regulating pml nuclear: Topics by WorldWideScience.org

Sample records for regulating pml nuclear

PML-associated repressor of transcription (PAROT), a novel KRAB-zinc finger repressor, is regulated through association with PML nuclear bodies

International Nuclear Information System (INIS)

Fleischer, Sandra; Wiemann, Stefan; Will, Hans; Hofmann, Thomas G.

2006-01-01

Promyelocytic leukemia nuclear bodies (PML-NBs) are implicated in transcriptional regulation. Here we identify a novel transcriptional repressor, PML-associated repressor of transcription (PAROT), which is regulated in its repressor activity through recruitment to PML-NBs. PAROT is a Krueppel-associated box ( KRAB) zinc-finger (ZNF) protein, which comprises an amino terminal KRAB-A and KRAB-B box, a linker domain and 8 tandemly repeated C 2 H 2 -ZNF motifs at its carboxy terminus. Consistent with its domain structure, when tethered to DNA, PAROT represses transcription, and this is partially released by the HDAC inhibitor trichostatin A. PAROT colocalizes with members of the heterochromatin protein 1 (HP1) family and with transcriptional intermediary factor-1β/KRAB-associated protein 1 (TIF-1β/KAP1), a transcriptional corepressor for the KRAB-ZNF family. Interestingly, PML isoform IV, in contrast to PML-III, efficiently recruits PAROT and TIF-1β from heterochromatin to PML-NBs. PML-NB recruitment of PAROT partially releases its transcriptional repressor activity, indicating that PAROT can be regulated through subnuclear compartmentalization. Taken together, our data identify a novel transcriptional repressor and provide evidence for its regulation through association with PML-NBs
SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies

International Nuclear Information System (INIS)

Haekli, Marika; Karvonen, Ulla; Jaenne, Olli A.; Palvimo, Jorma J.

2005-01-01

Small nuclear RING finger protein SNURF (RNF4) is involved in transcriptional and cell growth regulation. We show here that a significant portion of endogenous SNURF localizes to nuclear bodies (NBs) that overlap with or are adjacent to domains containing endogenous promyelocytic leukemia (PML) protein and small ubiquitin-like modifier-1 (SUMO-1). In biochemical assays, SNURF efficiently binds SUMO-1 in a noncovalent fashion. SNURF is also covalently modified by SUMO-1 at nonconsensus attachment sites. Ectopic expression of SUMO-1 markedly enhances the interaction between PML3 (PML IV) and SNURF, but covalent attachment of SUMO-1 to neither protein is required. Moreover, overexpression of PML3, but not PML-L (PML III), abolishes the coactivation function of SNURF in transactivation assays, which parallels the ability of PML3 to recruit SNURF to nuclear bodies. In sum, we have identified SNURF as a novel component in PML bodies and suggest that SUMO-1-facilitated sequestration into these nuclear domains regulates the transcriptional activity of SNURF
Regulation of the tumor suppressor PML by sequential posttranslational modifications

Directory of Open Access Journals (Sweden)

Lienhard eSchmitz

2012-12-01

Full Text Available Posttranslational modifications (PTMs regulate multiple biological functions of the PML (promyelocytic leukemia protein and also the fission, disassembly and rebuilding of PML nuclear bodies (PML-NBs during the cell cycle. Pathway-specific PML modification patterns ensure proper signal output from PML-NBs that suit the specific functional requirements. Here we comprehensively review the signaling pathways and enzymes that modify PML and also the oncogenic PML-RARα fusion protein. Many PTMs occur in a hierarchical and timely organized fashion. Phosphorylation or acetylation constitute typical starting points for many PML modifying events, while degradative ubiquitination is an irreversible end point of the modification cascade. As this hierarchical organization of PTMs frequently turns phosphorylation events as primordial events, kinases or phosphatases regulating PML phosphorylation may be interesting drug targets to manipulate the downstream modifications and thus the stability and function of PML or PML-RARα.
Inhibition of Sp1 functions by its sequestration into PML nuclear bodies.

Directory of Open Access Journals (Sweden)

June Li

Full Text Available Promyelocytic leukemia nuclear bodies (PML NBs are comprised of PML and a striking variety of its associated proteins. Various cellular functions have been attributed to PML NBs, including the regulation of gene expression. We report here that induced expression of PML recruits Sp1 into PML NBs, leading to the reduction of Sp1 transactivation function. Specifically, Chromatin immunoprecipitation (ChIP assay demonstrated that induced expression of PML significantly diminishes the amount of Sp1 binding to its target gene promoter, immunofluorescence staining showed dramatic increase in the co-localization between PML and Sp1 upon induction of PML expression, moreover, PML and Sp1 co-fractionated in the core nuclear matrix. Our study further showed that PML promotes SUMOylation of Sp1 in a RING-motif-dependent manner, SUMOylation of Sp1 facilitates physical interaction between Sp1 and PML and recruitment of Sp1 into the PML NBs, the SUMO binding motif of PML was also important for its interaction with Sp1. The results of this study demonstrate a novel mechanism by which PML regulates gene expression through sequestration of the transcription factor into PML NBs.
Regulation of the tumor suppressor PML by sequential post-translational modifications

International Nuclear Information System (INIS)

Schmitz, M. Lienhard; Grishina, Inna

2012-01-01

Post-translational modifications (PTMs) regulate multiple biological functions of the promyelocytic leukemia (PML) protein and also the fission, disassembly, and rebuilding of PML nuclear bodies (PML-NBs) during the cell cycle. Pathway-specific PML modification patterns ensure proper signal output from PML-NBs that suit the specific functional requirements. Here we comprehensively review the signaling pathways and enzymes that modify PML and also the oncogenic PML-RARα fusion protein. Many PTMs occur in a hierarchical and timely organized fashion. Phosphorylation or acetylation constitutes typical starting points for many PML modifying events, while degradative ubiquitination is an irreversible end point of the modification cascade. As this hierarchical organization of PTMs frequently turns phosphorylation events as primordial events, kinases or phosphatases regulating PML phosphorylation may be interesting drug targets to manipulate the downstream modifications and thus the stability and function of PML or PML-RARα.
Mitosis-specific phosphorylation of PML at T409 regulates spindle checkpoint.

Science.gov (United States)

Jin, J; Liu, J

2016-08-31

During mitosis, Promyelocytic leukemia nuclear bodies (PML NBs) change dramatically in morphology and composition, but little is known about function of PML in mitosis. Here, we show that PML is phosphorylated at T409 (PML p409) in a mitosis-specific manner. More importantly, PML p409 contributes to maintain the duration of pro-metaphase and regulates spindle checkpoint. Deficient PML p409 caused a shortening of pro-metaphase and challenged the nocodazole-triggered mitotic arrest. T409A mutation led to a higher frequency of misaligned chromosomes on metaphase plate, and subsequently death in late mitosis. In addition, inhibition of PML p409 repressed growth of tumor cells, suggesting that PML p409 is a potential target for cancer therapy. Collectively, our study demonstrated an important phosphorylated site of PML, which contributed to explore the role of PML in mitosis.
The translation initiation factor 3 subunit eIF3K interacts with PML and associates with PML nuclear bodies

Energy Technology Data Exchange (ETDEWEB)

Salsman, Jayme; Pinder, Jordan; Tse, Brenda [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Corkery, Dale [Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada); Dellaire, Graham, E-mail: dellaire@dal.ca [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada)

2013-10-15

The promyelocytic leukemia protein (PML) is a tumor suppressor protein that regulates a variety of important cellular processes, including gene expression, DNA repair and cell fate decisions. Integral to its function is the ability of PML to form nuclear bodies (NBs) that serve as hubs for the interaction and modification of over 90 cellular proteins. There are seven canonical isoforms of PML, which encode diverse C-termini generated by alternative pre-mRNA splicing. Recruitment of specific cellular proteins to PML NBs is mediated by protein–protein interactions with individual PML isoforms. Using a yeast two-hybrid screen employing peptide sequences unique to PML isoform I (PML-I), we identified an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in the process identified a novel eIF3K isoform, which we term eIF3K-2. We further demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as well as in vivo within human cells by co-immunoprecipitation and co-immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3 translation pre-initiation complex to interact directly with the PML protein, and provide data implicating alternative splicing of both PML and eIF3K as a possible regulatory mechanism for eIF3K localization at PML NBs. - Highlights: • The PML-I C-terminus, encoded by exon 9, interacts with translation factor eIF3K. • We identify a novel eIF3K isoform that excludes exon 2 (eIF3K-2). • eIF3K-2 preferentially associates with PML bodies enriched in PML-I vs. PML-IV. • Alternative splicing of eIF3K regulates association with PML bodies.
Role of the SUMO-interacting motif in HIPK2 targeting to the PML nuclear bodies and regulation of p53

International Nuclear Information System (INIS)

Sung, Ki Sa; Lee, Yun-Ah; Kim, Eui Tae; Lee, Seung-Rock; Ahn, Jin-Hyun; Choi, Cheol Yong

2011-01-01

Homeodomain-interacting protein kinase 2 (HIPK2) is a key regulator of various transcription factors including p53 and CtBP in the DNA damage signaling pathway. PML-nuclear body (NB) is required for HIPK2-mediated p53 phosphorylation at Ser46 and induction of apoptosis. Although PML-NB targeting of HIPK2 has been shown, much is not clear about the molecular mechanism of HIPK2 recruitment to PML-NBs. Here we show that HIPK2 colocalizes specifically with PML-I and PML-IV. Mutational analysis showed that HIPK2 recruitment to PML-IV-NBs is mediated by the SUMO-interaction motifs (SIMs) of both PML-IV and HIPK2. Wild-type HIPK2 associated with SUMO-conjugated PML-IV at a higher affinity than with un-conjugated PML-IV, while the association of a HIPK2 SIM mutant with SUMO-modified PML-IV was impaired. In colony formation assays, HIPK2 strongly suppressed cell proliferation, but HIPK2 SIM mutants did not. In addition, activation and phosphorylation of p53 at the Ser46 residue were impaired by HIPK2 SIM mutants. These results suggest that SIM-mediated HIPK2 targeting to PML-NBs is crucial for HIPK2-mediated p53 activation and induction of apoptosis.
Modulation of PML protein expression regulates JCV infection

International Nuclear Information System (INIS)

Gasparovic, Megan L.; Maginnis, Melissa S.; O'Hara, Bethany A.; Dugan, Aisling S.; Atwood, Walter J.

2009-01-01

JC virus (JCV) is a human polyomavirus that infects the majority of the human population worldwide. It is responsible for the fatal demyelinating disease Progressive Multifocal Leukoencephalopathy. JCV binds to cells using the serotonin receptor 5-HT 2A R and α(2-6)- or α(2-3)-linked sialic acid. It enters cells using clathrin-dependent endocytosis and traffics to the early endosome and possibly to the endoplasmic reticulum. Viral DNA is then delivered to the nucleus where transcription, replication, and assembly of progeny occur. We found that the early regulatory protein large T antigen accumulates in microdomains in the nucleus adjacent to ND-10 or PML domains. This observation prompted us to explore the role of these domains in JCV infection. We found that a reduction of nuclear PML enhanced virus infection and that an increase in nuclear PML reduced infection. Infection with JCV did not directly modulate nuclear levels of PML but our data indicate that a host response involving interferon beta is likely to restrict virus infection by increasing nuclear PML.
An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies.

Science.gov (United States)

Komatsu, Tetsuro; Nagata, Kyosuke; Wodrich, Harald

2016-02-01

Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. The immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral genomes and
PML nuclear bodies in the pathogenesis of acute promyelocytic leukemia: active players or innocent bystanders?

Science.gov (United States)

Brown, Nicola J M; Ramalho, Michal; Pedersen, Eva W; Moravcsik, Eva; Solomon, Ellen; Grimwade, David

2009-01-01

The promyelocytic leukemia gene (PML) encodes a protein which localizes to PML-nuclear bodies (NBs), sub-nuclear multi-protein structures, which have been implicated in diverse biological functions such as apoptosis, cell proliferation and senescence. However, the exact biochemical and molecular basis of PML function up until now has not been defined. Strikingly, over a decade ago, PML-NBs were found to be disrupted in acute promyelocytic leukemia (APL) in which PML is fused to the gene encoding retinoic acid receptor alpha (RARA) due to the t(15;17) chromosomal translocation, generating the PML-RARA chimeric protein. The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. This review focuses on the current theories for molecular and biochemical functions of the PML-NBs, which would imply a role in the pathogenesis of APL, whilst also discussing the intriguing possibility that their disruption may not be in itself a significant oncogenic event.
Nuclear body formation and PML body remodeling by the human cytomegalovirus protein UL35

International Nuclear Information System (INIS)

Salsman, Jayme; Wang Xueqi; Frappier, Lori

2011-01-01

The human cytomegalovirus (HCMV) UL35 gene encodes two proteins, UL35 and UL35a. Expression of UL35 in transfected cells results in the formation of UL35 nuclear bodies that associate with promyelocytic leukemia (PML) protein. PML forms the basis for PML nuclear bodies that are important for suppressing viral lytic gene expression. Given the important relationship between PML and viral infection, we have further investigated the association of UL35 with PML bodies. We demonstrate that UL35 bodies form independently of PML and subsequently recruit PML, Sp100 and Daxx. In contrast, UL35a did not form bodies; however, it could bind UL35 and inhibit the formation of UL35 bodies. The HCMV tegument protein pp71 promoted the formation of UL35 bodies and the cytoplasmic localization of UL35a. Similarly, UL35a shifted pp71 to the cytoplasm. These results indicate that the interplay between UL35, UL35a and pp71 affects their subcellular localization and likely their functions throughout infection.
Distinct temporal roles for the promyelocytic leukaemia (PML protein in the sequential regulation of intracellular host immunity to HSV-1 infection.

Directory of Open Access Journals (Sweden)

Thamir Alandijany

2018-01-01

Full Text Available Detection of viral nucleic acids plays a critical role in the induction of intracellular host immune defences. However, the temporal recruitment of immune regulators to infecting viral genomes remains poorly defined due to the technical difficulties associated with low genome copy-number detection. Here we utilize 5-Ethynyl-2'-deoxyuridine (EdU labelling of herpes simplex virus 1 (HSV-1 DNA in combination with click chemistry to examine the sequential recruitment of host immune regulators to infecting viral genomes under low multiplicity of infection conditions. Following viral genome entry into the nucleus, PML-nuclear bodies (PML-NBs rapidly entrapped viral DNA (vDNA leading to a block in viral replication in the absence of the viral PML-NB antagonist ICP0. This pre-existing intrinsic host defence to infection occurred independently of the vDNA pathogen sensor IFI16 (Interferon Gamma Inducible Protein 16 and the induction of interferon stimulated gene (ISG expression, demonstrating that vDNA entry into the nucleus alone is not sufficient to induce a robust innate immune response. Saturation of this pre-existing intrinsic host defence during HSV-1 ICP0-null mutant infection led to the stable recruitment of PML and IFI16 into vDNA complexes associated with ICP4, and led to the induction of ISG expression. This induced innate immune response occurred in a PML-, IFI16-, and Janus-Associated Kinase (JAK-dependent manner and was restricted by phosphonoacetic acid, demonstrating that vDNA polymerase activity is required for the robust induction of ISG expression during HSV-1 infection. Our data identifies dual roles for PML in the sequential regulation of intrinsic and innate immunity to HSV-1 infection that are dependent on viral genome delivery to the nucleus and the onset of vDNA replication, respectively. These intracellular host defences are counteracted by ICP0, which targets PML for degradation from the outset of nuclear infection to promote v
Incoming human papillomavirus 16 genome is lost in PML protein-deficient HaCaT keratinocytes.

Science.gov (United States)

Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Keiffer, Timothy R; Guion, Lucile G M; DiGiuseppe, Stephen; Scott, Rona S; Sapp, Martin

2017-05-01

Human papillomaviruses (HPVs) target promyelocytic leukemia (PML) nuclear bodies (NBs) during infectious entry and PML protein is important for efficient transcription of incoming viral genome. However, the transcriptional down regulation was shown to be promoter-independent in that heterologous promoters delivered by papillomavirus particles were also affected. To further investigate the role of PML protein in HPV entry, we used small hairpin RNA to knockdown PML protein in HaCaT keratinocytes. Confirming previous findings, PML knockdown in HaCaT cells reduced HPV16 transcript levels significantly following infectious entry without impairing binding and trafficking. However, when we quantified steady-state levels of pseudogenomes in interphase cells, we found strongly reduced genome levels compared with parental HaCaT cells. Because nuclear delivery was comparable in both cell lines, we conclude that viral pseudogenome must be removed after successful nuclear delivery. Transcriptome analysis by gene array revealed that PML knockdown in clonal HaCaT cells was associated with a constitutive interferon response. Abrogation of JAK1/2 signaling prevented genome loss, however, did not restore viral transcription. In contrast, knockdown of PML protein in HeLa cells did not affect HPV genome delivery and transcription. HeLa cells are transformed by HPV18 oncogenes E6 and E7, which have been shown to interfere with the JAK/Stat signaling pathway. Our data imply that PML NBs protect incoming HPV genomes. Furthermore, they provide evidence that PML NBs are key regulators of the innate immune response in keratinocytes. Promyelocytic leukemia nuclear bodies (PML NBs) are important for antiviral defense. Many DNA viruses target these subnuclear structures and reorganize them. Reorganization of PML NBs by viral proteins is important for establishment of infection. In contrast, HPVs require the presence of PML protein for efficient transcription of incoming viral genome. Our
Solubility shift and SUMOylaltion of promyelocytic leukemia (PML) protein in response to arsenic(III) and fate of the SUMOylated PML

Energy Technology Data Exchange (ETDEWEB)

Hirano, Seishiro, E-mail: seishiro@nies.go.jp [Center for Environmental Risk Research, National Institute for Environmental Studies (Japan); Graduate School of Pharmaceutical Sciences, Chiba University (Japan); Tadano, Mihoko [Center for Environmental Risk Research, National Institute for Environmental Studies (Japan); Kobayashi, Yayoi [Center for Environmental Health Sciences, National Institute for Environmental Studies (Japan); Graduate School of Pharmaceutical Sciences, Chiba University (Japan); Udagawa, Osamu [Center for Environmental Risk Research, National Institute for Environmental Studies (Japan); Kato, Ayaka [Graduate School of Pharmaceutical Sciences, Chiba University (Japan)

2015-09-15

Promyelocytic leukemia (PML), which is a tumor suppressor protein that nevertheless plays an important role in the maintenance of leukemia initiating cells, is known to be biochemically modified by As{sup 3+}. We recently developed a simple method to evaluate the modification of PML by As{sup 3+} resulting in a change in solubility and the covalent binding of small ubiquitin-like modifier (SUMO). Here we semi-quantitatively investigated the SUMOylation of PML using HEK293 cells which were stably transfected with PML-VI (HEK-PML). Western blot analyses indicated that PML became insoluble in cold RadioImmunoPrecipitation Assay (RIPA) lysis buffer and was SUMOylated by both SUMO2/3 and SUMO1 by As{sup 3+}. Surprisingly SUMO1 monomers were completely utilized for the SUMOylation of PML. Antimony (Sb{sup 3+}) but not bismuth (Bi{sup 3+}), Cu{sup 2+}, or Cd{sup 2+} biochemically modified PML similarly. SUMOylated PML decreased after removal of As{sup 3+} from the culture medium. However, unSUMOylated PML was still recovered in the RIPA-insoluble fraction, suggesting that SUMOylation is not requisite for changing the RIPA-soluble PML into the RIPA-insoluble form. Immunofluorescence staining of As{sup 3+}-exposed cells indicated that SUMO2/3 was co-localized with PML in the nuclear bodies. However, some PML protein was present in peri-nuclear regions without SUMO2/3. Functional Really Interesting New Gene (RING)-deleted mutant PML neither formed PML nuclear bodies nor was biochemically modified by As{sup 3+}. Conjugation with intracellular glutathione may explain the accessibility of As{sup 3+} and Sb{sup 3+} to PML in the nuclear region evading chelation and entrapping by cytoplasmic proteins such as metallothioneins. - Highlights: • As{sup 3+} is a carcinogen and also a therapeutic agent for leukemia. • PML becomes insoluble in RIPA and SUMOylated by As{sup 3+}. • Sb{sup 3+} modifies PML similar to As{sup 3+}. • Functional RING motif is necessary for As{sup 3
Detection of O-propargyl-puromycin with SUMO and ubiquitin by click chemistry at PML-nuclear bodies during abortive proteasome activities

Energy Technology Data Exchange (ETDEWEB)

Uozumi, Naoki; Matsumoto, Hotaru [Course for Biological Sciences, Faculty of Science, Kumamoto University, Kumamoto (Japan); Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp [Course for Biological Sciences, Faculty of Science, Kumamoto University, Kumamoto (Japan); Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto (Japan)

2016-05-27

The amino-nucleoside antibiotic, puromycin, acts by covalently linking to elongating polypeptide chains on ribosomes to generate prematurely terminated immature polypeptides. The trafficking of puromycin-conjugated (puromycylated) immature polypeptides within cell has, however, remained elusive. In this study, using O-propargyl-puromycin (OP-Puro), the distribution of puromycylated polypeptides was assessed in HeLa cells by click chemistry. Under standard culture conditions, OP-Puro signals were detected in the cytoplasm and nucleus with the highest concentrations in the nucleolus. Intriguingly, when proteasome activities were aborted using MG132, OP-Puro signals began to accumulate at promyelocytic leukemia nuclear bodies (PML-NBs) in addition to the nucleolus. We also found promiscuous association of OP-Puro signals with SUMO-2/3 and ubiquitin at PML-NBs, but not at the nucleolus, during abortive proteasome activities. This study reveals a previously unknown distribution of OP-Puro that argues for a nuclear function in regulating immature protein homeostasis. -- Highlights: •Click chemistry detects O-propargyl-puromycin (OP-Puro) signals in the nucleus. •OP-Puro accumulates at PML-NBs during abortive proteasome activities. •SUMO and ubiquitin are promiscuously associated with OP-Puro at PML-NBs. •The nucleus may function in immature protein homeostasis.
Detection of O-propargyl-puromycin with SUMO and ubiquitin by click chemistry at PML-nuclear bodies during abortive proteasome activities

International Nuclear Information System (INIS)

Uozumi, Naoki; Matsumoto, Hotaru; Saitoh, Hisato

2016-01-01

The amino-nucleoside antibiotic, puromycin, acts by covalently linking to elongating polypeptide chains on ribosomes to generate prematurely terminated immature polypeptides. The trafficking of puromycin-conjugated (puromycylated) immature polypeptides within cell has, however, remained elusive. In this study, using O-propargyl-puromycin (OP-Puro), the distribution of puromycylated polypeptides was assessed in HeLa cells by click chemistry. Under standard culture conditions, OP-Puro signals were detected in the cytoplasm and nucleus with the highest concentrations in the nucleolus. Intriguingly, when proteasome activities were aborted using MG132, OP-Puro signals began to accumulate at promyelocytic leukemia nuclear bodies (PML-NBs) in addition to the nucleolus. We also found promiscuous association of OP-Puro signals with SUMO-2/3 and ubiquitin at PML-NBs, but not at the nucleolus, during abortive proteasome activities. This study reveals a previously unknown distribution of OP-Puro that argues for a nuclear function in regulating immature protein homeostasis. -- Highlights: •Click chemistry detects O-propargyl-puromycin (OP-Puro) signals in the nucleus. •OP-Puro accumulates at PML-NBs during abortive proteasome activities. •SUMO and ubiquitin are promiscuously associated with OP-Puro at PML-NBs. •The nucleus may function in immature protein homeostasis.
PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis.

Science.gov (United States)

Granito, Alessandro; Yang, Wei-Hong; Muratori, Luigi; Lim, Mark J; Nakajima, Ayako; Ferri, Silvia; Pappas, Georgios; Quarneti, Chiara; Bianchi, Francesco B; Bloch, Donald B; Muratori, Paolo

2010-01-01

Some patients with primary biliary cirrhosis (PBC) have antinuclear antibodies (ANAs). These ANAs include the "multiple nuclear dots" (MND) staining pattern, targeting promyelocytic leukemia protein (PML) nuclear body (NB) components, such as "speckled 100-kD" protein (Sp100) and PML. A new PML NB protein, designated as Sp140, was identified using serum from a PBC patient. The aim of this study was to analyze the immune response against Sp140 protein in PBC patients. We studied 135 PBC patients and 157 pathological controls with type 1 autoimmune hepatitis, primary sclerosing cholangitis, and systemic lupus erythematosus. We used indirect immunofluorescence and a neuroblastoma cell line expressing Sp140 for detecting anti-Sp140 antibodies, and a commercially available immunoblot for detecting anti-Sp100 and anti-PML antibodies. Anti-Sp140 antibodies were present in 20 (15%) PBC patients but not in control samples, with a higher frequency in antimitochondrial antibody (AMA)-negative cases (53 vs. 9%, P<0.0001). Anti-Sp140 antibodies were found together with anti-Sp100 antibodies in all but one case (19 of 20, 90%) and with anti-PML antibodies in 12 (60%) cases. Anti-Sp140 positivity was not associated with a specific clinical feature of PBC. Our study identifies Sp140 as a new, highly specific autoantigen in PBC for the first time. The very frequent coexistence of anti-Sp140, anti-Sp100 and anti-PML antibodies suggests that the NB is a multiantigenic complex in PBC and enhances the diagnostic significance of these reactivities, which are particularly useful in AMA-negative cases.
PML tumor suppressor protein is required for HCV production

International Nuclear Information System (INIS)

Kuroki, Misao; Ariumi, Yasuo; Hijikata, Makoto; Ikeda, Masanori; Dansako, Hiromichi; Wakita, Takaji; Shimotohno, Kunitada; Kato, Nobuyuki

2013-01-01

Highlights: ► PML tumor suppressor protein is required for HCV production. ► PML is dispensable for HCV RNA replication. ► HCV could not alter formation of PML-NBs. ► INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.
PML tumor suppressor protein is required for HCV production

Energy Technology Data Exchange (ETDEWEB)

Kuroki, Misao [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Research Fellow of the Japan Society for the Promotion of Science (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Ariumi, Yasuo, E-mail: ariumi@kumamoto-u.ac.jp [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Hijikata, Makoto [Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan); Ikeda, Masanori; Dansako, Hiromichi [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640 (Japan); Shimotohno, Kunitada [Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516 (Japan); Kato, Nobuyuki [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan)

2013-01-11

Highlights: Black-Right-Pointing-Pointer PML tumor suppressor protein is required for HCV production. Black-Right-Pointing-Pointer PML is dispensable for HCV RNA replication. Black-Right-Pointing-Pointer HCV could not alter formation of PML-NBs. Black-Right-Pointing-Pointer INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.

The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein

DEFF Research Database (Denmark)

Alcalay, M; Tomassoni, L; Colombo, E

1998-01-01

PML is a nuclear protein with growth-suppressive properties originally identified in the context of the PML-retinoic acid receptor alpha (RAR alpha) fusion protein of acute promyelocytic leukemia. PML localizes within distinct nuclear structures, called nuclear bodies, which are disrupted by the ...
The cell biology of disease: Acute promyelocytic leukemia, arsenic, and PML bodies.

Science.gov (United States)

de Thé, Hugues; Le Bras, Morgane; Lallemand-Breitenbach, Valérie

2012-07-09

Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor α (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation.
In situ SUMOylation analysis reveals a modulatory role of RanBP2 in the nuclear rim and PML bodies

International Nuclear Information System (INIS)

Saitoh, Noriko; Uchimura, Yasuhiro; Tachibana, Taro; Sugahara, Satoko; Saitoh, Hisato; Nakao, Mitsuyoshi

2006-01-01

SUMO modification plays a critical role in a number of cellular functions including nucleocytoplasmic transport, gene expression, cell cycle and formation of subnuclear structures such as promyelocytic leukemia (PML) bodies. In order to identify the sites where SUMOylation takes place in the cell, we developed an in situ SUMOylation assay using a semi-intact cell system and subsequently combined it with siRNA-based knockdown of nucleoporin RanBP2, also known as Nup358, which is one of the known SUMO E3 proteins. With the in situ SUMOylation assay, we found that both nuclear rim and PML bodies, besides mitotic apparatuses, are major targets for active SUMOylation. The ability to analyze possible SUMO conjugation sites would be a valuable tool to investigate where SUMO E3-like activities and/or SUMO substrates exist in the cell. Specific knockdown of RanBP2 completely abolished SUMOylation along the nuclear rim and dislocated RanGAP1 from the nuclear pore complexes. Interestingly, the loss of RanBP2 markedly reduced the number of PML bodies, in contrast to other, normal-appearing nuclear compartments including the nuclear lamina, nucleolus and chromatin, suggesting a novel link between RanBP2 and PML bodies. SUMOylation facilitated by RanBP2 at the nuclear rim may be a key step for the formation of a particular subnuclear organization. Our data imply that SUMO E3 proteins like RanBP2 facilitate spatio-temporal SUMOylation for certain nuclear structure and function
Gammaherpesviral Tegument Proteins, PML-Nuclear Bodies and the Ubiquitin-Proteasome System

Directory of Open Access Journals (Sweden)

Florian Full

2017-10-01

Full Text Available Gammaherpesviruses like Epstein-Barr virus (EBV and Kaposi’s sarcoma-associated herpesvirus (KSHV subvert the ubiquitin proteasome system for their own benefit in order to facilitate viral gene expression and replication. In particular, viral tegument proteins that share sequence homology to the formylglycineamide ribonucleotide amidotransferase (FGARAT, or PFAS, an enzyme in the cellular purine biosynthesis, are important for disrupting the intrinsic antiviral response associated with Promyelocytic Leukemia (PML protein-associated nuclear bodies (PML-NBs by proteasome-dependent and independent mechanisms. In addition, all herpesviruses encode for a potent ubiquitin protease that can efficiently remove ubiquitin chains from proteins and thereby interfere with several different cellular pathways. In this review, we discuss mechanisms and functional consequences of virus-induced ubiquitination and deubiquitination for early events in gammaherpesviral infection.
Nuclear organization of PML bodies in leukaemic and multiple myeloma cells

Czech Academy of Sciences Publication Activity Database

Kroupová, Jana; Harničarová, Andrea; Kůrová, Jana; Uhlířová, Radka; Kozubek, Stanislav; Legartová, Soňa; Hájek, R.; Bártová, Eva

2008-01-01

Roč. 32, č. 12 (2008), s. 1866-1877 ISSN 0145-2126 R&D Projects: GA ČR(CZ) GA204/06/0978; GA MŠk(CZ) LC06027 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : PML bodies * nuclear arrangement * leukaemic cells Subject RIV: BO - Biophysics Impact factor: 2.390, year: 2008
SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells

International Nuclear Information System (INIS)

Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M.; Heery, David M.

2010-01-01

The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBPΔ998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.
SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells

Energy Technology Data Exchange (ETDEWEB)

Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M. [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom); Heery, David M., E-mail: david.heery@nottingham.ac.uk [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)

2010-01-01

The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBP{Delta}998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.
Role of nuclear bodies in apoptosis signalling.

Science.gov (United States)

Krieghoff-Henning, Eva; Hofmann, Thomas G

2008-11-01

Promyelocytic leukemia nuclear bodies (PML NBs) are dynamic macromolecular multiprotein complexes that recruit and release a plethora of proteins. A considerable number of PML NB components play vital roles in apoptosis, senescence regulation and tumour suppression. The molecular basis by which PML NBs control these cellular responses is still just beginning to be understood. In addition to PML itself, numerous further tumour suppressors including transcriptional regulator p53, acetyl transferase CBP (CREB binding protein) and protein kinase HIPK2 (homeodomain interacting protein kinase 2) are recruited to PML NBs in response to genotoxic stress or oncogenic transformation and drive the senescence and apoptosis response by regulating p53 activity. Moreover, in response to death-receptor activation, PML NBs may act as nuclear depots that release apoptotic factors, such as the FLASH (FLICE-associated huge) protein, to amplify the death signal. PML NBs are also associated with other nuclear domains including Cajal bodies and nucleoli and share apoptotic regulators with these domains, implying crosstalk between NBs in apoptosis regulation. In conclusion, PML NBs appear to regulate cell death decisions through different, pathway-specific molecular mechanisms.
Human herpesvirus 6B U19 protein is a PML-regulated transcriptional activator that localizes to nuclear foci in a PML-independent manner

DEFF Research Database (Denmark)

Kofod-Olsen, Emil; Ross-Hansen, Katrine; Mikkelsen, Jacob Giehm

2008-01-01

Human herpesvirus 6B (HHV-6B) contains an IE-B domain spanning open reading frames U16/17-U19, based on homology with human cytomegalovirus. Here, the protein product, U19, of the HHV-6B U19 gene is identified as a 47 kDa transcriptional activator. HHV-6B infection or overexpression of U19...... transactivated the RANTES promoter. Mutational analysis of the promoter indicated that transactivation was not critically dependent on the promoter sites CRE, NF-kappaB, ISRE or NF-IL6. ND10 are nuclear substructures that are involved in several cellular regulatory pathways, including those controlling gene...... structure, U19 also localized to the centre of ND10. Knockdown of PML by small interfering RNA did not prevent U19 localization to ND10-like foci, but instead led to a fourfold increase in U19-induced transcription from the RANTES promoter. Generation of four truncated U19 proteins indicated that the N...
Role of SUMO in RNF4-mediated promyelocytic leukemia protein (PML) degradation: sumoylation of PML and phospho-switch control of its SUMO binding domain dissected in living cells.

Science.gov (United States)

Percherancier, Yann; Germain-Desprez, Delphine; Galisson, Frédéric; Mascle, Xavier H; Dianoux, Laurent; Estephan, Patricia; Chelbi-Alix, Mounira K; Aubry, Muriel

2009-06-12

Promyelocytic leukemia protein (PML) is a tumor suppressor acting as the organizer of subnuclear structures called PML nuclear bodies (NBs). Both covalent modification of PML by the small ubiquitin-like modifier (SUMO) and non-covalent binding of SUMO to the PML SUMO binding domain (SBD) are necessary for PML NB formation and maturation. PML sumoylation and proteasome-dependent degradation induced by the E3 ubiquitin ligase, RNF4, are enhanced by the acute promyelocytic leukemia therapeutic agent, arsenic trioxide (As2O3). Here, we established a novel bioluminescence resonance energy transfer (BRET) assay to dissect and monitor PML/SUMO interactions dynamically in living cells upon addition of therapeutic agents. Using this sensitive and quantitative SUMO BRET assay that distinguishes PML sumoylation from SBD-mediated PML/SUMO non-covalent interactions, we probed the respective roles of covalent and non-covalent PML/SUMO interactions in PML degradation and interaction with RNF4. We found that, although dispensable for As2O3-enhanced PML sumoylation and RNF4 interaction, PML SBD core sequence was required for As2O3- and RNF4-induced PML degradation. As confirmed with a phosphomimetic mutant, phosphorylation of a stretch of serine residues, contained within PML SBD was needed for PML interaction with SUMO-modified protein partners and thus for NB maturation. However, mutation of these serine residues did not impair As2O3- and RNF4-induced PML degradation, contrasting with the known role of these phosphoserine residues for casein kinase 2-promoted PML degradation. Altogether, these data suggest a model whereby sumoylation- and SBD-dependent PML oligomerization within NBs is sufficient for RNF4-mediated PML degradation and does not require the phosphorylation-dependent association of PML with other sumoylated partners.
PML, SUMOylation and senescence

Directory of Open Access Journals (Sweden)

Hugues eDe Thé

2013-07-01

Full Text Available Since its discovery, 25 years ago, PML has been an enigma. Implicated in the oncogenic PML/RARA fusion, forming elusive intranuclear domains, triggering cell death or senescence, controlled by and perhaps controlling SUMOylation... there are multiple PML-related issues. Here we review the reciprocal interactions between PML, senescence and SUMOylation, notably in the context of cellular transformation.
Expression and function of PML-RARA in the hematopoietic progenitor cells of Ctsg-PML-RARA mice.

Directory of Open Access Journals (Sweden)

Lukas D Wartman

Full Text Available Because PML-RARA-induced acute promyelocytic leukemia (APL is a morphologically differentiated leukemia, many groups have speculated about whether its leukemic cell of origin is a committed myeloid precursor (e.g. a promyelocyte versus an hematopoietic stem/progenitor cell (HSPC. We originally targeted PML-RARA expression with CTSG regulatory elements, based on the early observation that this gene was maximally expressed in cells with promyelocyte morphology. Here, we show that both Ctsg, and PML-RARA targeted to the Ctsg locus (in Ctsg-PML-RARA mice, are expressed in the purified KLS cells of these mice (KLS = Kit(+Lin(-Sca(+, which are highly enriched for HSPCs, and this expression results in biological effects in multi-lineage competitive repopulation assays. Further, we demonstrate the transcriptional consequences of PML-RARA expression in Ctsg-PML-RARA mice in early myeloid development in other myeloid progenitor compartments [common myeloid progenitors (CMPs and granulocyte/monocyte progenitors (GMPs], which have a distinct gene expression signature compared to wild-type (WT mice. Although PML-RARA is indeed expressed at high levels in the promyelocytes of Ctsg-PML-RARA mice and alters the transcriptional signature of these cells, it does not induce their self-renewal. In sum, these results demonstrate that in the Ctsg-PML-RARA mouse model of APL, PML-RARA is expressed in and affects the function of multipotent progenitor cells. Finally, since PML/Pml is normally expressed in the HSPCs of both humans and mice, and since some human APL samples contain TCR rearrangements and express T lineage genes, we suggest that the very early hematopoietic expression of PML-RARA in this mouse model may closely mimic the physiologic expression pattern of PML-RARA in human APL patients.
Classifying PML risk with disease modifying therapies.

Science.gov (United States)

Berger, Joseph R

2017-02-01

To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk. A method of contextualizing PML risk for DMTs is warranted. Classification of PML risk was predicated on three criteria:: 1) whether the underlying condition being treated predisposes to PML in the absence of the drug; 2) the latency from initiation of the drug to the development of PML; and 3) the frequency with which PML is observed. Among the DMTs, natalizumab occupies a place of its own with respect to PML risk. Significantly lesser degrees of risk exist for fingolimod and dimethyl fumarate. Whether PML will be observed with other DMTs in use for MS, such as, rituximab, teriflunomide, and alemtuzumab, remains uncertain. A logical classification for stratifying DMT PML risk is important for both the physician and patient in contextualizing risk/benefit ratios. As additional experience accumulates regarding PML and the DMTs, this early effort will undoubtedly require revisiting. Copyright © 2016 Elsevier B.V. All rights reserved.
The tumor suppressor SHIP1 colocalizes in nucleolar cavities with p53 and components of PML nuclear bodies.

Science.gov (United States)

Ehm, Patrick; Nalaskowski, Marcus M; Wundenberg, Torsten; Jücker, Manfred

2015-01-01

The inositol 5-phosphatase SHIP1 is a negative regulator of signaling processes in haematopoietic cells. By converting PI(3,4,5)P3 to PtdIns(3,4)P2 at the plasma membrane, SHIP1 modifies PI3-kinase mediated signaling. We have recently demonstrated that SHIP1 is a nucleo-cytoplasmic shuttling protein and SHIP1 nuclear puncta partially colocalize with FLASH, a component of nuclear bodies. In this study, we demonstrate that endogenous SHIP1 localizes to intranucleolar regions of both normal and leukemic haematopoietic cells. In addition, we report that ectopically expressed SHIP1 accumulates in nucleolar cavities and colocalizes with the tumor suppressor protein p53 and components of PML nuclear bodies (e.g. SP100, SUMO-1 and CK2). Moreover, SHIP1 also colocalizes in nucleolar cavities with components of the ubiquitin-proteasome pathway. By using confocal microscopy data, we generated 3D-models revealing the enormous extent of the SHIP1 aggresomes in the nucleolus. Furthermore, treatment of cells with the proteasome inhibitor MG132 causes an enlargement of nucleolar SHIP1 containing structures. Unexpectedly, this accumulation can be partially prevented by treatment with the inhibitor of nuclear protein export Leptomycin B. In recent years, several proteins aggregating in nucleolar cavities were shown to be key factors of neurodegenerative diseases and cancerogenesis. Our findings support current relevance of nuclear localized SHIP1.
A Role for PML in Innate Immunity

Science.gov (United States)

Lunardi, Andrea; Gaboli, Mirella; Giorgio, Marco; Rivi, Roberta; Bygrave, Anne; Antoniou, Michael; Drabek, Dubravka; Dzierzak, Elaine; Fagioli, Marta; Salmena, Leonardo; Botto, Marina; Cordon-Cardo, Carlos; Luzzatto, Lucio; Pelicci, Pier Giuseppe; Grosveld, Frank; Pandolfi, Pier Paolo

2011-01-01

The promyelocytic leukemia gene (PML) of acute promyelocytic leukemia is an established tumor suppressor gene with critical functions in growth suppression, induction of apoptosis, and cellular senescence. Interestingly, although less studied, PML seems to play a key role also in immune response to viral infection. Herein, we report that Pml −/− mice spontaneously develop an atypical invasive and lethal granulomatous lesion known as botryomycosis (BTM). In Pml −/− mice, BTM is the result of impaired function of macrophages, whereby they fail to become activated and are thus unable to clear pathogenic microorganisms. Accordingly, Pml −/− mice are resistant to lipopolysaccharide (LPS)–induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-κB prosurvival pathway. These results not only shed light on a new fundamental function of PML in innate immunity, but they also point to a proto-oncogenic role for PML in certain cellular and pathological contexts. PMID:21779477
Coiled-coil domain of PML is essential for the aberrant dynamics of PML-RARα, resulting in sequestration and decreased mobility of SMRT

International Nuclear Information System (INIS)

Huang Ying; Qiu Jihui; Chen Guoqiang; Dong Shuo

2008-01-01

Promyelocytic leukemia-retinoic acid receptor α (PML-RARα) is the most frequent RARα fusion protein in acute promyelocytic leukemia (APL). Our previous study has demonstrated that, compared with RARα, PML-RARα had reduced intranuclear mobility accompanied with mislocalization. To understand the molecular basis for the altered dynamics of PML-RARα fusion protein, we performed FRAP analysis at a single cell level. Results indicated that three known sumoylation site mutated PML-RARα had same intracellular localization and reduced mobility as wild-type counterpart. The coiled-coil domain of PML is responsible for the aberrant dynamics of PML-RARα. In addition, we revealed that co-repressor SMRT co-localized with PML-RARα, resulting in the immobilization of SMRT while ATRA treatment eliminated their association and reversed the immobile effect of SMRT. Furthermore, co-activator CBP, co-localized with PML-RARα in an ATRA-independent way, was demonstrated as a high dynamic intranuclear molecule. These results would shed new insights for the molecular mechanisms of PML-RARα-associated leukemogenesis
Androgen receptor regulates nuclear trafficking and nuclear domain residency of corepressor HDAC7 in a ligand-dependent fashion

International Nuclear Information System (INIS)

Karvonen, Ulla; Jaenne, Olli A.; Palvimo, Jorma J.

2006-01-01

In addition to chromosomal proteins, histone deacetylases (HDACs) target transcription factors in transcriptional repression. Here, we show that the class II HDAC family member HDAC7 is an efficient corepressor of the androgen receptor (AR). HDAC7 resided in the cytoplasm in the absence of AR or a cognate ligand, but hormone-occupancy of AR induced nuclear transfer of HDAC7. Nuclear colocalization pattern of AR and HDAC7 was dependent on the nature of the ligand. In the presence of testosterone, a portion of HDAC7 localized to pearl-like nuclear domains, whereas AR occupied with antagonistic ligands cyproterone acetate- or casodex (bicalutamide) recruited HDAC7 from these domains to colocalize with the receptor in speckles and nucleoplasm in a more complete fashion. Ectopic expression of PML-3 relieved the repressive effect of HDAC7 on AR function by sequestering HDAC7 to PML-3 domains. AR acetylation at Lys630/632/633 was not the target of HDAC7 repression, since repression of AR function was independent of these acetylation sites. Moreover, the deacetylase activity of HDAC7 was in part dispensable in the repression of AR function. In sum, our results identify HDAC7 as a novel AR corepressor whose subcellular and subnuclear compartmentalization can be regulated in an androgen-selective manner
Reassessing the risk of natalizumab-associated PML.

Science.gov (United States)

Berger, Joseph R; Fox, Robert J

2016-08-01

The risk algorithm for natalizumab-associated PML was first established in 2012 using the observations that JC virus antibody status, prolonged duration of natalizumab therapy (>2 years), and prior exposure to immunosuppressive therapy increased the risk for the disease. Prior to the publication of Biogen's algorithm, a risk algorithm was created by Fox and Rudick using an Excel spreadsheet in order to address the concerns of their patients. Applying the most recently available data regarding natalizumab-associated PML, the risk assessments for PML were recalculated. The current numbers indicate substantially higher risks for PML in 2015 than in 2012. Our calculations suggest that an individual having all three risk factors has an approximately 1 in 44 chance of developing PML.
Advances in the management of PML: focus on natalizumab.

Science.gov (United States)

Fox, Robert

2011-11-01

Progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the central nervous system, occurs mainly in the setting of broad-based and selective immunosuppression. The immunomodulatory agent most often implicated in the development of PML is the monoclonal antibody natalizumab. Management of PML begins with risk stratification. Factors that predict the risk of PML are JC virus (JCV) antibody status, history of chemotherapy use, and cumulative exposure to natalizumab. The risk of natalizumab-related PML increases up to a duration of 36 months of therapy, after which the risk appears to level off. If suspicious for PML, the use of a sensitive JCV polymerase chain reaction assay permits early diagnosis. Immune reconstitution represents the mainstay of treatment for PML. With rapid reversal of immunosuppression followed by immunologic recovery, almost all patients suffer clinical deterioration termed immune reconstitution inflammatory syndrome (IRIS). High-dose corticosteroids are often recommended if a clinical and imaging syndrome resembling IRIS develops after immune restoration.
Ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (PML protein in cultured cells

Directory of Open Access Journals (Sweden)

Szekely Laszlo

2003-04-01

Full Text Available Abstract Background Ebola virus causes severe, often fatal hemorrhagic fever in humans. The mechanism of escape from cellular anti-viral mechanisms is not yet fully understood. The promyelocytic leukaemia (PML associated nuclear body is part of the interferon inducible cellular defense system. Several RNA viruses have been found to interfere with the anti-viral function of the PML body. The possible interaction between Ebola virus and the PML bodies has not yet been explored. Results We found that two cell lines, Vero E6 and MCF7, support virus production at high and low levels respectively. The expression of viral proteins was visualized and quantified using high resolution immunofluorescence microscopy. Ebola encoded NP and VP35 accumulated in cytoplasmic inclusion bodies whereas VP40 was mainly membrane associated but it was also present diffusely in the cytoplasm as well as in the euchromatic areas of the nucleus. The anti-VP40 antibody also allowed the detection of extracellular virions. Interferon-alpha treatment decreased the production of all three viral proteins and delayed the development of cytopathic effects in both cell lines. Virus infection and interferon-alpha treatment induced high levels of PML protein expression in MCF7 but much less in Vero E6 cells. No disruption of PML bodies, a common phenomenon induced by a variety of different viruses, was observed. Conclusion We have established a simple fixation and immunofluorescence staining procedure that allows specific co-detection and precise sub-cellular localization of the PML nuclear bodies and the Ebola virus encoded proteins NP, VP35 and VP40 in formaldehyde treated cells. Interferon-alpha treatment delays virus production in vitro. Intact PML bodies may play an anti-viral role in Ebola infected cells.

PML and rheumatology: the contribution of disease and drugs.

LENUS (Irish Health Repository)

Molloy, Eamonn S

2011-11-01

Progressive multifocal leukoencephalopathy (PML), a rare, typically fatal, opportunistic infection caused by the JC virus, is becoming relevant to physicians in multiple specialties, including those who prescribe biologic agents for the treatment of autoimmune disorders. Reports of PML have led to US Food and Drug Administration alerts and warning letters regarding four immunosuppressive agents in recent years (natalizumab, rituximab, efalizumab, and mycophenolate mofetil). Consequently, informed clinical decision-making requires understanding the risk of PML associated with these therapies. An estimate of the relative frequency of PML associated with specific rheumatic conditions has been generated. Systemic lupus erythematosus appears to be associated with susceptibility to PML that cannot be fully explained by the intensity of immunosuppressive therapy. Further, the use of rituximab in patients with rheumatic disease has raised concerns. However, definitive attribution of cause is precluded by the limitations of the currently available data. All patients with rheumatic disease, regardless of the intensity of their current immunosuppressive therapy, should be considered potentially at risk of PML. With an evolving understanding of a greater clinical heterogeneity of PML, advances in diagnostic methods, and significant implications for therapy, PML should be considered in the differential diagnosis of neurologic manifestations of rheumatic diseases.
A role for PML in innate immunity

NARCIS (Netherlands)

A. Lunardi (Andrea); M. Gaboli (Mirella); M. Giorgio (Marco); R. Rivi (Roberta); A. Bygrave (Anne); D.D. Drabek (Dubravka); E.A. Dzierzak (Elaine); M. Fagioli (Marta); L. Salmena (Leonardo); M. Antoniou (Michael); M. Botto (Marina); C. Cordon-Cardo (Carlos); L. Luzzatto (Lucio); P.G. Pelicci; F.G. Grosveld (Frank); P.P. Pandolfi

2011-01-01

textabstractThe promyelocytic leukemia gene (PML) of acute promyelocytic leukemia is an established tumor suppressor gene with critical functions in growth suppression, induction of apoptosis, and cellular senescence. Interestingly, although less studied, PML seems to play a key role also in immune
PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy.

Science.gov (United States)

Vincenzi, Bruno; Santini, Daniele; Schiavon, Gaia; Frezza, Anna Maria; Silletta, Marianna; Crucitti, Pierfilippo; Casali, Paolo; Dei Tos, Angelo P; Rossi, Sabrina; Rizzo, Sergio; Badalamenti, Giuseppe; Tomasino, Rosa Maria; Russo, Antonio; Butrynski, James E; Tonini, Giuseppe

2012-04-01

Soft tissue sarcomas are aggressive tumors representing alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7-41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down-regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis. Copyright © 2011 Wiley Periodicals, Inc.
Analysis of a Cartesian PML approximation to acoustic scattering problems in and

KAUST Repository

Bramble, James H.

2013-08-01

We consider the application of a perfectly matched layer (PML) technique applied in Cartesian geometry to approximate solutions of the acoustic scattering problem in the frequency domain. The PML is viewed as a complex coordinate shift ("stretching") and leads to a variable complex coefficient equation for the acoustic wave posed on an infinite domain, the complement of the bounded scatterer. The use of Cartesian geometry leads to a PML operator with simple coefficients, although, still complex symmetric (non-Hermitian). The PML reformulation results in a problem whose solution coincides with the original solution inside the PML layer while decaying exponentially outside. The rapid decay of the PML solution suggests truncation to a bounded domain with a convenient outer boundary condition and subsequent finite element approximation (for the truncated problem). This paper provides new stability estimates for the Cartesian PML approximations both on the infinite and the truncated domain. We first investigate the stability of the infinite PML approximation as a function of the PML strength σ0. This is done for PML methods which involve continuous piecewise smooth stretching as well as piecewise constant stretching functions. We next introduce a truncation parameter M which determines the size of the PML layer. Our analysis shows that the truncated PML problem is stable provided that the product of Mσ0 is sufficiently large, in which case the solution of the problem on the truncated domain converges exponentially to that of the original problem in the domain of interest near the scatterer. This justifies the simple computational strategy of selecting a fixed PML layer and increasing σ0 to obtain the desired accuracy. The results of numerical experiments varying M and σ0 are given which illustrate the theoretically predicted behavior. © 2013 Elsevier B.V. All rights reserved.
Nuclear bodies reorganize during myogenesis in vitro and are differentially disrupted by expression of FSHD-associated DUX4

Directory of Open Access Journals (Sweden)

Sachiko Homma

2016-12-01

Full Text Available Abstract Background Nuclear bodies, such as nucleoli, PML bodies, and SC35 speckles, are dynamic sub-nuclear structures that regulate multiple genetic and epigenetic processes. Additional regulation is provided by RNA/DNA handling proteins, notably TDP-43 and FUS, which have been linked to ALS pathology. Previous work showed that mouse cell line myotubes have fewer but larger nucleoli than myoblasts, and we had found that nuclear aggregation of TDP-43 in human myotubes was induced by expression of DUX4-FL, a transcription factor that is aberrantly expressed and causes pathology in facioscapulohumeral dystrophy (FSHD. However, questions remained about nuclear bodies in human myogenesis and in muscle disease. Methods We examined nucleoli, PML bodies, SC35 speckles, TDP-43, and FUS in myoblasts and myotubes derived from healthy donors and from patients with FSHD, laminin-alpha-2-deficiency (MDC1A, and alpha-sarcoglycan-deficiency (LGMD2D. We further examined how these nuclear bodies and proteins were affected by DUX4-FL expression. Results We found that nucleoli, PML bodies, and SC35 speckles reorganized during differentiation in vitro, with all three becoming less abundant in myotube vs. myoblast nuclei. In addition, though PML bodies did not change in size, both nucleoli and SC35 speckles were larger in myotube than myoblast nuclei. Similar patterns of nuclear body reorganization occurred in healthy control, MDC1A, and LGMD2D cultures, as well as in the large fraction of nuclei that did not show DUX4-FL expression in FSHD cultures. In contrast, nuclei that expressed endogenous or exogenous DUX4-FL, though retaining normal nucleoli, showed disrupted morphology of some PML bodies and most SC35 speckles and also co-aggregation of FUS with TDP-43. Conclusions Nucleoli, PML bodies, and SC35 speckles reorganize during human myotube formation in vitro. These nuclear body reorganizations are likely needed to carry out the distinct gene transcription and
PML-RARα stabilized by zinc in human acute promyelocytic leukemia NB4 cells.

Science.gov (United States)

Zhu, Bo; Wang, Jia-Yu; Zhou, Jun-Jie; Zhou, Feng; Cheng, Wei; Liu, Ying-Ting; Wang, Jie; Chen, Xiao; Chen, Dian-Hua; Luo, Lan; Hua, Zi-Chun

2017-10-01

Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway. In contrast, autophagy protected TPEN-mediated PML-RARα degradation in NB4 APL cells. We further demonstrated that crosstalk between zinc homeostasis and nitric oxide pathway played a key role in maintaining PML-RARα stability in NB4 APL cells. These results demonstrate that zinc homeostasis is vital for maintaining PML-RARα stability, and zinc depletion by TPEN may be useful as a potential strategy to trigger PML-RARα degradation in APL cells. We also found that TPEN triggered apoptosis of NB4 APL cells in a time-dependent manner. The relationship between PML-RARα degradation and apoptosis triggered by TPEN deserves further study. Copyright © 2017 Elsevier Inc. All rights reserved.
SUMOylation of the Forkhead transcription factor FOXL2 promotes its stabilization/activation through transient recruitment to PML bodies.

Directory of Open Access Journals (Sweden)

Adrien Georges

Full Text Available BACKGROUND: FOXL2 is a transcription factor essential for ovarian development and maintenance. It is mutated in the genetic condition called Blepharophimosis Ptosis Epicantus inversus Syndrome (BPES and in cases of isolated premature ovarian failure. We and others have previously shown that FOXL2 undergoes several post-translational modifications. METHODS AND PRINCIPAL FINDINGS: Here, using cells in culture, we show that interference with FOXL2 SUMOylation leads to a robust inhibition of its transactivation ability, which correlates with a decreased stability. Interestingly, FOXL2 SUMOylation promotes its transient recruitment to subnuclear structures that we demonstrate to be PML (Promyelocytic Leukemia Nuclear Bodies. Since PML bodies are known to be sites where post-translational modifications of nuclear factors take place, we used tandem mass spectrometry to identify new post-translational modifications of FOXL2. Specifically, we detected four phosphorylated, one sulfated and three acetylated sites. CONCLUSIONS: By analogy with other transcription factors, we propose that PML Nuclear Bodies might transiently recruit FOXL2 to the vicinity of locally concentrated enzymes that could be involved in the post-translational maturation of FOXL2. FOXL2 acetylation, sulfation, phosphorylation as well as other modifications yet to be discovered might alter the transactivation capacity of FOXL2 and/or its stability, thus modulating its global intracellular activity.
Analysis of a finite PML approximation to the three dimensional elastic wave scattering problem

KAUST Repository

Bramble, James H.

2010-01-01

We consider the application of a perfectly matched layer (PML) technique to approximate solutions to the elastic wave scattering problem in the frequency domain. The PML is viewed as a complex coordinate shift in spherical coordinates which leads to a variable complex coefficient equation for the displacement vector posed on an infinite domain (the complement of the scatterer). The rapid decay of the PML solution suggests truncation to a bounded domain with a convenient outer boundary condition and subsequent finite element approximation (for the truncated problem). We prove existence and uniqueness of the solutions to the infinite domain and truncated domain PML equations (provided that the truncated domain is sufficiently large). We also show exponential convergence of the solution of the truncated PML problem to the solution of the original scattering problem in the region of interest. We then analyze a Galerkin numerical approximation to the truncated PML problem and prove that it is well posed provided that the PML damping parameter and mesh size are small enough. Finally, computational results illustrating the efficiency of the finite element PML approximation are presented. © 2010 American Mathematical Society.
Protein kinase A activation enhances β-catenin transcriptional activity through nuclear localization to PML bodies.

Directory of Open Access Journals (Sweden)

Mei Zhang

Full Text Available The Protein Kinase A (PKA and Wnt signaling cascades are fundamental pathways involved in cellular development and maintenance. In the osteoblast lineage, these pathways have been demonstrated functionally to be essential for the production of mineralized bone. Evidence for PKA-Wnt crosstalk has been reported both during tumorigenesis and during organogenesis, and the nature of the interaction is thought to rely on tissue and cell context. In this manuscript, we analyzed bone tumors arising from mice with activated PKA caused by mutation of the PKA regulatory subunit Prkar1a. In primary cells from these tumors, we observed relocalization of β-catenin to intranuclear punctuate structures, which were identified as PML bodies. Cellular redistribution of β-catenin could be recapitulated by pharmacologic activation of PKA. Using 3T3-E1 pre-osteoblasts as a model system, we found that PKA phosphorylation sites on β-catenin were required for nuclear re-localization. Further, β-catenin's transport to the nucleus was accompanied by an increase in canonical Wnt-dependent transcription, which also required the PKA sites. PKA-Wnt crosstalk in the cells was bi-directional, including enhanced interactions between β-catenin and the cAMP-responsive element binding protein (CREB and transcriptional crosstalk between the Wnt and PKA signaling pathways. Increases in canonical Wnt/β-catenin signaling were associated with a decrease in the activity of the non-canonical Wnt/Ror2 pathway, which has been shown to antagonize canonical Wnt signaling. Taken together, this study provides a new understanding of the complex regulation of the subcellular distribution of β-catenin and its differential protein-protein interaction that can be modulated by PKA signaling.
JC virus chromogenic in situ hybridization in brain biopsies from patients with and without PML.

Science.gov (United States)

Procop, Gary W; Beck, Rose C; Pettay, James D; Kohn, Debra J; Tuohy, Marion J; Yen-Lieberman, Belinda; Prayson, Richard A; Tubbs, Raymond R

2006-06-01

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC polyoma virus. Electron microscopy and immunohistochemistry are the traditional methods of confirming the presence of the virus in brain biopsies from these patients. We studied the brain biopsies from 7 patients with PML and 6 patients without PML with chromogenic in situ hybridization (CISH) for the JC polyoma virus using a commercially available probe. The biopsies from the patients with the PML cases were proven to contain the JC polyoma virus by traditional and molecular methods. The CISH findings were compared with the known state of infection. All (7/7) of the biopsies from patients with PML were positive for the presence of polyoma virus by CISH, whereas the biopsies from patients without PML were uniformly negative. CISH seems to be a useful tool for the detection of the JC virus in brain biopsies from patients with PML, and is more accessible because a commercial probe is available.
A combined ADER-DG and PML approach for simulating wave propagation in unbounded domains

KAUST Repository

Amler, Thomas

2012-09-19

In this work, we present a numerical approach for simulating wave propagation in unbounded domains which combines discontinuous Galerkin methods with arbitrary high order time integration (ADER-DG) and a stabilized modification of perfectly matched layers (PML). Here, the ADER-DG method is applied to Bérenger’s formulation of PML. The instabilities caused by the original PML formulation are treated by a fractional step method that allows to monitor whether waves are damped in PML region. In grid cells where waves are amplified by the PML, the contribution of damping terms is neglected and auxiliary variables are reset. Results of 2D simulations in acoustic media with constant and discontinuous material parameters are presented to illustrate the performance of the method.
Host transcription factor Speckled 110 kDa (Sp110), a nuclear body protein, is hijacked by hepatitis B virus protein X for viral persistence.

Science.gov (United States)

Sengupta, Isha; Das, Dipanwita; Singh, Shivaram Prasad; Chakravarty, Runu; Das, Chandrima

2017-12-15

Promyelocytic leukemia nuclear bodies (PML-NB) are sub-nuclear organelles that are the hub of numerous proteins. DNA/RNA viruses often hijack the cellular factors resident in PML-NBs to promote their proliferation in host cells. Hepatitis B virus (HBV), belonging to Hepadnaviridae family, remains undetected in early infection as it does not induce the innate immune response and is known to be the cause of several hepatic diseases leading to cirrhosis and hepatocellular carcinoma. The association of PML-NB proteins and HBV is being addressed in a number of recent studies. Here, we report that the PML-NB protein Speckled 110 kDa (Sp110) is SUMO1-modified and undergoes a deSUMOylation-driven release from the PML-NB in the presence of HBV. Intriguingly, Sp110 knockdown significantly reduced viral DNA load in the culture supernatant by activation of the type I interferon-response pathway. Furthermore, we found that Sp110 differentially regulates several direct target genes of hepatitis B virus protein X (HBx), a viral co-factor. Subsequently, we identified Sp110 as a novel interactor of HBx and found this association to be essential for the exit of Sp110 from the PML-NB during HBV infection and HBx recruitment on the promoter of these genes. HBx, in turn, modulates the recruitment of its associated transcription cofactors p300/HDAC1 to these co-regulated genes, thereby altering the host gene expression program in favor of viral persistence. Thus, we report a mechanism by which HBV can evade host immune response by hijacking the PML-NB protein Sp110, and therefore, we propose it to be a novel target for antiviral therapy. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Assessment of a PML Boundary Condition for Simulating an MRI Radio Frequency Coil

Directory of Open Access Journals (Sweden)

Yunsuo Duan

2008-01-01

Full Text Available Computational methods such as the finite difference time domain (FDTD play an important role in simulating radiofrequency (RF coils used in magnetic resonance imaging (MRI. The choice of absorbing boundary conditions affects the final outcome of such studies. We have used FDTD to assess the Berenger's perfectly matched layer (PML as an absorbing boundary condition for computation of the resonance patterns and electromagnetic fields of RF coils. We first experimentally constructed a high-pass birdcage head coil, measured its resonance pattern, and used it to acquire proton (1H phantom MRI images. We then computed the resonance pattern and B1 field of the coil using FDTD with a PML as an absorbing boundary condition. We assessed the accuracy and efficiency of PML by adjusting the parameters of the PML and comparing the calculated results with measured ones. The optimal PML parameters that produce accurate (comparable to the experimental findings FDTD calculations are then provided for the birdcage head coil operating at 127.72 MHz, the Larmor frequency of 1H at 3 Tesla (T.
DAXX-dependent supply of soluble (H3.3-H4) dimers to PML bodies pending deposition into chromatin.

Science.gov (United States)

Delbarre, Erwan; Ivanauskiene, Kristina; Küntziger, Thomas; Collas, Philippe

2013-03-01

Replication-independent chromatin deposition of histone variant H3.3 is mediated by several chaperones. We report a multistep targeting of newly synthesized epitope-tagged H3.3 to chromatin via PML bodies. H3.3 is recruited to PML bodies in a DAXX-dependent manner, a process facilitated by ASF1A. DAXX is required for enrichment of ATRX, but not ASF1A or HIRA, with PML. Nonetheless, the chaperones colocalize with H3.3 at PML bodies and are found in one or more complexes with PML. Both DAXX and PML are necessary to prevent accumulation of a soluble, nonincorporated pool of H3.3. H3.3 targeting to PML is enhanced with an (H3.3-H4)2 tetramerization mutant of H3.3, suggesting H3.3 recruitment to PML as an (H3.3-H4) dimer rather than as a tetramer. Our data support a model of DAXX-mediated recruitment of (H3.3-H4) dimers to PML bodies, which may function as triage centers for H3.3 deposition into chromatin by distinct chaperones.
Design and fabrication of a hybrid maglev model employing PML and SML

Science.gov (United States)

Sun, R. X.; Zheng, J.; Zhan, L. J.; Huang, S. Y.; Li, H. T.; Deng, Z. G.

2017-10-01

A hybrid maglev model combining permanent magnet levitation (PML) and superconducting magnetic levitation (SML) was designed and fabricated to explore a heavy-load levitation system advancing in passive stability and simple structure. In this system, the PML was designed to levitate the load, and the SML was introduced to guarantee the stability. In order to realize different working gaps of the two maglev components, linear bearings were applied to connect the PML layer (for load) and the SML layer (for stability) of the hybrid maglev model. Experimental results indicate that the hybrid maglev model possesses excellent advantages of heavy-load ability and passive stability at the same time. This work presents a possible way to realize a heavy-load passive maglev concept.
SUMO Ligase Protein Inhibitor of Activated STAT1 (PIAS1) Is a Constituent Promyelocytic Leukemia Nuclear Body Protein That Contributes to the Intrinsic Antiviral Immune Response to Herpes Simplex Virus 1.

Science.gov (United States)

Brown, James R; Conn, Kristen L; Wasson, Peter; Charman, Matthew; Tong, Lily; Grant, Kyle; McFarlane, Steven; Boutell, Chris

2016-07-01

Aspects of intrinsic antiviral immunity are mediated by promyelocytic leukemia nuclear body (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the small ubiquitin-like modifier (SUMO) signaling pathway. However, the participating SUMOylation enzymes are not fully characterized. We identify the SUMO ligase protein inhibitor of activated STAT1 (PIAS1) as a constituent PML-NB protein. We show that PIAS1 localizes at PML-NBs in a SUMO interaction motif (SIM)-dependent manner that requires SUMOylated or SUMOylation-competent PML. Following infection with herpes simplex virus 1 (HSV-1), PIAS1 is recruited to nuclear sites associated with viral genome entry in a SIM-dependent manner, consistent with the SIM-dependent recruitment mechanisms of other well-characterized PML-NB proteins. In contrast to that of Daxx and Sp100, however, the recruitment of PIAS1 is enhanced by PML. PIAS1 promotes the stable accumulation of SUMO1 at nuclear sites associated with HSV-1 genome entry, whereas the accumulation of other evaluated PML-NB proteins occurs independently of PIAS1. We show that PIAS1 cooperatively contributes to HSV-1 restriction through mechanisms that are additive to those of PML and cooperative with those of PIAS4. The antiviral mechanisms of PIAS1 are counteracted by ICP0, the HSV-1 SUMO-targeted ubiquitin ligase, which disrupts the recruitment of PIAS1 to nuclear domains that contain infecting HSV-1 genomes through mechanisms that do not directly result in PIAS1 degradation. Adaptive, innate, and intrinsic immunity cooperatively and efficiently restrict the propagation of viral pathogens. Intrinsic immunity mediated by constitutively expressed cellular proteins represents the first line of intracellular defense against infection. PML
(PML): A retrospective study from Pretoria, South Africa

African Journals Online (AJOL)

Two cases of PML have been reported from Gambia, and 4 additional ... impaired co-ordination (41%), and speech disturbances (12%), and CSF analysis showed .... leukoencephalopathy in India and Africa: Is there a biological explanation?
Expression of PML tumor suppressor in A 431 cells reduces cellular growth by inhibiting the epidermal growth factor receptor expression

International Nuclear Information System (INIS)

Vallian, S.; Chang, K.S.

2004-01-01

Our previous studies showed that the promyelocytic leukemia, PML, protein functions as a cellular and growth suppressor. Transient expression of PML was also found to repress the activity of the epidermal growth factor receptor gene promoter. In this study we have examined the effects of PML on A431 cells, which express a high level of + protein. The PML gene was introduced into the cells using the adenovirus-mediated gene transfer system. Western blot analysis on the extracts from the cells expressing PML showed a significant repression in the expression of the epidermal growth factor receptor protein. The cells were examined for growth and DNA synthesis. The data showed a marked reduction in both growth and DNA synthesis rate in the cells expressing PML compared with the control cells. Furthermore, in comparison with the controls, the cells expressing PML were found to be more in G1 phase, fewer in S and about the same number in the G2/M phase. This data clearly demonstrated that the repression of epidermal growth factor receptor expression in A 431 cells by PML was associated with inhibition of cell growth and alteration of the cell cycle distribution, suggesting a novel mechanism for the known growth inhibitory effects of PML
AIDS-related progressive multifocal leukoencephalopathy (PML): A ...

African Journals Online (AJOL)

Patients with positive cerebrospinal fluid (CSF) JC virus confirmed by real-time polymerase chain reaction (PCR) were retrospectively identified from January 2008 to June 2012. Adults seen at Neurology with PML were identified, and clinical features, laboratory findings and imaging studies were analysed. Results. Of 121 ...
Replication of Merkel cell polyomavirus induces reorganization of promyelocytic leukemia nuclear bodies.

Science.gov (United States)

Neumann, Friederike; Czech-Sioli, Manja; Dobner, Thomas; Grundhoff, Adam; Schreiner, Sabrina; Fischer, Nicole

2016-11-01

Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC), a rare but aggressive skin cancer. The virus is highly prevalent: 60-80 % of adults are seropositive; however, cells permissive for MCPyV infection are unknown. Consequently, very little information about the MCPyV life cycle is available. Until recently, MCPyV replication could only be studied using a semi-permissive in vitro replication system (Neumann et al., 2011; Feng et al., 2011, Schowalter et al., 2011). MCPyV replication most likely depends on subnuclear structures such as promyelocytic leukemia protein nuclear bodies (PML-NBs), which are known to play regulatory roles in the infection of many DNA viruses. Here, we investigated PML-NB components as candidate host factors to control MCPyV DNA replication. We showed that PML-NBs change in number and size in cells actively replicating MCPyV proviral DNA. We observed a significant increase in PML-NBs in cells positive for MCPyV viral DNA replication. Interestingly, a significant amount of cells actively replicating MCPyV did not show any Sp100 expression. While PML and Daxx had no effect on MCPyV DNA replication, MCPyV replication was increased in cells depleted for Sp100, strongly suggesting that Sp100 is a negative regulator of MCPyV DNA replication.

The interferon-induced antiviral protein PML (TRIM19) promotes the restriction and transcriptional silencing of lentiviruses in a context-specific, isoform-specific fashion.

Science.gov (United States)

Masroori, Nasser; Merindol, Natacha; Berthoux, Lionel

2016-03-22

The promyelocytic leukemia (PML) protein, a type I interferon (IFN-I)-induced gene product and a member of the tripartite motif (TRIM) family, modulates the transcriptional activity of viruses belonging to various families. Whether PML has an impact on the replication of HIV-1 has not been fully addressed, but recent studies point to its possible involvement in the restriction of HIV-1 in human cells and in the maintenance of transcriptional latency in human cell lines in which HIV-1 is constitutively repressed. We investigated further the restriction of HIV-1 and a related lentivirus, SIVmac, by PML in murine cells and in a lymphocytic human cell line. In particular, we studied the relevance of PML to IFN-I-mediated inhibition and the role of individual human isoforms. We demonstrate that both human PML (hPML) and murine PML (mPML) inhibit the early post-entry stages of the replication of HIV-1 and a related lentivirus, SIVmac. In addition, HIV-1 was transcriptionally silenced by mPML and by hPML isoforms I, II, IV and VI in MEFs. This PML-mediated transcriptional repression was attenuated in presence of the histone deacetylase inhibitor SAHA. In contrast, depletion of PML had no effect on HIV-1 gene expression in a human T cell line. PML was found to contribute to the inhibition of HIV-1 by IFN-I. Specifically, IFN-α and IFN-β treatments of MEFs enhanced the PML-dependent inhibition of HIV-1 early replication stages. We show that PML can inhibit HIV-1 and other lentiviruses as part of the IFN-I-mediated response. The restriction takes place at two distinct steps, i.e. reverse transcription and transcription, and in an isoform-specific, cellular context-specific fashion. Our results support a model in which PML activates innate immune antilentiviral effectors. These data are relevant to the development of latency reversal-inducing pharmacological agents, since PML was previously proposed as a pharmacological target for such inhibitors. This study also has
Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML)

NARCIS (Netherlands)

W. Yang; E.L. Beaudoin; L. Lu; R.A. Du Pasquier (Renaud); M.J. Kuroda; R.A. Willemsen (Ralph); I.J. Koralnik; R.P. Junghans

2007-01-01

textabstractProgressive multifocal leukoencephalopathy (PML) is a deadly brain disease caused by the polyomavirus JC (JCV). The aim of this study is to develop 'designer T cells' armed with anti-JCV TCR-based chimeric immune receptors (CIRs) by gene modification for PML immunotherapy. Two T cell
Nuclear safety and regulation

International Nuclear Information System (INIS)

Kim, Hho Jung

2000-03-01

This book contains 12 chapters, which are atom and radiation, nuclear reactor and kinds of nuclear power plant, safeguard actuation system and stability evaluation for rock foundation of nuclear power plant, nuclear safety and principle, safety analysis and classification of incident, probabilistic safety assessment and major incident, nuclear safety regulation, system of nuclear safety regulation, main function and subject of safety regulation in nuclear facilities, regulation of fuel cycle and a nuclear dump site, protection of radiation and, safety supervision and, safety supervision and measurement of environmental radioactivity.
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
Paraspeckles. A novel nuclear domain

DEFF Research Database (Denmark)

Fox, Archa H; Lam, Yun Wah; Leung, Anthony K L

2002-01-01

BACKGROUND: The cell nucleus contains distinct classes of subnuclear bodies, including nucleoli, splicing speckles, Cajal bodies, gems, and PML bodies. Many nuclear proteins are known to interact dynamically with one or other of these bodies, and disruption of the specific organization of nuclear...
Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

Energy Technology Data Exchange (ETDEWEB)

Komatsu, Tetsuro [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France); Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Will, Hans [Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg (Germany); Nagata, Kyosuke [Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Wodrich, Harald, E-mail: harald.wodrich@u-bordeaux.fr [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France)

2016-04-22

Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.
Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

International Nuclear Information System (INIS)

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

2016-01-01

Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.
The proteins of intra-nuclear bodies: a data-driven analysis of sequence, interaction and expression

Directory of Open Access Journals (Sweden)

Bodén Mikael

2010-04-01

Full Text Available Abstract Background Cajal bodies, nucleoli, PML nuclear bodies, and nuclear speckles are morpohologically distinct intra-nuclear structures that dynamically respond to cellular cues. Such nuclear bodies are hypothesized to play important regulatory roles, e.g. by sequestering and releasing transcription factors in a timely manner. While the nucleolus and nuclear speckles have received more attention experimentally, the PML nuclear body and the Cajal body are still incompletely characterized in terms of their roles and protein complement. Results By collating recent experimentally verified data, we find that almost 1000 proteins in the mouse nuclear proteome are known to associate with one or more of the nuclear bodies. Their gene ontology terms highlight their regulatory roles: splicing is confirmed to be a core activity of speckles and PML nuclear bodies house a range of proteins involved in DNA repair. We train support-vector machines to show that nuclear proteins contain discriminative sequence features that can be used to identify their intra-nuclear body associations. Prediction accuracy is highest for nucleoli and nuclear speckles. The trained models are also used to estimate the full protein complement of each nuclear body. Protein interactions are found primarily to link proteins in the nuclear speckles with proteins from other compartments. Cell cycle expression data provide support for increased activity in nucleoli, nuclear speckles and PML nuclear bodies especially during S and G2 phases. Conclusions The large-scale analysis of the mouse nuclear proteome sheds light on the functional organization of physically embodied intra-nuclear compartments. We observe partial support for the hypothesis that the physical organization of the nucleus mirrors functional modularity. However, we are unable to unambiguously identify proteins' intra-nuclear destination, suggesting that critical drivers behind of intra-nuclear translocation are yet to
Detection of Promyelocytic Leukemia/Retinoic Acid Receptor α (PML/RARα Fusion Gene with Functionalized Graphene Oxide

Directory of Open Access Journals (Sweden)

Hongwei Wang

2013-06-01

Full Text Available An attempt was made to use functionalized graphene oxide (GO to detect the Promyelocytic leukemia/Retinoic acid receptor α fusion gene (PML/RARα fusion gene, a marker gene of acute promyelocytic leukemia. The functionalized GO was prepared by chemical exfoliation method, followed by a polyethylene glycol grafting. It is found that the functionalized GO can selectively adsorb the fluorescein isothiocyanate (FITC-labeled single-stranded DNA probe and quench its fluorescence. The probe can be displaced by the PML/RARα fusion gene to restore the fluorescence, which can be detected by laser confocal microscopy and flow cytometry. These can be used to detect the presence of the PML/RARα fusion gene. This detection method is verified to be fast, simple and reliable.
Application of CPML to two-dimension numerical simulation of nuclear electromagnetic pulse from air explosions

International Nuclear Information System (INIS)

Gao Chunxia; Wang Lianghou

2005-01-01

The characteristics of different types of PML were analyzed and the convolutional PML was chosen to truncate the open boundaries in numerical simulation of nuclear electromagnetic pulse from air explosions. On the basis of the split-field PML and the plane-wave solution of electromagnetic field in free space, the unsplit-field PML was constructed. By applying the convolutional theorem of Fourier transform, the discrete iterative equations of electromagnetic field components were presented in the CPML media under the two-dimension prolate-spheroidal coordinate system. The numerical results indicate that the method of CPML can largely decrease calculation errors of boundary fields. (authors)
Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

International Nuclear Information System (INIS)

Sides, Mark D.; Block, Gregory J.; Shan, Bin; Esteves, Kyle C.; Lin, Zhen; Flemington, Erik K.; Lasky, Joseph A.

2011-01-01

Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.
Nuclear regulation in transition

International Nuclear Information System (INIS)

Tomain, J.P.

1986-01-01

The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed. (author)
Nuclear regulation in transition

Energy Technology Data Exchange (ETDEWEB)

Tomain, J.P. (Cincinnati Univ., OH, US. Coll. of Law)

1986-01-01

The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed.
A prominent lactate peak as a potential key magnetic resonance spectroscopy (MRS feature of progressive multifocal leukoencephalopathy (PML: Spectrum pattern observed in three patients

Directory of Open Access Journals (Sweden)

Duško Kozić

2017-11-01

Full Text Available Progressive multifocal leukoencephalopathy (PML is a rare, often fatal, opportunistic infection, associated with demyelinating process. PML is caused by John Cunningham (JC polyomavirus, and predominantly affects patients with human immunodeficiency virus (HIV infection or other immunocompromised patients. The purpose of this study was to determine the role of magnetic resonance spectroscopy (MRS in establishing the diagnosis of PML. MRS with long and short echo time was performed in two patients with PML associated with HIV infection and in one PML patient associated with chronic lymphocytic leukemia. The most prominent peak on the obtained spectra was for lactate; it showed 2-3 times higher concentration of lactate compared to choline, almost 4-6 times higher lactate concentration compared to creatine, and 4-11 times higher lactate in comparison to N-acetylaspartate concentration. Similar spectrum pattern was observed in all patients. To the best of our knowledge, this is a new finding that might be useful in early diagnosis of PML. Nevertheless, further confirmation of our results is needed, since we analyzed the spectrum pattern only in three patients. Overall, our results could help in early detection of PML, especially in non-HIV patients, and thus prevent the fatal outcome of the disease. MRS could also be useful in detecting “tumefactive” demyelinating lesions in PML patients, associated with immune reconstitution inflammatory syndrome, to avoid misdiagnosis of neoplasm.
New Nuclear Safety Regulations

International Nuclear Information System (INIS)

Novosel, N.; Prah, M.; Cizmek, A.

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 conditions for individual activities to be performed by expert organizations which perform activities in the area 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 announcing the intention to perform nuclear activity, submitting an application for the issue of a license to perform nuclear activity, and the procedure for adoption a decision on issuing a nuclear activity license. The Ordinance also regulates the contents of the application form for the announcement of the intention to perform nuclear activity, as well as of the application for the issue of a nuclear activity license and the method of keeping a nuclear activity register. The Ordinance on special conditions for individual activities to be performed by expert organizations which perform activities in the area of nuclear safety regulates these mentioned conditions, whereas compliance is established by a decision passed by the SONS. Special conditions for individual activities to be performed by expert organizations which perform activities in the area of nuclear safety are organizational, technical, technological conditions and established system of quality assurance. In 2007, SONS finalized the text of new Ordinance on nuclear safety and protection conditions for location, design, construction, operation and decommissioning of facility in which nuclear activity is performed. This Ordinance regulates nuclear safety and protection conditions for location, design, construction, operation and decommissioning of facility in which nuclear activity is performed. This Ordinance defines facilities in which nuclear activity is
High-resolution altitude profiles of the atmospheric turbulence with PML at the Sutherland Observatory

Science.gov (United States)

Catala, L.; Ziad, A.; Fanteï-Caujolle, Y.; Crawford, S. M.; Buckley, D. A. H.; Borgnino, J.; Blary, F.; Nickola, M.; Pickering, T.

2017-05-01

With the prospect of the next generation of ground-based telescopes, the extremely large telescopes, increasingly complex and demanding adaptive optics systems are needed. This is to compensate for image distortion caused by atmospheric turbulence and fully take advantage of mirrors with diameters of 30-40 m. This requires a more precise characterization of the turbulence. The Profiler of Moon Limb (PML) was developed within this context. The PML aims to provide high-resolution altitude profiles of the turbulence using differential measurements of the Moon limb position to calculate the transverse spatio-angular covariance of the angle of arrival fluctuations. The covariance of differential image motion for different separation angles is sensitive to the altitude distribution of the seeing. The use of the continuous Moon limb provides a large number of separation angles allowing for the high-resolution altitude of the profiles. The method is presented and tested with simulated data. Moreover, a PML instrument was deployed at the Sutherland Observatory in South Africa in 2011 August. We present here the results of this measurement campaign.
Regulating nuclear fuel waste

International Nuclear Information System (INIS)

1995-01-01

When Parliament passed the Atomic Energy Control Act in 1946, it erected the framework for nuclear safety in Canada. Under the Act, the government created the Atomic Energy Control Board and gave it the authority to make and enforce regulations governing every aspect of nuclear power production and use in this country. The Act gives the Control Board the flexibility to amend its regulations to adapt to changes in technology, health and safety standards, co-operative agreements with provincial agencies and policy regarding trade in nuclear materials. This flexibility has allowed the Control Board to successfully regulate the nuclear industry for more than 40 years. Its mission statement 'to ensure that the use of nuclear energy in Canada does not pose undue risk to health, safety, security and the environment' concisely states the Control Board's primary objective. The Atomic Energy Control Board regulates all aspects of nuclear energy in Canada to ensure there is no undue risk to health, safety, security or the environment. It does this through a multi-stage licensing process
Flow cytometric immunobead assay for fast and easy detection of PML-RARA fusion proteins for the diagnosis of acute promyelocytic leukemia

NARCIS (Netherlands)

E.H.A. Dekking (E. H A); V.H.J. van der Velden (Vincent); A. Varro (Andras); H. Wai; S. Böttcher (Stephan); M. Kneba (Michael); E. Sonneveld (Edwin); A. Koning; N. Boeckx; N. Van Poecke; P. Lucio (Paulo); A. Mendonça; L. Sedek (Lukasz); T. Szczepanski (Tomasz); T. Kalina (Tomas); V. Kanderová (V.); P.G. Hoogeveen (Patricia); J. Flores-Montero (Juan); C. Chillón (Carmen); A. Orfao (Alberto); J.M.M. Almeida (Julia); P.A.S. Evans; C. Cullen; A.L. Noordijk; P.M. Vermeulen (P.); M.T. de Man (M.); E.P. Dixon (Eric); W.M. Comans-Bitter; J.J.M. van Dongen (Jacques)

2012-01-01

textabstractThe PML-RARA fusion protein is found in approximately 97% of patients with acute promyelocytic leukemia (APL). APL can be associated with life-threatening bleeding complications when undiagnosed and not treated expeditiously. The PML-RARA fusion protein arrests maturation of myeloid
Requirement of the coiled-coil domain of PML-RARα oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation

International Nuclear Information System (INIS)

Kim, Young-Eui; Kim, Dong-Yeon; Lee, Jang-Mi; Kim, Seong-Tae; Han, Tae-Hee; Ahn, Jin-Hyun

2005-01-01

Homo-oligomerization via a coiled-coil (C-C) domain has been shown to be necessary for the promyelocytic leukemia (PML)-retinoic acid receptor-α (RARα) fusion protein to acquire oncogenic potential in acute promyelocytic leukemia. We show here that PML(ΔC-C)-RARα, which contains a deletion in its C-C domain, is neither localized as characteristic microspeckles nor modified by small ubiquitin-like modifiers (SUMO). The absence of sumoylation of the ΔC-C mutant was due to the lack of binding to Ubc9, a SUMO conjugation enzyme. The integrity of RING finger domain was also needed for both sumoylation and microspeckle formation. In GAL4-DNA tethering assays, the ΔC-C mutant completely lost the inhibitory effect on retinoic acid (RA)-mediated transactivation. Furthermore, the expression of CD14 in U937 cells expressing the ΔC-C mutant in response to vitamin D3 was markedly higher than in cells expressing PML-RARα. However, the RA-mediated induction of C/EBPβ in cells expressing the ΔC-C mutant was comparable to that of control cells. Thus, our results suggest that the C-C domain-associated functions of sumoylation, localization as microspeckles, and the inhibition of monocyte differentiation all contribute to the oncogenic activity of PML-RARα
Nuclear regulations and environment

International Nuclear Information System (INIS)

Oliveira, Antonio A.

2001-01-01

After an historical overview of the nuclear regulation system in Argentina a description is made of the country's Nuclear Regulatory Authority (ARN) and of its regulation and control functions. Its organic structure is also outlined. A detailed report is given of the environmental monitoring activities in the sites of the operating Argentine nuclear power plants as well as those of the nuclear research centres. A special reference is made of the monitoring of the relevant uranium mining districts in Argentina. The radon determination in houses of several regions of the country is also mentioned

Nuclear fuel cycle and legal regulations

International Nuclear Information System (INIS)

Shimoyama, Shunji; Kaneko, Koji.

1980-01-01

Nuclear fuel cycle is regulated as a whole in Japan by the law concerning regulation of nuclear raw materials, nuclear fuel materials and reactors (hereafter referred to as ''the law concerning regulation of reactors''), which was published in 1957, and has been amended 13 times. The law seeks to limit the use of atomic energy to peaceful objects, and nuclear fuel materials are controlled centering on the regulation of enterprises which employ nuclear fuel materials, namely regulating each enterprise. While the permission and report of uses are necessary for the employment of nuclear materials under Article 52 and 61 of the law concerning regulation of reactors, the permission provisions are not applied to three kinds of enterprises of refining, processing and reprocessing and the persons who install reactors as the exceptions in Article 52, when nuclear materials are used for the objects of the enterprises themselves. The enterprises of refining, processing and reprocessing and the persons who install reactors are stipulated respectively in the law. Accordingly the nuclear material regulations are applied only to the users of small quantity of such materials, namely universities, research institutes and hospitals. The nuclear fuel materials used in Japan which are imported under international contracts including the nuclear energy agreements between two countries are mostly covered by the security measures of IAEA as internationally controlled substances. (Okada, K.)
Harmonization of nuclear and radiation safety regulations for nuclear power plants with reference levels of Western European Nuclear Regulators Association (WENRA)

International Nuclear Information System (INIS)

Bojchuk, V.S.; Mikolajchuk, O.A.; Gromov, G.V.; Dibach, O.M.; Godovanyuk, G.M.; Nosovs'kij, A.V.

2014-01-01

Self-evaluation of the Ukrainian regulations on nuclear and radiation safety that apply to nuclear power plants for compliance with the reference levels of the Western European Nuclear Regulators Association (WENRA) is presented. Proposals on improvement of the regulations upon self-evaluation are provided
The CFS-PML for 2D Auxiliary Differential Equation FDTD Method Using Associated Hermite Orthogonal Functions

Directory of Open Access Journals (Sweden)

Feng Jiang

2017-01-01

Full Text Available The complex frequency shifted (CFS perfectly matched layer (PML is proposed for the two-dimensional auxiliary differential equation (ADE finite-difference time-domain (FDTD method combined with Associated Hermite (AH orthogonal functions. According to the property of constitutive parameters of CFS-PML (CPML absorbing boundary conditions (ABCs, the auxiliary differential variables are introduced. And one relationship between field components and auxiliary differential variables is derived. Substituting auxiliary differential variables into CPML ABCs, the other relationship between field components and auxiliary differential variables is derived. Then the matrix equations are obtained, which can be unified with Berenger’s PML (BPML and free space. The electric field expansion coefficients can thus be obtained, respectively. In order to validate the efficiency of the proposed method, one example of wave propagation in two-dimensional free space is calculated using BPML, UPML, and CPML. Moreover, the absorbing effectiveness of the BPML, UPML, and CPML is discussed in a two-dimensional (2D case, and the numerical simulations verify the accuracy and efficiency of the proposed method.
Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts.

Science.gov (United States)

Xu, Wen-Xiao; Liu, Sheng-Zhi; Wu, Di; Qiao, Guo-Fen; Yan, Jinglong

2015-01-01

Promyelocytic leukemia (PML) protein is a tumor suppressor that fuses with retinoic acid receptor-α (PML-RARα) to contribute to the initiation of acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) upregulates expression of TGF-β1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. However, how ATO upregulates TGF-β1 expression is uncertain. Thus, we suggested that PML sumoylation is responsible for regulation of TGF-β1 protein expression. Kunming mice were treated with ATO, and osteoblasts were counted under scanning electron microscopy. Masson's staining was used to quantify collagen content. hFOB1.19 cells were transfected with siRNA against UBC9 or RNF4, and then treated with ATO or FBS. TGF-β1, PML expression, and sumoylation were quantified with Western blot, and collagen quantified via immunocytochemistry. ATO enhanced osteoblast accumulation, collagen synthesis, and PML-NB formation in vivo. Knocking down UBC9 in hFOB1.19 cells inhibited ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conversely, knocking down RNF4 enhanced ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. These data suggest that PML sumoylation is required for ATO-induced collagen synthesis in osteoblasts. © 2015 S. Karger AG, Basel.
Analysis of a Cartesian PML approximation to acoustic scattering problems in and

KAUST Repository

Bramble, James H.; Pasciak, Joseph E.

2013-01-01

to that of the original problem in the domain of interest near the scatterer. This justifies the simple computational strategy of selecting a fixed PML layer and increasing σ0 to obtain the desired accuracy. The results of numerical experiments varying M and σ0 are given
Nuclear regulation - the Canadian approach

International Nuclear Information System (INIS)

Jennekens, J.

1981-09-01

Although the Atomic Energy Control Board was established 35 years ago the basic philosophy of nuclear regulation in Canada and the underlying principles of the regulatory process remain essentially unchanged. This paper outlines the Canadian approach to nuclear regulation and explains in practical terms how the principles of regulation are applied. (author)
Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection

Directory of Open Access Journals (Sweden)

Benjamin A. Diner

2016-11-01

Full Text Available The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS. Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1 and human cytomegalovirus (HCMV infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses.
Nuclear safety regulations

International Nuclear Information System (INIS)

1998-01-01

The Departmental Rules and The Safety Guides were issued by the NNSA in 1998. The NNSA performed the activities of propagation and implementation of nuclear safety regulations at QTNPP in order to improve the nuclear safety culture of operating organization and construct and contract organizations
High-Risk Microgranular Acute Promyelocytic Leukemia with a Five-Way Complex Translocation Involving PML-RARA

Directory of Open Access Journals (Sweden)

Benjamin Powers

2015-01-01

Full Text Available Acute promyelocytic leukemia (APL is classically characterized by chromosomal translocation (15;17, resulting in the PML-RARA fusion protein leading to disease. Here, we present a case of a 50-year-old man who presented with signs and symptoms of acute leukemia with concern for APL. Therapy was immediately initiated with all-trans retinoic acid. The morphology of his leukemic blasts was consistent with the hypogranular variant of APL. Subsequent FISH and cytogenetic analysis revealed a unique translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. Molecular testing demonstrated PML/RARA fusion transcripts. Treatment with conventional chemotherapy was added and he went into a complete remission. Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given. The patient remains on maintenance therapy and remains in remission. This is the first such report of a 5-way chromosomal translocation leading to APL. Similar to APL with chromosomal translocations other than classical t(15;17 which result in the typical PML-RARA fusion, our patient responded promptly to an ATRA-containing regimen and remains in complete remission.
Nuclear regulation and safety

International Nuclear Information System (INIS)

Hendrie, J.M.

1982-01-01

Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed
NRC - regulator of nuclear safety

International Nuclear Information System (INIS)

1997-01-01

The U.S. Nuclear Regulatory Commission (NRC) was formed in 1975 to regulate the various commercial and institutional uses of nuclear energy, including nuclear power plants. The agency succeeded the Atomic Energy Commission, which previously had responsibility for both developing and regulating nuclear activities. Federal research and development work for all energy sources, as well as nuclear weapons production, is now conducted by the U.S. Department of Energy. Under its responsibility to protect public health and safety, the NRC has three principal regulatory functions: (1) establish standards and regulations, (2) issue licenses for nuclear facilities and users of nuclear materials, and (3) inspect facilities and users of nuclear materials to ensure compliance with the requirements. These regulatory functions relate to both nuclear power plants and to other uses of nuclear materials - like nuclear medicine programs at hospitals, academic activities at educational institutions, research work, and such industrial applications as gauges and testing equipment. The NRC places a high priority on keeping the public informed of its work. The agency recognizes the interest of citizens in what it does through such activities as maintaining public document rooms across the country and holding public hearings, public meetings in local areas, and discussions with individuals and organizations
A combined ADER-DG and PML approach for simulating wave propagation in unbounded domains

KAUST Repository

Amler, Thomas; Hoteit, Ibrahim; Alkhalifah, Tariq A.

2012-01-01

cells where waves are amplified by the PML, the contribution of damping terms is neglected and auxiliary variables are reset. Results of 2D simulations in acoustic media with constant and discontinuous material parameters are presented to illustrate
A PML-FDTD ALGORITHM FOR SIMULATING PLASMA-COVERED CAVITY-BACKED SLOT ANTENNAS. (R825225)

Science.gov (United States)

A three-dimensional frequency-dependent finite-difference time-domain (FDTD) algorithm with perfectly matched layer (PML) absorbing boundary condition (ABC) and recursive convolution approaches is developed to model plasma-covered open-ended waveguide or cavity-backed slot antenn...
Analysis of the spectrum of a Cartesian Perfectly Matched Layer (PML) approximation to acoustic scattering problems

KAUST Repository

Kim, Seungil

2010-01-01

In this paper, we study the spectrum of the operator which results when the Perfectly Matched Layer (PML) is applied in Cartesian geometry to the Laplacian on an unbounded domain. This is often thought of as a complex change of variables or "complex stretching." The reason that such an operator is of interest is that it can be used to provide a very effective domain truncation approach for approximating acoustic scattering problems posed on unbounded domains. Stretching associated with polar or spherical geometry lead to constant coefficient operators outside of a bounded transition layer and so even though they are on unbounded domains, they (and their numerical approximations) can be analyzed by more standard compact perturbation arguments. In contrast, operators associated with Cartesian stretching are non-constant in unbounded regions and hence cannot be analyzed via a compact perturbation approach. Alternatively, to show that the scattering problem PML operator associated with Cartesian geometry is stable for real nonzero wave numbers, we show that the essential spectrum of the higher order part only intersects the real axis at the origin. This enables us to conclude stability of the PML scattering problem from a uniqueness result given in a subsequent publication. © 2009 Elsevier Inc. All rights reserved.
Paraspeckles. A novel nuclear domain

DEFF Research Database (Denmark)

Fox, Archa H; Lam, Yun Wah; Leung, Anthony K L

2002-01-01

BACKGROUND: The cell nucleus contains distinct classes of subnuclear bodies, including nucleoli, splicing speckles, Cajal bodies, gems, and PML bodies. Many nuclear proteins are known to interact dynamically with one or other of these bodies, and disruption of the specific organization of nuclear...... relocalize quantitatively to unique cap structures at the nucleolar periphery when transcription is inhibited. CONCLUSIONS: We have identified a novel nuclear compartment, termed paraspeckles, found in both primary and transformed human cells. Paraspeckles contain at least three RNA binding proteins that all...
The Characteristics of an Effective Nuclear Regulator

International Nuclear Information System (INIS)

Cheok, Michael; Wertelaers, An; Lojk, Robert; Santini, Miguel; Alm-Lytz, Kirsi; Rigail, Anne-Cecile; Weidenbruck, Kai-Jochen; Stoppa, Gisela; Rainieri, Roberto; Aoki, Masahiro; Gonzalez-Mercado; Miroshnichenko, Mikhail; Kuznetsov, Nikolay; Kudryavtsev, Evgeny; Cid, Rafael; Franzen, Anna; Skanberg, Lars; Gibson, Steve; Golshan, Mina; Cheok, Michael; Nicic, Adriana; Salgado, Nancy; Creswell, Len

2014-01-01

Both national and international organisations agree that the fundamental objective of all nuclear safety regulatory bodies - the regulator's prime purpose - is to ensure that nuclear licensees operate their facilities at all times in a safe manner. Much has been written about ways to improve regulatory processes or to improve the effectiveness of a regulatory body, including in previous OECD/NEA regulatory guidance booklets. But until now, none have focused on the characteristics of an effective nuclear safety regulator. Effective organisations are those that have good leadership and are able to transform strategic direction into operational programmes. Effectiveness is about how well the organisation is achieving its fundamental purpose - in the case of a nuclear safety regulator, ensuring that licensees operate their facilities and discharge their obligations in a safe manner. This regulatory guidance booklet describes the characteristics of an effective nuclear safety regulator in terms of roles and responsibilities, principles and attributes. Each of the characteristics discussed in this report is a necessary feature of an effective nuclear safety regulator but no one characteristic is sufficient on its own. It is the combination of these characteristics that leads to the effectiveness of a nuclear regulatory body. The report provides a unique resource to countries with existing, mature regulators and can be used for benchmarking as well as training and developing staff. It will also be useful for new entrant countries in the process of developing and maintaining an effective nuclear safety regulator. (authors)
The regulations of the Nuclear Technology Committee

International Nuclear Information System (INIS)

Schwarzer, W.

1984-01-01

The work of the Nuclear Technology Committee (NTC) is characterised by the key words 'safety related regulations' and 'nuclear technology'. The rationalisation effect desired from regulations and the not unlimited number of experts qualified for working out regulations, make it necessary to establish priorities. The NTC has almost exclusively worked out regulations for nuclear powerstations and mainly for light water reactors. The program defined at present seems to cover the most important areas. Future developments can be foreseen in the execution of the part of the program not yet concluded, the maintenance of the regulations and, depending on the development of nuclear technology, the greater inclusion of the HTR and possibly the expansion of the regulations to fast breeder reactors and plant of the fuel circuit. (orig./HSCH) [de
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
Public regulation of nuclear plants

International Nuclear Information System (INIS)

Burtheret, M.; Cormis, de

1980-01-01

The construction and operation of nuclear plants are subject to a complex system of governmental administration. The authors list the various governmental authorisations and rules applicable to these plants. In the first part, they describe the national regulations which relate specifically to nuclear plants, and emphasize the provisions which are intended to ensure the safety of the installations and the protection of the public against ionizing radiation. However, while the safety of nuclear plants is a major concern of the authorities, other interests are also protected. This is accomplished by various laws or regulations which apply to nuclear plants as well as other industrial installations. The duties which these texts, and the administrative practice based thereon, impose on Electricite de France are covered in the second part [fr
Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice.

Directory of Open Access Journals (Sweden)

Hiromichi Matsushita

Full Text Available Recent advances in cancer biology have revealed that many malignancies possess a hierarchal system, and leukemic stem cells (LSC or leukemia-initiating cells (LIC appear to be obligatory for disease progression. Acute promyelocytic leukemia (APL, a subtype of acute myeloid leukemia characterized by the formation of a PML-RARα fusion protein, leads to the accumulation of abnormal promyelocytes. In order to understand the precise mechanisms involved in human APL leukemogenesis, we established a humanized in vivo APL model involving retroviral transduction of PML-RARA into CD34(+ hematopoietic cells from human cord blood and transplantation of these cells into immunodeficient mice. The leukemia well recapitulated human APL, consisting of leukemic cells with abundant azurophilic abnormal granules in the cytoplasm, which expressed CD13, CD33 and CD117, but not HLA-DR and CD34, were clustered in the same category as human APL samples in the gene expression analysis, and demonstrated sensitivity to ATRA. As seen in human APL, the induced APL cells showed a low transplantation efficiency in the secondary recipients, which was also exhibited in the transplantations that were carried out using the sorted CD34- fraction. In order to analyze the mechanisms underlying APL initiation and development, fractionated human cord blood was transduced with PML-RARA. Common myeloid progenitors (CMP from CD34(+/CD38(+ cells developed APL. These findings demonstrate that CMP are a target fraction for PML-RARA in APL, whereas the resultant CD34(- APL cells may share the ability to maintain the tumor.

An algebraic method to develop well-posed PML models Absorbing layers, perfectly matched layers, linearized Euler equations

International Nuclear Information System (INIS)

Rahmouni, Adib N.

2004-01-01

In 1994, Berenger [Journal of Computational Physics 114 (1994) 185] proposed a new layer method: perfectly matched layer, PML, for electromagnetism. This new method is based on the truncation of the computational domain by a layer which absorbs waves regardless of their frequency and angle of incidence. Unfortunately, the technique proposed by Berenger (loc. cit.) leads to a system which has lost the most important properties of the original one: strong hyperbolicity and symmetry. We present in this paper an algebraic technique leading to well-known PML model [IEEE Transactions on Antennas and Propagation 44 (1996) 1630] for the linearized Euler equations, strongly well-posed, preserving the advantages of the initial method, and retaining symmetry. The technique proposed in this paper can be extended to various hyperbolic problems
The tumor suppressor SHIP1 colocalizes in nucleolar cavities with p53 and components of PML nuclear bodies

OpenAIRE

Ehm, Patrick; Nalaskowski, Marcus M; Wundenberg, Torsten; Jücker, Manfred

2015-01-01

The inositol 5-phosphatase SHIP1 is a negative regulator of signaling processes in haematopoietic cells. By converting PI(3,4,5)P3 to PtdIns(3,4)P2 at the plasma membrane, SHIP1 modifies PI3-kinase mediated signaling. We have recently demonstrated that SHIP1 is a nucleo-cytoplasmic shuttling protein and SHIP1 nuclear puncta partially colocalize with FLASH, a component of nuclear bodies. In this study, we demonstrate that endogenous SHIP1 localizes to intranucleolar regions of both normal and ...
Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies

Energy Technology Data Exchange (ETDEWEB)

Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); Adams, Matthew [BioScreening Technology Group, Biomedical Health Research Center, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); High, Alec S. [Department of Histopathology, Bexley Wing, St. James' s University Hospital, Beckett Street, Leeds, LS9 7TF West Yorkshire (United Kingdom); Johnson, Colin A., E-mail: c.johnson@leeds.ac.uk [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); Robinson, Philip A. [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom)

2013-02-01

HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies including Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies. -- Highlights: ► We produce and validate new antibody reagents for the ubiquitin-protein ligase HHARI. ► HHARI colocalizes with nuclear bodies including Cajal, PML and SC35 bodies. ► We establish new functions in cell proliferation regulation for HHARI. ► Increased HHARI expression associates with squamous cell carcinoma and proliferation.
Discussion about risk-informed regulations on the nuclear safety

International Nuclear Information System (INIS)

Gu Yeyi

2008-01-01

The article introduces the background and status quo of regulations on the nuclear safety in China, and points out the inadequacies existing with the current regulations. The author explains the risk-informed safety management concerning its development, status quo, and achievements made, in an attempt to make out the trend of improving regulations on the nuclear safety through risk-informed methods. Combining the U.S. development program of establishing risk-informed regulations on the nuclear safety, the author narrates principles and features of the new regulations system, and provides suggestions for the promotion of risk-informed safety management and establishment of risk-informed regulations on the nuclear safety. (author)
Self trust, a major challenge for nuclear regulators

Energy Technology Data Exchange (ETDEWEB)

Eibenschutz, J. [National Nuclear Safety and Safeguards Commission (CNSN), Mexico City (Mexico)

2014-07-01

Self trust. The nuclear community and particularly nuclear regulators overreact to accidents, this has been the case with the three NPP major accidents. Lowering admissible radiation levels, for example, conveys the wrong message to politicians and the general public, and contributes to enhance mistrust towards nuclear. Industry as well as regulators should mature and act with self respect, since the scientific bases of regulation are very solid and should be trusted. Lessons learned should be seriously pursued in spite of the 'uneven playing field'. Obviously safety continues as the main priority, but paranoid reactions from the nuclear professionals could destroy the future of nuclear power. (author)
Self trust, a major challenge for nuclear regulators

International Nuclear Information System (INIS)

Eibenschutz, J.

2014-01-01

Self trust. The nuclear community and particularly nuclear regulators overreact to accidents, this has been the case with the three NPP major accidents. Lowering admissible radiation levels, for example, conveys the wrong message to politicians and the general public, and contributes to enhance mistrust towards nuclear. Industry as well as regulators should mature and act with self respect, since the scientific bases of regulation are very solid and should be trusted. Lessons learned should be seriously pursued in spite of the 'uneven playing field'. Obviously safety continues as the main priority, but paranoid reactions from the nuclear professionals could destroy the future of nuclear power. (author)
Analysis of the spectrum of a Cartesian Perfectly Matched Layer (PML) approximation to acoustic scattering problems

KAUST Repository

Kim, Seungil; Pasciak, Joseph E.

2010-01-01

is stable for real nonzero wave numbers, we show that the essential spectrum of the higher order part only intersects the real axis at the origin. This enables us to conclude stability of the PML scattering problem from a uniqueness result given in a
Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model

DEFF Research Database (Denmark)

Agrawal-Singh, Shuchi; Koschmieder, Steffen; Gelsing, Sandra

2010-01-01

Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative...... role of Pim2 with promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha), we used a well-established PML-RARalpha (PRalpha) mouse model. Pim2 coexpression in PRalpha-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PRalpha cells...... were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PRalpha alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PRalpha cells contained a slightly higher fraction...
Latency Entry of Herpes Simplex Virus 1 Is Determined by the Interaction of Its Genome with the Nuclear Environment

Science.gov (United States)

Cohen, Camille; Streichenberger, Nathalie; Texier, Pascale; Takissian, Julie; Rousseau, Antoine; Poccardi, Nolwenn; Welsch, Jérémy; Corpet, Armelle; Schaeffer, Laurent; Labetoulle, Marc; Lomonte, Patrick

2016-01-01

Herpes simplex virus 1 (HSV-1) establishes latency in trigeminal ganglia (TG) sensory neurons of infected individuals. The commitment of infected neurons toward the viral lytic or latent transcriptional program is likely to depend on both viral and cellular factors, and to differ among individual neurons. In this study, we used a mouse model of HSV-1 infection to investigate the relationship between viral genomes and the nuclear environment in terms of the establishment of latency. During acute infection, viral genomes show two major patterns: replication compartments or multiple spots distributed in the nucleoplasm (namely “multiple-acute”). Viral genomes in the “multiple-acute” pattern are systematically associated with the promyelocytic leukemia (PML) protein in structures designated viral DNA-containing PML nuclear bodies (vDCP-NBs). To investigate the viral and cellular features that favor the acquisition of the latency-associated viral genome patterns, we infected mouse primary TG neurons from wild type (wt) mice or knock-out mice for type 1 interferon (IFN) receptor with wt or a mutant HSV-1, which is unable to replicate due to the synthesis of a non-functional ICP4, the major virus transactivator. We found that the inability of the virus to initiate the lytic program combined to its inability to synthesize a functional ICP0, are the two viral features leading to the formation of vDCP-NBs. The formation of the “multiple-latency” pattern is favored by the type 1 IFN signaling pathway in the context of neurons infected by a virus able to replicate through the expression of a functional ICP4 but unable to express functional VP16 and ICP0. Analyses of TGs harvested from HSV-1 latently infected humans showed that viral genomes and PML occupy similar nuclear areas in infected neurons, eventually forming vDCP-NB-like structures. Overall our study designates PML protein and PML-NBs to be major cellular components involved in the control of HSV-1 latency
Improving the rationality of nuclear safety regulations

International Nuclear Information System (INIS)

Choi, Byung Sun; Choi, Y. G.; Mun, G. H.

2005-03-01

This study focuses on human nature and institutions around the risk management in Korean Nuclear Installations. Nuclear safety regulatory system in Korea has had a tendency to overvalue the technical or engineering areas. But just like other risk management system, the knowledge of social science is also required to design more valid safety regulatory system. As a result of analysis, this study suggest that performance regulation need to be introduced to current nuclear safety regulation system. In this advanced regulatory system, each nuclear generation unit have to be evaluated by performance of its own regulatory implementation and would be treated differently by the performance. Additionally, self-regulation could be very effective was to guarantee nuclear safety. Because KHNP could be judged to have an considerable capabilities to manage its own regulatory procedures. To make self-regulatory system established successfully, it is also important to arrange the appropriate incentive and compensate structures
Improvement and rationalization of nuclear energy laws and regulations

International Nuclear Information System (INIS)

Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chum; Kim, Hak Man; Oh, Ho Chul

2002-03-01

Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea
Improvement and rationalization of nuclear energy laws and regulations

Energy Technology Data Exchange (ETDEWEB)

Lee, Mo Sung; Chung, Gum Chun; Kim, Hak Man; Oh, Ho Chul [Cheongju Univ., Cheongju (Korea, Republic of)

2001-03-15

Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea.
Improvement and rationalization of nuclear energy laws and regulations

Energy Technology Data Exchange (ETDEWEB)

Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chum; Kim, Hak Man; Oh, Ho Chul [Chongju Univ., Cheongju (Korea, Republic of)

2002-03-15

Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea.
Investigation of dust particles with future Russian lunar missions: achievements of further development of PmL instrument.

Science.gov (United States)

Kuznetsov, Ilya; Zakharov, Alexander; Afonin, Valeri; Seran, Elena; Godefroy, Michel; Shashkova, Inna; Lyash, Andrey; Dolnikov, Gennady; Popel, Sergey; Lisin, Evgeny

2016-07-01

, solar emission. Dust analyzer instrument PmL for future Russian lander missions intends for investigation the dynamics of dusty plasma near lunar surface. PmL consists of three parts in the case of Luna-Glob: Impact Sensor and two Electric Field Sensors (EFC). There are 9 parts of PmL instrument for Luna-Resource mission: two Impact Sensors, 5 EFC (three on the Boom and two on the lander) and 2 Solar Wind and Dust Analyzers. These days the engineering model of PmL for LG-mission is finished. We obtained first practical results from the simulating chambers with dust particles injectors and plasma inside. All the important achievements are presented in this report as well as the roadmap for further development of PmL instruments in both of Russian lunar missions.
Development regulation regarding with licensing of nuclear installation

International Nuclear Information System (INIS)

Bambang Riyono; Yudi Pramono; Dahlia Cakrawati Sinaga

2011-01-01

Provisions of Article 17 paragraph (3) of Law Number 10 Year 1997 on Nuclear cleary mandates for the establishment of government regulations (GR) on Nuclear licensing containing the requirements and procedure, both from the standpoint of their utilization and installation. To use has been rising GR No.29 Year 2008 on the Use of Ionizing Radiation Sources and Nuclear Materials, while for the installation has been published PP No.43 Year 2006 on Nuclear Reactor Licensing, and BAPETEN Chairman Decree No.3 Year 2006 on Non-reactor Nuclear Installation Licensing. Based on the background of the preparation of both the aforementioned are just regulate the reactor and utilization, not yet fully meet the mandate of Article 17 paragraph (3) of Law No.10 of 1997 on Nuclear, including other nuclear installations. For these reasons, it initiated the need for a separate regulation containing provisions concerning licensing of non-reactor nuclear installations. On the other side from the understanding the legal aspects and interpretations of the Law No.10 of 2004 on the Establishment Regulation Legislation, should be in single mandate of Article 17 paragraph (3) of Law No.10 of 1997 on Nuclear would only produce one of the requirements and procedure for the use or installation, or a maximum of two (2) GR related licensing the use and installation. This is encourages conducted the assessing or studies related to how possible it is according to the legal aspect is justified to combine in one Nuclear licensing regulations regarding both the use and installation, by looking at the complexity of installation and wide scope of utilization of nuclear energy in Indonesia. The results of this paper is expected to provide input in the preparation of GR on licensing of nuclear installations. (author)
Subtipos moleculares de PML/RARα en pacientes con leucemia promielocítica aguda

Directory of Open Access Journals (Sweden)

María del Carmen Castro-Mujica

2013-03-01

Full Text Available El objetivo fue describir la frecuencia de los subtipos moleculares de PML/RARα en pacientes con leucemia promielocítica aguda (LPA y su distribución según grupo de riesgo de recaída y citomorfología. Se realizó una serie de casos que incluyó a cincuenta pacientes registrados en el Instituto Nacional de Enfermedades Neoplásicas (INEN, durante el periodo 2010-2012, con diagnóstico molecular de LPA PML/RARα y subtipos bcr1, bcr2 y bcr3 por reacción en cadena de la polimerasa con transcriptasa reversa (RT-PCR. El subtipo bcr1 fue el más frecuente (62%. Los pacientes con riesgo de recaída intermedio y morfología hipergranular fueron, en su mayoría, bcr1 (70% y todos los que poseían riesgo de recaída alto y morfología hipogranular fueron bcr3. Se concluye que en la población estudiada hay un predomino del subtipo bcr1 y que existen diferencias en la distribución de los subtipos bcr1 y bcr3 según el grupo de riesgo de recaída y citomorfología
Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores.

Science.gov (United States)

Elosegui-Artola, Alberto; Andreu, Ion; Beedle, Amy E M; Lezamiz, Ainhoa; Uroz, Marina; Kosmalska, Anita J; Oria, Roger; Kechagia, Jenny Z; Rico-Lastres, Palma; Le Roux, Anabel-Lise; Shanahan, Catherine M; Trepat, Xavier; Navajas, Daniel; Garcia-Manyes, Sergi; Roca-Cusachs, Pere

2017-11-30

YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation. Copyright © 2017 Elsevier Inc. All rights reserved.
Regulation at nuclear fuel cycle

International Nuclear Information System (INIS)

2002-01-01

This bulletin contains information about activities of the Nuclear Regulatory Authority of the Slovak Republic (UJD). In this leaflet the role of the UJD in regulation at nuclear fuel cycle is presented. The Nuclear Fuel Cycle (NFC) is a complex of activities linked with production of nuclear fuel for nuclear reactors as a source of energy used for production of electricity and heat, and of activities linked with spent nuclear fuel handling. Activities linked with nuclear fuel (NF) production, known as the Front-End of Nuclear Fuel Cycle, include (production of nuclear fuel from uranium as the most frequently used element). After discharging spent nuclear fuel (SNF) from nuclear reactor the activities follow linked with its storage, reprocessing and disposal known as the Back-End of Nuclear Fuel Cycle. Individual activity, which penetrates throughout the NFC, is transport of nuclear materials various forms during NF production and transport of NF and SNF. Nuclear reactors are installed in the Slovak Republic only in commercial nuclear power plants and the NFC is of the open type is imported from abroad and SNF is long-term supposed without reprocessing. The main mission of the area of NFC is supervision over: - assurance of nuclear safety throughout all NFC activities; - observance of provisions of the Treaty on Non-Proliferation of Nuclear Weapons during nuclear material handling; with an aim to prevent leakage of radioactive substances into environment (including deliberated danage of NFC sensitive facilities and misuse of nuclear materials to production of nuclear weapons. The UJD carries out this mission through: - assessment of safety documentation submitted by operators of nuclear installations at which nuclear material, NF and SNF is handled; - inspections concentrated on assurance of compliance of real conditions in NFC, i.e. storage and transport of NF and SNF; storage, transport and disposal of wastes from processing of SNF; with assumptions of the safety
Energy policy study. Volume 10. Nuclear power regulation

International Nuclear Information System (INIS)

Nikodem, Z.D.; Reynolds, A.W.; Clark, R.G.

1980-05-01

This report examines the programs for regulating the safety, design, and operation of domestic nuclear power plants. The first part of the study describes the Federal and State regulatory procedures. It describes the legal foundations for the Federal licensing process and the associated State regulatory activities. It then analyzes the aspects of these procedures that affect the cost and supply of nuclear-generated electricity. The second part of this study examines the effects of nuclear safety regulations on the planning and construction lead time for nuclear power stations, the cost of nuclear power, and, ultimately, the decision to invest in nuclear power
Synergism in regulation of nuclear and radiological activities

International Nuclear Information System (INIS)

Buzdugan, A.

2009-01-01

In 2006 the reform of nuclear activity regulation in Moldova was initiated. On May 11, 2006, the Parliament of the Republic of Moldova passed the law Nr 111-XVI 'About Safe Accomplishment of Nuclear and Radiological Activity'. On the 23rd of March, 2007 the National Agency for Regulation of Nuclear and Radiological Activities (NARNRA) was founded due to the decree of the Government under the Ministry of Ecology and Natural Resources. Its first objective was elaboration of necessary regulation documents in this field

Improving nuclear regulation. Compilation of Nea regulatory guidance booklets

International Nuclear Information System (INIS)

2009-01-01

A common theme throughout the series of NEA regulatory guidance reports, or 'green booklets', is the premise that the fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are operated at all times and later decommissioned in an acceptably safe manner. In meeting this objective the regulator must keep in mind that it is the operator that has responsibility for safely operating a nuclear facility; the role of the regulator is to oversee the operator's activities as related to assuming that responsibility. For the first time, the full series of these reports have been brought together in one edition. As such, it is intended to serve as a knowledge management tool both for current regulators and the younger generation of nuclear experts entering the regulatory field. While the audience for this publication is primarily nuclear regulators, the information and ideas may also be of interest to nuclear operators, other nuclear industry organisations and the general public. (author)
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)
Order for execution of the law concerning regulations of nuclear source materials, nuclear fuel materials and reactors

International Nuclear Information System (INIS)

1987-01-01

Chapeter 1 specifies regulations concerning business management for refining and processing, which cover application for designation of refining operation, application for permission for processing operation, and approval of personnel responsible for handling nuclear fuel. Chapter 2 specifies regulations concerning construction and operation of nuclear reactors, which cover application for construction of nuclear reactors, reactors in a research and development stage, application for permission concerning nuclear reactors mounted on foreign nuclear powered ships, application for permission for alteration concerning construction of nuclear reactors, application for permission for alteration concerning nuclear reactors mounted on foreign nuclear powered ships, nuclear reactor facilities to be subjected to regular inspection, nuclear reactor for which submission of operation plan is not required, and application for permission for transfer of nuclear reactor. Chapter 2 also specifies regulations concerning business management for reprocessing and waste disposal. Chapter 3 stipulates regulations concerning use of nuclear fuel substances, nuclear material substances and other substances covered by international regulations, which include rules for application for permission for use of nuclear fuel substances, etc. Supplementary provisions are provided in Chapter 4. (Nogami, K.)
Regulatory risks associated with nuclear safety legislation after Fukushima Daiichi Nuclear Accident in Japan. Focus on legal structure of the nuclear reactor regulation act

International Nuclear Information System (INIS)

Tanabe, Tomoyuki; Maruyama, Masahiro

2016-01-01

Nuclear safety regulations enforced after Fukushima Daiichi Nuclear Accident under the Nuclear Reactor Regulation Act face the following regulatory problems that involve potential risk factors for nuclear businesses; 1) 'entity based regulation' unable to cope with business cessation or bankruptcy of the entity subject of regulation, 2) potential risk of the Nuclear Regulation Authority's inappropriate involvement in nuclear industry policy beyond their duty, and 3) compliance of backfits under vague regulations. In order to alleviate them, this report, through analyzing these regulatory problems from the view point of sound development of the nuclear industry, proposes the following regulatory reforms; (1) To clarify the rule for industry policy in nuclear regulations and enable the authority, Ministry of Economy, Trade and Industry, to choose most appropriate industrial policy measure. (2) Through establishing safety goals as measures to promote continuous improvement of nuclear safety regulations, to stimulate timely adjustments of the regulations, and to introduce a legal mechanism into the nuclear regulation systems under which validity of administrative law and its application can be checked. (author)
Pakistan nuclear safety and radiation protection regulation 1990

International Nuclear Information System (INIS)

1990-01-01

In this act regulations of nuclear safety and radiation protection in Pakistan has been explained. A legal and licensing procedure to handle protection of nuclear materials, processing storage of radioactive products has been described under this regulation. In these regulations full explanation of accidental exposure, delegation of powers and record keeping/waste disposal of radioactive has been given. (A.B.)
Robust optimal self tuning regulator of nuclear reactors

International Nuclear Information System (INIS)

Nouri Khajavi, M.; Menhaj, M.B.; Ghofrani, M.B.

2000-01-01

Nuclear power reactors are, in nature nonlinear and time varying. These characteristics must be considered, if large power variations occur in their working regime. In this paper a robust optimal self-tuning regulator for regulating the power of a nuclear reactor has been designed and simulated. The proposed controller is capable of regulating power levels in a wide power range (10% to 100% power levels). The controller achieves a fast and good transient response. The simulation results show that the proposed controller outperforms the fixed optimal control recently cited in the literature for nuclear power plants
Nuclear and radiological regulation in Moldova

International Nuclear Information System (INIS)

Buzdugan, Artur

2013-01-01

The nuclear security and safety legal framework in Moldova has changed significantly over the last 6 years. This has mainly been the result of implementation of IAEA nuclear safety and nuclear security standards, European directives, which are based on new data and evolving concepts at the international level, on adopted in May 2006 of the Law no. 111 On safe deployment of nuclear and radiological activities and establishing on established on March 2007 of a sole regulatory authority - the National Agency for the Regulation of Nuclear and Radiological Activities. (author)
Regulation on control of nuclear fuel materials

International Nuclear Information System (INIS)

Ikeda, Kaname

1976-01-01

Some comment is made on the present laws and the future course of consolidating the regulation of nuclear fuel materials. The first part gives the definitions of the nuclear fuel materials in the laws. The second part deals with the classification and regulation in material handling. Refinement undertaking, fabrication undertaking, reprocessing undertaking, the permission of the government to use the materials, the permission of the government to use the materials under international control, the restriction of transfer and receipt, the reporting, and the safeguard measures are commented. The third part deals with the strengthening of regulation. The nuclear fuel safety deliberation special committee will be established at some opportunity of revising the ordinance. The nuclear material safeguard special committee has been established in the Atomic Energy Commission. The last part deals with the future course of legal consolidation. The safety control will be strengthened. The early investigation of waste handling is necessary, because low level solid wastes are accumulating at each establishment. The law for transporting nuclear materials must be consolidated as early as possible to correspond to foreign transportation laws. Physical protection is awaiting the conclusions of the nuclear fuel safeguard special committee. The control and information systems for the safeguard measures must be consolidated in the laws. (Iwakiri, K.)
Regulation of nuclear and radiological activities; Reglementarea activitatilor nucleare si radiologice

Energy Technology Data Exchange (ETDEWEB)

Sidorencu, Angela; Vasilieva, Natalia; Buzdugan, Artur; Balan, Ionel [Agentia Nationala de Reglementare a Activitatilor Nucleare si Radiologice, Alecu Russo, 1, MD 2068, Chisinau (Moldova, Republic of)

2012-08-15

The paper presents a review of the Moldovan regulatory framework regarding nuclear and radiological activities and of the competence of state regulatory authority - the National Agency for the Regulation of Nuclear and Radiological Activities.
Improving nuclear regulation. NEA regulatory guidance booklets volumes 1-14

International Nuclear Information System (INIS)

2011-01-01

A common theme throughout the series of NEA regulatory guidance reports, or 'green booklets', is the premise that the fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are continuously maintained and operated in an acceptably safe manner. In meeting this objective the regulator must bear in mind that it is the operator that has responsibility for safely operating the nuclear facility; the role of the regulator is to assess and to provide assurance regarding the operator's activities in terms of assuming that responsibility. The full series of these reports was brought together in one edition for the first time in 2009 and was widely found to be a useful resource. This second edition comprises 14 volumes, including the latest on The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services. The reports address various challenges that could apply throughout the lifetime of a nuclear facility, including design, siting, manufacturing, construction, commissioning, operation, maintenance and decommissioning. The compilation is intended to serve as a knowledge management tool both for current regulators and the new nuclear professionals and organisations entering the regulatory field. Contents: Executive Summary; Regulatory Challenges: 1. The Role of the Nuclear Regulator in Promoting and Evaluating Safety Culture; 2. Regulatory Response Strategies for Safety Culture Problems; 3. Nuclear Regulatory Challenges Related to Human Performance; 4. Regulatory Challenges in Using Nuclear Operating Experience; 5. Nuclear Regulatory Review of Licensee Self-assessment (LSA); 6. Nuclear Regulatory Challenges Arising from Competition in Electricity Markets; 7. The Nuclear Regulatory Challenge of Judging Safety Back-fits; 8. The Regulatory Challenges of Decommissioning Nuclear Reactors; 9. The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services
Regulations concerning the fabricating business of nuclear fuel materials

International Nuclear Information System (INIS)

1985-01-01

In the Law for the Regulations of Nuclear Source Material, Nuclear Fuel Material and Reactors, the regulations have all been revised on the fabrication business of nuclear fuel materials. The revised regulations are given : application for permission of the fabrication business, application for permission of the alteration, application for approval of the design and the construction methods, application for approval of the alteration, application for the facilities inspection, facilities inspection, recordings, entry limitations etc. for controlled areas, measures concerning exposure radiation doses etc., operation of the fabrication facilities, transport within the site of the business, storage, disposal within the site of the business, security regulations, designation etc. of the licensed engineer of nuclear fuels, collection of reports, etc. (Mori, K.)
Comprehensive Plan for Public Confidence in Nuclear Regulator

International Nuclear Information System (INIS)

Choi, Kwang Sik; Choi, Young Sung; Kim, Ho ki

2008-01-01

Public confidence in nuclear regulator has been discussed internationally. Public trust or confidence is needed for achieving regulatory goal of assuring nuclear safety to the level that is acceptable by the public or providing public ease for nuclear safety. In Korea, public ease or public confidence has been suggested as major policy goal in the 'Nuclear regulatory policy direction' annually announced. This paper reviews theory of trust, its definitions and defines nuclear safety regulation, elements of public trust or public confidence developed based on the study conducted so far. Public ease model developed and 10 measures for ensuring public confidence are also presented and future study directions are suggested
Legislation on and regulation of nuclear activities

International Nuclear Information System (INIS)

1984-05-01

This work is a compilation of legislative texts and regulations published by the Atomic Energy Commission's Legal Affairs Department (CEA). It provides a comprehensive source of knowledge and information on nuclear energy law. Legislative texts published over the last forty years, are collected and analytically indexed. The publication covers both French regulations and regulations of international organisations such as the International Atomic Energy Agency and Euratom. It is divided into eight different chapters, dealing with regulations relevant to international and national institutions, nuclear installations, third party liability, protection of persons and the environment, etc. A chronological table of the texts of international and national laws is also included in this work. (NEA) [fr
The regulations concerning refining business of nuclear source material and nuclear fuel materials

International Nuclear Information System (INIS)

1979-01-01

The regulations are provided for under the law for the regulations of nuclear source materials, nuclear fuel materials and reactors and provisions concerning refining business in the enforcement order for the law. The basic concepts and terms are defined, such as: exposure dose, accumulative dose; controlled area; inspected surrounding area and employee. Refining facilities listed in the application for designation shall be classified into clushing and leaching, thickning, refining facilities, storage facilities of nuclear source materials and nuclear fuel materials, disposal facilities of contaminated substances and building for refining, etc. Business program attached to the application shall include expected time of beginning of refining, estimated production amount of nuclear source materials or nuclear fuel materials for the first three years and funds necessary for construction, etc. Records shall be made and kept for particular periods on delivery and storage of nuclear source materials and nuclear fuel materials, control of radiation, maintenance and accidents of refining facilities. Safety securing, application of internationally regulated substances and measures in dangerous situations are stipulated respectively. Exposure dose of employees and other specified matters shall be reported by the refiner yearly to the Director General of Science and Technology Agency and the Minister of International Trade and Industry. (Okada, K.)
The evolution of nuclear regulation

International Nuclear Information System (INIS)

Martin, A.

1997-01-01

The already not so young history of nuclear regulations shows patterns and specific causes that have characterized and influenced its own evolution as well as the industry itself. Today's regulation is facing relevant challenges with potential significant effects. The quest for higher regulatory efficiency brings up the increasing need to base future actions on firmly established strategies. (Author) 7 refs
The Regulation of Nuclear Trade: Non-Proliferation-Supply-safety

International Nuclear Information System (INIS)

1988-01-01

Volume II of the study on the regulation of nuclear trade deals with the national legislation of OECD countries with significant nuclear programmes and regulations in that field and, in essence, covers two aspects. The first concerns political and administrative controls over imports and exports of sensitive products, namely fissile materials and large nuclear equipment as well as technology transfers. In most cases, this description of the provisions applicable is completed with the list of nuclear items whose export is restricted. The second aspect concerns the licensing system governing trade in as well as the import and export of nuclear material to protect users and the public against the hazards created by its radioactive properties. This volume also contains information on regulations concerning physical protection, industrial property and transport, as well as on multilateral and bilateral agreements involving nuclear trade. (NEA) [fr
Nuclear safety regulations in the Republic of Croatia

International Nuclear Information System (INIS)

Cizmek, A.; Horvatic, M.; Ilijas, B.; Medakovic, S.

2009-01-01

Based on Nuclear Safety Act (Official Gazette No. 173/03) in 2006 State Office for Nuclear Safety (SONS) adopted beside Ordinance on performing nuclear activities (Official Gazette No. 74/06) and Ordinance on special conditions for individual activities to be performed by expert organizations which perform activities in the area of nuclear safety (Official Gazette No. 74/06) the new Ordinance on the control of nuclear material and special equipment (Official Gazette No. 15/08) and Ordinance on conditions for nuclear safety and protection with regard to the sitting, design, construction, use and decommissioning of a facility in which a nuclear activity is to be performed (Official Gazette No. 71/08). 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 license to perform nuclear activity. The Ordinance also regulates the content of the form 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 conditions, whereas compliance is established by the decision passed by SONS. Ordinance on special conditions (requirements) for individual activities to be performed by expert organizations which perform activities in the area of nuclear safety regulates these mentioned activities Ordinance on the control of nuclear material and special equipment lays down the list of nuclear materials and special equipment as well as of nuclear activities covered by the system of control of production of special equipment and non-nuclear material, the procedure for notifying the intention to and filing the application for a licence to carry out nuclear activities, and the format and contents of the forms for doing so. This Ordinance
The politics of nuclear safety regulation

International Nuclear Information System (INIS)

Adam, G.

2002-01-01

The paper discusses political aspects of decision making about the safety of nuclear power plants especially in Eastern Europe and in connection with the enlargement of the European Union. The problem of the Kozloduy NPP safety is also discussed. Recommendations on the policy and tasks for nuclear regulators are given
CEQ regulations called peril to nuclear licensing process

International Nuclear Information System (INIS)

O'Neill, J.V.

1979-01-01

Court challenges are expected over regulations of the Council on Environmental Quality (CEQ) that were designed to improve nuclear-licensing decisions, but that have actually changed the meanings of National Environmental Policy Act (NEPA) regulations. The legal implications of these changes could, unless resolved, make the licensing process for nuclear facilities even more uncertain. Agency comments are thought to be critical, although the CEQ has declined to release them, and some question the Council's legality. The Nuclear Regulatory Commission faults the CEQ regulations for revising existing law, being inconsistent with the responsibilities of an independent regulatory body, and extending the CEQ's authority beyond the role assigned by NEPA and the President's Executive Order
The regulations concerning refining business of nuclear source material and nuclear fuel materials

International Nuclear Information System (INIS)

1981-01-01

This rule is established under the provisions concerning refining business in the law concerning the regulation of nuclear raw materials, nuclear fuel materials and nuclear reactors and the ordinance for the execution of this law, and to enforce them. Basic terms are defined, such as: exposure radiation dose, cumulative dose, control area, surrounding monitoring area and worker. The application for the designation for refining business under the law shall be classified into the facilities for crushing and leaching-filtration, thikening, and refining, the storage facilities for nuclear raw materials and nuclear fuel materials, and the disposal facilities for radioactive wastes, etc. To the application, shall be attached business plans, the explanations concerning the technical abilities of applicants and the prevention of hazards by nuclear raw materials and nuclear fuel materials regarding refining facilities, etc. Records shall be made on the accept, delivery and stock of each kind of nuclear raw materials and nuclear fuel materials, radiation control, the maintenance of and accidents in refining facilities, and kept for specified periods, respectively. Security regulations shall be enacted for each works or enterprise on the functions and organizations of persons engaged in the control of refining facilities, the operation of the apparatuses which must be controlled for the prevention of accidents, and the establishment of control area and surrounding monitoring area, etc. The report on the usage of internationally regulated goods and the measures taken at the time of danger are defined particularly. (Okada, K.)

International Nuclear Officials Discuss IAEA Peer Reviews of Nuclear Safety Regulations

International Nuclear Information System (INIS)

2011-01-01

Full text: Senior nuclear regulators today concluded a Workshop on the Lessons Learned from the IAEA Integrated Regulatory Review Service (IRRS) Missions. The U.S. Nuclear Regulatory Commission (NRC) hosted the workshop, in cooperation with the International Atomic Energy Agency, in Washington, DC, from 26 to 28 October 2011. About 60 senior regulators from 22 IAEA Member States took part in this workshop. The IRRS programme is an international peer review service offered by the IAEA to its Member States to provide an objective evaluation of their nuclear safety regulatory framework. The review is based on the internationally recognized IAEA Safety Standards. ''The United States Nuclear Regulatory Commission was pleased to host the IAEA's IRRS meeting this week. The discussions over the past three days have provided an important opportunity for regulators from many countries to come together to strengthen the international peer review process,'' said U.S. NRC Chairman Gregory B. Jaczko. ''Especially after the Fukushima Daiichi accident, the global community recognizes that IRRS missions fill a vital role in strengthening nuclear safety and security programs around the world, and we are proud to be a part of this important effort.'' The IAEA Action Plan on Nuclear Safety includes actions focused towards strengthening the existing IAEA peer reviews, incorporating lessons learned and improving their effectiveness. The workshop provided a platform for the exchange of information, experience and lessons learned from the IRRS missions, as well as expectations for the IRRS programme for the near future. Further improvements in the planning and implementation of the IRRS missions in the longer term were discussed. A strong commitment of all relevant national authorities to the IRRS programme was identified as a key element of an effective regulatory framework. The conclusions of the workshop will be issued in November 2011 and the main results will be reported to the IAEA
Economic consideration of nuclear safety and cost benefit analysis in nuclear safety regulation

International Nuclear Information System (INIS)

Choi, Y. S.; Choi, K. S.; Choi, K. W.; Song, I. J.; Park, D. K.

2001-01-01

For the optimization of nuclear safety regulation, understanding of economic aspects of it becomes increasingly important together with the technical approach used so far to secure nuclear safety. Relevant economic theories on private and public goods were reviewed to re-illuminate nuclear safety from the economic perspective. The characteristics of nuclear safety as a public good was reviewed and discussed in comparison with the car safety as a private safety good. It was shown that the change of social welfare resulted from the policy change induced can be calculated by the summation of compensating variation(CV) of individuals. It was shown that the value of nuclear safety could be determined in monetary term by this approach. The theoretical background and history of cost benefit analysis of nuclear safety regulation were presented and topics for future study were suggested
Legislation for the countermeasures on special issues of nuclear safety regulations

International Nuclear Information System (INIS)

Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chun; Kim, Hak Man; Oh, Ho Chul

2003-02-01

Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea
Legislation for the countermeasures on special issues of nuclear safety regulations

Energy Technology Data Exchange (ETDEWEB)

Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chun; Kim, Hak Man; Oh, Ho Chul [Chongju Univ., Cheongju (Korea, Republic of)

2003-02-15

Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea.
Steps towards Nuclear Power Regulator in Kenya

International Nuclear Information System (INIS)

Gatebe, E.

2017-01-01

The first radiation protection law in Kenya was passed in 1948 and it was referred to as the''Radiological Protection Ordinance -1948''. The ordinance established the Radiological Protection Board (RPB). The current law is the Radiation Protection Act, Cap 243.that was amended in 2014. To regulate the peaceful use of atomic energy through provision of nuclear safety and security culture for the protection of persons, society and the environment against radiation. The Establishment of Nuclear Electricity Project Committee in 2010 is Predecessor of KNEB (2012). Whose mandate among others: Assist in coming up with a legalisation and regulatory framework for support of nuclear power. Human resource development for support of Nuclear Power programme. The country hosted Integrated Nuclear Infrastructure Review (INIR) and Integrated Regulatory Review Service (IRRS) Missions in 2015 and 2016 respectively to addressed legal and regulatory framework. A Multi-agency cooperation has resulted to the Nuclear Regulatory Bill. The Government has been sponsoring 15 students annually for post graduate studies in Nuclear Science at University of Nairobi. IAEA has been a great partner in the development of Kenya's nuclear regulatory regime; It is expected that in the next two years, Kenya will have the core capacity for regulating a nuclear power program. The Bill has taken into consideration suggestions and recommendation of the INIR & IRRS Missions, and comments from the office of Legal Affairs-IAEA and local stakeholders
Identification of three redundant segments responsible for herpes simplex virus 1 ICP0 to fuse with ND10 nuclear bodies.

Science.gov (United States)

Zheng, Yi; Gu, Haidong

2015-04-01

Infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) is a key regulator in both lytic and latent infections. In lytic infection, an important early event is the colocalization of ICP0 to nuclear domain 10 (ND10), the discrete nuclear bodies that impose restrictions on viral expression. ICP0 contains an E3 ubiquitin ligase that degrades promyelocytic leukemia protein (PML) and Sp100, two major components of ND10, and disperses ND10 to alleviate repression. We previously reported that the association between ICP0 and ND10 is a dynamic process that includes three steps: adhesion, fusion, and retention. ICP0 residues 245 to 474, defined as ND10 entry signal (ND10-ES), is a region required for the fusion step. Without ND10-ES, ICP0 adheres at the ND10 surface but fails to enter. In the present study, we focus on characterizing ND10-ES. Here we report the following. (i) Fusion of ICP0 with ND10 relies on specific sequences located within ND10-ES. Replacement of ND10-ES by the corresponding region from ORF61 of varicella-zoster virus did not rescue ND10 fusion. (ii) Three tandem ND10 fusion segments (ND10-FS1, ND10-FS2, and ND10-FS3), encompassing 200 amino acids within ND10-ES, redundantly facilitate fusion. Each of the three segments is sufficient to independently drive the fusion process, but none of the segments by themselves are necessary for ND10 fusion. Only when all three segments are deleted is fusion blocked. (iii) The SUMO interaction motif located within ND10-FS2 is not required for ND10 fusion but is required for the complete degradation of PML, suggesting that PML degradation and ND10 fusion are regulated by different molecular mechanisms. ND10 nuclear bodies are part of the cell-intrinsic antiviral defenses that restrict viral gene expression upon virus infection. As a countermeasure, infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) localizes to ND10s, degrades the ND10 organizer, and disperses ND10 components in order to
Regulations concerning the fabricating business of nuclear fuel materials

International Nuclear Information System (INIS)

1978-01-01

The Regulation is revised on the basis of ''The law for the regulations of nuclear source materials, nuclear fuel materials and reactors'' and the ''Provisions concerning the enterprises processing nuclear fuel materials'' in the Enforcement Ordinance for the Law, to enforce such provisions. This is the complete revision of the regulation of the same name in 1957. Terms are explained, such as exposure radiation dose, cumulative dose, control area, surrounding inspection area, persons engaged in works, radioactive wastes, area for incoming and outgoing of materials, fluctuation of stocks, batch, real stocks, effective value and main measuring points. For the applications for the permission of the enterprises processing nuclear fuel materials, the location of an enterprise, the construction of buildings and the construction of and the equipments for facilities of chemical processing, forming, coating, assembling, storage of nuclear fuel materials, disposal of radioactive wastes and radiation control must be written. Records shall be made and maintained for the periods specified on the inspection of processing facilities, nuclear fuel materials, radiation control, operation, maintainance, accidents of processing facilities and weather. Limit to entrance into the control area, measures for exposure radiation dose, patrol and inspection, operation of processing facilities, transport of materials, disposal of radioactive wastes, safety regulations are provided for. Reports to be filed by the persons engaging in the enterprises processing nuclear fuel materials are prescribed. (Okada, K.)
The law for the regulations of nuclear source materials, nuclear fuel materials and reactors

International Nuclear Information System (INIS)

1980-01-01

The law intends under the principles of the atomic energy act to regulate the refining, processing and reprocessing businesses of nuclear raw and fuel metarials and the installation and operation of reactors for the peaceful and systematic utilization of such materials and reactors and for securing public safety by preventing disasters, as well as to control internationally regulated things for effecting the international agreements on the research, development and utilization of atomic energy. Basic terms are defined, such as atomic energy; nuclear fuel material; nuclear raw material; nuclear reactor; refining; processing; reprocessing; internationally regulated thing. Any person who is going to engage in refining businesses other than the Power Reactor and Nuclear Fuel Development Corporation shall get the special designation by the Prime Minister and the Minister of International Trade Industry. Any person who is going to engage in processing businesses shall get the particular admission of the Prime Minister. Any person who is going to establish reactors shall get the particular admission of the Prime Minister, The Minister of International Trade and Industry or the Minister of Transportation according to the kinds of specified reactors, respectively. Any person who is going to engage in reprocessing businesses other than the Power Reactor and Nuclear Fuel Development Corporation and the Japan Atomic Energy Research Institute shall get the special designation by the Prime Minister. The employment of nuclear fuel materials and internationally regulated things is defined in detail. (Okada, K.)
Sub-nuclear distribution and mobility of nuclear proteins involved in histone acetylation and pre-mRNA splicing

International Nuclear Information System (INIS)

Kruhlak, Michael John

2001-01-01

The mitotic relationship between levels of highly acetylated chromatin, chromatin condensation, and HAT/HDAC organization was examined. HATs and HDACs were found to dissociate from chromosomes along with a loss of highly acetylated histones in condensed chromatin in mitosis. We demonstrate that, rather than being enzymatically inactivated, HAT and HDAC activities are decreased in mitosis because the enzymes are sequestered to a non-chromatin domain. Highly acetylated histone species reappear coincident with the reassociation of HATs and HDACs in late telophase/early interphase and before reinitiation of transcription. We propose that HATs and HDACs are spatially regulated through the cell cycle and that this regulation influences which chromatin domains are available for acetylation and deacetylation. We examined the movement of a splicing factor, ASF, green fluorescent fusion protein (ASF:GFP) using timelapse microscopy and the technique fluorescence recovery after photobleaching (FRAP). We found that ASF:GFP moves significantly slower than free diffusion when it is associated with speckles and, surprisingly, also when it is dispersed in the nucleoplasm. The mobility of ASF is consistent with frequent but transient interactions with relatively immobile nuclear binding sites. This mobility is slightly increased in the presence of transcription inhibitors and the ASF molecules further enrich in speckles. We propose that the nonrandom organization of splicing factors reflects spatial differences in the concentration of relatively immobile binding sites. Through a careful analysis of HDAC4 expression we found that HDAC4-containing MAD bodies are not a consistent component of the interphase nucleus. By comparing MAD bodies to PML bodies we found that the assembly, maintenance and distribution of PML bodies is regulated. We investigated the involvement of chromatin condensation in establishing mitotic transcription repression, by analyzing transcriptional activity in
Strategy for public understanding and participation in nuclear safety regulation

Energy Technology Data Exchange (ETDEWEB)

Kim, H. J.; Chung, Yun Hyung

2004-02-15

The objective of this study is to help the general public and local residents to better understand and trust nuclear safety regulation. In order to obtain public confidence in nuclear safety regulation, the emotion and demand of public should be first understood and the change in an attitude to meet the present circumstances actively is requisite. Hence it is intended that a genuine communication shall be newly arranged and accomplished on the basis of mutual understanding. To achieve this, a series of public opinion poll have performed periodically and symposium for the public acceptance is held in order to frame a policy based on the understanding of nuclear safety and regulation of the general public and local residents. Besides nuclear safety indicators including safety sentiment indicators are being developed as a means to understand the safety of operating nuclear power plants from the viewpoint of the general public, a plan for the harmonious communication of nuclear safety information is established, and handbooks of nuclear terminologies and report-writing are under development in part. Finally plans for convergence of the public opinions and a wide public involvement in nuclear safety regulation are formulated and their applicability as organization and administration program is now under consideration.
Limit regulation system for pressurized water nuclear reactors

International Nuclear Information System (INIS)

Aleite, W.; Bock, H.W.

1976-01-01

Described is a limit regulation system for a pressurized water nuclear reactor in combination with a steam generating system connected to a turbine, the nuclear reactor having control rods as well as an operational regulation system and a protective system, which includes reactor power limiting means operatively associated with the control rods for positioning the same and having response values between operating ranges of the operational regulation system, on the one hand, and response values of the protective system, on the other hand, and a live steam-minimal pressure regulation system cooperating with the reactor power limiting means and operatively connected to a steam inlet valve to the turbine for controlling the same
Earthquake response spectra for seismic design of nuclear power plants in the UK

International Nuclear Information System (INIS)

Bommer, Julian J.; Papaspiliou, Myrto; Price, Warren

2011-01-01

Highlights: → Seismic design of UK nuclear power plants usually based on PML response spectra. → We review derivation of PML spectra in terms of earthquake data used and procedure. → The data include errors and represent a small fraction of what is now available. → Seismic design loads in current practice are derived as mean uniform hazard spectra. → The need to capture epistemic uncertainty makes use of single equation indefensible. - Abstract: Earthquake actions for the seismic design of nuclear power plants in the United Kingdom are generally based on spectral shapes anchored to peak ground acceleration (PGA) values obtained from a single predictive equation. Both the spectra and the PGA prediction equation were derived in the 1980s. The technical bases for these formulations of seismic loading are now very dated if compared with the state-of-the-art in this field. Alternative spectral shapes are explored and the options, and the associated benefits and challenges, for generating uniform hazard response spectra instead of fixed shapes anchored to PGA are discussed.
A New Regulation Policy for Accounting and Control of Nuclear Material

Energy Technology Data Exchange (ETDEWEB)

Kim, K. H.; Kim, M. S.; Ahn, S. H. [Korea Institute of Nuclear nonproliferation and Control, Daejeon (Korea, Republic of)

2016-05-15

Nuclear Safety and Security Commission(NSSC) has amended two public notices about the regulation of nuclear material accounting and control(NMAC). Those notices were declared in November 2014 and entry into force since 2015. According to this legislation, a new type of NMAC inspection system was introduced and facility rules for NMAC approved by the government should be revised subsequently. These changes were one of the preemptive actions to cope with the emergence of new international safeguards policy and increasing demand on advanced nuclear technology. Generally, the regulation policy affects the nuclear business including research and development. Therefore, understanding of the new policy and its making process may help stakeholders to minimize unnecessary financial and operational burden. This study describes background, features, and institutionalization of the new regulation policy for NMAC. The new regulation policy for NMAC was established and institutionalized to preemptively cope with the internal and external demand on 'better' national system of accounting and control of nuclear material. This new policy and regulation system may call not only the regulator but also nuclear business operators for new works to make their system more effective and efficient.
A New Regulation Policy for Accounting and Control of Nuclear Material

International Nuclear Information System (INIS)

Kim, K. H.; Kim, M. S.; Ahn, S. H.

2016-01-01

Nuclear Safety and Security Commission(NSSC) has amended two public notices about the regulation of nuclear material accounting and control(NMAC). Those notices were declared in November 2014 and entry into force since 2015. According to this legislation, a new type of NMAC inspection system was introduced and facility rules for NMAC approved by the government should be revised subsequently. These changes were one of the preemptive actions to cope with the emergence of new international safeguards policy and increasing demand on advanced nuclear technology. Generally, the regulation policy affects the nuclear business including research and development. Therefore, understanding of the new policy and its making process may help stakeholders to minimize unnecessary financial and operational burden. This study describes background, features, and institutionalization of the new regulation policy for NMAC. The new regulation policy for NMAC was established and institutionalized to preemptively cope with the internal and external demand on 'better' national system of accounting and control of nuclear material. This new policy and regulation system may call not only the regulator but also nuclear business operators for new works to make their system more effective and efficient
Legislation for the countermeasures on special issues of nuclear safety regulations

International Nuclear Information System (INIS)

Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chun; Kim, Heon Jin; Oh, Ho Chul

2004-02-01

Since the present nuclear safety regulation has some legal problems that refer to special issues and contents of regulatory provisions, this report has preformed research on the legal basic theory of nuclear safety regulation to solve the problems. In addition, this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation
Legislation for the countermeasures on special issues of nuclear safety regulations

Energy Technology Data Exchange (ETDEWEB)

Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chun; Kim, Heon Jin; Oh, Ho Chul [Chongju Univ., Cheongju (Korea, Republic of)

2004-02-15

Since the present nuclear safety regulation has some legal problems that refer to special issues and contents of regulatory provisions, this report has preformed research on the legal basic theory of nuclear safety regulation to solve the problems. In addition, this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation.
Localized Movement and Levels of 53BP1 Protein Are Changed by gamma-irradiation in PML Deficient Cells

Czech Academy of Sciences Publication Activity Database

Legartová, Soňa; Sehnalová, Petra; Malyšková, B.; Kuntziger, T.; Collas, P.; Cmarko, D.; Raška, I.; Sorokin, D.V.; Kozubek, Stanislav; Bártová, Eva

2016-01-01

Roč. 117, č. 11 (2016), s. 2583-2596 ISSN 0730-2312 R&D Projects: GA ČR GBP302/12/G157; GA ČR GA13-07822S; GA MŠk 7F14369 Institutional support: RVO:68081707 Keywords : DNA REPAIR * 53BP1 PROTEIN * PML BODIES Subject RIV: BO - Biophysics Impact factor: 3.085, year: 2016
Physical and functional interactions between ZIP kinase and UbcH5

International Nuclear Information System (INIS)

Ohbayashi, Norihiko; Okada, Katsuya; Kawakami, Shiho; Togi, Sumihito; Sato, Noriko; Ikeda, Osamu; Kamitani, Shinya; Muromoto, Ryuta; Sekine, Yuichi; Kawai, Taro; Akira, Shizuo; Matsuda, Tadashi

2008-01-01

Zipper-interacting protein kinase (ZIPK) is a widely expressed serine/threonine kinase that has been implicated in cell death and transcriptional regulation, but its mechanism of regulation remains unknown. In our previous study, we showed that leukemia inhibitory factor stimulated threonine-265 phosphorylation of ZIPK, thereby leading to phosphorylation and activation of signal transducer and activator of transcription 3. Here, we identified UbcH5c as a novel ZIPK-binding partner by yeast two-hybrid screening. Importantly, we found that UbcH5c induced ubiquitination of ZIPK. Small-interfering RNA-mediated reduction of endogenous UbcH5 expression decreased ZIPK ubiquitination. Furthermore, coexpression of UbcH5c with ZIPK influenced promyelocytic leukemia protein nuclear body (PML-NB) formation. These results suggest that UbcH5 regulates ZIPK accumulation in PML-NBs by interacting with ZIPK and stimulating its ubiquitination
Nuclear regulation in Australia - future possibilities

International Nuclear Information System (INIS)

Carlson, J.; Bardsley, J.

1997-01-01

Australia's current nuclear regulatory arrangements reflect two major factors: that we are a federation, with a constitutional division of powers between the Commonwealth and the States, and that we have no nuclear industry, other than uranium mining. Australia's only nuclear facilities are operated by a Commonwealth instrumentality, ANSTO. Current Commonwealth regulatory arrangements are a response to international treaty commitments -principally the NPT (Treaty on the Non-Proliferation of Nuclear Weapons) -and to the commencement of commercial uranium mining and export in the late 1970's. Although at present no nuclear industry activities, other than mining, are in prospect, this might not always be the case, and with the establishment of ARPANSA (the Australian Radiation Protection and Nuclear Safety Agency) it is timely to give some thought to regulatory arrangements which might be appropriate to Australia's future circumstances. This paper will discuss the regulation activities relating to the nuclear fuel cycle , i e activities involved with the production and use of nuclear materials (uranium, thorium and plutonium) for the generation of energy through nuclear fission
Legal issues in amending nuclear rules and regulations

International Nuclear Information System (INIS)

Ossenbuehl, F.

2006-01-01

Nuclear rules and regulations are composed of a multitude of provisions, benchmarks, etc. of different origins and different levels of legal quality. The Safety Criteria and Guidelines for Nuclear Power Plants published in the 'Bundesanzeiger' (Federal Gazette) by the competent federal ministry after consultation of the competent highest state authorities are of particular importance. The Safety Criteria were adopted by the States Committee for Atomic Energy on October 12, 1977 and published in the 'Bundesanzeiger'. The Federal Ministry for the Environment, Nature Conservation, and Nuclear Safety (BMU) intends to revise and amend the contents of the safety criteria and guidelines applying to nuclear power plants. The question underlying this article is this: In what legal way can such an 'amendment' be achieved in a permissible fashion? This leaves out of consideration the question of the contents and applicability of amended provisions, such as the question to what extent amended regulations can also be applied to the nuclear power plants already licensed and in operation, or whether the concept of finality and the constitutional ban on retroactive effect or other constitutional or paramount rules contain restrictions on the contents of such regulations. Solely the question of a permissible amending procedure is under study. (orig.)

Use of the perfect electric conductor boundary conditions to discretize a diffractor in FDTD/PML environment

OpenAIRE

Calderón-Ramón, C.; Gómez-Aguilar, J. F.; Rodríguez-Achach, M.; Morales- Mendoza, L. J.; Laguna-Camacho, J. R.; Benavides-Cruz, M.; Cruz-Orduna, M. I.; González-Lee, M.; Pérez-Meana, H.; Enciso-Aguilar, M.; Chávez-Pérez, R.; Martínez-García, H.

2015-01-01

In this paper we present a computational electromagnetic simulation of a multiform diffractor placed at the center of an antenna array. Our approach is to solve Maxwell's differential equations with a discrete space-time formulation, using the Finite Difference Time Domain (FDTD) method. The Perfectly Matched Layers (PML) method is used as an absorbing boundary condition, to prevent further spread of the electromagnetic wave to the outside of the calculation region. The Perfect Electric Condu...
Regulation and quality in nuclear medicine 2 october 1998

International Nuclear Information System (INIS)

Kouchner, B.; Huriet, C.; Le Deaut, J.Y.

1999-01-01

The aim of this meeting is to examine how the regulations are liable to decrease the patient taking charge. The problem of the public information and opinion in the nuclear medicine domain is also presented. The nineteen presentations are proposed in 2 sessions. The first one deals with the state of the art of the nuclear medicine in France (techniques and regulations). The second one deals with the environment of the nuclear medicine (irradiation limits, public opinion, doctors and medicine quality). (A.L.B.)
Leadership for Safety in Practice: Perspectives from a Nuclear Regulator

International Nuclear Information System (INIS)

Tyobeka, B. M.

2016-01-01

The principal responsibility for a nuclear regulator is to assure compliance with regulations and safety standards by operators. One of these requirements is demonstration of, and adherence to, nuclear safety culture by the operators. At the same time, the regulators themselves are expected to live the talk and practice what they preach, i.e., demonstrate highest levels of nuclear safety culture within their organizations. Consequently, it is recognised that leadership is important in the creation of a culture that supports and promotes a strong nuclear safety performance of an organization. The leaders of a regulatory body are vital in inspiring employees to a higher level of safety and productivity, which means that they must apply good leadership attributes on a daily basis. This paper will attempt to bring forth and share attributes for strong leadership role in promoting a safety culture within a nuclear regulatory body by surveying world-wide practices and examples in developing and advanced nuclear countries. (author)
Nuclear localization signal regulates porcine circovirus type 2 capsid protein nuclear export through phosphorylation.

Science.gov (United States)

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

2018-02-15

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

International Nuclear Information System (INIS)

Yook, Dong Il; Kuk, Doe Hyeong; Lee, Seong Min; Kim, Jong Sam; Hwang, Sun Ho

2001-03-01

One of the most important tasks to improve nuclear safety regulation system is to separate nuclear regulatory institutes from public agencies which promote the development nuclear power. Moreover, nuclear safety regulation should be not only specialized but optimized to be adapted for new environments such as high-tech information age. Especially, it is necessary to reform the current nuclear safety regulation systems both to be effective under the local self-administration which began to operate in recent years and to be supported by local residents
A study in improvement of administrative system in the nuclear safety regulation

Energy Technology Data Exchange (ETDEWEB)

Yook, Dong Il; Kuk, Doe Hyeong; Lee, Seong Min; Kim, Jong Sam; Hwang, Sun Ho [Chungnam National Univ., Taejon (Korea, Republic of)

2001-03-15

One of the most important tasks to improve nuclear safety regulation system is to separate nuclear regulatory institutes from public agencies which promote the development nuclear power. Moreover, nuclear safety regulation should be not only specialized but optimized to be adapted for new environments such as high-tech information age. Especially, it is necessary to reform the current nuclear safety regulation systems both to be effective under the local self-administration which began to operate in recent years and to be supported by local residents.
Review of Policy Documents for Nuclear Safety and Regulation

International Nuclear Information System (INIS)

Kim, Woong Sik; Choi, Kwang Sik; Choi, Young Sung; Kim, Hho Jung; Kim, Ho Ki

2006-01-01

The goal of regulation is to protect public health and safety as well as environment from radiological hazards that may occur as a result of the use of atomic energy. In September 1994, the Korean government issued the Nuclear Safety Policy Statement (NSPS) to establish policy goals of maintaining and achieving high-level of nuclear safety and also help the public understand the national policy and a strong will of the government toward nuclear safety. It declares the importance of establishing safety culture in nuclear community and also specifies five nuclear regulatory principles (Independence, Openness, Clarity, Efficiency and Reliability) and provides the eleven regulatory policy directions. In 2001, the Nuclear Safety Charter was declared to make the highest goal of safety in driving nuclear business clearer; to encourage atomic energy- related institutions and workers to keep in mind the mission and responsibility for assuring safety; to guarantee public confidence in related organizations. The Ministry of Science and Technology (MOST) also issues Yearly Regulatory Policy Directions at the beginning of every year. Recently, the third Atomic Energy Promotion Plan (2007-2011) has been established. It becomes necessary for the relevant organizations to prepare the detailed plans on such areas as nuclear development, safety management, regulation, etc. This paper introduces a multi-level structure of nuclear safety and regulation policy documents in Korea and presents some improvements necessary for better application of the policies
Review of Policy Documents for Nuclear Safety and Regulation

Energy Technology Data Exchange (ETDEWEB)

Kim, Woong Sik; Choi, Kwang Sik; Choi, Young Sung; Kim, Hho Jung; Kim, Ho Ki [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of)

2006-07-01

The goal of regulation is to protect public health and safety as well as environment from radiological hazards that may occur as a result of the use of atomic energy. In September 1994, the Korean government issued the Nuclear Safety Policy Statement (NSPS) to establish policy goals of maintaining and achieving high-level of nuclear safety and also help the public understand the national policy and a strong will of the government toward nuclear safety. It declares the importance of establishing safety culture in nuclear community and also specifies five nuclear regulatory principles (Independence, Openness, Clarity, Efficiency and Reliability) and provides the eleven regulatory policy directions. In 2001, the Nuclear Safety Charter was declared to make the highest goal of safety in driving nuclear business clearer; to encourage atomic energy- related institutions and workers to keep in mind the mission and responsibility for assuring safety; to guarantee public confidence in related organizations. The Ministry of Science and Technology (MOST) also issues Yearly Regulatory Policy Directions at the beginning of every year. Recently, the third Atomic Energy Promotion Plan (2007-2011) has been established. It becomes necessary for the relevant organizations to prepare the detailed plans on such areas as nuclear development, safety management, regulation, etc. This paper introduces a multi-level structure of nuclear safety and regulation policy documents in Korea and presents some improvements necessary for better application of the policies.
Building, measuring and improving public confidence in the nuclear regulator

International Nuclear Information System (INIS)

2006-01-01

An important factor for public confidence in the nuclear regulator is the general public trust of the government and its representatives, which is clearly not the same in all countries. Likewise, cultural differences between countries can be considerable, and similar means of communication between government authorities and the public may not be universally effective. Nevertheless, this workshop identified a number of common principles for the communication of nuclear regulatory decisions that can be recommended to all regulators. They have been cited in particular for their ability to help build, measure and/or improve overall public confidence in the nuclear regulator. (author)
Public opinion poll on safety and regulations of nuclear energy

Energy Technology Data Exchange (ETDEWEB)

Park, M. I.; Park, B. I.; Lee, S. M. [Gallup Korea, Seoul (Korea, Republic of)

2004-02-15

The purpose of this poll is not only to research understanding on safety and regulations of nuclear energy and to compare the result by time series followed 2003 to 2002 years, also to establish the public relations strategies and to offer information for developing long-term policies. The contents of the study are on the general perception, safety, management of nuclear power station, regulations and surroundings about nuclear energy.
Special feature article. Nuclear new age. Towards reform of laws and regulations

International Nuclear Information System (INIS)

Madarame, Haruki; Morokuzu, Muneo; Shiroyama, Hideaki; Nishiwaki, Yoshihiro; Marumo, Syunji; Suzuki, Takahiro; Hariyama, Hideo

2007-01-01

Since about half a century passes after the peaceful use of nuclear energy began in Japan, the safety laws and regulations of the nuclear energy becomes difficult to cope enough with the current situation without regulation structure changing. In March 2007, Tokyo University set up nuclear energy legislation study meeting' consisting of members from regulatory bodies, electric utilities, nuclear industries and others. The special feature introduces five opinions obtained through the argument in the meeting. As an example, Law for the Regulations of Nuclear Sources Material, Nuclear Fuel Material and Reactors is applied to basic design about the commercial reactors, but Electric Utilities Industry Law is applied to a detailed design, and different licensing standard is applied in each. Taking the adjustment of licensing standard with unifying these is necessary for efficiency. In addition, current law for the Regulations of Nuclear Sources Material, Nuclear Fuel Material and Reactors regulates according to the businesses such as reactor facilities, fuel fabrication plants and radioactive waste disposal. As for plural businesses, a low procedure and safety measures are demanded every each business. It is also necessary to include structure of the comprehensive licensing that assumed an enterprise running plural businesses. (T. Tanaka)
Search for greater stability in nuclear regulation

International Nuclear Information System (INIS)

Asselstine, J.K.

1985-01-01

The need for greater stability in nuclear regulation is discussed. Two possible approaches for dealing with the problems of new and rapidly changing regulatory requirements are discussed. The first approach relies on the more traditional licensing reform initiatives that have been considered off and on for the past decade. The second approach considers a new regulator philosophy aimed at the root causes of the proliferation of new safety requirements that have been imposed in recent years. For the past few years, the concepts of deregulation and regulatory reform have been in fashion in Washington, and the commercial nuclear power program has not remained unaffected. Many look to these concepts to provide greater stability in the regulatory program. The NRC, the nuclear industry and the administration have all been avidly pursuing regulatory reform initiatives, which take the form of both legislative and administrative proposals. Many of these proposals look to the future, and, if adopted, would have little impact on currently operating nuclear power plants or plants now under construction
Nuclear safety: risks and regulation

International Nuclear Information System (INIS)

Wood, W.C.

1983-01-01

Taking a fresh look at nuclear safety regulations, this study finds that the mandate and organization of the Nuclear Regulatory Commission (NRC) militate against its making sound decisions. The author criticizes failures to make hard decisions on societal risk, to clarify responsibility, and to implement cost-effective safety measures. Among his recommendations are reorganization of the NRC under a single authoritative administrator, separation of technical issues from social ones, and reform of the Price-Anderson Act. The author concludes that the worst eventuality would be to continue the current state of indecision. 161 references, 6 figures, 4 tables
Managing and regulating organisational change in nuclear installations

International Nuclear Information System (INIS)

Pyy, P.; Reiersen, C.

2004-01-01

To the extent that organisational change in nuclear installations can potentially impact nuclear safety, it is imperative to ensure that such change is property managed and regulated. A number of key elements can help achieve successful management of change. (author)
The Swedish Nuclear Power Inspectorate's Regulations concerning Safety in connection with the Disposal of Nuclear Material and Nuclear Waste. General Recommendations concerning the Application of the Swedish Nuclear Power Inspectorate's Regulations above

International Nuclear Information System (INIS)

2002-06-01

An english translation of the original Swedish regulations concerning the safety in disposal of nuclear wastes is published in this booklet, together with recommendations on how these regulations can be applied
Legal principles of regulatory administration and nuclear safety regulation

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyeong Hui; Cheong, Sang Kee [Hannam Univ., Taejon (Korea, Republic of)

2000-12-15

This research presents a critical analysis and evaluation of principles of administrative laws in order to provide framework of structural reform on the nuclear safety regulation system. The focus of this analysis and evaluation is centered around the area of origin of regulatory administrative laws; authorities of regulation; procedures of regulatory actions; regulatory enforcement; and administrative relief system. In chapter 2 the concept of regulatory administration is analysed. Chapter 3 identifies the origin of regulatory administration and the principles of administration laws. It also examines legal nature of the nuclear safety standard. In relation to regulatory authorities. Chapter 4 identifies role and responsibility of administration authorities and institutions. It also examines fundamental principles of delegation of power. Then the chapter discusses the nuclear safety regulation authorities and their roles and responsibilities. Chapter 5 classifies and examines regulatory administration actions. Chapter 6 evaluates enforcement measure for effectiveness of regulation. Finally, chapter 7 discusses the administrative relief system for reviewing unreasonable regulatory acts.
Duty and role of Nuclear Regulation Authority facing a crucial moment

International Nuclear Information System (INIS)

Asaoka, Mie

2013-01-01

Duty of Nuclear Regulation Authority (NRA) was to restore public trust on nuclear regulation spoiled by the Fukushima nuclear accident. How applied such regulation as mandatory back-fitting based on latest knowledge and 40 year operational limit in principle became of great concern. Active faults issue on existing nuclear power station could be a touchstone. Safety side judgment and electric utilities side's proof responsibilities were required as more stringent criteria for active faults. The expert group had been working on assessment of fracture zones under the field survey. Reform of safety regulations should be done based on three important standpoints: (1) not business easiness but public safety was first (2) NRA keeping stance to judge its own safety standard and how NRA ought to be and (3) importance of public disclosure of information and participation in decision-making judging from greatness of public effects caused by nuclear disaster. (T. Tanaka)
Development of Comprehensive Nuclear Safety Regulation Plan for 2007-2011

International Nuclear Information System (INIS)

Choi, Young Sung; Kim, Woong Sik; Park, Dong Keuk; Kim, Ho Ki

2006-01-01

The Article 8-2 of Atomic Energy Act requires the government to establish Atomic Energy Promotion Plan every five years. It sets out national nuclear energy policies in a systematic and consistent way. The plan presents the goals and basic directions of national nuclear energy policies on the basis of current status and prospects. Both areas of utilization and safety management of nuclear energy are included and various projects and schedules are delineated based on the national policy directions. The safety management area in this plan deals with the overall safety and regulation policy. Its detail projects and schedule should be developed in separate plans by responsible ministries under the mediation of the MOST. As a regulatory authority, MOST is responsible for safety management area and its technical support organization, KINS has developed Comprehensive Nuclear Safety Regulation Plan as an implementation plan of safety area. This paper presents the development process and specific projects contained in the Comprehensive Nuclear Safety Regulation Plan which is under development now
The experience on public consultation in the elaboration of nuclear regulations

International Nuclear Information System (INIS)

Monteiro, Iara A.; Pitta, Maria Adelia R.; Pereira, Enneite S.; Wieland, Patricia

2009-01-01

This paper presents and discusses the process of public consultation followed by the regulatory body, Nuclear Energy National Commission (CNEN), during the elaboration of nuclear regulations. In this paper, the due legislation on federal administration, law n. 9784/99, is referred to and the procedures established by CNEN for the elaboration of a nuclear regulation are described. The public consultation has the objective of improving the democratization of nuclear regulations elaboration process, allowing the participation of interested parties such as professional associations directly involved, organizations interested in its application and the general public. During the process of elaboration of a nuclear regulation, the basic text is, first of all, discussed and improved by a task group. This group is composed by CNEN's officials and representatives of organizations, enterprises and public agencies involved in the related area. Once the first version of the proposed regulation is ready, it is formally open to consultation and posted at CNEN website for a period of time. The suggestions, therein presented on-line, are analyzed by the task group and the conclusions are also posted at the site; those considered pertinent are incorporated to proposed regulation. As an example, the public consultation results obtained in 2008 with the revision of the CNEN-NN-6.02: Licensing of Radioactive Facilities regulation, are presented. Such results cover two aspects: the analysis of the participants profile and the analysis of the contributions. Public participation in the elaboration of nuclear regulations is a new way for CNEN to know the licensees and public demands, doubts and needs. This tool has demonstrated usefulness and therefore must be maintained by the regulatory body. (author)
Regulation of nuclear power in the UK after Chernobyl

International Nuclear Information System (INIS)

Ryder, E.A.

1987-01-01

The essential philosophy underlying safe nuclear power in the UK is to establish a safe design and then monitor the manufacture, construction, commissioning, operation and maintenance to ensure that the safe design intent is not violated either deliberately or unintentionally. In the UK any commercial nuclear installation must have a nuclear site licence. The Nuclear Installations Inspectorate (NII) is the agency responsible for granting licences and ensuring the safe design and operation of the installation by the licensee. The way in which the NII does this for the 27 licensed sites that it regulates in the UK is explained. This covers plant assessment and site inspection. Following the accident at Chernobyl the NII reviewed the way in which it regulates nuclear power in the UK. Some changes in specific areas were recommended but no changes in the general philosophy were considered necessary. (UK)

The UK nuclear regulator's view of external influences on safety

International Nuclear Information System (INIS)

Summers, J.L.

2001-01-01

Over the past forty or so years, significant changes have taken place in the UK nuclear industry and the pace of change is continually increasing. As a consequence, the Nuclear Installations Inspectorate (NII), the UK's nuclear regulator, has also had to change. This paper describes some of the challenges to safety that have arisen in recent years and how NII's style of regulation has had to adapt to ensure that safety is maintained and improved. NII's approach has been to: be proactive in its relations with Government and market regulators; adopt new competencies to equip it for the challenges it faces; strive to improve its efficiency and effectiveness; and develop new approaches to regulating changes in licensees' organisations and ways of working. Importantly, NII seeks to anticipate change rather than react to it. (author)
Rules and Regulations on the 27th. Article for Nuclear Aspects

International Nuclear Information System (INIS)

1985-01-01

This law constitutes the Regulations of the Article 27 of the Constitution on nuclear matters, which in turn regulates the exploration, exploitation and benefits of radioactive minerals, as well as the use of nuclear fuels, the use of nuclear energy, research on nuclear techniques and sciences, nuclear industry and all matters related to it. All dispositions of this law are public and to be observed and complied with all throughout Mexico, and state that in this Country, the use of nuclear energy may only have pacific purposes. Likewise, it states all regulations for exploration, exploitation and benefits to be derived from radioactive materials, at the same time comprising the compliance with all facets of the cycle of fuel comprised from its refining to the manufacture or combustible elements. This law also comprises aspects of nuclear, radiologic and physic safety, as well as the safeguards appointed by the National Commission on Nuclear Safety and the compliance with this functions. The research aspect falls on the ININ. This law is constituted by 52 Articles and 6 Transitories
The regulations concerning the uses of nuclear fuel materials

International Nuclear Information System (INIS)

1978-01-01

The Regulations are established on the basis of ''The law for the regulations of nuclear source materials, nuclear fuel materials and reactors'' and the ''Provisions concerning the usage of nuclear fuel materials'' in the Enforcement Ordinance of the Law, to enforce such provisions. Terms are explained, such as exposure radiation dose, cumulative dose, control area, surrounding inspection area, persons engaging in works, area for incoming and outgoing of materials, batch, real stocks, effective value and main measuring points. In the applications for the permission to use nuclear fuel materials, the expected period and quantity of usage of each kind of such materials and the other party and the method of selling, lending and returning spent fuel or the process of disposal of such fuel must be written. Explanations concerning the technical ability required for the usage of nuclear fuel materials shall be attached to the applications. Applications shall be filed for the inspection of facilities for use, in which the name and the address of the applicant, the name and the address of the factory or the establishment, the range of the facilities for use, the maximum quantity of nuclear fuel materials to be used or stocked, and the date, the place and the kind of the expected inspection are written. Prescriptions cover the records to be held, safety regulations, the technical standards for usage, the disposal, transport and storage of nuclear fuel materials and the reports to be filed. (Okada, K.)
The Nuclear Installations (Excepted Matter) Regulations 1978 (Statutory Instrument No. 1779, 4 December 1978)

International Nuclear Information System (INIS)

1979-01-01

These Regulations prescribe, for the purposes of the definition of 'excepted matter' in the Nuclear Installations Act 1965, certain specified quantities and forms of nuclear matter, and supersede the Nuclear Installations (excepted Matter) Regulations 1965. They bring the definition of excepted matter in those Regulations into line with the decisions of 27 October 1977 of the OECD Nuclear Energy Agency's Steering Committee excluding certain kinds and quantities of nuclear substances from the scope of the Paris Convention on Third Party Liability in the Field of Nuclear Energy. Compared with the 1965 Regulations, the principal changes in relation to consignments are that activity limits and packing requirements now take account of the most recent IAEA Regulations. (NEA) [fr
Lifetime Management in Non-US-Technology Nuclear Power Plants using US Regulations

International Nuclear Information System (INIS)

Cornelius Steenkamp, J.; Encabo Espartero, J.; Garcia Iglesias, R.

2013-01-01

In July 2009 the Spanish Nuclear Regulator (CSN) issued a Safety Instruction (IS-22) for the development of Lifetime Management in the Nuclear Power Plants within Spain. The context of this Safety Instruction is based on the American Regulations 10CFR54, NUREG1800/1801 and the technical guide NEI95-10. All these regulations are aimed at US-Technology Nuclear Power Plants. Lifetime Management of Nuclear Power Plants with a plant design different from US technologies can most certainly be developed with the mentioned US regulations. The successful development of Lifetime Management in these cases depends on the adaptation of the different requirements of the regulations. Challenges resulting from the adaptation process can be resolved by taking into consideration the plant design of the plant in question.
The Brussels I Regulation and Liability for Nuclear Damage

International Nuclear Information System (INIS)

Handrlica, J.

2010-01-01

Prior to 2004, the map of the European Union seemed to be basically identical to the map of the contracting parties to the Paris Convention on Third Party Liability in the Field of Nuclear Energy of 1960 ('the Paris Convention'). The 2004 and 2007 enlargements were mainly composed of the contracting parties to the Vienna Convention on Civil Liability for Nuclear Damage of 1963 ('the Vienna Convention'). In various discussions, the term 'nuclear liability patchwork' is used to describe this existing situation. One of the problems arising from this 'patchwork' is that, while a uniform legal framework was established for matters of jurisdiction and the enforcement of decisions under the authority given to the European Union ('EU') by the Council Regulation on jurisdiction and the recognition and enforcement of judgements in civil and commercial matters ('Brussels Regulation'), this overall framework does not apply to particular matters governed by the special conventions to which member states may be contracting parties, see Article 71 of the Brussels Regulation. This paper aims to outline the 'patchwork' of these rules that are applicable to nuclear third party liability cases in the EU and to point out the main consequences arising from this legal framework difficult to comprehend.5 Its scope, however, is limited to the legal issues arising from a nuclear incident occurring in a nuclear installation situated within the territory of the European Union
Critical Reflections on Conservatism in Nuclear Safety Regulation

International Nuclear Information System (INIS)

Choi, Young Sung; Choi, Kwang Sik

2007-01-01

A recent report published by the Committee on Nuclear Regulatory Activities (CNRA) of the OECD Nuclear Energy Agency (NEA) says that a fundamental principle for safety regulators is the practice of conservative decision making. Nuclear regulators frequently face challenging issues surrounded by uncertainties or lack of data and information. No matter what efforts will be made to collect the available information and to assess the issues, nobody can clear all the uncertainties and make absolutely certain decision. More often than not, the regulators have to make a decision in light of continuing uncertainties and limited information. It is at this point that the principle of conservatism should play a role. However the principle comes in many diverse forms such as default conservatism, precautionary principle, defense in depth and realistic conservatism. These different forms of conservatism have different roles and meanings that will take a decision maker to drastically different results. This paper reviews different forms of conservatism in critical way, presents analytical framework for decision making under uncertainty and suggests future research works needed
Merits and difficulties in adopting codes, standards and nuclear regulations

International Nuclear Information System (INIS)

El-Saiedi, A.F.; Morsy, S.; Mariy, A.

1978-01-01

Developing countries planning for introducing nuclear power plants as a source of energy have to develop or adopt sound regulatory practices. These are necessary to help governmental authorities to assess the safety of nuclear power plants and to perform inspections needed to confirm the established safe and sound limits. The first requirement is to form an independent regulatory body capable of setting up and enforcing proper safety regulations. The formation of this body is governed by several considerations related to local conditions in the developing countries, which may not always be favourable. It is quite impractical for countries with limited experience in the nuclear power field to develop their own codes, standards and regulations required for the nuclear regulatory body to perform its tasks. A practical way is to adopt codes, standards and regulations of a well-developed country. This has merits as well as drawbacks. The latter are related to problems of personnel, software, equipment and facilities. The difficulties involved in forming a nuclear regulatory body, and the merits and difficulties in adopting foreign codes, standards and regulations required for such body to perform its tasks, are discussed in this paper. Discussions are applicable to many developing countries and particular emphasis is given to the conditions and practices in Egypt. (author)
Nuclear safety regulation in the People's Republic of China

International Nuclear Information System (INIS)

Shi Guangchang

1987-01-01

The present report gives a general view of how the problem of nuclear safety is dealt with in China, with particular reference to the nuclear power plants. The most relevant nuclear legal regulations and procedures are reported. Organization of the National Nuclear Safety Administration (NNSA) of China and its working activities are presented. The report gives also the principle and practice with regard to licensing process and regulatory inspection of nuclear power plant in China. (author)
Promyelocytic leukemia bodies tether to early endosomes during mitosis.

Science.gov (United States)

Palibrk, Vuk; Lång, Emma; Lång, Anna; Schink, Kay Oliver; Rowe, Alexander D; Bøe, Stig Ove

2014-01-01

During mitosis the nuclear envelope breaks down, leading to potential interactions between cytoplasmic and nuclear components. PML bodies are nuclear structures with tumor suppressor and antiviral functions. Early endosomes, on the other hand, are cytoplasmic vesicles involved in transport and growth factor signaling. Here we demonstrate that PML bodies form stable interactions with early endosomes immediately following entry into mitosis. The 2 compartments remain stably associated throughout mitosis and dissociate in the cytoplasm of newly divided daughter cells. We also show that a minor subset of PML bodies becomes anchored to the mitotic spindle poles during cell division. The study demonstrates a stable mitosis-specific interaction between a cytoplasmic and a nuclear compartment.
The law for the regulations of nuclear source materials, nuclear fuel materials and reactors

International Nuclear Information System (INIS)

1979-01-01

The law aims to perform regulations on enterprises of refining, processing and reprocessing of nuclear source and fuel materials and on establishment and operation of reactors to realize the peaceful and deliberate utilization of atomic energy according to the principle of the atomic energy basic law. Regulations of use of internationally regulated substances are also envisaged to observe international agreements. Basic concepts and terms are defined, such as: atomic energy; nuclear fuel material; nuclear source material; reactor; refining; processing; reprocessing and internationally regulated substance. Any person besides the Power Reactor and Nuclear Fuel Material Developing Corporation who undertakes refining shall be designated by the Prime Minister and the Minister of International Trade and Industry. An application shall be filed to the ministers concerned, listing name and address of the person, name and location of the refining works, equipment and method of refining, etc. The permission of the Prime Minister is necessary for any person who engages in processing. An application shall be filed to the Prime Minister, listing name and address of the person, name and location of the processing works and equipment and method of processing, etc. Permission of the Prime Minister, the Minister of International Trade and Industry or the Minister of Transport is necessary for any person who sets up reactors. An application shall be filed to the minister concerned, listing name and address of the person, purpose of operation, style, thermal output of reactor and number of units, etc. (Okada, K.)
The UAE. Lessons learned from a new nuclear regulator

International Nuclear Information System (INIS)

Kraev, Kamen

2015-01-01

The United Arab Emirates (UAE) is building four South Korean APR-1400 reactors at the Barakah nuclear site. The first is scheduled to enter into commercial operation in 2017. Christer Viktorsson, Director General of the United Arabic Emirate's(UAE) Federal Office for Nuclear Regulation, talks to NucNet about the challenges of establishing a nuclear regulatory body from scratch in a country where nuclear stations have never been built before.
The UAE. Lessons learned from a new nuclear regulator

Energy Technology Data Exchange (ETDEWEB)

Kraev, Kamen [NucNet, Brussels (Belgium)

2015-12-15

The United Arab Emirates (UAE) is building four South Korean APR-1400 reactors at the Barakah nuclear site. The first is scheduled to enter into commercial operation in 2017. Christer Viktorsson, Director General of the United Arabic Emirate's(UAE) Federal Office for Nuclear Regulation, talks to NucNet about the challenges of establishing a nuclear regulatory body from scratch in a country where nuclear stations have never been built before.
Review of Nuclear Regulation using Principal-Agent Model

Energy Technology Data Exchange (ETDEWEB)

Choi, Kwang Sik; Lee, Young Eal; Ryu, Yong Ho [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2010-05-15

Regulation is performed by the government on behalf of the public to accomplish a societal goal. However, the public is not necessarily confident that regulatory authority does well enough for the benefit of the public. That is partly because they have less information, competence and resources for monitoring regulatory activities. However, it is a problem that cannot be solved easily only by efforts of the personnel involved. In nuclear industry and regulation, there is increasing concerns of the local community on the decision making related to the safety matters on nuclear facilities. Resident people on NPP sites realize that radiation risk caused by the NPPs is their first concern, whereas the general public as a whole is less concerned with the radiation risk or nuclear safety. Regulatory organizations have less motivation to do their best because they pursue their private or group interests. In this paper, the above mentioned issue has been reviewed in terms of principal agent problem(PAP) theory and also the PAP model for Korean nuclear regulatory system has been developed
Review of Nuclear Regulation using Principal-Agent Model

International Nuclear Information System (INIS)

Choi, Kwang Sik; Lee, Young Eal; Ryu, Yong Ho

2010-01-01

Regulation is performed by the government on behalf of the public to accomplish a societal goal. However, the public is not necessarily confident that regulatory authority does well enough for the benefit of the public. That is partly because they have less information, competence and resources for monitoring regulatory activities. However, it is a problem that cannot be solved easily only by efforts of the personnel involved. In nuclear industry and regulation, there is increasing concerns of the local community on the decision making related to the safety matters on nuclear facilities. Resident people on NPP sites realize that radiation risk caused by the NPPs is their first concern, whereas the general public as a whole is less concerned with the radiation risk or nuclear safety. Regulatory organizations have less motivation to do their best because they pursue their private or group interests. In this paper, the above mentioned issue has been reviewed in terms of principal agent problem(PAP) theory and also the PAP model for Korean nuclear regulatory system has been developed
Safety regulation KTA 3901: Communication systems for nuclear power plants

International Nuclear Information System (INIS)

1981-01-01

The regulation applies to communication systems in stationary nuclear power plants with at least one power plant unit, i.e. alarm systems, staff locator systems, communicators, and systems for external communication. The regulation determines the type and extent of staff communication systems as well as the demands to be made on layout, installation, operating systems, and testing of communication systems for nuclear power plants. (orig./HP) [de
Transparency in Nuclear Regulation: Trends and Future Prospects

International Nuclear Information System (INIS)

Choi, Kwang Sik; Choi, Young Sung; Kim, Seong Ho

2007-01-01

Recently, improving transparency (or openness) has been one of important issues related to nuclear safety worldwide. As for the transparency in nuclear regulatory activities in Korea, openness has been declared as one of five principles of the nuclear regulation in the 'nuclear safety policy statement' announced in 1994. Transparency has been discussed and emphasized in various international meetings such as the Convention on Nuclear Safety, OECD/NEA meetings, etc. For example, Working Group on Public Communication of nuclear regulatory organizations (WGPC) of the OECD/NEA/CNRA held a workshop on 'the transparency of nuclear regulatory activities' in May 2007 in Tokyo, Japan. In this paper, definition of transparency and its international trends ranging from a general administration to nuclear safety activities are discussed based on the results of meetings and workshops held so far. Measures for improvement associated with transparency are also proposed
Nuclear power for energy production and hazardous waste regulations in India

International Nuclear Information System (INIS)

Sharma, Prabhakar; Goel, Gaurav

2010-01-01

Before installing any nuclear power- generation plants in India, it is important to implement stringent regulations for the health and safety of the people and for protection of the environment, soil and water from the nuclear and hazardous waste produced in the power plants. Although some initiatives have been taken for radioactive waste disposal in India, the current hazardous and nuclear waste storage/disposal regulations are still too soft and are not being implemented properly in the country
The nuclear import of ribosomal proteins is regulated by mTOR

Science.gov (United States)

Kazyken, Dubek; Kaz, Yelimbek; Kiyan, Vladimir; Zhylkibayev, Assylbek A.; Chen, Chien-Hung; Agarwal, Nitin K.; Sarbassov, Dos D.

2014-01-01

Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins. PMID:25294810
Nuclear regulation of South African mines: An industry perspective

International Nuclear Information System (INIS)

Wymer, D.G.

2001-01-01

South African mines have become subject to a rigid and prescriptive system of nuclear regulation that has its roots in the past when South Africa embarked upon a period of nuclear development spanning the full nuclear fuel cycle, and in which the South African gold mining industry once played a major part in the supply of uranium as a low grade by-product. Radiation hazards in the mines are generally very moderate, even in the few gold mines associated with uranium by-product, and to not warrant the type of regulatory attention normally applied to nuclear installations, or even to uranium mines. The continued imposition of strict nuclear regulatory requirements has caused severe financial hardship and threatens the survival of certain mining operations, while seemingly having little or no health benefits to workers or the public. With the development of modern, comprehensive mine health and safety legislation, a more appropriate, effective, and far less costly vehicle for controlling radiation hazards in mines now exists, utilizing the resources of the Mine Health and Safety Inspectorate. This approach is now being proposed, in the drafting of new legislation, as constituting a better alternative to the nuclear regulation of mines. (author)

Regulations and financing for decommissioning of nuclear facilities

International Nuclear Information System (INIS)

Kumakura, Osamu

1981-01-01

The purpose of this report is to survey the French legislation concerning the decommissioning of nuclear facilities and the method of financing for it. There is no clause in French regulations, which states any specific criterion or licensing procedure for the proper decommissioning. The legal problems in this domain are treated within the general regulation system on atomic energy. The decommissioning of nuclear facilities is carried out in accordance with the licensing procedure for constructing nuclear facilities or the permission procedure for operating them, according to the ''Decree on nuclear installations, 1963''. The works for the final shut-down and decommissioning are regarded as the modification to the safety report or the general operation instructions, and new permit is required. In the case that the radioactivity of substances after decommissioning is above the criteria of the Decree, 1963, the new license is required. In the case of below the criteria, the facilities are governed by the ''Act on installations classified for environmental protection, 1976''. The ''Decree on general radiation protection, 1966'', the ''Decree on radiation protection of workers in nuclear installations, 1975'', the ''Ministerial order on transport of dangerous materials, 1945'', and two ministerial orders on radioactive effluent discharge, 1974, are applied to the decommissioning works. (Kako, I.)
The regulations concerning the uses of nuclear source materials

International Nuclear Information System (INIS)

1981-01-01

This rule is established under the provisions of the law concerning the regulation of nuclear raw materials, nuclear fuel materials and nuclear reactors and the ordinance for the execution of this law, and to enforce them. Basic terms are defined, such as exposure radiation dose, cumulative dose, control area, surrounding monitoring area, worker and radioactive waste. Nuclear raw materials shall be used at the facilities for using them, and control areas and surrounding monitoring areas shall be set up. Cumulative dose and exposure radiation dose of workers shall not exceed the permissible quantities defined by the General Director of the Science and Technology Agency. Records shall be made in each works or enterprise on the accept, delivery and stock of each kind of nuclear raw materials, radiation control and the accidents in the facilities of using nuclear raw materials, and kept for specified periods, respectively. The users of nuclear raw materials shall present reports in each works or enterprise on the stock of these materials on July 30 and December 31, every year. They shall submit reports immediately to the Director General on the particular accidents concerning nuclear raw materials and their facilities and on the circumstances and the measures taken against such accidents within ten days. These reports shall be presented on internationally regulated raw materials too. (Okada, K.)
Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection.

Science.gov (United States)

Diner, Benjamin A; Lum, Krystal K; Toettcher, Jared E; Cristea, Ileana M

2016-11-15

The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses. How mammalian cells detect and respond to DNA viruses that replicate in the nucleus is poorly understood. Here, we decipher the distinct functions of two viral DNA sensors, IFI16 and cGAS, during active immune signaling upon infection with two herpesviruses, herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV). We show that IFI16
Safety experts complete second IAEA regulatory review of UK nuclear regulator

International Nuclear Information System (INIS)

2009-01-01

Full text: Nuclear safety experts today concluded a 10-day mission to peer-review the UK Nuclear Regulator: Health and Safety Executive (HSE), Nuclear Directorate (ND). At the request of the UK Government, the International Atomic Energy Agency assembled a team of ten high-level regulatory experts from eight nations to conduct the Integrated Regulatory Review Service (IRRS) mission. The mission was the second of three planned IRRS missions for the United Kingdom. The first was held in March 2006 to begin a process to assess the nation's readiness to regulate and license new reactor designs, considered as a result of the Energy Policy review initiated by the British Prime Minister and the Secretary of State for Trade and Industry (DTI) in 2005. The IRRS team leader Mr. William Borchardt, Executive Director of Operations from the US Nuclear Regulatory Commission, stated, ''The IAEA IRRS serves an important role in both benchmarking against its safety standards and in promoting dialogue between nuclear safety regulators from around the world.'' During the 2nd mission the IRRS the team reviewed HSE/ND progress since the first IRRS mission and recent regulatory developments, the regulation of operating power plants and fuel cycle facilities, the inspection and enforcement programme for nuclear power plants and fuel cycle facilities, and the emergency preparedness and response programme. The IAEA found that HSE/ND has made significant progress toward improving its effectiveness in regulating existing nuclear power plants and in preparing to license new nuclear reactors designs. Many of the findings identified in the 2006 report had been fully addressed and therefore could be considered closed, the others are being addressed in accordance with a comprehensive action plan. IRRS team members visited the Heysham 1 Nuclear Power Plant near Lancaster, the Sellafield site at Cumbria and the Strategic Control Centre at Hutton, and they met senior managers from HSE and a UK
The Relationship Between Nuclear Regulators and Their Stakeholders

International Nuclear Information System (INIS)

Burns, Stephen G.

2017-01-01

Mr Burns, Chairman of the United States Nuclear Regulatory Commission, delivered a keynote speech. He recognised there is a global movement towards broadening information flow and participation. He displayed the so-called Arnstein 'ladder' that can be applied to assess the degree of public involvement and influence achieved in any state or private decision making. The lower rungs depict non-participation and the middle rungs focus on education and information as well as consultation. Mr Burns suggested that the higher level of partnership was of most interest to the workshop. In his experience, partnership between stakeholders and regulatory organisations, as well as openness and transparency, are today seen as traits of a good regulator, and are increasingly set out as goals in regulatory strategic plans throughout the world. Mr Burns highlighted a broad definition of 'stakeholder' as 'one who is involved in or affected by a course of action'. Nuclear stakeholders thus include those who live near or work in nuclear facilities; own or run the facilities; govern at the national, regional or local level; manufacture the components or the fuel; regulate the output or use of the facility; benefit from the use of radiological material and nuclear installations; and those who might be adversely affected in any way by materials or facilities. Stakeholders also include the media who convey information to others, and the non-governmental organisations that represent the views of many individuals. Mr Burns focused on the concept of trust as enabling public confidence in technical calculations and risk management. He suggested that listening carefully to stakeholders is an important element of trust-building. He closed by affirming that regulators can maintain their independence while nonetheless considering others' opinions. Mr Burns emphasised that at the end of the day, the regulator holds sole responsibility for achieving its own regulatory objectives and consistent, well
The regulations concerning the uses of nuclear fuel materials

International Nuclear Information System (INIS)

1979-01-01

The regulations are defined under the law for the regulations of nuclear source materials, nuclear fuel materials and reactors and provisions concerning the uses of nuclear fuel materials in the order for execution of the law. Basic concepts and terms are explained, such as: exposure dose; accumulative dose; controlled area; inspected surrounding area and employee. The application for permission shall state the expected period and amount of the uses for each kind of nuclear fuel materials. Persons to whom spent fuels shall be sold, lent or returned and the method of disposal of such fuels shall be also indicated. Records shall be made and kept for particular periods for each works and enterprise on inspection of facilities, control of dose, maintenance and accident of facilities in use. The application for permission of the safeguard regulations shall report rules for each works and enterprise on the faculty and organization of controllers of facilities in use, safeguard education of employees, operation of apparatus which needs special control for prevention of disaster, establishment of controlled and inspected surrounding areas, entrance limitation, inspection of exposure dose, etc. Technical standards of the uses of nuclear fuel materials, disposal and transportation in the works and the enterprise and storage are stipulated in detail. Reports on exposure dose of employees and other specified matters shall be submitted every year to the Director General of Science and Technology Agency according to the forms attached. (Okada, K.)
Recent achievements in regulating nuclear power activities in taiwan

International Nuclear Information System (INIS)

Ouyang, M.S.

2006-01-01

Full text: The energy resources in Taiwan are very scarce with more than 98% of the fuel sources imported from foreign countries. The nuclear power became essential because of its stability and economy in price. There are six operating nuclear power units in Taiwan, and two more advanced boiling water reactor units under construction. As the country's nuclear power still plays an important role, the Atomic Energy Council (AEC) devotes its great efforts working on reactor safety regulation, radiation protection, nuclear security, nuclear emergency preparedness, nuclear waste management and environmental monitoring. Recent achievements of AEC on the above mentioned topics will be covered in this presentation
Regulation on the transport of nuclear fuel materials by vehicles

International Nuclear Information System (INIS)

1984-01-01

The regulations applying to the transport of nuclear fuel materials by vehicles, mentioned in the law for the regulations of nuclear source materials, nuclear fuel materials and reactors. The transport is for outside of the factories and the site of enterprises by such modes of transport as rail, trucks, etc. Covered are the following: definitions of terms, places of fuel materials handling, loading methods, limitations on mix loading with other cargo, radiation dose rates concerning the containers and the vehicles, transport indexes, signs and indications, limitations on train linkage during transport by rail, security guards, transport of empty containers, etc. together with ordinary rail cargo and so on. (Mori, K.)
Regulations on nuclear materials control of the People's Republic of China

International Nuclear Information System (INIS)

1996-01-01

The present 'Regulations on Nuclear Materials Control of the People's Republic of China' were promulgated by the State Council on June 15, 1987, which are enacted to ensure safe and lawful use of nuclear materials, to prevent theft, sabotage, lose, unlawful diversion and unlawful use, to protect the security of the State and the Public and to facilitate the development of nuclear undertakings. The nuclear materials controlled are: 1. Uranium-235 (materials and products); 2. Uranium-233 (material and products); 3. Plutonium-239 (materials and products); 4. tritium (materials and products); 5. lithium-6 (materials and products); 6. Other nuclear materials requiring control. The present regulations are not applicable to the control of uranium ore and its primary products. The control measures for nuclear products transferred to the armed forces shall be laid down by the national defence department
A new Brazilian regulation for the security of nuclear material and nuclear facilities

Energy Technology Data Exchange (ETDEWEB)

Tavares, Renato L.A.; Filho, Josélio S.M.; Torres, Luiz F.B.; Lima, Alexandre R., E-mail: renato.tavares@cnen.gov.br, E-mail: joselio@cnen.gov.br, E-mail: ltorres@cnen.gov.br, E-mail: alexandre.lima@cnen.gov.br [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Diretoria de Radioproteção e Segurança Nuclear; Lima, Fabiano P.C., E-mail: fabianopetruceli@outlook.com [Presidência da República, Brasilia, DF (Brazil). Gabinete de Segurança Institucional

2017-07-01

The present paper aims to outline the challenges related to the elaboration and concepts involved in a regulatory transition from a purely prescriptive approach to a combined approach that mixes performance-based concepts and evaluation metrics based on statistical data of equipment and personnel. This methodology might represent an improvement compared to a purely prescriptive approach, in which the regulatory authority defines the measures to be taken by operators of nuclear facilities to prevent theft, sabotage events, and mitigate their consequences. The prescriptive approach, despite having the advantages of clarity in the definition of requirements, simplicity in regulatory terms (inspections to verify compliance), and homogeneity in relation to various facilities, does not allow a clear and effective performance measurement, may provide insufficient or excessive security measures (with excessive expenditure of material and human resources), and the possibility of providing a false sense of security. It is known that, in many countries, the state-sponsored nuclear security regime mixes elements of the two mentioned approaches, prescriptive and based on performance, which is not Brazilian practice nowadays. Such methodological developments happened globally due to the increase of threat level for nuclear facilities and materials. The currently regulation in force is CNEN-NE 2.01, which provides a set of measures intended to implement Physical Protection Systems in Nuclear, Radiological Facilities as well as Transport Operations, and all documents related to security of such issues. The new regulation, named CNEN-NN 2.01, will focus only on Nuclear Material and Facilities (two other regulations specific for Security of Radioactive Sources and Transport Operations are under elaboration process). CNEN NN 2.01 is intended to provide further adherence to new international recommendations, e.g, IAEA INFCIRC 225 Rev.5 (NSS 13), which is currently regarded as the �
A new Brazilian regulation for the security of nuclear material and nuclear facilities

International Nuclear Information System (INIS)

Tavares, Renato L.A.; Filho, Josélio S.M.; Torres, Luiz F.B.; Lima, Alexandre R.; Lima, Fabiano P.C.

2017-01-01

The present paper aims to outline the challenges related to the elaboration and concepts involved in a regulatory transition from a purely prescriptive approach to a combined approach that mixes performance-based concepts and evaluation metrics based on statistical data of equipment and personnel. This methodology might represent an improvement compared to a purely prescriptive approach, in which the regulatory authority defines the measures to be taken by operators of nuclear facilities to prevent theft, sabotage events, and mitigate their consequences. The prescriptive approach, despite having the advantages of clarity in the definition of requirements, simplicity in regulatory terms (inspections to verify compliance), and homogeneity in relation to various facilities, does not allow a clear and effective performance measurement, may provide insufficient or excessive security measures (with excessive expenditure of material and human resources), and the possibility of providing a false sense of security. It is known that, in many countries, the state-sponsored nuclear security regime mixes elements of the two mentioned approaches, prescriptive and based on performance, which is not Brazilian practice nowadays. Such methodological developments happened globally due to the increase of threat level for nuclear facilities and materials. The currently regulation in force is CNEN-NE 2.01, which provides a set of measures intended to implement Physical Protection Systems in Nuclear, Radiological Facilities as well as Transport Operations, and all documents related to security of such issues. The new regulation, named CNEN-NN 2.01, will focus only on Nuclear Material and Facilities (two other regulations specific for Security of Radioactive Sources and Transport Operations are under elaboration process). CNEN NN 2.01 is intended to provide further adherence to new international recommendations, e.g, IAEA INFCIRC 225 Rev.5 (NSS 13), which is currently regarded as the �
Basic principles for regulating nuclear activities

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

The AECB has developed as its mission statement: `To ensure that the use of nuclear energy in Canada does not pose undue risk to health, safety, security and the environment`. This report proposes eleven qualitative principles for regulating nuclear activities whose achievement would satisfy the broad policy enunciated in the statement. They would further provide a basis for the specific regulatory requirements expressed by the AECB in its Regulations and other documents. They would thus represent a connecting link between the policy enunciated in the mission statement and the requirements. The proposed principles are largely concerned with how the allowable risk should be set for members of the public, for industry workers, for society as a whole, and for the environment. In making these recommendations the risks from normal operation of the licensed facility and those from a possible serious accident are considered separately. The distribution of risk between geographic communities and between generations is also addressed in the proposed principles. These are listed in the final section of the report. 23 refs.
Basic principles for regulating nuclear activities

International Nuclear Information System (INIS)

1996-03-01

The AECB has developed as its mission statement: 'To ensure that the use of nuclear energy in Canada does not pose undue risk to health, safety, security and the environment'. This report proposes eleven qualitative principles for regulating nuclear activities whose achievement would satisfy the broad policy enunciated in the statement. They would further provide a basis for the specific regulatory requirements expressed by the AECB in its Regulations and other documents. They would thus represent a connecting link between the policy enunciated in the mission statement and the requirements. The proposed principles are largely concerned with how the allowable risk should be set for members of the public, for industry workers, for society as a whole, and for the environment. In making these recommendations the risks from normal operation of the licensed facility and those from a possible serious accident are considered separately. The distribution of risk between geographic communities and between generations is also addressed in the proposed principles. These are listed in the final section of the report. 23 refs
The improvement of nuclear safety regulation : American, European, Japanese, and South Korean experiences

International Nuclear Information System (INIS)

Cho, Byung Sun

2005-01-01

Key concepts in South Korean nuclear safety regulation are safety and risk. Nuclear regulation in South Korea has required reactor designs and safeguards that reduce the risk of a major accident to less than one in a million reactor-years-a risk supposedly low enough to be acceptable. To data, in South Korean nuclear safety regulation has involved the establishment of many technical standards to enable administration enforcement. In scientific lawsuits in which the legal issue is the validity of specialized technical standards that are used for judge whether a particular nuclear power plant is to be licensed, the concept of uncertainty law is often raised with regard to what extent the examination and judgement by the judicial power affects a discretion made by the administrative office. In other words, the safety standards for nuclear power plants has been adapted as a form of the scientific technical standards widely under the idea of uncertainty law. Thus, the improvement of nuclear safety regulation in South Korea seems to depend on the rational lawmaking and a reasonable, judicial examination of the scientific standards on nuclear safety
Safety culture in nuclear installations - The role of the regulator

International Nuclear Information System (INIS)

Karigi, Alice W.

2002-01-01

Safety culture is an amalgamation of values, standards, morals and norms of acceptable behavior by the licensees, Radiation workers and the Regulator. The role played by a Regulator in establishing safety culture in a nuclear installation is that related to Authorization, review, assessment, inspection and enforcement. The regulator is to follow the development of a facility or activity from initial selection of the site through design, construction, commissioning, radioactive waste management through to decommissioning and closure. He is to ensure safety measures are followed through out the operation of the facility by laying down in the license conditions of controlling construction of nuclear installations and ensuring competence of the operators. (author)
Some issues on the Law for the Regulations of Nuclear Source Material, Nuclear Fuel Material and Reactors Amendment after JCO criticality accident

International Nuclear Information System (INIS)

Tanabe, Tomoyuki

2001-01-01

As the Amendment of the Law for the Regulation of Nuclear Material, Nuclear Fuel Material and Reactors on an opportunity of the JCO criticality accident can be almost evaluated at a viewpoint of upgrading on effectiveness of safety regulation, it is thought to remain a large problem to rely on only enforcement of regulation due to amendment of the Law at future accident. In future, it can be also said to be important subjects to further expand a philosophy on the regulation (material regulation) focussed to hazards of nuclear material itself, not only to secure effectiveness on the multi-complementary safety regulation due to the administrative agency and the Nuclear Safety Commission but also to prepare a mechanism reflexible of a new information to the safety regulation, and to prepare a mechanism to assist adequate business execution and so forth of enterprises. (G.K.)
Incentive regulation of investor-owned nuclear power plants by public utility regulators

International Nuclear Information System (INIS)

McKinney, M.D.; Elliot, D.B.

1993-01-01

The US Nuclear Regulatory Commission (NRC) periodically surveys the Federal Energy Regulatory Commission (FERC) and state regulatory commissions that regulate utility owners of nuclear power plants. The NRC is interested in identifying states that have established economic or performance incentive programs applicable to nuclear power plants, including states with new programs, how the programs are being implemented, and in determining the financial impact of the programs on the utilities. The NRC interest stems from the fact that such programs have the potential to adversely affect the safety of nuclear power plants. The information in this report was obtained from interviews conducted with each state regulatory agency that administers an incentive program and each utility that owns at least 10% of an affected nuclear power plant. The agreements, orders, and settlements that form the basis for each incentive program 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 radioactive waste regulation in the new Czech Nuclear Energy Act

International Nuclear Information System (INIS)

Kucerka, M.

1995-01-01

Recently, in the Czech Republic, there is in the phase of development the Act on Peaceful Use of Nuclear Energy and Ionizing Radiation, so called the Nuclear Energy Act. This Act has to replace existing regulations and fulfill some not yet covered fields of that area. The act is developed as so called ''umbrella act'' and has to cover all aspects of the nuclear energy and ionizing radiation use, from uranium mining or isotopes use in medicine, to the power generation in nuclear power plants. It will include among others also provisions on registration and licensing, liability for nuclear damage, decommissioning and radioactive waste management funding, and some other topics, that were missing in the regulations up to today. The paper describes recent state policy in the field of radioactive waste management and the main provisions of proposed Nuclear Energy Act, concerning the radioactive waste management
Compact, self-regulating nuclear power source

International Nuclear Information System (INIS)

Peterson, Otis G.; Kimpland, Robert H.

2008-01-01

An inherently safe nuclear power source has been designed, that is self-stabilizing and requires no moving mechanical components. Unlike conventional designs, the proposed reactor is self-regulating through the inherent properties of uranium hydride, which serves as a combination fuel and moderator. The temperature driven mobility of the hydrogen contained in the hydride will control the nuclear activity. If the core temperature increases over the set point, the hydrogen is driven out of the core, the moderation drops and the power production decreases. If the temperature drops, the hydrogen returns and the process is reversed. Thus the design is inherently fail-safe and requires only minimal human oversight. The compact nature and inherent safety opens the possibility for low-cost mass production and operation of the reactors. This design has the capability to dramatically alter the manner in which nuclear energy is harnessed for commercial use. (author)
FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia

Directory of Open Access Journals (Sweden)

Mariko Takenokuchi

2012-10-01

Full Text Available Acute promyelocytic leukemia (APL is characterized by the specific PML-RARa fusion gene resulting from translocation t(15;17 (q22;q12. Internal tandem duplication (ITD of the FLT3 gene has been observed in approximately 35% of APLs, and large-scale studies have identified the presence of ITD as an adverse prognostic factor for acute myeloblastic leukemia (AML patients. Aberrant expressions of surface antigens, such as CD2, CD34, and CD56, have been found in APL, but the implications of this are not well understood. We investigated the incidence of the FLT3/ITD mutation and FLT3/D835 (I836 point mutation in 25 APL patients. Incidence ratios of FLT3/ITD, D835 (I836, and both FLT3/ITD and D835 (I836 were 36%, 36% and 8%, respectively. FLT3/ITD+ cases showed a predominance of the bcr3 isoform (P=0.008 and M3v morphology (P<0.001. We found that all FLT3/ITD+ cases expressed CD2 (9 of 9 more frequently than that of FLT3/ITD- (1 of 16 (P<0.001, while only one of the CD2+ cases (1 of 10, 10% did not harbor FLT3/ITD, and all CD2+CD34+ cases (5 of 5, 100% harbored FLT3/ITD. In addition, quantitative polymerase chain reaction analysis showed that FLT3 mRNA was more abundantly expressed in FLT3/ITD+ than that in FLT3/ITD- (P=0.025, while there was no difference between D835(I836+ and D835(I836- with regards to aberrant surface-antigen expression, expression levels of FLT3 mRNA, M3v morphology, and the bcr3 isoform of PML-RARa mRNA. This study demonstrates that the presence of FLT3/ITD, but not D835 (I836, is closely related to aberrant CD2 expression and high expression levels of FLT3 mRNA. Our findings also suggest that FLT3/ITD as a secondary genetic event may block differentiation at the immature stage of APL.

Synthesis of the panel information principles for nuclear regulators: the journalist's view

International Nuclear Information System (INIS)

Lippman, T.W.

1994-01-01

The four journalists who participated in the OECD Nuclear Energy Agency seminar were M. Thomas Lippman, United States; Ms. Anna Schytt, Sweden; M. Michel Lemeret, Belgium; and M. Francis Sorin, France. Although the nuclear industry is structured differently in each of these countries, the journalists who have written about it for many years agreed on certain basic points. In order to have the confidence of the public, nuclear regulators must function openly, provide accurate and dispassionate information, have a reservoir of available technical knowledge and be independent of government and politics. Their purpose should be to regulate, rather than to promote the nuclear energy industry. The participants agreed that it is part of the regulators' role to provide information to the public on a regular basis, to forestall misunderstanding and potential panic. But this must be done in a way that does not appear to be promoting the nuclear power industry as such. (author)
Procedural problems in phase-out regulations in nuclear law

International Nuclear Information System (INIS)

Kloepfer, Michael

2012-01-01

The contribution discusses the legal regulations accompanying German nuclear policy during the past twelve years. There were several radical changes in 2002, 2010, and 2011 which reflect the opinions of the then German governments; some of these regulations, according to the author, were not compatible with German constitutional law.
Risk analysis of nuclear safeguards regulations

International Nuclear Information System (INIS)

Al-Ayat, R.A.; Altman, W.D.; Judd, B.R.

1982-06-01

The Aggregated Systems Model (ASM), a probabilisitic risk analysis tool for nuclear safeguards, was applied to determine benefits and costs of proposed amendments to NRC regulations governing nuclear material control and accounting systems. The objective of the amendments was to improve the ability to detect insiders attempting to steal large quantities of special nuclear material (SNM). Insider threats range from likely events with minor consequences to unlikely events with catastrophic consequences. Moreover, establishing safeguards regulations is complicated by uncertainties in threats, safeguards performance, and consequences, and by the subjective judgments and difficult trade-offs between risks and safeguards costs. The ASM systematically incorporates these factors in a comprehensive, analytical framework. The ASM was used to evaluate the effectiveness of current safeguards and to quantify the risk of SNM theft. Various modifications designed to meet the objectives of the proposed amendments to reduce that risk were analyzed. Safeguards effectiveness was judged in terms of the probability of detecting and preventing theft, the expected time to detection, and the expected quantity of SNM diverted in a year. Data were gathered in tours and interviews at NRC-licensed facilities. The assessment at each facility was begun by carefully selecting scenarios representing the range of potential insider threats. A team of analysts and facility managers assigned probabilities for detection and prevention events in each scenario. Using the ASM we computed the measures of system effectiveness and identified cost-effective safeguards modifications that met the objectives of the proposed amendments
ER-E3 regulation. Minimal instrumentation that must operate nuclear medicine in Cuba

International Nuclear Information System (INIS)

2015-01-01

The purpose of this regulation is to define the instrumentation that must exist in any institution conducting the practice of nuclear medicine in Cuba. This regulation emphasizes two aspects: The minimum equipment necessary to operate a nuclear medicine laboratory for use 'in vitro' and the minimum equipment required to operate a Nuclear Medicine use 'in vivo'
Connections or conflicts between nuclear regulations and other regulations

International Nuclear Information System (INIS)

Shapar, H.K.

1976-01-01

The potential for conflicts between nuclear and other regulations stems in large part from overlapping jurisdictional lines which reflect not only the basic governmental structure but the political realities as well. A completely logical pattern - with a clear differentiation of responsibilities assigned to the various departments and agencies involved - is assuredly a worthy goal, but one not often, if ever, achieved. Fortunately, innovative means for obviating or mitigating the conflicts can be and have been found. (Auth) [fr
Cryptic PML-RARα positive acute promyelocytic leukemia with unusual morphology and cytogenetics

Directory of Open Access Journals (Sweden)

Goyal Manu

2010-10-01

Full Text Available Acute Promyelocytic Leukemia (APL is different from other forms of acute myeloid leukemia (AML, to the reason being the potential devastating coagulopathy and the sensitivity to all-trans retinoic acid (ATRA and arsenic trioxide (As 2 O 3 . We hereby present a case of APL, morphologically distinct from the hypergranular APL; however, the flow cytometry revealed a characteristic phenotype showing dim CD45, bright CD13, bright CD33 and dim CD117 positivity. These were negative for CD34, HLA-DR, B-lymphoid and T-lymphoid lineage markers. Conventional cytogenetics revealed a distinct karyotype of a male with translocation t(4;15(q34.2:q26.3. However, interphase florescence-in-situ hybridization (FISH revealed PML/RARA fusion signal on chromosome 15 in 90% cells. The cryptic translocations may be missed on conventional cytogenetics, however, need to be picked by other techniques as FISH.
Design of an optimal automatic regulator for regulating the power levels of a nuclear reactor in a wind power range

International Nuclear Information System (INIS)

Noori Khajavi, M.; Menhaj, M.B.; Ghofrani, M.B.

2000-01-01

Nuclear power reactors are, in nature nonlinear and time varying. These characteristics must be considered, if large power variations occur in their working regime. In this paper a robust optimal self-tuning regulator for regulating the power of a nuclear reactor has been designed and simulated. The proposed controller is capable of regulating power levels in a wide power range (10% to 100% power levels). The controller achieves a fast and good transient response. The simulation results show that the proposed controller outperforms the fixed optimal control recently cited in the literature for nuclear power plants
The trilogy nuclear technology-quality-reliability in nuclear energy: the interface technical regulation/industrial norm in the nuclear industry

International Nuclear Information System (INIS)

Costa, Jose Ribeiro da

1995-01-01

In this paper, it is tried to find out a compatibility among Regulations (mandatory) documents governing Quality Assurance Requirements for the Nuclear Industry (like IAEA/50-C-QA, IAEA/50-SG-QA1, IAEA/50-SG-QA7, and others), with similar documents prescribing same requirements for COnventional Industry (like ISO/900 Series), using the technical support of the prescriptions contained in the IAEA/TR-328 documents. Harmonization and compatibility of these documents is a great deal for Industries engaged -directly or indirectly - in the Nuclear Technology, taking into account that such compatibility can avoid troubles for already ISO/9000 Series Certified Industries in the fulfillment of its contract requirements in the nuclear field. Its also represents in that field a symbiosis between Technical Regulations (mandatory) and Voluntary Standards (Industrial, Consensual Standards). (author). 7 refs., 1 fig., 1 tab
Co-operative development of nuclear safety regulations, guides and standards based on NUSS

International Nuclear Information System (INIS)

Pachner, J.; Boyd, F.C.; Yaremy, E.M.

1985-01-01

A major need of developing Member States building nuclear power plants (NPPs) of foreign origin is to acquire a capability to regulate such nuclear plants independently. Among other things, this requires the development of national nuclear safety regulations, guides and standards to govern the development and use of nuclear technology. Recognizing the importance and complexity of this task, it seems appropriate that the NPP-exporting Member States share their experience and assist the NPP-importing Member States in the development of their national regulations and guides. In 1983, the Atomic Energy Control Board and Atomic Energy of Canada Ltd. conducted a study of a possible joint programme involving Canada, an NPP-importing Member State and the IAEA for the development of the national nuclear safety regulations and guides based on NUSS documents. During the study, a work plan with manpower estimates for the development of design regulations, safety guides and a guide for regulatory evaluation of design was prepared as an investigatory exercise. The work plan suggests that a successful NUSS implementation in developing Member States will require availability of significant resources at the start of the programme. The study showed that such a joint programme could provide an effective mechanism for transfer of nuclear safety know-how to the developing Member States through NUSS implementation. (author)
The Competence Promoting by NNSA for Keeping High Level Nuclear Safety: The Corner Stone of the Nuclear Safety Regulation Edifice

International Nuclear Information System (INIS)

Hu, L.

2016-01-01

Facing the fast development of the nuclear power industry and the application of radioactive sources, The MEP(NNSA) is endeavoured to promoting its competency, including: complementing the law system, training and recruiting staff to keep a capable team, constructing the R&D base to keep the basic capability, promoting safety culture both for the industry and the regulator. After the Fukushima nuclear accident, the MEP(NNSA) planned to construct R&D base, in which the Platform Nuclear Safety Monitoring and Emergency Responding, the Platform of Safety Technology of PWR Testing, the Laboratory of Safety Management Technology of Nuclear Waste Verification, the Laboratory of Environmental Radiation Monitoring and the Center of International Cooperation are included. On the other hand, the MEP(NNSA) issued Chinese nuclear safety culture policy declaration in 2014, and carried out a large scale Specialized Action for Nuclear Safety Promotion to promote the nuclear safety culture both for the industry and herself. For the nuclear regulator, It is essential to conduct the competence promoting by both “hardware” and “software”, the former is the material foundation of regulation authority, which will be effectively functioning under the facilitating of the latter. (author)
The regulations concerning refining business of nuclear source material and nuclear fuel materials

International Nuclear Information System (INIS)

1987-01-01

Regulations specified here cover application for designation of undertakings of refining (spallation and eaching filtration facilities, thickening facilities, refining facilities, nuclear material substances or nuclear fuel substances storage facilities, waste disposal facilities, etc.), application for permission for alteration (business management plan, procurement plan, fund raising plan, etc.), application for approval of merger (procedure, conditions, reason and date of merger, etc.), submission of report on alteration (location, structure, arrangements processes and construction plan for refining facilities, etc.), revocation of designation, rules for records, rules for safety (personnel, organization, safety training for employees, handling of important apparatus and tools, monitoring and removal of comtaminants, management of radioactivity measuring devices, inspection and testing, acceptance, transport and storage of nuclear material and fuel, etc.), measures for emergency, submission of report on abolition of an undertaking, submission of report on disorganization, measures required in the wake of revocation of designation, submission of information report (exposure to radioactive rays, stolen or missing nuclear material or nuclear fuel, unusual leak of nuclear fuel or material contaminated with nuclear fuel), etc. (Nogami, K.)
Development in France of nuclear safety technical regulations and standards used in the licensing procedure

International Nuclear Information System (INIS)

Lebouleux, P.

1983-04-01

Initially, the Commissariat a l'Energie Atomique was the overall structure which encompassed all nuclear activities in France, including those connected with radiological protection and nuclear safety. As other partners appeared, the Authorities have laid down national regulations relative to nuclear installations since 1963. These regulations more particularly provide for the addition of prescriptions with which the applicant must comply to obtain the necessary licenses and the establishment of General Technical Regulations pertaining to nuclear safety. The technical regulation related to nuclear safety in France is made of a set of regulation texts, of a different nature, that define the requirements for the construction, commissioning and operation of nuclear facilities. Simultaneously, the safety authorities (Service Central de Surete des Installations Nucleaires: SCSIN) issue recommendations or guides which are not strictly speaking regulations in the juridical sense; they are called ''Regles Fondamentales de Surete'' (RFS). The RFS set up and detail the conditions, the respect of which is deemed to be complying with the French regulation practice, for the subject to which they relate. Their purpose is to make known rules judged acceptable by safety authorities, thus making the safety review easier. A RFS, or a letter, can also give the result of the examination of the constructor and operator codes (RCC) by safety authorities
Nuclear organization during in vitro differentiation of porcine mesenchymal stem cells (MSCs) into adipocytes.

Science.gov (United States)

Stachecka, Joanna; Walczak, Agnieszka; Kociucka, Beata; Ruszczycki, Błażej; Wilczyński, Grzegorz; Szczerbal, Izabela

2018-02-01

Differentiation of progenitor cells into adipocytes is accompanied by remarkable changes in cell morphology, cytoskeletal organization, and gene expression profile. Mature adipocytes are filled with a large lipid droplet and the nucleus tends to move to the cell periphery. It was hypothesized that the differentiation process is also associated with changes of nuclear organization. The aim of this study was to determine the number and distribution of selected components of nuclear architecture during porcine in vitro adipogenesis. The pig is an important animal model sharing many similarities to humans at the anatomical, physiological, and genetic levels and has been recognized as a good model for human obesity. Thus, understanding how cellular structures important for fundamental nuclear processes may be altered during adipocyte differentiation is of great importance. Mesenchymal stem cells (MSCs) were derived from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) and were cultured for 7 days in the adipogenic medium. A variable differentiation potential of these cell populations towards adipogenic lineage was observed, and for further study, a comparative characteristic of the nuclear organization in BM-MSCs and AD-MSCs was performed. Nuclear substructures were visualized by indirect immunofluorescence (nucleoli, nuclear speckles, PML bodies, lamins, and HP1α) or fluorescence in situ hybridization (telomeres) on fixed cells at 0, 3, 5, and 7 days of differentiation. Comprehensive characterization of these structures, in terms of their number, size, dynamics, and arrangement in three-dimensional space of the nucleus, was performed. It was found that during differentiation of porcine MSCs into adipocytes, changes of nuclear organization occurred and concerned: (1) the nuclear size and shape; (2) reduced lamin A/C expression; and (3) reorganization of chromocenters. Other elements of nuclear architecture such as nucleoli, SC-35 nuclear speckles, and telomeres
Serum-dependent expression of promyelocytic leukemia protein suppresses propagation of influenza virus

International Nuclear Information System (INIS)

Iki, Shigeo; Yokota, Shin-ichi; Okabayashi, Tamaki; Yokosawa, Noriko; Nagata, Kyosuke; Fujii, Nobuhiro

2005-01-01

The rate of propagation of influenza virus in human adenocarcinoma Caco-2 cells was found to negatively correlate with the concentration of fetal bovine serum (FBS) in the culture medium. Virus replicated more rapidly at lower FBS concentrations (0 or 2%) than at higher concentrations (10 or 20%) during an early stage of infection. Basal and interferon (IFN)-induced levels of typical IFN-inducible anti-viral proteins, such as 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and MxA, were unaffected by variation in FBS concentrations. But promyelocytic leukemia protein (PML) was expressed in a serum-dependent manner. In particular, the 65 to 70 kDa isoform of PML was markedly upregulated following the addition of serum. In contrast, other isoforms were induced by IFN treatment, and weakly induced by FBS concentrations. Immunofluorescence microscopy indicated that PML was mainly formed nuclear bodies in Caco-2 cells at various FBS concentrations, and the levels of the PML-nuclear bodies were upregulated by FBS. Overexpression of PML isoform consisting of 560 or 633 amino acid residues by transfection of expression plasmid results in significantly delayed viral replication rate in Caco-2 cells. On the other hand, downregulation of PML expression by RNAi enhanced viral replication. These results indicate that PML isoforms which are expressed in a serum-dependent manner suppress the propagation of influenza virus at an early stage of infection
Regulations and guides for nuclear power plants

International Nuclear Information System (INIS)

1984-01-01

The purpose of the present Guide is to provide information, guidance and recommendations to assist the regulatory body of a Member State in establishing its own regulations and guides. It discusses the purpose, the method and procedure of establishment, and the content and legal status of these documents, and it explains how to use the Codes of Practice and Safety Guides issued by the IAEA under the Nuclear Safety Standards (NUSS) programme. Certain aspects of how to use other international standards and appropriate regulations and guides from other countries are discussed
Legal status of minister's notices and technology standards of 'Korea institute of nuclear safety'(KINS) to regulate nuclear safety

International Nuclear Information System (INIS)

Jung, S. K.; Jung, M. M.; Kim, S. W.; Jang, K. H.; Oh, B. J.

2003-01-01

Concerning nuclear safety or technology standards, each of 'notices' issued by minister of science and technology(MOST) empowered by law of its regulation is obviously forceful as a law, if not all. But the standards made by the chief of Korea institute of nuclear safety(KINS) to meet the tasks entrusted to KINS by MOST is only conditionally forceful as a law, that is, on the condition that law or regulation empowered the chief of KINS to make nuclear safety and/or technology standards
Dynamic regulation of Drosophila nuclear receptor activity in vivo.

Science.gov (United States)

Palanker, Laura; Necakov, Aleksandar S; Sampson, Heidi M; Ni, Ruoyu; Hu, Chun; Thummel, Carl S; Krause, Henry M

2006-09-01

Nuclear receptors are a large family of transcription factors that play major roles in development, metamorphosis, metabolism and disease. To determine how, where and when nuclear receptors are regulated by small chemical ligands and/or protein partners, we have used a 'ligand sensor' system to visualize spatial activity patterns for each of the 18 Drosophila nuclear receptors in live developing animals. Transgenic lines were established that express the ligand binding domain of each nuclear receptor fused to the DNA-binding domain of yeast GAL4. When combined with a GAL4-responsive reporter gene, the fusion proteins show tissue- and stage-specific patterns of activation. We show that these responses accurately reflect the presence of endogenous and exogenously added hormone, and that they can be modulated by nuclear receptor partner proteins. The amnioserosa, yolk, midgut and fat body, which play major roles in lipid storage, metabolism and developmental timing, were identified as frequent sites of nuclear receptor activity. We also see dynamic changes in activation that are indicative of sweeping changes in ligand and/or co-factor production. The screening of a small compound library using this system identified the angular psoralen angelicin and the insect growth regulator fenoxycarb as activators of the Ultraspiracle (USP) ligand-binding domain. These results demonstrate the utility of this system for the functional dissection of nuclear receptor pathways and for the development of new receptor agonists and antagonists that can be used to modulate metabolism and disease and to develop more effective means of insect control.
Regulation on control of nuclear materials of the 31 Oct 1986

International Nuclear Information System (INIS)

1986-01-01

The new regulation on accounting for and control of nuclear materials was issued on 31 October 1986 and put into force on 1 February 1987. The following provisions are included: aim and scope, responsibility for nuclear material accounting and control, rights and obligations of the nuclear material control officer, licensing, facility's instructions for nuclear material control, accounting, records, reporting, unusual events, inspections, nuclear material transfers, exemptions and termination of IAEA safeguards, final provisions, and definitions of terms
IAEA Assistance to developing countries in the regulation of nuclear installations

International Nuclear Information System (INIS)

Phuong, H.V.

1977-01-01

The paper analyses the IAEA assistance to developing countries in the regulation of nuclear installations. The projected growth of nuclear power both in industrialised and developing IAEA Member States has led to a reassessment of the role that the Agency should play pursuant to its statutory obligation in the area of nuclear safety. Accelerated work was begun nearly 3 years ago to establish a wide range of recommendations essential in matters of nuclear power plant safety so as to provide an internationally acceptable body of basic criteria and minimum requirements. In recent years the IAEA has increasingly provided advisory services to developing countries for the elaboration of enabling legislation; also intensive training programmes covering specific nuclear safety and regularoty topics have been carried out through special training courses and conducted in co-operation with host countries with extensive nuclear experience and appropriate training facilities. Experience has shown that these services have been of practical help to national authorities in providing guidance and initiatives for speeding up the process of framing laws and regulations. (NEA) [fr
R and D perspectives on the advanced nuclear safety regulation system

International Nuclear Information System (INIS)

Lee, Chang Ju; Ahn, Sang Kyu; Park, Jong Seuk; Chung, Dae Wook; Han, Sang Hoon; Lee, Jung Won

2009-01-01

As current licensing process is much desired to be optimized both plant safety and regulatory efficiency, an advanced safety regulation such as risk informed regulation has been come out. Also, there is a need to have a future oriented safety regulation since a lot of new reactors are conceptualized. Keeping pace with these needs, since early 2007, Korean government has launched a new project for preparing an advanced and future oriented nuclear safety regulation system. In order to get practical achievements, the project team sets up such specific research objectives for the development of: implementation program for graded regulation using risk and performance information; multi purpose PSA models for regulatory uses; a technology neutral regulatory framework for future innovative reactors; evaluation procedure of proliferation resistance; and, performance based fire hazard analysis method and evaluation system. This paper introduces major R and D outputs of this project, and provides some perspectives for achieving effectiveness and efficiency of the nuclear regulation system in Korea

R and D perspectives on the advanced nuclear safety regulation system

Energy Technology Data Exchange (ETDEWEB)

Lee, Chang Ju; Ahn, Sang Kyu; Park, Jong Seuk; Chung, Dae Wook [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Han, Sang Hoon; Lee, Jung Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2009-04-15

As current licensing process is much desired to be optimized both plant safety and regulatory efficiency, an advanced safety regulation such as risk informed regulation has been come out. Also, there is a need to have a future oriented safety regulation since a lot of new reactors are conceptualized. Keeping pace with these needs, since early 2007, Korean government has launched a new project for preparing an advanced and future oriented nuclear safety regulation system. In order to get practical achievements, the project team sets up such specific research objectives for the development of: implementation program for graded regulation using risk and performance information; multi purpose PSA models for regulatory uses; a technology neutral regulatory framework for future innovative reactors; evaluation procedure of proliferation resistance; and, performance based fire hazard analysis method and evaluation system. This paper introduces major R and D outputs of this project, and provides some perspectives for achieving effectiveness and efficiency of the nuclear regulation system in Korea.
Nuclear Regulator Knowledge Management in a Dynamic Nuclear Industry Environment

International Nuclear Information System (INIS)

Turner, J.

2016-01-01

Full text: The paper outlines the experiences to date in developing mature knowledge management within the UK’s nuclear regulatory body The Office for Nuclear Regulation (ONR). In 2010 concerns over the loss of knowledge due to the age profile within the organization instigated a review of knowledge management and the development of a knowledge management initiative. Initially activities focused on knowledge capture but in order to move to through life knowledge transfer, knowledge management was then aligned with organizational resilience initiatives. A review of progress highlighted the need to better engage the whole organization to achieve the desired level of maturity for knowledge management. Knowledge management activities now cover organizational culture and environment and all aspects of organizational resilience. Benefits to date include clear understanding of core knowledge requirements, better specifications for recruitment and training and the ability to deploy new regulatory approaches. During the period of implementing the knowledge management programme ONR undertook several organizational changes in moving to become a separate statutory body. The UK nuclear industry was in a period of increased activity including the planning of new nuclear reactors. This dynamic environment caused challenges for embedding knowledge management within ONR which are discussed in the paper. (author
Managing for safety and safety culture within the UK nuclear industry. A regulator's perspective

International Nuclear Information System (INIS)

Tyrer, M.J.

2002-01-01

This paper outlines the basis of the legal system for the regulation of health and safety at work within the United Kingdom (UK), and in particular, the regulation of the nuclear industry. The framework, formulated by the regulator, which has been published as a practical guide for directors, managers, health and safety professionals and employee representatives for the successful management of health and safety is explained. This guidance, however, concentrates, to a large extent, on management systems and only addresses in part the types of issues, such as behaviours, values, attitudes and beliefs which contribute to the safety culture of an organization. The regulator of the UK nuclear industry has considered research, and other work, carried out by several organizations in this area, notably the Advisory Committee on the Safety of Nuclear Installations (ACSNI) and the International Atomic Energy Agency (IAEA), and produced its own framework for managing for safety at nuclear installations. As a regulator, the Health and Safety Executive (HSE), and its inspectorate responsible for regulation of the nuclear industry, HM Nuclear Installations Inspectorate (HMNII), are not the appropriate organization to assess the safety culture of an organization, but positively encourage organizations to both carry out this assessment themselves and to monitor their performance. To this end, HSE has developed, and made available, the Health and Safety Climate Tool which is aimed at providing organizations with information which can be used as part of a continuous improvement process. (author)
Controlling the atom: The beginnings of nuclear regulation, 1946-1962

International Nuclear Information System (INIS)

Mazuzan, G.T.; Walker, S.

1985-01-01

The authors trace the political, legislative, technological, and administrative history of nuclear regulation in this country. Many groups have been involved in the regulatory process, but the Atomic Energy Commission (precursor of the Nuclear Regulatory Commission) had the primary mandate for protecting public health and safety from the nonmilitary uses of nuclear energy. The AEC had other important statutory functions, and the authors examine them in terms of how they influenced the agency's regulatory role
Assessment of policy issues in nuclear safety regulation according to circumstantial changes

Energy Technology Data Exchange (ETDEWEB)

Chang, Soon Heung; Chang, Soon Heung; Lee, Byong Ho; Baek, Won Pil; Roh, Chang Hyun; Lee, Kwang Gu; Kim, Hong Chae; Lee, Yong Ho [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

1999-03-15

The objective of the work is to assess various issues in nuclear safety regulation in consideration of circumstantial changes. Emphasis is given to the safety of operating NPPs. It is concluded that the Periodic Safety Review (PSR) should be implemented in Korea as soon as possible, in harmonization with the regulation for life extension of NPPs. The IAEA guidelines, including 10 year intervals and 11 safety factors, should be used as the basic guidelines. Efforts are also required to cope with other circumstantial changes such as the establishment of International Nuclear Regulators Association (INRA)
Education and Training of Safety Regulation for Nuclear Safety Infrastructure: Its Necessity and Unique Features

International Nuclear Information System (INIS)

Choi, Young Sung; Choi, Young Joon; Lee, Jae Cheon

2009-01-01

Faced with global warming and electricity demands, countries over the world recognize the comparative advantages of nuclear energy. It is estimated that about 300 nuclear power plants (NPPs) expect to be constructed until 2030 worldwide. In addition, according to the IAEA, approximately 20 new countries might have their first NPP in operation by 2030 in the high projection compared with bout 5 new countries in the low projection. When introducing nuclear power, the implementation of an appropriate infrastructure to address all of the relevant issues is a central concern of international community. In particular, nuclear power program requires, at an earlier stage than when construction starts, the development of a legal and regulatory framework and training of regulators and safety experts whose combined knowledge adequately covers all areas of nuclear safety and regulation applied at a NPP construction and operation. As an essential component of such human resource development, special attention was paid to the provision of education and training to regulators of which countries plan to introduce NPPs. In term of education theory, safety regulation has some unique features in learning and teaching, which are different from those of nuclear engineering or development. This paper overviews nuclear safety infrastructure, explores the roles of exporting countries, and presents features and components in education of nuclear safety regulation
Nuclear regulations: current status and proposed initiatives

International Nuclear Information System (INIS)

Domondon, D.B.; Valdezco, E.M.; Mateo, A.J.; Parami, V.K.

1996-01-01

The science Act of 1958 created the Philippine Atomic Energy Commission, presently known as the Philippine Nuclear Research Institute (PNRI), under the Department of Science and Technology (DOST). The PNRI is tasked with the dual role of promotion and control of the peaceful applications of atomic energy. To carry its mandate of regulation and control on the use of raioisotopes in various fields, the PNRI had promulgated and issued specific regulations known as the Code of PNRI regulations. This paper summarizes the activities undertaken by PNRI in the continuing process of review and subsequent revisions of the Code of PNRI regulations and related guidance documents. It highlights proposed modifications in the present regulations in an attempt to adopt the new international basic safety standards, the practical problems and related issues attendant to the implementation of these new standards, among others. In line with the overall objective of PNRI to ensure the safe application of nuclear energy and radiation technology in various fields, the institute conducted a series of regulatory information conferences to provide an opportunity for members of the regulatory staff of the PNRI and licenses to discuss safety initiatives and regulatory issues. This paper will also provide an in-depth assessment of the lessons learned from these conferences which were conducted by sector or by specific applications for a more focused approach, e.g. radiopharmaceuticals, industrial radiography, research, among others. Licensees' feedback on the PNRI regulatory process are presented as part of the overall objective of enhancing the operational experiences of the licensing, review and evaluation group as well as that of inspection, enforcement and compliance. Several proposed initiatives for consideration of the PNRI to further strengthen its regulatory functions are also briefly outlined. (author)
A study on the establishment of a nuclear regulators' association in the Northeast Asia

International Nuclear Information System (INIS)

Shin, Won Ky; Park, Y. S.; Lee, H. J.; Park, D. K.; Choi, K. S.; Park, C. H.; Hwang, S. C.; Do, K. S.; Choi, Y. S.

2001-12-01

It is desirable to make joint efforts among northeast countries in order to assure nuclear safety in northeast Asia where nuclear power development has been active. In this regard, through this study, it is developed the draft for the establishment of a regional cooperative mechanism in the field of nuclear safety regulation in this region. This will be utilized as a basic references to plan and conduct regional cooperation in the field of nuclear safety regulation in this region. Through this study, the status of multilateral cooperative mechanisms in nuclear safety field, domestic and international nuclear safety trends, and nuclear safety cooperation status in this region are investigated. Based on this investigation, the draft for the establishment of the Nuclear Regulators Meeting in the Northeast Asia (NUREMA) and its implementation plan are developed. If the NUREMA is successfully established and operated, it will serve as a central basis for exchanging regulatory related information, experience, and techniques, etc., which will strengthen domestic and regional nuclear safety. It is desirable to strengthen the MOST∼NNSA∼METI Tripartite Meeting on a step by step basis for the next few years (4 - 5 years) and finally establish a multilateral cooperative mechanism like NUREMA
Recent developments in the regulation of nuclear transportation

International Nuclear Information System (INIS)

Grella, A.W.

1978-01-01

In the past four years, almost all nations and international or intergovernmental transport organizations have effected transitions from the 1967 to 1973 IAEA standards as their basis for regulatory requirements for the safe transport of radioactive materials. One major exception to this transition is the USA itself, where this transition has not yet taken place. Major amendments to revise 49 CFR Parts 100-199 of the Department of Transportation regulations and 10 CFR Part 71 of the Nuclear Regulatory Commission regulations are required to effect this transition. The notices of proposed rulemaking to effect this transition in the USA are expected to be published by DOT and NRC concurrently sometime in 1978. Final amendments can be expected later, after the public comment period on the notices and considerations of those comments. This paper summarizes the status of current thinking on US adoption of the 1973 IAEA standards, as well as the status of adoption of those standards by international intergovernmental organizations, such as the Intergovernmental Maritime Consultative Organization, International Civil Aviation Organization, etc. A number of the differences between the expected US regulations and other regulations based on the 1973 IAEA standards are explained. This paper also discusses a number of other events or matters which have been taking place in the US in the past four years which have or may have an effect on transport of nuclear materials and its regulation, including air transport of plutonium, rail transport of spent fuel and other regulations by state or political subdivisions. The paper also discusses changes to US regulations accomplished in the past four years, which are not related to 1973 IAEA standards, as well as some other possible areas where regulatory proposals might be anticipated, such as control of radiation exposures to certain transport workers and other matters
Nuclear regulation in the 1980s - a leadership role

International Nuclear Information System (INIS)

Asselstine, J.K.

1983-01-01

An overview of cooperation between the Nuclear Regulatory Commission (NRC) and the nuclear industry cites the Institute of Nuclear Power Operations (INPO) as a model for other cooperative efforts, both in determining the need for and the appropriateness of regulatory requirements. The author addresses three needs of nuclear regulation that will be significant during the 1980s: to adapt our regulatory program to a changing workload; to address safety issues, and particularly the development of new safety requirements, for nuclear plants; and to modernize and improve the licensing process. Steps to improve licensing procedures could include standardization, the resolution of design issues before the start of construction, redefinition of the hearing process, limitations of later modifications, stable commission decision making authority, and recognition of the commission's authority to consider economic costs in making regulatory decisions
EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.

Directory of Open Access Journals (Sweden)

Kevin Tsai

2011-11-01

Full Text Available Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs, suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus.
EBV Tegument Protein BNRF1 Disrupts DAXX-ATRX to Activate Viral Early Gene Transcription

Science.gov (United States)

Tsai, Kevin; Thikmyanova, Nadezhda; Wojcechowskyj, Jason A.; Delecluse, Henri-Jacques; Lieberman, Paul M.

2011-01-01

Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus. PMID:22102817
The Process of Legal Drafting Regulation in the Development of the Nuclear Power Plant in Indonesia

International Nuclear Information System (INIS)

Amil Mardha

2009-01-01

In Indonesia, the process of legal drafting to establish the regulation is based on the Act No. 10 Year 2004 on the Establishment of Legislation. The process shall comply with the constitutional and institutional requirements of national political and legal system. In drafting the development of the regulation of nuclear energy, BAPETEN has been involving some other agencies or other related government agencies, and stakeholders such as utility, academic institutions, and publics. In general, in the process of legal drafting, international publications or other country regulations can be a reference and adopted. In the establishment of the regulations of nuclear energy, BAPETEN has issued some Government Regulations and Chairman Regulations of BAPETEN. For nuclear safety of NPP, the regulations have not been completed yet, but some regulations related in the area of siting of NPP have been already available. In this paper, it is discussed the process of the establishment of legislation and of the legal drafting nuclear regulation of NPP, and the current status of NPP regulations. (author)
Operating Nuclear Power Stations in a Regulated Cyber Security Environment

Energy Technology Data Exchange (ETDEWEB)

Dorman, E.

2014-07-01

The United States Nuclear Regulatory Commission (NRC) issued 10CFR73.54 to implement a regulated Cyber Security Program at each operating nuclear reactor facility. Milestones were implemented December 31, 2012 to mitigate the attack vectors for the most critical digital assets acknowledged by the industry and the NR C. The NRC inspections have begun. The nuclear Cyber Security Plan, implemented by the site Cyber Security Program (Program), is an element of the operating license at each facility. (Author)
Operating Nuclear Power Stations in a Regulated Cyber Security Environment

International Nuclear Information System (INIS)

Dorman, E.

2014-01-01

The United States Nuclear Regulatory Commission (NRC) issued 10CFR73.54 to implement a regulated Cyber Security Program at each operating nuclear reactor facility. Milestones were implemented December 31, 2012 to mitigate the attack vectors for the most critical digital assets acknowledged by the industry and the NR C. The NRC inspections have begun. The nuclear Cyber Security Plan, implemented by the site Cyber Security Program (Program), is an element of the operating license at each facility. (Author)
The law for the regulations of nuclear source materials, nuclear fuel materials and reactors

International Nuclear Information System (INIS)

1977-01-01

Concerning refining, fabrication and reprocessing operations of such materials as well as the installation and operation of reactors, necessary regulations are carried out. Namely, in case of establishing the business of refining, fabricating and reprocessing nuclear materials as well as installing nuclear reactors, applications for the permission of the Prime Minister and the Minister of International Trade and Industry should be filed. Change of such operations should be permitted after filing applications. These permissions are retractable. As regards the reactors installed aboard foreign ships, it must be reported to enter Japanese waters and the permission by the Prime Minister must be obtained. In case of nuclear fuel fabricators, a chief technician of nuclear fuel materials (qualified) must be appointed per each fabricator. In case of installing nuclear reactors, the design and methods of construction should be permitted by the Prime Minister. The standard for such permission is specified, and a chief engineer for operating reactors (qualified) must be appointed. Successors inherit the positions of ones who have operated nuclear material refining, fabrication and reprocessing businesses or operated nuclear reactors. (Rikitake, Y.)
State regulation of nuclear sector: comparative study of Argentina and Brazil models

International Nuclear Information System (INIS)

Monteiro Filho, Joselio Silveira

2004-08-01

This research presents a comparative assessment of the regulation models of the nuclear sector in Argentina - under the responsibility of the Autoridad Regulatoria Nuclear (ARN), and Brazil - under the responsibility of Comissao Nacional de Energia Nuclear (CNEN), trying to identify which model is more adequate aiming the safe use of nuclear energy. Due to the methodology adopted, the theoretical framework resulted in criteria of analysis that corresponds to the characteristics of the Brazilian regulatory agencies created for other economic sector during the State reform staring in the middle of the nineties. Later, these criteria of analysis were used as comparison patterns between the regulation models of the nuclear sectors of Argentina and Brazil. The comparative assessment showed that the regulatory structure of the nuclear sector in Argentina seems to be more adequate, concerning the safe use of nuclear energy, than the model adopted in Brazil by CNEN, because its incorporates the criteria of functional, institutional and financial independence, competence definitions, technical excellence and transparency, indispensable to the development of its functions with autonomy, ethics, exemption and agility. (author)
Working together with regulators on nuclear sites

International Nuclear Information System (INIS)

Holloway, N.J.

2004-01-01

A scheme for earlier and clearer communications with the Health and Safety Executive (HSE) and the Environment Agency (EA) on jointly regulated issues has been developed across the nuclear industry over the past two years. The matched pair of industry and regulators' 'Working Together' documents was published in January 2003. In the United Kingdom Atomic Energy Authority (UKAEA), the scheme is being put into practice through the issue of Initial Regulatory Notifications (IRN) of various projects and issues, to capture key regulatory topics and prompt regulators' initial responses. The IRN may be based on a safety and environment overview report or may be a precursor to it. Positive responses, in line with the Working Together documents, were received from HSE and the EA, following receipt of the first three UKAEA IRNs. (author)
Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

International Nuclear Information System (INIS)

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

2014-01-01

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

International Nuclear Information System (INIS)

Laaksonen, J.

2002-01-01

The workshop was held in Paris on the 29. November - 1. December 2000. Its objective was well captured in the title: Investing in Trust, Nuclear Regulators and the Public. The general public is concerned with the risks involved in the use of nuclear power, and has a legitimate desire for reliable and impartial information. The nuclear regulators have answers, but in order to fulfill the information needs of the general public and their elected representatives, they need to be regarded trustworthy. Most of the about 80 participants were from nuclear regulatory bodies and radiation protection agencies. The discussions gave regulators an opportunity to change views and experiences on how to gain trust in their openness and honesty, and in their will and capability to protect public interests. The weight given to the topic was indicated by participation of nine heads of national regulatory bodies, among them top regulators from four countries with largest nuclear programmes: the USA, Japan, France, and the UK. The number of papers presented was 33, and their topics were considered well chosen by the organizing committee. Throughout the workshop 'posters' were available; these were electronic links to the web sites of the attending regulatory bodies. Proceedings of the workshop will be published during the first half of 2001. (author)

Resolution 62/96 Regulation for the accounting and control of the nuclear materials

International Nuclear Information System (INIS)

1996-01-01

The present Regulation is a complementary disposition of the ordinance number 208 of May 24 National System of Accounting and Control of Nuclear Materials and it has as objective to establish the relative norms to this System. As for the responsibilities it establish that the National Center of Nuclear Security (CNSN) it is the responsible for the execution from the relative tasks to the National System of Accounting and Control of Nuclear Materials. It establishes the regulations for the following aspects: licenses and authorizations for the transportation of the nuclear material and important components, Of the ceasing of the Accounting and Control, Of the Accounting and Control of the Nuclear Materials, Control of the Important Components, The Inspections, International Organism of the Atomic Energy Safeguards
Investing in trust: nuclear regulators and the public

International Nuclear Information System (INIS)

2001-01-01

The workshop was held in Paris on the 29. November - 1. December 2000. Its objective was well captured in the title: Investing in Trust, Nuclear Regulators and the Public. The general public is concerned with the risks involved in the use of nuclear power, and has a legitimate desire for reliable and impartial information. It is important to convince the people that the regulatory body works for them and for their safety and is not promoting the use of nuclear energy or any other interests. A necessary condition for being trustworthy is to be well known, efficient channels are needed, a good information must be transferred to two directions, information must be easily available to the public are some important points developed in this workshop. (N.C.)
The role of research in nuclear regulation: A Korean perspective

International Nuclear Information System (INIS)

Yoon, Won-Hyo

1997-01-01

Korea has carried out a very ambitious nuclear power program since the 1970's as part of the nation's industrialization policy. Ever since, Korea has also maintained a strong commitment to nuclear power development as an integral part of the national energy policy which aims at reducing external vulnerability and ensuring against a global fossil fuel shortage. The introduction of nuclear power into Korea has progressed through three stages: the first was a turn-key package supplied by the manufacturer; the second involved a major contractor who was responsible for project management, and design and construction was contracted out, with Korean industry becoming more involved; the third stage has seen Korean industries involved as main contractors based on experience gained from earlier plants. The success of Korea's nuclear power program depends in large part on how to insure safety. Safety has the highest priority in nuclear energy development. Public acceptance has been the most critical problem faced by the nuclear industry in Korea. The public demands the highest level of safety all through the design, construction, and operation of nuclear power plants. Korea has learned that a nuclear plant designed with well addressed safety, implementation of a well grounded QA program during construction, and operated with a proven record of safety, are the only ways to earn public support. Competent and efficient regulation with a strong safety culture and openness in all issues is the most desirable image for regulators to strive for. Korea established a ten year R ampersand D program to obtain self-reliance in nuclear technology and international competitiveness by the early 2000's in 1992. It has actively participated in coordinated research programs in safety issues with bodies including the USNRC, AECB of Canada, IAEA, and OECD/NEA
The law for the regulations of nuclear source materials, nuclear fuel materials and reactors

International Nuclear Information System (INIS)

1987-01-01

General provisions specify the purpose of the Law and definitions of terms used in it. Provisions relating to control of business management for refining cover designation of business operation, requirements for designation, permission and report of alteration, report of commencement of business operation, revocation of designation, recording, and measures for wastes. Provisions relating to control of business management for processing cover permission of operation, requirements for permission, approval of design and construction plan, inspection of facilities, report of commencement of business management, measures for maintenance, suspension of use of facilities, responsible personnel for handling nuclear fuel, and permit, obligations, etc. of responsible personnel for handing nuclear fuel. Provisions relating to control of construction and operation of nuclear reactor cover permission of construction, permission concerning nuclear reactor mounted on foreign nuclear powered ships, requirements for permission, etc. Other articles stipulate provisions relating to control of business management for reprocessing, use of nuclear fuel substances, use of materials and substances covered by international regulations, designation of inspection organizations, and other rules. (Nogami, K.)
RNA polymerase III transcription - regulated by chromatin structure and regulator of nuclear chromatin organization.

Science.gov (United States)

Pascali, Chiara; Teichmann, Martin

2013-01-01

RNA polymerase III (Pol III) transcription is regulated by modifications of the chromatin. DNA methylation and post-translational modifications of histones, such as acetylation, phosphorylation and methylation have been linked to Pol III transcriptional activity. In addition to being regulated by modifications of DNA and histones, Pol III genes and its transcription factors have been implicated in the organization of nuclear chromatin in several organisms. In yeast, the ability of the Pol III transcription system to contribute to nuclear organization seems to be dependent on direct interactions of Pol III genes and/or its transcription factors TFIIIC and TFIIIB with the structural maintenance of chromatin (SMC) protein-containing complexes cohesin and condensin. In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF). Furthermore, chromosomal sites have been identified in yeast and humans that are bound by partial Pol III machineries (extra TFIIIC sites - ETC; chromosome organizing clamps - COC). These ETCs/COC as well as Pol III genes possess the ability to act as boundary elements that restrict spreading of heterochromatin.
Nuclear AMPK regulated CARM1 stabilization impacts autophagy in aged heart

International Nuclear Information System (INIS)

Li, Chen; Yu, Lu; Xue, Han; Yang, Zheng; Yin, Yue; Zhang, Bo; Chen, Mai; Ma, Heng

2017-01-01

Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart. We found that fasting could promote autophagy in young hearts but not in aged hearts. The CARM1 stabilization is markedly decrease in aged hearts, which impaired nucleus TFEB-CARM1 complex and autophagy flux. Further, S-phase kinase-associated protein 2(SKP2), responsible for CARM1 degradation, was increased in aged hearts. We further validated that AMPK dependent FoxO3 phosphorylation was markedly reduced in nucleus, the decreased nuclear AMPK-FoxO3 activity fails to suppress SKP2-E3 ubiquitin ligase. This loss of repression leads to The CARM1 level and autophagy in aged hearts could be restored through AMPK activation. Taken together, AMPK deficiency results in nuclear CARM1 decrease mediated in part by SKP2, contributing to autophagy dysfunction in aged hearts. Our results identified nuclear AMPK controlled CARM1 stabilization as a new actor that regulates cardiac autophagy. - Highlights: • AMPK-dependent CARM1 stabilization is an important nuclear mechanism in cardiac autophagy. • AMPK deficiency lead to SKP2-mediated decrease in CARM1. • AMPK–SKP2–CARM1 in the regulation of autophagy dysfunction in aged heart.
Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor

OpenAIRE

Giovannoni, Federico; Damonte, Elsa B.; Garc?a, Cybele C.

2015-01-01

The intrinsic antiviral defense is based on cellular restriction factors that are constitutively expressed and, thus, active even before a pathogen enters the cell. The promyelocytic leukemia (PML) nuclear bodies (NBs) are discrete nuclear foci that contain several cellular proteins involved in intrinsic antiviral responses against a number of viruses. Accumulating reports have shown the importance of PML as a DNA virus restriction factor and how these pathogens evade this antiviral activity....
On regulation of environmental responsibility in the final stage of the nuclear fuel cycle. - Parallel regulation within the framework of Euratom and the Lisbon-treaty

International Nuclear Information System (INIS)

Erhag, Thomas

2010-09-01

In Sweden, the responsibility for the disposal of spent nuclear fuel is regulated in various laws and regulations. This means that there is an overlap between laws providing a sometimes vague and weak legal situation. Although attempts have been made to coordinate environmental and nuclear law these attempts have not succeeded. Recently, several Swedish reports have again described the fact that we have a parallel system of legal rules for the handling of spent nuclear fuel and the consequences of this. Foremost attention has been drawn to the fact that the licensing of a repository must be made both under the Nuclear Safety Act and the Environmental Code. The regulation referred to above is Swedish, and both the parallel regulation of nuclear safety-, radiation protection- and environmental- responsibility, and the relationship between such legislation, has its own Swedish history. However, Swedish legislation in all these areas is also under the influence of international regulations. This article describes the parallel regulation of nuclear safety and radiation protection issues on a European level. It shows that the division and logic found in the relationship between the Swedish laws is only partially reflected at European level. First treated is the relationship between the EC-treaty and Euratom. The article then turns to examples of regulatory responsibility for waste management and communication of information relating to license applications (environmental impact assessments) for the final disposal of spent nuclear fuel within the framework of Euratom and the EC-treaty. Finally, it discusses the implications of this type of parallel regulation for the Swedish licensing procedure
On regulation of environmental responsibility in the final stage of the nuclear fuel cycle. - Parallel regulation within the framework of Euratom and the Lisbon-treaty

Energy Technology Data Exchange (ETDEWEB)

Erhag, Thomas (Dept. of Law, Univ. of Goeteborg, Goeteborg (Sweden)), e-mail: thomas.erhag@law.gu.se

2010-09-15

In Sweden, the responsibility for the disposal of spent nuclear fuel is regulated in various laws and regulations. This means that there is an overlap between laws providing a sometimes vague and weak legal situation. Although attempts have been made to coordinate environmental and nuclear law these attempts have not succeeded. Recently, several Swedish reports have again described the fact that we have a parallel system of legal rules for the handling of spent nuclear fuel and the consequences of this. Foremost attention has been drawn to the fact that the licensing of a repository must be made both under the Nuclear Safety Act and the Environmental Code. The regulation referred to above is Swedish, and both the parallel regulation of nuclear safety-, radiation protection- and environmental- responsibility, and the relationship between such legislation, has its own Swedish history. However, Swedish legislation in all these areas is also under the influence of international regulations. This article describes the parallel regulation of nuclear safety and radiation protection issues on a European level. It shows that the division and logic found in the relationship between the Swedish laws is only partially reflected at European level. First treated is the relationship between the EC-treaty and Euratom. The article then turns to examples of regulatory responsibility for waste management and communication of information relating to license applications (environmental impact assessments) for the final disposal of spent nuclear fuel within the framework of Euratom and the EC-treaty. Finally, it discusses the implications of this type of parallel regulation for the Swedish licensing procedure
Regulator's role in sustainability of nuclear power

International Nuclear Information System (INIS)

Bansal, Parikshat; Sinha, Soumen; Bhattacharya, Ramdas

2015-01-01

A development which is environmentally benign, economically viable as well socially acceptable is regarded as sustainable development. Nuclear power scores extremely well with the first two parameters: i.e its cost of production is competitive with that of other power sources and is considered a clean source of power as the greenhouse gas emissions and discharge of other hazardous pollutants are insignificant. However, when it comes to acceptability by the society at large, there are issues. Early shutting down of power plants like Superphénix at France, abandonment of Yucca mountain project, agitation during commissioning of KKNPP etc. are few examples where the public perception was the main reason for such actions. These events tell us about the importance of public perception in sustainability of a project or nuclear power as a whole. In this backdrop, the role of regulator to present the safety aspects in correct perspective assumes enormous significance and goes in a long way in clearing unwarranted apprehensions, thereby playing a pivotal role in sustainability of nuclear power. The nuclear regulator needs to build long lasting trust and confidence with stakeholders. Therefore it needs to be continuously in touch with public, not only during crisis but also during peace time, disseminating information on safe use of ionizing radiation and atomic energy without undue risk to the health of the people and environment. (author)
Administrative procedures for regulating construction and operation of nuclear power plants

International Nuclear Information System (INIS)

Cochaud, J.P.

1981-01-01

This article first explains that nuclear power plants in France are governed by a complex system of regulations within the framework of different laws concerning, in particular, protection of the environment, public health and workers. It then examines the administrative procedures and the licensing regime for nuclear power plants. (NEA) [fr
Regulation of spent nuclear fuel shipment: A state perspective

International Nuclear Information System (INIS)

Halstead, R.J.; Sinderbrand, C.; Woodbury, D.

1987-01-01

In 1985, the Wisconsin Department of Natural Resources (WDNR) sought to regulate rail shipments of spent nuclear fuel through the state, because federal regulations did not adequately protect the environmentally sensitive corridor along the route of the shipments. A state interagency working group identified five serious deficiencies in overall federal regulatory scheme: 1) failure to consider the safety or environmental risks associated with selected routes; 2) abscence of route-specific emergency response planning; 3) failure of the NRC to regulate the carrier of spent nuclear fuel or consider its safety record; 4) abscence of requirements for determination of need for, or the propriety of, specific shipments of spent nuclear fuel; and 5) the lack of any opportunity for meaningful public participation with respect to the decision to transport spent nuclear fuel. Pursuant to Wisconsin's hazardous substance statutes, the WDNR issues an order requiring the utility to file a spill prevention and mitigation plan or cease shipping through Wisconsin. A state trial court judge upheld the utility's challenge to Wisconsin's spill plan requirements, based on federal preemption of state authority. The state is now proposing federal legislation which would require: 1) NRC determination of need prior to approval of offsite shipment of spent fuel by the licensees; 2) NRC assessment of the potential environmental impacts of shipments along the proposed route, and comparative evaluation of alternative modes and routes; and 3) NRC approval of a route-specific emergency response and mitigation plan, including local training and periodic exercises. Additionally, the proposed legislation would authorize States and Indian Tribes to establish regulatory programs providing for permits, inspection, contingency plans for monitoring, containments, cleanup and decontamination, surveillance, enforcement and reasonable fees. 15 refs
Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway.

Science.gov (United States)

Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O

2017-08-15

Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans This finding suggests the existence of a conserved CYP4V2-POR-nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage.
ILK statement about the BMU project of updating nuclear rules and regulations

International Nuclear Information System (INIS)

2007-01-01

In 2003, the German Federal Ministry for the Environment (BMU) started its ''Updating Nuclear Rules and Regulations'' project. Proposals to this effect are currently in revision phase B. They comprise a total of eleven main topics, referred to as modules, under the heading of ''Basic Principles of Safety of Nuclear Power Plants - Safety Requirements in Accordance with the State of the Art.'' The International Nuclear Technology Committee (ILK), in 2005, dealt with the requirements to be met in an up-to-date code of nuclear rules and regulations. Its findings were published in a total of 10 recommendations. The current revision B of the 11 modules contains no discernible incorporation of these recommendations. ILK therefore once more dealt with the BMU project. A summary of its deliberations is available. ILK finds that the safety requirements to be met by nuclear power plants as outlined in the BMU draft are unable to support the implementation of the German Atomic Energy Act. In earlier statements, ILK had written that it deemed updating the code of rules and regulations desirable. The existing draft contains many elements serving this purpose, such as the inclusion of off-power conditions and a more pronounced incorporation of matters of organization and management. The main shortcomings of the present draft are identified and analyzed. (orig.)
Operating nuclear power stations in a regulated cyber security environment: a roadmap for success

Energy Technology Data Exchange (ETDEWEB)

Dorman, E., E-mail: Erik.Dorman@areva.com [AREVA Inc., Cyber Security Solutions, Charlotte, NC (United States)

2015-07-01

The United States Nuclear Regulatory Commission (NRC) issued 10CFR73.54 to implement a regulated Cyber Security Program at each operating nuclear reactor facility. Milestones were implemented December 31, 2012 to mitigate the attack vectors for the most critical digital assets acknowledged by the industry and the NRC. The NRC inspections have begun. The nuclear Cyber Security Plan, implemented by the site Cyber Security Program (Program), is an element of the operating license at each facility. The Program is designed to protect critical digital assets (CDAs) by applying and maintaining defense-in depth protective strategies to ensure the capability to detect, respond to, and recover from cyber-attacks. The Program references NEI 08-09 R. 6, the Nuclear Energy Institute Template that provides guidance for applying Cyber Security controls derived from NIST 800-53/82 and slightly modified to fit the nuclear environment. Many mature processes are in place at nuclear facilities in response to numerous regulations implemented over the past 30 years. Many of these processes such as the Physical Security Program offer protections that are leveraged to protect the functions of critical digital assets from unauthorized physical access. Other processes and technology such as engineering design control, work management and pre-job briefs, control of portable media and mobile devices, and deterministically segregated networks protect critical digital assets. By leveraging the regulated nuclear environment, integrating NIST type Cyber Security controls, and prudently deploying technology the Cyber Security posture of operating nuclear facilities supports on-demand base load electricity 24/7 with capacity factors exceeding 85%. This paper is designed to provide a glimpse into Cyber Security Programs that support safe operation and reliability in the regulated nuclear environment while supporting the on-demand base load electricity production 24/7. (author)
Operating nuclear power stations in a regulated cyber security environment: a roadmap for success

International Nuclear Information System (INIS)

Dorman, E.

2015-01-01

The United States Nuclear Regulatory Commission (NRC) issued 10CFR73.54 to implement a regulated Cyber Security Program at each operating nuclear reactor facility. Milestones were implemented December 31, 2012 to mitigate the attack vectors for the most critical digital assets acknowledged by the industry and the NRC. The NRC inspections have begun. The nuclear Cyber Security Plan, implemented by the site Cyber Security Program (Program), is an element of the operating license at each facility. The Program is designed to protect critical digital assets (CDAs) by applying and maintaining defense-in depth protective strategies to ensure the capability to detect, respond to, and recover from cyber-attacks. The Program references NEI 08-09 R. 6, the Nuclear Energy Institute Template that provides guidance for applying Cyber Security controls derived from NIST 800-53/82 and slightly modified to fit the nuclear environment. Many mature processes are in place at nuclear facilities in response to numerous regulations implemented over the past 30 years. Many of these processes such as the Physical Security Program offer protections that are leveraged to protect the functions of critical digital assets from unauthorized physical access. Other processes and technology such as engineering design control, work management and pre-job briefs, control of portable media and mobile devices, and deterministically segregated networks protect critical digital assets. By leveraging the regulated nuclear environment, integrating NIST type Cyber Security controls, and prudently deploying technology the Cyber Security posture of operating nuclear facilities supports on-demand base load electricity 24/7 with capacity factors exceeding 85%. This paper is designed to provide a glimpse into Cyber Security Programs that support safe operation and reliability in the regulated nuclear environment while supporting the on-demand base load electricity production 24/7. (author)
TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.

Science.gov (United States)

McCallum, Katie C; Liu, Bin; Fierro-González, Juan Carlos; Swoboda, Peter; Arur, Swathi; Miranda-Vizuete, Antonio; Garsin, Danielle A

2016-05-01

The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. Copyright © 2016 by the Genetics Society of America.
Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

Science.gov (United States)

Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

2013-01-01

Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Regulatory Body Safety Culture in Non-nuclear HROs: Lessons for Nuclear Regulators

International Nuclear Information System (INIS)

Fleming, M.; Bowers, K.

2016-01-01

Regulator safety culture is a relatively new area of investigation, even though deficiencies in regulatory oversight have been identified in a number of public inquiries (e.g., Piper Alpha, Deep Water Horizon). More recently the IAEA report into the Fukushima disaster specifically identified the need for regulatory bodies to have a positive safety culture. While there are clear parallels between duty holder safety culture and regulator safety culture there are also likely to be differences. To date they have been no published studies investigating regulator safety culture. In order to develop a framework to understand regulator safety culture we conducted a literature review and interviewed safety culture subject matter experts from a range of HRO domains (e.g., offshore oil and gas). There was general consensus among participants that regulatory safety culture was an important topic that was worthy of further investigation. That there was general agreement that regulatory safety culture was multi-dimensional and that some of the elements of existing safety culture models applied to regulator culture (e.g., learning and leadership). The participants also identified unique dimensions of regulator safety culture including commitment to high standards and ethics, transparency and perceived role of the regulator. In this paper we will present the results of the interviews and present a model of regulator safety culture. This model will be contrasted with models being used in the nuclear industry. Implications for assessing regulatory safety culture will be discussed. (author)
Slow return of reason to nuclear regulation

International Nuclear Information System (INIS)

McGranery, J.P. Jr.

1983-01-01

During the 1970s, the promise of nuclear power as a cheap source of electricity was seriously eroded in practice. A variety of reasons, including governmental vacillation and delay, have been offered for those circumstances. With a different administration and an apparently improving national economy, it seems appropriate to look at some of the governmental developments of the last year to see if there is hope for the return of reasonable and predictable regulation to nuclear power. This article summarizes some of the principal actions by the courts, the regulatory agency, the administration, and the Congress during that period, as well as pending actions. It concludes that there is a favorable climate and reason to hope, but that success will depend, in the final analysis, upon the conduct of the industry itself. 73 references

Regulations of 19 August 1978 on the optional principles of the Nuclear Safety Committee

International Nuclear Information System (INIS)

1978-01-01

These regulations were published in the Turkish Official Gazette of 19 August 1978 and were made pursuant to Decree no. 7/9141 of 1975 on licensing of nuclear installations which established the Nuclear Safety Committee. They determine the duties and responsibilities of the Committee, its qualifications, its operating principles and its relations with the Nuclear Safety Assistance Service set up in the Turkish Atomic Energy Commission for the purposes of assisting its Secretary General. The regulations also lay down the procedures to be applied for consultations on granting licences. (NEA) [fr
The Establishment of Regulation for Supporting the Development of the First Nuclear Power Plant in Indonesia

International Nuclear Information System (INIS)

Mardha, Amil

2011-01-01

To support construction and operation of the first Nuclear Power Plant (NPP), Government of Indonesia through BAPETEN as a national authority in nuclear energy usage has pushed ahead in enhancing the development of regulatory system. BAPETEN is currently focusing its activities to the development of regulations in the form of Chairman Decree, the development of licensing and inspection system, and manpower for NPP regulators. The process of the establishment of national legislation is based on the Act No.10 Year 2004 on The establishment of legislation. The process of legal drafting to establish or to revise a regulation for controlling of the use of nuclear energy shall comply with the constitutional and institutional requirements of national political and legal system. In drafting the regulation of nuclear safety of NPP, BAPETEN has been involving some other agencies or other related government agencies, and also stakeholders such as utility, academic institutions, and publics. In general, in the process of legal drafting, international publications or other country regulations can be a reference. Present paper deals with the legal basis of regulation, the establishment of legislation in Indonesia, the process in legal drafting regulations of NPP, and the current status of NPP regulations. (author)
The role of the nuclear safety regulator

International Nuclear Information System (INIS)

Mellado, I.

2007-01-01

The Consejo de Seguridad Nuclear (CSN), or Nuclear Safety Council, is the only Spanish institution qualified in nuclear safety and radiological protection. Created in 1980, the CSN is independent of the Central State Administration, and possesses its own legal standing, estate and resources acquired directly from tax revenues. The CSN proposes regulations and advises the government on subjects within its competence, including the criteria for siting nuclear facilities once the autonomous regions have been informed. The CSN is responsible for issuing mandatory and binding reports to the Ministry of Industry. Tourism and Commerce, and for inspections and evaluation of the facilities included within its realm of competence throughout their phases (construction, start-up, operating and decommissioning). It is also responsible for the radiological control and surveillance of workers, the general public and the environment, as described below. In 1999, a new responsibility was assigned to the CSN to perform studies, assessment and inspections in relation to all phases of radioactive waste and spent fuel management. The CSN reports to the Spanish Parliament and is not subject to the hierarchy or auspices of the Government or the organisations in charge of promoting nuclear energy. The Council itself is an Associative Body comprised of 5 members, appointed by Parliament for a 6 year term (these members cannot be removed). Under this Council is situated an extensive technical body. A General Secretary is seconded by Technical Directors in the area of Nuclear Safety and Radiological Protection. As well there are a R and D Office, an Inspection Office, and a Technical Standards Office. The CSN counts 446 workers, of which 191 are university graduate specialists in nuclear safety or radiological protection. The average age is 45 years. Ongoing training is provided in technical specialties and management. (author)
Improving the regulation of safety at DOE nuclear facilities. Final report

International Nuclear Information System (INIS)

1995-12-01

The report strongly recommends that, with the end of the Cold War, safety and health at DOE facilities should be regulated by outside agencies rather than by DOE itself. The three major recommendations are: under any regulatory scheme, DOE must maintain a strong internal safety management system; essentially all aspects of safety at DOE's nuclear facilities should be externally regulated; and existing agencies rather than a new one should be responsible for external regulation
1990 No. 1918. The Nuclear Installations Act 1965 (Repeal and Modifications) Regulations 1990

International Nuclear Information System (INIS)

1990-01-01

These Regulations entered into force on 31 October 1990. They repeal part of Section (1) of the Nuclear Installations Act 1965 to remove the exemption of the United Kingdom Atomic Energy Authority (UKAEA) from licensing under the Act. The Regulations also amend the 1965 Act to ensure that the UKAEA's duties in respect of the safety of premises it occupies will continue to apply whether or not a nuclear site licence has been granted. (NEA) [fr
Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

Science.gov (United States)

Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

2017-10-19

Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.
Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

Science.gov (United States)

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

2017-02-01

HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide
Regulations concerning the fabricating business of nuclear fuel materials

International Nuclear Information System (INIS)

1979-01-01

The regulations are entirely revised under the law for the regulations of nuclear materials, nuclear fuel materials and reactors and provisions concerning the fabricating business in the order for execution of the law. Basic concepts and terms are defined, such as: exposure dose; accumulative dose; controlled area; inspected surrounding area; employee and radioactive waste. The application for permission of the fabricating business shall include: location of processing facilities; structure of building structure and equipment of chemical processing facilities; molding facilities; structure and equipment of covering and assembling facilities, storage facilities of nuclear fuel materials and disposal facilities of radioactive waste, etc. Records shall be made and kept for particular periods in each works and place of enterprise on inspection of processing facilities, control of dose, operation, maintenance, accident of processing facilities and weather. Specified measures shall be taken in controlled area and inspected surrounding area to restrict entrance. Measures shall be made not to exceed permissible exposure dose for employees defined by the Director General of Science and Technology Agency. Inspection and check up of processing facilities shall be carried on by employees more than once a day. Operation of processing facilities, transportation in the works and enterprise, storage, disposal, safety securing, report and measures in dangerous situations, etc. are in detail prescribed. (Okada, K.)
Toward introduction of risk informed safety regulation. Nuclear Safety Commission taskforce's interim report

International Nuclear Information System (INIS)

2006-01-01

Nuclear Safety Commission's taskforce on 'Introduction of Safety Regulation Utilizing Risk Information' completed the interim report on its future subjects and directions in December 2005. Although current safety regulatory activities have been based on deterministic approach, this report shows the risk informed approach is expected to be very useful for making nuclear safety regulation and assurance activities reasonable and also for appropriate allocation of regulatory resources. For introduction of risk informed regulation, it also recommends pileups of experiences with gradual introduction and trial of the risk informed approach, improvement of plant maintenance rules and regulatory requirements utilizing risk information, and establishment of framework to assure quality of risk evaluation. (T. Tanaka)
An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

International Nuclear Information System (INIS)

Garcia, C.C.; Topisirovic, I.; Djavani, M.; Borden, K.L.B.; Damonte, E.B.; Salvato, M.S.

2010-01-01

The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.
Experimental nuclear thermoelectric assembly open-quotes Gammaclose quotes-a prototype of an unattended self-regulating nuclear thermoelectric station

International Nuclear Information System (INIS)

Buinitskii, B.A.; Kaplar, E.P.; Kondrat'ev, F.V.; Leppik, P.A.; Nafikov, D.Ya.; Pavelko, V.I.; Rychev, A.S.; Tarasov, V.P.; Khlopkin, N.S.

1993-01-01

At the beginning of the seventies, the concept of building small atomic power stations with direct conversion of the thermal energy of a reactor for supplying electricity and heat to consumers located at remote and inaccessible regions was developed on the basis of assessment calculations and technical studies made in the I.V. Kurchatov Institute of Atomic Energy. When new technical solutions were adopted to put this concept into practice, combined trials on a test stand were required. For this purpose, the nuclear thermoelectric test-demonstration assembly open-quotes Gammaclose quotes was built and put into operation in 1981. It is based on the three principles which determine the development of unattended self-regulating nuclear thermoelectric stations: using a water-water reactor with self-regulation of the power as a source of heat; using a cooling system without pumps but with natural circulation of the coolant in the primary and intermediate circuits for removing the hend thermoelectric conversion of heat into electricity. During the ten years of operation of the open-quotes Gammaclose quotes assembly, a research program on the principles of unattended self-regulating nuclear thermoelectric stations was carried out and the results are summarized
The Role of the Regulator in the Field of Safety Culture to Shun Nuclear Accident

International Nuclear Information System (INIS)

Kandil, M.M.

2016-01-01

The 2011 accident at the Fukushima Daiichi nuclear power plant in Japan has, as might be expected, led to improvements in equipment at plants around the world that have fortified safety systems and allowed for better protection against rare, extreme natural events. Equally important to the process of improving nuclear safety is the emphasis placed on implementing quality improvements to the human side of nuclear safety, a crucial element that is often not considered by those outside the nuclear sector. Ensuring nuclear reactor safety is not only a question of physical protection against all credible threats, enhancing robustness of important safety systems and increasing redundancy of back-up power and water cooling systems, but also one of making certain that qualified and trained staff are supported by effective procedures. However, these assets are valued only in an organizational culture that places a premium on ensuring high levels of safety, or implementing what is called an effective “nuclear safety culture”. Principles, characteristics and factors for effective safety culture are to great extent similar between licencees and regulatory bodies and can be applied for developing RB’s safety. Safety is the primary purpose of the regulatory body, Regulator plays a significant role in the field of nuclear safety even though the prime responsibility for safety belongs to the operator, and it is the regulator which actually decides what is considered to be safe. In order to effectively implement the international principle of high level of nuclear safety, nuclear safety culture should be clearly named as an objective in international nuclear legal acts and the regulator’s responsibility for promotion of nuclear safety culture should be established. What is more difficult for the regulator is finding the right balance of firmness but fairness in dealing with the operator. In addition to enforcing safety regulations, the regulator should have a positive
Order for execution of the law concerning regulations of nuclear source materials, nuclear fuel materials and reactors

International Nuclear Information System (INIS)

1985-01-01

This ordinance is stipulated under the law concerning the regulation of nuclear raw materials, nuclear fuel materials and reactors. The designation for refining and processing businesses under the law shall be obtained for each works or enterprise where these operations are to be practiced. Persons who intend to accept the designation shall file applications attaching business plans and the other documents specified by the ordinances of the Prime Minister's Office and other ministry orders. The permission for the installation of nuclear reactors under the law shall be received for each works or enterprise where reactors are to be set up. Persons who intend to get the permission shall file applications attaching the financing plans required for the installation of reactors and the other documents designated by the orders of the competent ministry. The permission concerning the reactors installed on foreign ships shall be obtained for each ship which is going to enter into the Japanese waters. Persons who ask for the permission shall file applications attaching the documents which explain the safety of reactor facilities and the other documents defined by the orders of the Ministry of Transportation. The designation for reprocessing business and the application for it are provided for, respectively. The usage of nuclear fuel materials, nuclear raw materials and internationally regulated goods is ruled in detail. (Kubozone, M.)
Order for execution of the law concerning regulations of nuclear source materials, nuclear fuel materials and reactors

International Nuclear Information System (INIS)

1981-01-01

This ordinance is stipulated under the law concerning the regulation of nuclear raw materials, nuclear fuel materials and reactors. The designation for refining and processing businesses under the law shall be obtained for each works or enterprise where these operations are to be practiced. Persons who intend to accept the designation shall file applications attaching business plans and the other documents specified by the ordinances of the Prime Minister's Office and other ministry orders. The permission for the installation of nuclear reactors under the law shall be received for each works or enterprise where reactors are to be set up. Persons who intend to get the permission shall file applications attaching the financing plans required for the installation of reactors and the other documents designated by the orders of the competent ministry. The permission concerning the reactors installed on foreign ships shall be obtained for each ship which is going to enter into the Japanese waters. Persons who ask for the permission shall file applications attaching the documents which explain the safety of reactor facilities and the other documents defined by the orders of the Ministry of Transportation. The designation for reprocessing business and the application for it are provided for, respectively. The usage of nuclear fuel materials, nuclear raw materials and internationally regulated goods is ruled in detail.(Okada, K.)
Probabilistic risk assessment in nuclear power plant regulation

Energy Technology Data Exchange (ETDEWEB)

Wall, J B

1980-09-01

A specific program is recommended to utilize more effectively probabilistic risk assessment in nuclear power plant regulation. It is based upon the engineering insights from the Reactor Safety Study (WASH-1400) and some follow-on risk assessment research by USNRC. The Three Mile Island accident is briefly discussed from a risk viewpoint to illustrate a weakness in current practice. The development of a probabilistic safety goal is recommended with some suggestions on underlying principles. Some ongoing work on risk perception and the draft probabilistic safety goal being reviewed on Canada is described. Some suggestions are offered on further risk assessment research. Finally, some recent U.S. Nuclear Regulatory Commission actions are described.
Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors

Directory of Open Access Journals (Sweden)

Jasmine Kolb

2018-04-01

Full Text Available Summary: Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate. : A hallmark of adult neurogenesis is its strong dependence on physiological stimuli and environmental signals. Schulte and colleagues show that the nuclear localization and activity of a transcriptional regulator of adult neurogenesis is controlled by posttranslational modification. Their results link intrinsic control over neuron production to external signals and help to explain how adult neurogenesis can occur “on demand.” Keywords: subventricular zone, stem cell niche, posttranslational modification, controlled nuclear import, TALE-homdomain protein, MEIS2, PBX1, CRM1, neurogenesis, stem cell niche
Statutory Instrument No. 2056, The Nuclear Installations Act 1965 etc. (Repeals and Modifications) Regulations 1974

International Nuclear Information System (INIS)

1975-01-01

These Regulations contain repeals and modifications of provisions of the Nuclear Installations Act 1965 and a modification of the Nuclear Installations (Dangerous Occurrences) Regulations 1965. They are made in consequence of the establishment on 1st January 1975 of the Health and Safety Executive and the coming into operation on that date of provisions of the Health and Safety at Work etc. Act 1974 which supersede or affect provisions of the 1965 Act and the 1965 Regulations. (NEA) [fr
The regulation of radioactive effluent release in France (mainly from large nuclear installations)

International Nuclear Information System (INIS)

Hebert, Jean.

1978-01-01

In parallel with the licensing system for construction and operation of classified or so-called large nuclear installations (INB) there are in France regulations for the release of radioactive effuents from such installations. The regulations applicable to installations other than INBs are not specifically of a nuclear nature, while those covering INBs, which are analysed in this study, in particular, cover effluent release in liquid or gaseous form. The licensing and control procedures for such release are analysed in detail. (NEA) [fr
Spatiotemporal Regulation of Nuclear Transport Machinery and Microtubule Organization

Science.gov (United States)

Okada, Naoyuki; Sato, Masamitsu

2015-01-01

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

International Nuclear Information System (INIS)

Kim, Daesik; Ahn, Seunghoon; Auh, Geunsun; Lee, Jonghyeok

2015-01-01

The so-called Periodic Safety Review (PSR) has been carried out such safety assessment throughout its life, on a periodic basis. In January 2001, the Atomic Energy Act and related regulations were amended to adopt the PSR institutional scheme from IAEA Nuclear Safety Guide 50-SG-O12. At that time the safety assessment was made to review the plant safety on 10 safety factors, such as aging management and emergency planning, where the safety factor indicates the important aspects of safety of an operating NPP to be addressed in the PSR. According to this legislation, the domestic utility, the KHNP has conducted the PSR for the operating NPP of 10 years coming up from operating license date, starting since May 2000. Some revisions in the PSR rule were made to include the additional safety factors last year. This paper introduces the current status of the PSR review and regulation, in particular new safety factors and updated technical regulation. Comprehensive safety assessment for Korea Nuclear Power Plants have performed a reflecting design and procedure changes and considering the latest technology every 10 years. This paper also examined the PSR system changes in Korea. As of July 2015, reviews for PSR of 18 units have been completed, with 229 nuclear safety improvement items. And implementation have been completed for 165 of them. PSR system has been confirmed that it has contributed to improvement of plant safety. In addition, this paper examined the PSR system change in Korea

Improving the regulation of safety at DOE nuclear facilities. Final report: Appendices

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-12-01

The report strongly recommends that, with the end of the Cold War, safety and health at DOE facilities should be regulated by outside agencies rather than by any regulatory scheme, DOE must maintain a strong internal safety management system; essentially all aspects of safety at DOE`s nuclear facilities should be externally regulated; and existing agencies rather than a new one should be responsible for external regulation.
Improving the regulation of safety at DOE nuclear facilities. Final report: Appendices

International Nuclear Information System (INIS)

1995-12-01

The report strongly recommends that, with the end of the Cold War, safety and health at DOE facilities should be regulated by outside agencies rather than by any regulatory scheme, DOE must maintain a strong internal safety management system; essentially all aspects of safety at DOE's nuclear facilities should be externally regulated; and existing agencies rather than a new one should be responsible for external regulation
Cost-benefit comparison of nuclear and nonnuclear health and safety protective measures and regulations

International Nuclear Information System (INIS)

O'Donnell, E.P.; Mauro, J.J.

1979-01-01

This article compares the costs and benefits of health and safety measures and regulations in the nuclear and nonnuclear fields. A cost-benefit methodology for nuclear safety concerns is presented and applied to existing nuclear plant engineered safety features. Comparisons in terms of investment costs to achieve reductions in mortality rates are then made between nuclear plant safety features and the protective measures and regulations associated with nonnuclear risks, particularly with coal-fired power plants. These comparisons reveal a marked inconsistency in the cost effectiveness of health and safety policy, in which nuclear regulatory policy requires much greater investments to reduce the risk of public mortality than is required in nonnuclear areas where reductions in mortality rates could be achieved at much lower cost. A specific example of regulatory disparity regarding gaseous effluent limits for nuclear and fossil-fuel power plants is presented. It is concluded that a consistent health and safety regulatory policy based on uniform risk and cost-benefit criteria should be adopted and that future proposed Nuclear Regulatory Commission regulatory requirements should be critically evaluated from a cost-benefit viewpoint
Regulation of the life cycle of nuclear installations. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-06-01

This report arises from the sixth series of peer discussions on regulatory practices entitled 'Regulation of Life Cycle of Nuclear Installations'. Senior regulators from 18 Member States participated in three peer group discussions during 1997-1998. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the nominating organizations, or the IAEA. The purpose of this report is to disseminate the views which the senior regulators presented at the meetings relating to the policies, principles and requirements imposed by regulatory bodies for the safe management of the life cycle of a nuclear installation. The intention of doing this is to assist Member States in the formulation and enhancement of their regulatory control over PLCM by identifying commonly accepted good practices. This report is structured to cover the subject matter under the following main headings: Policies and Principles for the Life Cycle Management of Nuclear Installations; Responsibilities of the Regulatory Body and the Operating Organization; Requirements and Criteria Imposed by the Regulatory Body; Licensing and Regulatory Assessment for Plant Life Cycle Management; and Good Practices
Nuclear regulator practices for communicating with the public

International Nuclear Information System (INIS)

Hayden, E.

2007-01-01

For decades, the U.S. Nuclear Regulatory Commission has communicated with members of the public so that they are aware of what the NRC does to protect them from the hazards of unnecessary radiation from nuclear power plants and other uses of radioactive material. Because the agency views nuclear regulation as the public's business, it should be transacted openly and candidly in order to maintain the public's confidence. The NRC recognizes that the public must be informed about, and have a reasonable opportunity to participate meaningfully in, the Agency's regulatory processes. The agency uses a variety of means to ensure openness in its regulatory process and thereby increasing public confidence. With rapidly expanding electronic capability, the agency has looked to new ways to reach out to the American public to let them know we are on the job overseeing nuclear safety. While we continue to communicate in some of the traditional ways - news releases, news conferences, briefing, speeches, Internet, brochures, and meetings - we are also exploring using blogs, mobile cell phone notifications, focus groups, open houses, and e-mail alerts to name a few. (author)
Regulation and inspection support radiation protection in nuclear and other installations

International Nuclear Information System (INIS)

Williams, M.K.; Potter, C.; Harbison, S.A.

1996-01-01

Over the past fifty years, radiation protection legislation in the UK has developed from a narrow industry-specific base to a comprehensive package of regulations and supporting Approved Code of Practice, with additional provisions for nuclear installations. Development of this legislation mirrors progress in international understanding about the risks from exposure to ionising radiation. The current Ionising Radiations Regulations 1985 largely implement the Euratom 1980 Basic Safety Standards Directive and place particular emphasis on the need to keep exposure as low as reasonably practicable. The regulations have been underpinned by the development of the concept of the Tolerability of Risk and the application of the ALARP/ALARA principle, particularly at nuclear installations. Analysis of dose data on HSE's Central Index of Dose Information has shown the general success of this approach in the UK; the data have also allowed targeting of inspection effort. Currently, the Health and Safety Commission and Executive are developing plans for implementing the revised EU Basic Safety Standards Directive. (author)
Regulations by the DFTCE concerning the Fund for the decommissioning of nuclear installations

International Nuclear Information System (INIS)

1985-02-01

These Regulations were made by the Federal Ministry of Transport, Communications and Energy in implementation of the Ordinance of 5 December 1983 establishing a fund for the decommissioning of nuclear installations. They specify the way in which nuclear operators must contribute to the fund and the method for calculating the contributions. The costs of decommissioning also include dismantling and disposal of the resulting waste. The Regulations entered into force retroactively, on 1 January 1984, on the same date as the 1983 Ordinance. (NEA) [fr
The Swedish Radiation Protection Institute's regulations concerning the final management of spent nuclear fuel and nuclear waste - with background and comments

International Nuclear Information System (INIS)

2000-11-01

This report presents and comments on the Swedish Radiation Protection Institute's Regulations concerning the Protection of Human Health and the Environment in connection with the Final Management of Spent Nuclear Fuel or Nuclear Waste, SSI FS 1998: 1
Some internationl law elements of national nuclear regulations from the Polish point of view

International Nuclear Information System (INIS)

Gadkowski, T.

1992-01-01

The essential contents of the Polish Nuclear Act from 1986 reflects on one hand needs and possibilities of the industrial use of nuclear energy and, on the other, international obligations of Poland. Poland is a State with a limited activity regarding to industrial use of nuclear energy; the main international-law elements of national nuclear regulations can be described as follows: 1. The good-neighborliness principle concerning the siting of nuclear installations in border areas. 2. An adequate concept of nuclear damage. 3. An adequate concept of liability for nuclear damage. (orig./HSCH)
The nuclear safety regulation in Japan and the response to changes of circumstances surrounding the nuclear electricity generation

International Nuclear Information System (INIS)

Hombu, K.; Hirota, M.; Taniguchi, T.; Tanaka, N.; Akimoto, S.

2001-01-01

The influences of external factors on nuclear safety are discussed in this paper, based on the views on the circumstances of nuclear electricity generation. The following external factors, which might have some potential impacts on nuclear safety, are selected for discussion: (1) The deregulation in the electricity generation industry; (2) The modification of approval/certification system in the regulation of electricity generation; (3) The influences on social atmosphere due to the occurrence of a series of troubles; (4) The government reform and the structural adjustment of industry and (5) Others. Our further discussion seems to focus on the following 2 issues: (a) Whether nuclear power and the other electrical sources should compete with each other for short term economical cost, or whether factors of cost stability and competitiveness as well as longer term energy supply security and global environmental issues ranging over several decades should be considered; (b) How to realize the appropriate regulation from the perspective of public acceptance and confidence (when a series of troubles occur) without imposing unnecessary burdens on industry and without jeopardizing safety. These issues may be common among many countries and can be widely discussed. (author)
Governmental organization for the regulation of nuclear power plants. A code of practice

International Nuclear Information System (INIS)

1978-01-01

This Code of Practice recommends requirements for a regulatory body responsible for regulating the siting, construction, commissioning, operation and decommissioning of nuclear power plants for safety. It forms part of the Agency's programme, referred to as the NUSS programme, for establishing Codes of Practice and Safety Guides relating to land-based stationary thermal neutron power plants. This Code has been prepared to provide recommendations for Member States embarking on a nuclear power programme and covers: (1) Establishing and maintaining a regulatory body to which is assigned the responsibility for authorizing the siting, construction, commissioning, operation and decommissioning of nuclear power plants after appropriate review and assessment (2) Organizing for and conducting the review and assessment of the safety of nuclear power plants (3) Conducting the necessary regulatory inspections and taking necessary enforcement actions during all stages of the licensing process in order to ensure that the limits and conditions of the licences are being complied with by the applicants/licensees and their contractors (4) Establishing regulations and criteria for nuclear-related health, safety and environmental protection
The legal regime governing the peaceful uses of nuclear energy. II. International Regulations. Pt.1. Regulations on peaceful uses

International Nuclear Information System (INIS)

1979-12-01

The first volume on atomic energy law published by CNEN reproduced national laws and regulations in that field. This book constitutes part one of the second volume and deals with international nuclear conventions and cooperation as at 30 June 1978. It reproduces the instruments and conventions which set up the international nuclear agencies, recommendations in the field of radiation protection and nuclear safety, the nuclear third party liability conventions, the international instruments concerning technical and scientific cooperation and finally, the bilateral cooperation agreements between Italy and other nations and its agreements with international organizations (NEA) [fr
Nuclear translocation contributes to regulation of DNA excision repair activities

DEFF Research Database (Denmark)

Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne

2009-01-01

for regulation of nuclear import that is necessary for proper localization of the repair proteins. This review summarizes the current knowledge on nuclear import mechanisms of DNA excision repair proteins and provides a model that categorizes the import by different mechanisms, including classical nuclear import......DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA......, it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927-939; M. Christmann, M...
Different regulatory strategies in regulation of nuclear power projects: An Indian experience

International Nuclear Information System (INIS)

Khan, Sohail Ahmad

2002-01-01

Regulatory strategy needed for management of safety and safety culture involves careful planning and use of engineering concepts keeping in mind feasibility to implement certain safety requirements. It also requires adequate attention on working environment and mental conditions of designers, operating and maintenance staff and regulators. Different strategies followed during safety review and regulatory inspection of nuclear power projects for improving status of safety management and safety cultures have given certain results. The present paper brings out certain experience gained during regulation of Indian Nuclear Power Projects by Atomic Energy Regulatory Board of India in the area of management of safety and safety culture. (author)
Regulatory control, nuclear safety regulation and waste management in Spain

International Nuclear Information System (INIS)

Martin, A.

2000-01-01

This article presents the challenges that faces the spanish regulatory authority. The deregulation of electricity industry imposes severe changes in nuclear power economics and forces nuclear power to compete with other sources of electricity. A pressure is perceived for regulatory effectiveness primarily since the cost of regulation is a component of the cost of the product. This effectiveness gain in regulatory control will be reached through systematic strategic analysis, formulation and implementation. The regulatory aspects of plant life extension and of waste management are examined
Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID.

Directory of Open Access Journals (Sweden)

Quy Le

2015-09-01

Full Text Available AID (Activation Induced Deaminase deaminates cytosines in DNA to initiate immunoglobulin gene diversification and to reprogram CpG methylation in early development. AID is potentially highly mutagenic, and it causes genomic instability evident as translocations in B cell malignancies. Here we show that AID is cell cycle regulated. By high content screening microscopy, we demonstrate that AID undergoes nuclear degradation more slowly in G1 phase than in S or G2-M phase, and that mutations that affect regulatory phosphorylation or catalytic activity can alter AID stability and abundance. We directly test the role of cell cycle regulation by fusing AID to tags that destabilize nuclear protein outside of G1 or S-G2/M phases. We show that enforced nuclear localization of AID in G1 phase accelerates somatic hypermutation and class switch recombination, and is well-tolerated; while nuclear AID compromises viability in S-G2/M phase cells. We identify AID derivatives that accelerate somatic hypermutation with minimal impact on viability, which will be useful tools for engineering genes and proteins by iterative mutagenesis and selection. Our results further suggest that use of cell cycle tags to regulate nuclear stability may be generally applicable to studying DNA repair and to engineering the genome.
PHITS code improvements by Regulatory Standard and Research Department Secretariat of Nuclear Regulation Authority

International Nuclear Information System (INIS)

Goko, Shinji

2017-01-01

As for the safety analysis to be carried out when a nuclear power company applies for installation permission of facility or equipment, business license, design approval etc., the Regulatory Standard and Research Department Secretariat of Nuclear Regulation Authority continuously conducts safety research for the introduction of various technologies and their improvement in order to evaluate the adequacy of this safety analysis. In the field of the shielding analysis of nuclear fuel transportation materials, this group improved the code to make PHITS applicable to this field, and has been promoting the improvement as a tool used for regulations since FY2013. This paper introduced the history and progress of this safety research. PHITS 2.88, which is the latest version as of November 2016, was equipped with the automatic generation function of variance reduction parameters [T-WWG] etc., and developed as the tool equipped with many effective functions in practical application to nuclear power regulations. In addition, this group conducted the verification analysis against nuclear fuel packages, which showed a good agreement with the analysis by MCNP, which is extensively used worldwide and abundant in actual results. It also shows a relatively good agreement with the measured values, when considering differences in analysis and measurement. (A.O.)
Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors.

Science.gov (United States)

Kolb, Jasmine; Anders-Maurer, Marie; Müller, Tanja; Hau, Ann-Christin; Grebbin, Britta Moyo; Kallenborn-Gerhardt, Wiebke; Behrends, Christian; Schulte, Dorothea

2018-04-10

Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Influence on UK Nuclear Regulation from the Fukushima Daiichi Accident

International Nuclear Information System (INIS)

Savage, R.

2016-01-01

This paper provides an overview of the UKs response to the Fukushima Daiichi Accident and highlights the influence that this has had on UK nuclear regulation since March 2011. ONR’s Incident Suite was staffed from the first day of the accident and remained active on a 24 hours basis for over two weeks. The purpose was to provide advice to the UK government specifically prompt assurance of why this accident couldn’t take place in the UK and practical advice in relation to the 17,000 UK nationals in Japan at that time. In the early phase of the accident ONR took part in international cooperation with the US, Canadian and French regulators in order to determine the actual technical status of the Fukushima Daiichi power plant units. The UK Secretary of State requested that the ONR Chief Inspector identify any lessons to be learnt by the UK nuclear industry and in doing so cooperate and coordinate with international colleagues. The Interim report was produced (May 2011) this focused on civil NPP’s, provided background to radiation, technology and regulations. This report compared the Japan situation with the UK and identified 11 conclusions and 26 recommendations.
A fresh start of nuclear safety regulation and international perspective

International Nuclear Information System (INIS)

Oshima, Kenzo

2013-01-01

It should be explained more to the outside modestly the Fukushima nuclear accident would be a man-made complex disaster, which might be reluctant to do but not be neglected. Utmost efforts to change inward-looking attitude and reform safety culture should be done so as to prevent superficial reflection of the Fukushima nuclear accident. Since all nuclear regulatory functions ('3S': safety, security, safeguards) were integrated in Nuclear Regulation Authority (NRA), NRA and secretariat of NRA became more responsible for international response, and strengthening of organization system and human resources development would be an urgent necessity. This article described present stage of NRA focusing on international dimension including personal views. Overseas strong concern over the Fukushima nuclear accident and international communications were reviewed. The Fukushima nuclear accident started from natural disaster and enlarged as a man-made complex disaster with many human factors (mainly inaction, wilful negligence) overlapping and safety culture flawed. Examples of overseas and Japanese action plan to learn and absorb lessons from the Fukushima accident were introduced. NRA's started activities on inviting IAEA's IRRS and OPPAS as soon as ready, strengthening nuclear security measures, safeguards to prevent nuclear proliferation, bilateral cooperation and international advisors were also presented. (T. Tanaka)

Comparative Study Between The IAEA Model Regulations and The Egyptian Nuclear Law

International Nuclear Information System (INIS)

Abaza, A.; Hosni, M.

2015-01-01

This study deals with the security of radioactive sources due to its great importance, in order to provide the adequate security of these sources from the threat of theft, sabotage, illegal seizure through doing a comparison between the model regulations of the International Atomic Energy Agency (IAEA) (11) and the Egyptian law (No. 7/2010) that regulates nuclear and radiation activities and its executive regulations. The Egyptian legislator has put a chapter entitled n uclear security w ith the aim of organizing the security of nuclear materials. However, there was a review to some regulatory rules issued by the IAEA on the security of these sources which include the responsibilities of the licensee towards it. This chapter also, addressed the security culture through rehabilitation and training, in addition to the obligations of the competent authorities who is responsible for the process of issuing the license when full requirements are met. It has been shown that the Egyptian law and its executive regulations contained the rule that provides the necessary protection for these radioactive sources. Furthermore, more regulations are still needed to provide adequate security and more protection for the radioactive sources and its facilities
Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition

International Nuclear Information System (INIS)

Matsumoto, Hotaru; Saitoh, Hisato

2016-01-01

We have previously reported the co-localization of O-propargyl-puromycin (OP-Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML-NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of the SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus. -- Highlights: •Puromycin exhibits the O-propargyl-puromycin effect. •Puromycin induces SUMO redistribution upon proteasome inhibition. •Ubiquitin and RNF4 accumulate at PML-nuclear bodies with SUMO-2/3. •The ubiquitin family may function in nuclear sequestration of immature proteins.
Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition

Energy Technology Data Exchange (ETDEWEB)

Matsumoto, Hotaru [Course for Biological Sciences, Faculty of Science, Kumamoto University, Kumamoto (Japan); Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp [Course for Biological Sciences, Faculty of Science, Kumamoto University, Kumamoto (Japan); Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto (Japan)

2016-07-29

We have previously reported the co-localization of O-propargyl-puromycin (OP-Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML-NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of the SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus. -- Highlights: •Puromycin exhibits the O-propargyl-puromycin effect. •Puromycin induces SUMO redistribution upon proteasome inhibition. •Ubiquitin and RNF4 accumulate at PML-nuclear bodies with SUMO-2/3. •The ubiquitin family may function in nuclear sequestration of immature proteins.
The Independence of the Nuclear Regulator: Notes from the Canadian Experience

International Nuclear Information System (INIS)

MacKenzie, B.

2010-01-01

The firing of Linda Keen as president and chief executive Officer of the Canadian Nuclear Safety Commission provoked considerable debate within Canada and internationally about the independence of the canadian nuclear regulator. ms. Keen was dismissed from her position from her position at the height of the crisis over a world-wide shortage of medical isotopes caused by the shutdown of the research reactor in Chalk river, Ontario. Under the terms of its licence, the reactor was required to have cooling pumps connected to an emergency power supply as a backup in case of a power outage caused by an event such an earthquake. In november 2007, after it was discovered that the pumps were not connected, the reactor was shut down. As panic over the shortage of medical isotopes grew, the government took three extraordinary measures: first, it issued a directive; second, it introduced emergency legislation in Parliament; and finally, it fired Linda Keen as President of the Commission. This paper examines those three measures and whether they constituted an unwarranted interference with the independence of the Canadian nuclear regulator. (N.C.)
Regulations concerning the transport of nuclear fuel materials outside the works or the enterprise

International Nuclear Information System (INIS)

1979-01-01

The regulations are defined under the law for the regulations of nuclear source materials, nuclear fuel materials and reactors and the order for execution of the law. Basic concepts and terms are explained, such as: vehicle transport; easy transport; nuclear fuel material load, exclusive loading, employee, accumulative dose and exposure dose. Technical standards of vehicle transport are specified in detail on nucler fuel materials as nuclear fuel load, L,A, EM and BU type of load, nuclear fuel load of fission substances, the second and third type of fission load and materials contaminated by nuclear fuel substances to be carried not as nuclear fuel loads. Special exceptional measures to such transport and technical standards of easy transport are also designated. The application for confirmation of the transport shall be filed to the Director General of Science and Technology Agency according to the form attached with documents explaining nuclear fuel materials to be transferred, the vessel of such materials and construction, material and method of production of such a vessel, safety of nuclear materials contained, etc. Measures in dangerous situations shall be taken to fight a fire or prohibit the entrance of persons other than the staff concerned. Reports shall be presented in 10 days to the Director, when theft, loss or irregular leaking of nuclear fuel materials or personal troubles occur on the way. (Okada, K.)
Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export

Directory of Open Access Journals (Sweden)

Marriott Susan J

2007-12-01

Full Text Available Abstract Background The HTLV-I oncoprotein, Tax, is a pleiotropic protein whose activity is partially regulated by its ability to interact with, and perturb the functions of, numerous cellular proteins. Tax is predominantly a nuclear protein that localizes to nuclear foci known as Tax Speckled Structures (TSS. We recently reported that the localization of Tax and its interactions with cellular proteins are altered in response to various forms of genotoxic and cellular stress. The level of cytoplasmic Tax increases in response to stress and this relocalization depends upon the interaction of Tax with CRM1. Cellular pathways and signals that regulate the subcellular localization of Tax remain to be determined. However, post-translational modifications including sumoylation and ubiquitination are known to influence the subcellular localization of Tax and its interactions with cellular proteins. The sumoylated form of Tax exists predominantly in the nucleus while ubiquitinated Tax exists predominantly in the cytoplasm. Therefore, we hypothesized that post-translational modifications of Tax that occur in response to DNA damage regulate the localization of Tax and its interactions with cellular proteins. Results We found a significant increase in mono-ubiquitination of Tax in response to UV irradiation. Mutation of specific lysine residues (K280 and K284 within Tax inhibited DNA damage-induced ubiquitination. In contrast to wild-type Tax, which undergoes transient nucleocytoplasmic shuttling in response to DNA damage, the K280 and K284 mutants were retained in nuclear foci following UV irradiation and remained co-localized with the cellular TSS protein, sc35. Conclusion This study demonstrates that the localization of Tax, and its interactions with cellular proteins, are dynamic following DNA damage and depend on the post-translational modification status of Tax. Specifically, DNA damage induces the ubiquitination of Tax at K280 and K284
p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1.

Directory of Open Access Journals (Sweden)

Xiao-Su Zhao

Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC-interacting factor 1 (NIF-1, is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.
p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1).

Science.gov (United States)

Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W Y; Li, Zhen; Fu, Amy K Y; Ip, Nancy Y

2014-01-01

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.
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
The Process of Legal Drafting Regulation in the Development of the Nuclear Power Plant in Indonesia

OpenAIRE

Mardha, Amil

2009-01-01

THE PROCESS OF LEGAL DRAFTING REGULATION IN THE DEVELOPMENT OF THE NUCLEAR POWER PLANT IN INDONESIA. In Indonesia, the process of legal drafting to establish the regulation is based on the Act No. 10 Year 2004 on the Establishment of Legislation. The process shall comply with the constitutional and institutional requirements of national political and legal system. In drafting the development of the regulation of nuclear energy, BAPETEN has been involving some other agencies or other related g...
A decade of natalizumab and PML: Has there been a tacit transfer of risk acceptance?

Science.gov (United States)

Clifford, David B; Yousry, Tarek A; Major, Eugene O

2017-06-01

The interplay between each of the stakeholder's responsibilities and desires clearly has resulted in continued widespread use of natalizumab with substantial risks and an ongoing quest for better risk mitigation. In the United States, regulatory actions codified the process of risk acceptance-and risk transfer-by escalating monitoring and information transfer to physicians and patients. Management of medication-related risks is a core function of regulatory agencies such as the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the medical community. The interaction among stakeholders in medicine, pharma, regulatory bodies, physicians, and patients, sometimes has changed without overt review and discussion. Such is the case for natalizumab, an important and widely used disease-modifying therapy for multiple sclerosis. A rather silent but very considerable shift, effectively transferring increased risk for progressive multifocal leukoencephalopathy (PML) to the physicians and patients, has occurred in the past decade. We believe this changed risk should be clearly recognized and considered by all the stakeholders.
Nuclear deterrents: Intrinsic regulators of IL-1β-induced effects on hippocampal neurogenesis.

Science.gov (United States)

O'Léime, Ciarán S; Cryan, John F; Nolan, Yvonne M

2017-11-01

Hippocampal neurogenesis, the process by which new neurons are born and develop into the host circuitry, begins during embryonic development and persists throughout adulthood. Over the last decade considerable insights have been made into the role of hippocampal neurogenesis in cognitive function and the cellular mechanisms behind this process. Additionally, an increasing amount of evidence exists on the impact of environmental factors, such as stress and neuroinflammation on hippocampal neurogenesis and subsequent impairments in cognition. Elevated expression of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the hippocampus is established as a significant contributor to the neuronal demise evident in many neurological and psychiatric disorders and is now known to negatively regulate hippocampal neurogenesis. In order to prevent the deleterious effects of IL-1β on neurogenesis it is necessary to identify signalling pathways and regulators of neurogenesis within neural progenitor cells that can interact with IL-1β. Nuclear receptors are ligand regulated transcription factors that are involved in modulating a large number of cellular processes including neurogenesis. In this review we focus on the signalling mechanisms of specific nuclear receptors involved in regulating neurogenesis (glucocorticoid receptors, peroxisome proliferator activated receptors, estrogen receptors, and nuclear receptor subfamily 2 group E member 1 (NR2E1 or TLX)). We propose that these nuclear receptors could be targeted to inhibit neuroinflammatory signalling pathways associated with IL-1β. We discuss their potential to be therapeutic targets for neuroinflammatory disorders affecting hippocampal neurogenesis and associated cognitive function. Copyright © 2017 Elsevier Inc. All rights reserved.
Nuclear movement regulated by non-Smad Nodal signaling via JNK is associated with Smad signaling during zebrafish endoderm specification.

Science.gov (United States)

Hozumi, Shunya; Aoki, Shun; Kikuchi, Yutaka

2017-11-01

Asymmetric nuclear positioning is observed during animal development, but its regulation and significance in cell differentiation remain poorly understood. Using zebrafish blastulae, we provide evidence that nuclear movement towards the yolk syncytial layer, which comprises extraembryonic tissue, occurs in the first cells fated to differentiate into the endoderm. Nodal signaling is essential for nuclear movement, whereas nuclear envelope proteins are involved in movement through microtubule formation. Positioning of the microtubule-organizing center, which is proposed to be crucial for nuclear movement, is regulated by Nodal signaling and nuclear envelope proteins. The non-Smad JNK signaling pathway, which is downstream of Nodal signaling, regulates nuclear movement independently of the Smad pathway, and this nuclear movement is associated with Smad signal transduction toward the nucleus. Our study provides insight into the function of nuclear movement in Smad signaling toward the nucleus, and could be applied to the control of TGFβ signaling. © 2017. Published by The Company of Biologists Ltd.
Legal and administrative problems in regulating public participation in licensing of nuclear installations

International Nuclear Information System (INIS)

Cornelis, J.C.

1981-10-01

This general analysis of the question of public acceptance of nuclear activities focuses on the problems met by all governmental authorities in implementing their nuclear programmes. The author highlights the need for more specific regulations aimed at guaranteeing fuller information of the public and ensuring closer participation by it. (NEA) [fr
Regulations for the safe management of radioactive wastes and spent nuclear fuel

International Nuclear Information System (INIS)

Voica, Anca

2007-01-01

The paper presents the national, international and European regulations regarding radioactive waste management. ANDRAD is the national authority charged with nation wide coordination of safe management of spent fuel and radioactive waste including their final disposal. ANDRAD's main objectives are the following: - establishing the National Strategy concerning the safety management of radioactive waste and spent nuclear fuel; - establishing the national repositories for the final disposal of the spent nuclear fuel and radioactive waste; - developing the technical procedures and establishing norms for all stages of management of spent nuclear fuel and radioactive waste, including the disposal and the decommissioning of the nuclear and radiologic facilities
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.)
The regulator as nuclear communicator

International Nuclear Information System (INIS)

Beecher, William

2000-01-01

Early last year the Nuclear Regulatory Commission decided on a sea-change in the way it inspects and evaluates the safety performance of the 103 commercial nuclear power reactors in the United States, which together produce about 20 percent of the nation's electricity. The new program takes into account the improvements in performance of the U.S. nuclear industry over the past 20 years and the NRC's desire to apply more objective, timely, safety significant criteria in assessing performance, as well as the need to effectively regulate at a time of shrinking staff and budgets. There also was a desire to increase efficiency and reduce unnecessary regulatory burden on plant operators as they begin to transition from their traditional postures as regional monopolies, with rates fixed by local public utility commissions, into a highly competitive deregulated energy marketplace. A pilot project was decided upon to test the new approach at thirteen power plants at nine sites. At first the pilot was to have run six months, but this was subsequently extended. The current timetable, which itself is subject to change, would review the results of the pilot program, make prudent adjustments, and apply it to the entire industry this spring. To explain the entirely new procedures, the technical staff produced a thick document which Albert Einstein-on his best day-would have had trouble understanding. Thus we found ourselves on the verge of what might have been a public perception disaster undermining faith that the NRC was determined to fulfill our transcendent mission and responsibility to protect public health and safety in the application of nuclear power. The first thing we required was a relatively brief plain language translation, of the highly technical staff paper into something any interested member of the public could readily understand. We urgently needed a clear and simple primer to explain the new program, its rationale, and its advantages over the old approach. In
Human herpesvirus 6B U19 protein is a PML-regulated transcriptional activator that localizes to nuclear foci in a PML-independent manner

DEFF Research Database (Denmark)

Kofod-Olsen, Emil; Ross-Hansen, Katrine; Mikkelsen, Jacob Giehm

2008-01-01

Human herpesvirus 6B (HHV-6B) contains an IE-B domain spanning open reading frames U16/17-U19, based on homology with human cytomegalovirus. Here, the protein product, U19, of the HHV-6B U19 gene is identified as a 47 kDa transcriptional activator. HHV-6B infection or overexpression of U19...
Guidelines for authorities and operators from the EURATOM regulation according to nuclear safety

International Nuclear Information System (INIS)

Karpenstein, Ulrich

2010-01-01

At 22nd July, 2009 the guideline 2009/71/EURATOM on a community framework for the nuclear security of nuclear installations comes into effect. A lot of regulations of this guideline intervene very deeply in the competencies of the member states. In acknowledgment of the national responsibility for nuclear security, the guideline grants large free space to the member states. Thereby, the guideline aims at a general legal framework and a mutual learning process off.
Controlling the atom. The beginnings of nuclear regulation 1946--1962

Energy Technology Data Exchange (ETDEWEB)

Mazuzan, G.T.; Walker, J.S.

1997-08-01

This book traces the early history of nuclear power regulation in the US. It focuses on the Atomic Energy Commission (AEC), the federal agency that until 1975 was primarily responsible for planning and carrying out programs to protect public health and safety from the hazards of the civilian use of nuclear energy. It also describes the role of other groups that figured significantly in the development of regulatory policies, including the congressional Joint Committee on Atomic Energy, federal agencies other than the AEC, state governments, the nuclear industry, and scientific organizations. And it considers changes in public perceptions of and attitudes toward atomic energy and the dangers of radiation exposure. The context in which regulatory programs evolved is a rich and complex mixture of political, legislative, legal, technological, scientific, and administrative history. The basic purpose of this book is to provide the Nuclear Regulatory Commission (NRC), which inherited responsibility for nuclear safety after Congress disbanded the AEC, and the general public with information on the historical antecedents and background of regulatory issues.

Identification of a chemical inhibitor for nuclear speckle formation: Implications for the function of nuclear speckles in regulation of alternative pre-mRNA splicing

Energy Technology Data Exchange (ETDEWEB)

Kurogi, Yutaro; Matsuo, Yota; Mihara, Yuki; Yagi, Hiroaki; Shigaki-Miyamoto, Kaya; Toyota, Syukichi; Azuma, Yuko [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Chuo-ku, Kumamoto 860-8555 (Japan); Igarashi, Masayuki [Laboratory of Disease Biology, Institute of Microbial Chemistry, Shinagawa-ku, Tokyo 141-0021 (Japan); Tani, Tokio, E-mail: ttani@sci.kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Chuo-ku, Kumamoto 860-8555 (Japan)

2014-03-28

Highlights: • We identified tubercidin as a compound inducing aberrant formation of the speckles. • Tubercidin causes delocalization of poly (A){sup +}RNAs from nuclear speckles. • Tubercidin induces dispersion of splicing factors from nuclear speckles. • Tubercidin affects alternative pre-mRNA splicing. • Nuclear speckles play a role in regulation of alternative pre-mRNA splicing. - Abstract: Nuclear speckles are subnuclear structures enriched with RNA processing factors and poly (A){sup +} RNAs comprising mRNAs and poly (A){sup +} non-coding RNAs (ncRNAs). Nuclear speckles are thought to be involved in post-transcriptional regulation of gene expression, such as pre-mRNA splicing. By screening 3585 culture extracts of actinomycetes with in situ hybridization using an oligo dT probe, we identified tubercidin, an analogue of adenosine, as an inhibitor of speckle formation, which induces the delocalization of poly (A){sup +} RNA and dispersion of splicing factor SRSF1/SF2 from nuclear speckles in HeLa cells. Treatment with tubercidin also decreased steady-state MALAT1 long ncRNA, thought to be involved in the retention of SRSF1/SF2 in nuclear speckles. In addition, we found that tubercidin treatment promoted exon skipping in the alternative splicing of Clk1 pre-mRNA. These results suggest that nuclear speckles play a role in modulating the concentration of splicing factors in the nucleoplasm to regulate alternative pre-mRNA splicing.
Sweden: The Swedish nuclear archive regulations and projects related to corporate memory. Annex I-2

International Nuclear Information System (INIS)

2008-01-01

The Swedish radiation protection authority regulations on Filing at Nuclear Plants, SSI FS 1997:1, apply to filing of documentation that has been drawn up or received in connection with practices at nuclear plants. The regulations set out: -The minimum level of documentation; - Archiving requirements; -Availability periods; - Choice of data carrier; - Timely transfer to new media; - Requirements regarding safe keeping of documents. The regulations require that, if the nuclear activity ceases, the archives must be transferred to the Swedish national archives. Examples of the availability periods required for records and environmental specimens are as follows: (a) Operations related measurements - 25 years; (b) Emergency response plan - 50 years; (c) Report of an unusual event - 50 years; (d) Documents relating to final disposal - long term; (e) Environmental specimens - 10 years; (f) Records of measurements on specimens - long term
Isolation of nuclear proteins from flax (Linum usitatissimum L. seed coats for gene expression regulation studies

Directory of Open Access Journals (Sweden)

Renouard Sullivan

2012-01-01

Full Text Available Abstract Background While seed biology is well characterized and numerous studies have focused on this subject over the past years, the regulation of seed coat development and metabolism is for the most part still non-elucidated. It is well known that the seed coat has an essential role in seed development and its features are associated with important agronomical traits. It also constitutes a rich source of valuable compounds such as pharmaceuticals. Most of the cell genetic material is contained in the nucleus; therefore nuclear proteins constitute a major actor for gene expression regulation. Isolation of nuclear proteins responsible for specific seed coat expression is an important prerequisite for understanding seed coat metabolism and development. The extraction of nuclear proteins may be problematic due to the presence of specific components that can interfere with the extraction process. The seed coat is a rich source of mucilage and phenolics, which are good examples of these hindering compounds. Findings In the present study, we propose an optimized nuclear protein extraction protocol able to provide nuclear proteins from flax seed coat without contaminants and sufficient yield and quality for their use in transcriptional gene expression regulation by gel shift experiments. Conclusions Routinely, around 250 μg of nuclear proteins per gram of fresh weight were extracted from immature flax seed coats. The isolation protocol described hereafter may serve as an effective tool for gene expression regulation and seed coat-focused proteomics studies.
Increase of apatite dissolution rate by Scots pine roots associated or not with Burkholderia glathei PML1(12)Rp in open-system flow microcosms

Science.gov (United States)

Calvaruso, Christophe; Turpault, Marie-Pierre; Frey-Klett, Pascale; Uroz, Stéphane; Pierret, Marie-Claire; Tosheva, Zornitza; Kies, Antoine

2013-04-01

The release of nutritive elements through apatite dissolution represents the main source of phosphorus, calcium, and several micronutrients (e.g., Zn, Cu) for organisms in non-fertilized forest ecosystems. The aim of this study was to quantify, for the first time, the dissolution rate of apatite grains by tree roots that were or were not associated with a mineral weathering bacterial strain, and by various acids known to be produced by tree roots and soil bacterial strains in open-system flow microcosms. In addition, we explored whether the mobilization of trace elements (including rare earth elements) upon apatite dissolution was affected by the presence of trees and associated microorganisms. The dissolution rate of apatite by Scots pine plants that were or were not inoculated with the strain Burkholderia glathei PML1(12)Rp, and by inorganic (nitric) and organic (citric, oxalic and gluconic) acids at pH 5.5, 4.8, 3.8, 3.5, 3.0, and 2.0 was monitored in two controlled experiments: "plant-bacteria interaction" and "inorganic and organic acids". Analyses of the outlet solutions in the "plant-bacteria interaction" experiment showed that Scots pine roots and B. glathei PML1(12)Rp produced protons and organic acids such as gluconate, oxalate, acetate, and lactate. The weathering budget calculation revealed that Scots pines (with or without PML1(12)Rp) significantly increased (factor > 10) the release of Ca, P, As, Sr, Zn, U, Y, and rare earth elements such as Ce, La, Nd from apatite, compared to control abiotic treatment. Scanning electron microscopy observation confirmed traces of apatite dissolution in contact of roots. Most dissolved elements were taken up by Scots pine roots, i.e., approximately 50% of Ca, 70% of P, 30% of As, 70% of Sr, 90% of Zn, and 100% of U, Y, and rare earth elements. Interestingly, no significant additional effect due to the bacterial strain PML1(12)Rp on apatite dissolution and Scots pine nutrition and growth was observed. The "inorganic
78 FR 71675 - Update of the Office of Nuclear Reactor Regulation's Electronic Operating Reactor Correspondence

Science.gov (United States)

2013-11-29

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0260] Update of the Office of Nuclear Reactor Regulation's Electronic Operating Reactor Correspondence The U.S. Nuclear Regulatory Commission (NRC) is issuing this Federal Register notice to inform the public of a slight change in the manner of distribution of publicly available operating reactor licensing...
Improved nuclear power plant operations through performance-based safety regulation

International Nuclear Information System (INIS)

Golay, M.W.

1998-01-01

The US Nuclear Regulatory Commission (NRC) has recently instituted use of Risk-Informed, Performance-Based Regulation (RIPBR) for protecting public safety in the use of nuclear power. This was done most importantly during June 1997 in issuance of revised Regulatory Guides and Standard Review Plan (SRP) guidance to licensees and the NRC staff. The propose of RIPBR is to replace the previously-used system of prescriptive regulation, which focuses upon what licensees must do, to a system which focuses upon what they must achieve. RIPBR is goals-oriented and the previous system is means-oriented. This regulatory change is potentially revolutionary, and offers many opportunities for improving the efficiency of improving both nuclear power operations and safety. However, it must be nurtured carefully if is to be successful. The work reported in this paper is concerned with showing how RIPBR can be implemented successfully, with benefits in both areas being attained. It is also concerned with how several of the practical barriers to establishing a workable new regulatory system can be overcome. This work, sponsored by the US Dept. of Energy, is being performed in collaboration with Northeast Utilities Services Crop. and the Idaho National Engineering Laboratory. In our work we have examined a practical safety-related example at the Millstone 3 nuclear power station for implementation of RIPBR. In this examination we have formulated a set of modifications to the plant's technical specifications, and are in the process of investigating their bases and refining the modifications. (author)
Regulation of p53 tetramerization and nuclear export by ARC.

Science.gov (United States)

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

2007-12-26

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

International Nuclear Information System (INIS)

1981-01-01

This rule is established under the provisions of the law concerning the regulation of nuclear raw materials, nuclear fuel materials and reactors, and the former notification No. 26, 1961, is hereby abolished. Internationally regulated goods under the law are as follows: nuclear raw materials, nuclear fuel materials and moderator materials transferred by sale or other means from the governments of the U.S., U.K., Canada, Australia and France or the persons under their jurisdictions according to the agreements concluded between the governments of Japan and these countries, respectively, the nuclear fuel materials recovered from these materials or produced by their usage, nuclear reactors, the facilities and heavy water transferred by sale or other means from these governments or the persons under their jurisdictions, the nuclear fuel materials produced by the usage of such reactors, facilities and heavy water, the nuclear fuel materials sold by the International Atomic Energy Agency under the contract between the Japanese government and the IAEA, the nuclear fuel materials recovered from these materials or produced by their usage, the heavy water produced by the facilities themselves transferred from the Canadian government, Canadian governmental enterprises or the persons under the jurisdiction of the Canadian government or produced by the usage of these facilities, etc. (Okada, K.)
Nuclear safety: economic analysis of American, French and Japanese regulations

International Nuclear Information System (INIS)

Leveque, Francois

2013-05-01

While discussing and comparing the American, Japanese and French approaches and practices, and identifying the strengths and weaknesses of each of them, the author discusses why self-regulation and civil responsibility cannot guarantee a sufficient nuclear safety level, why the safety regulation authority must be independent from industry and government, whether a figure must be put to the safety objective (for example with a risk threshold), whether it is better to define detailed standards to be applied by manufacturers and operators or to define general performance criteria to be reached
Protein Sub-Nuclear Localization Prediction Using SVM and Pfam Domain Information

Science.gov (United States)

Kumar, Ravindra; Jain, Sohni; Kumari, Bandana; Kumar, Manish

2014-01-01

The nucleus is the largest and the highly organized organelle of eukaryotic cells. Within nucleus exist a number of pseudo-compartments, which are not separated by any membrane, yet each of them contains only a specific set of proteins. Understanding protein sub-nuclear localization can hence be an important step towards understanding biological functions of the nucleus. Here we have described a method, SubNucPred developed by us for predicting the sub-nuclear localization of proteins. This method predicts protein localization for 10 different sub-nuclear locations sequentially by combining presence or absence of unique Pfam domain and amino acid composition based SVM model. The prediction accuracy during leave-one-out cross-validation for centromeric proteins was 85.05%, for chromosomal proteins 76.85%, for nuclear speckle proteins 81.27%, for nucleolar proteins 81.79%, for nuclear envelope proteins 79.37%, for nuclear matrix proteins 77.78%, for nucleoplasm proteins 76.98%, for nuclear pore complex proteins 88.89%, for PML body proteins 75.40% and for telomeric proteins it was 83.33%. Comparison with other reported methods showed that SubNucPred performs better than existing methods. A web-server for predicting protein sub-nuclear localization named SubNucPred has been established at http://14.139.227.92/mkumar/subnucpred/. Standalone version of SubNucPred can also be downloaded from the web-server. PMID:24897370
Regulations concerning the fabricating business of nuclear fuel materials

International Nuclear Information System (INIS)

1987-01-01

Regulations specified here cover application for such matters as permission for an undertaking of processing, alteration (of location, structure, arrangements, processing method, etc.), approval of design and construction plan, approval of alteration (of design and construction plan of processing facilities), and inspection of the facilities. The regulations also cover execution of facilities inspection, certificate of facilities inspection, processing facilities subject to welding inspection, application for welding inspection, execution of welding inspection, facilities not subject to welding inspection, approval of welding method, welding inspection for imported equipment, certificate of welding inspection, application for approval of joint management, notice of alteration, etc., cancellation of permission, record keeping, restriction on access to areas under management measures concerning exposure to radioactive rays, patrol and checking in processing facilities, operation of processing equipment, transportation within plant or operation premises, storage, waste disposal within plant or operation premises, safety rules, public notification concerning examination and successful applicants, procedure for application for examination, reissue of certificate for nuclear fuel handling expert, return of certificate for nuclear fuel handling expert, submission of report, measures for emergency, notice of abolition of business, measures concerning cancellation of permission, identification card, etc. (Nogami, K.)
Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.

Science.gov (United States)

Ihara, Akiko; Uno, Masaharu; Miyatake, Koichi; Honjoh, Sakiko; Nishida, Eisuke

2017-01-01

Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.
Nuclear receptor 4a3 (nr4a3 regulates murine mast cell responses and granule content.

Directory of Open Access Journals (Sweden)

Gianni Garcia-Faroldi

Full Text Available Nuclear receptor 4a3 (Nr4a3 is a transcription factor implicated in various settings such as vascular biology and inflammation. We have recently shown that mast cells dramatically upregulate Nuclear receptor 4a3 upon activation, and here we investigated the functional impact of Nuclear receptor 4a3 on mast cell responses. We show that Nuclear receptor 4a3 is involved in the regulation of cytokine/chemokine secretion in mast cells following activation via the high affinity IgE receptor. Moreover, Nuclear receptor 4a3 negatively affects the transcript and protein levels of mast cell tryptase as well as the mast cell's responsiveness to allergen. Together, these findings identify Nuclear receptor 4a3 as a novel regulator of mast cell function.
Nuclear regulation. License renewal questions for nuclear plants need to be resolved

International Nuclear Information System (INIS)

Fultz, Keith O.; Kruslicky, Mary Ann; McDowell, William D. Jr.; Coleman, Robert L.

1989-04-01

A December 1986 pipe rupture at Virginia Power's Surry unit 2 nuclear power plant injured eight workers; four later died. As a result of this accident, Representative Edward J. Markey requested GAO to examine the Surry accident and assess the problems confronting aging nuclear plants. In March 1988 we reported our findings concerning the accident and a July 1987 incident at the Trojan nuclear plant in Oregon. This report addresses problems confronting aging nuclear plants by examining the Nuclear Regulatory Commission's (NRC) program to develop a license renewal policy and accompanying regulations, and the initiatives underway by the Department of Energy (DOE) and the electric utility industry to extend the operating lives of these plants. Nuclear power has become second only to coal as the largest producer of electricity in the United States. The 110 nuclear plants currently in service are operated by 54 utilities, provide about 20 percent of the nation's electricity, and represent a capital investment of over $200 billion. The Atomic Energy Act authorizes NRC to issue nuclear plant operating licenses for up to 40 years and provides for license extensions beyond the initial operating period. The act does not, however, stipulate the criteria for evaluating a utility request to operate a nuclear plant longer than 40 years. The oldest operating license currently in effect will expire in the year 2000. According to NRC, about one-half of the existing operating licenses will terminate by the year 2015, and most licenses will expire by about 2030. Many utilities will have to decide in the early 1990s whether to continue operating older nuclear plants or to construct new generating capacity. A clear understanding of the terms and conditions governing the license renewal process will be a key element in deciding how to meet future electricity demand. Although NRC has developed 3 possible license renewal policy options and identified 15 areas of regulatory uncertainty that
The evolving image and role of the regulator for implementing repositories for nuclear waste and spent nuclear fuel

International Nuclear Information System (INIS)

Melin, J.

2005-01-01

A country introducing nuclear power in their energy strategy has a life long obligation. The obligation is not mainly a question of energy production. It is an obligation to maintain safety during the phase of construction, energy production and decommissioning as well as to take care of all the waste streams from nuclear installations. I believe that one of the most controversial siting projects in the society is a waste repository for spent nuclear fuel. Competence, available funds and a clear responsibility between the stakeholders as well as the trust of the public is indispensable to obtain a good result. The Swedish programme for managing nuclear waste and spent nuclear fuel has been in progress for more than 25 years. The pre-licensing process of a repository for spent nuclear fuel is much alike a pre-licensing process for the first nuclear power plant in a country. You need a clear political will, you have to involve the nuclear regulator without jeopardizing his integrity and you need the money to perform research and make the investments. The enthusiasm of politicians and industry may however differ between these two projects. (author)
COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

International Nuclear Information System (INIS)

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

2010-01-01

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

International Nuclear Information System (INIS)

Dupraz, B.

1986-01-01

This article describes the general principles underlying nuclear safety regulations to counter external violent forces to which plants can be exposed. It then examines the statutory directives concerning external violences connected with human activities or originating from natural phenomena. 3 refs [fr
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.)
The Swedish Radiation Protection Institute's regulations concerning the final management of spent nuclear fuel and nuclear waste - with background and comments

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-11-01

This report presents and comments on the Swedish Radiation Protection Institute's Regulations concerning the Protection of Human Health and the Environment in connection with the Final Management of Spent Nuclear Fuel or Nuclear Waste, SSI FS 1998: 1.
An N-terminal nuclear localization sequence but not the calmodulin-binding domain mediates nuclear localization of nucleomorphin, a protein that regulates nuclear number in Dictyostelium

International Nuclear Information System (INIS)

Myre, Michael A.; O'Day, Danton H.

2005-01-01

Nucleomorphin is a novel nuclear calmodulin (CaM)-binding protein (CaMBP) containing an extensive DEED (glu/asp repeat) domain that regulates nuclear number. GFP-constructs of the 38 kDa NumA1 isoform localize as intranuclear patches adjacent to the inner nuclear membrane. The translocation of CaMBPs into nuclei has previously been shown by others to be mediated by both classic nuclear localization sequences (NLSs) and CaM-binding domains (CaMBDs). Here we show that NumA1 possesses a CaMBD ( 171 EDVSRFIKGKLLQKQQKIYKDLERF 195 ) containing both calcium-dependent-binding motifs and an IQ-like motif for calcium-independent binding. GFP-constructs containing only NumA1 residues 1-129, lacking the DEED and CaMBDs, still localized as patches at the internal periphery of nuclei thus ruling out a direct role for the CaMBD in nuclear import. These constructs contained the amino acid residues 48 KKSYQDPEIIAHSRPRK 64 that include both a putative bipartite and classical NLS. GFP-bipartite NLS constructs localized uniformly within nuclei but not as patches. As with previous work, removal of the DEED domain resulted in highly multinucleate cells. However as shown here, multinuclearity only occurred when the NLS was present allowing the protein to enter nuclei. Site-directed mutation analysis in which the NLS was changed to 48 EF 49 abolished the stability of the GFP fusion at the protein but not RNA level preventing subcellular analyses. Cells transfected with the 48 EF 49 construct exhibited slowed growth when compared to parental AX3 cells and other GFP-NumA1 deletion mutants. In addition to identifying an NLS that is sufficient for nuclear translocation of nucleomorphin and ruling out CaM-binding in this event, this work shows that the nuclear localization of NumA1 is crucial to its ability to regulate nuclear number in Dictyostelium

Case definition for progressive multifocal leukoencephalopathy following treatment with monoclonal antibodies.

Science.gov (United States)

Mentzer, Dirk; Prestel, Jürgen; Adams, Ortwin; Gold, Ralf; Hartung, Hans-Peter; Hengel, Hartmut; Kieseier, Bernd C; Ludwig, Wolf-Dieter; Keller-Stanislawski, Brigitte

2012-09-01

Novel immunosuppressive/modulating therapies with monoclonal antibodies (MABs) have been associated with progressive multifocal leukoencephalopathy (PML), a potentially fatal disease of the brain caused by the JC virus. Taking the complex diagnostic testing and heterogeneous clinical presentation of PML into account, an agreed case definition for PML is a prerequisite for a thorough assessment of PML. A working group was established to develop a standardised case definition for PML which permits data comparability across clinical trials, postauthorisation safety studies and passive postmarketing surveillance. The case definition is designed to define levels of diagnostic certainty of reported PML cases following treatment with MABs. It was subsequently used to categorise retrospectively suspected PML cases from Germany reported to the Paul-Ehrlich-Institute as the responsible national competent authority. The algorithm of the case definition is based on clinical symptoms, PCR for JC virus DNA in cerebrospinal fluid, brain MRI, and brain biopsy/autopsy. The case definition was applied to 119 suspected cases of PML following treatment with MABs and is considered to be helpful for case ascertainment of suspected PML cases for various MABs covering a broad spectrum of indications. Even if the available information is not yet complete, the case definition provides a level of diagnostic certainty. The proposed case definition permits data comparability among different medicinal products and among active as well as passive surveillance settings. It may form a basis for meaningful risk analysis and communication for regulators and healthcare professionals.
Concerning enactment of regulations on burying of waste of nuclear fuel material or waste contaminated with nuclear fuel material

International Nuclear Information System (INIS)

1988-01-01

The Atomic Safety Commission of Japan, after examining a report submitted by the Science and Technology Agency concerning the enactment of regulations on burying of waste of nuclear fuel material or waste contaminated with nuclear fuel material, has approved the plan given in the report. Thus, laws and regulations concerning procedures for application for waste burying business, technical standards for implementation of waste burying operation, and measures to be taken for security should be established to ensure the following. Matters to be described in the application for the approval of such business and materials to be attached to the application should be stipulated. Technical standards concerning inspection of waste burying operation should be stipulated. Measures to be taken for the security of waste burying facilities and security concerning the transportation and disposal of nuclear fuel material should be stipulated. Matters to be specified in the security rules should be stipulated. Matters to be recorded by waste burying business operators, measures to be taken to overcome dangers and matters to be reported to the Science and Technology Agency should be stipulated. (Nogami, K.)
Assessment of policy issues in nuclear safety regulation according to circumstantial changes

Energy Technology Data Exchange (ETDEWEB)

Chang, Soon Heung; Lee, Byong Ho; Baek, Won Pil; Lee, Kwang Gu; Huh, Gyun Young; Hahn, Young Tae [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

2000-03-15

The objective of the work is to assess various issues in nuclear safety regulation in consideration of circumstantial changes. Emphasis is given to the safety of operating NPPs. It is concluded that the Periodic Safety Review (PSR) should be implemented in Korea as soon as possible, in harmonization with the regulation for life extension of NPPs. The IAEA guidelines, including 10 year intervals and 11 safety factors, should be used as the basic guidelines. The approach to improve regulatory effectiveness is also reviewed and a transition to 'knowledge-based regulation' is suggested.
Decommissioning commercial nuclear facilities: a review and analysis of current regulations

International Nuclear Information System (INIS)

Schilling, A.H.; Lippek, H.E.; Tegeler, P.D.; Easterling, J.D.

1979-08-01

This report describes and analyzes the regulatory requirements and guidelines applicable to the decommissioning of commercial light water reactors, other commercial nuclear fuel cycle facilities, and byproduct utilization facilities, as contained principally in the United States Code, the United States Code of Federal Regulations, and the United States Nuclear Regulatory Commission's Regulatory Guides. State requirements are discussed where appropriate. The report provides general background informaion to license applicants and to other interested parties. Included is an outline of procedural steps required of an applicant to comply with decommissioning regulatory requiremets
Motif analysis unveils the possible co-regulation of chloroplast genes and nuclear genes encoding chloroplast proteins.

Science.gov (United States)

Wang, Ying; Ding, Jun; Daniell, Henry; Hu, Haiyan; Li, Xiaoman

2012-09-01

Chloroplasts play critical roles in land plant cells. Despite their importance and the availability of at least 200 sequenced chloroplast genomes, the number of known DNA regulatory sequences in chloroplast genomes are limited. In this paper, we designed computational methods to systematically study putative DNA regulatory sequences in intergenic regions near chloroplast genes in seven plant species and in promoter sequences of nuclear genes in Arabidopsis and rice. We found that -35/-10 elements alone cannot explain the transcriptional regulation of chloroplast genes. We also concluded that there are unlikely motifs shared by intergenic sequences of most of chloroplast genes, indicating that these genes are regulated differently. Finally and surprisingly, we found five conserved motifs, each of which occurs in no more than six chloroplast intergenic sequences, are significantly shared by promoters of nuclear-genes encoding chloroplast proteins. By integrating information from gene function annotation, protein subcellular localization analyses, protein-protein interaction data, and gene expression data, we further showed support of the functionality of these conserved motifs. Our study implies the existence of unknown nuclear-encoded transcription factors that regulate both chloroplast genes and nuclear genes encoding chloroplast protein, which sheds light on the understanding of the transcriptional regulation of chloroplast genes.
CT and MRI in progressive multifocal leukoencephalopathy. CT und MRT der progressiven multifokalen Leukenzephalopathie (PML)

Energy Technology Data Exchange (ETDEWEB)

Lanfermann, H. (Inst. und Poliklinik fuer Radiologische Diagnostik, Koeln Univ. (Germany)); Heindel, W. (Inst. und Poliklinik fuer Radiologische Diagnostik, Koeln Univ. (Germany)); Schroeder, R. (Neuropathologie des Inst. fuer Pathologie, Koeln Univ. (Germany)); Lackner, K. (Inst. und Poliklinik fuer Radiologische Diagnostik, Koeln Univ. (Germany))

1994-07-01

Radiological findings and course of progressive multifocal leukoencephalopathy in 14 patients (1 woman, 13 men; 13 HIV seropositive, 1 chronic lymphatic leukaemia) were analysed retrospectively and correlated with clinical symptoms. A total of 21 CT and 16 MRI studies were evaluated. CT scans and MR images of 9 patients, which had been obtained in less than two weeks, could be compared to each other. MRI was superior to CT: 6 lesions with a diameter of 1 cm and below were not detected on CT scans, in 5 patients the extent of lesions was underestimated. Cortical involvement, mass effect or signs of atrophy were missing. Only 1 of 65 lesions showed a tiny enhancement after Gd injection. Due to the pattern and spread of lesions, which showed a close correlation to the neurologic symptoms, three different types of PML are suggested: 1. Initial precentral demyelinisation with contralateral hemiparesis (n=8); 2. lesions in temporo-occipital locations with visual disturbances (n=2); 3. predominantly bilateral lesions of cerebellar white matter with ataxia (n=4). (orig.)
Nuclear regulation in the United States : Policy directions and future prospects

International Nuclear Information System (INIS)

Shirley, Ann Jackson

1996-01-01

Just before leaving the United States to come to Korea, I addressed the U. S. Nuclear Regulatory Commission (NRC) annual regulatory information conference, with which some of you might be familiar. The overall theme this year focused on enhancing and promoting a better understanding of future trends for improving nuclear safety. Specific sessions addressed an array of nuclear safety topics including: dry cask storage of spent fuel; performance-based changes in the inspection program; core performance and reactor fuel issues; the revised decommissioning rule; utility restructuring and NRC licensing activities; steam generators; implementation of the maintenance rule; an update on license renewal; the shutdown rule; and spent fuel pool issues. The number and range of topics addressed tells US that the nuclear field is by no means static. On the contrary. there are numerous areas in which regulatory policy is evolving in response to technological, governmental, and other developments. while not all nations with nuclear programs face the same issues at the same time, there is enough overlap from one nation to another that it may be useful to describe the challenges facing the NRC today. the nuclear regulatory policy is moving. The challenges that we are dealing with at the NRC today may well be those which other nations will be confronting shortly? of they are not doing so already. In addressing the question of my vision for the NRC, I am sometimes asked whether it is possible to have a vision for the agency, given that no new nuclear plants are being built in the U. S. and none are on the immediate horizon. The answer, of course, is that the original licensing of nuclear power plants is only a part of the job of the NRC? an important part, to be sure, be but because safety must be built into nuclear plants from the beginning -- but nevertheless just one part. The task of the nuclear regulator is to ensure not only that plants are designed and constructed safely, but
Lessons learned from application of the Swedish regulations for decommissioning of nuclear facilities - The regulator's perspective

International Nuclear Information System (INIS)

Efraimsson, Henrik; Amft, Martin; Leisvik, Mathias

2016-01-01

The paper presents an overview of the Swedish regulations for decommissioning of nuclear facilities. It describes some of the experiences that the Swedish Radiation Safety Authority has gained from the application of these regulations. The focus of the present paper lies on administrative aspects of the care and maintenance operation and on the safety related documentation that has to be prepared before dismantling commences. Lessons learned during recent years will be considered when revising the regulations for decommissioning. Also these lessons learned will help to streamline the administration of the large NPP decommissioning projects that are anticipated to commence in Sweden in the near future. (authors)
An international comparison of commercial nuclear power plant staffing regulations and practice, 1980--1990

International Nuclear Information System (INIS)

Melber, B.; Hauth, J.; Terrill, E.; Berk, B.; Gore, B.

1994-03-01

In this report an international review of regulatory and industry practices is provided in the area of nuclear power plant staffing during the 1980s in Canada, France, Germany, Japan, Sweden, and the United Kingdom. The objective of this review is to highlight trends in staffing regulatory approaches, industry practices, and issues of concern in other countries that have potential relevance to nuclear power plant staffing issues in the United States. The decade of the 1980s was marked by a great deal of growth in nuclear power operations internationally; however, growth of nuclear power is not expected to continue in the 1990s except in France and Japan. A continuum of regulatory approaches to staffing was identified, ranging from prescribed regulations that are applied to all licensees (Germany is most similar to the United States in this regard), to indirect staffing regulations where the regulatory authority oversees plant operating practices that are agreed to in the plant operating license (most notably, France and the United Kingdom). Most of the changes observed in staffing regulations and practices in the early 1980s were made in response to the accident at the Three Mile Island Unit 2 nuclear power plant (TMI) in 1979. These changes included the widespread issuance of new operator and licensing requirements and the establishment of national training centers. After the post-TMI changes were implemented, a period of relative stability followed. Changes in the latter half of the 1980s have focused on continuing improvements and additions to training curricula and methods, most notably increased reliance on simulator training
PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia.

Science.gov (United States)

Padua, Rose Ann; Larghero, Jerome; Robin, Marie; le Pogam, Carol; Schlageter, Marie-Helene; Muszlak, Sacha; Fric, Jan; West, Robert; Rousselot, Philippe; Phan, Thi Hai; Mudde, Liesbeth; Teisserenc, Helene; Carpentier, Antoine F; Kogan, Scott; Degos, Laurent; Pla, Marika; Bishop, J Michael; Stevenson, Freda; Charron, Dominique; Chomienne, Christine

2003-11-01

Despite improved molecular characterization of malignancies and development of targeted therapies, acute leukemia is not curable and few patients survive more than 10 years after diagnosis. Recently, combinations of different therapeutic strategies (based on mechanisms of apoptosis, differentiation and cytotoxicity) have significantly increased survival. To further improve outcome, we studied the potential efficacy of boosting the patient's immune response using specific immunotherapy. In an animal model of acute promyelocytic leukemia, we developed a DNA-based vaccine by fusing the human promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) oncogene to tetanus fragment C (FrC) sequences. We show for the first time that a DNA vaccine specifically targeted to an oncoprotein can have a pronounced effect on survival, both alone and when combined with all-trans retinoic acid (ATRA). The survival advantage is concomitant with time-dependent antibody production and an increase in interferon-gamma (IFN-gamma). We also show that ATRA therapy on its own triggers an immune response in this model. When DNA vaccination and conventional ATRA therapy are combined, they induce protective immune responses against leukemia progression in mice and may provide a new approach to improve clinical outcome in human leukemia.
Recent development in safety regulation of nuclear fuel cycle activities

International Nuclear Information System (INIS)

Kato, S.

2001-01-01

Through the effort of deliberation and legislation over five years, Japanese government structure was reformed this January, with the aim of realizing simple, efficient and transparent administration. Under the reform, the Agency for Nuclear and Industrial Safety (ANIS) was founded in the Ministry of Economy, Trade and Industry (METI) to be responsible for safety regulation of energy-related nuclear activities, including nuclear fuel cycle activities, and industrial activities, including explosives, high-pressure gasses and mining. As one of the lessons learned from the JCO criticality accident of September 1999, it was pointed out that the government's inspection function was not enough for fuel fabrication facilities. Accordingly, new statutory regulatory activities were introduced, namely, inspection of observance of safety rules and procedures for all kinds of nuclear operators and periodic inspection of fuel fabrication facilities. In addition, in order to cope with insufficient safety education and training of workers in nuclear facilities, licensees of nuclear facilities are required by law to specify safety education and training for their workers. ANIS is committed to enforce these new regulatory activities effectively and efficiently. In addition, it is going to be prepared, in its capacity as safety regulatory authority, for future development of Japanese fuel cycle activities, including commissioning of JNFL Rokkasho reprocessing plant and possible application for licenses for JNFL MOX fabrication plant and for spent fuel interim storage facilities. (author)
The Regulation of Major Risks in Relation to Large Nuclear Installations in France

International Nuclear Information System (INIS)

Phan Van, L.

1991-01-01

Recently, major risk prevention has generated legislative and regulatory texts in French law, particularly regarding nuclear installations. This article reviews the context and analyses the scope of the new regulations. They require the nuclear operator to take preventive measures, namely more stringent obligations from the safety viewpoint to inform the public. These include risk assessments and preparing emergency plans in case if accidents. (NEA)
Framework for applying probabilistic safety analysis in nuclear regulation

International Nuclear Information System (INIS)

Dimitrijevic, V.B.

1997-01-01

The traditional regulatory framework has served well to assure the protection of public health and safety. It has been recognized, however, that in a few circumstances, this deterministic framework has lead to an extensive expenditure on matters hat have little to do with the safe and reliable operation of the plant. Developments of plant-specific PSA have offered a new and powerful analytical tool in the evaluation of the safety of the plant. Using PSA insights as an aid to decision making in the regulatory process is now known as 'risk-based' or 'risk-informed' regulation. Numerous activities in the U.S. nuclear industry are focusing on applying this new approach to modify regulatory requirements. In addition, other approaches to regulations are in the developmental phase and are being evaluated. One is based on the performance monitoring and results and it is known as performance-based regulation. The other, called the blended approach, combines traditional deterministic principles with PSA insights and performance results. (author)
Promoting nuclear energy: market price or regulated tariffs? - 5042

International Nuclear Information System (INIS)

Percebois, J.

2015-01-01

Because of its negative effects, the scheme for aiding renewable energies presently in force in Europe is likely to penalise investments in nuclear energy. The F.I.T. system is a costly mechanism and a source of perverse effects as a switching of the merit order curve on the spot electricity market (with sometimes negative prices). Restoring an equity and 'equal opportunity' for nuclear energy in Europe needs to implement a 'Contract for Differences' scheme for nuclear energy, like the model now gaining favour in the U.K. The contract for differences signed between EDF and the UK government means that if the wholesale price that EDF secures for Hinckley's power falls below the index-linked preset value, the difference will be covered by payments from the UK government. It appears that nuclear power has weakened in Europe by the system of guaranteed purchase prices for renewable energies. Moreover this system is costly. New fairer rules must be implemented in the market. Either the market is left on its own to send the signals to all investors (including renewable energies), or a minimum of regulation is introduced in order to limit the costly surges of under and over capacity. But in the latter case it is necessary to treat all the energy sources in an equal way and guarantee the nuclear industry that it will also recover its fixed costs over the long term)
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.
A comparison between regulation of nuclear power in Canada and the United States

International Nuclear Information System (INIS)

Ahearne, J.F.

1988-01-01

The agencies that regulate commercial nuclear power in Canada and the United States differ in five significant characteristics: size and responsibility; use of legalism and formality; inspection and enforcement approaches; relationships to the government, public and industry; and the basic philosophy of regulation. Examination shows strengths and weaknesses in each approach, tied to basic differences in philosophy of government. (author)
Fixes regulations for application of dispositives of the Law 4,118 (as of August 27, 1962), and its regulation approved by the Decree 51,726 (as of February 19, 1963) referred to the nuclear minerals, ores and of interest for nuclear energy

International Nuclear Information System (INIS)

1965-01-01

The present resolution establishes regulations for provision of the Law 4118 (dated of August 27, 1962) and his regulation a proved by Decree 51,726 (dated of February 19, 1963) as referring to the minerals, nuclear ores and of interest for the nuclear energy, substituting the Resolution 1/63
Proposal of guidelines for structuring an independent regulation body for the Brazilian nuclear sector

International Nuclear Information System (INIS)

Nicoll Junior, Ricardo

2016-01-01

Regulatory bodies are responsible for regulation in various sectors of society. In Brazil, they work in various areas for the development of the country and have as main objective the social, economic and national development. The progress of new technologies in the nuclear field and their commercialization underscores the need for regulation according to international safety standards. The present research searches through an extensive review of the literature identify the international guidelines for regulatory bodies and make a comparative analysis between Brazil and five countries that have independent regulatory bodies in the nuclear sector. The purpose of the work is to contribute to the Brazilian public sectors, with an evaluation of the country's regulation in the perception of specialists and propose guidelines for the structuring of an independent regulatory body, respecting international agreements and the legislation in force in the country. (author)
Regulation of behaviour by the nuclear receptor TLX.

Science.gov (United States)

O'Leary, J D; O'Leary, O F; Cryan, J F; Nolan, Y M

2018-03-01

The orphan nuclear receptor Tlx (Nr2e1) is a key regulator of both embryonic and adult hippocampal neurogenesis. Several different mouse models have been developed which target Tlx in vivo including spontaneous deletion models (from birth) and targeted and conditional knockouts. Although some conflicting findings have been reported, for the most part studies have demonstrated that Tlx is important in regulating processes that underlie neurogenesis, spatial learning, anxiety-like behaviour and interestingly, aggression. More recent data have demonstrated that disrupting Tlx during early life induces hyperactivity and that Tlx plays a role in emotional regulation. Moreover, there are sex- and age-related differences in some behaviours in Tlx knockout mice during adolescence and adulthood. Here, we discuss the role of Tlx in motor-, cognitive-, aggressive- and anxiety-related behaviours during adolescence and adulthood. We examine current evidence which provides insight into Tlx during neurodevelopment, and offer our thoughts on the function of Tlx in brain and behaviour. We further hypothesize that Tlx is a key target in understanding the emergence of neurobiological disorders during adolescence and early adulthood. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
State regulation of nuclear sector: comparative study of Argentina and Brazil models; Regulacao estatal do setor nuclear: estudo comparativo dos modelos da Argentina e do Brasil

Energy Technology Data Exchange (ETDEWEB)

Monteiro Filho, Joselio Silveira

2004-08-01

This research presents a comparative assessment of the regulation models of the nuclear sector in Argentina - under the responsibility of the Autoridad Regulatoria Nuclear (ARN), and Brazil - under the responsibility of Comissao Nacional de Energia Nuclear (CNEN), trying to identify which model is more adequate aiming the safe use of nuclear energy. Due to the methodology adopted, the theoretical framework resulted in criteria of analysis that corresponds to the characteristics of the Brazilian regulatory agencies created for other economic sector during the State reform staring in the middle of the nineties. Later, these criteria of analysis were used as comparison patterns between the regulation models of the nuclear sectors of Argentina and Brazil. The comparative assessment showed that the regulatory structure of the nuclear sector in Argentina seems to be more adequate, concerning the safe use of nuclear energy, than the model adopted in Brazil by CNEN, because its incorporates the criteria of functional, institutional and financial independence, competence definitions, technical excellence and transparency, indispensable to the development of its functions with autonomy, ethics, exemption and agility. (author)

A study on environmental regulation and public inquiry system of nuclear facilities

International Nuclear Information System (INIS)

Lee, Sang Hun; Kang, Chang Sun; Son, Ki Yon; Cho, Young Ho; Yang, Ji Won; Lee, Young Wook; Ko, Hyun Suk

2000-03-01

Public hearing system for domestic and foreign nuclear facilities are investigated and analyzed. As a result, Korean public hearing system are developed. Atomic Energy Act, Environmental Impact Assessment Act and Administrative Procedure Act of Korea are reviewed and appropriate acts, regulations, procedures and mandates of foreign countries including U.S.A are reviewed and analyzed. On the basis of these results the role of device to collect public opinion is identified for nuclear facility of Korea and the elementary principle of the system and recommendations are developed
A study on environmental regulation and public inquiry system of nuclear facilities

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Hun [Korea Association for Nuclear Technology, Taejon (Korea, Republic of); Kang, Chang Sun; Son, Ki Yon; Cho, Young Ho; Yang, Ji Won; Lee, Young Wook; Ko, Hyun Suk [Seoul National Univ., Seoul (Korea, Republic of)

2000-03-15

Public hearing system for domestic and foreign nuclear facilities are investigated and analyzed. As a result, Korean public hearing system are developed. Atomic Energy Act, Environmental Impact Assessment Act and Administrative Procedure Act of Korea are reviewed and appropriate acts, regulations, procedures and mandates of foreign countries including U.S.A are reviewed and analyzed. On the basis of these results the role of device to collect public opinion is identified for nuclear facility of Korea and the elementary principle of the system and recommendations are developed.
Underground nuclear power station using self-regulating heat-pipe controlled reactors

International Nuclear Information System (INIS)

Hampel, V.E.

1989-01-01

The author presents a nuclear reactor for generating electricity disposed underground at the bottom of a vertical hole that can be drilled using conventional drilling technology. The primary coolant of the reactor core is the working fluid in a plurality of thermodynamically coupled heat pipes emplaced in the hole between the heat source at the bottom of the hole and heat exchange means near the surface of the earth. Additionally, the primary coolant (consisting of the working fluid in the heat pipes in the reactor core) moderates neutrons and regulates their reactivity, thus keeping the power of the reactor substantially constant. At the end of its useful life, the reactor core may be abandoned in place. Isolation from the atmosphere in case of accident or for abandonment is provided by the operation of explosive closures and mechanical valves emplaced along the hole. This invention combines technology developed and tested for small, highly efficient, space-based nuclear electric power plants with the technology of fast-acting closure mechanisms developed and used for underground testing of nuclear weapons. This invention provides a nuclear power installation which is safe from the worst conceivable reactor accident, namely, the explosion of a nuclear weapon near the ground surface of a nuclear power reactor
Underground nuclear power station using self-regulating heat-pipe controlled reactors

Science.gov (United States)

Hampel, Viktor E.

1989-01-01

A nuclear reactor for generating electricity is disposed underground at the bottom of a vertical hole that can be drilled using conventional drilling technology. The primary coolant of the reactor core is the working fluid in a plurality of thermodynamically coupled heat pipes emplaced in the hole between the heat source at the bottom of the hole and heat exchange means near the surface of the earth. Additionally, the primary coolant (consisting of the working flud in the heat pipes in the reactor core) moderates neutrons and regulates their reactivity, thus keeping the power of the reactor substantially constant. At the end of its useful life, the reactor core may be abandoned in place. Isolation from the atmosphere in case of accident or for abandonment is provided by the operation of explosive closures and mechanical valves emplaced along the hole. This invention combines technology developed and tested for small, highly efficient, space-based nuclear electric power plants with the technology of fast-acting closure mechanisms developed and used for underground testing of nuclear weapons. This invention provides a nuclear power installation which is safe from the worst conceivable reactor accident, namely, the explosion of a nuclear weapon near the ground surface of a nuclear power reactor.
Challenges for nuclear regulators

International Nuclear Information System (INIS)

Allen, M.R.

1994-01-01

The paper discusses issues that will present particular challenges to the nuclear industry, during the next decade, that should be addressed in order to achieve increased public acceptance of the industry. The issues of safety culture, peer review of safety, severe accidents, transport accidents and public communication are suggest as meriting special consideration. The need for nuclear regulatory agencies to establish credibility and for operating organisations to demonstrate accountability is emphasised, and the Australian experiences are reviewed. Increased collaboration by nuclear regulatory agencies in the Asian-pacific region is suggested, in order to encourage consistency of regulatory safety standards for the nuclear safety issues identified. Methods whereby this could be achieved within the framework of existing agreements and arrangements are suggested. 2 refs
Nuclear safety philosophy and its general application to fuel management and handling - a regulator's viewpoint

International Nuclear Information System (INIS)

Petty, I.C.

1995-01-01

The Nuclear Safety Division (NSD) of the Health and Safety Executive (HSE) informs the UK Nuclear Industry of the principles that it applies in assessing whether licensees have demonstrated that their nuclear plants are as safe as is reasonably practicable. The paper commences with a discussion of the non-prescriptive approach to health and safety regulation which is the basis of the regulatory activities of NSD's operating arm -the Nuclear Installations Inspectorate (NII). It then describes in broad terms the overall approach used by NII for analysing the safety of nuclear plant, including fuel, which will cover both deterministic and probabilistic methodologies. The paper then introduces the sections of the Safety Assessment Principles which apply to nuclear fuel safety (both fuel handling and management). Most of these principles are of a general nature and do not just apply to fuel. The paper explains how safety cases might relate to the SAPs and offers some views on how a licensee might interpret them in developing his safety case. Particular emphasis is placed on the importance of submitting a high quality safety case and the type of information that should be in it. The advantages of the approach proposed, to the licensee as well as to the regulator, are identified. (author)
Physical protection of nuclear materials: Experience in regulation, implementation and operations. Proceedings of a conference

International Nuclear Information System (INIS)

1998-01-01

The conference was held at IAEA Headquarters in Vienna from 10 to 14 November 1997. It was attended by 162 registered participants from 42 countries and eight international organizations. The 58 papers presented dealt with the experience of regulators, designers and facility operators, including response forces, in meeting the demands and requirements in this changing area of physical protection of nuclear materials and facilities. Individual abstracts were prepared for each of the papers. Topics covered include contemporary and emerging issues, experience in regulation, implementation at facilities, program assessment and cooperation, hardware and software, illicit trafficking in nuclear materials, and transportation
Incentive regulation of nuclear power plants by state public utility commissions

International Nuclear Information System (INIS)

Petersen, J.C.

1987-12-01

This report on incentive regulation of nuclear power plants by state public utility commissions (PUCs). Economic performance incentives established by state PUCs are applicable to the construction or operation of about 45 nuclear power reactors owned by 30 utilities in 17 states. The NRC staff monitors development of the incentives and periodically provides an updated report on all nuclear plant incentives to its regional offices. The staff maintains contact with the PUCs and the utilities responsible for implementing the incentives in order to obtain the updated information and to consider potential safety effects of the incentives. This report presents the NRC staff's concerns on potential safety effects of economic performance incentives. It also includes a plant-by-plant survey that describes the mechanics of each incentive and discusses the financial effects of the incentive on the utility-owner(s) of the plant
Assessment of policy issues in nuclear safety regulation according to circumstantial changes

Energy Technology Data Exchange (ETDEWEB)

Chang, Soon Heung; Lee, Byong Ho; Baek, Woon Pil; Lee, Seong Wook; Choi, Seong Soo; Roh, Chang Hyun; Lee, Kwang Gu [Korea Advanced Institute of Scienc and Technology, Taejon (Korea, Republic of)

1998-03-15

The objective of the work is to assess various issues in nuclear safety regulation in consideration of circumstantial changes. Emphasis is given to the safety of operating NPPs. The derivation of an effective regulation system considering 'Rhodic Safety Review (PSR)', 'operating License Renewal (LR)', 'backfitting' and 'maintenance rule' is the main objective of the first two years. It is found that those approaches should be introduced in Korea as soon as possible, with cross lingkage to maximize the effectiveness of regulation. In particular, the approaches for PSR are discussed with consultation of IAEA document and foreign practices.
DMPD: Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17349209 Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. Carmody...uclear factor-kappaB: activation and regulation during toll-like receptorsignaling. Authors Carmody
Bases of updating of nuclear safety regulations for NPP in Romania

International Nuclear Information System (INIS)

Biro, Lucian; Serbanescu, Dan

1999-01-01

The paper presents the basic principles of reviewing and updating process of the regulatory environment pyramid. The main part of this review process refers to Cernavoda NPP Unit 2. However, there is an important impact on Cernavoda NPP Unit 1. The basic principles were defined in 1993/1994 when the licensing process for Unit 1 was resumed in order to be in accordance with the latest developments of Candu 600 worldwide and with the IAEA and NEA latest recommended documents and practices. After the licensing process for the Unit 1 was completed up to operation stage, CNCAN developed new updated regulations on nuclear safety and the regulatory pyramid in the framework of the RAMG PHARE project. CNCAN issued in 1996 the regulatory Policy for Unit 2, self-sustained and independent of future possible revisions of the regulations. The use of the concept of hierarchical systems, systematic review of safety criteria and objectives and margins along with the feedback from international and national experience on this topic ensured issuance of a reference document for future approach of nuclear safety in Romania. (authors)
Control of Nuclear Materials and Special Equipment (Nuclear Safety Regulations)

International Nuclear Information System (INIS)

Cizmek, A.; Prah, M.; Medakovic, S.; Ilijas, B.

2008-01-01

Based on Nuclear Safety Act (OG 173/03) the State Office for Nuclear Safety (SONS) in 2008 adopted beside Ordinance on performing nuclear activities (OG 74/06) and Ordinance on special conditions for individual activities to be performed by expert organizations which perform activities in the area of nuclear safety (OG 74/06) the new Ordinance on the control of nuclear material and special equipment (OG 15/08). Ordinance on the control of nuclear material and special equipment lays down the list of nuclear materials and special equipment as well as of nuclear activities covered by the system of control of production of special equipment and non-nuclear material, the procedure for notifying the intention to and filing the application for a license to carry out nuclear activities, and the format and contents of the forms for doing so. This Ordinance also lays down the manner in which nuclear material records have to be kept, the procedure for notifying the State administration organization (regulatory body) responsible for nuclear safety by the nuclear material user, and the keeping of registers of nuclear activities, nuclear material and special equipment by the State administration organization (regulatory body) responsible for nuclear safety, as well as the form and content of official nuclear safety inspector identification card and badge.(author)
Phosphorylation of zona occludens-2 by protein kinase C epsilon regulates its nuclear exportation.

Science.gov (United States)

Chamorro, David; Alarcón, Lourdes; Ponce, Arturo; Tapia, Rocio; González-Aguilar, Héctor; Robles-Flores, Martha; Mejía-Castillo, Teresa; Segovia, José; Bandala, Yamir; Juaristi, Eusebio; González-Mariscal, Lorenza

2009-09-01

Here, we have analyzed the subcellular destiny of newly synthesized tight junction protein zona occludens (ZO)-2. After transfection in sparse cells, 74% of cells exhibit ZO-2 at the nucleus, and after 18 h the value decreases to 17%. The mutation S369A located within the nuclear exportation signal 1 of ZO-2 impairs the nuclear export of the protein. Because Ser369 represents a putative protein kinase C (PKC) phosphorylation site, we tested the effect of PKC inhibition and stimulation on the nuclear export of ZO-2. Our results strongly suggest that the departure of ZO-2 from the nucleus is regulated by phosphorylation at Ser369 by novel PKCepsilon. To test the route taken by ZO-2 from synthesis to the plasma membrane, we devised a novel nuclear microinjection assay in which the nucleus served as a reservoir for anti-ZO-2 antibody. Through this assay, we demonstrate that a significant amount of newly synthesized ZO-2 goes into the nucleus and is later relocated to the plasma membrane. These results constitute novel information for understanding the mechanisms that regulate the intracellular fate of ZO-2.
Cooperative development of nuclear safety regulations, guides and standards based on NUSS

International Nuclear Information System (INIS)

Pachner, J.; Boyd, F.C.; Yaremy, E.M.

1984-10-01

In 1983, the Atomic Energy Control Board and Atomic Energy of Canada Limited conducted a study of a possible joint program involving Canada, a nuclear power plant importing Member State and the IAEA for the development of the national nuclear safety regulations and guides based on NUSS documents. During the study, a work plan with manpower estimates for the development of design was prepared as an investigatory exercise. The work plan suggests that a successful NUSS implementation in developing Member States will require availability of significant resources at the start of the program. The study showed that such a joint program could provide an effective mechanism for transfer of nuclear safety know-how to the developing Member States through NUSS implementation
Nitrosative/oxidative stress conditions regulate thioredoxin-interacting protein (TXNIP) expression and thioredoxin-1 (TRX-1) nuclear localization.

Science.gov (United States)

Ogata, Fernando Toshio; Batista, Wagner Luiz; Sartori, Adriano; Gesteira, Tarsis Ferreira; Masutani, Hiroshi; Arai, Roberto Jun; Yodoi, Junji; Stern, Arnold; Monteiro, Hugo Pequeno

2013-01-01

Thioredoxin (TRX-1) is a multifunctional protein that controls the redox status of other proteins. TRX-1 can be found in the extracellular milieu, cytoplasm and nucleus, and it has distinct functions in each environment. Previously, we studied the intracellular localization of TRX-1 and its relationship with the activation of the p21Ras-ERK1/2 MAP Kinases signaling pathway. In situations where this pathway was activated by stress conditions evoked by a nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), TRX-1 accumulated in the nuclear compartment due to nitrosylation of p21Ras and activation of downstream ERK1/2 MAP kinases. Presently, we demonstrate that ERK1/2 MAP Kinases activation and spatial distribution within cells trigger TRX-1 nuclear translocation through down-regulation of the physiological inhibitor of TRX-1, Thioredoxin Interacting Protein (TXNIP). Once activated by the oxidants, SNAP and H₂O₂, the ERK1/2 MAP kinases migrate to the nucleus. This is correlated with down-regulation of TXNIP. In the presence of the MEK inhibitors (PD98059 or UO126), or in cells transfected with the Protein Enriched in Astrocytes (PEA-15), a cytoplasmic anchor of ERK1/2 MAP kinases, TRX-1 nuclear migration and TXNIP down-regulation are no longer observed in cells exposed to oxidants. On the other hand, over-expression of TXNIP abolishes nuclear migration of TRX-1 under nitrosative/oxidative stress conditions, whereas gene silencing of TXNIP facilitates nuclear migration even in the absence of stress conditions. Studies based on the TXNIP promoter support this regulation. In conclusion, changes in TRX-1 compartmentalization under nitrosative/oxidative stress conditions are dependent on the expression levels of TXNIP, which are regulated by cellular compartmentalization and activation of the ERK1/2 MAP kinases.
Nitrosative/oxidative stress conditions regulate thioredoxin-interacting protein (TXNIP expression and thioredoxin-1 (TRX-1 nuclear localization.

Directory of Open Access Journals (Sweden)

Fernando Toshio Ogata

Full Text Available Thioredoxin (TRX-1 is a multifunctional protein that controls the redox status of other proteins. TRX-1 can be found in the extracellular milieu, cytoplasm and nucleus, and it has distinct functions in each environment. Previously, we studied the intracellular localization of TRX-1 and its relationship with the activation of the p21Ras-ERK1/2 MAP Kinases signaling pathway. In situations where this pathway was activated by stress conditions evoked by a nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP, TRX-1 accumulated in the nuclear compartment due to nitrosylation of p21Ras and activation of downstream ERK1/2 MAP kinases. Presently, we demonstrate that ERK1/2 MAP Kinases activation and spatial distribution within cells trigger TRX-1 nuclear translocation through down-regulation of the physiological inhibitor of TRX-1, Thioredoxin Interacting Protein (TXNIP. Once activated by the oxidants, SNAP and H₂O₂, the ERK1/2 MAP kinases migrate to the nucleus. This is correlated with down-regulation of TXNIP. In the presence of the MEK inhibitors (PD98059 or UO126, or in cells transfected with the Protein Enriched in Astrocytes (PEA-15, a cytoplasmic anchor of ERK1/2 MAP kinases, TRX-1 nuclear migration and TXNIP down-regulation are no longer observed in cells exposed to oxidants. On the other hand, over-expression of TXNIP abolishes nuclear migration of TRX-1 under nitrosative/oxidative stress conditions, whereas gene silencing of TXNIP facilitates nuclear migration even in the absence of stress conditions. Studies based on the TXNIP promoter support this regulation. In conclusion, changes in TRX-1 compartmentalization under nitrosative/oxidative stress conditions are dependent on the expression levels of TXNIP, which are regulated by cellular compartmentalization and activation of the ERK1/2 MAP kinases.
Nuclear regulation. NRC's security clearance program can be strengthened

International Nuclear Information System (INIS)

Fultz, Keith O.; Kruslicky, Mary Ann; Bagnulo, John E.

1988-12-01

that this policy is waived for about 99 percent of new employees. Waivers have become routine because waiting for background investigation results would adversely affect hiring and recruiting, according to NRC staff. NRC policies do not require reinvestigation of the backgrounds of nearly 50 percent of its clearance holders. Therefore, NRC does not know whether circumstances in some employees' lifestyles have changed, making them security risks. NRC security staff cited financial reasons for not requiring reinvestigations for all other employees. Further, NRC does not have accurate clearance information, for example, data to determine when reinvestigations are needed to effectively manage its program. In addition, for over a decade, NRC has debated the need for regulations to ensure that nuclear power plant employees requiring unescorted access to power plants do not pose a threat of radiological sabotage. NRC still has not decided whether it will issue a regulation or endorse industry-developed guidelines
Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression

International Nuclear Information System (INIS)

Kim, Sung Young; Ryu, Sung Jin; Ahn, Hong Ju; Choi, Hae Ri; Kang, Hyun Tae; Park, Sang Chul

2010-01-01

One of the characteristic natures of senescent cells is the hypo- or irresponsiveness not only to growth factors but also to apoptotic stress. In the present study, we confirmed the inhibition of nuclear translocation of activated p-ERK1/2 and NF-kB p50 in response to growth stimuli or LPS in the senescent human diploid fibroblasts. In order to elucidate the underlying mechanism for the senescence-associated hypo-responsiveness, we carried out the comparison study for gene expression profiles through microarray analysis. In consequence, we observed the vast reduction in expression of nucleo-cytoplasmic trafficking genes in senescent cells, when compared with those in young cells. Expression levels of several nucleoporins, karyopherin α, karyopherin β, Ran, and Ran-regulating factors were confirmed to be down-regulated in senescent HDFs by using RT-PCR and Western blot methods. Taken together, these data suggest the operation of certain senescence-associated functional nuclear barriers by down-regulation of the nucleo-cytoplasmic trafficking genes in the senescent cells.
Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Young; Ryu, Sung Jin; Ahn, Hong Ju; Choi, Hae Ri; Kang, Hyun Tae [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Park, Sang Chul, E-mail: scpark@snu.ac.kr [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

2010-01-01

One of the characteristic natures of senescent cells is the hypo- or irresponsiveness not only to growth factors but also to apoptotic stress. In the present study, we confirmed the inhibition of nuclear translocation of activated p-ERK1/2 and NF-kB p50 in response to growth stimuli or LPS in the senescent human diploid fibroblasts. In order to elucidate the underlying mechanism for the senescence-associated hypo-responsiveness, we carried out the comparison study for gene expression profiles through microarray analysis. In consequence, we observed the vast reduction in expression of nucleo-cytoplasmic trafficking genes in senescent cells, when compared with those in young cells. Expression levels of several nucleoporins, karyopherin {alpha}, karyopherin {beta}, Ran, and Ran-regulating factors were confirmed to be down-regulated in senescent HDFs by using RT-PCR and Western blot methods. Taken together, these data suggest the operation of certain senescence-associated functional nuclear barriers by down-regulation of the nucleo-cytoplasmic trafficking genes in the senescent cells.
De-regulated electric power markets and operating nuclear power plants: the case of British energy

International Nuclear Information System (INIS)

Hewlett, James G.

2005-01-01

One issue addressed in almost all electric power restructuring/de-regulation plans in both the United States (US) and the United Kingdom (UK) was the recovery of operating nuclear power plant's spent fuel disposal costs and the expenditures to decommission the units when they are retired. Prior to restructuring, in theory at least, in both countries, electricity consumers were paying for the back end costs from operating nuclear power plants. Moreover, in virtually all cases in the US, states included special provisions to insure that consumers would continue to do so after power markets were de-regulated. When power markets in the UK were initially restructured/de-regulated and nuclear power privatized, the shareholders of British Energy (BE) were initially responsible for these costs. However, after electricity prices fell and BE collapsed, the British government shifted many of the costs to future taxpayers, as much as a century forward. If this was not done, the book value of BE's equity would have been about -3.5 billion pounds. That is, BE's liabilities would have been about -3.5 billion pounds greater than their assets. It is difficult to see how BE could remain viable under such circumstances

The nuclear industry's transition to risk-informed regulation and operation in the United States

International Nuclear Information System (INIS)

Kadak, Andrew C.; Matsuo, Toshihiro

2007-01-01

This paper summarizes a study of the transition of the United States nuclear industry from a prescriptive regulatory structure to a more risk informed approach to operations and regulations. The transition occurred over a 20 yr period in which gradual changes were made in the fundamental regulations and to the approach to nuclear safety and operations. While the number of actual regulatory changes were few, they are continuing. The utilities that embraced risk informed operations made dramatic changes in the way they approached operations and outage management. Those utilities that used risk in operations showed dramatic improvement in safety based on Institute of Nuclear Power Operations (INPO) performance indicators. It was also shown that the use of risk did not negatively affect safety performance of the plants compared to standard prescriptive approaches. This was despite having greater flexibility in compliance to regulatory standards and the use of the newly instituted risk-informed reactor oversight process. Key factors affecting the successful transition to a more risk-informed approach to regulations and operations are: strong top management support and leadership both at the regulator and the utility; education and training in risk principles and probabilistic risk Assessment tools for engineers, operators and maintenance staff; a slow and steady introduction of risk initiatives in areas that can show value to both the regulator and the industry; a transparent regulatory foundation built around a safety goal policy and the development of a strong safety culture at the utility to allow for more independence in safety compliance and risk management. The experience of the United States shows positive results in both safety and economics. The INPO and NRC metrics presented show that the use of risk information in operations and regulation is marginally better with no degradation in safety when plants that have embraced risk-informed approaches are compared
Public regulation of site selection for nuclear power plants. Present procedures and reform proposals: an annotated bibliography

International Nuclear Information System (INIS)

Klema, E.D.; West, R.L.

1977-01-01

Part I of this bibliography contains literature which describes the process of power-plant siting as conducted by the utilities, siting procedures at the point of initiative, analytical tools employed or proposed for site assessment by enterprises in the industry, and the wide range of considerations which the utilities take into account in making site assessments. Part II contains studies and reports on the structure and process of public regulation of power plant siting: the licensing of nuclear facilities by the NRC under terms of the special Government powers in the field of nuclear energy that have evolved since World War II; the steady expansion of regulatory objectives bearing on site approval for nuclear power plants; local government, State, and other Federal agency regulation of siting; survey siting procedures in other countries; the role of regulatory delay in the long lead-time required for construction and operation of nuclear plants. Part III incudes citations on regulatory structure and practice that are unresponsive to the public interest; regulatory decision making's insufficient accessible to public scrutiny and participation; and regulatory procedures that encourage and protect inefficient practices of the regulated industries. Some legal decisions and case studies are included. Part IV, Reform Proposals, includes citations on regulatory reform and reform of siting regulations. Abstracts are provided with 157 of the citations with many more papers cited by title, author, and accession data
Incentive regulation of nuclear power plants by state Public Utility Commissions

International Nuclear Information System (INIS)

Martin, R.L.; Olson, J.; Hendrickson, P.

1989-12-01

Economic performance incentives established by state Public Utility Commissions (PUCs) currently are applicable to the construction or operation of approximately 73 nuclear power reactors owned by 27 utilities with investment greater than 10% in 18 states. The NRC staff monitors development of the incentives and periodically provides an updated report on all nuclear plant incentives to its headquarters and regional offices. The staff maintains contact with the PUCs and the utilities responsible for implementing the incentives in order to obtain the updated information and to consider potential safety effects of the incentives. This report on incentive regulation of nuclear power plants by state PUCs presents the NRC staff's concerns on potential safety effects of economic performance incentives. It also includes a plant-by-plant survey that describes the mechanics of each incentive and discusses the financial effects of the incentive on the utility-owner(s) of the plant
Note n. SD3-DEM-01 regulations procedures relative to the based nuclear installations dismantling

International Nuclear Information System (INIS)

2003-02-01

This note aims to define the regulations procedures relative to the safety of based nuclear installations dismantling defined by the decree of the 11 december 1963 modified. The first part describes the two main phases of a based nuclear installation life, the operating and the dismantling phase. The second part is devoted to the procedures. (A.L.B.)
Organization and regulation of nuclear medicine and radiotherapy in Argentina

International Nuclear Information System (INIS)

Degrossi, O.J.; Altschuler, Noe; Mugliaroli, H.A.

1982-01-01

After describing the efforts carried out in Argentina during the decade of 1970 to consolidate nuclear medicine as a new clinical specialty, reference is made to the constitution, in 1979, of a Joint Advisory Committee on Nuclear Medicine and Radiotherapy integrated by members of the National Atomic Energy Commission and by members of the Public Health Ministry of the Nation, with the purpose to coordinate and plan said activities within the country. Two recommendations of said Advisory Committee are transcribed. The first one defines the different specialties of the professionals and technicians working in the new discipline. The second recommendation is referred to the regulations on ''Operation of Nuclear Medicine Units'', which set up different categories of medical establishments of the specialty (''unit'', ''service'' and ''center''), define their respective functions as well as the equipment and specialized personnel that they should be fitted with in each case, and institute the requirement to demonstrate having the corresponding academic and professional up-dating in the specialty to obtain the periodic revalidation of operation licences. (C.A.K.) [es
New quantitative approaches reveal the spatial preference of nuclear compartments in mammalian fibroblasts.

Science.gov (United States)

Weston, David J; Russell, Richard A; Batty, Elizabeth; Jensen, Kirsten; Stephens, David A; Adams, Niall M; Freemont, Paul S

2015-03-06

The nuclei of higher eukaryotic cells display compartmentalization and certain nuclear compartments have been shown to follow a degree of spatial organization. To date, the study of nuclear organization has often involved simple quantitative procedures that struggle with both the irregularity of the nuclear boundary and the problem of handling replicate images. Such studies typically focus on inter-object distance, rather than spatial location within the nucleus. The concern of this paper is the spatial preference of nuclear compartments, for which we have developed statistical tools to quantitatively study and explore nuclear organization. These tools combine replicate images to generate 'aggregate maps' which represent the spatial preferences of nuclear compartments. We present two examples of different compartments in mammalian fibroblasts (WI-38 and MRC-5) that demonstrate new knowledge of spatial preference within the cell nucleus. Specifically, the spatial preference of RNA polymerase II is preserved across normal and immortalized cells, whereas PML nuclear bodies exhibit a change in spatial preference from avoiding the centre in normal cells to exhibiting a preference for the centre in immortalized cells. In addition, we show that SC35 splicing speckles are excluded from the nuclear boundary and localize throughout the nucleoplasm and in the interchromatin space in non-transformed WI-38 cells. This new methodology is thus able to reveal the effect of large-scale perturbation on spatial architecture and preferences that would not be obvious from single cell imaging.
Value-impact analysis of regulations for the nuclear industry

International Nuclear Information System (INIS)

Al-Ayat, R.; Judd, B.; Huntsman, J.

1980-01-01

This paper summarizes a quantitative tool developed at Lawrence Livermore National Laboratory to aid the NRC in establishing Material Control and Accounting (MC and A) regulations for safeguarding Special Nuclear Material (SNM). Illustrative Value-Impact results of demonstrating the methodology at a facility handling SNM to evaluate alternative safeguards rules is given. The methodology developed also offers a useful framework for facility designers to choose safeguards measures that meet the NRC's criteria in a cost-effective manner. Furthermore, the methodology requires very modest computing capability and is straightforward to apply
National policies and regulations for decommissioning nuclear facilities

International Nuclear Information System (INIS)

1993-07-01

This report, though produced as a follow-up to Safety Series No. 105, The Regulatory Process for the Decommissioning of Nuclear Facilities, is not primarily intended as guidance. Rather, its objective is to provide an overview of national decommissioning policies and regulatory practices as part of the background knowledge which is an essential precondition for good decision making. It discusses the reasons for the similarities and differences in national approach using specific examples but without giving preference to any particular scheme; it aims rather to provide factual, general information on the choices that have been or are being made, and why. As many Member States are in a transient situation between the case-by-case approach to decommissioning and the establishment of national policies, strategies and regulations, this seems the right moment to assess existing national practices worldwide and that is the purpose for which the document is issued at this time. The information gathered in this report is based on submissions by Member States which have developed or are in the process of developing decommissioning oriented policies and regulations. 29 refs
An Overview of the Regulation of Low Dose Radiation in the Nuclear and Non-nuclear Industries

International Nuclear Information System (INIS)

Menon, Shankar; Valencia, Luis; Teunckens, Lucien

2003-01-01

Now that increasing numbers of nuclear power stations are reaching the end of their commercially useful lives, the management of the large quantities of very low level radioactive material that arises during their decommissioning has become a major subject of discussion, with very significant economic implications. Much of this material can, in an environmentally advantageous manner, be recycled for reuse without radiological restrictions. Much larger quantities--2-3 orders of magnitude larger--of material, radiologically similar to the candidate material for recycling from the nuclear industry, arise in non-nuclear industries like coal, fertilizer, oil and gas, mining, etc. In such industries, naturally occurring radioactivity is artificially concentrated in products, by-products or waste to form TENORM (Technologically Enhanced Naturally Occurring Radioactive Material). It is only in the last decade that the international community has become aware of the prevalence of TENORM, specially the activity levels and quantities arising in so many non-nuclear industries. The first reaction of international organizations seems to have been to propose different standards for the nuclear and non-nuclear industries, with very stringent release criteria for radioactive material from the regulated nuclear industry and up to thirty to a hundred times more liberal criteria for the release/exemption of TENORM from the as yet unregulated non-nuclear industries. There are significant strategic issues that need to be discussed and resolved. Some examples of these are: - Disposal aspects of long-lived nuclides, - The use of radioactive residues in building materials, - Commercial aspects of differing and discriminating criteria in competing power industries in a world of deregulated electric power production. Of even greater importance is the need for the discussion of certain basic issues, such as - The quantitative risk levels of exposure to ionizing radiation, - The need for in
An underground nuclear power station using self-regulating heat-pipe controlled reactors

Science.gov (United States)

Hampel, V.E.

1988-05-17

A nuclear reactor for generating electricity is disposed underground at the bottom of a vertical hole that can be drilled using conventional drilling technology. The primary coolant of the reactor core is the working fluid in a plurality of thermodynamically coupled heat pipes emplaced in the hole between the heat source at the bottom of the hole and heat exchange means near the surface of the earth. Additionally, the primary coolant (consisting of the working fluid in the heat pipes in the reactor core) moderates neutrons and regulates their reactivity, thus keeping the power of the reactor substantially constant. At the end of its useful life, the reactor core may be abandoned in place. Isolation from the atmosphere in case of accident or for abandonment is provided by the operation of explosive closures and mechanical valves emplaced along the hole. This invention combines technology developed and tested for small, highly efficient, space-based nuclear electric power plants with the technology of fast- acting closure mechanisms developed and used for underground testing of nuclear weapons. This invention provides a nuclear power installation which is safe from the worst conceivable reactor accident, namely, the explosion of a nuclear weapon near the ground surface of a nuclear power reactor. 5 figs.
Dual personality of Mad1: regulation of nuclear import by a spindle assembly checkpoint protein.

Science.gov (United States)

Cairo, Lucas V; Ptak, Christopher; Wozniak, Richard W

2013-01-01

Nuclear transport is a dynamic process that can be modulated in response to changes in cellular physiology. We recently reported that the transport activity of yeast nuclear pore complexes (NPCs) is altered in response to kinetochore-microtubule (KT-MT) interaction defects. Specifically, KT detachment from MTs activates a signaling pathway that prevents the nuclear import of cargos by the nuclear transport factor Kap121p. This loss of Kap121p-mediated import is thought to influence the nuclear environment, including the phosphorylation state of nuclear proteins. A key regulator of this process is the spindle assembly checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss the underlying mechanisms and the physiological relevance of Mad1p cycling and the inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions within the pathway.
Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity.

Directory of Open Access Journals (Sweden)

Nadja Knoll

Full Text Available There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1 16 nuclear regulators of mitochondrial genes, (2 91 genes for oxidative phosphorylation and (3 966 nuclear-encoded mitochondrial genes. Gene set enrichment analysis (GSEA showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents and a population-based GWAS sample (KORA F4, n = 1,743. A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th and 95(th percentile of the set of all gene-wise corrected p-values as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50 = 0.0103. This finding was not confirmed in the trios (p(GSEA,50 = 0.5991, but in KORA (p(GSEA,50 = 0.0398. The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50 = 0.1052, p(MAGENTA,75 = 0.0251. The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes.
24th WRSM panel discussion: open-quotes The role of research in nuclear regulation: The case of qualified importersclose quotes

International Nuclear Information System (INIS)

Alonso, A.

1997-01-01

Scientific knowledge and technological maturity are needed to establish regulatory requirements, what also needs talent and skills. Scientists are rarely interested in regulation and regulators not always are closely connected to scientific research. This has created gaps in regulations, mainly within qualified importers. A qualified importer, in the sense of this presentation, is a country who has acquired nuclear power plants from more technologically advanced exporters but with an increasing participation of its own industry and institutions in the design, construction, component manufacture and assembly of such nuclear power plants and is fully responsible for the operation of the nuclear units and the corresponding fuel cycle. These countries have also a long standing and independent nuclear regulatory organization and the corresponding technical body. Spain is a qualified importer. In the case of Spain, it originally adopted the codes and regulations of the UE which it was a member of, as well as the codes and standards of the country from which their reactors were produced. Since Spain added KWU plants they even went to German regulations. Plant operation rested with Spain. As problems began to appear in operating plants, local research projects were funded to study the problems, aimed at immediate solutions, but also providing training for local personnel in addition to information of use for regulators. Spain has participated in many joint research projects, which have trained people, and given confidence to Spaniards involved in science and regulations. Qualified importers, like Spain, participate in research, even though it may not translate itself into regulation. Such participation will always serve to give self-confidence and independence to regulators and licensees, to better understand the adopted regulations of the most advanced countries and to solve specific problems
Star-PAP Control of BIK Expression and Apoptosis Is Regulated by Nuclear PIPKIα and PKCδ Signaling

Science.gov (United States)

Li, Weimin; Laishram, Rakesh S.; Ji, Zhe; Barlow, Christy A.; Tian, Bin; Anderson, Richard A.

2012-01-01

SUMMARY BIK protein is an initiator of mitochondrial apoptosis and BIK expression is induced by pro-apoptotic signals including DNA damage. Here we demonstrate that 3′-end processing and expression of BIK mRNA are controlled by the nuclear PI4,5P2-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKCδ is a key mediator of apoptosis and DNA damage stimulates PKCδ association with the Star-PAP complex where PKCδ is required for Star-PAP-dependent BIK expression. PKCδ binds the PI4,5P2-generating enzyme PIPKIα, which is essential for PKCδ interaction with the Star-PAP complex and PKCδ activity is directly stimulated by PI4,5P2. Features in the BIK 3′-UTR uniquely define Star-PAP specificity and may block canonical PAP activity toward BIK mRNA. This reveals a nuclear phosphoinositide signaling nexus where PIPKIα, PI4,5P2 and PKCδ regulate Star-PAP control of BIK expression and induction of apoptosis. This pathway is distinct from the Star-PAP-mediated oxidative stress pathway indicating signal-specific regulation of mRNA 3′-end processing. PMID:22244330
Policy for introduction of risk-informed regulation for nuclear facilities in Japan

International Nuclear Information System (INIS)

Akihide Hidaka; Shoichiro Sakaguchi; Toshihiro Bannai; Kunihiro Matsui

2005-01-01

The nuclear safety regulations in Japan place a basis on the deterministic approach with the defence-in-depth philosophy and engineering judgments. However, as the development of PSA (Probabilistic Safety Assessment) technologies in recent years, the Nuclear Safety Commission (NSC) began to consider that the utilization of risk information in addition to the traditional deterministic approach could be very effective for the safety regulations to improve rationality, consistency, transparency and efficiency by appropriate allocation of limited resources for the regulatory activities. In order to show the basic strategy, the NSC published the policy for introduction of Risk-Informed Regulation (RIR) in November 2003. The safety goals that play an important role in RIR were tentatively established in December 2003 while the performance goals are under development as of May, 2005. It is expected that RIR be gradually introduced from the applicable area. The NSC is now examining what the RIR system in Japan should be by making each role and incentive of the competent organizations clear. In the future, when the experiences on application of the safety goals are accumulated, RIR will be consistently applied from design to operational area. This paper describes the recent activities of the NSC for introduction of RIR in Japan and development of the safety goals including the performance goals. (authors)
The Swedish radiation protection institute's regulations and general advice on nuclear medicine; issued on April 28, 2000

International Nuclear Information System (INIS)

2000-04-01

These regulations and general advice are applicable to nuclear medicine within human medical care. The regulations are also applicable to activities where radioactive substances are administered to individuals in connection to medical or biomedical research and medical examinations for insurance or legal purposes
Is self-regulation possible

International Nuclear Information System (INIS)

Barkenbus, J.N.

1983-01-01

The Nuclear Regulatory Commission's increasingly prescriptive regulation of the nuclear industry can have deleterious effects, perhaps the most serious being the shift in responsibility for safety from the utility to the NRC. Several factors account for this type of regulation including the nature and structure of the nuclear industry, public opinion and bureaucratic incentives, and the nature of the technology itself. The opportunities to create heightened industry self-regulation (performance-based regulation) deserve further examination. The key to self-regulation is to structure incentives so that it is clearly within the nuclear utilities' interests to build and operate nuclear power facilities in the safest manner possible. 27 references
Regulation of nuclear materials control and accountability and inspection practices in the Russian Federation

International Nuclear Information System (INIS)

Volodin, Y.G.; Dimitriev, A.M.; Krouptchatnikov, B.N.

1999-01-01

Review and assessment of the resent state orders and directives regulating nuclear materials control and accountability, defining responsibilities and incorporation of different agencies in nuclear materials control and accountability (MC and A) area in Russia, related actions to stipulate tasks in developing the State System of Accounting for and Control of Nuclear Materials (SSAC) and a role of the Federal Nuclear and Radiation Safety Authority of Russia (Gosatomnadzor) in this process is presented. Main principles, elements and practical results of Gosatomnadzor inspection activities are reported. Elements of the SSAC, status of works in establishment of the SSAC and in implementation of fragments of the SSAC, an international assistance in up-grading MC and A systems at some of the Russian facilities and in establishing the SSAC in Russia is outlined. (author)
Impact of the Application of Exemption Regulation to the Non-nuclear Industry in Indonesia

International Nuclear Information System (INIS)

Eri-Hiswara

2001-01-01

Nuclear Energy Control Board (BAPETEN) as a nuclear regulatory authority in Indonesia has published the exemption regulation that establishes the value of activity, activity concentration, and dose rate for practices that their operations do not require a licence. From an assessment it was found that the value of activity concentration and dose rate have been exceeded by technologically enhanced naturally occurring radioactive materials (TENORM) present in the raw material and product/waste of some mining and mineral industries known so far as non-nuclear industry. The result has the impact that those industries should be categorized as nuclear industry, with the implication that they need to have licence from regulatory authority, and their activities need to be inspected regularly from the radiation safety point of view by the authority. (author)
RNAi-Based Identification of Gene-Specific Nuclear Cofactor Networks Regulating Interleukin-1 Target Genes

Directory of Open Access Journals (Sweden)

Johanna Meier-Soelch

2018-04-01

Full Text Available The potent proinflammatory cytokine interleukin (IL-1 triggers gene expression through the NF-κB signaling pathway. Here, we investigated the cofactor requirements of strongly regulated IL-1 target genes whose expression is impaired in p65 NF-κB-deficient murine embryonic fibroblasts. By two independent small-hairpin (shRNA screens, we examined 170 genes annotated to encode nuclear cofactors for their role in Cxcl2 mRNA expression and identified 22 factors that modulated basal or IL-1-inducible Cxcl2 levels. The functions of 16 of these factors were validated for Cxcl2 and further analyzed for their role in regulation of 10 additional IL-1 target genes by RT-qPCR. These data reveal that each inducible gene has its own (quantitative requirement of cofactors to maintain basal levels and to respond to IL-1. Twelve factors (Epc1, H2afz, Kdm2b, Kdm6a, Mbd3, Mta2, Phf21a, Ruvbl1, Sin3b, Suv420h1, Taf1, and Ube3a have not been previously implicated in inflammatory cytokine functions. Bioinformatics analysis indicates that they are components of complex nuclear protein networks that regulate chromatin functions and gene transcription. Collectively, these data suggest that downstream from the essential NF-κB signal each cytokine-inducible target gene has further subtle requirements for individual sets of nuclear cofactors that shape its transcriptional activation profile.

TBLR1 regulates the expression of nuclear hormone receptor co-repressors

Directory of Open Access Journals (Sweden)

Brown Stuart

2006-08-01

Full Text Available Abstract Background Transcription is regulated by a complex interaction of activators and repressors. The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes. Results TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone transcription factors. A single highly conserved gene encodes a small family of protein molecules. Different isoforms are produced by differential exon utilization. Although the ORF of the predominant form contains only 1545 bp, the human gene occupies ~200 kb of genomic DNA on chromosome 3q and contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank: NM030921] locus. The murine homologue is structurally similar and is also located on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level to TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form of TBLR1 has been demonstrated in human material and it too has an unique pattern of expression. TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. In resting cells TBLR1 is primarily cytoplasmic but after perturbation the protein translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C-terminal deletion variants, have elevated levels of endogenous N-CoR. Co-transfection of TBLR1 and SMRT results in increased expression of SMRT. This co-repressor undergoes ubiquitin-mediated degradation and we suggest that the stabilization of
Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

Science.gov (United States)

Pak, Jhang Ho; Shin, Jimin; Song, In-Sung; Shim, Sungbo; Jang, Sung-Wuk

2017-01-01

Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory-secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of IκBα and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of IκBα and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.
Virion assembly factories in the nucleus of polyomavirus-infected cells.

Directory of Open Access Journals (Sweden)

Kimberly D Erickson

Full Text Available Most DNA viruses replicate in the cell nucleus, although the specific sites of virion assembly are as yet poorly defined. Electron microscopy on freeze-substituted, plastic-embedded sections of murine polyomavirus (PyV-infected 3T3 mouse fibroblasts or mouse embryonic fibroblasts (MEFs revealed tubular structures in the nucleus adjacent to clusters of assembled virions, with virions apparently "shed" or "budding" from their ends. Promyelocytic leukemia nuclear bodies (PML-NBs have been suggested as possible sites for viral replication of polyomaviruses (BKV and SV40, herpes simplex virus (HSV, and adenovirus (Ad. Immunohistochemistry and FISH demonstrated co-localization of the viral T-antigen (Tag, PyV DNA, and the host DNA repair protein MRE11, adjacent to the PML-NBs. In PML⁻/⁻ MEFs the co-localization of MRE11, Tag, and PyV DNA remained unchanged, suggesting that the PML protein itself was not responsible for their association. Furthermore, PyV-infected PML⁻/⁻ MEFs and PML⁻/⁻ mice replicated wild-type levels of infectious virus. Therefore, although the PML protein may identify sites of PyV replication, neither the observed "virus factories" nor virus assembly were dependent on PML. The ultrastructure of the tubes suggests a new model for the encapsidation of small DNA viruses.
The UK health and safety executive's policies on information relating to nuclear safety regulation

International Nuclear Information System (INIS)

Williams, L.

1994-01-01

How a message is transmitted can be as important as what is said. To be effective a message has to be timely, targeted and clear. People do not always remember what was said, by how and when it was said. This paper discusses some of the tools which the Nuclear Safety Division (NSD), the UK's nuclear regulator, has used and emphasizes the need to recognize the importance of a recipient interest in attempting to transmit a message. (author). 4 refs
The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells

Energy Technology Data Exchange (ETDEWEB)

Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang, E-mail: wchai@wsu.edu

2017-06-15

Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. - Highlights: • CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle. • CST is important for promoting telomeric DNA replication in ALT cells. • CST deficiency decreases ECTR formation and increases T-SCE. • CST deficiency impairs ALT cell proliferation and results in multinucleation.
Redefining interrelationship between nuclear safety, nuclear security and safeguards

International Nuclear Information System (INIS)

Irie, Kazutomo

2011-01-01

Since the beginning of this century, the so-called 3Ss (Nuclear Safety, Nuclear Security and Safeguards) have become major regulatory areas for peaceful uses of nuclear energy. The importance of the 3Ss is now emphasized to countries which are newly introducing nuclear power generation. However, as role models for those newcomers, existing nuclear power countries are also required to strengthen their regulatory infrastructure for the 3Ss. In order to rationalize the allocation of regulatory resources, interrelationship of the 3Ss should be investigated. From the viewpoint of the number of the parties concerned in regulation, nuclear security is peculiar with having 'aggressors' as the third party. From the viewpoint of final goal of regulation, nuclear security in general and safeguards share the goal of preventing non-peaceful uses of nuclear energy, though the goal of anti-sabotage within nuclear security is rather similar to nuclear safety. As often recognized, safeguards are representative of various policy tools for nuclear non-proliferation. Strictly speaking, it is not safeguards as a policy tool but nuclear non-proliferation as a policy purpose that should be parallel to other policy purposes (nuclear safety and nuclear security). That suggests 'SSN' which stands for Safety, Security and Non-proliferation is a better abbreviation rather than 3Ss. Safeguards as a policy tool should be enumerated along with nuclear safety regulation, nuclear security measures and trade controls on nuclear-related items. Trade controls have been playing an important role for nuclear non-proliferation. These policy tools can be called 'SSST' in which Trade controls are also emphasized along with Safety regulation, Security measures and Safeguards. Recently, it becomes quite difficult to clearly demarcate these policy tools. As nuclear security concept is expanding, the denotation of nuclear security measures is also expanding. Nuclear security measures are more and more
Dual localized mitochondrial and nuclear proteins as gene expression regulators in plants?

Directory of Open Access Journals (Sweden)

Philippe eGiegé

2012-09-01

Full Text Available Mitochondria heavily depend on the coordinated expression of both mitochondrial and nuclear genomes because some of their most significant activities are held by multi-subunit complexes composed of both mitochondrial and nuclear encoded proteins. Thus, precise communication and signaling pathways are believed to exist between the two compartments. Proteins dual localized to both mitochondria and the nucleus make excellent candidates for a potential involvement in the envisaged communication. Here, we review the identified instances of dual localized nucleo-mitochondrial proteins with an emphasis on plant proteins and discuss their functions, which are seemingly mostly related to gene expression regulation. We discuss whether dual localization could be achieved by dual targeting and / or by re-localization and try to apprehend the signals required for the respective processes. Finally, we propose that in some instances, dual localized mitochondrial and nuclear proteins might act as retrograde signaling molecules for mitochondrial biogenesis.
CSNI technical opinion papers no.5. Managing and regulating organisational change in nuclear installations

International Nuclear Information System (INIS)

2004-01-01

Nuclear licensees are increasingly required to adapt to a more challenging commercial environment as electricity markets are liberalized. One of the costs that is often perceived as being amenable to control is staffing, and hence there is significant exploration of new strategies for managing this cost - for example, by reducing staffing levels, changing organisational structures, adopting new shift strategies, introducing new technology or increasing the proportion of work carried out by external contractors. However, if changes to staffing levels or organisational structures and systems are inadequately conceived or executed they have the potential to affect the way in which safety is managed. In this context, the NEA Committee on the Safety of Nuclear Installations (CSNI) and its Special Expert Group on Human and Organisational Factors (SEGHOF) organised an international workshop to discuss the management and regulation of organisational change in 2001. This technical opinion paper distills the findings of that workshop and sets out the factors that regulatory bodies might reasonably expect to be addressed within licensees arrangements to manage organisational change. The paper should be of particular interest to both regulators and managers of nuclear utilities. (author)
Challenges Faced by Regulators and Technical, Scientific and Support Organizations (TSOs) in Enhancing Nuclear Safety and Security

International Nuclear Information System (INIS)

Travers, W.D.

2011-01-01

Renewed interest in new reactor build programmes, not only in countries with already established nuclear programmes but also in many other countries with limited or no workforce experienced in the design, licensing, construction and operation of nuclear power plants, has resulted in a need for technical, scientific and support organizations (TSOs) to support regulatory bodies in carrying out their mandated responsibilities. The primary function of a regulatory body, such as the Federal Authority for Nuclear Regulation (FANR) in the United Arab Emirates (UAE), is to regulate the safe use of nuclear facilities and radioactive material for peaceful civilian purposes. In so doing, the regulatory body needs to provide a clear and focused approach to: safety, security and safeguards for licensing; inspection and enforcement of reactor design; construction; commissioning; operation; decommissioning; nuclear waste management activities; and the use, possession or transfer of special nuclear materials and activities within the country. Accomplishing this goal requires a highly educated, multidisciplinary, diverse workforce with significant work experience. Recognizing that it takes several decades and a lot of resources to achieve self-sufficiency, many countries, particularly emergent nuclear countries, would have to rely on TSOs to start their programmes and to carry out their oversight responsibilities. Towards that end, FANR is working closely with international counterparts, the International Atomic Energy Agency and TSOs to exchange information, expertise, industry experience and ongoing research to ensure that high levels of safety, security and safeguards are established and maintained in reactor design and operation throughout the life of the facility, and that special nuclear material within the UAE is properly documented and controlled, is not stolen, lost or diverted to any illicit or non-peaceful activities, and does not pose unreasonable radiological risk due
Sun-mediated mechanical LINC between nucleus and cytoskeleton regulates βcatenin nuclear access.

Science.gov (United States)

Uzer, Gunes; Bas, Guniz; Sen, Buer; Xie, Zhihui; Birks, Scott; Olcum, Melis; McGrath, Cody; Styner, Maya; Rubin, Janet

2018-06-06

βcatenin acts as a primary intracellular signal transducer for mechanical and Wnt signaling pathways to control cell function and fate. Regulation of βcatenin in the cytoplasm has been well studied but βcatenin nuclear trafficking and function remains unclear. In a previous study we showed that, in mesenchymal stem cells (MSC), mechanical blockade of adipogenesis relied on inhibition of βcatenin destruction complex element GSK3β (glycogen synthase kinase 3β) to increase nuclear βcatenin as well as the function of Linker of Cytoskeleton and Nucleoskeleton (LINC) complexes, suggesting that these two mechanisms may be linked. Here we show that shortly after inactivation of GSK3β due to either low intensity vibration (LIV), substrate strain or pharmacologic inhibition, βcatenin associates with the nucleoskeleton, defined as the insoluble nuclear fraction that provides structure to the integrated nuclear envelope, nuclear lamina and chromatin. Co-depleting LINC elements Sun-1 and Sun-2 interfered with both nucleoskeletal association and nuclear entry of βcatenin, resulting in decreased nuclear βcatenin levels. Our findings reveal that the insoluble structural nucleoskeleton actively participates in βcatenin dynamics. As the cytoskeleton transmits applied mechanical force to the nuclear surface to influence the nucleoskeleton and its LINC mediated interaction, our results suggest a pathway by which LINC mediated connectivity may play a role in signaling pathways that depend on nuclear access of βcatenin. Copyright © 2018 Elsevier Ltd. All rights reserved.
Status of the support researches for the regulation of nuclear facilities decommissioning in Japan

International Nuclear Information System (INIS)

Masuda, Yusuke; Iguchi, Yukihiro; Kawasaki, Satoru; Kato, Masami

2011-01-01

In Japan, 4 nuclear power stations are under decommissioning and some nuclear fuel cycle facilities are expected to be decommissioned in the future. On the other hand, the safety regulation of decommissioning of nuclear facilities was changed by amending act in 2005. An approval system after review process of decommissioning plan was adopted and applied to the power stations above. In this situation, based on the experiences of the new regulatory system, the system should be well established and moreover, it should be improved and enhanced in the future. Nuclear Industry and Safety Agency (NISA) is in charge of regulation of commercial nuclear facilities in Japan and decommissioning of them is included. Japan Nuclear Energy Safety Organization (JNES) is in charge of technical supports for NISA as a TSO (Technical Support Organization) also in this field. As for decommissioning, based on regulatory needs, JNES has been continuing research activities from October 2003, when JNES has been established. Considering the 'Prioritized Nuclear Safety Research Plan (August 2009)' of the Nuclear Safety Commission of Japan and the situation of operators facilities, 'Regulatory Support Research Plan between FY 2010-2014' was established in November 2009, which shows the present regulatory needs and a research program. This program consists of researches for 1. review process of decommissioning plan of power reactors, 2. review process of decommissioning plan of nuclear fuel cycle facilities, 3. termination of license at the end of decommissioning and 4. management of decommissioning waste. For the item 1, JNES studied safety assessment methods of dismantling, e.g. obtaining data and analysis of behavior of dust diffusion and risk assessment during decommissioning, which are useful findings for the review process. For the item 2, safety requirements for the decommissioning of nuclear fuel cycle facilities was compiled, which will be used in the future review. For the item 3
Redefining interrelationship between nuclear safety, nuclear security and safeguards

International Nuclear Information System (INIS)

Irie, Kazutomo

2012-01-01

Since the beginning of this century, the so-called 3Ss (Nuclear Safety, Nuclear Security and Safeguards) have become major regulatory areas for peaceful uses of nuclear energy. In order to rationalize the allocation of regulatory resources, interrelationship of the 3Ss should be investigated. From the viewpoint of the number of the parties concerned in regulation, nuclear security is peculiar with having “aggressors” as the third party. From the viewpoint of final goal of regulation, nuclear security in general and safeguards share the goal of preventing non-peaceful uses of nuclear energy, though the goal of anti-sabotage within nuclear security is rather similar to nuclear safety. As often recognized, safeguards are representative of various policy tools for nuclear non-proliferation. Strictly speaking, it is not safeguards as a policy tool but nuclear non-proliferation as a policy purpose that should be parallel to other policy purposes (nuclear safety and nuclear security). That suggests “SSN” which stands for Safety, Security and Non-proliferation is a better abbreviation rather than 3Ss. Safeguards as a policy tool should be enumerated along with nuclear safety regulation, nuclear security measures and trade controls on nuclear-related items. Trade controls have been playing an important role for nuclear non-proliferation. These policy tools can be called “SSST” in which Trade controls are also emphasized along with Safety regulation, Security measures and Safeguards. (author)
Nuclear IL-33 is a transcriptional regulator of NF-{kappa}B p65 and induces endothelial cell activation

Energy Technology Data Exchange (ETDEWEB)

Choi, Yeon-Sook; Park, Jeong Ae; Kim, Jihye; Rho, Seung-Sik; Park, Hyojin [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Young-Myeong [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon (Korea, Republic of); Kwon, Young-Guen, E-mail: ygkwon@yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2012-05-04

Highlights: Black-Right-Pointing-Pointer IL-33 as nuclear factor regulated expression of ICAM-1 and VCAM-1. Black-Right-Pointing-Pointer Nuclear IL-33 increased the transcription of NF-{kappa}B p65 by binding to the p65 promoter. Black-Right-Pointing-Pointer Nuclear IL-33 controls NF-{kappa}B-dependent inflammatory responses. -- Abstract: Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-{kappa}B complex and is involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-{alpha}-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-{kappa}B pathway; NF-{kappa}B p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-{kappa}B p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-{kappa}B p65.
A decade of understanding spatio-temporal regulation of DNA repair by the nuclear architecture.

Science.gov (United States)

Saad, Hicham; Cobb, Jennifer A

2016-10-01

The nucleus is a hub for gene expression and is a highly organized entity. The nucleoplasm is heterogeneous, owing to the preferential localization of specific metabolic factors, which lead to the definition of nuclear compartments or bodies. The genome is organized into chromosome territories, as well as heterochromatin and euchromatin domains. Recent observations have indicated that nuclear organization is important for maintaining genomic stability. For example, nuclear organization has been implicated in stabilizing damaged DNA, repair-pathway choice, and in preventing chromosomal rearrangements. Over the past decade, several studies have revealed that dynamic changes in the nuclear architecture are important during double-strand break repair. Stemming from work in yeast, relocation of a damaged site prior to repair appears to be at least partially conserved in multicellular eukaryotes. In this review, we will discuss genome and nucleoplasm architecture, particularly the importance of the nuclear periphery in genome stability. We will also discuss how the site of relocation regulates repair-pathway choice.
The nuclear IκB family of proteins controls gene regulation and immune homeostasis.

Science.gov (United States)

MaruYama, Takashi

2015-10-01

The inhibitory IκB family of proteins is subdivided into two groups based on protein localization in the cytoplasm or in the nucleus. These proteins interact with NF-κB, a major transcription factor regulating the expression of many inflammatory cytokines, by modulating its transcriptional activity. However, nuclear IκB family proteins not only interact with NF-κB to change its transcriptional activity, but they also bind to chromatin and control gene expression. This review provides an overview of nuclear IκB family proteins and their role in immune homeostasis. Copyright © 2015 Elsevier B.V. All rights reserved.
Risk informed regulation of nuclear facilities: Overview of the current status

International Nuclear Information System (INIS)

2005-02-01

This report provides guidance on the use of risk information by regulatory bodies as part of an integrated decision making process. This addresses the way in which risk information is being used in decisions about safety issues at nuclear plants, sometimes referred to as risk informed decision making, and how risk information is being used by regulatory bodies as an input into the activities that they carry out, sometimes referred to as risk informed regulation
Styles of nuclear regulation and their consequences

International Nuclear Information System (INIS)

Wilpert, B.

2005-01-01

This contribution is about the document published as 'Announcement of the Basic Principles of Safety Management Systems in Nuclear Power Plants' in the Federal Gazette (Bundesanzeiger) by the German Federal Ministry for the Environment, Nature Conservation, and Nuclear Safety (BMU) on July 27, 2004. A kind of checklist contains requirements to be taken into account as 'boundary conditions' in the implementation of safety management systems. In fact, every sentence in the document begins with a 'must' provision. Remarkably enough, these 'Basic Principles' were promulgated by the Ministry without any consultation with advisory bodies, such as the Advisory Committee on Reactor Safeguards (RSK), or organizations of plant operators. The paper contains much that is worth considering, but also many truisms. This article was written because of the way in which the document had been prepared and publicized. An effort is made in this article to generate some understanding of the consequences, in terms of labor psychology and organizational psychology, of the different approaches pursued by regulatory authorities. A key point in this respect is the fundamental difference it makes whether regulations (reglementations) by supervisory authorities address the design of technical components or human behavior. In the former case, precise criteria without any constraints can serve the purpose. Behavioral rules, on the other hand, need a certain measure of flexibility, also in the way mistakes are handled, in order to avoid negative reactions on the part of those concerned. (orig.)
Regulation of nuclear radiation exposures in India

International Nuclear Information System (INIS)

Mishra, U.C.

2004-01-01

India has a long-term program of wide spread applications of nuclear radiations and radioactive sources for peaceful applications in medicine, industry, agriculture and research and is already having several thousand places in the country where such sources are being routinely used. These places are mostly outside the Department of Atomic Energy (DAE) installations. DAE supplies such sources. The most important application of nuclear energy in DAE is in electricity generation through nuclear power plants. Fourteen such plants are operating and many new plants are at various stages of construction. In view of the above mentioned wide spread applications, Indian parliament through an Act, called Atomic Energy Act, 1964 created an autonomous body called Atomic Energy Regulatory Board (AERB) with comprehensive authority and powers. This Board issues codes, guides, manuals, etc., to regulate such installations so as to ensure safe use of such sources and personnel engaged in such installations and environment receives radiation exposures within the upper bounds prescribed by them. Periodic reports are submitted to AERB to demonstrate compliance of its directives. Health, Safety and Environment Group of Bhabha Atomic Research Centres, Mumbai carries out necessary surveillance and monitoring of all installations of the DAE on a routine basis and also periodic inspections of other installations using radiation sources. Some of the nuclear fuel cycle plants like nuclear power plants and fuel reprocessing involve large radioactive source inventories and have potential of accidental release of radio activity into the environment, an Environmental Surveillance Laboratory (ESL) is set up at each such site much before the facility goes into operation. These ESL's collect baseline data and monitor the environment throughout the life of the facilities including the de- commissioning stage. The data is provided to AERB and is available to members of the public. In addition, a multi
Regulation of nuclear radiation exposures in India

Energy Technology Data Exchange (ETDEWEB)

Mishra, U.C. E-mail: ucmishra@yahoo.com

2004-07-01

India has a long-term program of wide spread applications of nuclear radiations and radioactive sources for peaceful applications in medicine, industry, agriculture and research and is already having several thousand places in the country where such sources are being routinely used. These places are mostly outside the Department of Atomic Energy (DAE) installations. DAE supplies such sources. The most important application of nuclear energy in DAE is in electricity generation through nuclear power plants. Fourteen such plants are operating and many new plants are at various stages of construction. In view of the above mentioned wide spread applications, Indian parliament through an Act, called Atomic Energy Act, 1964 created an autonomous body called Atomic Energy Regulatory Board (AERB) with comprehensive authority and powers. This Board issues codes, guides, manuals, etc., to regulate such installations so as to ensure safe use of such sources and personnel engaged in such installations and environment receives radiation exposures within the upper bounds prescribed by them. Periodic reports are submitted to AERB to demonstrate compliance of its directives. Health, Safety and Environment Group of Bhabha Atomic Research Centres, Mumbai carries out necessary surveillance and monitoring of all installations of the DAE on a routine basis and also periodic inspections of other installations using radiation sources. Some of the nuclear fuel cycle plants like nuclear power plants and fuel reprocessing involve large radioactive source inventories and have potential of accidental release of radio activity into the environment, an Environmental Surveillance Laboratory (ESL) is set up at each such site much before the facility goes into operation. These ESL's collect baseline data and monitor the environment throughout the life of the facilities including the de- commissioning stage. The data is provided to AERB and is available to members of the public. In addition, a
Localization and dynamics of small circular DNA in live mammalian nuclei

DEFF Research Database (Denmark)

Mearini, Giulia; Nielsen, Peter E; Fackelmayer, Frank O

2004-01-01

with intranuclear structural sites that strongly reduce its mobility and restrict the DNA to regions excluding nucleoli and nuclear bodies such as PML bodies. The labeled plasmids partially co-localize with SAF-A, a well characterized marker protein for the nuclear 'scaffold' or 'matrix', and are resistant towards...

Characterization of DNA binding, transcriptional activation, and regulated nuclear association of recombinant human NFATp

Directory of Open Access Journals (Sweden)

Seto Anita G

2000-11-01

Full Text Available Abstract Background NFATp is one member of a family of transcriptional activators whose nuclear accumulation and hence transcriptional activity is regulated in mammalian cells. Human NFATp exists as a phosphoprotein in the cytoplasm of naive T cells. Upon antigen stimulation, NFATp is dephosphorylated, accumulates in nuclei, and functions to regulate transcription of genes including those encoding cytokines. While the properties of the DNA binding domain of NFATp have been investigated in detail, biochemical studies of the transcriptional activation and regulated association with nuclei have remained unexplored because of a lack of full length, purified recombinant NFATp. Results We developed methods for expressing and purifying full length recombinant human NFATp that has all of the properties known to be associated with native NFATp. The recombinant NFATp binds DNA on its own and cooperatively with AP-1 proteins, activates transcription in vitro, is phosphorylated, can be dephosphorylated by calcineurin, and exhibits regulated association with nuclei in vitro. Importantly, activation by recombinant NFATp in a reconstituted transcription system required regions of the protein outside of the central DNA binding domain. Conclusions We conclude that NFATp is a bona fide transcriptional activator. Moreover, the reagents and methods that we developed will facilitate future studies on the mechanisms of transcriptional activation and nuclear accumulation by NFATp, a member of an important family of transcriptional regulatory proteins.
Strategies to regulate transcription factor-mediated gene positioning and interchromosomal clustering at the nuclear periphery.

Science.gov (United States)

Randise-Hinchliff, Carlo; Coukos, Robert; Sood, Varun; Sumner, Michael Chas; Zdraljevic, Stefan; Meldi Sholl, Lauren; Garvey Brickner, Donna; Ahmed, Sara; Watchmaker, Lauren; Brickner, Jason H

2016-03-14

In budding yeast, targeting of active genes to the nuclear pore complex (NPC) and interchromosomal clustering is mediated by transcription factor (TF) binding sites in the gene promoters. For example, the binding sites for the TFs Put3, Ste12, and Gcn4 are necessary and sufficient to promote positioning at the nuclear periphery and interchromosomal clustering. However, in all three cases, gene positioning and interchromosomal clustering are regulated. Under uninducing conditions, local recruitment of the Rpd3(L) histone deacetylase by transcriptional repressors blocks Put3 DNA binding. This is a general function of yeast repressors: 16 of 21 repressors blocked Put3-mediated subnuclear positioning; 11 of these required Rpd3. In contrast, Ste12-mediated gene positioning is regulated independently of DNA binding by mitogen-activated protein kinase phosphorylation of the Dig2 inhibitor, and Gcn4-dependent targeting is up-regulated by increasing Gcn4 protein levels. These different regulatory strategies provide either qualitative switch-like control or quantitative control of gene positioning over different time scales. © 2016 Randise-Hinchliff et al.
Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity

Science.gov (United States)

Shimamoto, Yuta; Tamura, Sachiko; Masumoto, Hiroshi; Maeshima, Kazuhiro

2017-01-01

Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers. PMID:28428255
Food safety regulations: what we learned from the Fukushima nuclear accident

International Nuclear Information System (INIS)

Hamada, Nobuyuki; Ogino, Haruyuki

2012-01-01

On 11 March 2011, the magnitude-9.0 earthquake and a substantial tsunami struck off the northeast coast of Japan. The Fukushima nuclear power plants were inundated and stricken, followed by radionuclide releases outside the crippled reactors. Provisional regulation values for radioactivity in food and drink were set on 17 March and were adopted from the preset index values, except that for radioiodines in water and milk ingested by infants. For radiocesiums, uranium, plutonium and transuranic α emitters, index values were defined in all food and drink not to exceed a committed effective dose of 5 mSv/year. Index values for radioiodines were defined not to exceed a committed equivalent dose to the thyroid of 50 mSv/year, and set in water, milk and some vegetables, but not in other foodstuffs. Index values were calculated as radioactive concentrations of indicator radionuclides ( 131 I for radioiodines, 134 Cs and 137 Cs for radiocesiums) by postulating the relative radioactive concentration of coexisting radionuclides (e.g., 132 I, 133 I, 134 I, 135 I and 132 Te for 131 I). Surveys were thence conducted to monitor levels of 131 I, 134 Cs and 137 Cs. Provisional regulation values were exceeded in tap water, raw milk and some vegetables, and restrictions on distribution and consumption began on 21 March. Fish contaminated with radioiodines at levels of concern were then detected, so that the provisional regulation value for radioiodines in seafood adopted from that in vegetables were additionally set on 5 April. Overall, restrictions started within 25 days after the first excess in each food or drink item, and maximum levels were detected in leafy vegetables (54,100 Bq/kg for 131 I, and a total of 82,000 Bq/kg for 134 Cs and 137 Cs). This paper focuses on the logic behind such food safety regulations, and discusses its underlying issues. The outlines of the food monitoring results for 24,685 samples and the enforced restrictions will also be described. - Highlights
Importance of ERK activation in As2O3-induced differentiation and promyelocytic leukemia nuclear bodies formation in neuroblastoma cells.

Science.gov (United States)

Petit, A; Delaune, A; Falluel-Morel, A; Goullé, J-P; Vannier, J-P; Dubus, I; Vasse, M

2013-11-01

Neuroblastoma malignant cell growth is dependent on their undifferentiated status. Arsenic trioxide (As2O3) induces neuroblastoma cell differentiation in vitro, but its mechanisms still remains unknown. We used three human neuroblastoma cell lines (SH-SY5Y, IGR-N-91, LAN-1) that differ from their MYCN and p53 status to explore the intracellular events activated by As2O3 and involved in neurite outgrowth, a morphological marker of differentiation. As2O3 (2μM) induced neurite outgrowth in all cell lines, which was dependent on ERK activation but independent on MYCN status. This process was induced either by a sustained (3 days) or a transient (2h) incubation with As2O3, indicating that very early events trigger the induction of differentiation. In parallel, As2O3 induced a rapid assembly of promyelocytic leukemia nuclear bodies (PML-NB) in an ERK-dependent manner. In conclusion, mechanisms leading to neuroblastoma cell differentiation in response to As2O3 appear to involve the ERK pathway activation and PML-NB formation, which are observed in response to other differentiating molecules such as retinoic acid derivates. This open new perspectives based on the use of treatment combinations to potentiate the differentiating effects of each drug alone and reduce their adverse side effects. Copyright © 2013 Elsevier Ltd. All rights reserved.
Demonstration of risk-based approaches to nuclear plant regulation

International Nuclear Information System (INIS)

Rahn, F.J.; Sursock, J.P.; Darling, S.S.; Oddo, J.M.

1993-01-01

This paper describes generic technical support EPRI is providing to the nuclear power industry relative to its recent initiatives in the area of risk-based regulations (RBR). A risk-based regulatory approach uses probabilistic risk assessment (PRA), or similar techniques, to allocate safety resources commensurate with the risk posed by nuclear plant operations. This approach will reduce O ampersand M costs, and also improve nuclear plant safety. In order to enhance industry, Nuclear Regulatory Commission (NRC) and public confidence in RBR, three things need to be shown: (1) manpower/resource savings are significant for both NRC and industry; (2) the process is doable in a reasonable amount of time; and (3) the process, if uniformly applied, results in demonstrably cheaper power and safer plants. In 1992, EPRI performed a qualitative study of the key RBR issues contributing to high O ampersand M costs. The results are given on Table 1. This study is being followed up by an in-depth quantitative cost/benefit study to focus technical work on producing guidelines/procedures for licensing submittals to NRC. The guidelines/procedures necessarily will be developed from successful demonstration projects such as the Fitzpatrick pilot plant study proposed by the New York Power Authority and other generic applications. This paper presents three examples: two motor operated valve projects performed by QUADREX Energy Services Corporation working with utilities in responding to NRC Generic Letter 89-10, and a third project working with Yankee Atomic Electric Company on service water systems at a plant in its service system. These demonstration projects aim to show the following: (1) the relative ease of putting together a technical case based on RBR concepts; (2) clarity in differentiating the various risk trade-offs, and in communicating overall reductions in risk with NRC; and (3) improved prioritization of NRC directives
HIV-1 uncoating: connection to nuclear entry and regulation by host proteins

Energy Technology Data Exchange (ETDEWEB)

Ambrose, Zandrea, E-mail: zaa4@pitt.edu [Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261 (United States); Aiken, Christopher [Department of Pathology, Microbiology and Immunology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States)

2014-04-15

The RNA genome of human immunodeficiency virus type 1 (HIV-1) is enclosed by a capsid shell that dissociates within the cell in a multistep process known as uncoating, which influences completion of reverse transcription of the viral genome. Double-stranded viral DNA is imported into the nucleus for integration into the host genome, a hallmark of retroviral infection. Reverse transcription, nuclear entry, and integration are coordinated by a capsid uncoating process that is regulated by cellular proteins. Although uncoating is not well understood, recent studies have revealed insights into the process, particularly with respect to nuclear import pathways and protection of the viral genome from DNA sensors. Understanding uncoating will be valuable toward developing novel antiretroviral therapies for HIV-infected individuals.
Nuclear exportin receptor CAS regulates the NPI-1-mediated nuclear import of HIV-1 Vpr.

Directory of Open Access Journals (Sweden)

Eri Takeda

Full Text Available Vpr, an accessory protein of human immunodeficiency virus type 1, is a multifunctional protein that plays an important role in viral replication. We have previously shown that the region between residues 17 and 74 of Vpr (Vpr(N17C74 contained a bona fide nuclear localization signal and it is targeted Vpr(N17C74 to the nuclear envelope and then imported into the nucleus by importin α (Impα alone. The interaction between Impα and Vpr is important not only for the nuclear import of Vpr but also for HIV-1 replication in macrophages; however, it was unclear whether full-length Vpr enters the nucleus in a manner similar to Vpr(N17C74. This study investigated the nuclear import of full-length Vpr using the three typical Impα isoforms, Rch1, Qip1 and NPI-1, and revealed that full-length Vpr is selectively imported by NPI-1, but not Rch1 and Qip1, after it makes contact with the perinuclear region in digitonin-permeabilized cells. A binding assay using the three Impα isoforms showed that Vpr bound preferentially to the ninth armadillo repeat (ARM region (which is also essential for the binding of CAS, the export receptor for Impα in all three isoforms. Comparison of biochemical binding affinities between Vpr and the Impα isoforms using surface plasmon resonance analysis demonstrated almost identical values for the binding of Vpr to the full-length isoforms and to their C-terminal domains. By contrast, the data showed that, in the presence of CAS, Vpr was released from the Vpr/NPI-1 complex but was not released from Rch1 or Qip1. Finally, the NPI-1-mediated nuclear import of Vpr was greatly reduced in semi-intact CAS knocked-down cells and was recovered by the addition of exogenous CAS. This report is the first to show the requirement for and the regulation of CAS in the functioning of the Vpr-Impα complex.
Identification of nuclear protein targets for six leukemogenic tyrosine kinases governed by post-translational regulation.

Directory of Open Access Journals (Sweden)

Andrew Pierce

Full Text Available Mutated tyrosine kinases are associated with a number of different haematological malignancies including myeloproliferative disorders, lymphoma and acute myeloid leukaemia. The potential commonalities in the action of six of these leukemogenic proteins on nuclear proteins were investigated using systematic proteomic analysis. The effects on over 3600 nuclear proteins and 1500 phosphopeptide sites were relatively quantified in seven isogenic cell lines. The effects of the kinases were diverse although some commonalities were found. Comparison of the nuclear proteomic data with transcriptome data and cytoplasmic proteomic data indicated that the major changes are due to post-translational mechanisms rather than changes in mRNA or protein distribution. Analysis of the promoter regions of genes whose protein levels changed in response to the kinases showed the most common binding site found was that for NFκB whilst other sites such as those for the glucocorticoid receptor were also found. Glucocorticoid receptor levels and phosphorylation were decreased by all 6 PTKs. Whilst Glucocorticoid receptor action can potentiate NFκB action those proteins where genes have NFκB binding sites were in often regulated post-translationally. However all 6 PTKs showed evidence of NFkB pathway modulation via activation via altered IkB and NFKB levels. Validation of a common change was also undertaken with PMS2, a DNA mismatch repair protein. PMS2 nuclear levels were decreased in response to the expression of all 6 kinases, with no concomitant change in mRNA level or cytosolic protein level. Response to thioguanine, that requires the mismatch repair pathway, was modulated by all 6 oncogenic kinases. In summary common targets for 6 oncogenic PTKs have been found that are regulated by post-translational mechanisms. They represent potential new avenues for therapies but also demonstrate the post-translational regulation is a key target of leukaemogenic kinases.
Basis for applying for exemption according to species protection regulation. Final repository for spent nuclear fuel at Forsmark

International Nuclear Information System (INIS)

2011-02-01

SKB will submit applications for permits and admissibility under the Environmental Act and under the Nuclear Activities Act to construct and operate a disposal facility for spent nuclear fuel at Forsmark. In the final repository the spent nuclear fuel from Swedish nuclear power plants is placed in order to protect human health and the environment against harmful effects of ionizing radiation. Construction and operation of the disposal facility in Forsmark will make an impact, give effects and consequences for the natural environment. Utilization of land for the construction of the facility and the impact on ground water as a result of groundwater drainage is expected to have negative consequences for the species included in species protection regulation. Thus, the planned activity require exemption from species protection regulation (SFS 2007:845). The purpose of this document is to provide a basis for an application for exemption under 14 paragraph species protection regulation from the prohibitions of 4, 6, 7 and 8 paragraph species protection regulation. A basis for the exemption application is that the proposed activity is considered to have an 'overriding public interest' prescribed in 14 paragraph species protection regulation. The document reports the impact, effects and consequences of the planned activities on species covered in the species protection regulation. The impact on protected species can be divided into two categories: - Direct effects on protected species and their habitats by utilization of the land. - Indirect effects on protected species and their habitats in the drainage of groundwater and the effect on groundwater levels. The document also includes a description of planned actions to prevent, restrict and compensate for the effects and consequences that the activity may cause. By applying for an exemption under 14 paragraph species protection regulation in a separate order from the application for permit according to chapters 9 and 11
For improvements of issues behind food safety regulations implemented following the Fukushima nuclear accident

International Nuclear Information System (INIS)

Hamada, Nobuyuki; Ogino, Haruyuki

2011-01-01

The great quake and a subsequent tsunami seriously damaged the Fukushima nuclear power plants on 11 March 2011, followed by radionuclide releases outside the crippled reactors. Regulatory limits stipulated as 'provisional regulation values' were set to minimize internal exposure via ingestion of contaminated food and drink. Tap water, raw milk, vegetables, seafood and tea exceeded the limit, and distribution and/or consumption of these stuffs were temporality restricted. It took 7 and 11 days to set the provisional regulation values and to order the first restriction after the declaration of nuclear emergency situations, respectively. All restrictions began within 25 days after the first excess in each item, but the commencement of restrictions was concomitant with the social dislocations. All restrictions for tap water were withdrawn within 51 days, but restrictions for food have yet to be lifted. Among all items, maximum levels were detected in leafy vegetables (54,100 Bq/kg of 131 I, 82,000 Bq/kg of 134 Cs and 137 Cs). Most provisional regulation values were adopted from the preexisting 'index values'. Index values were logically designed and practically convenient. However, food and radionuclides were not comprehensively covered, and the same value was given to emergency and existing exposure situations. Also, different provisional regulation values were set for infants and others. In this respect, we here propose the concept of the 'graded triphasic reference level system' to optimize food safety regulations in early, intermediate and late phases following the accident, where each example phase-specific reference level value is provided. This paper focuses on the logic and issues behind such food safety regulations. The food monitoring data of 24,685 samples and the enforced restrictions shall also be outlined predicated on the information available as of 12 June 2011. (author)
Concerning partial revision of regulations on installation, operation, etc., of nuclear reactor, etc., for test and research

International Nuclear Information System (INIS)

1989-01-01

To enforce the rules relating to nuclear material protection at nuclear power facilities as covered by the Nuclear Reactor Control Law, which was revised in May last year, orders should be issued by the Prime Minister's Office (or Ministry of International Trade and Industry) to specify the following matters: (1) measures to be carried out by the operators of nuclear facilities to ensure the protection of specially designated nuclear fuel materials, (2) procedures for the application for permission as covered by nuclear material protection rules, and (3) requirements for managers in charge of nuclear material protection. The new regulations should cover the following: (1) rules relating to the business of refining of nuclear fuels, and raw materials for nuclear substances, (2) rules relating to the business of processing of nuclear fuels, (3) rules relating to the installation, operation, etc., of nuclear reactor, etc., for test and research, (4) rules relating to the business of reprocessing of spent fules, (5) rules relating to the business of management of nuclear fuels or waste contaminated with nuclear fuels, and (6) rules relating to the application of nuclear fuels. (N.K)
The Nuclear Non-Proliferation Treaty: Regulating Nuclear Weapons around the World

Science.gov (United States)

Middleton, Tiffany Willey

2010-01-01

In May 2010, scientists, national security experts, and state delegates from nations around the world will convene in New York for the 2010 Nuclear Non-Proliferation Treaty Review Conference. They will review current guidelines for nuclear testing and possession of nuclear weapons in accordance with the Nuclear Non-Proliferation Treaty of 1968,…
Statement at NRC International Regulators Conference on Nuclear Security, 4 December 2012, Washington, United States

International Nuclear Information System (INIS)

Amano, Y.

2012-01-01

I would like to begin by thanking NRC Chairman Allison Macfarlane for hosting this first regulatory Conference on nuclear security involving regulators, law enforcement agencies and the IAEA. The United States has been a very important partner in the IAEA's nuclear security activities right from the start. It is by far the largest donor to our Nuclear Security Fund. It has actively supported our programmes and has been generous in providing funding, equipment and training to other Member States. When President Obama hosted the first Nuclear Security Summit in April 2010, he said it was important that that event should be part of a ''serious and sustained effort'' to improve nuclear security throughout the world. Since then, a growing number of governments have given high-level attention to this vitally important issue. This is very encouraging. Today, I am especially pleased to see regulators coming together to focus on this subject. I am confident that your meeting will make a valuable contribution to strengthening global nuclear security. I would like to share with you some important recent milestones in the IAEA's nuclear security work. As you know, primary responsibility for ensuring nuclear security lies with national governments. However, governments have recognized that international cooperation is vital. Terrorists and other criminals do not respect international borders and no country can respond effectively on its own to the threat which they pose. In September, our Member States - there are now 158 - reaffirmed the central role of the IAEA in e nsuring coordination of international activities in the field of nuclear security, while avoiding duplication and overlap . Our central role reflects the Agency's extensive membership, our mandate, our unique expertise and our long experience of providing technical assistance and specialist, practical guidance to countries. To put it simply, our work focuses on helping to minimize the risk of nuclear and other
The Nuclear Regulator's Role in Assessing Licensee. Oversight of Vendor and Other Contracted Services

International Nuclear Information System (INIS)

2011-01-01

Contracted services are an integral part of the design, construction and operation of a nuclear facility. Changes in the nuclear industry sector, including varied availability of nuclear expertise, the expansion of the international supply market and the introduction of new technologies, have tended to increase licensees' use of contracted services. These changes have created challenges for licensees and regulators related to the retention of nuclear expertise, the effective management of the interfaces between the licensees and contractors, and the oversight of contractor manufacturing quality in the context of greater multinational diversity. The regulatory body must address these challenges to provide assurance that the licensees maintain their responsibility for the safety of the facilities, regardless of who provides goods and services or where the activities involved in the supply chain take place. This report is intended to assist regulatory bodies in assessing their current practices for the regulatory oversight of licensees' use of contractors, and adapting them where necessary to meet the evolving situation
European Community (Radiological and Nuclear Medicine Installations) Regulations, 1998. Statutory Instrument S.I. No. 250 of 1998

International Nuclear Information System (INIS)

1998-01-01

These regulations establish the criteria of acceptability to be met for radiological installations and nuclear medicine installations. The regulations implement the provisions of EC Directive 84/466 Euratom of 3 September 1984 laying down the basic measures for radiation protection of persons undergoing medical examinations or treatment and to provide protection for workers and the general public. (author)
Nuclear Law: A Key Against Nuclear Terrorism

International Nuclear Information System (INIS)

Cardozo, P.

2004-01-01

The role of the legal instruments in the war against nuclear terrorism. Control of radioactive sources. Elements of Nuclear Law: Definition: it is the body of special legislation that regulates the pacific uses of nuclear energy and the conduct of the persons engaged in activities related to fissionable materials and ionizing radiation . Objective: to provide a legal framework in order to protect individuals , property and the environment against the harmful effects of the use of nuclear energy and ionising radiation. Principles of nuclear energy legislation: safety principle, exclusively operator responsibility, authorization, independence of the regulatory body, inspections and enforcement, nuclear damage compensation, international cooperation. National regulatory infrastructure. Establishment of special law in Emergency Preparedness for nuclear or radiological disaster. IAEA Conventions. Transportation of nuclear material. IAEA regulations on radioactive material. Compensation for nuclear damage. Nuclear safety, security and terrorism. International and domestic instruments. Anti terrorism acts. International agreements on Safety Cooperation. (Author)
Regulating Nuclear Reactor Construction and Commissioning, and Preparation for Operation – Challenges for a New Regulatory Body

International Nuclear Information System (INIS)

Viktorsson, C.

2016-01-01

Following an introduction with a description of the peaceful nuclear energy program in the United Arab Emirates (UAE) and an overview of the regulatory framework for safety, security and safeguards, this paper describes the regulatory approach for oversight of construction and the granting of an Operating Licence for the first nuclear power plant in the UAE. The paper describes the inspection programme set up by the Federal Authority for Nuclear Regulation (FANR) to verify construction and preoperational testing by the licensee. Moreover, it outlines the content of the operating licence application and focus areas for the regulatory review and assessment. Also, the paper describes the basic elements required by FANR for the decision-making regarding the issuance of the Operating Licence including integration of the results of review and assessment and the implementation of a systematic inspection programme to ensure operational readiness to operate and maintain the plant in accordance with FANR regulations. Finally, the paper addresses the preparation for regulatory oversight and the skill-set needed at FANR to ensure an effective and efficient oversight of safety, security of the nuclear energy power in the UAE. (author)
A regulator's viewpoint on the use of AI in the nuclear industry

International Nuclear Information System (INIS)

Wainwright, N.

1995-01-01

The regulatory position within the UK places the responsibility for safety on a nuclear site with the licensee. The licensee must produce a safety case that demonstrates that the plant is safe. Assessment of this safety case is performed by the regulator in the Health and Safety Executive (HSE) using HSE's published Safety Assessment Principles. This paper presents the personal views of a regulator on the use of artificial intelligence (AI) in the nuclear industry. The AI-based system considered are restricted to expert systems, neural networks and fuzzy logic. Some of the safety issues are discussed. The particular concerns associated with software-based systems are compounded by some of the inherent problems of AI-based systems. Such is the nature of these concerns that an acceptable safety case will be difficult to mount for safety systems and post-accident monitoring systems. However, given the present maturity of the technology, acceptable safety cases might be formulated in the areas of operator advisory systems designed to reduce accident frequencies, and robotics where dose reduction is important. There are also arguments that suggests that suitable safety cases could be formulated for AI-based plant control systems. Nevertheless, AI-based systems should be treated with caution - further research is required into suitable designs and safety demonstration techniques. (author)
Cross-regulation of signaling pathways: An example of nuclear hormone receptors and the canonical Wnt pathway

Energy Technology Data Exchange (ETDEWEB)

Beildeck, Marcy E. [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States); Gelmann, Edward P. [Columbia University, Department of Medicine, New York, NY (United States); Byers, Stephen W., E-mail: byerss@georgetown.edu [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States)

2010-07-01

Predicting the potential physiological outcome(s) of any given molecular pathway is complex because of cross-talk with other pathways. This is particularly evident in the case of the nuclear hormone receptor and canonical Wnt pathways, which regulate cell growth and proliferation, differentiation, apoptosis, and metastatic potential in numerous tissues. These pathways are known to intersect at many levels: in the intracellular space, at the membrane, in the cytoplasm, and within the nucleus. The outcomes of these interactions are important in the control of stem cell differentiation and maintenance, feedback loops, and regulating oncogenic potential. The aim of this review is to demonstrate the importance of considering pathway cross-talk when predicting functional outcomes of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as an example.

Cross-regulation of signaling pathways: An example of nuclear hormone receptors and the canonical Wnt pathway

International Nuclear Information System (INIS)

Beildeck, Marcy E.; Gelmann, Edward P.; Byers, Stephen W.

2010-01-01

Predicting the potential physiological outcome(s) of any given molecular pathway is complex because of cross-talk with other pathways. This is particularly evident in the case of the nuclear hormone receptor and canonical Wnt pathways, which regulate cell growth and proliferation, differentiation, apoptosis, and metastatic potential in numerous tissues. These pathways are known to intersect at many levels: in the intracellular space, at the membrane, in the cytoplasm, and within the nucleus. The outcomes of these interactions are important in the control of stem cell differentiation and maintenance, feedback loops, and regulating oncogenic potential. The aim of this review is to demonstrate the importance of considering pathway cross-talk when predicting functional outcomes of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as an example.
Report of the Office of Nuclear Reactor Regulation technical assistance task force

International Nuclear Information System (INIS)

1981-11-01

In 1981, the Director of the Office of Nuclear Reactor Regulation (NRR) of the Nuclear Regulatory Commission (NRC) chartered a task force to assess the office program of technical assistance and to recommend improvements. The task force divided the technical assistance program into four areas, and the practices in each area were assessed through a series of surveys of staff, management, and contractor personnel. The task force placed emphasis in its interview and assessment process on the problem areas that exist in the technical assistance program. The report thus reflects a weight on the faults found as a result of the inquiries made. The four major areas of technical assistance contracting studied were program planning, program management and execution, program control and management information systems, and program administration and coordination
The Swedish radiation protection institute's regulations and general advice on nuclear medicine; issued on April 28, 2000

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-04-01

These regulations and general advice are applicable to nuclear medicine within human medical care. The regulations are also applicable to activities where radioactive substances are administered to individuals in connection to medical or biomedical research and medical examinations for insurance or legal purposes.
Order for execution of the law concerning regulations of nuclear source materials, nuclear fuel materials and reactors

International Nuclear Information System (INIS)

1979-01-01

The order is enacted under the law for the regulations of nuclear source materials, nuclear fuel materials and reactors. Any person who engages in refining business shall get designation for each works or place of enterprise. The application shall be filed through the director of International Trade and Industry Office in charge of the location of the works or the enterprise with a business program and other specified documents attached. Any person who undertakes processing business shall get permission for each works or place of enterprise. The application shall be submitted with a business program and other documents defined by the Ordinance of the Prime Minister's Office. Any person who sets up reactor shall get permission for each works or place of enterprise. The application shall be presented with a financial project and other documents stipulated by the ordinance. Fast breeding reactor, heavy-water moderated boiling water reactor and light-water moderated pressurized water reactor are designated as reactor in the phase of research and development. Each foreign nuclear ship equipped with reactor which enters into Japanese waters shall get permission of the Minister of Transport. The application shall be presented with the papers explaining safety of reactor facilities and other documents provided by the ordinance of the ministry concerned. (Okada, K.)
Regulation for the decommissioning of nuclear power plants in U.S.A

International Nuclear Information System (INIS)

Oishi, Yuichi

2001-01-01

Since beginning of operation in nuclear reactor for practical power generation for the first one in Japan in 1966, the rector already passed more than 30 years are found and some investigations on its abolition method and its countermeasure accompanied with its permanent operation finishing of the reactor for future have been progressed by government and the relative organizations. The Japan Engineering and Inspection Corporation, under trust of the Ministry of Economy and Industry, has carried out some surveys on abolition measure regulation in the world. On the regulation in U.S.A. as a part of the surveys, abstract of the survey results performed before 1999 was introduced. Items in the survey were regulation system, definition and configuration of the abolition measure, legal procedures on the measure, and the last radiation survey and evaluating method. In U.S.A., as contents on legal procedure and document to be proposed are in detail and concretely regulated, the abolition measure activity can be progressed in standard according to the legal regulation, difference between every plants is thought to be very small. And, in spite of being regulated in details, participation of regulation agency on the procedures is less than that under operation, and there are some exempted items automatically. This is to say, it is a method to be processed under check of the abolition measure activity by NRC through its notice, inspection and approval, under agreeing with desires of applicants. (G.K.)
The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

OpenAIRE

Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S.

2009-01-01

Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-choleste...
Regulations concerning the transport of nuclear fuel materials outside the works or the enterprise

International Nuclear Information System (INIS)

1981-01-01

This rule is established under the provisions of the law concerning the regulation of nuclear raw materials, nuclear fuel materials and nuclear reactors and the ordinance for its execution, and to enforce the law. Basic terms are defined, such as vehicle transport, simplified transport, nuclear fuel transport goods, exclusive loading, worker, cumulative dose and exposure radiation dose. Nuclear fuel transport goods are classified into types of L, A, BM and BU according to their radioactivities. Radiation dose rate shall not exceed 0.5 milli-rem an hour on the surface of the type L, and 200 milli-rem an hour on the surface of the type A. For the type BM, the rate shall not surpass 1,000 milli-rem an hour at the distance of 1 meter from the surface in the special test conditions. The transport goods of fissile materials must not reach criticality on the way, but also shall conform to the stipulated technical standards. The particular things contaminated by nuclear fuel materials can be transported without specifying as nuclear fuel transport goods, and their radiation dose rate shall not go beyond 0.5 milli-rem an hour on the surface. The transport by special measures, the technical standards of simplified transport and measures to be taken in danger in transit are defined, respectively.(Okada, K.)
Radiation safety in the nuclear medicine department: impact of the UK Ionising Radiations Regulations

International Nuclear Information System (INIS)

Harding, L.K.

1987-01-01

The new 1985 regulations and guidance on radiation protection in the U.K. are discussed in relation to the needs for controlled areas in the nuclear medicine department and patient wards, admittance to hospital to comply with legislation, classification of workers, patient waiting rooms, handling flood sources, pregnancy and breast feeding. (U.K.)
Actualization of the Brazilian nuclear regulations

International Nuclear Information System (INIS)

Wieland, Patricia; Soares, Abner Duarte; Nogueira, Tindyua de Moraes; Monteiro, Iara Arraes; Pitta, Maria Adelia Rocha; Bruno, Natanael Carvalho; Pereira, Enneite Souza; Pinto, Marvio dos S.; Lidington, Regina Marcia Rocha; Rocha, Marco Aurelio Toledo

2011-01-01

The present work has the objective of making public the methodological approach adopted by the Brazilian Nuclear Energy Commission (CNEN) to create a nuclear normative structure up-dated and coherent. According to the Law 4118/62, 6189/74 and 7781/89, is the attribution the CNEN to establish specific guidelines for nuclear safety and radiological protection, and also do dictate safety norms through the emission of Resolutions
Catalogue and classification of technical safety standards, rules and regulations for nuclear power reactors and nuclear fuel cycle facilities

International Nuclear Information System (INIS)

Fichtner, N.; Becker, K.; Bashir, M.

1977-01-01

The present report is an up-dated version of the report 'Catalogue and Classification of Technical Safety Rules for Light-water Reactors and Reprocessing Plants' edited under code No EUR 5362e, August 1975. Like the first version of the report, it constitutes a catalogue and classification of standards, rules and regulations on land-based nuclear power reactors and fuel cycle facilities. The reasons for the classification system used are given and discussed
Application of the New Decommissioning Regulation to the Nuclear Licensed Facilities (NLF) at Fontenay-aux-Roses's Nuclear Center (CEA)

International Nuclear Information System (INIS)

Sauret, Josiane; Piketty, Laurence; Jeanjacques, Michel

2008-01-01

This abstract describes the application of the new decommissioning regulation on all Nuclear Licensed Facilities (NLF is to say INB in French) at Fontenay-aux-Roses's Center (CEA/FAR). The decommissioning process has been applied in six buildings which are out of the new nuclear perimeter proposed (buildings no 7, no 40, no 94, no 39, no 52/1 and no 32) and three buildings have been reorganized (no 54, no 91 and no 53 instead of no 40 and no 94) in order to increase the space for temporary nuclear waste disposal and to reduce the internal transports of nuclear waste on the site. The advantages are the safety and radioprotection improvements and a lower operating cost. A global safety file was written in 2002 and 2003 and was sent to the French Nuclear Authority on November 2003. The list of documents required is given in the paragraph I of this paper. The main goals were two ministerial decrees (one decree for each NLF) getting the authorization to modify the NLF perimeter and to carry out cleaning and dismantling activities leading to the whole decommissioning of all NLF. Some specific authorizations were necessary to carry out the dismantling program during the decommissioning procedure. They were delivered by the French Nuclear Safety Authority (FNSA) or with limited delegation by the General Executive Director (GED) on the CEA Fontenay-aux-Roses's Center, called internal authorization. Some partial dismantling or decontamination examples are given below: - evaporator for the radioactive liquid waste treatment station (building no 53): FNSA authorization: phase realised in 2002/2003. - disposal tanks for the radioactive liquid waste treatment station (building no 53) FNSA authorization: phase realised in 2004, - incinerator for the radioactive solid waste treatment station (building no 07): FNSA authorization: operation realised in 2004, - research equipments in the building no. 54 and building no. 91: internal authorization ; realised in 2005, - sample
Regulation of nuclear power: the case of the light water reactor

International Nuclear Information System (INIS)

Rolph, E.

1977-06-01

This report is one of a series of documents that trace the history of the development and commercialization of the light water reactor in the expectation that a better appreciation of the development and commercialization process of this complex technology could be instructive in understanding the regulatory and economic obstacles currently slowing diffusion of that technology and the problems that may be encountered in similar large-scale, high-technology development projects. This regulatory history of the Atomic Energy Commission chronicles the significant events between 1954, when the AEC was given responsibility for regulating nuclear power plants, and 1974, when the AEC was absorbed by the Energy Research and Development Administration and the Nuclear Regulatory Commission. It identifies the origins of regulatory problems that have arisen during the period and describes how the AEC dealt with them. The history is based, for the most part, on primary source documents: hearings, news reports, and AEC documents
The regulation for enforcing the law concerning indemnification of nuclear damage

International Nuclear Information System (INIS)

1980-01-01

The regulation is set up under the provisions of the law concerning the indemnification for atomic energy damages, to enforce them. An atomic energy business enterpriser who intends to get the approval of indemnification measures specified under the law shall file an application to the General Director of the Science Technology Agency, attaching particular documents and writing the following matters: his name and address; the kinds of operation of reactors; the names and addresses of works or places of business where reactors are operated; the thermal output of reactors; the kinds and quantities of nuclear fuel materials processed or employed; the kinds and quantities of nuclear fuel materials or contaminated materials to be transported; the kinds and quantities of nuclear fuel materials or contaminated materials to be disposed; beginning dates and expected ending dates of the operation of reactors; and other items stipulated concerning liability insurance and indemnification contracts. The negotiable securities qualified to be trusted include government bonds; municipal bonds; bonds issued by particular legal persons; bonds issued by banks, Central Cooperative Bank for Agriculture and Forestry, or Bank for Commerce and Industrial Cooperatives, and secured debentures under the secured debenture trust law. The recovering of trusted securities and identification cards are defined, respectively. (Okada, K.)
MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.

Science.gov (United States)

Posavec Marjanović, Melanija; Hurtado-Bagès, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Hélène; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M; Ahel, Ivan; Ladurner, Andreas G; Yanes, Oscar; Bouvet, Philippe; Suelves, Mònica; Teperino, Raffaele; Pospisilik, J Andrew; Buschbeck, Marcus

2017-11-01

Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD + -derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD + consumption. The resultant accumulation of the NAD + precursor NMN allows for maintenance of mitochondrial NAD + pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD + consumption and establishing a buffer of NAD + precursors in differentiated cells.
A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein*

Science.gov (United States)

Oksayan, Sibil; Wiltzer, Linda; Rowe, Caitlin L.; Blondel, Danielle; Jans, David A.; Moseley, Gregory W.

2012-01-01

Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1–P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3–P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection. PMID:22700958
Proposed new regulations for the limitation of releases of radioactive substances from nuclear power stations with light water reactors

International Nuclear Information System (INIS)

1975-07-01

In this publication the Swedish National Institute of Radiation Protection presents a proposed version of new regulations concerning the way in which the release of radioactive substances from nuclear power stations is to be limited. The regulations come into force on 1st January 1976. (Auth.)
Environmental regulations and their effects on the nuclear regulator

International Nuclear Information System (INIS)

McManus, J.G.

1994-01-01

Environmental regulations are discussed from the point of view of the Canadian Atomic Energy Control Board (AECB). The AECB's mission includes the environment, namely 'to ensure that the use of nuclear energy in Canada does not pose any undue risk to health, safety, security or the environment'. The regulatory process was governed by the Atomic Energy Control Act, which at the time of the conference was outdated and due for replacement by a new version, and by the Environmental Assessment and Review Process Guidelines Order, which was due to be replaced by the Canadian Environmental Assessment Act, still not in force at the time of the conference. Through court decisions, the Guidelines Order had effectively acquired statutory authority. Public hearings and review can result in some considerable delay to the approval of a project, yet the AECB has no choice but to ensure that the requirements of the Guidelines Order are fulfilled. Collaboration between the federal and provincial governments is very evident in Saskatchewan. Of six mining projects being considered by the AECB, five were being reviewed by a joint federal provincial panel. For the future, it was hoped that the new Atomic Energy Control Act would increase fines and the powers of inspectors, require financial guarantees for decommissioning, regularize cooperation with the provinces, and empower the AECB to hold hearings that could effectively substitute for those prescribed by the Canadian Environmental Assessment Act
Nuclear law - Nuclear safety

International Nuclear Information System (INIS)

Pontier, Jean-Marie; Roux, Emmanuel; Leger, Marc; Deguergue, Maryse; Vallar, Christian; Pissaloux, Jean-Luc; Bernie-Boissard, Catherine; Thireau, Veronique; Takahashi, Nobuyuki; Spencer, Mary; Zhang, Li; Park, Kyun Sung; Artus, J.C.

2012-01-01

This book contains the contributions presented during a one-day seminar. The authors propose a framework for a legal approach to nuclear safety, a discussion of the 2009/71/EURATOM directive which establishes a European framework for nuclear safety in nuclear installations, a comment on nuclear safety and environmental governance, a discussion of the relationship between citizenship and nuclear, some thoughts about the Nuclear Safety Authority, an overview of the situation regarding the safety in nuclear waste burying, a comment on the Nome law with respect to electricity price and nuclear safety, a comment on the legal consequences of the Fukushima accident on nuclear safety in the Japanese law, a presentation of the USA nuclear regulation, an overview of nuclear safety in China, and a discussion of nuclear safety in the medical sector
Development and utilization of the NRC policy statement on the regulation of advanced nuclear power plants

International Nuclear Information System (INIS)

Williams, P.M.; King, T.L.

1988-06-01

On March 26, 1985, the US Nuclear Regulatory Commission issued for public comment a ''Proposed Policy for Regulation of Advanced Nuclear Power Plants'' (50 FR 11884). This report presents and discusses the Commission's final version of that policy as titled and published on July 8, 1986 ''Regulation of Advanced Nuclear Power Plants, Statement of Policy'' (51 FR 24643). It provides an overview of comments received from the public, of the significant changes from the proposed Policy Statement to the final Policy Statement, and of the Commission's response to six questions contained in the proposed Policy Statement. The report also discusses the definition for advanced reactors, the establishment of an Advanced Reactors Group, the staff review approach and information needs, and the utilization of the Policy Statement in relation to other NRC programs, including the policies for safety goals, severe accidents and standardization. In addition, guidance for advanced reactors with respect to operating experience, technology development, foreign information and data, and prototype testing is provided. Finally, a discussion on the use of less prescriptive and nonprescriptive design criteria for advanced reactors, which the Policy Statement encourages, is presented
Nuclear magnetic resonance studies of metabolic regulation

International Nuclear Information System (INIS)

Sillerud, L.O.; Han, C.H.; Whaley, T.W.

1983-01-01

Nuclear magnetic resonance (NMR) techniques for the detection of the metabolic transformations of biological compounds labeled with stable isotopes, particularly carbon-13 have been explored. We have studied adipose tissue in the intact rat, the exteriorized epididymal fat pad, and the isolated adipocyte. Triacylglycerol metabolism in adipose tissue is regulated by lipogenic factors (insulin, corticosterone, thyroxine, and growth hormone) and lipolytic factors (glucagon and catecholamines). The synthesis of triglyceride from 5.5 mM glucose was stimulated by about 4-fold by 10 nM insulin. Triglyceride synthesis from glucose in the presence of insulin occurred at a rate of 330 nmol/hr/10 6 cells. Since the NMR signals from free and esterified fatty acids and glycerol are distinct, we could directly measure the rate of hormone-stimulated lipolysis. Epinephrine (10 μM) gave a lipolytic rate of 0.30 μmol/hr/10 6 cells as monitored by free-glycerol appearance in the medium. 13 C NMR provides a superior method for the measurement of triglyceride metabolism since it directly measures the changes in the substrates and products in situ

SUMO regulates p21Cip1 intracellular distribution and with p21Cip1 facilitates multiprotein complex formation in the nucleolus upon DNA damage.

Science.gov (United States)

Brun, Sonia; Abella, Neus; Berciano, Maria T; Tapia, Olga; Jaumot, Montserrat; Freire, Raimundo; Lafarga, Miguel; Agell, Neus

2017-01-01

We previously showed that p21Cip1 transits through the nucleolus on its way from the nucleus to the cytoplasm and that DNA damage inhibits this transit and induces the formation of p21Cip1-containing intranucleolar bodies (INoBs). Here, we demonstrate that these INoBs also contain SUMO-1 and UBC9, the E2 SUMO-conjugating enzyme. Furthermore, whereas wild type SUMO-1 localized in INoBs, a SUMO-1 mutant, which is unable to conjugate with proteins, does not, suggesting the presence of SUMOylated proteins at INoBs. Moreover, depletion of the SUMO-conjugating enzyme UBC9 or the sumo hydrolase SENP2 changed p21Cip1 intracellular distribution. In addition to SUMO-1 and p21Cip1, cell cycle regulators and DNA damage checkpoint proteins, including Cdk2, Cyclin E, PCNA, p53 and Mdm2, and PML were also detected in INoBs. Importantly, depletion of UBC9 or p21Cip1 impacted INoB biogenesis and the nucleolar accumulation of the cell cycle regulators and DNA damage checkpoint proteins following DNA damage. The impact of p21Cip1 and SUMO-1 on the accumulation of proteins in INoBs extends also to CRM1, a nuclear exportin that is also important for protein translocation from the cytoplasm to the nucleolus. Thus, SUMO and p21Cip1 regulate the transit of proteins through the nucleolus, and that disruption of nucleolar export by DNA damage induces SUMO and p21Cip1 to act as hub proteins to form a multiprotein complex in the nucleolus.
Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Executive summary

International Nuclear Information System (INIS)

Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

1982-08-01

This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations
Nuclear activity. Decree No. 1.390. Regulation of Law No. 24.804 (27-Nov-1998; B.O. 4-Dec-1998)

International Nuclear Information System (INIS)

1998-01-01

This decree regulates various aspects of the National Law of Nuclear Activity of the Argentine Republic, in order to determine its scope, define the procedures for its application, and establish the executive functions of the institutions emerging from this Law: Empresa Nucleoelectrica Argentina Sociedad Anonima (NASA), Comision Nacional de Energia Atomica (CNEA) and the Autoridad Regulatoria Nuclear (ARN), former Ente Nacional Regulador Nuclear. The National State shall establish the nuclear policy and shall develop the Research and Development functions through the Comision Nacional de Energia Atomica (CNEA) and the regulatory and control functions through the Autoridad Regulatoria Nuclear (ARN). The nuclear activities of production, research, development and service rendering which might be organised commercially, shall be implemented within the framework of the nuclear policy and regulation exercised within the competence of the above mentioned organisms. The Commission shall have to assume the responsibility of the management of radioactive wastes of low, medium and high activity and establish the acceptance requirements that shall have to be approved by the ARN. Moreover, it shall determine the shut-down of the nuclear power plants and any other relevant nuclear facility concurrently with ARN, through the Shut-down Project of each facility. With the aim of the privatisation of the nuclear power generation activity depending from the enterprise NASA, the constitution of a society is set up: 'Generadora Nuclear Argentina Sociedad Anonima' (GENUAR SA). Also, the amount of the royalty that shall be paid to CNEA for research and development activities is fixed. The above mentioned society will be the holder of the concession of the use of nuclear goods and the responsible entity for the construction and/or operation licenses
The nuclear risk

International Nuclear Information System (INIS)

Choudens, Henri de

2013-06-01

After a presentation of some general notions related to radioactivity, to the action and effects of radiation on matter and on living creatures, to natural irradiation and irradiation resulting from human activities, and to standards and regulation in radiation protection, this publication presents issues related to the safety of nuclear installations: presentation of the different types of nuclear installations, safety principles. The next part proposes an overview of different types of criticality accidents by distinguishing those occurring in medical or industrial installations and radioactive sources, those related to military activities, and those occurring in nuclear reactors. Other addressed topics are: radioactive wastes and effluents (definitions, classification, origin and quantity, packaging and storage), transportation of radioactive materials (regulation, parcel types, radiation protection during transportation, transport accidents), regulation of basic nuclear installations and safety organisation (safety control during normal operation, crisis management, post-accidental management, public information), the protection of sensitive nuclear materials (material types and general principles, regulation, arrangement to protect materials in installations, transports, audits, international controls). Nuclear fusion is then presented (principle, confinement types, the ITER project), and an overview of military applications is finally proposed (ship propulsion, nuclear weapons, the non proliferation issue)
NRC testimony before the Subcommittee on Nuclear Regulation of the Committee on Environment and Public Works, United States Senate

International Nuclear Information System (INIS)

1977-10-01

NRC staff testimony before the U.S. Senate's Subcommittee on Nuclear Regulation, Committee on Environment and Public, is presented. The testimony pertains to the staff's role in the licensing process affecting the Virginia Electric and Power Company's North Anna nuclear plant. It explains the steps taken since 1973, and particularly since formation of the U.S. Nuclear Regulatory Commission in January 1975, to improve the timeliness of submission of information from the staff to the Commission licensing boards
Orphan Nuclear Receptor Nur77 Is a Novel Negative Regulator of Endothelin-1 Expression In Vascular Endothelial Cells

OpenAIRE

Qin, Qing; Chen, Ming; Yi, Bing; You, Xiaohua; Yang, Ping; Sun, Jianxin

2014-01-01

Endothelin-1 (ET-1) produced by vascular endothelial cells plays essential roles in the regulation of vascular tone and development of cardiovascular diseases. The objective of this study is to identify novel regulators implicated in the regulation of ET-1 expression in vascular endothelial cells (ECs). By using quantitative real-time PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA), we show that either ectopic expression of orphan nuclear receptor Nur77 or pharmacological activati...
Regulatory analysis for amendments to regulations for the environmental review for renewal of nuclear power plant operating licenses. Final report

International Nuclear Information System (INIS)

1996-05-01

This regulatory analysis provides the supporting information for a proposed rule that will amend the Nuclear Regulatory Commission's environmental review requirements for applications for renewal of nuclear power plant operating licenses. The objective of the proposed rulemaking is to improve regulatory efficiency by providing for the generic evaluation of certain environmental impacts associated with nuclear plant license renewal. After considering various options, the staff identified and analyzed two major alternatives. With Alternative A, the existing regulations would not be amended. This option requires that environmental reviews be performed under the existing regulations. Alternative B is to assess, on a generic basis, the environmental impacts of renewing the operating license of individual nuclear power plants, and define the issues that will need to be further analyzed on a case-by-case basis. In addition, Alternative B removes from NRC's review certain economics-related issues. The findings of this assessment are to be codified in 10 CFR 51. The staff has selected Alternative B as the preferred alternative
Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

Energy Technology Data Exchange (ETDEWEB)

Wada, Takeyoshi [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Asahi, Toru [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Research Organization for Nano & Life Innovation, Waseda University #03C309, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Sawamura, Naoya, E-mail: naoya.sawamura@gmail.com [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Research Organization for Nano & Life Innovation, Waseda University #03C309, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan)

2016-08-26

The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as a thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. - Highlights: • We found that CRBN is a nucleocytoplasmic shutting protein and identified the key domain for nucleocytoplasmic shuttling. • CRBN associates with the transcription factor Ikaros via the N-terminal domain. • CRBN modulates Ikaros-mediated transcriptional regulation and its downstream target, enkephalin.
Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

International Nuclear Information System (INIS)

Wada, Takeyoshi; Asahi, Toru; Sawamura, Naoya

2016-01-01

The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as a thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. - Highlights: • We found that CRBN is a nucleocytoplasmic shutting protein and identified the key domain for nucleocytoplasmic shuttling. • CRBN associates with the transcription factor Ikaros via the N-terminal domain. • CRBN modulates Ikaros-mediated transcriptional regulation and its downstream target, enkephalin.
Case study of the effects of public safety regulation on the construction costs of coal-fired and nuclear power plants

International Nuclear Information System (INIS)

Morris, C.D.

1987-01-01

Regulations intended to reduce the number of accidents at nuclear plants and the discharge of sulfur and particulate wastes at coal-fired power plants have become an important cause of construction cost escalation. Measuring the costs of these regulatory interventions is a difficult research task. The three-unit Bruce Mansfield coal-fired plant and the two-unit Beaver Valley nuclear power station located in Shippingport, Pennsylvania, provide a unique opportunity for a case study of the costs of regulation in the construction of both kinds of plants. The units of each plant were built sequentially over a period of intensifying regulation. The method used to measure the costs of public safety regulation in the construction of each kind of plant is to determine the connections between the issuances of the regulatory agencies (EPA and NRC) and cost escalations of succeeding units. The small cost escalations of the Mansfield 3 unit, in comparison to the massive costs of the Beaver Valley 2 unit, suggest that the design and construction of new coal-fired plants are not disrupted by regulatory interventions nearly as extensively as are nuclear units. Certain technical features of Beaver Valley 2, especially its small size and a design that is identical to the first unit's, further contribute to its cost escalations
Moving from self-regulation to external regulation of Department of Energy facilities

International Nuclear Information System (INIS)

Wishau, R.J.; Dawson, J.; Lee, D.W.

1999-01-01

This paper discusses the initiative to transfer the regulation of Department of Energy (DOE) nuclear facilities to the US Nuclear Regulatory Commission (NRC). The paper gives an overview of some of the major technical, policy and legal issues that accompany this initiative. The paper focuses on specific issues and how they may be affected by external regulation of occupational radiation protection at DOE facilities. Differences between the NRC and the DOE approach to regulating nuclear safety are compared and contrasted. Some projected impacts from this transition are examined. Finally, recommendations are provided that may enhance the transition, increasing the likelihood of successful external NRC regulation
White paper on nuclear safety in 2009

International Nuclear Information System (INIS)

2009-06-01

It deals with a general introduction of nuclear safety like general safety, safety regulation and system law and standard. It indicates of nuclear energy facility safety about general safety, safety regulation of operating nuclear power plant safety regulation under constructing nuclear power plant. It deals with radiation facility safety, monitoring of environmental radiation, radiation protection, radiation control, international cooperating on nuclear energy safety and establishment of safety regulation.
Spatial and Temporal Resolution of Global Protein Synthesis during HSV Infection Using Bioorthogonal Precursors and Click Chemistry

Science.gov (United States)

Serwa, Remigiusz A.; O’Hare, Peter

2016-01-01

We used pulse-labeling with the methionine analogue homopropargylglycine (HPG) to investigate spatiotemporal aspects of protein synthesis during herpes simplex virus (HSV) infection. In vivo incorporation of HPG enables subsequent selective coupling of fluorochrome-capture reagents to newly synthesised proteins. We demonstrate that HPG labeling had no effect on cell viability, on accumulation of test early or late viral proteins, or on overall virus yields. HPG pulse-labeling followed by SDS-PAGE analysis confirmed incorporation into newly synthesised proteins, while parallel processing by in situ cycloaddition revealed new insight into spatiotemporal aspects of protein localisation during infection. A striking feature was the rapid accumulation of newly synthesised proteins not only in a general nuclear pattern but additionally in newly forming sub-compartments represented by small discrete foci. These newly synthesised protein domains (NPDs) were similar in size and morphology to PML domains but were more numerous, and whereas PML domains were progressively disrupted, NPDs were progressively induced and persisted. Immediate-early proteins ICP4 and ICP0 were excluded from NPDs, but using an ICP0 mutant defective in PML disruption, we show a clear spatial relationship between NPDs and PML domains with NPDs frequently forming immediately adjacent and co-joining persisting PML domains. Further analysis of location of the chaperone Hsc70 demonstrated that while NPDs formed early in infection without overt Hsc70 recruitment, later in infection Hsc70 showed pronounced recruitment frequently in a coat-like fashion around NPDs. Moreover, while ICP4 and ICP0 were excluded from NPDs, ICP22 showed selective recruitment. Our data indicate that NPDs represent early recruitment of host and viral de novo translated protein to distinct structural entities which are precursors to the previously described VICE domains involved in protein quality control in the nucleus, and reveal
Interferon β induces clearance of mutant ataxin 7 and improves locomotion in SCA7 knock-in mice.

Science.gov (United States)

Chort, Alice; Alves, Sandro; Marinello, Martina; Dufresnois, Béatrice; Dornbierer, Jean-Gabriel; Tesson, Christelle; Latouche, Morwena; Baker, Darren P; Barkats, Martine; El Hachimi, Khalid H; Ruberg, Merle; Janer, Alexandre; Stevanin, Giovanni; Brice, Alexis; Sittler, Annie

2013-06-01

We showed previously, in a cell model of spinocerebellar ataxia 7, that interferon beta induces the expression of PML protein and the formation of PML protein nuclear bodies that degrade mutant ataxin 7, suggesting that the cytokine, used to treat multiple sclerosis, might have therapeutic value in spinocerebellar ataxia 7. We now show that interferon beta also induces PML-dependent clearance of ataxin 7 in a preclinical model, SCA7(266Q/5Q) knock-in mice, and improves motor function. Interestingly, the presence of mutant ataxin 7 in the mice induces itself the expression of endogenous interferon beta and its receptor. Immunohistological studies in brains from two patients with spinocerebellar ataxia 7 confirmed that these modifications are also caused by the disease in humans. Interferon beta, administered intraperitoneally three times a week in the knock-in mice, was internalized with its receptor in Purkinje and other cells and translocated to the nucleus. The treatment induced PML protein expression and the formation of PML protein nuclear bodies and decreased mutant ataxin 7 in neuronal intranuclear inclusions, the hallmark of the disease. No reactive gliosis or other signs of toxicity were observed in the brain or internal organs. The performance of the SCA7(266Q/5Q) knock-in mice was significantly improved on two behavioural tests sensitive to cerebellar function: the Locotronic® Test of locomotor function and the Beam Walking Test of balance, motor coordination and fine movements, which are affected in patients with spinocerebellar ataxia 7. In addition to motor dysfunction, SCA7(266Q/5Q) mice present abnormalities in the retina as in patients: ataxin 7-positive neuronal intranuclear inclusions that were reduced by interferon beta treatment. Finally, since neuronal death does not occur in the cerebellum of SCA7(266Q/5Q) mice, we showed in primary cell cultures expressing mutant ataxin 7 that interferon beta treatment improves Purkinje cell survival.
Organisational culture at the Radiation and Nuclear Safety Authority of Finland's department of Nuclear Reactor Regulation

International Nuclear Information System (INIS)

Reiman, T.; Norros, L.

2001-03-01

A case study to investigate the organisational culture of the regulatory authority was conducted at the Radiation and Nuclear Safety Authority of Finland's (STUK) Nuclear Reactor Regulation (YTO) - department. Organisational culture is defined as a pattern of shared basic assumptions, which are basically unconscious. Objectives of the study were to conceptualise and describe the main characteristics of YTO's organisational culture and to carry out a tentative core task analysis of the inspectors' work. A combination of quantitative and qualitative methods was used in the research. YTO's culture was identified as a hierarchy-focused culture with less emphasis on innovation or social support. However, the ideal values of the personnel emphasised also social support and goal setting. Ambiguous goals were felt by some personnel as increased uncertainty about the meaningfulness of one's job. Also a lack of feedback was mentioned. The core task analysis identified the critical functions of the regulatory practice. These functions specify the three roles of the regulatory authority, the expert role, the public role and the authority role. The culture must support the fulfilment of the requirements of all the three roles. Development needs in YTO's culture were identified and recommendations were made. (au)
Nuclear Forensics International Technical Working Group (ITWG): a collaboration of scientists, law enforcement officials, and regulators working to combat nuclear terrorism and proliferation

Energy Technology Data Exchange (ETDEWEB)

Schwantes, Jon M.

2013-10-25

Founded in 1996 upon the initiative of the “Group of 8” governments (G8), the Nuclear Forensics International Technical Working Group (ITWG) is an ad hoc organization of official Nuclear Forensics practitioners (scientists, law enforcement, and regulators) that can be called upon to provide technical assistance to the global community in the event of a seizure of nuclear or radiological materials. The ITWG is supported by and is affiliated with nearly 40 countries and international partner organizations including the International Atomic Energy Agency (IAEA), EURATOM, INTERPOL, EUROPOL, and the United Nations Interregional Crime and Justice Research Institute (UNICRI) (Figure 1). Besides providing a network of nuclear forensics laboratories that are able to assist the global community during a nuclear smuggling event, the ITWG is also committed to the advancement of the science of nuclear forensic analysis, largely through participation in periodic table top and Collaborative Materials Exercises (CMXs). Exercise scenarios use “real world” samples with realistic forensics investigation time constraints and reporting requirements. These exercises are designed to promote best practices in the field and test, evaluate, and improve new technical capabilities, methods and techniques in order to advance the science of nuclear forensics. Past efforts to advance nuclear forensic science have also included scenarios that asked laboratories to adapt conventional forensics methods (e.g. DNA, fingerprints, tool marks, and document comparisons) for collecting and preserving evidence comingled with radioactive materials.
Themes in nuclear law; Temas de Derecho Nuclear

Energy Technology Data Exchange (ETDEWEB)

NONE

2003-07-01

The nuclear law was analyzed during a workshop. The main aspects were: the law of population to access to information on nuclear energy and the relationship between the Regulator Organism and the nuclear power plants managers.
Research section on optimization of nuclear safety regulation. Summary of research section

International Nuclear Information System (INIS)

Madarame, Haruki

2009-01-01

In order to make the inspection of nuclear facilities more effective, mutual understanding and respect between the regulatory body and the licensees, and a frank, open and yet formal relationship, shall be fostered. Thus the Research Section on Optimization of Nuclear Safety Regulation was established at JSME in 2005, where academic, regulatory and industrial members have frankly discussed for the improvement of inspection system. Agreed on the necessity of system renovation, the optimal inspection system was discussed. Suitable plant shutdown interval for the preventive maintenance was evaluated considering the current monitoring technique. At the same time, the U.S. and European inspection systems were reviewed to learn a lesson. The useful conclusion were published so that each member makes efforts for the effective inspection system. Some of the results have already been referred by the governmental task force on the inspection system improvement, and contributed to the system renovation. (author)
Establishment of the nuclear regulatory framework for the process of decommissioning of nuclear installations in Mexico; Establecimiento del marco regulador nuclear para el proceso de cierre de instalaciones nucleares en Mexico

Energy Technology Data Exchange (ETDEWEB)

Salmeron V, J. A.; Camargo C, R.; Nunez C, A., E-mail: juan.salmeron@cnsns.gob.mx [Comision Nacional de Seguridad Nuclear y Salvaguardias, Dr. Barragan 779, Col. Narvarte, 03020 Ciudad de Mexico (Mexico)

2015-09-15

Today has not managed any process of decommissioning of nuclear installations in the country; however because of the importance of the subject and the actions to be taken to long term, the Comision Nacional de Seguridad Nuclear y Salvaguardias (CNSNS) in Mexico, accordance with its objectives is developing a National Nuclear Regulatory Framework and defined requirements to ensure the implementation of appropriate safety standards when such activities are performed. In this regard, the national nuclear regulatory framework for nuclear installations and the particular case of nuclear power reactors is presented, as well as a proposed licensing process for the nuclear power plant of Laguna Verde based on international regulations and origin country regulations of the existing reactors in nuclear facilities in accordance with the license conditions of operation to allow to define and incorporate such regulation. (Author)
[The dynamic mitochondria-nuclear redistribution of FKBP51 during the process of adipocyte differentiation is regulated by PKA].

Science.gov (United States)

Toneatto, Judith; Charó, Nancy L; Susperreguy, Sebastián; Piwien-Pilipuk, Graciela

2013-01-01

Glucocorticoids play an important role in adipogenesis via the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90-Hsp70 and a high molecular weight immunophilin FKBP51 or FKBP52. We have found that FKBP51 level of expression progressively increases, FKBP52 decreases, whereas Hsp90, Hsp70, and p23 remain unchanged when 3T3-L1 preadipocytes differentiate. Interestingly, FKBP51 translocates from mitochondria to the nucleus at the onset of adipogenesis. FKBP51 transiently concentrates in the nuclear lamina, at a time that this nuclear compartment undergoes its reorganization. FKBP51 nuclear localization is transient, after 48 h it cycles back to mitochondria. We found that the dynamic FKBP51 mitochondrial-nuclear shuttling is regulated by glucocorticoids and mainly on cAMP-PKA signaling since PKA inhibition by myristoilated-PKI, abrogated FKBP51 nuclear translocation induced by 3-isobutyl-1-methylxanthine (IBMX). It has been reported that PKA interacts with GR in a ligand dependent manner potentiating its transcriptional capacity. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutyryl-cAMP, compounds that induced nuclear translocation of FKBP51, therefore PKA may exert a dual role in the control of GR. In summary, the presence of FKBP51 in the nucleus may be critical for GR transcriptional control, and possibly for the control of other transcription factors that are not members of the nuclear receptor family but are regulated by PKA signaling pathway, when transcription has to be strictly controlled to succeed in the acquisition of the adipocyte phenotype.

Some links on this page may take you to non-federal websites. Their policies may differ from this site.