations. This discussion showed that GIS can help in identifying and quantifying the threats to the distribution system and in assessing the consequences of an incident. Investing in GIS will not only help operators in complying with the regulations but will also help them make economically sound, risk-based decisions.

  8. Food Irradiation Regulations And Code Of Practice

    International Nuclear Information System (INIS)

    Jimba, B.W. Centre For Energy Research And Training, Ahmadu Bello University, Zaria,

    1996-01-01

    Official attitude towards irradiated food is determined by factors such as: level of scientific knowledge, consumer habits, food shortages, agricultural production and technological know-how. To date, 39 countries have accepted the process for one or more food items while 27 nations carry out the process on a commercial basis. Regulations and codes of practice is essential for consumer confidence while uniformity of regulations, at the international level, will enhance international trade in irradiated food items. The internationally accepted Codex Standard on irradiated food and Codes of Practice for the operation of irradiation facilities, adopted in 1983, forms the basis for International regulations and a template for nations in the development of regulations. This paper discusses the basic legal requirements for licensing the process, procedures, facility and the operator and suggests a framework for a national regulation based on experiences of Hungary, Brazil and Israel

  9. Implicit emotion regulation affects outcome evaluation.

    Science.gov (United States)

    Yang, Qiwei; Tang, Ping; Gu, Ruolei; Luo, Wenbo; Luo, Yue-jia

    2015-06-01

    Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  10. Preliminary waste acceptance requirements - Konrad repository project

    International Nuclear Information System (INIS)

    Brennecke, P.W.; Warnecke, E.H.

    1991-01-01

    In Germany, the planned Konrad repository is proposed for the disposal of all types of radioactive wastes whose thermal influence upon the host rock is negligible. The Bundesamt fuer Strahlenschutz has established Preliminary Waste Acceptance Requirements (as of April 1990) for this facility. The respective requirements were developed on the basis of the results of site-specific safety assessments. They include general requirements on the waste packages to be disposed of as well as more specific requirements on the waste forms, the packaging and the radionuclide inventory per waste package. In addition, the delivery of waste packages was regulated. An outline of the structure and the elements of the Preliminary Waste Acceptance Requirements of April 1990 is given including comments on their legal status. (Author)

  11. 7 CFR 1944.541 - Reporting requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting requirements. 1944.541 Section 1944.541 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... grantee of its appeal rights under subpart B of part 1900 of this chapter. (3) A copy of the memorandum...

  12. 77 FR 67366 - Federal Acquisition Regulation; Information Collection; Quality Assurance Requirements

    Science.gov (United States)

    2012-11-09

    .... Glover, Sr., Procurement Analyst, Contract Policy Division, GSA (202) 501-1448 or email [email protected] . SUPPLEMENTARY INFORMATION: A. Purpose Supplies and services acquired under Government contracts..., acceptance, warranty, and other measures associated with quality requirements. Standard clauses related to...

  13. The Education (Schools and Further Education) Regulations 1981 (23 July 1981)

    International Nuclear Information System (INIS)

    1981-01-01

    These Regulations concern the use of radioactive substances and apparatus in schools and further education establishments. The approval of the Secretary of State for Education and Science is required for the use of such substances and apparatus, and his approval may be withdrawn if arrangements for health and safety of pupils and staff are inadequate. The Regulations revoke the Schools Regulations, 1959 (as amended), and the Further Education Regulations, 1975. (NEA) [fr

  14. Safety evaluation and regulation of chemicals. 2. Impact of regulations - improvement of methods

    Energy Technology Data Exchange (ETDEWEB)

    Homburger, F [ed.

    1985-01-01

    This volume assesses the impact of new scientific knowledge on the testing and regulation of chemicals, including food additives, drugs, cosmetics, pesticides, and other commercial substances. Apart from describing the newest tests, regulations, and risk assessment strategies, chapters reflect changes forced by both the growing need for cost containment and the mounting pressure to find alternatives to animal testing. Based on an international congress, the book also brings the advantage of diversity in the background and nationality of the authors, thus allowing a view of central problems according to the different interests of academics, industry scientists, government scientists, and regulators. The book opens with coverage of national and international regulations designed to prevent and control damage to human health and the environment. Topics range from basic problems of policy design and enforcement to the specific requirements for chemical regulation in developing countries. The next chapters cover new tests, systems, and assays used in in vivo safety testing. Readers will find a critical assessment of tests used to determine teratogenicity, mutagenicity, carcinogenicity, neurotoxicity and chemical lethality. Other topics include factors operating in the public perception of chemical hazards, guidelines for decision making in the management and regulation of risks, and future trends in the methodology of safety evaluation. The volume concludes with an overview of in vitro methods for testing hepatotoxicity. Several short-term in vitro test models and limited in vivo bioassays are presented and evaluated in terms of their capacity to substitute for long-term animal studies. Expert and thorough in its coverage, the book offers a wealth of technical and practical information for toxicologists, pharmacologists, industrial policy makers, and government regulators. (orig.). With 67 figs., 34 tabs.

  15. 10 CFR 850 Implementation of Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S

    2012-01-05

    10 CFR 850 defines a contractor as any entity, including affiliated entities, such as a parent corporation, under contract with DOE, including a subcontractor at any tier, with responsibility for performing work at a DOE site in furtherance of a DOE mission. The Chronic Beryllium Disease Prevention Program (CBDPP) applies to beryllium-related activities that are performed at the Lawrence Livermore National Laboratory (LLNL). The CBDPP or Beryllium Safety Program is integrated into the LLNL Worker Safety and Health Program and, thus, implementation documents and responsibilities are integrated in various documents and organizational structures. Program development and management of the CBDPP is delegated to the Environment, Safety and Health (ES&H) Directorate, Worker Safety and Health Functional Area. As per 10 CFR 850, Lawrence Livermore National Security, LLC (LLNS) periodically submits a CBDPP to the National Nuclear Security Administration/Livermore Site Office (NNSA/LSO). The requirements of this plan are communicated to LLNS workers through ES&H Manual Document 14.4, 'Working Safely with Beryllium.' 10 CFR 850 is implemented by the LLNL CBDPP, which integrates the safety and health standards required by the regulation, components of the LLNL Integrated Safety Management System (ISMS), and incorporates other components of the LLNL ES&H Program. As described in the regulation, and to fully comply with the regulation, specific portions of existing programs and additional requirements are identified in the CBDPP. The CBDPP is implemented by documents that interface with the workers, principally through ES&H Manual Document 14.4. This document contains information on how the management practices prescribed by the LLNL ISMS are implemented, how beryllium hazards that are associated with LLNL work activities are controlled, and who is responsible for implementing the controls. Adherence to the requirements and processes described in the ES&H Manual ensures

  16. Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms

    DEFF Research Database (Denmark)

    Srinivasan, Supriya; Sadegh, Leila; Elle, Ida C

    2008-01-01

    We investigated serotonin signaling in C. elegans as a paradigm for neural regulation of energy balance and found that serotonergic regulation of fat is molecularly distinct from feeding regulation. Serotonergic feeding regulation is mediated by receptors whose functions are not required for fat...... feeding behavior. These findings suggest that, as in mammals, C. elegans feeding behavior is regulated by extrinsic and intrinsic cues. Moreover, obesity and thinness are not solely determined by feeding behavior. Rather, feeding behavior and fat metabolism are coordinated but independent responses...

  17. Establishing managerial requirements for low-and intermediate-level waste repository

    International Nuclear Information System (INIS)

    Chung, C. W.; Lee, Y. K.; Kim, H. T.; Park, W. J.; Suk, T. W.; Park, S. H.

    2004-01-01

    This paper reviews basic considerations for establishing managerial requirements on the domestic low-and intermediate-level radioactive waste repository and presents the corresponding draft requirements. The draft emphasizes their close linking with the related regulations, standards and safety assessment for the repository. It also proposes a desirable direction towards harmonizing together with the existing waste acceptance requirements for the repository

  18. The need for regulation in energy markets

    International Nuclear Information System (INIS)

    De Sampaio Nunes, P.

    2002-01-01

    The following topics are discussed: The need for effective regulation; Energy issues requiring regulatory policy; Models adopted in different Member States of the European Union; Results achieved by Member States; Infrastructure. (R.P.)

  19. Regulation, control, tele-management; Regulation, commande, telegestion

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    In 1998, the French public authorities have started an ambitious energy mastery policy under the auspices of the Agency of environment and energy mastery (Ademe). One aspect of this policy concerns the R and D, industrial development and applications of automation and computerized control to the energy systems of buildings. This RCT 2000 seminar takes stock of the recent advances in this domain 7 years after the previous RCT issue. The first day of the seminar was devoted to new developments in regulation and control (ergonomics aspects, lighting systems, air conditioning in accommodations, solar systems etc..). Stress was put on the revolution expected with the introduction of domestic computer applications and Internet. This first day ended with a precise status of the standardization and future regulatory aspects. The second day was dealing with tele-management and technical management systems for buildings with an analysis of the impact of Internet and of the sensors and actuators capacity in information processing. The consequences and new requirements of the thermal regulation 2000 and the factors of success of a new start-up of the tele-management market in local authorities and social accommodations were analyzed too. (J.S.)

  20. 78 FR 65744 - Reporting and Recordkeeping Requirements Under OMB Review

    Science.gov (United States)

    2013-11-01

    ... SBIC's compliance with applicable laws and regulations concerning capital requirements. SUPPLEMENTARY INFORMATION: Title: Stockholders Confirmation (Corporation): Ownership Confirmation (Partnership). Frequency...