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Sample records for e2f development safety

  1. Cell cycle regulator E2F4 is essential for the development of the ventral telencephalon.

    Science.gov (United States)

    Ruzhynsky, Vladimir A; McClellan, Kelly A; Vanderluit, Jacqueline L; Jeong, Yongsu; Furimsky, Marosh; Park, David S; Epstein, Douglas J; Wallace, Valerie A; Slack, Ruth S

    2007-05-30

    Early forebrain development is characterized by extensive proliferation of neural precursors coupled with complex structural transformations; however, little is known regarding the mechanisms by which these processes are integrated. Here, we show that deficiency of the cell cycle regulatory protein, E2F4, results in the loss of ventral telencephalic structures and impaired self-renewal of neural precursor cells. The mechanism underlying aberrant ventral patterning lies in a dramatic loss of Sonic hedgehog (Shh) expression specifically in this region. The E2F4-deficient phenotype can be recapitulated by interbreeding mice heterozygous for E2F4 with those lacking one allele of Shh, suggesting a genetic interaction between these pathways. Treatment of E2F4-deficient cells with a Hh agonist rescues stem cell self-renewal and cells expressing the homeodomain proteins that specify the ventral telencephalic structures. Finally, we show that E2F4 deficiency results in impaired activity of Shh forebrain-specific enhancers. In conclusion, these studies establish a novel requirement for the cell cycle regulatory protein, E2F4, in the development of the ventral telencephalon.

  2. The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors

    Science.gov (United States)

    Kim, So Yoon; Rane, Sushil G.

    2011-01-01

    Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1+ pancreatic progenitor cells. Expression of activated Cdk4R24C kinase leads to increased Nkx2.2+ and Nkx6.1+ cells and a rise in the number and proliferation of Ngn3+ endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors. PMID:21490060

  3. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

    Science.gov (United States)

    Kent, Lindsey N; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K; Ridolfi, Elisa; Miller, Grace C; Zorko, Sarah M; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J; Pohar, Kamal S; Pipas, James M; Leone, Gustavo

    2017-03-01

    Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

  4. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

    Science.gov (United States)

    Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

    2004-05-01

    E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

  5. Novel functions for atypical E2Fs, E2F7 and E2F8, in polyploidization and liver cancer

    NARCIS (Netherlands)

    Pandit, Shusil Kumar

    2014-01-01

    Atypical E2F transcription factors, E2F7 and E2F8, function as transcriptional repressors of E2F target genes and are crucial for controlling the cell proliferation. In this thesis, we reveal that these two factors are crucial for liver cell polyploidization, embryonic development and prevention of

  6. E2F4 is required for early eye patterning.

    Science.gov (United States)

    Ruzhynsky, Vladimir A; Furimsky, Marosh; Park, David S; Wallace, Valerie A; Slack, Ruth S

    2009-01-01

    Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.5 and characterized by aberrant shape of the optic cup, coloboma as well as abnormal eye pigmentation. Loss of E2F4 is associated with proximal-distal patterning defects in the optic vesicle. These defects are characterized by the expansion of optic stalk marker gene expression to the optic cup and reduced expression of ventral optic cup markers. These defects are associated with a split of Shh expression domain at the ventral midline of the forebrain and expansion of the Shh activity into the ventral optic cup. Despite these patterning defects, early neuronal differentiation and Shh expression in the retina are not affected by E2F4 deletion. Overall, the results of our studies show a novel role of E2F4 in the early eye development. 2009 S. Karger AG, Basel.

  7. Differential expression of members of the E2F family of transcription factors in rodent testes

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    Toppari Jorma

    2006-12-01

    Full Text Available Abstract Background The E2F family of transcription factors is required for the activation or repression of differentially expressed gene programs during the cell cycle in normal and abnormal development of tissues. We previously determined that members of the retinoblastoma protein family that interacts with the E2F family are differentially expressed and localized in almost all the different cell types and tissues of the testis and in response to known endocrine disruptors. In this study, the cell-specific and stage-specific expression of members of the E2F proteins has been elucidated. Methods We used immunohistochemical (IHC analysis of tissue sections and Western blot analysis of proteins, from whole testis and microdissected stages of seminiferous tubules to study the differential expression of the E2F proteins. Results For most of the five E2F family members studied, the localizations appear conserved in the two most commonly studied rodent models, mice and rats, with some notable differences. Comparisons between wild type and E2F-1 knockout mice revealed that the level of E2F-1 protein is stage-specific and most abundant in leptotene to early pachytene spermatocytes of stages IX to XI of mouse while strong staining of E2F-1 in some cells close to the basal lamina of rat tubules suggest that it may also be expressed in undifferentiated spermatogonia. The age-dependent development of a Sertoli-cell-only phenotype in seminiferous tubules of E2F-1 knockout males corroborates this, and indicates that E2F-1 is required for spermatogonial stem cell renewal. Interestingly, E2F-3 appears in both terminally differentiated Sertoli cells, as well as spermatogonial cells in the differentiative pathway, while the remaining member of the activating E2Fs, E2F-2 is most concentrated in spermatocytes of mid to late prophase of meiosis. Comparisons between wildtype and E2F-4 knockout mice demonstrated that the level of E2F-4 protein displays a distinct

  8. E2F1 is crucial for E2F-dependent apoptosis

    DEFF Research Database (Denmark)

    Lazzerini Denchi, Eros; Helin, Kristian

    2005-01-01

    Loss of the retinoblastoma protein, pRB, leads to apoptosis, and several results have suggested that this is dependent on the E2F transcription factors. However, so far, the ability of the different E2F family members to contribute to apoptosis is controversial. Here, we show that ectopic...

  9. E2F-5, a new E2F family member that interacts with p130 in vivo

    NARCIS (Netherlands)

    Hijmans, E.M.; Voorhoeve, P.M.; Beijersbergen, R.L.; Veer, L.J. van 't; Bernards, R.A.

    1995-01-01

    E2F DNA binding sites are found in a number of genes whose expression is tightly regulated during the cell cycle. The activity of E2F transcription factors is regulated by association with specific repressor molecules that can bind and inhibit the E2F transactivation domain. For E2F-1, E2F-2, and

  10. Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription

    DEFF Research Database (Denmark)

    Christensen, Jesper; Cloos, Paul; Toftegaard, Ulla

    2005-01-01

    The E2F family of transcription factors are downstream effectors of the retinoblastoma protein, pRB, pathway and are essential for the timely regulation of genes necessary for cell-cycle progression. Here we describe the characterization of human and murine E2F8, a new member of the E2F family...

  11. Transcriptional regulation of human RANK ligand gene expression by E2F1

    International Nuclear Information System (INIS)

    Hu Yan; Sun Meng; Nadiminty, Nagalakshmi; Lou Wei; Pinder, Elaine; Gao, Allen C.

    2008-01-01

    Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site

  12. Regulation of cell proliferation by the E2F transcription factors

    DEFF Research Database (Denmark)

    Helin, K

    1998-01-01

    Experimental data generated in the past year have further emphasized the essential role for the E2F transcription factors in the regulation of cell proliferation. Genetic studies have shown that E2F activity is required for normal development in fruitflies, and the generation of E2F-1(-/-) mice h......Fs in the proteasomes. Novel target genes for the E2F transcription factors have been identified that link the E2Fs directly to the initiation of DNA replication.......Experimental data generated in the past year have further emphasized the essential role for the E2F transcription factors in the regulation of cell proliferation. Genetic studies have shown that E2F activity is required for normal development in fruitflies, and the generation of E2F-1(-/-) mice has...... demonstrated that individual members of the E2F transcription factor family are likely to have distinct roles in mammalian development and homeostasis. Additional mechanisms regulating the activity of the E2F transcription factors have been reported, including subcellular localization and proteolysis of the E2...

  13. The Role of the E2F Transcription Factor Family in UV-Induced Apoptosis

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    Orla Gannon

    2011-12-01

    Full Text Available The E2F transcription factor family is traditionally associated with cell cycle control. However, recent data has shown that activating E2Fs (E2F1-3a are potent activators of apoptosis. In contrast, the recently cloned inhibitory E2Fs (E2F7 and 8 appear to antagonize E2F-induced cell death. In this review we will discuss (i the potential role of E2Fs in UV-induced cell death and (ii the implications of this to the development of UV-induced cutaneous malignancies.

  14. E2F6: a member of the E2F family that does not modulate squamous differentiation

    International Nuclear Information System (INIS)

    Wong, C.F.; Barnes, Liam M.; Smith, Louise; Popa, Claudia; Serewko-Auret, Magdalena M.; Saunders, Nicholas A.

    2004-01-01

    The inhibition of E2F has been demonstrated to be important in the initiation of squamous differentiation by two independent manners: promotion of growth arrest and the relief of the differentiation-suppressive properties of E2Fs. E2F6 is reported to behave as a transcriptional repressor of the E2F family. In this study, we examined the ability of E2F6 to act as the molecular switch required for E2F inhibition in order for keratinocytes to enter a terminal differentiation programme. Results demonstrated that whilst E2F6 was able to suppress E2F activity in proliferating keratinocytes, it did not modulate squamous differentiation in a differentiated keratinocyte. Furthermore, inhibition of E2F, by overexpressing E2F6, was not sufficient to sensitise either proliferating keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to differentiation-inducing agents. Significantly, although E2F6 could suppress E2F activity in proliferating cells, it could not inhibit proliferation of KJD-1/SV40 cells. These results demonstrate that E2F6 does not contain the domains required for modulation of squamous differentiation and imply isoform-specific functions for individual E2F family members

  15. E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription

    DEFF Research Database (Denmark)

    Cartwright, P; Müller, H; Wagener, C

    1998-01-01

    with E2Fs 1-5, especially within the DNA binding, heterodimerization and marked box domains. Unlike E2Fs 1-5, E2F-6 lacks a transactivation and a pocket protein binding domain, hence, forms a unique third group within the E2F family. E2F-6 is a nuclear protein that can form heterodimers with the DP......The E2F family of transcription factors are essential for the regulation of genes required for appropriate progression through the cell cycle. Five members of the E2F family have been previously reported, namely E2F1-5. All five are key elements in transcriptional regulation of essential genes......, and they can be divided into two functional groups, those that induce S-phase progression when overexpressed in quiescent cells (E2Fs 1-3), and those that do not (E2Fs 4-5). Here, we describe the identification of a novel member of this family, which we refer to as E2F-6. E2F-6 shares significant homology...

  16. Analysis list: E2f4 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f4 Blood,Embryonic fibroblast,Liver,Muscle,Pluripotent stem cell + mm9 http://dba...rchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4....5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.10.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/colo/E2f4.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4....Embryonic_fibroblast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4.Liver.tsv,htt

  17. Analysis list: E2f1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.5.tsv http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/E2f1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/E2f1.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  18. E2F transcription factors and digestive system malignancies: how much do we know?

    Science.gov (United States)

    Xanthoulis, Athanasios; Tiniakos, Dina G

    2013-06-07

    E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumor-promoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.

  19. Copy number variations of E2F1: a new genetic risk factor for testicular cancer.

    Science.gov (United States)

    Rocca, Maria Santa; Di Nisio, Andrea; Marchiori, Arianna; Ghezzi, Marco; Opocher, Giuseppe; Foresta, Carlo; Ferlin, Alberto

    2017-03-01

    Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years, many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer. E2F1 is a transcription factor that plays an important role in regulating cell growth, differentiation, apoptosis and response to DNA damage. Therefore, deficiency or overexpression of this protein might significantly influence fundamental biological processes involved in cancer development and progression, including TGCT. We analyzed E2F1 CNVs in 261 cases with TGCT and 165 controls. We found no CNVs in controls, but 17/261 (6.5%) cases showed duplications in E2F1 Blot analysis demonstrated higher E2F1 expression in testicular samples of TGCT cases with three copies of the gene. Furthermore, we observed higher phosphorylation of Akt and mTOR in samples with E2F1 duplication. Interestingly, normal, non-tumoral testicular tissue in patient with E2F1 duplication showed lower expression of E2F1 and lower AKT/mTOR phosphorylation with respect to adjacent tumor tissue. Furthermore, increased expression of E2F1 obtained in vitro in NTERA-2 testicular cell line induced increased AKT/mTOR phosphorylation. This study suggests for the first time an involvement of E2F1 CNVs in TGCT susceptibility and supports previous preliminary data on the importance of AKT/mTOR signaling pathway in this cancer. © 2017 Society for Endocrinology.

  20. Analysis of E2F factors during epidermal differentiation.

    Science.gov (United States)

    Chang, Wing Y; Dagnino, Lina

    2005-01-01

    The multigene E2F family of transcription factors is central in the control of cell cycle progression. The expression and activity of E2F proteins is tightly regulated transcriptionally and posttranslationally as a function of the proliferation and differentiation status of the cell. In this chapter, we review protocols designed to determine E2F mRNA abundance in tissues by in situ hybridization techniques. The ability to culture primary epidermal keratinocytes and maintain them as either undifferentiated or terminally differentiated cells allows the biochemical and molecular characterization of changes in E2F expression and activity. Thus, we also discuss in detail methods to analyze E2F protein abundance by immunoblot and their ability to bind DNA in cultured cells using electrophoretic mobility shift assays.

  1. The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

    Science.gov (United States)

    Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

    2008-01-01

    Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

  2. Molecular and functional characterisation of E2F-5, a new member of the E2F family

    NARCIS (Netherlands)

    Buck, V.; Allen, K.E.; Sørensen, T.; Bybee, A.; Hijmans, E.M.; Voorhoeve, P.M.; Bernards, R.A.; Thangue, N.B. La

    1995-01-01

    The transcription factor DRTF1/E2F is implicated in the control of cellular proliferation due to its interaction with key regulators of cell cycle progression, such as the retinoblastoma tumour suppressor gene product and related pocket proteins, cyclins and cyclin-dependent kinases. DRTF1/E2F DNA

  3. Atypical E2f functions are critical for pancreas polyploidization.

    Directory of Open Access Journals (Sweden)

    Ramadhan B Matondo

    Full Text Available The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

  4. Atypical E2f functions are critical for pancreas polyploidization.

    Science.gov (United States)

    Matondo, Ramadhan B; Moreno, Eva; Toussaint, Mathilda J M; Tooten, Peter C J; van Essen, Saskia C; van Liere, Elsbeth A; Youssef, Sameh A; Bongiovanni, Laura; de Bruin, Alain

    2018-01-01

    The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

  5. E2F6 Impairs Glycolysis and Activates BDH1 Expression Prior to Dilated Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Jennifer L Major

    Full Text Available The E2F pathway plays a critical role in cardiac growth and development, yet its role in cardiac metabolism remains to be defined. Metabolic changes play important roles in human heart failure and studies imply the ketogenic enzyme β-hydroxybutyrate dehydrogenase I (BDH1 is a potential biomarker.To define the role of the E2F pathway in cardiac metabolism and dilated cardiomyopathy (DCM with a focus on BDH1.We previously developed transgenic (Tg mice expressing the transcriptional repressor, E2F6, to interfere with the E2F/Rb pathway in post-natal myocardium. These Tg mice present with an E2F6 dose dependent DCM and deregulated connexin-43 (CX-43 levels in myocardium. Using the Seahorse platform, a 22% decrease in glycolysis was noted in neonatal cardiomyocytes isolated from E2F6-Tg hearts. This was associated with a 39% reduction in the glucose transporter GLUT4 and 50% less activation of the regulator of glucose metabolism AKT2. The specific reduction of cyclin B1 (70% in Tg myocardium implicates its importance in supporting glycolysis in the postnatal heart. No changes in cyclin D expression (known to regulate mitochondrial activity were noted and lipid metabolism remained unchanged in neonatal cardiomyocytes from Tg hearts. However, E2F6 induced a 40-fold increase of the Bdh1 transcript and 890% increase in its protein levels in hearts from Tg pups implying a potential impact on ketolysis. By contrast, BDH1 expression is not activated until adulthood in normal myocardium. Neonatal cardiomyocytes from Wt hearts incubated with the ketone β-hydroxybutyrate (β-OHB showed a 100% increase in CX-43 protein levels, implying a role for ketone signaling in gap junction biology. Neonatal cardiomyocyte cultures from Tg hearts exhibited enhanced levels of BDH1 and CX-43 and were not responsive to β-OHB.The data reveal a novel role for the E2F pathway in regulating glycolysis in the developing myocardium through a mechanism involving cyclin B1. We

  6. Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland

    DEFF Research Database (Denmark)

    Lazzerini Denchi, Eros; Attwooll, Claire; Pasini, Diego

    2005-01-01

    The retinoblastoma gene, RB1, is one of the most frequently mutated genes in human cancer. Rb heterozygous mice develop pituitary tumors with 100% incidence, and the E2F transcription factors are required for this. To assess whether deregulated E2F activity is sufficient to induce pituitary tumors...

  7. E2F target genes: unraveling the biology

    DEFF Research Database (Denmark)

    Bracken, Adrian P; Ciro, Marco; Cocito, Andrea

    2004-01-01

    The E2F transcription factors are downstream effectors of the retinoblastoma protein (pRB) pathway and are required for the timely regulation of numerous genes essential for DNA replication and cell cycle progression. Several laboratories have used genome-wide approaches to discover novel target...

  8. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma

    NARCIS (Netherlands)

    Kent, Lindsey N.; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K.; Ridolfi, Elisa; Miller, Grace C.; Zorko, Sarah M.; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J.; Pohar, Kamal S.; Pipas, James M.; Leone, Gustavo

    2017-01-01

    Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are

  9. Sibling rivalry in the E2F family.

    Science.gov (United States)

    Trimarchi, Jeffrey M; Lees, Jacqueline A

    2002-01-01

    The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators. The individual E2Fs can be divided into distinct subgroups that act in direct opposition to one another to promote either cellular proliferation or cell-cycle exit and terminal differentiation. What is the underlying molecular basis of this 'push-me-pull-you' regulation, and what are its biological consequences?

  10. A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting

    Science.gov (United States)

    Lindeman, Geoffrey J.; Dagnino, Lina; Gaubatz, Stefan; Xu, Yuhui; Bronson, Roderick T.; Warren, Henry B.; Livingston, David M.

    1998-01-01

    Homozygous E2F-5 knockout embryos and mice have been generated. Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production. Although the CSF-producing choroid plexus displayed normal cellular organization, it contained abundant electron-lucent epithelial cells, consistent with excessive CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was largely confined to the choroid plexus. Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation. Rather, it affects the secretory behavior of a differentiated neural tissue. PMID:9553039

  11. E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells.

    Science.gov (United States)

    Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

    2015-01-01

    E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

  12. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1

    DEFF Research Database (Denmark)

    Jenal, Mathias; Trinh, Emmanuelle; Britschgi, Christian

    2009-01-01

    to the HIC1 promoter was shown by chromatin immunoprecipitation assays in human TIG3 fibroblasts expressing tamoxifen-activated E2F1. In agreement, activation of E2F1 in TIG3-E2F1 cells markedly increased HIC1 expression. Interestingly, expression of E2F1 in the p53(-/-) hepatocellular carcinoma cell line...

  13. Distinct mechanisms of nuclear accumulation regulate the functional consequence of E2F transcription factors

    NARCIS (Netherlands)

    Allen, K.E.; Luna, S. de la; Kerkhoven, R.M.; Bernards, R.A.; Thangue, N.B. La

    1997-01-01

    Transcription factor E2F plays an important role in coordinating and integrating early cell cycle progression with the transcription apparatus. It is known that physiological E2F arises when a member of two families of proteins, E2F and DP, interact as E2F/DP heterodimers and that transcriptional

  14. Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.

    Science.gov (United States)

    Yan, Fang; Liu, Haihong; Hao, Junjun; Liu, Zengrong

    2012-01-01

    MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback loops in the regulation of Rb-E2F pathway are predicted and shown experimentally. Recently, it has been discovered that E2F induce a cluster of miRNAs called miR449. In turn, E2F is inhibited by miR449 through regulating different transcripts, thus forming negative feedback loops in the interaction network. Here, based on the integration of experimental evidence and quantitative data, we studied Rb-E2F pathway coupling the positive feedback loops and negative feedback loops mediated by miR449. Therefore, a mathematical model is constructed based in part on the model proposed in Yao-Lee et al. (2008) and nonlinear dynamical behaviors including the stability and bifurcations of the model are discussed. A comparison is given to reveal the implication of the fundamental differences of Rb-E2F pathway between regulation and deregulation of miR449. Coherent with the experiments it predicts that miR449 plays a critical role in regulating the cell cycle progression and provides a twofold safety mechanism to avoid excessive E2F-induced proliferation by cell cycle arrest and apoptosis. Moreover, numerical simulation and bifurcation analysis shows that the mechanisms of the negative regulation of miR449 to three different transcripts are quite distinctive which needs to be verified experimentally. This study may help us to analyze the whole cell cycle process mediated by other miRNAs more easily. A better knowledge of the dynamical behaviors of miRNAs mediated networks is also of interest for bio-engineering and artificial control.

  15. Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.

    Directory of Open Access Journals (Sweden)

    Fang Yan

    Full Text Available MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback loops in the regulation of Rb-E2F pathway are predicted and shown experimentally. Recently, it has been discovered that E2F induce a cluster of miRNAs called miR449. In turn, E2F is inhibited by miR449 through regulating different transcripts, thus forming negative feedback loops in the interaction network. Here, based on the integration of experimental evidence and quantitative data, we studied Rb-E2F pathway coupling the positive feedback loops and negative feedback loops mediated by miR449. Therefore, a mathematical model is constructed based in part on the model proposed in Yao-Lee et al. (2008 and nonlinear dynamical behaviors including the stability and bifurcations of the model are discussed. A comparison is given to reveal the implication of the fundamental differences of Rb-E2F pathway between regulation and deregulation of miR449. Coherent with the experiments it predicts that miR449 plays a critical role in regulating the cell cycle progression and provides a twofold safety mechanism to avoid excessive E2F-induced proliferation by cell cycle arrest and apoptosis. Moreover, numerical simulation and bifurcation analysis shows that the mechanisms of the negative regulation of miR449 to three different transcripts are quite distinctive which needs to be verified experimentally. This study may help us to analyze the whole cell cycle process mediated by other miRNAs more easily. A better knowledge of the dynamical behaviors of miRNAs mediated networks is also of interest for bio-engineering and artificial control.

  16. Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro

    Directory of Open Access Journals (Sweden)

    Luciana dos Reis Vasques

    2010-01-01

    Full Text Available E2F1 plays a key role in cell-cycle regulation in mammals, since its transcription factor activity controls genes required for DNA synthesis and apoptosis. E2F1 deregulation is a common feature among different tumor types and can be a major cause of cell proliferation. Thus, blocking E2F1 expression by RNA interference represents a promising therapeutic approach. In this study, the introduction of specific short hairpin RNAs (shRNAs reduced E2f1 expression by up to 77%, and impaired rat glioma cell proliferation by approximately 70%, as compared to control cells. Furthermore, we investigated the expression of E2f1 target genes, Cyclin A and Cyclin E. Cyclin A was found to be down-regulated, whereas Cyclin E had similar expression to control cells, indicating that gene(s other than E2f1 control its transcription. Other E2f family members, E2f2 and E2f3, which have been classified in the same subgroup of transcriptional activators, were also analyzed. Expression of both E2f2 and E2f3 was similar to control cells, showing no cross-inactivation or up-regulation to compensate for the absence of E2f1. Nevertheless, their expression was insufficient to maintain the initial proliferation potential. Taken together, our results suggest that shE2f1 is a promising therapy to control tumor cell proliferation.

  17. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuzhu Jiang; Seon-Hee Yim; Hai-Dong Xu; Seung-Hyun Jung; So Young Yang; Hae-Jin Hu; Chan-Kwon Jung; Yeun-Jun Chung

    2011-01-01

    AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

  18. The retinoblastoma protein binds to a family of E2F transcription factors

    DEFF Research Database (Denmark)

    Lees, J A; Saito, M; Vidal, M

    1993-01-01

    E2F is a transcription factor that helps regulate the expression of a number of genes that are important in cell proliferation. Recently, several laboratories have isolated a cDNA clone that encodes an E2F-like protein, known as E2F-1. Subsequent characterization of this protein showed that it had...... the properties of E2F, but it was difficult to account for all of the suggested E2F activities through the function of this one protein. Using low-stringency hybridization, we have isolated cDNA clones that encode two additional E2F-like proteins, called E2F-2 and E2F-3. The chromosomal locations of the genes...... protein in vivo. Finally, E2F-2 and E2F-3 were able to activate transcription of E2F-responsive genes in a manner that was dependent upon the presence of at least one functional E2F binding site. These observations suggest that the E2F activities described previously result from the combined action...

  19. E2F-HDAC complexes negatively regulate the tumor suppressor gene ARHI in breast cancer

    DEFF Research Database (Denmark)

    Lu, Z; Luo, R Z; Peng, H

    2006-01-01

    . While the retinoblastoma protein, pRB, alone had no effect on ARHI promoter activity, repression by E2F1, but not E2F4, was enhanced by the coexpression of pRB. Taken together, our results suggest that E2F1, 4 and their complexes with HDAC play an important role in downregulating the expression...

  20. E2F1 regulates cellular growth by mTORC1 signaling.

    Directory of Open Access Journals (Sweden)

    Sebastian Real

    2011-01-01

    Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

  1. E2F-1-Induced p53-independent apoptosis in transgenic mice

    DEFF Research Database (Denmark)

    Holmberg, Christian Henrik; Helin, K.; Sehested, M.

    1998-01-01

    The E2F transcription factors are key targets for the retinoblastoma protein, pRB. By inactivation of E2Fs, pRB prevents progression to the S phase. To test proliferative functions of E2F, we generated transgenic mice expressing human E2F-1 and/or human DP-1. When the hydroxymethyl glutaryl...... involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered...

  2. E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

    Science.gov (United States)

    Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

    2009-05-01

    E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

  3. MicroRNA-17-92 Regulates the Transcription Factor E2F3b during Myogenesis In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Zhixiong Tang

    2017-03-01

    Full Text Available Myogenic differentiation, which occurs during muscle development, is a highly ordered process that can be regulated by E2F transcription factors. Available data show that E2F3b, but not E2F3a, is upregulated and required for myogenic differentiation. However, the regulation of E2F3b expression in myogenic differentiation is not well understood. To investigate whether E2Fb expression is controlled by miRNAs, we used bioinformatics to combine the database of microRNAs downregulated during myogenesis and those predicted to target E2F3. This identified miR-17 and miR-20a as miRNAs potentially involved in E2F3 regulation. We found that miR-17-92 controls the expression of E2F3b in C2C12 cells during myogenic differentiation. Moreover, we confirmed that miR-20a regulates the expression of E2F3b proteins in vivo using a muscle regeneration model.

  4. The E2F2 transcription factor sustains hepatic glycerophospholipid homeostasis in mice.

    Directory of Open Access Journals (Sweden)

    Eduardo N Maldonado

    Full Text Available Increasing evidence links metabolic signals to cell proliferation, but the molecular wiring that connects the two core machineries remains largely unknown. E2Fs are master regulators of cellular proliferation. We have recently shown that E2F2 activity facilitates the completion of liver regeneration after partial hepatectomy (PH by regulating the expression of genes required for S-phase entry. Our study also revealed that E2F2 determines the duration of hepatectomy-induced hepatic steatosis. A transcriptomic analysis of normal adult liver identified "lipid metabolism regulation" as a major E2F2 functional target, suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type (E2F2+/+ and E2F2 deficient (E2F2-/- mice to investigate the in vivo role of E2F2 in the composition of liver lipids and fatty acids in two metabolically different contexts: quiescence and 48-h post-PH, when cellular proliferation and anabolic demands are maximal. We show that liver regeneration is accompanied by large triglyceride and protein increases without changes in total phospholipids both in E2F2+/+ and E2F2-/- mice. Remarkably, we found that the phenotype of quiescent liver tissue from E2F2-/- mice resembles the phenotype of proliferating E2F2+/+ liver tissue, characterized by a decreased phosphatidylcholine to phosphatidylethanolamine ratio and a reprogramming of genes involved in generation of choline and ethanolamine derivatives. The diversity of fatty acids in total lipid, triglycerides and phospholipids was essentially preserved on E2F2 loss both in proliferating and non-proliferating liver tissue, although notable exceptions in inflammation-related fatty acids of defined phospholipid classes were detected. Overall, our results indicate that E2F2 activity sustains the hepatic homeostasis of major membrane glycerolipid components while it is dispensable for storage glycerolipid balance.

  5. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas

    DEFF Research Database (Denmark)

    Liontos, Michalis; Niforou, Katerina; Velimezi, Georgia

    2009-01-01

    Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies...... in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network...

  6. CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes.

    Science.gov (United States)

    Singh, Randeep K; Dagnino, Lina

    2017-01-17

    The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation.

  7. Signalling in the epidermis: the E2F cell cycle regulatory pathway in epidermal morphogenesis, regeneration and transformation.

    Science.gov (United States)

    Ivanova, Iordanka A; D'Souza, Sudhir J A; Dagnino, Lina

    2005-01-01

    The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis.

  8. E2f1 mediates high glucose-induced neuronal death in cultured mouse retinal explants.

    Science.gov (United States)

    Wang, Yujiao; Zhou, Yi; Xiao, Lirong; Zheng, Shijie; Yan, Naihong; Chen, Danian

    2017-10-02

    Diabetic retinopathy (DR) is the most common complication of diabetes and remains one of the major causes of blindness in the world; infants born to diabetic mothers have higher risk of developing retinopathy of prematurity (ROP). While hyperglycemia is a major risk factor, the molecular and cellular mechanisms underlying DR and diabetic ROP are poorly understood. To explore the consequences of retinal cells under high glucose, we cultured wild type or E2f1 -/- mouse retinal explants from postnatal day 8 with normal glucose, high osmotic or high glucose media. Explants were also incubated with cobalt chloride (CoCl 2 ) to mimic the hypoxic condition. We showed that, at 7 days post exposure to high glucose, retinal explants displayed elevated cell death, ectopic cell division and intact retinal vascular plexus. Cell death mainly occurred in excitatory neurons, such as ganglion and bipolar cells, which were also ectopically dividing. Many Müller glial cells reentered the cell cycle; some had irregular morphology or migrated to other layers. High glucose inhibited the hyperoxia-induced blood vessel regression of retinal explants. Moreover, inactivation of E2f1 rescued high glucose-induced ectopic division and cell death of retinal neurons, but not ectopic cell division of Müller glial cells and vascular phenotypes. This suggests that high glucose has direct but distinct effects on retinal neurons, glial cells and blood vessels, and that E2f1 mediates its effects on retinal neurons. These findings shed new light onto mechanisms of DR and the fetal retinal abnormalities associated with maternal diabetes, and suggest possible new therapeutic strategies.

  9. Cell cycle-regulated expression of mammalian CDC6 is dependent on E2F

    DEFF Research Database (Denmark)

    Hateboer, G; Wobst, A; Petersen, B O

    1998-01-01

    The E2F transcription factors are essential regulators of cell growth in multicellular organisms, controlling the expression of a number of genes whose products are involved in DNA replication and cell proliferation. In Saccharomyces cerevisiae, the MBF and SBF transcription complexes have...... of this gene is dependent on E2F. In vivo footprinting data demonstrate that the identified E2F sites are occupied in resting cells and in exponentially growing cells, suggesting that E2F is responsible for downregulating the promoter in early phases of the cell cycle and the subsequent upregulation when cells...

  10. E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation

    International Nuclear Information System (INIS)

    Hao, Hongying; Dong, Yanbin; Bowling, Maria T; Gomez-Gutierrez, Jorge G; Zhou, H Sam; McMasters, Kelly M

    2007-01-01

    PUMA is a pro-apoptotic Bcl-2 family member that has been shown to be involved in apoptosis in many cell types. We sought to ascertain whether induction of PUMA plays a crucial role in E2F-1-induced apoptosis in melanoma cells. PUMA gene and protein expression levels were detected by real-time PCR and Western blot in SK-MEL-2 and HCT116 cell lines after Ad-E2F-1 infection. Activation of the PUMA promoter by E2F-1 overexpression was detected by dual luciferase reporter assay. E2F-1-induced Bax translocation was shown by immunocytochemistry. The induction of caspase-9 activity was measured by caspase-9 colorimetric assay kit. Up-regulation of the PUMA gene and protein by E2F-1 overexpression was detected by real-time PCR and Western blot analysis in the SK-MEL-2 melanoma cell line. In support of this finding, we found six putative E2F-1 binding sites within the PUMA promoter. Subsequent dual luciferase reporter assay showed that E2F-1 expression could increase the PUMA gene promoter activity 9.3 fold in SK-MEL-2 cells. The role of PUMA in E2F-1-induced apoptosis was further investigated in a PUMA knockout cell line. Cell viability assay showed that the HCT116 PUMA-/- cell line was more resistant to Ad-E2F-1-mediated cell death than the HCT116 PUMA+/+ cell line. Moreover, a 2.2-fold induction of the PUMA promoter was also noted in the HCT116 PUMA+/+ colon cancer cell line after Ad-E2F-1 infection. Overexpression of a truncated E2F-1 protein that lacks the transactivation domain failed to up-regulate PUMA promoter, suggesting that PUMA may be a transcriptional target of E2F-1. E2F-1-induced cancer cell apoptosis was accompanied by Bax translocation from the cytosol to mitochondria and the induction of caspase-9 activity, suggesting that E2F-1-induced apoptosis is mediated by PUMA through the cytochrome C/Apaf-1-dependent pathway. Our studies strongly demonstrated that E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. The signaling

  11. Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry

    DEFF Research Database (Denmark)

    Lomazzi, Marina; Moroni, M Cristina; Jensen, Michael R

    2002-01-01

    Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of cancer. In the absence of other genetic alterations, this deregulation results in lack of differentiation, hyperproliferation and apoptosis. The pRB protein acts as a transcriptional repressor by targeting the E2F...... transcription factors, whose functions are required for entry into S phase. Increased E2F activity can induce S phase in quiescent cells--this is a central element of most models for the development of cancer. We show that although E2F1 alone is not sufficient to induce S phase in diploid mouse and human...

  12. Induction of DNA synthesis and apoptosis are separable functions of E2F-1

    DEFF Research Database (Denmark)

    Phillips, A C; Bates, S; Ryan, K M

    1997-01-01

    The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic...... response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant...... apoptosis in the absence of p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E...

  13. E2F8 is essential for polyploidization in mammalian cells.

    Science.gov (United States)

    Pandit, Shusil K; Westendorp, Bart; Nantasanti, Sathidpak; van Liere, Elsbeth; Tooten, Peter C J; Cornelissen, Peter W A; Toussaint, Mathilda J M; Lamers, Wouter H; de Bruin, Alain

    2012-11-01

    Polyploidization is observed in all mammalian species and is a characteristic feature of hepatocytes, but its molecular mechanism and biological significance are unknown. Hepatocyte polyploidization in rodents occurs through incomplete cytokinesis, starts after weaning and increases with age. Here, we show in mice that atypical E2F8 is induced after weaning and required for hepatocyte binucleation and polyploidization. A deficiency in E2f8 led to an increase in the expression level of E2F target genes promoting cytokinesis and thereby preventing polyploidization. In contrast, loss of E2f1 enhanced polyploidization and suppressed the polyploidization defect of hepatocytes deficient for atypical E2Fs. In addition, E2F8 and E2F1 were found on the same subset of target promoters. Contrary to the long-standing hypothesis that polyploidization indicates terminal differentiation and senescence, we show that prevention of polyploidization through inactivation of atypical E2Fs has, surprisingly, no impact on liver differentiation, zonation, metabolism and regeneration. Together, these results identify E2F8 as a repressor and E2F1 as an activator of a transcriptional network controlling polyploidization in mammalian cells.

  14. Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line

    DEFF Research Database (Denmark)

    Saito, M; Helin, K; Valentine, M B

    1995-01-01

    , we isolated genomic clones encompassing the human E2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 20q11, telomeric to the p107 locus, a gene whose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22...

  15. E2F family members are differentially regulated by reversible acetylation

    DEFF Research Database (Denmark)

    Marzio, G; Wagener, C; Gutierrez, M I

    2000-01-01

    of the other E2F family members. Here we report that E2F-1, -2, and -3, but not E2F-4, -5, and -6, associate with and are acetylated by p300 and cAMP-response element-binding protein acetyltransferases. Acetylation occurs at three conserved lysine residues located at the N-terminal boundary of their DNA......The six members of the E2F family of transcription factors play a key role in the control of cell cycle progression by regulating the expression of genes involved in DNA replication and cell proliferation. E2F-1, -2, and -3 belong to a structural and functional subfamily distinct from those...

  16. E2F1-mediated transcriptional inhibition of the plasminogen activator inhibitor type 1 gene

    DEFF Research Database (Denmark)

    Koziczak, M; Müller, H; Helin, K

    2001-01-01

    but independent of binding to pocket-binding proteins, suggesting a novel mechanism for E2F-mediated negative gene regulation [Koziczak, M., Krek, W. & Nagamine, Y. (2000) Mol. Cell. Biol. 20, 2014-2022]. However, it remains to be seen whether endogenous E2F can exert a similar effect. We report here that down....... These results all indicate that endogenous E2F can directly repress the PAI-1 gene. DNase I hypersensitive-site analysis of the PAI-1 promoter suggested the involvement of conformation changes in chromatin structure of the PAI-1 promoter. 5' deletion analysis of the PAI-1 promoter showed that multiple sites...

  17. A lentiviral vector with expression controlled by E2F-1: A potential tool for the study and treatment of proliferative diseases

    International Nuclear Information System (INIS)

    Strauss, Bryan E.; Patricio, Juliana Rotelli; Vieira de Carvalho, Anna Carolina; Bajgelman, Marcio C.

    2006-01-01

    We have constructed a lentiviral vector with expression limited to cells presenting active E2F-1 protein, a potential advantage for gene therapy of proliferative diseases. For the FE2FLW vector, the promoter region of the human E2F-1 gene was utilized to drive expression of luciferase cDNA, included as a reporter of viral expression. Primary, immortalized, and transformed cells were transduced with the FE2FLW vector and cell cycle alterations were induced with serum starvation/replacement, contact inhibition or drug treatment, revealing cell cycle-dependent changes in reporter activity. Forced E2F-1 expression, but not E2F-2 or E2F-3, increased reporter activity, indicating a major role for this factor in controlling expression from the FE2FLW virus. We show the utility of this vector as a reporter of E2F-1 and proliferation-dependent cellular alterations upon cytotoxic/cytostatic treatment, such as the introduction of tumor suppressor genes. We propose that the FE2FLW vector may be a starting point for the development of gene therapy strategies for proliferative diseases, such as cancer or restinosis

  18. The RB/E2F pathway and regulation of RNA processing

    Energy Technology Data Exchange (ETDEWEB)

    Ahlander, Joseph [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States); Bosco, Giovanni, E-mail: gbosco@email.arizona.edu [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States)

    2009-07-03

    The retinoblastoma tumor suppressor protein (RB) is inactivated in a majority of cancers. RB restricts cell proliferation by inhibiting the E2F family of transcription factors. The current model for RB/E2F function describes its role in regulating transcription at gene promoters. Whether the RB or E2F proteins might play a role in gene expression beyond transcription initiation is not well known. This review describes evidence that points to a novel role for the RB/E2F network in the regulation of RNA processing, and we propose a model as a framework for future research. The elucidation of a novel role of RB in RNA processing will have a profound impact on our understanding of the role of this tumor suppressor family in cell and developmental biology.

  19. E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

    Science.gov (United States)

    Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

    2016-11-01

    Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

  20. E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Wang, Kai-Ling; Mei, Yan-Yan; Cui, Lei; Zhao, Xiao-Xi; Li, Wei-Jing; Gao, Chao; Liu, Shu-Guang; Jiao, Ying; Liu, Fei-Fei; Wu, Min-Yuan; Ding, Wei; Li, Zhi-Gang

    2014-10-01

    To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia (ALL). We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort (n = 48), receiver operating characteristic (ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort (n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed. ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival (LFS) and event-free survival (EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR-ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease (MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR-ABL fusion. Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Novel Approach for Coexpression Analysis of E2F1–3 and MYC Target Genes in Chronic Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Fengfeng Wang

    2014-01-01

    Full Text Available Background. Chronic myelogenous leukemia (CML is characterized by tremendous amount of immature myeloid cells in the blood circulation. E2F1–3 and MYC are important transcription factors that form positive feedback loops by reciprocal regulation in their own transcription processes. Since genes regulated by E2F1–3 or MYC are related to cell proliferation and apoptosis, we wonder if there exists difference in the coexpression patterns of genes regulated concurrently by E2F1–3 and MYC between the normal and the CML states. Results. We proposed a method to explore the difference in the coexpression patterns of those candidate target genes between the normal and the CML groups. A disease-specific cutoff point for coexpression levels that classified the coexpressed gene pairs into strong and weak coexpression classes was identified. Our developed method effectively identified the coexpression pattern differences from the overall structure. Moreover, we found that genes related to the cell adhesion and angiogenesis properties were more likely to be coexpressed in the normal group when compared to the CML group. Conclusion. Our findings may be helpful in exploring the underlying mechanisms of CML and provide useful information in cancer treatment.

  2. E2F1-Mediated Induction of NFYB Attenuates Apoptosis via Joint Regulation of a Pro-Survival Transcriptional Program.

    Directory of Open Access Journals (Sweden)

    Xiaolei Jiang

    Full Text Available The E2F1 transcription factor regulates cell proliferation and apoptosis through the control of a considerable variety of target genes. Previous work has detailed the role of other transcription factors in mediating the specificity of E2F function. Here we identify the NF-YB transcription factor as a novel direct E2F1 target. Genome-wide expression analysis of the effects of NFYB knockdown on E2F1-mediated transcription identified a large group of genes that are co-regulated by E2F1 and NFYB. We also provide evidence that knockdown of NFYB enhances E2F1-induced apoptosis, suggesting a pro-survival function of the NFYB/E2F1 joint transcriptional program. Bioinformatic analysis suggests that deregulation of these NFY-dependent E2F1 target genes might play a role in sarcomagenesis as well as drug resistance.

  3. Identification of E2F1 as a positive transcriptional regulator for δ-catenin

    International Nuclear Information System (INIS)

    Kim, Kwonseop; Oh, Minsoo; Ki, Hyunkyoung; Wang Tao; Bareiss, Sonja; Fini, M. Elizabeth.; Li Dawei; Lu Qun

    2008-01-01

    δ-Catenin is upregulated in human carcinomas. However, little is known about the potential transcriptional factors that regulate δ-catenin expression in cancer. Using a human δ-catenin reporter system, we have screened several nuclear signaling modulators to test whether they can affect δ-catenin transcription. Among β-catenin/LEF-1, Notch1, and E2F1, E2F1 dramatically increased δ-catenin-luciferase activities while β-catenin/LEF-1 induced only a marginal increase. Rb suppressed the upregulation of δ-catenin-luciferase activities induced by E2F1 but did not interact with δ-catenin. RT-PCR and Western blot analyses in 4 different prostate cancer cell lines revealed that regulation of δ-catenin expression is controlled mainly at the transcriptional level. Interestingly, the effects of E2F1 on δ-catenin expression were observed only in human cancer cells expressing abundant endogenous δ-catenin. These studies identify E2F1 as a positive transcriptional regulator for δ-catenin, but further suggest the presence of strong negative regulator(s) for δ-catenin in prostate cancer cells with minimal endogenous δ-catenin expression

  4. Stochastic E2F activation and reconciliation of phenomenological cell-cycle models.

    Science.gov (United States)

    Lee, Tae J; Yao, Guang; Bennett, Dorothy C; Nevins, Joseph R; You, Lingchong

    2010-09-21

    The transition of the mammalian cell from quiescence to proliferation is a highly variable process. Over the last four decades, two lines of apparently contradictory, phenomenological models have been proposed to account for such temporal variability. These include various forms of the transition probability (TP) model and the growth control (GC) model, which lack mechanistic details. The GC model was further proposed as an alternative explanation for the concept of the restriction point, which we recently demonstrated as being controlled by a bistable Rb-E2F switch. Here, through a combination of modeling and experiments, we show that these different lines of models in essence reflect different aspects of stochastic dynamics in cell cycle entry. In particular, we show that the variable activation of E2F can be described by stochastic activation of the bistable Rb-E2F switch, which in turn may account for the temporal variability in cell cycle entry. Moreover, we show that temporal dynamics of E2F activation can be recast into the frameworks of both the TP model and the GC model via parameter mapping. This mapping suggests that the two lines of phenomenological models can be reconciled through the stochastic dynamics of the Rb-E2F switch. It also suggests a potential utility of the TP or GC models in defining concise, quantitative phenotypes of cell physiology. This may have implications in classifying cell types or states.

  5. Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

    International Nuclear Information System (INIS)

    Kasim, Vivi; Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia; Yang, Li; Miyagishi, Makoto; Wu, Shourong

    2014-01-01

    Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73

  6. Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

    Energy Technology Data Exchange (ETDEWEB)

    Kasim, Vivi, E-mail: vivikasim78@gmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Yang, Li [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Miyagishi, Makoto [Molecular Composite Medicine Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566 (Japan); Wu, Shourong, E-mail: shourongwu@hotmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2014-07-04

    Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73.

  7. Conditional E2F1 activation in transgenic mice causes testicular atrophy and dysplasia mimicking human CIS

    DEFF Research Database (Denmark)

    Agger, Karl; Santoni-Rugiu, Eric; Holmberg, Christian

    2005-01-01

    E2F1 is a crucial downstream effector of the retinoblastoma protein (pRB) pathway. To address the consequences of short-term increase in E2F1 activity in adult tissues, we generated transgenic mice expressing the human E2F1 protein fused to the oestrogen receptor (ER) ligand-binding domain...

  8. An inverted repeat motif stabilizes binding of E2F and enhances transcription of the dihydrofolate reductase gene

    DEFF Research Database (Denmark)

    Wade, M; Blake, M C; Jambou, R C

    1995-01-01

    consensus E2F site, significantly decrease the binding stability of all of the forms of E2F tested. The rate of association of E2F-1/DP-1 heterodimers with the inverted repeat wild type site was not significantly different from those with the two single site mutated probes. Furthermore, the mutations...

  9. E2F1 activation is responsible for pituitary adenomas induced by HMGA2 gene overexpression

    Directory of Open Access Journals (Sweden)

    Fusco Alfredo

    2006-08-01

    Full Text Available Abstract The High Mobility Group protein HMGA2 is a nuclear architectural factor that plays a critical role in a wide range of biological processes including regulation of gene expression, embryogenesis and neoplastic transformation. Several studies are trying to identify the mechanisms by which HMGA2 protein is involved in each of these activities, and only recently some new significant insights are emerging from the study of transgenic and knock-out mice. Overexpression of HMGA2 gene leads to the onset of prolactin and GH-hormone induced pituitary adenomas in mice, suggesting a critical role of this protein in pituitary tumorigenesis. This was also confirmed in the human pathology by the finding that HMGA2 amplification and/or overexpression is present in human prolactinomas. This review focuses on recent data that explain the mechanism by which HMGA2 induces the development of pituitary adenomas in mice. This mechanism entails the activation of the E2F1 protein by the HMGA2-mediated displacement of HDAC1 from pRB protein.

  10. E2F repression by C/EBPalpha is required for adipogenesis and granulopoiesis in vivo

    DEFF Research Database (Denmark)

    Porse, B T; Pedersen TA; Xu, X

    2001-01-01

    -dependent transcription and found them to be impaired in their ability to suppress cellular proliferation, and to induce adipocyte differentiation in vitro. Using targeted mutagenesis of the mouse germline, we show that E2F repression-deficient C/EBPalpha alleles failed to support adipocyte and granulocyte...... differentiation in vivo. These results indicate that E2F repression by C/EBPalpha is critical for its ability to induce terminal differentiation, and thus provide genetic evidence that direct cell cycle control by a mammalian lineage-instructive transcription factor couples cellular growth arrest...

  11. The E2F transcription factors: key regulators of cell proliferation

    DEFF Research Database (Denmark)

    Müller, H; Helin, K

    2000-01-01

    Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression....... It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has...

  12. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan

    2010-02-24

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.Methods: Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.Results: Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity

  13. Clinical Utility Of Blood E2F3 MRNA Assay In The Early Diagnosis Of Prostatic Cancer By Real-Time Polymerase Chain Reaction

    International Nuclear Information System (INIS)

    Zaki, M.M.; Elzayat, T.M.; Mahmoud, M.A.; El Hadidi, E.S.; Abdel Al Ahmed, H.; Mohamed, N.A.

    2013-01-01

    Background: Based on the fact that prostate cancer development and progression is the result of the interaction between different molecular mechanisms, many efforts have been devoted to the identification of new circulating genes that could serve as non invasive, reliable early diagnostic and prognostic markers and where their specific functions allow potential therapeutic targets. E2F3 is a member of E2F family of transcription factors involved in cell cycle regulatory functions. It was found that E2F3 is over-expressed in some tumors including bladder and prostate cancer. Aim: The aim of the study was to evaluate the clinical significance of peripheral blood E2F3 mRNA assay in the early diagnosis of patients with localized prostate cancer and to compare its expression in the blood of age-matched prostate cancer, benign prostatic hypertrophy and healthy males. Methods: This study was conducted on 25 patients with cancer prostate, 15 patients with benign prostatic hyperplasia (serving as a pathological control group) in addition to 10 healthy men (serving as a healthy control group). Blood samples were collected and tested for the detection of E2F3 mRNA gene by real time RT-PCR and prostate specific antigen (PSA) by electro chemiluminescence immunoassay. E2F3 mRNA results were reported in relative quantification, where the target and housekeeping gene (GAPDH) were amplified from the same sample in two separate reaction plates. Results were then compared between different samples relying on direct comparison of threshold cycle (CT) values. Finally, the normalized level of target gene expression was calculated by using the formula: 2 δδCT Results: Total PSA at the cutoff 4 ng/mL had a diagnostic sensitivity of 88%, specificity of 84%, positive predictive value of 88%, negative predictive value of 84% and diagnostic efficacy of 86%. E2F3 mRNA was statistically higher in cancer prostate group than in benign prostatic hyperplasia and healthy control groups. At the cut

  14. G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter

    DEFF Research Database (Denmark)

    Dou, Q P; Zhao, S; Levin, A H

    1994-01-01

    report that MT2 includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following evidence. (i) MT2 bound specifically to an affinity-purified fusion human E2F protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound specifically to similar or identical nuclear protein complexes...... complexes were also investigated. Studies using specific antibodies revealed that p107, a retinoblastoma-like protein, was present in both E2F-G0/G1 and E2F.S, whereas cyclin E.cyclin A.cdk2 were only present in E2F.S complex(es). These data suggest that removal of the p107-containing E2F.G0/G1 complex...

  15. High Incidence of Thymic Epithelial Tumors in E2F2 Transgenic Mice

    NARCIS (Netherlands)

    Scheijen, B.; Bronk, M.; Meer, T. van der; Jong, D. de; Bernards, R.A.

    2004-01-01

    In virtually all human tumors, genetic and epigenetic alterations have been found which affect the INK4/-CYCLIN D/RB pathway, which regulates cell cycle entry and exit in normal cells. E2F transcription factors are important downstream components of this pathway, which act by controlling the

  16. Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4

    DEFF Research Database (Denmark)

    Farkas, Thomas; Hansen, Klaus; Holm, Karin

    2002-01-01

    The "pocket proteins" pRb (retinoblastoma tumor suppressor protein), p107, and p130 regulate cell proliferation via phosphorylation-sensitive interactions with E2F transcription factors and other proteins. We previously identified 22 in vivo phosphorylation sites in human p130, including three...

  17. Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch

    Directory of Open Access Journals (Sweden)

    Jungeun Sarah Kwon

    2017-09-01

    Full Text Available Quiescence is a non-proliferative cellular state that is critical to tissue repair and regeneration. Although often described as the G0 phase, quiescence is not a single homogeneous state. As cells remain quiescent for longer durations, they move progressively deeper and display a reduced sensitivity to growth signals. Deep quiescent cells, unlike senescent cells, can still re-enter the cell cycle under physiological conditions. Mechanisms controlling quiescence depth are poorly understood, representing a currently underappreciated layer of complexity in growth control. Here, we show that the activation threshold of a Retinoblastoma (Rb-E2F network switch controls quiescence depth. Particularly, deeper quiescent cells feature a higher E2F-switching threshold and exhibit a delayed traverse through the restriction point (R-point. We further show that different components of the Rb-E2F network can be experimentally perturbed, following computer model predictions, to coarse- or fine-tune the E2F-switching threshold and drive cells into varying quiescence depths.

  18. E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Zejun [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Gong, Chaoju [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058 (China); Liu, Hong [Zhejiang Normal University – Jinhua People' s Hospital Joint Center for Biomedical Research, Jinhua, Zhejiang, 321004 (China); Zhang, Xiaomin; Mei, Lingming [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Song, Mintao [Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005 (China); Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Chen, Xiang, E-mail: sychenxiang@126.com [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China)

    2015-08-21

    As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and

  19. Oct3/4 directly regulates expression of E2F3a in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki; Yokota, Takashi; Koide, Hiroshi

    2015-01-01

    Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activity by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction

  20. Oct3/4 directly regulates expression of E2F3a in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki; Yokota, Takashi; Koide, Hiroshi, E-mail: hkoide@med.kanazawa-u.ac.jp

    2015-04-10

    Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activity by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction.

  1. Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization.

    Science.gov (United States)

    Qi, Qian-Rong; Zhao, Xu-Yu; Zuo, Ru-Juan; Wang, Tong-Song; Gu, Xiao-Wei; Liu, Ji-Long; Yang, Zeng-Ming

    2015-01-01

    Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polyploidization of decidual cells. E2F8-mediated polyploidization is a response to stresses which are accompanied by decidualization. Interestingly, polyploidization is not detected during human decidualization with the down-regulation of E2F8, indicating differential expression of E2F8 may lead to the difference of decidual cell polyploidization between mice and humans.

  2. Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization

    OpenAIRE

    Qi, Qian-Rong; Zhao, Xu-Yu; Zuo, Ru-Juan; Wang, Tong-Song; Gu, Xiao-Wei; Liu, Ji-Long; Yang, Zeng-Ming

    2015-01-01

    Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polypl...

  3. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    DEFF Research Database (Denmark)

    Helin, K; Wu, C L; Fattaey, A R

    1993-01-01

    the hypophosphorylated form of the retinoblastoma protein (pRB). The other protein, murine DP-1, was purified from an E2F DNA-affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 and DP-1, we have now isolated a cDNA for the human...

  4. E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    David G. Johnson

    2012-10-01

    Full Text Available Many of the biochemical details of nucleotide excision repair (NER have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure. Interestingly, many of the players involved in modifying chromatin at sites of DNA damage were originally identified as regulators of transcription. These include ATP-dependent chromatin remodelers, histone modifying enzymes and several transcription factors. The p53 and E2F1 transcription factors are well known for their abilities to regulate gene expression in response to DNA damage. This review will highlight the underappreciated, transcription-independent functions of p53 and E2F1 in modifying chromatin structure in response to DNA damage to promote global NER.

  5. Apaf-1 is a transcriptional target for E2F and p53

    DEFF Research Database (Denmark)

    Moroni, M C; Hickman, E S; Lazzerini Denchi, E

    2001-01-01

    between the deregulation of the pRB pathway and apoptosis. Furthermore, because the pRB pathway is functionally inactivated in most cancers, the identification of Apaf-1 as a transcriptional target for E2F might explain the increased sensitivity of tumour cells to chemotherapy. We also show that......, independently of the pRB pathway, Apaf-1 is a direct transcriptional target of p53, suggesting that p53 might sensitize cells to apoptosis by increasing Apaf-1 levels....

  6. Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Hock Chuan Yeo

    Full Text Available Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs. We developed an integrated bioinformatics pipeline to understand the gene regulation and functions involved in maintaining such self-renewal properties of hPSCs compared to matched fibroblasts. An initial genome-wide screening of transcription factor activity using in silico binding-site and gene expression microarray data newly identified E2F as one of major candidate factors, revealing their significant regulation of the transcriptome. This is underscored by an elevated level of its transcription factor activity and expression in all tested pluripotent stem cell lines. Subsequent analysis of functional gene groups demonstrated the importance of the TFs to self-renewal in the pluripotency-coupled context; E2F directly targets the global signaling (e.g. self-renewal associated WNT and FGF pathways and metabolic network (e.g. energy generation pathways, molecular transports and fatty acid metabolism to promote its canonical functions that are driving the self-renewal of hPSCs. In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs.

  7. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F

    DEFF Research Database (Denmark)

    Helin, K; Lees, J A; Vidal, M

    1992-01-01

    The retinoblastoma protein (pRB) plays an important role in the control of cell proliferation, apparently by binding to and regulating cellular transcription factors such as E2F. Here we describe the characterization of a cDNA clone that encodes a protein with properties of E2F. This clone, RBP3...

  8. A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.

    Science.gov (United States)

    Sellers, W R; Rodgers, J W; Kaelin, W G

    1995-01-01

    An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor. Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest. In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter. These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F. Images Fig. 4 Fig. 5 PMID:8524800

  9. E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.

    Science.gov (United States)

    Carcagno, Abel L; Marazita, Mariela C; Ogara, María F; Ceruti, Julieta M; Sonzogni, Silvina V; Scassa, María E; Giono, Luciana E; Cánepa, Eduardo T

    2011-01-01

    A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity.

  10. E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.

    Directory of Open Access Journals (Sweden)

    Abel L Carcagno

    Full Text Available BACKGROUND: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. CONCLUSIONS/SIGNIFICANCE: The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell

  11. Induction of S-phase entry by E2F transcription factors depends on their nuclear localization

    DEFF Research Database (Denmark)

    Müller, H; Moroni, M C; Vigo, E

    1997-01-01

    The E2F transcription factors are essential for regulating the correct timing of activation of several genes whose products are implicated in cell proliferation and DNA replication. The E2Fs are targets for negative regulation by the retinoblastoma protein family, which includes pRB, p107, and p130......, and they are in a pathway that is frequently found altered in human cancers. There are five members of the E2F family, and they can be divided into two functional subgroups. Whereas, upon overexpression, E2F-1, -2, and -3 induce S phase in quiescent fibroblasts and override G1 arrests mediated by the p16INK4A tumor...... suppressor protein or neutralizing antibodies to cyclin D1, E2F-4 and -5 do not. Using E2F-1 and E2F-4 as representatives of the two subgroups, we showed here, by constructing a set of chimeric proteins, that the amino terminus of E2F-1 is sufficient to confer S-phase-inducing potential as well...

  12. Functional interrelationship between TFII-I and E2F transcription factors at specific cell cycle gene loci.

    Science.gov (United States)

    Shen, Yong; Nar, Rukiye; Fan, Alex X; Aryan, Mahmoud; Hossain, Mir A; Gurumurthy, Aishwarya; Wassel, Paul C; Tang, Ming; Lu, Jianrong; Strouboulis, John; Bungert, Jörg

    2018-01-01

    Transcription factor TFII-I is a multifunctional protein implicated in the regulation of cell cycle and stress-response genes. Previous studies have shown that a subset of TFII-I associated genomic sites contained DNA-binding motifs for E2F family transcription factors. We analyzed the co-association of TFII-I and E2Fs in more detail using bioinformatics, chromatin immunoprecipitation, and co-immunoprecipitation experiments. The data show that TFII-I interacts with E2F transcription factors. Furthermore, TFII-I, E2F4, and E2F6 interact with DNA-regulatory elements of several genes implicated in the regulation of the cell cycle, including DNMT1, HDAC1, CDKN1C, and CDC27. Inhibition of TFII-I expression led to a decrease in gene expression and in the association of E2F4 and E2F6 with these gene loci in human erythroleukemia K562 cells. Finally, TFII-I deficiency reduced the proliferation of K562 cells and increased the sensitivity toward doxorubicin toxicity. The results uncover novel interactions between TFII-I and E2Fs and suggest that TFII-I mediates E2F function at specific cell cycle genes. © 2017 Wiley Periodicals, Inc.

  13. Positive and negative regulation of cell proliferation by E2F-1: influence of protein level and human papillomavirus oncoproteins

    DEFF Research Database (Denmark)

    Melillo, R M; Helin, K; Lowy, D R

    1994-01-01

    E2F-1 is a member of a family of transcription factors implicated in the activation of genes required for the progression through the S phase of the cell cycle. We have examined the biological activities of E2F-1 with short-term colony-forming assays and long-term immortalization assays. High...... to immortalize NHFKs, or by a transdominant p53 mutant. High levels of E2F-1 also inhibited growth of primary and established fibroblasts. The growth-inhibitory activity required the DNA binding function of E2F-1 but not its transactivation or pRB binding activities. A positive role for lower levels of E2F-1...... in NHFK immortalization was established by examining the ability of E2F-1 to complement HPV16 E7 mutants that were unable to cooperate with HPV16 E6 to immortalize NHFKs. Although E2F-1 was unable by itself to cooperate with E6, it did, in conjunction with E6, complement a p24GLY mutant of E7...

  14. A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

    Science.gov (United States)

    Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

    2007-09-01

    E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

  15. E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair.

    Science.gov (United States)

    Singh, Randeep K; Dagnino, Lina

    2016-05-03

    Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis.

  16. EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

    Directory of Open Access Journals (Sweden)

    David Judah

    2010-11-01

    Full Text Available Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1 promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

  17. EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

    Science.gov (United States)

    Judah, David; Chang, Wing Y; Dagnino, Lina

    2010-11-10

    Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

  18. E2F-dependent induction of p14ARF during cell cycle re-entry in human T cells

    DEFF Research Database (Denmark)

    del Arroyo, Ana Gutierrez; El Messaoudi, Selma; Clark, Paula A

    2007-01-01

    The ARF protein, encoded by alternate exon usage within the CDKN2A locus, provides a link between the retinoblastoma (pRb) and p53 tumor suppressor pathways. Agents that disable pRb or otherwise impinge on the E2F family of transcription factors induce expression of ARF, resulting in stabilization...... of p53 and activation of p53-regulated genes. However, in some cell types ARF is not induced upon cell cycle re-entry, as expected of a conventional E2F target gene, leading to the suggestion that the ARF promoter only responds to supra-physiological or aberrant levels of E2F. These properties have...

  19. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    LENUS (Irish Health Repository)

    Rishi, Loveena

    2014-04-10

    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C\\/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C\\/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C\\/EBPα-p42, and in normal granulocyte\\/macrophage progenitor cells, we detect C\\/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C\\/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis.

  20. S-phase checkpoint elements of the E2F-1 family increase radiosensitivity in fibrosarcoma cells lacking p53

    International Nuclear Information System (INIS)

    Bodis, Stephan; Pruschy, Martin; Wirbelauer, Christiane; Glanzmann, Christoph; Krek, Wilhelm

    1997-01-01

    Purpose: Correct advance of cells through the S-phase of the mammalian cell cycle depends on the timely controlled activity of the E2F-1 transcription factor by cyclin A-cdk2. We are studying the reproductive integrity and radiosensitation of isogenic mouse fibrosarcoma cells, differing only in their p53 status, after expression of E2F-1 wildtype (wt) and specific E2F-1 mutants (mt) lacking the cyclin-A-binding domain. In this tumor model system only p53 wild-type expressing tumor cells are sensitive to ionizing radiation in vitro and in vivo. Material and Methods: Either wild-type p53 or genetically engineered p53 'null' mouse embryo fibroblasts were transfected with the oncogenes E1A and ras. These otherwise isogenic fibrosarcoma cells, with a malignant phenotype and tumorigenic in nude mice, were transfected with retroviruses containing either E2F-1 wild-type or specific E2F-1 mutants lacking the cyclin-A binding domain. Reproductive integrity after E2F-1 transfection with or without ionizing radiation (RT) was tested using the clonogenic assay. Tumor cell morphology of treated cells is analyzed for cell death mechanism. Results: E2F-1 wild-type expression in fibrosarcoma cells induced a clear p53 dependent cell death. While clonogenic survival of p53 'null' tumor cells was only slightly reduced with the expression of E2F-1 wild type (survival fraction of 0.5), the clonogenic survival of p53 wild-type fibrosarcoma tumor cells was reduced by at least one logarithm (survival fraction of 0.05). However, expression of the specific E2F-1 mutant lacking the cyclin-A binding domain reduced clonogenic survival in both the p53 'null' and the p53 wild-type fibrosarcoma cells by at least 2 logarithms (survival fraction 0.01 for p53 'null' and 0.002 for p53 wild-type). The mean values of the survival fractions after 2 and 5 Gy radiation alone in p53 'null' fibrosarcoma cells (SF 2 and SF 5) were SF 2 0.7, SF 5 = 0.15, respectively. The combination of ionizing RT in the p53

  1. Adenovirus E2F1 Overexpression Sensitizes LNCaP and PC3 Prostate Tumor Cells to Radiation In Vivo

    International Nuclear Information System (INIS)

    Udayakumar, Thirupandiyur S.; Stoyanova, Radka; Hachem, Paul; Ahmed, Mansoor M.; Pollack, Alan

    2011-01-01

    Purpose: We previously showed that E2F1 overexpression radiosensitizes prostate cancer cells in vitro. Here, we demonstrate the radiosensitization efficacy of adenovirus (Ad)-E2F1 infection in growing (orthotopic) LNCaP and (subcutaneous) PC3 nude mice xenograft tumors. Methods and Materials: Ad-E2F1 was injected intratumorally in LNCaP (3 x 10 8 plaque-forming units [PFU]) and PC3 (5 x 10 8 PFU) tumors treated with or without radiation. LNCaP tumor volumes (TV) were measured by magnetic resonance imaging, caliper were used to measure PC3 tumors, and serum prostate-specific antigen (PSA) levels were determined by enzyme-linked immunosorbent assay. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and key proteins involved in cell death signaling were analyzed by Western blotting. Results: Intracellular overexpression of Ad-E2F1 had a significant effect on the regression of TV and reduction of PSA levels relative to that of adenoviral luciferase (Ad-Luc)-infected control. The in vivo regressing effect of Ad-E2F1 on LNCaP tumor growth was significant (PSA, 34 ng/ml; TV, 142 mm 3 ) compared to that of Ad-Luc control (PSA, 59 ng/ml; TV, 218 mm 3 ; p 3 to Ad-Luc+RT/PSA, 42 ng/ml, and TV, 174 mm 3 , respectively; p <0.05). For PC3 tumors, the greatest effect was observed with Ad-E2F1 infection alone; there was little or no effect when radiotherapy (RT) was combined. However, addition of RT enhanced the level of in situ apoptosis in PC3 tumors. Molecularly, addition of Ad-E2F1 in a combination treatment abrogated radiation-induced BCL-2 protein expression and was associated with an increase in activated BAX, and together they caused a potent radiosensitizing effect, irrespective of p53 and androgen receptor functional status. Conclusions: We show here for the first time that ectopic overexpression of E2F1 in vivo, using an adenoviral vector, significantly inhibits orthotopic p53 wild-type LNCaP tumors and subcutaneous

  2. Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.

    Science.gov (United States)

    Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A

    2016-07-27

    Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Up-regulated MicroRNA-181a induces carcinogenesis in Hepatitis B virus-related hepatocellular carcinoma by targeting E2F5

    International Nuclear Information System (INIS)

    Zou, Chengcheng; Li, Yongguo; Cao, Yiyi; Zhang, Jinnan; Jiang, Jingrong; Sheng, Yanrui; Wang, Sen; Huang, Ailong; Tang, Hua

    2014-01-01

    Accumulating evidence showed that microRNAs are involved in development and progression of multiple tumors. Recent studies have found that miR-181a were dysregulated in several types of cancers, however, the function of miR-181a in hepatocellular carcinoma (HCC) remains unclear. In this study we assessed the potential association between miR-181a, HBV and HCC. The expression of miR-181a in HBV-expressing cells was determined by using qRT-PCR. Dual-Luciferase reporter Assay, qRT-PCR and western blot were performed to investigate the target genes of miR-181a. The effects of miR-181a on HCC proliferation were analyzed by MTS and colony formation assay. Tumor growth assay was used to analyze the effect of miR-181a on tumor formation. HBV up-regulated miR-181a expression by enhancing its promoter activity. Overexpression of miR-181a in hepatoma cells promoted cell growth in vitro and tumor formation in vivo. Conversely, inhibition of miR-181a suppressed the proliferation of HBV-expressing cells. Mechanism investigation revealed that miR-181a inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3′UTR. Moreover, E2F5 inhibition induced cell growth and rescued the suppressive effect of miR-181a inhibitor on the proliferation of SMMC-7721 cells. Interestingly, we also discovered that HBV could down-regulate E2F5 expression. Those results strongly suggested that HBV down-regulated E2F5 expression, in part, by up-regulating the expression of miR-181a. Up-regulation of miR-181a by HBV in hepatoma cells may contribute to the progression of HCC possibly by targeting E2F5, suggesting miR-181a plays important role in HCC development

  4. Transcription factors ETF, E2F, and SP-1 are involved in cytokine-independent proliferation of murine hepatocytes.

    Science.gov (United States)

    Zellmer, Sebastian; Schmidt-Heck, Wolfgang; Godoy, Patricio; Weng, Honglei; Meyer, Christoph; Lehmann, Thomas; Sparna, Titus; Schormann, Wiebke; Hammad, Seddik; Kreutz, Clemens; Timmer, Jens; von Weizsäcker, Fritz; Thürmann, Petra A; Merfort, Irmgard; Guthke, Reinhard; Dooley, Steven; Hengstler, Jan G; Gebhardt, Rolf

    2010-12-01

    The cellular basis of liver regeneration has been intensely investigated for many years. However, the mechanisms initiating hepatocyte "plasticity" and priming for proliferation are not yet fully clear. We investigated alterations in gene expression patterns during the first 72 hours of C57BL/6N mouse hepatocyte culture on collagen monolayers (CM), which display a high basal frequency of proliferation in the absence of cytokines. Although many metabolic genes were down-regulated, genes related to mitogen-activated protein kinase (MAPK) signaling and cell cycle were up-regulated. The latter genes showed an overrepresentation of transcription factor binding sites (TFBS) for ETF (TEA domain family member 2), E2F1 (E2F transcription factor 1), and SP-1 (Sp1 transcription factor) (P ETF, E2F1, and SP-1 and displayed increased expression of E2F1. Cultivation of murine hepatocytes on CM primes cells for proliferation through cytokine-independent activation of MAPK signaling. The transcription factors ETF, E2F1, and SP-1 seem to play a pronounced role in mediating proliferation-dependent differential gene expression. Similar events, but on a shorter time-scale, occur very early after liver damage in vivo. Copyright © 2010 American Association for the Study of Liver Diseases.

  5. The evaluation of anoxia responsive E2F DNA binding activity in the red eared slider turtle, Trachemys scripta elegans.

    Science.gov (United States)

    Biggar, Kyle K; Storey, Kenneth B

    2018-01-01

    In many cases, the DNA-binding activity of a transcription factor does not change, while its transcriptional activity is greatly influenced by the make-up of bound proteins. In this study, we assessed the protein composition and DNA-binding ability of the E2F transcription factor complex to provide insight into cell cycle control in an anoxia tolerant turtle through the use of a modified ELISA protocol. This modification also permits the use of custom DNA probes that are tailored to a specific DNA binding region, introducing the ability to design capture probes for non-model organisms. Through the use of EMSA and ELISA DNA binding assays, we have successfully determined the in vitro DNA binding activity and complex dynamics of the Rb/E2F cell cycle regulatory mechanisms in an anoxic turtle, Trachemys scripta elegans . Repressive cell cycle proteins (E2F4, Rb, HDAC4 and Suv39H1) were found to significantly increase at E2F DNA-binding sites upon anoxic exposure in anoxic turtle liver. The lack of p130 involvement in the E2F DNA-bound complex indicates that anoxic turtle liver may maintain G 1 arrest for the duration of stress survival.

  6. The evaluation of anoxia responsive E2F DNA binding activity in the red eared slider turtle, Trachemys scripta elegans

    Directory of Open Access Journals (Sweden)

    Kyle K. Biggar

    2018-05-01

    Full Text Available In many cases, the DNA-binding activity of a transcription factor does not change, while its transcriptional activity is greatly influenced by the make-up of bound proteins. In this study, we assessed the protein composition and DNA-binding ability of the E2F transcription factor complex to provide insight into cell cycle control in an anoxia tolerant turtle through the use of a modified ELISA protocol. This modification also permits the use of custom DNA probes that are tailored to a specific DNA binding region, introducing the ability to design capture probes for non-model organisms. Through the use of EMSA and ELISA DNA binding assays, we have successfully determined the in vitro DNA binding activity and complex dynamics of the Rb/E2F cell cycle regulatory mechanisms in an anoxic turtle, Trachemys scripta elegans. Repressive cell cycle proteins (E2F4, Rb, HDAC4 and Suv39H1 were found to significantly increase at E2F DNA-binding sites upon anoxic exposure in anoxic turtle liver. The lack of p130 involvement in the E2F DNA-bound complex indicates that anoxic turtle liver may maintain G1 arrest for the duration of stress survival.

  7. Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E

    1994-01-01

    Adenovirus infection leads to E1A-dependent activation of the transcription factor E2F. E2F has recently been identified in complexes with cellular proteins such as the retinoblastoma protein (pRB) and the two pRB family members p107 and p130. E1A dissociates E2F from these cellular proteins...

  8. E2F-Rb complexes assemble and inhibit cdc25A transcription in cervical carcinoma cells following repression of human papillomavirus oncogene expression

    DEFF Research Database (Denmark)

    Wu, L; Goodwin, E C; Naeger, L K

    2000-01-01

    in the absence of E2 expression. Expression of the E2 protein also led to posttranscriptional increase in the level of E2F4, p105(Rb), and p130 and induced the formation of nuclear E2F4-p130 and E2F4-p105(Rb) complexes. This resulted in marked rearrangement of the protein complexes that formed at the distal E2F...... site in the cdc25A promoter, including the replacement of free E2F complexes with E2F4-p105(Rb) complexes. These experiments indicated that repression of E2F-responsive promoters following HPV E6/E7 repression was mediated by activation of the Rb tumor suppressor pathway and the assembly of repressing...

  9. E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism.

    Science.gov (United States)

    Blanchet, Emilie; Annicotte, Jean-Sébastien; Pradelli, Ludivine A; Hugon, Gérald; Matecki, Stéfan; Mornet, Dominique; Rivier, François; Fajas, Lluis

    2012-09-01

    E2F1 deletion leads to increased mitochondrial number and function, increased body temperature in response to cold and increased resistance to fatigue with exercise. Since E2f1-/- mice show increased muscle performance, we examined the effect of E2f1 genetic inactivation in the mdx background, a mouse model of Duchenne muscular dystrophy (DMD). E2f1-/-;mdx mice demonstrated a strong reduction of physiopathological signs of DMD, including preservation of muscle structure, decreased inflammatory profile, increased utrophin expression, resulting in better endurance and muscle contractile parameters, comparable to normal mdx mice. E2f1 deficiency in the mdx genetic background increased the oxidative metabolic gene program, mitochondrial activity and improved muscle functions. Interestingly, we observed increased E2F1 protein levels in DMD patients, suggesting that E2F1 might represent a promising target for the treatment of DMD.

  10. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation

    DEFF Research Database (Denmark)

    Rishi, Loveena; Hannon, Maura; Salomè, Mara

    2014-01-01

    α (C/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop......The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein...... for E2F1, C/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPα-p42, and in normal granulocyte/macrophage progenitor cells, we detect C/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle...

  11. Cyclin E-induced S phase without activation of the pRb/E2F pathway

    DEFF Research Database (Denmark)

    Lukas, J; Herzinger, T; Hansen, Klaus

    1997-01-01

    In cells of higher eukaryotes, cyclin D-dependent kinases Cdk4 and Cdk6 and, possibly, cyclin E-dependent Cdk2 positively regulate the G1- to S-phase transition, by phosphorylating the retinoblastoma protein (pRb), thereby releasing E2F transcription factors that control S-phase genes. Here we...

  12. Identification of target genes of the p16INK4A-pRB-E2F pathway

    DEFF Research Database (Denmark)

    Vernell, Richard; Helin, Kristian; Müller, Heiko

    2003-01-01

    as physiological targets of the pRB pathway, and the further characterization of these genes should provide insights into how this pathway controls proliferation. We show that Gibbs sampling detects enrichment of several sequence motifs, including E2F consensus binding sites, in the upstream regions of these genes...

  13. Alpha-Tocopheryl succinate induces cytostasis and apoptosis in osteosarcoma cells: the role of E2F1

    Czech Academy of Sciences Publication Activity Database

    Alleva, R.; Benassi, M.S.; Tomasetti, M.; Gellert, N.; Ponticelli, F.; Borghi, B.; Picci, P.; Neužil, Jiří

    2005-01-01

    Roč. 331, č. 4 (2005), s. 1515-1521 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z5052915 Keywords : osteosarcoma * alpha-tocopheryl succinate * E2F1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  14. Telomerase Reverse Transcriptase Deficiency Prevents Neointima Formation Through Chromatin Silencing of E2F1 Target Genes.

    Science.gov (United States)

    Endorf, Elizabeth B; Qing, Hua; Aono, Jun; Terami, Naoto; Doyon, Geneviève; Hyzny, Eric; Jones, Karrie L; Findeisen, Hannes M; Bruemmer, Dennis

    2017-02-01

    Aberrant proliferation of smooth muscle cells (SMC) in response to injury induces pathological vascular remodeling during atherosclerosis and neointima formation. Telomerase is rate limiting for tissue renewal and cell replication; however, the physiological role of telomerase in vascular diseases remains to be determined. The goal of the present study was to determine whether telomerase reverse transcriptase (TERT) affects proliferative vascular remodeling and to define the molecular mechanism by which TERT supports SMC proliferation. We first demonstrate high levels of TERT expression in replicating SMC of atherosclerotic and neointimal lesions. Using a model of guidewire-induced arterial injury, we demonstrate decreased neointima formation in TERT-deficient mice. Studies in SMC isolated from TERT-deficient and TERT overexpressing mice with normal telomere length established that TERT is necessary and sufficient for cell proliferation. TERT deficiency did not induce a senescent phenotype but resulted in G1 arrest albeit hyperphosphorylation of the retinoblastoma protein. This proliferative arrest was associated with stable silencing of the E2F1-dependent S-phase gene expression program and not reversed by ectopic overexpression of E2F1. Finally, chromatin immunoprecipitation and accessibility assays revealed that TERT is recruited to E2F1 target sites and promotes chromatin accessibility for E2F1 by facilitating the acquisition of permissive histone modifications. These data indicate a previously unrecognized role for TERT in neointima formation through epigenetic regulation of proliferative gene expression in SMC. © 2016 American Heart Association, Inc.

  15. HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling

    Directory of Open Access Journals (Sweden)

    Choi Chan

    2010-05-01

    Full Text Available Abstract Background Androgen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained. Results In this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21waf tumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21waf; this inhibition largely affected HOXB13-mediated promotion of E2F signaling. Conclusions Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling.

  16. Differentiation and injury-repair signals modulate the interaction of E2F and pRB proteins with novel target genes in keratinocytes.

    Science.gov (United States)

    Chang, Wing Y; Andrews, Joseph; Carter, David E; Dagnino, Lina

    2006-08-01

    E2F transcription factors are central to epidermal morphogenesis and regeneration after injury. The precise nature of E2F target genes involved in epidermal formation and repair has yet to be determined. Identification of these genes is essential to understand how E2F proteins regulate fundamental aspects of epidermal homeostasis and transformation. We have conducted a genome-wide screen using CpG island microarray analysis to identify novel promoters bound by E2F3 and E2F5 in human keratinocytes. We further characterized several of these genes, and determined that multiple E2F and retinoblastoma (pRb) family proteins associate with them in exponentially proliferating cells. We also assessed the effect on E2F and pRb binding to those genes in response to differentiation induced by bone morphogenetic protein-6 (BMP-6), or to activation of repair mechanisms induced by transforming growth factor-beta (TGF-beta). These studies demonstrate promoter- and cytokine-specific changes in binding profiles of E2F and/or pRb family proteins. For example, E2F1, 3, 4 and p107 were recruited to the N-myc promoter in cells treated with BMP-6, whereas E2F1, 3, 4, 5, p107 and p130 were bound to this promoter in the presence of TGF-beta. Functionally, these different interactions resulted in transcriptional repression by BMP-6 and TGF-beta of the N-myc gene, via mechanisms that involved E2F binding to the promoter and association with pRb-family proteins. Thus, multiple combinations of E2F and pRb family proteins may associate with and transcriptionally regulate a given target promoter in response to differentiation and injury-repair stimuli in epidermal keratinocytes.

  17. Systems Biology-Based Identification of Crosstalk between E2F Transcription Factors and the Fanconi Anemia Pathway

    Directory of Open Access Journals (Sweden)

    Moe Tategu

    2007-01-01

    Full Text Available Fanconi anemia (FA is an autosomal recessive disorder characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. At least eleven members of the FA gene family have been identified using complementation experiments. Ubiquitin-proteasome has been shown to be a key regulator of FA proteins and their involvement in the repair of DNA damage. Here, we identifi ed a novel functional link between the FA/BRCA pathway and E2F-mediated cell cycle regulome. In silico mining of a transcriptome database and promoter analyses revealed that a significant number of FA gene members were regulated by E2F transcription factors, known to be pivotal regulators of cell cycle progression – as previously described for BRCA1. Our findings suggest that E2Fs partly determine cell fate through the FA/BRCA pathway.

  18. DEPDC1 promotes cell proliferation and tumor growth via activation of E2F signaling in prostate cancer.

    Science.gov (United States)

    Huang, Lin; Chen, Keng; Cai, Zhao-Peng; Chen, Fu-Chao; Shen, Hui-Yong; Zhao, Wei-Hua; Yang, Song-Jie; Chen, Xu-Biao; Tang, Guo-Xue; Lin, Xi

    2017-08-26

    DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo. Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex

    DEFF Research Database (Denmark)

    Lukas, C; Sørensen, Claus Storgaard; Kramer, E

    1999-01-01

    In mammalian somatic-cell cycles, progression through the G1-phase restriction point and initiation of DNA replication are controlled by the ability of the retinoblastoma tumour-suppressor protein (pRb) family to regulate the E2F/DP transcription factors. Continuing transcription of E2F target...

  20. Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic mobility and promotes pRB-binding in vitro

    DEFF Research Database (Denmark)

    Peeper, D S; Keblusek, P; Helin, K

    1995-01-01

    of the retinoblastoma gene (pRB). We find that E2F-1 proteins are heterogeneously phosphorylated in insect cells, as a result of which they migrate as a doublet on SDS-polyacrylamide gels. This electrophoretic shift is shown to be dependent upon specific phosphorylation of E2F-1 on serine-375 (S375), near the p...

  1. Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Morris Robert

    2010-03-01

    Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

  2. ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage.

    Science.gov (United States)

    Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

    2014-01-01

    The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein-protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage.

  3. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor

    International Nuclear Information System (INIS)

    Hiebert, S.W.; Lipp, M.; Nevins, J.R.

    1989-01-01

    E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here the authors show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, they also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. They conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription

  4. Emerging roles of the RB/E2F pathway in fatty liver disease and cancer

    NARCIS (Netherlands)

    Matondo, R.B.

    2018-01-01

    Liver cancer in humans is ranked number five concerning cancer related deaths accounted worldwide. Many risk factors related to liver cancer have been identified including hepatitis virus infection, exposure to mycotoxins, and fatty liver disease. These risk factors predispose livers to develop

  5. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E; Fattaey, A

    1993-01-01

    Loss of a functional retinoblastoma tumor suppressor gene product, pRB, is a key step in the development of many human tumors. pRB is a negative regulator of cell proliferation and appears to participate in control of entry into the S phase of the cell cycle. The recent demonstration that pRB binds...

  6. E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)

    DEFF Research Database (Denmark)

    Hsu, Jerry Y; Reimann, Julie D R; Sørensen, Claus S

    2002-01-01

    . At the G1-S transition, hEmi1 is transcriptionally induced by the E2F transcription factor, much like cyclin A. hEmi1 overexpression accelerates S phase entry and can override a G1 block caused by overexpression of Cdh1 or the E2F-inhibitor p105 retinoblastoma protein (pRb). Depleting cells of hEmi1...

  7. Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation

    International Nuclear Information System (INIS)

    Hong, Wei; Li, Jinru; Wang, Bo; Chen, Linfeng; Niu, Wenyan; Yao, Zhi; Baniahmad, Aria

    2011-01-01

    Highlights: ► Corepressor Alien interacts with histone methyltransferase ESET in vivo. ► Alien/ESET complex is recruited to nTRE of T3-responsive gene by liganded TRβ1. ► ESET-mediated H3K9 methylation is required for liganded TRβ1-repressed transcription. ► ESET is involved in T3-repressed G1/S phase transition and proliferation. -- Abstract: The ligand-bound thyroid hormone receptor (TR) is known to repress via a negative TRE (nTRE) the expression of E2F1, a key transcription factor that controls the G1/S phase transition. Alien has been identified as a novel interacting factor of E2F1 and acts as a corepressor of E2F1. The detailed molecular mechanism by which Alien inhibits E2F1 gene expression remains unclear. Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, the E2F1 and the nTRE site of the E2F1 gene while the recruitment to the negative thyroid hormone response element (nTRE) is induced by the ligand-bound TRβ1 within the E2F1 gene promoter. We show that, overexpression of ESET promotes, whereas knockdown of ESET releases, the inhibition of TRβ1-regulated gene transcription upon T3 stimulation; and H3K9 methylation is required for TRβ1-repressed transcription. Furthermore, depletion of ESET impairs thyroid hormone-repressed proliferation as well as the G1/S transition of the cell cycle. Taken together, our data indicate that ESET is involved in TRβ1-mediated transcription repression and provide a molecular basis of thyroid hormone-induced repression of proliferation.

  8. KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis

    Directory of Open Access Journals (Sweden)

    Ling-Yu Wang

    2016-09-01

    Full Text Available The histone lysine demethylase KDM4A/JMJD2A has been implicated in prostate carcinogenesis through its role in transcriptional regulation. Here, we describe KDM4A as a E2F1 coactivator and demonstrate a functional role for the E2F1-KDM4A complex in the control of tumor metabolism. KDM4A associates with E2F1 on target gene promoters and enhances E2F1 chromatin binding and transcriptional activity, thereby modulating the transcriptional profile essential for cancer cell proliferation and survival. The pyruvate dehydrogenase kinases (PDKs PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation. Downregulation of KDM4A leads to elevated activity of pyruvate dehydrogenase and mitochondrial oxidation, resulting in excessive accumulation of reactive oxygen species. The altered metabolic phenotypes can be partially rescued by ectopic expression of PDK1 and PDK3, indicating a KDM4A-dependent tumor metabolic regulation via PDK. Our results suggest that KDM4A is a key regulator of tumor metabolism and a potential therapeutic target for prostate cancer.

  9. Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression

    DEFF Research Database (Denmark)

    Lukas, J; Petersen, B O; Holm, K

    1996-01-01

    The E2F family of transcription factors regulate genes, whose products are essential for progression through the mammalian cell cycle. The transcriptional activity of the E2Fs is inhibited through the specific binding of the retinoblastoma protein, pRB, and the pRB homologs p107 and p130 to their......The E2F family of transcription factors regulate genes, whose products are essential for progression through the mammalian cell cycle. The transcriptional activity of the E2Fs is inhibited through the specific binding of the retinoblastoma protein, pRB, and the pRB homologs p107 and p130...

  10. The development of safety requirements

    International Nuclear Information System (INIS)

    Jorel, M.

    2009-01-01

    This document describes the safety approach followed in France for the design of nuclear reactors. This safety approach is based on safety principles from which stem safety requirements that set limiting values for specific parameters. The improvements in computerized simulation, the use of more adequate new materials, a better knowledge of the concerned physical processes, the changes in the reactor operations (higher discharge burnups for instance) have to be taken into account for the definition of safety criteria and the setting of limiting values. The developments of the safety criteria linked to the risks of cladding failure and loss of primary coolant are presented. (A.C.)

  11. Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Blanca L Valle

    Full Text Available Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.

  12. Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Wei, E-mail: hongwei@tijmu.edu.cn [Department of Immunology, Tianjin Medical University, 300070 Tianjin (China); College of Basic Medicine, Tianjin Medical University, 300070 Tianjin (China); Li, Jinru; Wang, Bo [College of Basic Medicine, Tianjin Medical University, 300070 Tianjin (China); Chen, Linfeng [Department of Medical Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, 02115 MA (United States); Niu, Wenyan; Yao, Zhi [Department of Immunology, Tianjin Medical University, 300070 Tianjin (China); Baniahmad, Aria, E-mail: aban@mti.uni-jena.de [Institute for Human Genetics, Jena University Hospital, 07740 Jena (Germany)

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Corepressor Alien interacts with histone methyltransferase ESET in vivo. Black-Right-Pointing-Pointer Alien/ESET complex is recruited to nTRE of T3-responsive gene by liganded TR{beta}1. Black-Right-Pointing-Pointer ESET-mediated H3K9 methylation is required for liganded TR{beta}1-repressed transcription. Black-Right-Pointing-Pointer ESET is involved in T3-repressed G1/S phase transition and proliferation. -- Abstract: The ligand-bound thyroid hormone receptor (TR) is known to repress via a negative TRE (nTRE) the expression of E2F1, a key transcription factor that controls the G1/S phase transition. Alien has been identified as a novel interacting factor of E2F1 and acts as a corepressor of E2F1. The detailed molecular mechanism by which Alien inhibits E2F1 gene expression remains unclear. Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, the E2F1 and the nTRE site of the E2F1 gene while the recruitment to the negative thyroid hormone response element (nTRE) is induced by the ligand-bound TR{beta}1 within the E2F1 gene promoter. We show that, overexpression of ESET promotes, whereas knockdown of ESET releases, the inhibition of TR{beta}1-regulated gene transcription upon T3 stimulation; and H3K9 methylation is required for TR{beta}1-repressed transcription. Furthermore, depletion of ESET impairs thyroid hormone-repressed proliferation as well as the G1/S transition of the cell cycle. Taken together, our data indicate that ESET is involved in TR{beta}1-mediated transcription repression and provide a molecular basis of thyroid hormone-induced repression of proliferation.

  13. Identification of an ovine atadenovirus gene whose product activates the viral E2 promoter: possible involvement of E2F-1

    International Nuclear Information System (INIS)

    Kuemin, Daniel; Hofmann, Christian; Uckert, Wolfgang; Both, Gerald W.; Loeser, Peter

    2004-01-01

    Activation of the adenoviral E2 promoter is an early step in adenovirus gene expression. For members of the mast- and aviadenoviruses, this requires induction of the cellular transcription factor E2F by virally encoded gene products such as E1A, E4orf6/7 and orf22/GAM-1. The newly recognized genus atadenovirus, of which the ovine isolate OAdV is the prototype, lacks any sequence homology to those genes. To find a possible link between E2 promoter activation and OAdV gene expression, we utilized a screening method to search for genes within the OAdV genome that were capable of stimulating the viral E2 promoter. One such gene, E43, was identified within the proposed E4 region toward the right-hand end of the OAdV genome. The E43 gene product was also found to be capable of stimulating E2F-1-dependent gene expression. A closer inspection of the E2 promoter revealed the presence of a non-palindromic E2F binding site within the OAdV E2 promoter. Mutation of this site markedly reduced both E2F-1- and E43-dependent promoter activation. Moreover, a direct protein-protein interaction of the E43 gene product with E2F, but not with the retinoblastoma protein pRb, suggested a possible cooperation between these two proteins in activating the E2 promoter. The importance of the E43 gene product for virus replication is also underlined by the finding that an OAdV recombinant with a functionally inactivated E43 gene showed severely inhibited virus growth

  14. Road safety in developing countries.

    NARCIS (Netherlands)

    Schreuder, D.A.

    1991-01-01

    This paper presents a classification of countries (developing and developed alike), divided into two main categories: an economical and historical entry. When road safety problems are placed into the economical context, it then appears that, among other things: (1) The road safety problem in the

  15. Regulation der FOXO-Gene durch E2F-1und die induzierbare systemische Rekombination eines konditionellen Allels in der Maus

    OpenAIRE

    Geßner, Christine Ruth

    2010-01-01

    1.) FOXO1 und FOXO3A sind Zielgene von E2F-1 in Neuroblastomzellen. 2.) In einem Mausstamm, der ubiquitär ein CRE-ER Fusionsprotein exprimiert, konnte nach Tamoxifen Gabe die Rekombination des konditionellen mutierten p300 AS Gens in der untersuchten Geweben des entsprechenden Mausstammes nachgewiesen werden. Auf Basis dieses Experimentes kann nun die Tumorsuppressor von p300 in vivo untersucht werden.

  16. E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation.

    Science.gov (United States)

    Carcagno, Abel L; Giono, Luciana E; Marazita, Mariela C; Castillo, Daniela S; Pregi, Nicolás; Cánepa, Eduardo T

    2012-07-01

    Central to the maintenance of genomic integrity is the cellular DNA damage response. Depending on the type of genotoxic stress and through the activation of multiple signaling cascades, it can lead to cell cycle arrest, DNA repair, senescence, and apoptosis. p19INK4d, a member of the INK4 family of CDK inhibitors, plays a dual role in the DNA damage response, inhibiting cell proliferation and promoting DNA repair. Consistently, p19INK4d has been reported to become upregulated in response to UV irradiation and a great variety of genotoxic agents. Here, this induction is shown to result from a transcriptional stimulatory mechanism that can occur at every phase of the cell cycle except during mitosis. Moreover, evidence is presented that demonstrates that E2F1 is involved in the induction of p19INK4d following UV treatment, as it is prevented by E2F1 protein ablation and DNA-binding inhibition. Specific inhibition of this regulation using triplex-forming oligonucleotides that target the E2F response elements present in the p19INK4d promoter also block p19INK4d upregulation and sensitize cells to DNA damage. These results constitute the first description of a mechanism for the induction of p19INK4d in response to UV irradiation and demonstrate the physiological relevance of this regulation following DNA damage.

  17. Sustainable Development of Food Safety

    DEFF Research Database (Denmark)

    Fabech, B.; Georgsson, F.; Gry, Jørn

    to food safety - Strengthen efforts against zoonoses and pathogenic microorganisms - Strengthen safe food handling and food production in industry and with consumers - Restrict the occurrence of chemical contaminants and ensure that only well-examined production aids, food additives and flavours are used...... - Strengthen scientific knowledge of food safety - Strengthen consumer knowledge The goals for sustainable development of food safety are listed from farm to fork". All of the steps and areas are important for food safety and consumer protection. Initiatives are needed in all areas. Many of the goals...... in other areas. It should be emphasized that an indicator will be an excellent tool to assess the efficacy of initiatives started to achieve a goal. Conclusions from the project are: - Sustainable development in food safety is important for humanity - Focus on the crucial goals would optimize the efforts...

  18. DEVELOPING CITIZEN SAFETY

    Directory of Open Access Journals (Sweden)

    VRABIE Catalin

    2013-12-01

    Full Text Available Is it possible to involve citizens in the process of increasing public safety? Police used, even from its beginnings, the help of citizens, otherwise they would encounter problems in performing its duty - many of its successes were due to the unification of Police forces with the citizens. How citizens get involved? (1 They may be directly asked by the Police officers (a time consuming method because many police officers needs to go on the field to speak with the potential witnesses or (2 by using the mass-media channels (television can address to a large number of potential witnesses in a very short time. We still can see on TV portraits of missing persons, or some other kind of images with which the Police is trying to solve some of its cases (thieves, robbers or burglars surprised by surveillance cameras – why not Internet software application?!

  19. E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection.

    Directory of Open Access Journals (Sweden)

    Yueting Zheng

    2016-01-01

    Full Text Available Interferons (IFNs are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNα and IFNγ blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC and TERT-immortalized normal human diploid fibroblasts (HDF-TERT. IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNα and IFNγ is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNα and IFNγ impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib, a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNα or IFNγ. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNγ suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.

  20. MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription factor in the context of anticancer chemotherapy resistance

    Science.gov (United States)

    Lai, Xin; Gupta, Shailendra K; Schmitz, Ulf; Marquardt, Stephan; Knoll, Susanne; Spitschak, Alf; Wolkenhauer, Olaf; Pützer, Brigitte M; Vera, Julio

    2018-01-01

    High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach for treating patients showing chemoresistance. Methods: We integrated bioinformatics, structural and kinetic modelling, and experiments to study cooperative regulation of E2F1 by microRNA (miRNA) pairs in the context of anticancer chemotherapy resistance. Results: We showed that an enhanced E2F1 repression efficiency can be achieved in chemoresistant tumour cells through two cooperating miRNAs. Sequence and structural information were used to identify potential miRNA pairs that can form tertiary structures with E2F1 mRNA. We then employed molecular dynamics simulations to show that among the identified triplexes, miR-205-5p and miR-342-3p can form the most stable triplex with E2F1 mRNA. A mathematical model simulating the E2F1 regulation by the cooperative miRNAs predicted enhanced E2F1 repression, a feature that was verified by in vitro experiments. Finally, we integrated this cooperative miRNA regulation into a more comprehensive network to account for E2F1-related chemoresistance in tumour cells. The network model simulations and experimental data indicate the ability of enhanced expression of both miR-205-5p and miR-342-3p to decrease tumour chemoresistance by cooperatively repressing E2F1. Conclusions: Our results suggest that pairs of cooperating miRNAs could be used as potential RNA therapeutics to reduce E2F1-related chemoresistance. PMID:29464002

  1. Radiation Safety for Sustainable Development

    International Nuclear Information System (INIS)

    2015-10-01

    The objective of radiation safety is Assessments of Natural Radioactivity and its Radiological. The following topics were discussed during the conference: AFROSAFE Championing Radiation Safety in Africa, Radiation Calibration, and Development and Validation of a Laser Induced Breakdown Spectrometry Method for Cancer Detection and Characterization. Young Generation in NUCLEAR Initiative to Promote Nuclear Science and Technology, Radiation Protection Safety Culture and Application of Nuclear Techniques in Industry and the Environment were discuss. Rapid Chemometric X-Ray Fluorescence approaches for spectral Diagnostics of Cancer utilizing Tissue Trace Metals and Speciation profiles. Fundamental role of medical physics in Radiation Therapy

  2. Vitamin E δ-tocotrienol induces p27(Kip1-dependent cell-cycle arrest in pancreatic cancer cells via an E2F-1-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Pamela J Hodul

    Full Text Available Vitamin E δ-tocotrienol has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we demonstrated that δ-tocotrienol exerted significant cell growth inhibition pancreatic ductal cancer (PDCA cells without affecting normal human pancreatic ductal epithelial cell growth. We also showed that δ-tocotrienol-induced growth inhibition occurred concomitantly with G(1 cell-cycle arrest and increased p27(Kip1 nuclear accumulation. This finding is significant considering that loss of nuclear p27(Kip1 expression is a well-established adverse prognostic factor in PDCA. Furthermore, δ-tocotrienol inactivated RAF-MEK-ERK signaling, a pathway known to suppress p27(Kip1 expression. To determine whether p27(Kip1 induction is required for δ-tocotrienol inhibition of PDCA cell proliferation, we stably silenced the CDKN1B gene, encoding p27(Kip1, in MIAPaCa-2 PDCA cells and demonstrated that p27(Kip1 silencing suppressed cell-cycle arrest induced by δ-tocotrienol. Furthermore, δ-tocotrienol induced p27(Kip1 mRNA expression but not its protein degradation. p27(Kip1 gene promoter activity was induced by δ-tocotrienol through the promoter's E2F-1 binding site, and this activity was attenuated by E2F-1 depletion using E2F-1 small interfering RNA. Finally, decreased proliferation, mediated by Ki67 and p27(Kip1 expression by δ-tocotrienol, was confirmed in vivo in a nude mouse xenograft pancreatic cancer model. Our findings reveal a new mechanism, dependent on p27(Kip1 induction, by which δ-tocotrienol can inhibit proliferation in PDCA cells, providing a new rationale for p27(Kip1 as a biomarker for δ-tocotrienol efficacy in pancreatic cancer prevention and therapy.

  3. Plant γH2AX foci are required for proper DNA DSB repair responses and colocalize with E2F factors

    OpenAIRE

    Smetana, Ondrej; Sanchez-Calderon, Lenin; Lincker, Frédéric; Genestier, Julie; Schmit, Anne-Catherine; Houlné, Guy; Chabouté, Marie Edith

    2012-01-01

    Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (cH2AX) repair foci which are multiproteic nuclear complexes responsible for DSB sensing and signalling. However, neither the components of these foci nor their role are yet known in plants. In this paper, we describe the effects of cH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional respo...

  4. Integrated genomic analyses identify KDM1A's role in cell proliferation via modulating E2F signaling activity and associate with poor clinical outcome in oral cancer.

    Science.gov (United States)

    Narayanan, Sathiya Pandi; Singh, Smriti; Gupta, Amit; Yadav, Sandhya; Singh, Shree Ram; Shukla, Sanjeev

    2015-10-28

    The histone demethylase KDM1A specifically demethylates lysine residues and its deregulation has been implicated in the initiation and progression of various cancers. However, KDM1A's molecular role and its pathological consequences, and prognostic significance in oral cancer remain less understood. In the present study, we sought to investigate the expression of KDM1A and its downstream role in oral cancer pathogenesis. By comparing mRNA expression profiles, we identified an elevated KDM1A expression in oral tumors when compared to normal oral tissues. In silico pathway prediction identified the association between KDM1A and E2F1 signaling in oral cancer. Pathway scanning, functional annotation analysis and In vitro assays showed the KDM1A's involvement in oral cancer cell proliferation and the cell cycle. Moreover, real time PCR and luciferase assays confirmed KDM1A's role in regulation of E2F1 signaling activity in oral cancer. Elevated KDM1A expression is associated with poor clinical outcome in oral cancer. Our data indicate that deregulated KDM1A expression is positively associated with proliferative phenotype of oral cancer and confers poor clinical outcome. These cumulative data suggest that KDM1A might be a potential diagnostic and therapeutic target for oral cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase.

    Science.gov (United States)

    Leng, Feng; Yu, Jiekai; Zhang, Chunxiao; Alejo, Salvador; Hoang, Nam; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-04-24

    Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4 DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4 DCAF5 . Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4 DCAF5 . Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.

  6. miR-24 inhibits cell proliferation by suppressing expression of E2F2, MYC and other cell cycle regulatory genes by binding to “seedless” 3′UTR microRNA recognition elements

    Science.gov (United States)

    Lal, Ashish; Navarro, Francisco; Maher, Christopher; Maliszewski, Laura E.; Yan, Nan; O'Day, Elizabeth; Chowdhury, Dipanjan; Dykxhoorn, Derek M.; Tsai, Perry; Hofman, Oliver; Becker, Kevin G.; Gorospe, Myriam; Hide, Winston; Lieberman, Judy

    2009-01-01

    Summary miR-24, up-regulated during terminal differentiation of multiple lineages, inhibits cell cycle progression. Antagonizing miR-24 restores post-mitotic cell proliferation and enhances fibroblast proliferation, while over-expressing miR-24 increases the G1 compartment. The 248 mRNAs down-regulated upon miR-24 over-expression are highly enriched for DNA repair and cell cycle regulatory genes that form a direct interaction network with prominent nodes at genes that enhance (MYC, E2F2, CCNB1, CDC2) or inhibit (p27Kip1, VHL) cell cycle progression. miR-24 directly regulates MYC and E2F2 and some genes they transactivate. Enhanced proliferation from antagonizing miR-24 is abrogated by knocking down E2F2, but not MYC, and cell proliferation, inhibited by miR-24 over-expression, is rescued by miR-24-insensitive E2F2. Therefore, E2F2 is a critical miR-24 target. The E2F2 3′UTR lacks a predicted miR-24 recognition element. In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4 and FEN1 by recognizing seedless, but highly complementary, sequences. PMID:19748357

  7. Development of fusion safety standards

    International Nuclear Information System (INIS)

    Longhurst, G.R.; Petti, D.A.; Dinneen, G.A.; Herring, J.S.; DeLooper, J.; Levine, J.D.; Gouge, M.J.

    1996-01-01

    Two new U.S. Department of Energy (DOE) standards have been prepared to assist in the design and regulation of magnetic fusion facilities. They are DOE-STD-6002-96, 'Safety of Magnetic Fusion Facilities - Requirements,' and DOE-STD-6003-96 'Safety of Magnetic Fusion Facilities - Guidance.' The first standard sets forth requirements, mostly based on the Code of Federal Regulations, deemed necessary for the safe design and operation of fusion facilities and a set of safety principles to use in the design. The second standard provides guidance on how to meet the requirements identified in DOE-STD-6002-96. It is written specifically for a facility such as the International Thermonuclear Experimental Reactor (ITER) in the DOE regulatory environment. As technical standards, they are applicable only to the extent that compliance with these standards is included in the contracts of the developers. 7 refs., 1 fig

  8. [miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway].

    Science.gov (United States)

    Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

    2017-10-01

    Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of T24 and EJ bladder cancer cells, and explore the possible molecular mechanism. Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells. The target gene of miR-503-5p was predicted by bioinformatics. The expressions of E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by Western blotting. The cell cycle of bladder cancer cell lines was determined by flow cytometry. MTT assay and plate cloning assay were performed to observe the proliferation ability of bladder cancer cells. Results After miR-503-5p mimics transfection, the expression of miR-503-5p in bladder cancer cells significantly increased. The increased expression of miR-503-5p significantly reduced the expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer cells. What's more, the expressions of Rb/E2F signal pathway proteins were down-regulated. The bladder cancer cells were arrested in G0/G1 phase, and their growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over-expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down-regulating the expression of the Rb/E2F signaling pathway.

  9. Nicotine-Mediated Regulation of Nicotinic Acetylcholine Receptors in Non-Small Cell Lung Adenocarcinoma by E2F1 and STAT1 Transcription Factors.

    Directory of Open Access Journals (Sweden)

    Courtney Schaal

    Full Text Available Cigarette smoking is the major risk factor for non-small cell lung cancer (NSCLC, which accounts for 80% of all lung cancers. Nicotine, the addictive component of tobacco smoke, can induce proliferation, migration, invasion, epithelial-mesenchymal transition (EMT, angiogenesis, and survival in NSCLC cell lines, as well as growth and metastasis of NSCLC in mice. This nicotine-mediated tumor progression is facilitated through activation of nicotinic acetylcholine receptors (nAChRs, specifically the α7 subunit; however, how the α7 nAChR gene is regulated in lung adenocarcinoma is not fully clear. Here we demonstrate that the α7 nAChR gene promoter is differentially regulated by E2F and STAT transcription factors through a competitive interplay; E2F1 induces the promoter, while STAT transcription factors repress it by binding to an overlapping site at a region -294 through -463bp upstream of the transcription start site. Treatment of cells with nicotine induced the mRNA and protein levels of α7 nAChR; this could be abrogated by treatment with inhibitors targeting Src, PI3K, MEK, α7 nAChR, CDK4/6 or a disruptor of the Rb-Raf-1 interaction. Further, nicotine-mediated induction of α7 nAChR was reduced when E2F1 was depleted and in contrast elevated when STAT1 was depleted by siRNAs. Interestingly, extracts from e-cigarettes, which have recently emerged as healthier alternatives to traditional cigarette smoking, can also induce α7 nAChR expression in a manner similar to nicotine. These results suggest an autoregulatory feed-forward loop that induces the levels of α7 nAChR upon exposure to nicotine, which enhances the strength of the signal. It can be imagined that such an induction of α7 nAChR contributes to the tumor-promoting functions of nicotine.

  10. Developing a strong safety culture - a safety management challenge

    International Nuclear Information System (INIS)

    Low, M.; Gipson, G. P.; Williams, M.

    1995-01-01

    The approach is presented adapted by Nuclear Electric to build a strong safety culture through the development of its safety management system. Two features regarded as critical to a strong safety culture are: provision of effective communications to promote an awareness and ownership of safety among craft, and commitment to continuous improvement with a genuine willingness to learn from own experiences and those from others. (N.T.) 5 refs., 4 figs., 1 tab

  11. LA VÍA RB/E2F Y LA FAMILIA DE PROTEÍNAS REPRESORAS POLYCOMB EN EL DESARROLLO DE CÁNCER

    Directory of Open Access Journals (Sweden)

    MERCEDES IMELDA DÁVALOS-SALAS

    2011-01-01

    Full Text Available El control adecuado del ciclo celular mediante la acción coordinada de la familia de factores de transcripción E2F resulta ser clave para la homeostasis celular. El entender su modo de acción desde una perspectiva epigenética resulta ser un tema de gran actualidad y cambia la visión de cómo es regulado el ciclo celular. Uno de los principales reguladores epigenéticos está conformado por el grupo de proteínas Polycomb (PcG, relacionadas con procesos patológicos como el cáncer, a través de la desregulación a nivel epigenético de genes supresores de tumores como BRCA1, p16 y p53, entre otros. Con relación a lo anterior, la regulación del gen supresor Retinoblastoma (Rb ha sido ampliamente estudiado dada su importante participación como regulador negativo del ciclo celular, pero más reciente se ha demostrado que su modo de acción está relacionado con el grupo de proteínas PcG. Cada uno de los procesos que involucran a componentes de la familia de factores E2F, los miembros de Polycomb y la familia de proteína Rb, parecen ser en cierta medida independientes y, por ende, poco relacionados. Sin embargo, existen evidencias de una convergencia a nivel epigenético en la acción de estos conjuntos de moléculas reguladoras de la progresión del ciclo celular y su desregulación nos puede llevar a entender mejor su contribución al desarrollo de procesos patológicos como el cáncer.

  12. Potent anti-tumor effect generated by a novel human papillomavirus (HPV antagonist peptide reactivating the pRb/E2F pathway.

    Directory of Open Access Journals (Sweden)

    Cai-ping Guo

    Full Text Available Human papillomavirus type 16 (HPV16 E7 is a viral oncoprotein believed to play a major role in cervical cancer. In this study, an antagonist peptide against HPV16E7 protein was first identified from screening the c7c phage display peptide library. The binding specificity and affinity of the selected peptide to HPV16E7 were tested by competitive enzyme-linked immunosorbent assay (ELISA. The antagonist peptide showed obvious anti-tumor efficacy both in cell lines and animal tumor models. Significant cell proliferation inhibition with high specificity was noted when HPV16-positive cells were treated with the peptide. This anti-tumor efficacy was resulted from overriding the activities of HPV16E7 and reactivating the pRb/E2F pathway, as shown by a series of experiments. Flow cytometry analysis revealed that the selected peptide induced G1 arrest in a dose-dependent manner. Competitive ELISA, pull down, and Co-IP experiments indicated that the selected peptide disrupted the interaction between HPV16E7 and pRb proteins both in vitro and in vivo. Luciferase reporter assay verified that transcription activities of E2F were suppressed by the peptide through restoration of pRb. RT-PCR and Western blot revealed that it reduced cyclins A, D1, and E1 expression, and led to HPV16E7 protein degradation, but pRb protein stabilization. The current study suggests that this specific peptide may serve as a potential therapeutic agent for HPV16-positive cervical cancer.

  13. BRD4 regulates cellular senescence in gastric cancer cells via E2F/miR-106b/p21 axis.

    Science.gov (United States)

    Dong, Xingchen; Hu, Xiangming; Chen, Jinjing; Hu, Dan; Chen, Lin-Feng

    2018-02-12

    Small molecules targeting bromodomains of BET proteins possess strong anti-tumor activities and have emerged as potential therapeutics for cancer. However, the underlying mechanisms for the anti-proliferative activity of these inhibitors are still not fully characterized. In this study, we demonstrated that BET inhibitor JQ1 suppressed the proliferation and invasiveness of gastric cancer cells by inducing cellular senescence. Depletion of BRD4, which was overexpressed in gastric cancer tissues, but not other BET proteins recapitulated JQ1-induced cellular senescence with increased cellular SA-β-Gal activity and elevated p21 levels. In addition, we showed that the levels of p21 were regulated at the post-transcriptional level by BRD4-dependent expression of miR-106b-5p, which targets the 3'-UTR of p21 mRNA. Overexpression of miR-106b-5p prevented JQ1-induced p21 expression and BRD4 inhibition-associated cellular senescence, whereas miR-106b-5p inhibitor up-regulated p21 and induced cellular senescence. Finally, we demonstrated that inhibition of E2F suppressed the binding of BRD4 to the promoter of miR-106b-5p and inhibited its transcription, leading to the increased p21 levels and cellular senescence in gastric cancer cells. Our results reveal a novel mechanism by which BRD4 regulates cancer cell proliferation by modulating the cellular senescence through E2F/miR-106b-5p/p21 axis and provide new insights into using BET inhibitors as potential anticancer drugs.

  14. Work safety and sustainable development in enterprise

    Institute of Scientific and Technical Information of China (English)

    TANG Min-kang; ZHOU Yue; XU Jian-hong

    2005-01-01

    The nature of work safety and the way insisting on sustainable development in enterprise were analyzed. It indicates that problem of work safety in enterprise is closely related to the public's consciousness, to the development of science and technology, and to the weakening of safety management during the economic transition period. However, it is the people's questions concerned in the final analysis for the forming and development of the problem of work safety. Therefore, in order to solve the problem of work safety radically, the most basic way of insisting on the sustainable development in safety administration is to do a good job of every aspect about people. We should improve all people quality in science and culture and strengthen their safety and legal consciousness to form correct safety value concept. We should fortify safety legislation and bring close attention to approach and apply new safety technology.

  15. The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study.

    Science.gov (United States)

    Chen, Shi; Zhang, Jia-Qiang; Chen, Jiang-Zhi; Chen, Hui-Xing; Qiu, Fu-Nan; Yan, Mao-Lin; Chen, Yan-Ling; Peng, Cheng-Hong; Tian, Yi-Feng; Wang, Yao-Dong

    2017-09-01

    This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Development of safety related technology and infrastructure for safety assessment

    International Nuclear Information System (INIS)

    Venkat Raj, V.

    1997-01-01

    Development and optimum utilisation of any technology calls for the building up of the necessary infrastructure and backup facilities. This is particularly true for a developing country like India and more so for an advanced technology like nuclear technology. Right from the inception of its nuclear power programme, the Indian approach has been to develop adequate infrastructure in various areas such as design, construction, manufacture, installation, commissioning and safety assessment of nuclear plants. This paper deals with the development of safety related technology and the relevant infrastructure for safety assessment. A number of computer codes for safety assessment have been developed or adapted in the areas of thermal hydraulics, structural dynamics etc. These codes have undergone extensive validation through data generated in the experimental facilities set up in India as well as participation in international standard problem exercises. Side by side with the development of the tools for safety assessment, the development of safety related technology was also given equal importance. Many of the technologies required for the inspection, ageing assessment and estimation of the residual life of various components and equipment, particularly those having a bearing on safety, were developed. This paper highlights, briefly, the work carried out in some of the areas mentioned above. (author)

  17. Safety culture development at Daya Bay NPP

    International Nuclear Information System (INIS)

    Zhang Shanming

    2001-01-01

    From view on Organization Behavior theory, the concept, development and affecting factors of safety culture are introduced. The focuses are on the establishment, development and management practice for safety culture at Daya Bay NPP. A strong safety culture, also demonstrated, has contributed greatly to improving performance at Daya Bay

  18. Overexpression of the E2F target gene CENPI promotes chromosome instability and predicts poor prognosis in estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Thangavelu, Pulari U; Lin, Cheng-Yu; Vaidyanathan, Srividya; Nguyen, Thu H M; Dray, Eloise; Duijf, Pascal H G

    2017-09-22

    During cell division, chromosome segregation is facilitated by the mitotic checkpoint, or spindle assembly checkpoint (SAC), which ensures correct kinetochore-microtubule attachments and prevents premature sister-chromatid separation. It is well established that misexpression of SAC components on the outer kinetochores promotes chromosome instability (CIN) and tumorigenesis. Here, we study the expression of CENP-I, a key component of the HIKM complex at the inner kinetochores, in breast cancer, including ductal, lobular, medullary and male breast carcinomas. CENPI mRNA and protein levels are significantly elevated in estrogen receptor-positive (ER+) but not in estrogen receptor-negative (ER-) breast carcinoma. Well-established prognostic tests indicate that CENPI overexpression constitutes a powerful independent marker for poor patient prognosis and survival in ER+ breast cancer. We further demonstrate that CENPI is an E2F target gene. Consistently, it is overexpressed in RB1 -deficient breast cancers. However, CENP-I overexpression is not purely due to cell cycle-associated expression. In ER+ breast cancer cells, CENP-I overexpression promotes CIN, especially chromosome gains. In addition, in ER+ breast carcinomas the degree of CENPI overexpression is proportional to the level of aneuploidy and CENPI overexpression is one of the strongest markers for CIN identified to date. Our results indicate that overexpression of the inner kinetochore protein CENP-I promotes CIN and forecasts poor prognosis for ER+ breast cancer patients. These observations provide novel mechanistic insights and have important implications for breast cancer diagnostics and potentially therapeutic targeting.

  19. Comparative modeling and docking studies of p16ink4/Cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1

    Directory of Open Access Journals (Sweden)

    e Zahra Syeda Naqsh

    2013-01-01

    Full Text Available Abstract Background Lung cancer is the major cause of mortality worldwide. Major signalling pathways that could play significant role in lung cancer therapy include (1 Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase (2 Growth inhibitory pathways (p53/Rb/P14ARF, STK11 (3 Apoptotic pathways (Bcl-2/Bax/Fas/FasL. Insilico strategy was implemented to solve the mystery behind selected lung cancer pathway by applying comparative modeling and molecular docking studies. Results YASARA [v 12.4.1] was utilized to predict structural models of P16-INK4 and RB1 genes using template 4ELJ-A and 1MX6-B respectively. WHAT CHECK evaluation tool demonstrated overall quality of predicted P16-INK4 and RB1 with Z-score of −0.132 and −0.007 respectively which showed a strong indication of reliable structure prediction. Protein-protein interactions were explored by utilizing STRING server, illustrated that CDK4 and E2F1 showed strong interaction with P16-INK4 and RB1 based on confidence score of 0.999 and 0.999 respectively. In order to facilitate a comprehensive understanding of the complex interactions between candidate genes with their functional interactors, GRAMM-X server was used. Protein-protein docking investigation of P16-INK4 revealed four ionic bonds illustrating Arg47, Arg80,Cys72 and Met1 residues as actively participating in interactions with CDK4 while docking results of RB1 showed four hydrogen bonds involving Glu864, Ser567, Asp36 and Arg861 residues which interact strongly with its respective functional interactor E2F1. Conclusion This research may provide a basis for understanding biological insights of P16-INK4 and RB1 proteins which will be helpful in future to design a suitable drug to inhibit the disease pathogenesis as we have determined the interacting amino acids which can be targeted in order to design a ligand in-vitro to propose a drug for clinical trials. Protein -protein docking of

  20. Developing patient safety in dentistry.

    Science.gov (United States)

    Pemberton, M N

    2014-10-01

    Patient safety has always been important and is a source of public concern. Recent high profile scandals and subsequent reports, such as the Francis report into the failings at Mid Staffordshire, have raised those concerns even higher. Mortality and significant morbidity associated with the practice of medicine has led to many strategies to help improve patient safety, however, with its lack of associated mortality and lower associated morbidity, dentistry has been slower at systematically considering how patient safety can be improved. Recently, several organisations, researchers and clinicians have discussed the need for a patient safety culture in dentistry. Strategies are available to help improve patient safety in healthcare and deserve further consideration in dentistry.

  1. Development of Safety Culture Indicators for HANARO

    International Nuclear Information System (INIS)

    Wu, Jong-Sup; Lee, Kye-Hong

    2007-01-01

    Safety culture is more important than a technical matter for the management of nuclear facilities. Some of the accidents that have occurred recently in nuclear plants are important as a social problem besides a technical problem. That's why the management of nuclear plants has been focused on the safety culture to improve confidence of nuclear facilities. As for a safety culture, there are difficulties in that a tangible result does not come out clearly in spite of an effort for a long time. Some IAEA guides and reports about a safety culture and its evaluation method for nuclear power plants (NPP) were published after the Chernobyl accident. Until now there is no tool to evaluate a safety culture of for research reactors. HANARO developed its own safety culture indicators based on the IAEA's documents. The purpose of the development of the safety culture indicators is to evaluate and enhance the safety attitude in HANARO

  2. MiRNA-362-3p induces cell cycle arrest through targeting of E2F1, USF2 and PTPN1 and is associated with recurrence of colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Tobiasen, Heidi; Holm, Anja

    2013-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer deaths in Western countries. A significant number of CRC patients undergoing curatively intended surgery subsequently develop recurrence and die from the disease. MicroRNAs (miRNAs) are aberrantly expressed in cancers and appear to have......-3p in a second independent cohort of 43 CRC patients, using single TaqMan® microRNA assays. In vitro functional analysis showed that over-expression of miR-362-3p in colon cancer cell lines reduced cell viability, and proliferation mainly due to cell cycle arrest. E2F1, USF2 and PTPN1 were identified...... as potential miR-362-3p targets by mRNA profiling of HCT116 cells over-expressing miR-362-3p. Subsequently, these genes were confirmed as direct targets by Luciferase reporter assays and their knockdown in vitro phenocopied the effects of miR-362-3p over-expression. We conclude that miR-362-3p may be a novel...

  3. Bioinformatic detection of E47, E2F1 and SREBP1 transcription factors as potential regulators of genes associated to acquisition of endometrial receptivity

    Directory of Open Access Journals (Sweden)

    Croxatto Horacio B

    2011-01-01

    Full Text Available Abstract Background The endometrium is a dynamic tissue whose changes are driven by the ovarian steroidal hormones. Its main function is to provide an adequate substrate for embryo implantation. Using microarray technology, several reports have provided the gene expression patterns of human endometrial tissue during the window of implantation. However it is required that biological connections be made across these genomic datasets to take full advantage of them. The objective of this work was to perform a research synthesis of available gene expression profiles related to acquisition of endometrial receptivity for embryo implantation, in order to gain insights into its molecular basis and regulation. Methods Gene expression datasets were intersected to determine a consensus endometrial receptivity transcript list (CERTL. For this cluster of genes we determined their functional annotations using available web-based databases. In addition, promoter sequences were analyzed to identify putative transcription factor binding sites using bioinformatics tools and determined over-represented features. Results We found 40 up- and 21 down-regulated transcripts in the CERTL. Those more consistently increased were C4BPA, SPP1, APOD, CD55, CFD, CLDN4, DKK1, ID4, IL15 and MAP3K5 whereas the more consistently decreased were OLFM1, CCNB1, CRABP2, EDN3, FGFR1, MSX1 and MSX2. Functional annotation of CERTL showed it was enriched with transcripts related to the immune response, complement activation and cell cycle regulation. Promoter sequence analysis of genes revealed that DNA binding sites for E47, E2F1 and SREBP1 transcription factors were the most consistently over-represented and in both up- and down-regulated genes during the window of implantation. Conclusions Our research synthesis allowed organizing and mining high throughput data to explore endometrial receptivity and focus future research efforts on specific genes and pathways. The discovery of possible

  4. Melatonin Reverses Fas, E2F-1 and Endoplasmic Reticulum Stress Mediated Apoptosis and Dysregulation of Autophagy Induced by the Herbicide Atrazine in Murine Splenocytes.

    Directory of Open Access Journals (Sweden)

    Shweta Sharma

    Full Text Available Exposure to the herbicide Atrazine (ATR can cause immunotoxicity, apart from other adverse consequences for animal and human health. We aimed at elucidating the apoptotic mechanisms involved in immunotoxicity of ATR and their attenuation by Melatonin (MEL. Young Swiss mice were divided into control, ATR and MEL+ATR groups based on daily (x14 intraperitoneal administration of the vehicle (normal saline, ATR (100 mg/kg body weight and MEL (20 mg/kg body weight with ATR. Isolated splenocytes were processed for detection of apoptosis by Annexin V-FITC and TUNEL assays, and endoplasmic reticulum (ER stress by immunostaining. Key proteins involved in apoptosis, ER stress and autophagy were quantified by immunoblotting. ATR treatment resulted in Fas-mediated activation of caspases 8 and 3 and inactivation of PARP1 which were inhibited significantly by co-treatment with MEL. MEL also attenuated the ATR-induced, p53 independent mitochondrial apoptosis through upregulation of E2F-1 and PUMA and suppression of their downstream target Bax. An excessive ER stress triggered by ATR through overexpression of ATF-6α, spliced XBP-1, CREB-2 and GADD153 signals was reversed by MEL. MEL also reversed the ATR-induced impairment of autophagy which was indicated by a decline in BECN-1, along with significant enhancement in LC3B-II and p62 expressions. Induction of mitochondrial apoptosis, ER stress and autophagy dysregulation provide a new insight into the mechanism of ATR immunotoxicity. The cytoprotective role of MEL, on the other hand, was defined by attenuation of ER stress, Fas-mediated and p53 independent mitochondria-mediated apoptosis as well as autophagy signals.

  5. Model-Driven Development of Safety Architectures

    Science.gov (United States)

    Denney, Ewen; Pai, Ganesh; Whiteside, Iain

    2017-01-01

    We describe the use of model-driven development for safety assurance of a pioneering NASA flight operation involving a fleet of small unmanned aircraft systems (sUAS) flying beyond visual line of sight. The central idea is to develop a safety architecture that provides the basis for risk assessment and visualization within a safety case, the formal justification of acceptable safety required by the aviation regulatory authority. A safety architecture is composed from a collection of bow tie diagrams (BTDs), a practical approach to manage safety risk by linking the identified hazards to the appropriate mitigation measures. The safety justification for a given unmanned aircraft system (UAS) operation can have many related BTDs. In practice, however, each BTD is independently developed, which poses challenges with respect to incremental development, maintaining consistency across different safety artifacts when changes occur, and in extracting and presenting stakeholder specific information relevant for decision making. We show how a safety architecture reconciles the various BTDs of a system, and, collectively, provide an overarching picture of system safety, by considering them as views of a unified model. We also show how it enables model-driven development of BTDs, replete with validations, transformations, and a range of views. Our approach, which we have implemented in our toolset, AdvoCATE, is illustrated with a running example drawn from a real UAS safety case. The models and some of the innovations described here were instrumental in successfully obtaining regulatory flight approval.

  6. Safety culture development in nuclear electric plc

    International Nuclear Information System (INIS)

    Gibson, G.P.; Low, M.B.J.

    1995-01-01

    Nuclear Electric plc (NE) has always given the highest priority to safety. However, past emphasis has been directed towards ensuring safety thorough engineering design and hazard control procedures. Whilst the company did achieve high safety standards, particularly with respect to accidents, it was recognized that further improvements could be obtained. Analysis of the safety performance across a wide range of industries showed that the key to improving safety performance lay in developing a strong safety culture within the company. Over the last five years, NE has made great strides to improve its safety culture. This has resulted in a considerable improvement in its measured safety performance indicators, such as the number of incidents at international nuclear event scale (INES) rating 1, the number of lost time accidents and the collective radiation dose. However, despite this success, the company is committed to further improvement and a means by which this process becomes self-sustaining. In this way the company will achieve its prime goal, to ''ensure the safety of people, plant and the environment''. The paper provides an overview of the development of safety culture in NE since its formation in November 1989. It describes the research and international developments that have influenced the company's understanding of safety culture, the key initiatives that the company has undertaken to enhance its safety culture and the future initiatives being considered to ensure continual improvement. (author). 5 refs, 2 figs, 2 tabs

  7. Advanced Messaging Concept Development Basic Safety Message

    Data.gov (United States)

    Department of Transportation — Contains all Basic Safety Messages (BSMs) collected during the Advanced Messaging Concept Development (AMCD) field testing program. For this project, all of the Part...

  8. Safety guides development process in Spain

    International Nuclear Information System (INIS)

    Butragueno, J.L.; Perello, M.

    1979-01-01

    Safety guides have become a major factor in the licensing process of nuclear power plants and related nuclear facilities of the fuel cycle. As far as the experience corroborates better and better engineering methodologies and procedures, the results of these are settled down in form of standards, guides, and similar issues. This paper presents the actual Spanish experience in nuclear standards and safety guides development. The process to develop a standard or safety guide is shown. Up to date list of issued and on development nuclear safety guides is included and comments on the future role of nuclear standards in the licensing process are made. (author)

  9. Setting clear expectations for safety basis development

    International Nuclear Information System (INIS)

    MORENO, M.R.

    2003-01-01

    DOE-RL has set clear expectations for a cost-effective approach for achieving compliance with the Nuclear Safety Management requirements (10 CFR 830, Nuclear Safety Rule) which will ensure long-term benefit to Hanford. To facilitate implementation of these expectations, tools were developed to streamline and standardize safety analysis and safety document development resulting in a shorter and more predictable DOE approval cycle. A Hanford Safety Analysis and Risk Assessment Handbook (SARAH) was issued to standardized methodologies for development of safety analyses. A Microsoft Excel spreadsheet (RADIDOSE) was issued for the evaluation of radiological consequences for accident scenarios often postulated for Hanford. A standard Site Documented Safety Analysis (DSA) detailing the safety management programs was issued for use as a means of compliance with a majority of 3009 Standard chapters. An in-process review was developed between DOE and the Contractor to facilitate DOE approval and provide early course correction. As a result of setting expectations and providing safety analysis tools, the four Hanford Site waste management nuclear facilities were able to integrate into one Master Waste Management Documented Safety Analysis (WM-DSA)

  10. Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein

    DEFF Research Database (Denmark)

    Mannervik, M; Fan, S; Ström, A C

    1999-01-01

    of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activity. The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had little effect on, for example, E4-ORF6/7 transactivation......Previous studies have shown that the cell cycle-regulated E2F transcription factor is subjected to both positive and negative control by phosphorylation. Here we show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression...... of the E2 promoter. We further show that the repressive effect of E4-ORF4 on E2 transcription works mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also show that E4-ORF4 inhibits E2 mRNA expression...

  11. DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans.

    Science.gov (United States)

    Reddien, Peter W; Andersen, Erik C; Huang, Michael C; Horvitz, H Robert

    2007-04-01

    The genes egl-1, ced-9, ced-4, and ced-3 play major roles in programmed cell death in Caenorhabditis elegans. To identify genes that have more subtle activities, we sought mutations that confer strong cell-death defects in a genetically sensitized mutant background. Specifically, we screened for mutations that enhance the cell-death defects caused by a partial loss-of-function allele of the ced-3 caspase gene. We identified mutations in two genes not previously known to affect cell death, dpl-1 and mcd-1 (modifier of cell death). dpl-1 encodes the C. elegans homolog of DP, the human E2F-heterodimerization partner. By testing genes known to interact with dpl-1, we identified roles in cell death for four additional genes: efl-1 E2F, lin-35 Rb, lin-37 Mip40, and lin-52 dLin52. mcd-1 encodes a novel protein that contains one zinc finger and that is synthetically required with lin-35 Rb for animal viability. dpl-1 and mcd-1 act with efl-1 E2F and lin-35 Rb to promote programmed cell death and do so by regulating the killing process rather than by affecting the decision between survival and death. We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death.

  12. Safety culture assessment developed by JANTI

    International Nuclear Information System (INIS)

    Hamada, Jun

    2009-01-01

    Japan's JCO accident in September 1999 provided a real-life example of what can happen when insufficient attention is paid to safety culture. This accident brought to light the importance of safety culture and reinforced the movement to foster a safety culture. Despite this, accidents and inappropriate conduct have continued to occur. Therefore, there is a strong demand to instill a safety culture throughout the nuclear power industry. In this context, Japan's nuclear power regulator, the Nuclear and Industrial Safety Agency (NISA), decided to include in its safety inspections assessments of the safety culture found in power utilities' routine safety operations to get signs of deterioration in the organizational climate. In 2007, NISA constructed guidelines for their inspectors to carry out these assessments. At the same time, utilities have embarked on their own independent safety culture initiatives, such as revising their technical specifications and building effective PDCA cycle to promote safety culture. In concert with these developments, JANTI has also instituted safety culture assessments. (author)

  13. AMP-activated protein kinase α2 and E2F1 transcription factor mediate doxorubicin-induced cytotoxicity by forming a positive signal loop in mouse embryonic fibroblasts and non-carcinoma cells.

    Science.gov (United States)

    Yang, Wookyeom; Park, In-Ja; Yun, Hee; Im, Dong-Uk; Ock, Sangmi; Kim, Jaetaek; Seo, Seon-Mi; Shin, Ha-Yeon; Viollet, Benoit; Kang, Insug; Choe, Wonchae; Kim, Sung-Soo; Ha, Joohun

    2014-02-21

    Doxorubicin is one of the most widely used anti-cancer drugs, but its clinical application is compromised by severe adverse effects in different organs including cardiotoxicity. In the present study we explored mechanisms of doxorubicin-induced cytotoxicity by revealing a novel role for the AMP-activated protein kinase α2 (AMPKα2) in mouse embryonic fibroblasts (MEFs). Doxorubicin robustly induced the expression of AMPKα2 in MEFs but slightly reduced AMPKα1 expression. Our data support the previous notion that AMPKα1 harbors survival properties under doxorubicin treatment. In contrast, analyses of Ampkα2(-/-) MEFs, gene knockdown of AMPKα2 by shRNA, and inhibition of AMPKα2 activity with an AMPK inhibitor indicated that AMPKα2 functions as a pro-apoptotic molecule under doxorubicin treatment. Doxorubicin induced AMPKα2 at the transcription level via E2F1, a transcription factor that regulates apoptosis in response to DNA damage. E2F1 directly transactivated the Ampkα2 gene promoter. In turn, AMPKα2 significantly contributed to stabilization and activation of E2F1 by doxorubicin, forming a positive signal amplification loop. AMPKα2 directly interacted with and phosphorylated E2F1. This signal loop was also detected in H9c2, C2C12, and ECV (human epithelial cells) cells as well as mouse liver under doxorubicin treatment. Resveratrol, which has been suggested to attenuate doxorubicin-induced cytotoxicity, significantly blocked induction of AMPKα2 and E2F1 by doxorubicin, leading to protection of these cells. This signal loop appears to be non-carcinoma-specific because AMPKα2 was not induced by doxorubicin in five different tested cancer cell lines. These results suggest that AMPKα2 may serve as a novel target for alleviating the cytotoxicity of doxorubicin.

  14. Sign up to Safety: developing a safety improvement plan.

    Science.gov (United States)

    Dight, Carol; Peters, Hayley

    2015-04-01

    The Sign up to Safety (SutS) programme was launched in June 2014 by health secretary Jeremy Hunt. It focuses on listening to patients, carers and staff, learning from what they say when things go wrong, and then taking action to improve patient safety. The programme aims to make the NHS the safest healthcare system in the world by creating a culture devoted to continuous learning and improvement (NHS England 2014). Musgrove Park Hospital, part of Taunton and Somerset NHS Foundation Trust, was one of 12 NHS organisations that signed up to the SutS programme, making public its commitment to the national pledges to be 'open and transparent' and to develop a safety improvement plan. This paper describes the development of the strategy.

  15. Developing safety culture in nuclear power engineering

    International Nuclear Information System (INIS)

    Tevlin, S.A.

    2000-01-01

    The new issue (no. 11) of the IAEA publications series Safety Reports, devoted to the safety culture in nuclear engineering Safety culture development in the nuclear activities. Practical recommendations to achieve success, is analyzed. A number of recommendations of international experts is presented and basic general indicators of satisfactory and insufficient safety culture in the nuclear engineering are indicated. It is shown that the safety culture has two foundations: human behavior and high quality of the control system. The necessity of creating the confidence by the management at all levels of the enterprise, development of individual initiative and responsibility of the workers, which make it possible to realize the structural hierarchic system, including technical, human and organizational constituents, is noted. Three stages are traced in the process of introducing the safety culture. At the first stage the require,emts of scientific-technical documentation and provisions of the governmental, regional and control organs are fulfilled. At the second stage the management of the organization accepts the safety as an important direction in its activities. At the third stage the organization accomplishes its work, proceeding from the position of constant safety improvement. The general model of the safety culture development is considered [ru

  16. Development of nuclear safety issues program

    Energy Technology Data Exchange (ETDEWEB)

    Cho, J. C.; Yoo, S. O.; Yoon, Y. K.; Kim, H. J.; Jeong, M. J.; Noh, K. W.; Kang, D. K

    2006-12-15

    The nuclear safety issues are defined as the cases which affect the design and operation safety of nuclear power plants and also require the resolution action. The nuclear safety issues program (NSIP) which deals with the overall procedural requirements for the nuclear safety issues management process is developed, in accordance with the request of the scientific resolution researches and the establishment/application of the nuclear safety issues management system for the nuclear power plants under design, construction or operation. The NSIP consists of the following 4 steps; - Step 1 : Collection of candidates for nuclear safety issues - Step 2 : Identification of nuclear safety issues - Step 3 : Categorization and resolution of nuclear safety issues - Step 4 : Implementation, verification and closure The NSIP will be applied to the management directives of KINS related to the nuclear safety issues. Through the identification of the nuclear safety issues which may be related to the potential for accident/incidents at operating nuclear power plants either directly or indirectly, followed by performance of regulatory researches to resolve the safety issues, it will be possible to prevent occurrence of accidents/incidents as well as to cope with unexpected accidents/incidents by analyzing the root causes timely and scientifically and by establishing the proper flow-up or remedied regulatory actions. Moreover, the identification and resolution of the safety issues related to the new nuclear power plants completed at the design stage are also expected to make the new reactor licensing reviews effective and efficient as well as to make the possibility of accidents/incidents occurrence minimize. Therefore, the NSIP developed in this study is expected to contribute for the enhancement of the safety of nuclear power plants.

  17. Development of nuclear safety issues program

    International Nuclear Information System (INIS)

    Cho, J. C.; Yoo, S. O.; Yoon, Y. K.; Kim, H. J.; Jeong, M. J.; Noh, K. W.; Kang, D. K.

    2006-12-01

    The nuclear safety issues are defined as the cases which affect the design and operation safety of nuclear power plants and also require the resolution action. The nuclear safety issues program (NSIP) which deals with the overall procedural requirements for the nuclear safety issues management process is developed, in accordance with the request of the scientific resolution researches and the establishment/application of the nuclear safety issues management system for the nuclear power plants under design, construction or operation. The NSIP consists of the following 4 steps; - Step 1 : Collection of candidates for nuclear safety issues - Step 2 : Identification of nuclear safety issues - Step 3 : Categorization and resolution of nuclear safety issues - Step 4 : Implementation, verification and closure The NSIP will be applied to the management directives of KINS related to the nuclear safety issues. Through the identification of the nuclear safety issues which may be related to the potential for accident/incidents at operating nuclear power plants either directly or indirectly, followed by performance of regulatory researches to resolve the safety issues, it will be possible to prevent occurrence of accidents/incidents as well as to cope with unexpected accidents/incidents by analyzing the root causes timely and scientifically and by establishing the proper flow-up or remedied regulatory actions. Moreover, the identification and resolution of the safety issues related to the new nuclear power plants completed at the design stage are also expected to make the new reactor licensing reviews effective and efficient as well as to make the possibility of accidents/incidents occurrence minimize. Therefore, the NSIP developed in this study is expected to contribute for the enhancement of the safety of nuclear power plants

  18. Developing IAM for Life Cycle Safety Assessment

    NARCIS (Netherlands)

    Toxopeus, Marten E.; Lutters, Diederick; Nee, Andrew Y.C.; Song, Bin; Ong, Soh-Khim

    2013-01-01

    This publication discusses aspects of the development of an impact assessment method (IAM) for safety. Compared to the many existing IAM’s for environmentally oriented LCA, this method should translate the impact of a product life cycle on the subject of safety. Moreover, the method should be

  19. Safety management in research and development organisation

    International Nuclear Information System (INIS)

    Nivedha, T.

    2016-01-01

    Health and safety is one of the most important aspects of an organizations smooth and effective functioning. It depends on the safety management, health management, motivation, leadership and training, welfare facilities, accident statistics, policy, organization and administration, hazard control and risk analysis, monitoring, statistics and reporting. Workplace accidents are increasingly common, main causes are untidiness, noise, too hot or cold environments, old or poorly maintained machines, and lack of training or carelessness of employees. One of the biggest issues facing employers today is the safety of their employees. This study aims at analyzing the occupational health and safety of Research organization in Indira Gandhi Centre for Atomic Research by gathering information on health management, safety management, motivation, leadership and training, welfare facilities, accident statistics, organization and administration, hazard control and risk analysis, monitoring, statistics and reporting. Data were collected by using questionnaires which were developed on health and safety management system. (author)

  20. Development of the Digital Reactor Safety System

    International Nuclear Information System (INIS)

    Lee, Dong Young; Lee, C. K.; Hwang, I. K.

    2008-04-01

    Objectives of Project - Development of Digital Safety Grade PLC and Licensing - Development of Safety System(RPS) and Licensing - Development of Safety System(ESF-CCS) and Licensing Content and Result of Project - POSAFE-Q PLC : Development of PLC platform for Shin-UCN unit 1 and 2 ·Development Scope : Processor module, Power module, 3 kinds of Communication module, Bus extension module(Master and Slave), 16 kinds of Input and Output module ·PLC application software development tool(pSET) - IDiPS RPS and IDiPS ESF-CCS : Development of PPS for Sin-UCN 1 and 2 ·Development Scope - 4-channels RPS with the KNICS inherent architecture - A part of 1-channels ESF-CCS with the KNICS inherent architecture - Licensing ·optical Report Submitted and Expected to finish the licensing process until Aug. 2008

  1. Development of a safety management protocol.

    Science.gov (United States)

    2008-09-01

    The UC Berkeley Traffic Safety Center (TSC) has produced this report under a contract from the California Department of Transportation : (Caltrans). The aim is to address workplace injuries and accidents among Caltrans employees and develop recommend...

  2. Development of safety analysis technology for LMR

    International Nuclear Information System (INIS)

    Hahn, Do Hee; Kwon, Y. M.; Kim, K. D.

    2000-05-01

    The analysis methodologies as well as the analysis computer code system for the transient, HCDA, and containment performance analyses, which are required for KALIMER safety analyses, have been developed. The SSC-K code has been developed based on SSC-L which is an analysis code for loop type LMR, by improving models necessary for the KALIMER system analysis, and additional models have been added to the code. In addition, HCDA analysis model has been developed and the containment performance analysis code has been also improved. The preliminary basis for the safety analysis has been established, and the preliminary safety analyses for the key design features have been performed. In addition, a state-of-art analysis for LMR PSA and overseas safety and licensing requirements have been reviewed. The design database for the systematic management of the design documents as well as design processes has been established as well

  3. Development of safety analysis technology for LMR

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, Do Hee; Kwon, Y. M.; Kim, K. D. [and others

    2000-05-01

    The analysis methodologies as well as the analysis computer code system for the transient, HCDA, and containment performance analyses, which are required for KALIMER safety analyses, have been developed. The SSC-K code has been developed based on SSC-L which is an analysis code for loop type LMR, by improving models necessary for the KALIMER system analysis, and additional models have been added to the code. In addition, HCDA analysis model has been developed and the containment performance analysis code has been also improved. The preliminary basis for the safety analysis has been established, and the preliminary safety analyses for the key design features have been performed. In addition, a state-of-art analysis for LMR PSA and overseas safety and licensing requirements have been reviewed. The design database for the systematic management of the design documents as well as design processes has been established as well.

  4. Developing safety in the nuclear fuel cycle

    International Nuclear Information System (INIS)

    Brown, M.L.

    1996-01-01

    The nuclear fuel cycle had its origins in the new technology developed in the 1940s and 50s involving novel physical and chemical processes. At the front end of the cycle, mining, milling and fuel fabrication all underwent development, but in general the focus of process development and safety concerns was the reprocessing stage, with radiation, contamination and criticality the chief hazards. Safety research is not over and there is still work to be done in advancing technical knowledge to new generation nuclear fuels such as Mixed Oxide Fuel and in refining knowledge of margins and of potential upset conditions. Some comments are made on potential areas for work. The NUCEF facility will provide many useful data to aid safety analysis and accident prevention. The routine operations in such plants, basically chemical factories, requires industrial safety and in addition the protection of workers against radiation or contamination. The engineering and management measures for this were novel and the early operation of such plants pioneering. Later commissioning and operating experience has improved routine operating safety, leading to a new generation of factories with highly developed worker protection, engineering safeguards and safety management systems. Ventilation of contamination control zones, remote operation and maintenance, and advanced neutron shielding are engineering examples. In safety management, dose control practices, formally controlled operating procedures and safety cases, and audit processes are comparable with, or lead, best industry practice in other hazardous industries. Nonetheless it is still important that the knowledge and experience from operating plants continue to be gathered together to provide a common basis for improvement. The NEA Working Group on Fuel Cycle Safety provides a forum for much of this interchange. Some activities in the Group are described in particular the FINAS incident reporting system. (J.P.N.)

  5. Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation.

    Science.gov (United States)

    Cui, J G; Zhao, Y; Sethi, P; Li, Y Y; Mahta, A; Culicchia, F; Lukiw, W J

    2010-07-01

    High density micro-RNA (miRNA) arrays, fluorescent-reporter miRNA assay and Northern miRNA dot-blot analysis show that a brain-enriched miRNA-128 is significantly down-regulated in glioblastoma multiforme (GBM) and in GBM cell lines when compared to age-matched controls. The down-regulation of miRNA-128 was found to inversely correlate with WHO tumor grade. Three bioinformatics-verified miRNA-128 targets, angiopoietin-related growth factor protein 5 (ARP5; ANGPTL6), a transcription suppressor that promotes stem cell renewal and inhibits the expression of known tumor suppressor genes involved in senescence and differentiation, Bmi-1, and a transcription factor critical for the control of cell-cycle progression, E2F-3a, were found to be up-regulated. Addition of exogenous miRNA-128 to CRL-1690 and CRL-2610 GBM cell lines (a) restored 'homeostatic' ARP5 (ANGPTL6), Bmi-1 and E2F-3a expression, and (b) significantly decreased the proliferation of CRL-1690 and CRL-2610 cell lines. Our data suggests that down-regulation of miRNA-128 may contribute to glioma and GBM, in part, by coordinately up-regulating ARP5 (ANGPTL6), Bmi-1 and E2F-3a, resulting in the proliferation of undifferentiated GBM cells.

  6. Safety critical software development qualification

    International Nuclear Information System (INIS)

    Marron, J. E.

    2006-01-01

    With the increasing use of digital systems in control applications, customers must acquire appropriate expectations for software development and quality assurance procedures. Purchasers and users of digital systems need to understand the benefits to the supplier of effective quality systems. These systems consist not only of procedures but tools that enable automation. Without the use of automation, quality can not be assured. A software and systems quality program starts with the documents you are very familiar with. But these documents must define more than the final system. They must address specific development environment characteristics and testing capabilities. Starting with the RFP, some of the items that should be introduced are Software Configuration Management, regression testing and defect tracking. The digital system customer is in the best position to enforce the use of software and systems quality programs by including them in project requirements as early as the Purchase Order. The customer's understanding of the full scope and implementation of a software quality program is essential to achieving the quality necessary in nuclear projects, and, incidentally, completing those projects on schedule. (authors)

  7. Global road safety online course development.

    Science.gov (United States)

    2017-06-01

    The Global Road Safety Online Curriculum Development project involved the adaptation of in-person classroom materials and development of new materials to be used in an online setting. A short-course format was selected to pilot the course, and four t...

  8. Network-based differential gene expression analysis suggests cell cycle related genes regulated by E2F1 underlie the molecular difference between smoker and non-smoker lung adenocarcinoma

    Science.gov (United States)

    2013-01-01

    Background Differential gene expression (DGE) analysis is commonly used to reveal the deregulated molecular mechanisms of complex diseases. However, traditional DGE analysis (e.g., the t test or the rank sum test) tests each gene independently without considering interactions between them. Top-ranked differentially regulated genes prioritized by the analysis may not directly relate to the coherent molecular changes underlying complex diseases. Joint analyses of co-expression and DGE have been applied to reveal the deregulated molecular modules underlying complex diseases. Most of these methods consist of separate steps: first to identify gene-gene relationships under the studied phenotype then to integrate them with gene expression changes for prioritizing signature genes, or vice versa. It is warrant a method that can simultaneously consider gene-gene co-expression strength and corresponding expression level changes so that both types of information can be leveraged optimally. Results In this paper, we develop a gene module based method for differential gene expression analysis, named network-based differential gene expression (nDGE) analysis, a one-step integrative process for prioritizing deregulated genes and grouping them into gene modules. We demonstrate that nDGE outperforms existing methods in prioritizing deregulated genes and discovering deregulated gene modules using simulated data sets. When tested on a series of smoker and non-smoker lung adenocarcinoma data sets, we show that top differentially regulated genes identified by the rank sum test in different sets are not consistent while top ranked genes defined by nDGE in different data sets significantly overlap. nDGE results suggest that a differentially regulated gene module, which is enriched for cell cycle related genes and E2F1 targeted genes, plays a role in the molecular differences between smoker and non-smoker lung adenocarcinoma. Conclusions In this paper, we develop nDGE to prioritize

  9. Safety case development with SBVR-based controlled language

    NARCIS (Netherlands)

    Luo, Y.; van den Brand, M.G.J.; Kiburse, A.; Desfray, P.; Philipe, J.; Hammoudi, S.; Pires, L.F.

    2015-01-01

    Safety case development is highly recommended by some safety standards to justify the safety of a system. The Goal Structuring Notation (GSN) is a popular approach to construct a safety case. However, the content of the safety case elements, such as safety claims, is in natural language. Therefore,

  10. Safety policy for nuclear power development

    International Nuclear Information System (INIS)

    Uchida, Hideo

    1987-01-01

    The report discusses various aspects of the safety policy for nuclear power development in Japan. Nuclear power development over three decades in Japan has led to operating performance which is highly safe and reliable. This has been appreciated internationally. Discussed here is the Japanese basic safety policy for nuclear power development that is essential first to design, manufacture and construction using high technology. The current careful quality assurance and reliable operation management by skilled operators are relied upon, on the basis of the fact that measures to prevent abnormal events are given first priority rather than those to mitigate consequences of abnormal events or accidents. Lessons learned from accidents and failures within or outside Japan such as the TMI accident and Chernobyl accident have been reflected in the improvement of safety through careful and thorough examinations of them. For further improvement in nuclear safety, deliberate studies and investigations on severe accidents and probabilistic safety assessment are considered to be important. Such efforts are currently being promoted. For this purpose, it is important to advance international cooperation and continue technical exchanges, based on operation experience in nuclear power stations in Japan. (Nogami, K.)

  11. Status of SPACE Safety Analysis Code Development

    International Nuclear Information System (INIS)

    Lee, Dong Hyuk; Yang, Chang Keun; Kim, Se Yun; Ha, Sang Jun

    2009-01-01

    In 2006, the Korean the Korean nuclear industry started developing a thermal-hydraulic analysis code for safety analysis of PWR(Pressurized Water Reactor). The new code is named as SPACE(Safety and Performance Analysis Code for Nuclear Power Plant). The SPACE code can solve two-fluid, three-field governing equations in one dimensional or three dimensional geometry. The SPACE code has many component models required for modeling a PWR, such as reactor coolant pump, safety injection tank, etc. The programming language used in the new code is C++, for new generation of engineers who are more comfortable with C/C++ than old FORTRAN language. This paper describes general characteristics of SPACE code and current status of SPACE code development

  12. Understanding adolescent development: implications for driving safety.

    Science.gov (United States)

    Keating, Daniel P

    2007-01-01

    The implementation of Graduated Driver Licensing (GDL) programs has significantly improved the crash and fatality rates of novice teen drivers, but these rates remain unacceptably high. A review of adolescent development research was undertaken to identify potential areas of improvement. Research support for GDL was found to be strong, particularly regarding early acquisition of expertise in driving safety (beyond driving skill), and to limitations that reduce opportunities for distraction. GDL regimes are highly variable, and no US jurisdictions have implemented optimal regimes. Expanding and improving GDL to enhance acquisition of expertise and self-regulation are indicated for implementation and for applied research. Driver training that effectively incorporates safety goals along with driving skill is another target. The insurance industry will benefit from further GDL enhancements. Benefits may accrue to improved driver training, improved simulation devices during training, and automated safety feedback instrumentation.

  13. Development of a measure of safety climate

    Directory of Open Access Journals (Sweden)

    N. R. Barnes

    1990-06-01

    Full Text Available A measure of safety climate was developed to aid management in identifying safety problems and responding proactively to safety issues; to assess the general mood of the workforce to safety; and as a standard for comparison with other organizations. The measure of safety climate was based on items extracted from the Chamber of Mines "Loss Control" audit manual. Reliability analysis performed on the scale indicated consistently high reliability coefficients across three ethnic groups. Factor analysis gave support for the construct validity of the scale. Opsomming 'n Meting vir veiligheidsklimaat is ontwikkel ten einde bestuur in staat te stel om veiligheidsprobleme te identifiseer en om pro-aktiefop te tree; om die algemene gevoel van die werkskragte rakende veiligheid te bepaal en om 'n maatstaf vir vergelyking met ander organisasies daar te stel. 'n Betroubaarheidssanalise wat op die skaal uitgevoer is het daarop gedui dat daar konsekwent hoe betroubaarheidskoefisiënte vir drie etniese groepe verkry word. 'n Faktoranalise het die konstrukgeldigheid van die skaal bevestig. The author acknowledges the financial assistance provided by the Human Sciences Research Council for this research.

  14. Developing software for safety-critical applications

    International Nuclear Information System (INIS)

    Chudleigh, M.

    1989-01-01

    The effective implementation of many safety-critical systems involves microprocessors running software which needs to be of very high integrity. This article describes some of the problems of producing such software and the place of software within the total system. A development strategy is proposed based on three principles: the goal of defect-free development, the use of mathematical formalism, and the use of an independent team for testing. (author)

  15. Development of Safety Assessment Information System (SAIS)

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Shik; Lee, Kyung Jin; Lee, Byung Chul [FNC Tech. Co. Ltd. SNU, Seoul (Korea, Republic of); Song, Tae Young; Lee, Chang Ho [KHNP, Daejeon (Korea, Republic of)

    2007-10-15

    Many reports and documents about nuclear power plant safety analysis like a Periodic Safe Review (PSR), Periodic Safety Analysis (PSA) and Severe Accident Management Guideline (SAMG) come to be drawn up from KHNP. Since these are not arranged easy to look up, the systematic arrangement of data was necessary. The solution against hereupon is to store database, and it was developed with the name, SAIS, by FNC Tech. Co. together with NETEC KHNP. In this web program it is easy to manage (registration, search and statistics) data. And the authorized user can approach this system. This was developed, and was verified under the development environment of; - Web Server : Apache 2.2.5 - Program Language : PHP 5.2 - DBMS : Oracle 10g.

  16. Development of Safety Assessment Information System (SAIS)

    International Nuclear Information System (INIS)

    Park, Byung Shik; Lee, Kyung Jin; Lee, Byung Chul; Song, Tae Young; Lee, Chang Ho

    2007-01-01

    Many reports and documents about nuclear power plant safety analysis like a Periodic Safe Review (PSR), Periodic Safety Analysis (PSA) and Severe Accident Management Guideline (SAMG) come to be drawn up from KHNP. Since these are not arranged easy to look up, the systematic arrangement of data was necessary. The solution against hereupon is to store database, and it was developed with the name, SAIS, by FNC Tech. Co. together with NETEC KHNP. In this web program it is easy to manage (registration, search and statistics) data. And the authorized user can approach this system. This was developed, and was verified under the development environment of; - Web Server : Apache 2.2.5 - Program Language : PHP 5.2 - DBMS : Oracle 10g

  17. Development of safety analysis technology for LMR

    International Nuclear Information System (INIS)

    Lee, Y. B.; Kwon, Y. M.; Suk, S. D.

    2005-03-01

    The MATRA-LMR-FB has been developed internally for the damage prevention as well as the safety assessment during a channel blockage accident and, as a the result, the quality of the code becomes comparable to that developed in the leading countries. For a code-to-code comparison, KAERI could have access to the SASSYS-1 through a bilateral collaboration between KAERI and ANL. The study could bring into the reliability improvements both on the reactivity models in the SSC-K and on the SSC-K prediction capability. It finally leads to the completion of the SSC-K version 1.3 resulting from the qualitative and quantitative code-to-code comparison. The preliminary analysis for a metal fueled LMR could also become possible with the MELT-III and the VENUS-II, which had originally been developed for the HCDA analysis with an oxidized fuel, by developing the relevant models For the development of the safety evaluation technology, the safety limits have been set up, and the analyses of the internal and external channel blockages in an assembly have also been performed. Besides, the more reliable analysis results on the key design concepts could be obtained by way of the methodology improvement resulting from the qualitative and quantitative comparison study. For an efficient and systematic control of the main project, the integration of the developed technologies and the establishment of their data base have been pursued. It has gone through the development of the process control with taking account of interfaces among the sub-projects, the overall coordination of the developed technologies, the data base for the design products, and so on

  18. Development of the reactor safety film

    International Nuclear Information System (INIS)

    Sheheen, N.N.; Hodson, P.J.

    1981-01-01

    The first computer-generated film of LASL's Reactor Safety efforts was developed using the ANIMATE framework, a program that adds visual capabilities to MAPPER. Numerous software limitations had to be overcome within a very limited production schedule. A significant achievement was the 15,000-vector-per-frame sequence depicting a pressurized water reactor core with parts flashing while pumps circulate fluid through the system

  19. Development of safety analysis technology for LMR

    International Nuclear Information System (INIS)

    Hahn, Do Hee; Kwon, Y. M.; Suk, S. D.

    2002-05-01

    In the present study, the KALIMER safety analysis has been made for the transients considered in the design concept, hypothetical core disruptive accident (HCDA), and containment performance with the establishment of the design basis. Such analyses have not been possible without the computer code improvement, and the experience attained during this research period must have greatly contributed to the achievement of the self reliance in the domestic technology establishment on the safety analysis areas of the conceptual design. The safety analysis codes have been improved to extend their applicable ranges for detailed conceptual design, and a basic computer code system has been established for HCDA analysis. A code-to-code comparison analysis has been performed as a part of code verification attempt, and the leading edge technology of JNC also has been brought for the technology upgrade. In addition, the research and development on the area of the database establishment has been made for the efficient and systematic project implementation of the conceptual design, through performances on the development of a project scheduling management, integration of the individually developed technology, establishment of the product database, and so on, taking into account coupling of the activities conducted in each specific area

  20. Development of French technical safety regulations: safety fundamental rules

    International Nuclear Information System (INIS)

    Lebouleux, P.

    1982-09-01

    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 operations 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 pratice, 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. The RFS program is described. A RFS -or a letter- can also give the result of the examination of the constructor and operator code (RCC) by safety authorities

  1. Development of French technical safety regulations: safety fundamental rules

    International Nuclear Information System (INIS)

    Lebouleux, P.

    1983-01-01

    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 operating 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 juridicial 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. The RFS program is described. A RFS - or a letter - can also give the result of the examination of the constructor and operator codes (RCC) by safety authorities

  2. Development and formation of safety cultures

    International Nuclear Information System (INIS)

    Merry, M.W.J.; Rycraft, H.S.

    1995-01-01

    The Thermal Oxide Reprocessing Plant (THORP) is the largest project ever undertaken by British Nuclear Fuels plc (BNFL) and its success is important for the future of the company. The company recognised at the planning stage that to be profitable, THORP had to operate both safely and with a smaller workforce. The establishment of an appropriate culture which saw safety and productivity as essential and complimentary at the beginning of the life of the plant was therefore vital for the future success of THORP The key factors in the THORP Culture formation were : The recruitment policy; the training policy; measures taken to ensure participation from the workforce; teamworking support; communication initiatives; clear statement of cultural principles; clear and demonstrable leadership. The current stage of evolution has seen some positive results namely: A clear commitment to involving all personnel in problem solving and task organisation, including safety; a confident workforce with an improved ability to communicate; the capability of the majority of the workforce to work as a team; safety awareness of the workforce is generally high along with an awareness of environmental, commercial and (political) external issues affecting the THORP business; a commitment to continuous improvement. The development of the safety culture within THORP has also had challenges, some as a result of the composite nature of the workforce, and others as side effects of the culture shaping measures. Management have recognised these, and using the results of attitude surveys, are working with the workforce to overcome their effects. Clear recognition has been achieved that the establishment of positive behaviours is a key. step in generating the culture required summarising, there is recognition that the design of safety management systems and improvement programmes, should be based on the principles of human psychology and behaviour. which includes wide participation by the workforce

  3. E2F1-Mediated Upregulation of p19INK4d Determines Its Periodic Expression during Cell Cycle and Regulates Cellular Proliferation

    OpenAIRE

    Carcagno, Abel L.; Marazita, Mariela C.; Ogara, María F.; Ceruti, Julieta M.; Sonzogni, Silvina V.; Scassa, María E.; Giono, Luciana E.; Cánepa, Eduardo T.

    2011-01-01

    Background: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality o...

  4. Developments in safety standards and regulation

    International Nuclear Information System (INIS)

    Harbison, S.A.

    1994-01-01

    This paper explains, in broad terms, how regulatory control is exercised over licensed nuclear installations in the UK and how HSE has developed its safety standards to support its regulatory approach. It first sets out the scope of HSE's regulatory responsibilities, which NII exercises on its behalf, and briefly describes the licensing process and compliance monitoring through inspection over the life of a nuclear plant. It also refers to the role of assessment in NII's decision-making processes, and the part played in this by the consideration of costs and safety benefits. It then moves on to consider the challenges that HSE/NII are likely to face from the changing nuclear industry in the second half of the 1990s. (author)

  5. Statistical modelling of traffic safety development

    DEFF Research Database (Denmark)

    Christens, Peter

    2004-01-01

    there were 6861 injury trafficc accidents reported by the police, resulting in 4519 minor injuries, 3946 serious injuries, and 431 fatalities. The general purpose of the research was to improve the insight into aggregated road safety methodology in Denmark. The aim was to analyse advanced statistical methods......, that were designed to study developments over time, including effects of interventions. This aim has been achieved by investigating variations in aggregated Danish traffic accident series and by applying state of the art methodologies to specific case studies. The thesis comprises an introduction...

  6. New developments enhancing MCNP for criticality safety

    International Nuclear Information System (INIS)

    Hendricks, J.S.; McKinney, G.W.; Forster, R.A.

    1993-01-01

    Since the early 80's MCNP has had three estimates of k eff : collision, absorption, and track length. MCNP has also had collision and absorption estimators of removal lifetime. These are calculated for every cycle and are averaged over the cycles as simple averages and covariance weighted averages. Correlation coefficients between estimators are also calculated. These criticality estimators are all in addition to the extensive summary information and tally edits used in shielding and other problems. A number of significant new developments have been made to enhance the MCNP Monte Carlo radiation transport code for criticality safety applications. These are available in the newly released MCNP4A version of the code

  7. Development of NUMO safety case for geological disposal

    International Nuclear Information System (INIS)

    Suzuki, Satoru; Deguchi, Akira

    2016-01-01

    NUMO has developed a generic safety ease based on the latest knowledge to show the feasibility and safety of geological disposal in Japan. The NUMO safety case has been developed to provide a basic structure for subsequent safety cases that would be applied to any selected site, emphasising practical approaches and methodology, which will be applicable for the conditions/constraints during an actual siting process. This paper will provide a brief overview of the NUMO safety case. (author)

  8. Accident simulator development for probabilistic safety analysis

    International Nuclear Information System (INIS)

    Cacciabue, P.C.; Amendola, A.; Mancini, G.

    1985-01-01

    This paper describes the basic features of a new concept of incident simulator, Response System Analyzed (RSA) which is being developed within the CEC JRC Research Program on Reactor Safety. Focusing on somewhat different aims than actual simulators, RSA development extends the field of application of simulators to the area of risk and reliability analysis and in particular to the identification of relevant sequences, to the modeling of human behavior and to the validation of operating procedures. The fundamental components of the project, i.e. the deterministic transient model of the plant, the automatic probabilistic driver and the human possible intervention modeling, are discussed in connection with the problem of their dynamic interaction. The analyses so far performed by separately testing RSA on significant study cases have shown encouraging results and have proven the feasibility of the overall program

  9. Development of a new methodology for quantifying nuclear safety culture

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kiyoon; Jae, Moosung [Hanyang Univ., Seoul (Korea, Republic of). Dept. of Nuclear Engineering

    2017-01-15

    The present study developed a Safety Culture Impact Assessment Model (SCIAM) which consists of a safety culture assessment methodology and a safety culture impact quantification methodology. The SCIAM uses a safety culture impact index (SCII) to monitor the status of safety culture of NPPs periodically and it uses relative core damage frequency (RCDF) to present the impact of safety culture on the safety of NPPs. As a result of applying the SCIAM to the reference plant (Kori 3), the standard for the healthy safety culture of the reference plant is suggested. SCIAM might contribute to improve the safety of NPPs (Nuclear Power Plants) by monitoring the status of safety culture periodically and presenting the standard of healthy safety culture.

  10. Development of a new methodology for quantifying nuclear safety culture

    International Nuclear Information System (INIS)

    Han, Kiyoon; Jae, Moosung

    2017-01-01

    The present study developed a Safety Culture Impact Assessment Model (SCIAM) which consists of a safety culture assessment methodology and a safety culture impact quantification methodology. The SCIAM uses a safety culture impact index (SCII) to monitor the status of safety culture of NPPs periodically and it uses relative core damage frequency (RCDF) to present the impact of safety culture on the safety of NPPs. As a result of applying the SCIAM to the reference plant (Kori 3), the standard for the healthy safety culture of the reference plant is suggested. SCIAM might contribute to improve the safety of NPPs (Nuclear Power Plants) by monitoring the status of safety culture periodically and presenting the standard of healthy safety culture.

  11. Development of Safety Culture Assessment Strategy for Korean NPP

    International Nuclear Information System (INIS)

    Park, Jung Hwan; Kim, Jong Hyun

    2014-01-01

    This paper aims at developing the requirements for a method to evaluate the operational safety culture, evaluating currently available methods based on the requirements, and suggesting a method to evaluate and improve the operational safety culture for Korean nuclear power plants. This paper reviews the widely-used methods to assess safety culture for NPPs and their basis. Then, this paper develops the requirements for the method to evaluate operational safety culture for Korean NPPs. Based on these requirements, Korean Safety Culture Indicators (KSCI) and evaluation measures are also suggested. Finally this paper proposes the guidelines to develop improvements to safety culture from the evaluation results

  12. Development of Safety Culture Assessment Strategy for Korean NPP

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jung Hwan; Kim, Jong Hyun [KEPCO, Ulsan (Korea, Republic of)

    2014-08-15

    This paper aims at developing the requirements for a method to evaluate the operational safety culture, evaluating currently available methods based on the requirements, and suggesting a method to evaluate and improve the operational safety culture for Korean nuclear power plants. This paper reviews the widely-used methods to assess safety culture for NPPs and their basis. Then, this paper develops the requirements for the method to evaluate operational safety culture for Korean NPPs. Based on these requirements, Korean Safety Culture Indicators (KSCI) and evaluation measures are also suggested. Finally this paper proposes the guidelines to develop improvements to safety culture from the evaluation results.

  13. Development of a nuclear ship safety philosophy

    International Nuclear Information System (INIS)

    Thompson, T.E.

    1978-01-01

    A unique safety philosophy must be recognized and accepted as an integral part of the design and operation of a nuclear ship. For the nuclear powered ship, the ultimate safety of the reactor and therefore the crew and the environment lies with the safety of the ship itself. The basis for ship safety is its ability to navigate and survive the conditions or the environment in which it may find itself. The subject of traditional ship safety is examined along with its implication for reactor protection and safety. Concepts of reactor safety are also examined. These two philosophies are combined in a manner so as to provide a sound philosophy for the safety of nuclear ships, their crews, and the environment

  14. Development of NPP safety regulation in Russia

    International Nuclear Information System (INIS)

    Vishnevsky, Y.G.; Gutsalov, A.T.; Bukrinsky, A.M.; Gordon, B.G.

    1999-01-01

    The presentation describes the organisation scheme of Russian safety regulatory bodies, their tasks and responsibilities. Legislative and regulatory basis of NPP safety regulations rely on the federal laws: Law on the Use of Nuclear Energy and Law on Radiation Safety of the Population. Role of international cooperation and Improvement of regulatory activities in Russia are emphasised

  15. Development of Network Protocol for the Integrated Safety System

    Energy Technology Data Exchange (ETDEWEB)

    Park, S. W.; Baek, J. I.; Lee, S. H.; Park, C. S.; Park, K. H.; Shin, J. M. [Hannam Univ., Daejeon (Korea, Republic of)

    2007-06-15

    Communication devices in the safety system of nuclear power plants are distinguished from those developed for commercial purposes in terms of a strict requirement of safety. The concept of safety covers the determinability, the reliability, and the separation/isolation to prevent the undesirable interactions among devices. The safety also requires that these properties be never proof less. Most of the current commercialized communication products rarely have the safety properties. Moreover, they can be neither verified nor validated to satisfy the safety property of implementation process. This research proposes the novel architecture and protocol of a data communication network for the safety system in nuclear power plants.

  16. Development of Network Protocol for the Integrated Safety System

    International Nuclear Information System (INIS)

    Park, S. W.; Baek, J. I.; Lee, S. H.; Park, C. S.; Park, K. H.; Shin, J. M.

    2007-06-01

    Communication devices in the safety system of nuclear power plants are distinguished from those developed for commercial purposes in terms of a strict requirement of safety. The concept of safety covers the determinability, the reliability, and the separation/isolation to prevent the undesirable interactions among devices. The safety also requires that these properties be never proof less. Most of the current commercialized communication products rarely have the safety properties. Moreover, they can be neither verified nor validated to satisfy the safety property of implementation process. This research proposes the novel architecture and protocol of a data communication network for the safety system in nuclear power plants

  17. Path to development of quantitative safety goals

    International Nuclear Information System (INIS)

    Joksimovic, V.; Houghton, W.J.

    1980-04-01

    There is a growing interest in defining numerical safety goals for nuclear power plants as exemplified by an ACRS recommendation. This paper proposes a lower frequency limit of approximately 10 -4 /reactor-year for design basis events. Below this frequency, down, to a small frequency such as 10 -5 /reactor-year, safety margin can be provided by, say, site emergency plans. Accident sequences below 10 -5 should not impact public safety, but it is prudent that safety research programs examine sequences with significant consequences. Once tentatively agreed upon, quantitative safety goals together with associated implementation tools would be factored into regulatory and design processes

  18. Development of safety analysis technology for integral reactor

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Suk K.; Song, J. H.; Chung, Y. J. and others

    1999-03-01

    Inherent safety features and safety system characteristics of the SMART integral reactor are investigated in this study. Performance and safety of the SMART conceptual design have been evaluated and confirmed through the performance and safety analyses using safety analysis system codes as well as a preliminary performance and safety analysis methodology. SMART design base events and their acceptance criteria are identified to develop a preliminary PIRT for the SMART integral reactor. Using the preliminary PIRT, a set of experimental program for the thermal hydraulic separate effect tests and the integral effect tests was developed for the thermal hydraulic model development and the system code validation. Safety characteristics as well as the safety issues of the integral reactor has been identified during the study, which will be used to resolve the safety issues and guide the regulatory criteria for the integral reactor. The results of the performance and safety analyses performed during the study were used to feedback for the SMART conceptual design. The performance and safety analysis code systems as well as the preliminary safety analysis methodology developed in this study will be validated as the SMART design evolves. The performance and safety analysis technology developed during the study will be utilized for the SMART basic design development. (author)

  19. Developing and maintaining national food safety control systems ...

    African Journals Online (AJOL)

    The establishment of effective food safety systems is pivotal to ensuring the safety of the national food supply as well as food products for regional and international trade. The development, structure and implementation of modern food safety systems have been driven over the years by a number of developments.

  20. Development of safety performance indicators for HANARO

    International Nuclear Information System (INIS)

    Wu, Jong-Sup; Jung, Hoan-Sung; Ahn, Guk-Hoon; Lee, Kye-Hong; Lim, In-Cheol

    2007-01-01

    The nuclear facilities need an extensive basis for ensuring their safety. An operating organization should conduct its operation and utilization important to the safety in accordance with approved procedures and regulations. The general aims of a management system for nuclear facilities are to improve the safety performance through a planning, control and supervision of safety related activities and to foster a strong safety culture. The effectiveness of a management system can be monitored and measured to confirm the ability of its processes to achieve the intended safety performance by an assessment of the operational performance. The Operational Safety Performance Indicators, also known as SPI, help an organization define and measure a progress with regard to safety activity goals. The elements of a SPI are quantifiable measurements that reflect the critical success factors of an organizational safety. Since 1995, efforts have been directed towards the elaboration of a framework for the establishment of an operational safety performance indicator program in nuclear power plants (NPP). IAEA-TECDOC-1141, 'Operational safety performance indicators for NPP' attempted to provide a frame work for an identification of performance indicators which have a relationship to the desired safety attributes, and therefore, to a safe plant operation. Three key attributes of a smooth operation, an operation with a low risk, and an operation with a positive safety attitude, were recommended, which are associated with a safe operation. Because these attributes cannot be directly measured, an indicator structure is expanded further until a level of easily quantifiable or directly measurable indicators is identified. The intention of this approach is to use quantitative information provided by the specific indicators and to analyze performance trends relative to established goals. The safety activities in HANARO have been continuously conducted to enhance its safe operation. HANARO

  1. Assessing progress in the development of safety culture

    International Nuclear Information System (INIS)

    Rotaru, Ioan; Ghita, Sorin

    1999-01-01

    visible prescriptive formula for developing a strong safety culture. However, a prerequisite is genuine and consistent commitment by the top management of an organization to improving safety . Providing this commitment exists, the best recommendation is to due something tangible and visible to improve safety, preferably involving employees from the outset. The choice of practices for developing an improved safety culture should take account of the existing national and organizational culture in order to ensure effective implementation. The importance of the learning process has been emphasized. A mechanism is necessary to ensure that international experience of practices to develop a strong safety culture is shared on a regular and frequent basis. The maintenance and improvement of a safety culture is a process of continuous evolution. Indicators are available to assess positive progress in this evolution and to detect a weakening safety culture. (authors)

  2. Producing health, producing safety. Developing a collective safety culture in radiotherapy

    International Nuclear Information System (INIS)

    Nascimento, Adelaide

    2009-01-01

    This research thesis aims at a better understanding of safety management in radiotherapy and at proposing improvements for patient safety through the development of a collective safety culture. A first part presents the current context in France and abroad, addresses the transposition of other safety methods to the medical domain, and discusses the peculiarities of radiotherapy in terms of risks and the existing quality-assurance approaches. The second part presents the theoretical framework by commenting the intellectual evolution with respect to system safety and the emergence of the concept of safety culture, and by presenting the labour collective aspects and their relationship with system safety. The author then comments the variety of safety cultures among the different professions present in radiotherapy, highlights the importance of the collective dimension in correcting discrepancies at the end of the treatment process, and highlights how physicians take their colleagues work into account. Recommendations are made to improve patient safety in radiotherapy

  3. Development of inspection safety evaluation technology

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Seok Chul; Yoon, Yeo Chang; Kim, Jong Soo; Lee, Tae Young; Kim, Chang Ryol; Lee, Hyung Sub; Kim, Jong Soo

    1995-12-01

    The purpose of this project is to protection nation inspector`s over exposure from radiation that can be occurred by inspection activity at nuclear facilities and its environment, and to ensure the safety of inspection activity at the nuclear facilities. To effectively carry out the domestic inspection task to be enforced from 1996, the evaluation for special radiation exposure rate of nuclear facilities, air and surface contamination level, and measurement and monitoring of water contamination level were made to determine whether these measured values exceeded permissible limitations, and to protect the inspector`s over exposure from radiation at domestic nuclear facilities. Management of inspector`s exposure was carried out under assistance of the Department of Health Physics. Performance tests of two gamma detectors, one neutron detector, alpha and beta detector, and gamma spectroscopy analyzer were carried out to control dose on extremity, the characteristic test for extremity dosimeter was carried out and the theoretical calculation of gamma dose conversion factors based on ANSI N13.32 standard was performed. Under the 93+2 program, IAEA began to recognize the necessity of environmental observation technology development of air-borne particulates travelled from long distance location. Associated with the necessity of this technology development, a proposal of international joint research for development of the special radiation measurement and analysis has been prepared. (author). 21 tabs., 24 figs., 20 refs.

  4. History of aviation safety; the satisfying sighs of relief due to developments in Aviation safety

    NARCIS (Netherlands)

    Stoop, J.A.A.M.

    2014-01-01

    ”Aviation safety is an Integral part of my career. Being part of TU Delft’s impressive record of research on Aviation safety, my career has been with a sense of purpose and a responsibility to equip students to deal with the status quo challenges on Aviation safety, developments, Investigations and

  5. The Development of child road safety competence : the new approach tо road safety education

    OpenAIRE

    Vilkonis, Rytis

    2005-01-01

    The education and information are the strategies of the Road safety. However, some of the documents and scientific findings revealed the chaotic, desultory and theoretically groundless Road safety education and it can be stated that Road safety education system in Lithuania is still being established. The shortage of the theoretical and empirical base of Road safety education is slowing down the process of the system development. Aim of the research is to disclose the assumptions for developm...

  6. Developing a generic environmental safety case

    International Nuclear Information System (INIS)

    Bailey, Lucy

    2014-01-01

    The Nuclear Decommissioning Authority (NDA) has been charged with implementing the United Kingdom government's policy for the long-term management of higher activity radioactive waste by planning, building and operating a geological disposal facility (GDF). Within the NDA, we - the Radioactive Waste Management Directorate (RWMD) - are tasked with the development of a GDF. The UK government has also decided that a process of voluntarism and partnership will be followed to identify a suitable site for the GDF. To date there is no volunteer community and the site selection process to find a volunteer host community is under review. RWMD has an ongoing role to provide advice to UK radioactive waste producers on the conditioning and packaging of wastes and to undertake disposability assessments of waste packaging proposals to determine their suitability for eventual disposal in a GDF. We also need to demonstrate our confidence that a GDF would be safe. Therefore RWMD has published a generic Environmental Safety Case (ESC) (NDA, 2010) to demonstrate that we are confident that a GDF could be developed to meet the guidelines set down by the environmental regulators (EA/NIEA, 2009) in a range of geological settings. The ESC includes reference case calculations that are used as a benchmark for disposability assessments. (author)

  7. Development of a highway safety fundamental course.

    Science.gov (United States)

    2015-05-01

    Although the need for road safety education was first recognized in the 1960s, it has become an increasingly urgent issue : in recent years. To fulfill the hefty goal set up by the AASHTO Highway Safety Strategy and by state DOTS, it is critical : to...

  8. Health and safety at DNE [Dounreay Nuclear Power Development Establishment

    International Nuclear Information System (INIS)

    Walford, J.G.; Tyler, G.R.

    1988-11-01

    This report reviews health and safety experience at the UKAEA's Dounreay Nuclear Power Development Establishment for 1986 and gives relevant data in the fields of health physics and general safety. It includes sections on: organization, policy and training; monitoring of the working environment; personnel monitoring; protection of the public; radiological incidents; and non-radiological health and safety. (author)

  9. Development of web-based safety review advisory system

    International Nuclear Information System (INIS)

    Kim, M. W.; Lee, H. C.; Park, S. O.; Lee, K. H.; Hur, K. Y.; Lee, S. J.; Choi, S. S.; Kang, C. M.

    2002-01-01

    For the development of an expert system supporting the safety review of nuclear power plants, the application was implemented after gathering necessary theoretical background and practical requirements. The general and the detail functional specifications were established, and they are investigated by KINS (Korea Institute of Nuclear Safety). The Safety Review Advisory System(SRAS), this application on web-server environment was developed according to the above specifications. Reviews can do their safety reviewing regardless of their speciality or reviewing experiences because SRAS is operated by the safety review plans which are converted to standardized format. When the safety reviewing is carried out by using SRAS, the results of safety reviewing are accumulated in the database and may be utilized later usefully, and we can grasp safety reviewing progress. Users of SRAS are categorized into four groups, administrator, project manager, project reviewer and general reviewer. Each user group is delegated appropriate access capability. The function and some screen shots of SRAS are described

  10. Development of safety review advisory system for nuclear power plants

    International Nuclear Information System (INIS)

    Kim, M. W.; Lee, H. C.; Park, S. O.; Park, W. J.; Lee, J. I.; Hur, K. Y.; Choi, S. S.; Lee, S. J.; Kang, C. M.

    2001-01-01

    For the development of an expert system supporting the safety review of nuclear power plants, the application program was implemented after gathering necessary theoretical background and practical requirements. The general and the detail functional specifications were established, and they were investigated by the safety review experts at KINS. Safety Review Advisory System (SRAS), the windows application on client-server environment was developed according to the above specifications. Reviewers can do their safety reviewing regardless of speciality or reviewing experiences because SRAS is operated by the safety review plans which are converted to standardized format. When the safety reviewing is carried out by using SRAS, the results of safety reviewing are accumulated in the database and may be utilized later usefully, and we can grasp safety reviewing progress. Users of SRAS are categorized into three groups, administrator, project manager, and reviewer. Each user group has appropriate access capability. The function and some screen shots of SRAS are described in this paper

  11. Safety analysis of DUPIC fuel development facility

    International Nuclear Information System (INIS)

    Lee, H. H.; Park, J. J.; Shin, J. M.; Yang, M. S.; Baek, S. Y.; Ahn, J. Y.

    2001-01-01

    Various experimental facilities are necessary in order to perform experimental verification for development of DUPIC fuel fabrication technology. In special, since highly radioactive material such as spent PWR fuel is used for this experiment, DUPIC fuel fabrication has to be performed in hot cell by remote handling. Therefore, it should be provided with proper engineering requirement and safety. M6 hot cell of IMEF which is to used for DUPIC fuel fabrication experiment was constructed as an α-γ hot cell for material examination of small amount of high-burnup fuel. The characteristics and amount of spent fuel for DUPIC fuel fabrication experiment will be different from the original design criteria. Therefore, the increased amount of spent fuel and different characteristics of experiment result in not only change of shielding and enviornmental evaluation results but new requirement of nuclear criticality evaluation. Therefore, this study includes evaluation of shielding, environmental effect and nuclear criticality in case that IMEF M6 hot cell is used for DUPIC fuel fabrication

  12. Development of digital safety system logic and control

    International Nuclear Information System (INIS)

    Nishikawa, H.; Sakamoto, H.

    1995-01-01

    Advanced-BWR (ABWR) uses total digital control and instrumentation (C and I) system. In particular, ABWR adopts a newly developed safety system using advanced digital technology. In the presentation the digital safety system design, manufacturing and factory validation test method are shortly overviewed. The digital safety system consists of micro-processor based digital controllers, data and information transmission by optical fibers and human-machine interface using color flat displays. This new developed safety system meet the nuclear safety requirements such as high reliability, independence of divisions, operability and maintainability. (2 refs., 4 figs., 1 tab.)

  13. Developing an integrated dam safety program

    International Nuclear Information System (INIS)

    Nielsen, N. M.; Lampa, J.

    1996-01-01

    An effort has been made to demonstrate that dam safety is an integral part of asset management which, when properly done, ensures that all objectives relating to safety and compliance, profitability, stakeholders' expectations and customer satisfaction, are achieved. The means to achieving this integration of the dam safety program and the level of effort required for each core function have been identified using the risk management approach to pinpoint vulnerabilities, and subsequently to focus priorities. The process is considered appropriate for any combination of numbers, sizes and uses of dams, and is designed to prevent exposure to unacceptable risks. 5 refs., 1 tab

  14. Development and applications of a safety assessment system for promoting safety culture in nuclear power plants

    International Nuclear Information System (INIS)

    Takano, Ken-ichi; Hasegawa, Naoko; Hirose, Ayako; Hayase, Ken-ichi

    2004-01-01

    For past five years, CRIEPI has been continuing efforts to develop and make applications of a 'safety assessment system' which enable to measure the safety level of organization. This report describe about frame of the system, assessment results and its reliability, and relation between labor accident rate in the site and total safety index (TSI), which can be obtained by the principal factors analysis. The safety assessment in this report is based on questionnaire survey of employee. The format and concrete questionnaires were developed using existing literatures including organizational assessment tools. The tailored questionnaire format involved 124 questionnaire items. The assessment results could be considered as a well indicator of the safety level of organization, safety management, and safety awareness of employee. (author)

  15. SAFETY BASIS DESIGN DEVELOPMENT CHALLENGES IMECE2007-42747

    International Nuclear Information System (INIS)

    RYAN GW

    2007-01-01

    'Designing in Safety' is a desired part of the development of any new potentially hazardous system, process, or facility. It is a required part of nuclear safety activities as specified in the U.S. Department of Energy (DOE) Order 420.B, Facility Safety. This order addresses the design of nuclear related facilities developed under federal regulation IOCFR830, Nuclear Safety Management. IOCFR830 requires that safety basis documentation be provided to identify how nuclear safety is being adequately addressed as a condition for system operation (e.g., the safety basis). To support the development of the safety basis, a safety analysis is performed. Although the concept of developing a design that addresses 'Safety is simple, the execution can be complex and challenging. This paper addresses those complexities and challenges for the design activity of a system to treat sludge, a corrosion product of spent nuclear fuel, at DOE's Hanford Site in Washington State. The system being developed is referred to as the Sludge Treatment Project (STP). This paper describes the portion of the safety analysis that addresses the selection of design basis events using the experience gained from the STP and the development of design requirements for safety features associated with those events. Specifically, the paper describes the safety design process and the application of the process for two types of potential design basis accidents associated with the operation of the system, (1) flashing spray leaks and (2) splash and splatter leaks. Also presented are the technical challenges that are being addressed to develop effective safety features to deal with these design basis accidents

  16. SAFETY BASIS DESIGN DEVELOPMENT CHALLENGES IMECE2007-42747

    Energy Technology Data Exchange (ETDEWEB)

    RYAN GW

    2007-09-24

    'Designing in Safety' is a desired part of the development of any new potentially hazardous system, process, or facility. It is a required part of nuclear safety activities as specified in the U.S. Department of Energy (DOE) Order 420.B, Facility Safety. This order addresses the design of nuclear related facilities developed under federal regulation IOCFR830, Nuclear Safety Management. IOCFR830 requires that safety basis documentation be provided to identify how nuclear safety is being adequately addressed as a condition for system operation (e.g., the safety basis). To support the development of the safety basis, a safety analysis is performed. Although the concept of developing a design that addresses 'Safety is simple, the execution can be complex and challenging. This paper addresses those complexities and challenges for the design activity of a system to treat sludge, a corrosion product of spent nuclear fuel, at DOE's Hanford Site in Washington State. The system being developed is referred to as the Sludge Treatment Project (STP). This paper describes the portion of the safety analysis that addresses the selection of design basis events using the experience gained from the STP and the development of design requirements for safety features associated with those events. Specifically, the paper describes the safety design process and the application of the process for two types of potential design basis accidents associated with the operation of the system, (1) flashing spray leaks and (2) splash and splatter leaks. Also presented are the technical challenges that are being addressed to develop effective safety features to deal with these design basis accidents.

  17. The development of international safety standards on geological disposal

    International Nuclear Information System (INIS)

    McCartin, T.

    2005-01-01

    The IAEA is developing a set of safety requirements for geologic disposal to be used by both developers and regulators for planning, designing, operating, and closing a geologic disposal facility. Safety requirements would include quantitative criteria for assessing safety of geologic disposal facilities as well as requirements for development of the facility and the safety strategy including the safety case. Geologic disposal facilities are anticipated to be developed over a period of at least a few decades. Key decisions, e.g., on the disposal concept, siting, design, operational management and closure, are expected to be made in a series of steps. Decisions will be made based on the information available at each step and the confidence that may be placed in that information. A safety strategy is important for ensuring that at each step during the development of the disposal facility, an adequate understanding of the safety implications of the available options is developed such that the ultimate goal of providing an acceptable level of operational and post closure safety will be met. A safety case for a geologic disposal facility would present all the safety relevant aspects of the site, the facility design and the managerial and regulatory controls. The safety case and its supporting assessments illustrates the level of protection provided and shall give reasonable assurance that safety standards will be met. Overall, the safety case provides confidence in the feasibility of implementing the disposal system as designed, convincing estimates of the performance of the disposal system and a reasonable assurance that safety standards will be met. (author)

  18. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    Marrer, Estelle; Dieterle, Frank

    2010-01-01

    Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

  19. Development of web-based safety review advisory system

    International Nuclear Information System (INIS)

    Kim, M. W.; Hur, K. Y.; Lee, S. J.; Choi, S. J.

    2002-01-01

    For the development of an expert system supporting the safety review of nuclear power plants, the application was implemented after gathering necessary theoretical background and practical requirements. The general and the detail functional specifications were established, and they are investigated by KINS. Safety Review Advisory System (SRAS), this application on web-server environment was developed according to the above specifications. Reviews can do their safety reviewing regardless of their speciality or reviewing experiences because SRAS is operated by the safety review plans which are converted to standardized format. When the safety reviewing is carried out by using SRAS, the results of safety reviewing are accumulated in the database and may be utilized later usefully, and we can grasp safety reviewing progress. Users of SRAS are categorized into four groups, administrator, project manager, project reviewer and general reviewer. Each user group is delegated appropriate access capability. The function and some screen shots of SRAS are described

  20. Safety Case Development as an Information Modelling Problem

    Science.gov (United States)

    Lewis, Robert

    This paper considers the benefits from applying information modelling as the basis for creating an electronically-based safety case. It highlights the current difficulties of developing and managing large document-based safety cases for complex systems such as those found in Air Traffic Control systems. After a review of current tools and related literature on this subject, the paper proceeds to examine the many relationships between entities that can exist within a large safety case. The paper considers the benefits to both safety case writers and readers from the future development of an ideal safety case tool that is able to exploit these information models. The paper also introduces the idea that the safety case has formal relationships between entities that directly support the safety case argument using a methodology such as GSN, and informal relationships that provide links to direct and backing evidence and to supporting information.

  1. Ensuring ecology safety, furthering the development of nuclear energy

    International Nuclear Information System (INIS)

    Shang Zhaorong; Chen Xiaoqiu; Tang Senming

    2008-01-01

    Ecology safety is as important as political safety, national defense safety, economy safety, food safety, etc. The nuclear power development is an important step for the national energy structure optimization, ecology caring, and implementing sustainable development. The aquatic ecology is important on disposal of low-level liquid waste and cooling water from NPPs and nuclear fuel cycle facilities, and people pay more attention to ecology impact and human threat from the nuclear energy. The author describes relevant ecology problems correlated with nuclear energy such as impact of thermal discharge, ecology sensitive zone, ecology restoration, etc. in order to emphasis that development of nuclear energy should guarantee ecology safety for the sustainable development of nuclear energy. (authors)

  2. Development of safety performance indicators in Japan

    International Nuclear Information System (INIS)

    Ohashi, H.; Tamao, S.; Tanaka, J.; Sawayama, T.

    2001-01-01

    For the purpose of safety regulations of operating nuclear power stations in Japan, the regulatory authorities utilize two types of regulations. One is the direct regulation, such as periodical inspection to inspect the function and performance of equipment important to safety, and the other is the audit type regulation such as preservation inspection to audit the compliance with the safety preservation rules. As performance indicators are expected to be an effective tool to evaluate the activities by audit type regulations, NUPEC is studying a comprehensive set of operational performance indicators to meet the effective evaluation method for the safety preservation activities in the audit type regulations under the frame of current safety regulation system. The study includes the establishment of comprehensive operational performance indicators applicable in Japan, the effective application of performance indicators to the current Japanese regulation, the clarification of the applicable scope of utilization, the possibility of applying the performance indicators. This report describes the present status of our performance indicator studies. After the completion of these studies the regulatory authorities will evaluate if and how the new set of comprehensive performance indicators could be introduced to Japanese regulatory scheme. (author)

  3. ENTREPRENEURSHIP ECONOMIC SAFETY AND DEVELOPMENT OF SECURITY SERVICES

    Directory of Open Access Journals (Sweden)

    G. V. Goudkov

    2011-01-01

    Full Text Available Successful functioning of the industry that provides for safety of organizations and physical entities exercises strategic impacts on development of society and economics of any state including Russia. Economic safety of Russia is directly linked with economic and information safety of itsbusiness structures. Extension of the scope and use of services offered by experienced state and private security enterprises including licensed individuals is one of most important directions of business safety perfection. Further improvement of Russian legislation on non-governmentalsecurity structures and coordination of their activities with those of state law enforcement bodies is obligatory condition of attaining higherpublic and economic safety levels.

  4. Safety Design Approach for the Development of Safety Requirements for Design of Commercial HTGR

    International Nuclear Information System (INIS)

    Ohashi, Hirofumi; Sato, Hiroyuki; Nakagawa, Shigeaki; Tachibana, Yukio; Nishihara, Tetsuo; Yan, Xing; Sakaba, Nariaki; Kunitomi, Kazuhiko

    2014-01-01

    The research committee on “Safety requirements for HTGR design” was established in 2013 under the Atomic Energy Society of Japan to develop the draft safety requirements for the design of commercial High Temperature Gas-cooled Reactors (HTGRs), which incorporate the HTGR safety features demonstrated using the High Temperature Engineering Test Reactor (HTTR), lessons learned from the accident of Fukushima Daiichi Nuclear Power Station and requirements for the integration of the hydrogen production plants. The safety design approach for the commercial HTGRs which is a basement of the safety requirements is determined prior to the development of the safety requirements. The safety design approaches for the commercial HTGRs are to confine the radioactive materials within the coated fuel particles not only during normal operation but also during accident conditions, and the integrity of the coated fuel particles and other requiring physical barriers are protected by the inherent and passive safety features. This paper describes the main topics of the research committee, the safety design approaches and the safety functions of the commercial HTGRs determined in the research committee. (author)

  5. Patient Safety in Pediatrics: a Developing Discipline

    NARCIS (Netherlands)

    C. van der Starre (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ The publication of the breakthrough report “To Err is Human” by the Institute of Medicine was the launch of patient safety initiatives all over the world. In the intensive care unit (ICU) of the Erasmus MC-Sophia Children’s Hospital this resulted in the institution

  6. Assessing progress in the development of safety culture

    International Nuclear Information System (INIS)

    Rotaru, I.; Ghita, S.; Biro, L.

    2002-01-01

    This paper is focussed on the organizational culture and learning processes required for the implementation of all aspects of safety culture. There is no prescriptive formula for improving safety culture. However, some common characteristics and practices are emerging that can be adopted by organizations in order to make progress. The paper refers to some approaches that have been successful in a number of countries. The experience of the international nuclear industry in the development and improvement of safety culture could be extended and found useful in other nuclear activities, irrespective of scale. The examples given of specific practice cover a wide range of activities including analysis of events, the regulatory approach on safety culture, employee participation and safety performance measures. Many of these practices may be relevant to smaller organizations and could contribute to improving safety culture, whatever the size of the organization. The most effective approach is to pursue a range of practices that can be mutually supportive in the development of a progressive safety culture, supported by professional standards, organizational and management commitment. Some guidance is also given on the assessment of safety culture and on the detection of a weakening safety culture. Few suggestions for accelerating the safety culture development and improvement process are also provided. (author)

  7. Development and initial validation of an Aviation Safety Climate Scale.

    Science.gov (United States)

    Evans, Bronwyn; Glendon, A Ian; Creed, Peter A

    2007-01-01

    A need was identified for a consistent set of safety climate factors to provide a basis for aviation industry benchmarking. Six broad safety climate themes were identified from the literature and consultations with industry safety experts. Items representing each of the themes were prepared and administered to 940 Australian commercial pilots. Data from half of the sample (N=468) were used in an exploratory factor analysis that produced a 3-factor model of Management commitment and communication, Safety training and equipment, and Maintenance. A confirmatory factor analysis on the remaining half of the sample showed the 3-factor model to be an adequate fit to the data. The results of this study have produced a scale of safety climate for aviation that is both reliable and valid. This study developed a tool to assess the level of perceived safety climate, specifically of pilots, but may also, with minor modifications, be used to assess other groups' perceptions of safety climate.

  8. Development Trends in Nuclear Technology and Related Safety Aspects

    International Nuclear Information System (INIS)

    Kuczera, B.; Juhn, P.E.; Fukuda, K.

    2002-01-01

    The IAEA Safety Standards Series include, in a hierarchical manner, the categories of Safety Fundamentals, Safety Requirements and Safety Guides, which define the elements necessary to ensure the safety of nuclear installations. In the same way as nuclear technology and scientific knowledge advance continuously, also safety requirements may change with these advances. Therefore, in the framework of the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) one important aspect among others refers to user requirements on the safety of innovative nuclear installations, which may come into operation within the next fifty years. In this respect, the major objectives of the INPRO sub-task 'User Requirements and Nuclear Energy Development Criteria in the Area of Safety' have been: a. to overview existing national and international requirements in the safety area, b. to define high level user requirements in the area of safety of innovative nuclear technologies, c. to compile and to analyze existing innovative reactor and fuel cycle technology enhancement concepts and approaches intended to achieve a high degree of safety, and d. to identify the general areas of safety R and D needs for the establishment of these technologies. During the discussions it became evident that the application of the defence in depth strategy will continue to be the overriding approach for achieving the general safety objective in nuclear power plants and fuel cycle facilities, where the emphasis will be shifted from mitigation of accident consequences more towards prevention of accidents. In this context, four high level user requirements have been formulated for the safety of innovative nuclear reactors and fuel cycles. On this basis safety strategies for innovative reactor designs are highlighted in each of the five levels of defence in depth and specific requirements are discussed for the individual components of the fuel cycle. (authors)

  9. Development of safety analysis technology for integral reactor; evaluation on safety concerns of integral reactor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Chul; Kim, Woong Sik; Lee, J. H. [Korea Institute of Nuclear Safety, Taejeon (Korea)

    2002-03-01

    The Nuclear Desalination Plant (NDP) is being developed to produce electricity and fresh water, and is expected to locate near population zone. In the aspect of safety, it is required to protect the public and environment from the possible releases of fission products and to prevent the fresh water from the contamination of radioactivity. Thus, in this study, the safety characteristics of the integral reactor adopting passive and inherent safety features significantly different from existing nuclear power plants were investigated. Also, safety requirements applicable to the NDP were analyzed based on the regulatory requirements for current light water reactor and advanced reactor designs, and user requirements for small-medium size reactors. Based on these analyses, some safety concerns to be considered in the design stage have been identified and discussed. They include the use of proven technology for new safety features, systematic event classification and selection, strengthening containment function, and the safety impacts on desalination-related systems. The study presents the general safety requirements applicable to licensing of an integral reactor and suggests additional regulatory requirements, which need to be developed, based on the direction to resolution of the safety concerns. The efforts to identify and technically resolve the safety concerns in the design stage will provide the early confidence of SMART safety and the technical basis to evaluate the safety to designers and reviewers in the future. Suggestion on the development of additional regulatory requirements will contribute for the regulator to taking actions for licensing of an integral reactor. 66 refs., 5 figs., 24 tabs. (Author)

  10. Development of Safety Review Guidance for Research and Training Reactors

    International Nuclear Information System (INIS)

    Oh, Kju-Myeng; Shin, Dae-Soo; Ahn, Sang-Kyu; Lee, Hoon-Joo

    2007-01-01

    The KINS already issued the safety review guidance for pressurized LWRs. But the safety review guidance for research and training reactors were not developed. So, the technical standard including safety review guidance for domestic research and training reactors has been applied mutates mutandis to those of nuclear power plants. It is often difficult for the staff to effectively perform the safety review of applications for the permit by the licensee, based on peculiar safety review guidance. The NRC and NSC provide the safety review guidance for test and research reactors and European countries refer to IAEA safety requirements and guides. The safety review guide (SRG) of research and training reactors was developed considering descriptions of the NUREG- 1537 Part 2, previous experiences of safety review and domestic regulations for related facilities. This study provided the safety review guidance for research and training reactors and surveyed the difference of major acceptance criteria or characteristics between the SRG of pressurized light water reactor and research and training reactors

  11. Development of an environmental safety case guidance manual

    International Nuclear Information System (INIS)

    Wellstead, Matthew John

    2014-01-01

    NDA RWMD is currently considering the scope, purpose and structure of a safety case manual that covers the development of nuclear operational, transport and environmental safety cases for a geological disposal facility in the United Kingdom. This paper considers the Environmental Safety Case (ESC) input into such a manual (herein referred to as the 'ESC Manual'), looking at the drivers and benefits that a guidance manual in this area may provide. (authors)

  12. Development of Safety Kit for Industrial Radiography Application

    International Nuclear Information System (INIS)

    Mohd Noorul Ikhsan Ahmad; Amry Amin Abas

    2011-01-01

    A safety kit for industrial radiography has been developed. The safety kit that consist of a set of technical rod and various size of base that can be used in radiograph of pipe with diameter between half and one and half inch with utilization of collimator. With the kit, radiographers will not having anymore problem to use collimator in their work. The paper discuss about the technical measures of the safety kit and the importance of introducing it to the industry. (author)

  13. Development of Safety Analysis Technology for Integral Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Sim, S. K. [Korea Atomic Energy Research Institute, Taejeon (Korea); Seul, K. W.; Kim, W. S.; Kim, W. K.; Yun, Y. G.; Ahn, H. J.; Lee, J. S.; Sin, A. D. [Korea Institute of Nuclear Safety, Taejeon (Korea)

    2000-03-01

    The Nuclear Desalination Plant(NDP) is being developed to produce electricity and fresh water, and is expected to locate near population zone. In the aspect of safety, it is required to protect the public and environment from the possible releases of fission products and to prevent the fresh water from the contamination of radioactivity. Thus, in a present study, the safety characteristics of the integral reactor adopting passive and inherent safety features significantly different from existing nuclear power plants were investigated based on the design of foreign and domestic integral reactors. Also, safety requirements applicable to the NDP were analyzed based on the regulatory requirements for current and advanced reactor designs, and use requirements for small-medium size reactors. Based on these analyses, some safety concerns to be considered in the design stage have been identified. They includes the use of proven technology for new safety systems, the systematic classification and selection of design basis accidents, and the safety assurance of desalination-related systems. These efforts to identify and resolve the safety concerns in the design stage will provide the early confidence of SMART safety to designers, and the technical basis to evaluate the safety to reviewers in the future. 8 refs., 20 figs., 4 tabs. (Author)

  14. Cyber safety education in developing countries

    CSIR Research Space (South Africa)

    Von Solms, R

    2015-07-01

    Full Text Available . The baseline curriculum was built on a selection of publicly available videos from YouTube.com and ThinkYouKnow.co.uk that can be used in a classroom environment to educate children on various cyber-safety issues. Three "curriculum tables" for age groups 7... and fun to the learners, it was decided that only cartoon videos with an applicable educational message would be used. Thus, the core presentation resource for each lesson was envisaged to be a cartoon video from the online video- sharing website, YouTube...

  15. Development of a British Road Safety Education Support Materials Curriculum.

    Science.gov (United States)

    Bouck, Linda H.

    Road safety education needs to be a vital component in the school curriculum. This paper describes a planned road safety education support materials curriculum developed to aid educators in the Wiltshire County (England) primary schools. Teaching strategies include topic webs, lecture, class discussion, group activities, and investigative learning…

  16. Collaborating with nurse leaders to develop patient safety practices.

    Science.gov (United States)

    Kanerva, Anne; Kivinen, Tuula; Lammintakanen, Johanna

    2017-07-03

    Purpose The organisational level and leadership development are crucial elements in advancing patient safety, because patient safety weaknesses are often caused by system failures. However, little is known about how frontline leader and director teams can be supported to develop patient safety practices. The purpose of this study is to describe the patient safety development process carried out by nursing leaders and directors. The research questions were: how the chosen development areas progressed in six months' time and how nursing leaders view the participatory development process. Design/methodology/approach Participatory action research was used to engage frontline nursing leaders and directors into developing patient safety practices. Semi-structured group interviews ( N = 10) were used in data collection at the end of a six-month action cycle, and data were analysed using content analysis. Findings The participatory development process enhanced collaboration and gave leaders insights into patient safety as a part of the hospital system and their role in advancing it. The chosen development areas advanced to different extents, with the greatest improvements in those areas with simple guidelines to follow and in which the leaders were most participative. The features of high-reliability organisation were moderately identified in the nursing leaders' actions and views. For example, acting as a change agent to implement patient safety practices was challenging. Participatory methods can be used to support leaders into advancing patient safety. However, it is important that the participants are familiar with the method, and there are enough facilitators to steer development processes. Originality/value Research brings more knowledge of how leaders can increase their effectiveness in advancing patient safety and promoting high-reliability organisation features in the healthcare organisation.

  17. Development of a Safety Management Web Tool for Horse Stables.

    Science.gov (United States)

    Leppälä, Jarkko; Kolstrup, Christina Lunner; Pinzke, Stefan; Rautiainen, Risto; Saastamoinen, Markku; Särkijärvi, Susanna

    2015-11-12

    Managing a horse stable involves risks, which can have serious consequences for the stable, employees, clients, visitors and horses. Existing industrial or farm production risk management tools are not directly applicable to horse stables and they need to be adapted for use by managers of different types of stables. As a part of the InnoEquine project, an innovative web tool, InnoHorse, was developed to support horse stable managers in business, safety, pasture and manure management. A literature review, empirical horse stable case studies, expert panel workshops and stakeholder interviews were carried out to support the design. The InnoHorse web tool includes a safety section containing a horse stable safety map, stable safety checklists, and examples of good practices in stable safety, horse handling and rescue planning. This new horse stable safety management tool can also help in organizing work processes in horse stables in general.

  18. Development and implementation of setpoint tolerances for special safety systems

    International Nuclear Information System (INIS)

    Oliva, A.F.; Balog, G.; Parkinson, D.G.; Archinoff, G.H.

    1991-01-01

    The establishment of tolerances and impairment limits for special safety system setpoints is part of the process whereby the plant operator demonstrates to the regulatory authority that the plant operates safely and within the defined plant licensing envelope. The licensing envelope represents the set of limits and plant operating state and for which acceptably safe plant operation has been demonstrated by the safety analysis. By definition, operation beyond this envelope contributes to overall safety system unavailability. Definition of the licensing envelope is provided in a wide range of documents including the plant operating licence, the safety report, and the plant operating policies and principles documents. As part of the safety analysis, limits are derived for each special safety system initiating parameter such that the relevant safety design objectives are achieved for all design basis events. If initiation on a given parameter occurs at a level beyond its limit, there is a potential reduction in safety system effectiveness relative to the performance credited in the plant safety analysis. These safety system parameter limits, when corrected for random and systematic instrument errors and other errors inherent in the process of periodic testing or calibration, are then used to derive parameter impairment levels and setpoint tolerances. This paper describes the methodology that has evolved at Ontario Hydro for developing and implementing tolerances for special safety system parameters (i.e., the shutdown systems, emergency coolant injection system and containment system). Tolerances for special safety system initiation setpoints are addressed specifically, although many of the considerations discussed here will apply to performance limits for other safety system components. The first part of the paper deals with the approach that has been adopted for defining and establishing setpoint limits and tolerances. The remainder of the paper addresses operational

  19. Reactor safety computer code development at INEL

    International Nuclear Information System (INIS)

    Johnsen, G.W.

    1985-01-01

    This report provides a brief overview of the computer code development programs being conducted at EG and G Idaho, Inc. on behalf of US Nuclear Regulatory Commission and the Department of Energy, Idaho Operations Office. Included are descriptions of the codes being developed, their development status as of the date of this report, and resident code development expertise

  20. Development of a Nevada Statewide Database for Safety Analyst Software

    Science.gov (United States)

    2017-02-02

    Safety Analyst is a software package developed by the Federal Highway Administration (FHWA) and twenty-seven participating state and local agencies including the Nevada Department of Transportation (NDOT). The software package implemented many of the...

  1. Challenges on innovations of newly-developed safety analysis codes

    International Nuclear Information System (INIS)

    Yang, Yanhua; Zhang, Hao

    2016-01-01

    With the development of safety analysis method, the safety analysis codes meet more challenges. Three challenges are presented in this paper, which are mathematic model, code design and user interface. Combined with the self-reliance safety analysis code named COSINE, the ways of meeting these requirements are suggested, that is to develop multi-phases, multi-fields and multi-dimension models, to adopt object-oriented code design ideal and to improve the way of modeling, calculation control and data post-processing in the user interface.

  2. SCALE Graphical Developments for Improved Criticality Safety Analyses

    International Nuclear Information System (INIS)

    Barnett, D.L.; Bowman, S.M.; Horwedel, J.E.; Petrie, L.M.

    1999-01-01

    New computer graphic developments at Oak Ridge National Ridge National Laboratory (ORNL) are being used to provide visualization of criticality safety models and calculational results as well as tools for criticality safety analysis input preparation. The purpose of this paper is to present the status of current development efforts to continue to enhance the SCALE (Standardized Computer Analyses for Licensing Evaluations) computer software system. Applications for criticality safety analysis in the areas of 3-D model visualization, input preparation and execution via a graphical user interface (GUI), and two-dimensional (2-D) plotting of results are discussed

  3. Challenges on innovations of newly-developed safety analysis codes

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yanhua [Shanghai Jiao Tong Univ. (China). School of Nuclear Science and Engineering; Zhang, Hao [State Nuclear Power Software Development Center, Beijing (China). Beijing Future Science and Technology City

    2016-05-15

    With the development of safety analysis method, the safety analysis codes meet more challenges. Three challenges are presented in this paper, which are mathematic model, code design and user interface. Combined with the self-reliance safety analysis code named COSINE, the ways of meeting these requirements are suggested, that is to develop multi-phases, multi-fields and multi-dimension models, to adopt object-oriented code design ideal and to improve the way of modeling, calculation control and data post-processing in the user interface.

  4. Suggestions on the Development of Safety Culture Assessment Method

    International Nuclear Information System (INIS)

    Choi, Young Sung; Choi, Kwang Sik; Kim, Woong Sik

    2006-01-01

    Several efforts have been made to assess safety culture of organization that operates nuclear power plants in Korea. The MOST and KINS played a major role to develop assessment methods and KHNP applied them to its NPPs. This paper explains the two methods developed by KINS briefly and presents the insights obtained from the two different applications. It concludes with some suggestions for safety culture assessment based on the insights

  5. Development of Safety Review Guide for the Periodic Safety Review of Reactor Vessel Internals

    International Nuclear Information System (INIS)

    Park, Jeongsoon; Ko, Hanok; Kim, Seonjae; Jhung, Myungjo

    2013-01-01

    Aging management of the reactor vessel internals (RVIs) is one of the important issues for long-term operation of nuclear power plants (NPPs). Safety review on the assessment and management of the RVI aging is conducted through the process of a periodic safety review (PSR). The regulatory body should check that reactor facilities sustain safety functions in light of degradation due to aging and that the operator of a nuclear power reactor establishes and implements management program to deal with degradation due to aging in order to guarantee the safety functions and the safety margin as a result of PSR. KINS(Korea Institute of Nuclear Safety) has utilized safety review guides (SRG) which provide guidance to KINS staffs in performing safety reviews in order to assure the quality and uniformity of staff safety reviews. The KINS SRGs for the continued operation of pressurized water reactors (PWRs) published in 2006 contain areas of review regarding aging management of RVIs in chapter 2 (III.2.15, Appendix 2.0.1). However unlike the SRGs for the continued operation, KINS has not officially published the SRGs for the PSR of PWRs, but published them as a form of the research report. In addition to that, the report provides almost same review procedures for aging assessment and management of RVIs with the ones provided in the SRGs for the continued operation, it cannot provide review guidance specific to PSRs. Therefore, a PSR safety review guide should be developed for RVIs in PWRs. In this study, a draft PSR safety review guide for reactor vessel internals in PWRs is developed and provided. In this paper, a draft PSR safety review guide for reactor vessel internals (PSR SRG-RVIs) in PWRs is introduced and main contents of the draft are provided. However, since the PSR safety review guides for areas other than RVIs in the pressurized water reactors (PWRs) are expected to be developed in the near future, the draft PSR SRG-RVIs should be revisited to be compatible with

  6. Nuclear safety culture in Finland and Sweden - Developments and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Reiman, T.; Pietikaeinen, E. (Technical Research Centre of Finland, VTT (Finland)); Kahlbom, U. (RiskPilot AB (Sweden)); Rollenhagen, C. (Royal Institute of Technology (KTH) (Sweden))

    2011-02-15

    The project aimed at studying the concept of nuclear safety culture and the Nordic nuclear branch safety culture. The project also aimed at looking how the power companies and the regulators view the current responsibilities and role of subcontractors in the Nordic nuclear safety culture as well as to inspect the special demands for safety culture in subcontracting chains. Interview data was collected in Sweden (n = 14) and Finland (n = 16) during 2009. Interviewees represented the major actors in the nuclear field (regulators, power companies, expert organizations, waste management organizations). Results gave insight into the nature and evaluation of safety culture in the nuclear industry. Results illustrated that there is a wide variety of views on matters that are considered important for nuclear safety within the Nordic nuclear community. However, the interviewees considered quite uniformly such psychological states as motivation, mindfulness, sense of control, understanding of hazards and sense of responsibility as important for nuclear safety. Results also gave insight into the characteristics of Nordic nuclear culture. Various differences in safety cultures in Finland and Sweden were uncovered. In addition to the differences, historical reasons for the development of the nuclear safety cultures in Finland and Sweden were pointed out. Finally, results gave implications that on the one hand subcontractors can bring new ideas and improvements to the plants' practices, but on the other hand the assurance of necessary safety attitudes and competence of the subcontracting companies and their employees is considered as a challenge. The report concludes that a good safety culture requires a deep and wide understanding of nuclear safety including the various accident mechanisms of the power plants as well as a willingness to continuously develop one's competence and understanding. An effective and resilient nuclear safety culture has to foster a constant

  7. Nuclear safety culture in Finland and Sweden - Developments and challenges

    International Nuclear Information System (INIS)

    Reiman, T.; Pietikaeinen, E.; Kahlbom, U.; Rollenhagen, C.

    2011-02-01

    The project aimed at studying the concept of nuclear safety culture and the Nordic nuclear branch safety culture. The project also aimed at looking how the power companies and the regulators view the current responsibilities and role of subcontractors in the Nordic nuclear safety culture as well as to inspect the special demands for safety culture in subcontracting chains. Interview data was collected in Sweden (n = 14) and Finland (n = 16) during 2009. Interviewees represented the major actors in the nuclear field (regulators, power companies, expert organizations, waste management organizations). Results gave insight into the nature and evaluation of safety culture in the nuclear industry. Results illustrated that there is a wide variety of views on matters that are considered important for nuclear safety within the Nordic nuclear community. However, the interviewees considered quite uniformly such psychological states as motivation, mindfulness, sense of control, understanding of hazards and sense of responsibility as important for nuclear safety. Results also gave insight into the characteristics of Nordic nuclear culture. Various differences in safety cultures in Finland and Sweden were uncovered. In addition to the differences, historical reasons for the development of the nuclear safety cultures in Finland and Sweden were pointed out. Finally, results gave implications that on the one hand subcontractors can bring new ideas and improvements to the plants' practices, but on the other hand the assurance of necessary safety attitudes and competence of the subcontracting companies and their employees is considered as a challenge. The report concludes that a good safety culture requires a deep and wide understanding of nuclear safety including the various accident mechanisms of the power plants as well as a willingness to continuously develop one's competence and understanding. An effective and resilient nuclear safety culture has to foster a constant sense of

  8. The development of integrated safety assessment technology

    International Nuclear Information System (INIS)

    Yoo, Keon Joong; Park, Chang Kyu; Kim, Tae Un; Han, Sang Hoon; Yang, Joon Eon; Lim, Tae Jin; Han, Jae Joo; Je, Moo Seong; An, Kwang Il; Kim, Shi Dal; Jeong, Jong Tae; Jeong, Kwang Seop; Jin, Yeong Ho; Kim, Dong Ha; Kim, Kil Yoo; Cho, Yeong Kyoon; Jeong, Won Dae; Jang, Seung Cheol; Choi, Yeong; Park, Soo Yong; Seong, Tae Yong; Song, Yong Man; Kang, Dae Il; Park, Jin Hee; Jang, Seon Joo; Hwang, Mi Jeong; Choi, Seon Yeong

    1993-05-01

    For the purpose of developing the integrated PSA methodology and computer codes, Level-1 and Level-2 PSA methodology and tools were reviewed and improved. The Level-1 PSA computer code package KIRAP was improved and released by the name of KIRAP Release 2.0 Several Human reliability analysis and common cause failure analysis methods was reviewed and compared. For the development of Level-2 PSA computer code, several level-1 and Level-2 interface methods and containment event tree development methods were reviewed and compared. And the new technology such as artificial intelligence was reviewed if the technology can be applied to the development of PSA methodology.(Author)

  9. Development of ABWR-2 and its safety design

    International Nuclear Information System (INIS)

    Takafumi, Anegawa; Kenji, Tateiwa

    2002-01-01

    This paper reports the current status of development project on ABWR-II, a next generation reactor design based on ABWR, and its safety design. This project was initiated over a decade ago and has completed three phases to date. In Phase I (1991-92), basic design requirements were discussed and several plant concepts were studied. In Phase II (1993-95), key design features were selected in order to establish a reference reactor concept. In Phase III (1996-2000), based on the reference reactor concept, modifications and improvements were made to fulfill the design requirements. By adopting large electric output (1 700 MW), large fuel bundle, modified ECCS, and passive heat removal systems, among other design features, we achieved a design concept capable of increasing both economic competitiveness and safety performance. Main focus of this paper will be on the safety design, safety performance, and further research needs related to safety. (authors)

  10. Generic Safety Requirements for Developing Safe Insulin Pump Software

    Science.gov (United States)

    Zhang, Yi; Jetley, Raoul; Jones, Paul L; Ray, Arnab

    2011-01-01

    Background The authors previously introduced a highly abstract generic insulin infusion pump (GIIP) model that identified common features and hazards shared by most insulin pumps on the market. The aim of this article is to extend our previous work on the GIIP model by articulating safety requirements that address the identified GIIP hazards. These safety requirements can be validated by manufacturers, and may ultimately serve as a safety reference for insulin pump software. Together, these two publications can serve as a basis for discussing insulin pump safety in the diabetes community. Methods In our previous work, we established a generic insulin pump architecture that abstracts functions common to many insulin pumps currently on the market and near-future pump designs. We then carried out a preliminary hazard analysis based on this architecture that included consultations with many domain experts. Further consultation with domain experts resulted in the safety requirements used in the modeling work presented in this article. Results Generic safety requirements for the GIIP model are presented, as appropriate, in parameterized format to accommodate clinical practices or specific insulin pump criteria important to safe device performance. Conclusions We believe that there is considerable value in having the diabetes, academic, and manufacturing communities consider and discuss these generic safety requirements. We hope that the communities will extend and revise them, make them more representative and comprehensive, experiment with them, and use them as a means for assessing the safety of insulin pump software designs. One potential use of these requirements is to integrate them into model-based engineering (MBE) software development methods. We believe, based on our experiences, that implementing safety requirements using MBE methods holds promise in reducing design/implementation flaws in insulin pump development and evolutionary processes, therefore improving

  11. Development of Safety Enhancement Technology Containment Building

    Energy Technology Data Exchange (ETDEWEB)

    Woo, S.K.; Song, Y.C. [Korea Electric Power Research Institute, Taejon (Korea)

    2002-07-01

    This study is to develop the nondestructive testing method for the detection of internal defects and thickness of concrete using IE(Impact Echo)-SASW(Spectral Analysis of Surface Wave). (author). 20 refs., 24 figs., 8 tabs.

  12. Development and application of digital safety system in NPPs

    International Nuclear Information System (INIS)

    Kwon, Keechoon; Kim, Changhwoi; Lee, Dongyoung

    2012-01-01

    This paper describes the development of digital safety system in NPPs based on safety- grade programmable logic controller (PLC) platform and its application to real NPP construction. The digital safety system consists of a reactor protection system and an engineered safety feature-component control system. The safety-grade PLC platform was developed so that it meets the requirements of the regulation. The PLC consists of various modules such as a power module, a processor module, communication modules, digital input/output modules, analog input/output modules, a LOCA bus extension module, and a high-speed pulse counter module. The reactor protection system is designed with a redundant 4-channel architecture, and every channel is implemented with the same architecture. A single channel consists of a redundant bi-stable processor, a redundant coincidence processor, an automatic test and interface processor, and a cabinet operator module. The engineered safety feature-component control system is designed with four redundant divisions, and implemented with the PLC platform. The principal components of an individual division are fault tolerant group controllers, loop controllers, a test and interface processor, a cabinet operator module and a control channel gateway. The topical report is submitted to the regulatory body, and got safety evaluation report from the regulatory body. Also, the developed system is tested in the integrated performance validation facility. It is decided that the digital safety system applied to Shin-Uljin unit 1 and 2 after a topical report approval and validation test. Design changes occur in the digital safety system that is applied to an actual nuclear power plant construction, and the PLC has also been upgraded

  13. Development and application of digital safety system in NPPs

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Keechoon; Kim, Changhwoi; Lee, Dongyoung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-03-15

    This paper describes the development of digital safety system in NPPs based on safety- grade programmable logic controller (PLC) platform and its application to real NPP construction. The digital safety system consists of a reactor protection system and an engineered safety feature-component control system. The safety-grade PLC platform was developed so that it meets the requirements of the regulation. The PLC consists of various modules such as a power module, a processor module, communication modules, digital input/output modules, analog input/output modules, a LOCA bus extension module, and a high-speed pulse counter module. The reactor protection system is designed with a redundant 4-channel architecture, and every channel is implemented with the same architecture. A single channel consists of a redundant bi-stable processor, a redundant coincidence processor, an automatic test and interface processor, and a cabinet operator module. The engineered safety feature-component control system is designed with four redundant divisions, and implemented with the PLC platform. The principal components of an individual division are fault tolerant group controllers, loop controllers, a test and interface processor, a cabinet operator module and a control channel gateway. The topical report is submitted to the regulatory body, and got safety evaluation report from the regulatory body. Also, the developed system is tested in the integrated performance validation facility. It is decided that the digital safety system applied to Shin-Uljin unit 1 and 2 after a topical report approval and validation test. Design changes occur in the digital safety system that is applied to an actual nuclear power plant construction, and the PLC has also been upgraded.

  14. Initial development of a practical safety audit tool to assess fleet safety management practices.

    Science.gov (United States)

    Mitchell, Rebecca; Friswell, Rena; Mooren, Lori

    2012-07-01

    Work-related vehicle crashes are a common cause of occupational injury. Yet, there are few studies that investigate management practices used for light vehicle fleets (i.e. vehicles less than 4.5 tonnes). One of the impediments to obtaining and sharing information on effective fleet safety management is the lack of an evidence-based, standardised measurement tool. This article describes the initial development of an audit tool to assess fleet safety management practices in light vehicle fleets. The audit tool was developed by triangulating information from a review of the literature on fleet safety management practices and from semi-structured interviews with 15 fleet managers and 21 fleet drivers. A preliminary useability assessment was conducted with 5 organisations. The audit tool assesses the management of fleet safety against five core categories: (1) management, systems and processes; (2) monitoring and assessment; (3) employee recruitment, training and education; (4) vehicle technology, selection and maintenance; and (5) vehicle journeys. Each of these core categories has between 1 and 3 sub-categories. Organisations are rated at one of 4 levels on each sub-category. The fleet safety management audit tool is designed to identify the extent to which fleet safety is managed in an organisation against best practice. It is intended that the audit tool be used to conduct audits within an organisation to provide an indicator of progress in managing fleet safety and to consistently benchmark performance against other organisations. Application of the tool by fleet safety researchers is now needed to inform its further development and refinement and to permit psychometric evaluation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Preliminary Study on the Development of Quantitative Safety Culture Index

    International Nuclear Information System (INIS)

    Lee, Young Eal; Kim, Hun Sil; Ahn, Nam Sung

    2005-01-01

    Safety culture is that assembly of characteristics and attitudes in organizations and individuals which establishes that, as an overriding priority, nuclear plant safety issues receive the attention warranted by their significance. Because it needs to be recognized as the most significant consciousness to achieve the nuclear safety performance, Korean government and nuclear power generation company have tried to develop the practical method to improve the safety culture from the long term point view. In this study, based on the site interviews to define the potential issues on organizational behavior for the safe operation and the survey on the level of safety culture of occupied workers are conducted. Survey results are quantified as a few indicators of nuclear safety by the statistical method and it can be simulated by the dynamic modeling as time goes on. Currently index and dynamic modeling are still being developed, however, results can be used to suggest the long term strategy which safety is clearly integrated into all activities in the nuclear organization

  16. Development of the Advanced Nuclear Safety Information Management (ANSIM) System

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jae Min; Ko, Young Cheol; Song, Tai Gil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-05-15

    Korea has become a technically independent nuclear country and has grown into an exporter of nuclear technologies. Thus, nuclear facilities are increasing in significance at KAERI (Korea Atomic Energy Research Institute), and it is time to address the nuclear safety. The importance of nuclear safety cannot be overemphasized. Therefore, a management system is needed urgently to manage the safety of nuclear facilities and to enhance the efficiency of nuclear information. We have established ISP (Information Strategy Planning) for the Integrated Information System of nuclear facility and safety management. The purpose of this paper is to develop a management system for nuclear safety. Therefore, we developed the Advanced Nuclear Safety Information Management system (hereinafter referred to as the 'ANSIM system'). The ANSIM system has been designed and implemented to computerize nuclear safety information for standardization, integration, and sharing in real-time. Figure 1 shows the main home page of the ANSIM system. In this paper, we describe the design requirements, contents, configurations, and utilizations of the ANSIM system

  17. Developing safety culture-rocket science or common sense?

    International Nuclear Information System (INIS)

    Mahn, J.A.

    1998-01-01

    Despite evidence of significant management contributions to the causes of major accidents, recent events at Millstone Nuclear Power Station in the US and Ontario Hydro in Canada might lead one to conclude that the significance of safety culture, and the role of management in developing and maintaining an appropriate safety culture, is either not being understood or not being taken serious as integral to the safe operation of some complex, high-reliability operations. It is the purpose of this paper to address four aspects of management that are particularly important to safety culture, and to illustrate how development of an appropriate safety culture is more a matter of common sense than rocket science

  18. Developing safety culture-rocket science or common sense?

    Energy Technology Data Exchange (ETDEWEB)

    Mahn, J.A.

    1998-08-01

    Despite evidence of significant management contributions to the causes of major accidents, recent events at Millstone Nuclear Power Station in the US and Ontario Hydro in Canada might lead one to conclude that the significance of safety culture, and the role of management in developing and maintaining an appropriate safety culture, is either not being understood or not being taken serious as integral to the safe operation of some complex, high-reliability operations. It is the purpose of this paper to address four aspects of management that are particularly important to safety culture, and to illustrate how development of an appropriate safety culture is more a matter of common sense than rocket science.

  19. Development of IFC based fire safety assesment tools

    DEFF Research Database (Denmark)

    Taciuc, Anca; Karlshøj, Jan; Dederichs, Anne

    2016-01-01

    Due to the impact that the fire safety design has on the building's layout and on other complementary systems, as installations, it is important during the conceptual design stage to evaluate continuously the safety level in the building. In case that the task is carried out too late, additional...... changes need to be implemented, involving supplementary work and costs with negative impact on the client. The aim of this project is to create a set of automatic compliance checking rules for prescriptive design and to develop a web application tool for performance based design that retrieves data from...... Building Information Models (BIM) to evacuate the safety level in the building during the conceptual design stage. The findings show that the developed tools can be useful in AEC industry. Integrating BIM from conceptual design stage for analyzing the fire safety level can ensure precision in further...

  20. Development of a Safety Assessment Information System for the Management of Periodic Safety Assessment Activities

    International Nuclear Information System (INIS)

    Song, Tae Young

    2007-01-01

    At present, the 10-year Periodic Safety Review(PSR) has been performing to confirm all the aspects of safety issues for all the operating plants in compliance with domestic nuclear law of article 23, subarticle 3. For each plant, in addition, Probabilistic Safety Assessment(PSA) and Severe Accident Management Guideline(SAMG) are being implemented and revised periodically to reflect the latest safety level according to principle fulfillment of severe accident policy statement. The assessment reports, as one of outcomes from these activities, are submitted into and reviewed by domestic regulatory body. During reviewing (in-office duty) and licensing (regulatory duty) process, a large number of outcomes of which most are the formal technical reports and licensing materials, are inevitably produced. Moreover, repeated review process over the plants can make them accumulated and produce a variety of documents additionally. This circumstance motivates to develop effective tool or system for the management of these reports and related technical documents for the future use in licensing process and for subsequent plant assessments. This paper presents the development status of Safety Assessment Information System(SAIS) which manages safety-related documents of PSR, PSA and SAMG for practical use for experienced engineers in charge of these areas

  1. Development of a Safety Assessment Information System for the Management of Periodic Safety Assessment Activities

    Energy Technology Data Exchange (ETDEWEB)

    Song, Tae Young [Nuclear Engineering and Technology Institute, Daejeon (Korea, Republic of)

    2007-07-01

    At present, the 10-year Periodic Safety Review(PSR) has been performing to confirm all the aspects of safety issues for all the operating plants in compliance with domestic nuclear law of article 23, subarticle 3. For each plant, in addition, Probabilistic Safety Assessment(PSA) and Severe Accident Management Guideline(SAMG) are being implemented and revised periodically to reflect the latest safety level according to principle fulfillment of severe accident policy statement. The assessment reports, as one of outcomes from these activities, are submitted into and reviewed by domestic regulatory body. During reviewing (in-office duty) and licensing (regulatory duty) process, a large number of outcomes of which most are the formal technical reports and licensing materials, are inevitably produced. Moreover, repeated review process over the plants can make them accumulated and produce a variety of documents additionally. This circumstance motivates to develop effective tool or system for the management of these reports and related technical documents for the future use in licensing process and for subsequent plant assessments. This paper presents the development status of Safety Assessment Information System(SAIS) which manages safety-related documents of PSR, PSA and SAMG for practical use for experienced engineers in charge of these areas.

  2. Research and development program in reactor safety for NUCLEBRAS

    International Nuclear Information System (INIS)

    Pinheiro, R.B.; Resende Lobo, A.A. de; Horta, J.A.L.; Avelar Esteves, F. de; Lepecki, W.P.S.; Mohr, K.; Selvatici, E.

    1984-01-01

    With technical assistance from the IAEA, it was established recently an analytical and experimental Research and Development Program for NUCLEBRAS in the area of reactor safety. The main objectives of this program is to make possible, with low investments, the active participation of NUCLEBRAS in international PWR safety research. The analytical and experimental activities of the program are described with some detail, and the main results achieved up to now are presented. (Author) [pt

  3. Development of the safety PLC for plant protection system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Hwoi; Lee, Dong Young [Korea Atomic Energy Research Institute, Taejeon (Korea, Republic of)

    2005-11-15

    The safety PLC (POSAFE-Q) is developing in the Korea Nuclear Instrumentation and Control System (KNICS) R and D project. The PLC satisfies Safety Class 1E, Quality Class 1, and Seismic Category I. The software such as RTOS and firmware are developed according to safety critical software life cycle. Especially, the formal method is applied to design SRS (Software Requirement Spec.) and SDS (Software Design Specification.) for error-free. The developed software according to software life cycle is verified by independent software V and V team. The overall response time from an input to the outputs shall be 50ms or less. The prototype for the POSAFE-Q was developed and functional testing and equipment qualification tests have been underway.

  4. Automated Systems for Road Safety control in a Developing World ...

    African Journals Online (AJOL)

    An Automated system was finally designed and developed for road safety control. This Automated system is believed to have the capacity to minimize or eliminate the problems identified in this study on traffic control in a developing world. Key words: drivers, traffic situation information, accident causation, FRSC ...

  5. Inspire and develop people, two key competence for safety leadership

    International Nuclear Information System (INIS)

    Gonzalez, F.; Perez, O.; Fernandez, M.; Alvarez, N.; Villadoniga, J. I.

    2014-01-01

    Developing leadership skills in organizations is key to ensuring the sustainability of excellent results in industries with high standards of safety and reliability element. In order to have a model of development of specific leadership for these organizations, Tecnatom in 2011, we initiated an internal project to find and adapt a competency model to these requirements. (Author)

  6. Development of small reactor safety criteria in Canada

    International Nuclear Information System (INIS)

    Ernst, P.C.; French, P.M.; Axford, D.J.; Snell, V.G.

    1990-01-01

    A number of new small reactor designs have been proposed in Canada over the last several years and some have reached the stage where licensing discussions have been initiated with the Atomic Energy Control Board (AECB). An inter-organizational Small Reactor Criteria (SRC) working group was formed in 1988 to propose safety and licensing criteria for these small reactors. Two levels of criteria are proposed. The first level forms a safety philosophy and the second is a set of criteria for specific reactor applications. The safety philosophy consists of three basic safety objectives together with evaluation criteria, and fourteen fundamental principles measured by specific criteria, which must be implemented to meet the safety objectives. Two of the fourteen principles are prime: defence in depth, and safety culture; the other twelve principles can be seen as deriving from them. A benefit of this approach is that the concepts of defence in depth and safety culture become well-defined. The objectives and principles are presented in the paper and their criteria are summarized. The second level of criteria, under development, will form a safety application set and will provide small reactor criteria in a number of general areas, such as regulatory process and safety assessment, as well as for specific reactor life-cycle activities, from siting through to decommissioning. The criteria are largely deterministic. However, the frequencies and consequences of postulated accidents are assessed against numerical criteria to assist in judging the acceptability of plant design, operation, and proposed siting. All criteria proposed are designed to be testable in some evidentiary fashion, readily enabling an assessment of compliance for a given proposal

  7. Development of safety analysis technology for integral reactor

    International Nuclear Information System (INIS)

    Kim, Hee Cheol; Kim, K. K.; Kim, S. H.

    2002-04-01

    The state-of-the-arts for the integral reactor was performed to investigate the safety features. The safety and performance of SMART were assessed using the technologies developed during the study. For this purpose, the computer code system and the analysis methodology were developed and the safety and performance analyses on SMART basic design were carried out for the design basis event and accident. The experimental facilities were designed for the core flow distribution test and the self-pressurizing pressurizer performance test. The tests on the 2-phase critical flow with non-condensable gas were completed and the results were used to assess the critical flow model. Probabilistic Safety Assessment(PSA) was carried out to evaluate the safety level and to optimize the design by identifying and remedying any weakness in the design. A joint study with KINS was carried out to promote licensing environment. The generic safety issues of integral reactors were identified and the solutions were formulated. The economic evaluation of the SMART desalination plant and the activities related to the process control were carried out in the scope of the study

  8. Development and improvement of safety analysis code for geological disposal

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    In order to confirm the long-term safety concerning geological disposal, probabilistic safety assessment code and other analysis codes, which can evaluate possibility of each event and influence on engineered barrier and natural barrier by the event, were introduced. We confirmed basic functions of those codes and studied the relation between those functions and FEP/PID which should be taken into consideration in safety assessment. We are planning to develop 'Nuclide Migration Assessment System' for the purpose of realizing improvement in efficiency of assessment work, human error prevention for analysis, and quality assurance of the analysis environment and analysis work for safety assessment by using it. As the first step, we defined the system requirements and decided the system composition and functions which should be mounted in them based on those requirements. (author)

  9. Technology and Tool Development to Support Safety and Mission Assurance

    Science.gov (United States)

    Denney, Ewen; Pai, Ganesh

    2017-01-01

    The Assurance Case approach is being adopted in a number of safety-mission-critical application domains in the U.S., e.g., medical devices, defense aviation, automotive systems, and, lately, civil aviation. This paradigm refocuses traditional, process-based approaches to assurance on demonstrating explicitly stated assurance goals, emphasizing the use of structured rationale, and concrete product-based evidence as the means for providing justified confidence that systems and software are fit for purpose in safely achieving mission objectives. NASA has also been embracing assurance cases through the concepts of Risk Informed Safety Cases (RISCs), as documented in the NASA System Safety Handbook, and Objective Hierarchies (OHs) as put forth by the Agency's Office of Safety and Mission Assurance (OSMA). This talk will give an overview of the work being performed by the SGT team located at NASA Ames Research Center, in developing technologies and tools to engineer and apply assurance cases in customer projects pertaining to aviation safety. We elaborate how our Assurance Case Automation Toolset (AdvoCATE) has not only extended the state-of-the-art in assurance case research, but also demonstrated its practical utility. We have successfully developed safety assurance cases for a number of Unmanned Aircraft Systems (UAS) operations, which underwent, and passed, scrutiny both by the aviation regulator, i.e., the FAA, as well as the applicable NASA boards for airworthiness and flight safety, flight readiness, and mission readiness. We discuss our efforts in expanding AdvoCATE capabilities to support RISCs and OHs under a project recently funded by OSMA under its Software Assurance Research Program. Finally, we speculate on the applicability of our innovations beyond aviation safety to such endeavors as robotic, and human spaceflight.

  10. Development and validation of a remote home safety protocol.

    Science.gov (United States)

    Romero, Sergio; Lee, Mi Jung; Simic, Ivana; Levy, Charles; Sanford, Jon

    2018-02-01

    Environmental assessments and subsequent modifications conducted by healthcare professionals can enhance home safety and promote independent living. However, travel time, expense and the availability of qualified professionals can limit the broad application of this intervention. Remote technology has the potential to increase access to home safety evaluations. This study describes the development and validation of a remote home safety protocol that can be used by a caregiver of an elderly person to video-record their home environment for later viewing and evaluation by a trained professional. The protocol was developed based on literature reviews and evaluations from clinical and content experts. Cognitive interviews were conducted with a group of six caregivers to validate the protocol. The final protocol included step-by-step directions to record indoor and outdoor areas of the home. The validation process resulted in modifications related to safety, clarity of the protocol, readability, visual appearance, technical descriptions and usability. Our final protocol includes detailed instructions that a caregiver should be able to follow to record a home environment for subsequent evaluation by a home safety professional. Implications for Rehabilitation The results of this study have several implications for rehabilitation practice The remote home safety evaluation protocol can potentially improve access to rehabilitation services for clients in remote areas and prevent unnecessary delays for needed care. Using our protocol, a patient's caregiver can partner with therapists to quickly and efficiently evaluate a patient's home before they are released from the hospital. Caregiver narration, which reflects a caregiver's own perspective, is critical to evaluating home safety. In-home safety evaluations, currently not available to all who need them due to access barriers, can enhance a patient's independence and provide a safer home environment.

  11. 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)

  12. Development and use of safety indicators at STUK

    International Nuclear Information System (INIS)

    Tiipana, P.

    2001-01-01

    This paper gives an outline of the development and use of STUK's indicator system at the department of Nuclear Reactor Regulation (YTO) in the Radiation and Nuclear Safety Authority, STUK. Indicators used at YTO are measures related to the safety of nuclear installations and regulatory activities. Indicators are numbers, ratios, percentages and amounts of interested matters that are for suitable for regulatory purposes, that is assessment and trending of the safety of nuclear installations and regulatory activities. STUK's indicator system is divided into two main areas: safety of nuclear facilities and regulatory activities. Safety of nuclear facilities is divided into 3 areas based on the concept of defence in de safety and quality culture, operational events and physical barriers. Regulatory activities are divided into 3 areas: working processes, resource management and regeneration and ability to work. These areas are measured using several indicators. At the moment some of indicators are included in YTO's management system to measure whether or not internally set goals are achieved. (author)

  13. MORT: a safety management program developed for ERDA

    International Nuclear Information System (INIS)

    1977-03-01

    ERDA's System Safety Development Center (SSDC) is located at the Idaho National Engineering Laboratory under the EG and G Idaho, Inc., contract administered by the Idaho Operations Office. The SSDC performs a variety of tasks for ERDA's Division of Safety, Standards, and Compliance, for the purpose of improvement and application of safety program elements. Primary among these tasks are development and demonstration of new methodologies, training, consultation, and technical writing. This information package (ERDA 77-38) is an example of the later task, aimed at communicating to a general audience the nature and purpose of major features of the Management Oversight and Risk Tree (MORT) program. The SSDC also originates a guideline series of monographs (the ERDA 76-45 series) for individuals who desire more specific explanations of the MORT program

  14. Review of TSOs technical needs in safety research and development

    International Nuclear Information System (INIS)

    Rintamaa, R.; Bruna, G.

    2012-01-01

    ETSON is the network of European Technical Safety Organizations. The ETSON members have elaborated together a position paper which identifies and ranks the main research and development fields of endeavor in a short, mid and long term perspective. The main research areas and major needs are grouped in 7 areas: 1) safety assessment methods, 2) multi-physics safety approach (several disciplines, macroscopic and microscopic level), 3) Ageing of materials, 4) fuel behaviour, 5) human and organisational factors, 6) instrumentation and control, 7) Severe accidents: phenomenology and methodology, and severe accidents: crisis preparedness and major needs. ETSON has coordinated the activities with other European platforms and has widely contributed to the NUGENIA (Nuclear Generation 2 and 3 Association) topic research and development areas. The next step will be a prioritization of these needs

  15. Development of photovoltaic array and module safety requirements

    Science.gov (United States)

    1982-01-01

    Safety requirements for photovoltaic module and panel designs and configurations likely to be used in residential, intermediate, and large-scale applications were identified and developed. The National Electrical Code and Building Codes were reviewed with respect to present provisions which may be considered to affect the design of photovoltaic modules. Limited testing, primarily in the roof fire resistance field was conducted. Additional studies and further investigations led to the development of a proposed standard for safety for flat-plate photovoltaic modules and panels. Additional work covered the initial investigation of conceptual approaches and temporary deployment, for concept verification purposes, of a differential dc ground-fault detection circuit suitable as a part of a photovoltaic array safety system.

  16. To improve the safety of treatments in radiotherapy by developing a safety culture

    International Nuclear Information System (INIS)

    2008-01-01

    Following the radiotherapy accidents between 2004 and 2006, the I.R.S.N. deemed necessary to lead a study on the safety of treatments in radiotherapy and on the use and the adaptation to the medical domain of safety analysis approach developed for the nuclear installations. Of this study, six mains lines of investigation appear: Endow the radiotherapy services with real referential of safety, reinforce the robustness of the organization of radiotherapy services, improve the safety of the equipment and software at the design and operating stages, improve the management of the expertise and reinforce the operating feed back on incidents and accidents. The main learning from this study is the benefit that could be gained by fitting the safety analysis concepts and methods to the specificities of radiotherapy considering the organization of it collective work, the cooperation between actors stemming from different jobs as well as the interactions between actors and technical systems in the process of the treatments, when they are put into service and during their periodic checks. (author)

  17. Safety of High Speed Ground Transportation Systems : Analytical Methodology for Safety Validation of Computer Controlled Subsystems : Volume 2. Development of a Safety Validation Methodology

    Science.gov (United States)

    1995-01-01

    This report describes the development of a methodology designed to assure that a sufficiently high level of safety is achieved and maintained in computer-based systems which perform safety cortical functions in high-speed rail or magnetic levitation ...

  18. Developing glovebox robotics to meet the national robot safety standard and nuclear safety criteria

    International Nuclear Information System (INIS)

    McMahon, T.T.; Sievers, R.H.

    1991-09-01

    Development of a glove box based robotic system by the Lawrence Livermore National Laboratory (LLNL) is reported. Safety issues addressed include planning to meet the special constraints of operations within a hazardous material glove box and with hostile environments, compliance with the current and draft national robotic system safety standards, and eventual satisfaction of nuclear material handling requirements. Special attention has been required for the revision to the robot and control system models which antedate adoption of the present national safety standard. A robotic test bed, using non-radioactive surrogates is being activated at the Lawrence Livermore National Laboratory to develop the material handling system and the process interfaces for future special nuclear material processing applications. Part of this effort is to define, test, and revise adequate safety controls to ensure success when the system is eventually deployed at a DOE site. The current system is primarily for demonstration and testing, but will evolve into the baseline configuration from which the production system is to be derived. This results in special hazards associated with research activities which may not be present on a production line. Nuclear safety is of paramount importance and has been successfully addressed for 50 years in the DOE weapons production complex. It carries its particular requirements for robot systems and manual operations, as summarized below: Criticality must be avoided (materials cannot consolidate or accumulate to approach a critical mass). Radioactive materials must be confined. The public and workers must be protected from accountable radiation exposure. Nuclear material must be readily retrievable. Nuclear safety must be conclusively demonstrated through hazards analysis. 7 refs

  19. Nutrition, Health and Safety in Early Childhood Development ...

    African Journals Online (AJOL)

    This article investigates the nutrition, health and safety status in Early Childhood Development (ECD) programmes and its impact thereof on the quality of care and education in Harare primary schools as perceived by the school heads, ECD teachers and parents. The study is part of a larger study on assessing the quality of ...

  20. Microbiological food safety: a dilemma of developing societies.

    Science.gov (United States)

    Akhtar, Saeed; Sarker, Mahfuzur R; Hossain, Ashfaque

    2014-11-01

    Current food safety issues are deleteriously reshaping the life style of the population in the developing world. Socioeconomic status of the population in poorer economies is one of the major determinants to delineate the availability of safe food to the vulnerable population. Assessment of the prevalence of foodborne illness in developing world is the most neglected area to control disease. Botulism, Shigellosis, Campylobacteriosis, Escherichia coli infection, Staphylococcus aureus infection, Salmonellosis, Listeriosis and Cholerae are extensively prevalent and pose a major threat to human health in underdeveloped communities. The existing food safety status of many African, South Asian, Central, and South American developing countries is distressing therefore; it seems much timely to highlight the areas for the improvement to ensure the supply of safe food to the population in these regions. Extensive literature search at PubMed, Science Direct and Medline was carried out during the current year to catch on relevant data from 1976 to date, using selective terms like food safety, South East Asia, Africa, Central and South America, and foodborne illness etc. Efforts were made to restrict the search to low income countries of these regions with reference to specific foodborne pathogens. This report briefly discusses the present food safety situation in these developing countries and associated consequences as prime issues, suggesting foodborne illness to be the most distressing threat for human health and economic growth.

  1. Development of main steam safety valve set pressure evaluating system

    International Nuclear Information System (INIS)

    Oketani, Koichiro; Manabe, Yoshihisa.

    1991-01-01

    A main steam safety valve set pressure test is conducted for all valves during every refueling outage in Japan's PWRs. Almost all operations of the test are manually conducted by a skilled worker. In order to obtain further reliability and reduce the test time, an automatic test system using a personnel computer has been developed in accordance with system concept. Quality assurance was investigated to fix system specifications. The prototype of the system was manufactured to confirm the system reliability. The results revealed that this system had high accuracy measurement and no adverse influence on the safety valve. This system was concluded to be applicable for actual use. (author)

  2. Developing the health, safety and environment excellence instrument.

    Science.gov (United States)

    Mohammadfam, Iraj; Saraji, Gebraeil Nasl; Kianfar, Ali; Mahmoudi, Shahram

    2013-01-07

    Quality and efficiency are important issues in management systems. To increase quality, to reach best results, to move towards the continuous improvement of system and also to make the internal and external customers satisfied, it is necessary to consider the system performance measurement. In this study the Health, Safety and Environment Excellence Instrument was represented as a performance measurement tool for a wide range of health, safety and environment management systems. In this article the development of the instrument overall structure, its parts, and its test results in three organizations are presented. According to the results, the scores ranking was the managership organization, the manufacturing company and the powerhouse construction project, respectively. The results of the instrument test in three organizations show that, on the whole, the instrument has the ability to measure the performance of health, safety and environment management systems in a wide range of organizations.

  3. Development of E-Learning Materials for Machining Safety Education

    Science.gov (United States)

    Nakazawa, Tsuyoshi; Mita, Sumiyoshi; Matsubara, Masaaki; Takashima, Takeo; Tanaka, Koichi; Izawa, Satoru; Kawamura, Takashi

    We developed two e-learning materials for Manufacturing Practice safety education: movie learning materials and hazard-detection learning materials. Using these video and sound media, students can learn how to operate machines safely with movie learning materials, which raise the effectiveness of preparation and review for manufacturing practice. Using these materials, students can realize safety operation well. Students can apply knowledge learned in lectures to the detection of hazards and use study methods for hazard detection during machine operation using the hazard-detection learning materials. Particularly, the hazard-detection learning materials raise students‧ safety consciousness and increase students‧ comprehension of knowledge from lectures and comprehension of operations during Manufacturing Practice.

  4. Multi-dimensional Code Development for Safety Analysis of LMR

    International Nuclear Information System (INIS)

    Ha, K. S.; Jeong, H. Y.; Kwon, Y. M.; Lee, Y. B.

    2006-08-01

    A liquid metal reactor loaded a metallic fuel has the inherent safety mechanism due to the several negative reactivity feedback. Although this feature demonstrated through experiments in the EBR-II, any of the computer programs until now did not exactly analyze it because of the complexity of the reactivity feedback mechanism. A multi-dimensional detail program was developed through the International Nuclear Energy Research Initiative(INERI) from 2003 to 2005. This report includes the numerical coupling the multi-dimensional program and SSC-K code which is used to the safety analysis of liquid metal reactors in KAERI. The coupled code has been proved by comparing the analysis results using the code with the results using SAS-SASSYS code of ANL for the UTOP, ULOF, and ULOHS applied to the safety analysis for KALIMER-150

  5. Integrated risk management of safety and development on transportation corridors

    International Nuclear Information System (INIS)

    Thekdi, Shital A.; Lambert, James H.

    2015-01-01

    Prioritization of investments to protect safety and performance of multi-regional transportation networks from adjacent land development is a key concern for infrastructure agencies, land developers, and other stakeholders. Despite ample literature describing relationships between transportation and land use, no evidence-based methods exist for monitoring corridor needs on a large scale. Risk analysis is essential to the preservation of system safety and capacity, including avoidance of costly retrofits, regret, and belated action. This paper introduces the Corridor Trace Analysis (CTA) for prioritizing corridor segments that are vulnerable to adjacent land development. The method integrates several components: (i) estimation of likelihood of adjacent land development, using influence diagram and rule-based modeling, (ii) characterization of access point density using geospatial methods, and (iii) plural-model evaluation of corridors, monitoring indices of land development likelihood, access point densities, and traffic volumes. The results inform deployment of options that include closing access points, restricting development, and negotiation of agencies and developers. The CTA method is demonstrated on a region encompassing 6000 centerline miles (about 10,000 km) of transportation corridors. The method will be of interest to managers investing in safety and performance of infrastructure systems, balancing safety, financial, and other criteria of concern for diverse stakeholders. - Highlights: • The Corridor Trace Analysis (CTA) method for prioritizing transportation corridors. • The CTA method studies corridors vulnerable to adjacent land development. • The CTA method quantifies the influence of risk scenarios on agency priorities. • The CTA method is demonstrated on 6000 miles of critical transportation corridor

  6. Application of software to development of reactor-safety codes

    International Nuclear Information System (INIS)

    Wilburn, N.P.; Niccoli, L.G.

    1980-09-01

    Over the past two-and-a-half decades, the application of new techniques has reduced hardware cost for digital computer systems and increased computational speed by several orders of magnitude. A corresponding cost reduction in business and scientific software development has not occurred. The same situation is seen for software developed to model the thermohydraulic behavior of nuclear systems under hypothetical accident situations. For all cases this is particularly noted when costs over the total software life cycle are considered. A solution to this dilemma for reactor safety code systems has been demonstrated by applying the software engineering techniques which have been developed over the course of the last few years in the aerospace and business communities. These techniques have been applied recently with a great deal of success in four major projects at the Hanford Engineering Development Laboratory (HEDL): 1) a rewrite of a major safety code (MELT); 2) development of a new code system (CONACS) for description of the response of LMFBR containment to hypothetical accidents, and 3) development of two new modules for reactor safety analysis

  7. Radiation safety assessment and development of environmental radiation monitoring technology

    CERN Document Server

    Choi, B H; Kim, S G

    2002-01-01

    The Periodic Safety Review(PSR) of the existing nuclear power plants is required every ten years according to the recently revised atomic energy acts. The PSR of Kori unit 1 and Wolsong unit 1 that have been operating more than ten years is ongoing to comply the regulations. This research project started to develop the techniques necessary for the PSR. The project developed the following four techniques at the first stage for the environmental assessment of the existing plants. 1) Establishment of the assessment technology for contamination and accumulation trends of radionuclides, 2) alarm point setting of environmental radiation monitoring system, 3) Development of Radiation Safety Evaluation Factor for Korean NPP, and 4) the evaluation of radiation monitoring system performance and set-up of alarm/warn set point. A dynamic compartment model to derive a relationship between the release rates of gas phase radionuclides and the concentrations in the environmental samples. The model was validated by comparing ...

  8. Development of regulatory technology for thermal-hydraulic safety analysis

    International Nuclear Information System (INIS)

    Bang, Young Seok; Lee, S. H.; Ryu, Y. H.

    2001-02-01

    The present study aims to develop the regulation capability in thermal-hydraulic safety analysis which was required for the reasonable safety regulation in the current NPP, the next generation reactors, and the future-type reactors. The fourth fiscal year of the first phase of the research was focused on the following research topics: Investigation on the current status of the thermal-hydraulic safety analysis technology outside and inside of the country; Review on the improved features of the thermal-hydraulic safety analysis regulatory audit code, RELAP5/MOD3; Assessments of code with LOFT L9-3 ATWS experiment and LSTF SB-SG-10 multiple SGTR experiment; Application of the RELAP5/CANDU code to analyses of SLB and LBLOCA and evaluation of its effect on safety; Application of the code to IAEA PHWR ISP analysis; Assessments of RELAP5 and TRAC with UPTF downcomer injection test and Analysis of LBLOCA with RELAP5 for the performance evaluation of KNGR DVI; Setup of a coupled 3-D kinetics and thermal-hydraulics and application it to a reactivity accident analysis; and Extension of database and improvement of plant input decks. For supporting the resolution of safety issues, loss of RHR event during midloop operation was analyzed for Kori Unit 3, issues on high burnup fuel were reviewed and performance of FRAPCON-3 assessed. Also MSLB was analyzed to figure out the sensitivity of downcomer temperature supporting the PTS risk evaluation of Kori Unit 1. Thermal stratification in pipe was analyzed using the method proposed. And a method predicting the thermal-hydraulic performance of IRWST of KNGR was explored. The PWR ECCS performance criteria was issued as a MOST Article 200-19.and a regulatory guide on evaluation methodology was improved to cover concerns raised from the related licensing review process

  9. Safety

    International Nuclear Information System (INIS)

    1998-01-01

    A brief account of activities carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. These activities are reported under the headings: (1) Nuclear safety; (2) Industrial and health safety; (3) Radiation safety; and Fire protection

  10. Improving occupational safety and health by integration into product development

    DEFF Research Database (Denmark)

    Broberg, Ole

    1996-01-01

    A cross-sectional case study was performed in a large company producing electro-mechanical products for industrial application. The objectives were: (i) to study the product development process and the role of key actors', (ii) to identify current practice on integrating occupational safety and h...... and studies of documents. A questionnaire regarding product development tasks and occupational safety and health were distributed to 30 design and production engineers. A total of 27 completed the questionnaire corresponding to a response rate of 90 per cent.......A cross-sectional case study was performed in a large company producing electro-mechanical products for industrial application. The objectives were: (i) to study the product development process and the role of key actors', (ii) to identify current practice on integrating occupational safety...... and health into the development process, especially the efforts and attitudes of design and production engineers', and (iii) to identify key actors'reflections on how to improve this integration. The study was based on qualitative as well as quantitative methods including interviews, questionnaires...

  11. Reactor safety research and development in Chalk River Laboratories

    Energy Technology Data Exchange (ETDEWEB)

    Nitheanandan, T. [Atomic Energy of Canada Limited, Chalk River, ON (Canada)

    2014-07-01

    Atomic Energy of Canada Limited's Chalk River Laboratories provides three different services to stakeholders and customers. The first service provided by the laboratory is the implementation of Research and Development (R&D) programs to provide the underlying technological basis of safe nuclear power reactor designs. A significant portion of the Canadian R&D capability in reactor safety resides at Atomic Energy of Canada Limited's Chalk River Laboratories, and this capability was instrumental in providing the science and technology required to aid in the safety design of CANDU power reactors. The second role of the laboratory has been in supporting nuclear facility licensees to ensure the continued safe operation of nuclear facilities, and to develop safety cases to justify continued operation. The licensing of plant life extension is a key industry objective, requiring extensive research on degradation mechanisms, such that safety cases are based on the original safety design data and valid and realistic assumptions regarding the effect of ageing and management of plant life. Recently, Chalk River Laboratories has been engaged in a third role in research to provide the technical basis and improved understanding for decision making by regulatory bodies. The state-of-the-art test facilities in Chalk River Laboratories have been contributing to the R&D needs of all three roles, not only in Canada but also in the international community, thorough Canada's participation in cooperative programs lead by International Atomic Energy Agency and the OECD's Nuclear Energy Agency. (author)

  12. Development of a Novel Nuclear Safety Culture Evaluation Method for an Operating Team Using Probabilistic Safety Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sangmin; Lee, Seung Min; Seong, Poong Hyun [KAIST, Daejeon (Korea, Republic of)

    2015-05-15

    IAEA defined safety culture as follows: 'Safety Culture is that assembly of characteristics and attitudes in organizations and individuals which establishes that, as an overriding priority, nuclear plant safety issues receive the attention warranted by their significance'. Also, celebrated behavioral scientist, Cooper, defined safety culture as,'safety culture is that observable degree of effort by which all organizational members direct their attention and actions toward improving safety on a daily basis' with his internal psychological, situational, and behavioral context model. With these various definitions and criteria of safety culture, several safety culture assessment methods have been developed to improve and manage safety culture. To develop a new quantitative safety culture evaluation method for an operating team, we unified and redefined safety culture assessment items. Then we modeled a new safety culture evaluation by adopting level 1 PSA concept. Finally, we suggested the criteria to obtain nominal success probabilities of assessment items by using 'operational definition'. To validate the suggested evaluation method, we analyzed the collected audio-visual recording data collected from a full scope main control room simulator of a NPP in Korea.

  13. Development of a Novel Nuclear Safety Culture Evaluation Method for an Operating Team Using Probabilistic Safety Analysis

    International Nuclear Information System (INIS)

    Han, Sangmin; Lee, Seung Min; Seong, Poong Hyun

    2015-01-01

    IAEA defined safety culture as follows: 'Safety Culture is that assembly of characteristics and attitudes in organizations and individuals which establishes that, as an overriding priority, nuclear plant safety issues receive the attention warranted by their significance'. Also, celebrated behavioral scientist, Cooper, defined safety culture as,'safety culture is that observable degree of effort by which all organizational members direct their attention and actions toward improving safety on a daily basis' with his internal psychological, situational, and behavioral context model. With these various definitions and criteria of safety culture, several safety culture assessment methods have been developed to improve and manage safety culture. To develop a new quantitative safety culture evaluation method for an operating team, we unified and redefined safety culture assessment items. Then we modeled a new safety culture evaluation by adopting level 1 PSA concept. Finally, we suggested the criteria to obtain nominal success probabilities of assessment items by using 'operational definition'. To validate the suggested evaluation method, we analyzed the collected audio-visual recording data collected from a full scope main control room simulator of a NPP in Korea

  14. The development of NPP operational safety training courses

    International Nuclear Information System (INIS)

    Lee, Chang Kun; Lee, Duk Sun; Lee, Byung Sun; Lee, Won Koo; Juhn, Heng Run; Moon, Byung Soo; Cho, Min Sik; Lee, Han Young; Moon, Hak Won; Seo, Yeon Ho

    1987-12-01

    The objective of the project is to develop a training course text for the betterment of reactor operation and assurance of its safety in general by providing training materials of the advanced compact nuclear simulator which will become operation in September 1988. Main scope and contents of the project are as follows: - compilation of basic data related to simulator operation and maintenance as well as the comparative analysis with respect to simulator materials in foreign countries - method of training by simulator - review the training status by simulator in foreign countries - development of training course in the field of reactor safety It is expected that the results will be reflected to the actual training and retraining of the reactor operating crew so as to improve and update their capabilities in training fashion. (Author)

  15. Health and safety in clinical laboratories in developing countries: safety considerations.

    Science.gov (United States)

    Ejilemele, A A; Ojule, A C

    2004-01-01

    Clinical laboratories are potentially hazardous work areas. Health and safety in clinical laboratories is becoming an increasingly important subject as a result of the emergence of highly infectious diseases such as hepatitis and HIV. This is even more so in developing countries where health and safety have traditionally been regarded as low priority issues, considering the more important health problems confronting the health authorities in these countries. We conducted a literature search using the medical subheadings titles on the INTERNET over a period of twenty years and summarized our findings. This article identifies hazards in the laboratories and highlights measures to make the laboratory a safer work place. It also emphasizes the mandatory obligations of employers and employees towards the attainment of acceptable safety standards in clinical laboratories in Third World countries in the face of the current HIV/AIDS epidemic in many of these developing countries especially in the sub-Saharan Africa while accommodating the increasing work load in these laboratories. Both the employer and the employee have major roles to play in the maintenance of a safe working environment. This can be achieved if measures discussed are incorporated into everyday laboratory practice.

  16. Nuclear-safety institution in France: emergence and development

    International Nuclear Information System (INIS)

    Vallet, B.M.

    1986-01-01

    This research work examines the social construction of the nuclear-safety institution in France, and the concurrent increased focus on the nuclear-risk issue. Emphasis on risk and safety, as primarily technical issues, can partly be seen as a strategy. Employed by power elites in the nuclear technostructure, this diverts emphasis away from controversial and normative questions regarding the political and social consequences of technology to questions of technology that appear to be absolute to the technology itself. Nuclear safety, which started from a preoccupation with risk related to the nuclear energy research and development process, is examined using the analytic concept of field. As a social arena patterned to achieve specific tasks, this field is dominated by a body of state engineers recognized to have high-level scientific and administrative competences. It is structured by procedures and administrative hierarchies as well as by technical rules, norms, and standards. These are formalized and rationalized through technical, economic, political, and social needs; over time; they consolidate the field into an institution. The study documents the nuclear-safety institution as an integral part of the nuclear technostructure, which has historically used the specificity of its expertise as a buffer against outside interference

  17. Additional methodology development for statistical evaluation of reactor safety analyses

    International Nuclear Information System (INIS)

    Marshall, J.A.; Shore, R.W.; Chay, S.C.; Mazumdar, M.

    1977-03-01

    The project described is motivated by the desire for methods to quantify uncertainties and to identify conservatisms in nuclear power plant safety analysis. The report examines statistical methods useful for assessing the probability distribution of output response from complex nuclear computer codes, considers sensitivity analysis and several other topics, and also sets the path for using the developed methods for realistic assessment of the design basis accident

  18. Safety activities and human resource development at NCA

    International Nuclear Information System (INIS)

    Kumanomido, Hironori; Sakurada, Koichi; Yanagisawa, Shigeru; Masuyama, Tadaharu

    2015-01-01

    Toshiba Nuclear Critical Assembly (NCA) has been safely operated since the first criticality in December 1963. The topics covered in this Yayoi Meeting Report are: (1) the outline of NCA, (2) the safety control situation mainly after the Great East Japan Earthquake in 2011, (3) educational training incorporates the lessons learned in this earthquake, and (4) human resource development during 2008-2015. Regarding safety control, facility maintenance has been conducted systematically according to the maintenance plan from the viewpoint of preventive maintenance. Regarding educational training, two disaster handling training based on the safety regulation and one nuclear emergency drill based on the emergency drill plan for licensee of nuclear energy activity based on the Act of Special Measures Concerning Nuclear Emergency Preparedness every year. Regarding human resource development, development training was given to 358 people including students. This year, training that does not require NCA operation was conducted including gamma-ray spectrum measurement of NCA fuel rod and neutron deceleration property measurement using 252 Cf neutron source. (S.K.)

  19. Safety-related operator actions: methodology for developing criteria

    International Nuclear Information System (INIS)

    Kozinsky, E.J.; Gray, L.H.; Beare, A.N.; Barks, D.B.; Gomer, F.E.

    1984-03-01

    This report presents a methodology for developing criteria for design evaluation of safety-related actions by nuclear power plant reactor operators, and identifies a supporting data base. It is the eleventh and final NUREG/CR Report on the Safety-Related Operator Actions Program, conducted by Oak Ridge National Laboratory for the US Nuclear Regulatory Commission. The operator performance data were developed from training simulator experiments involving operator responses to simulated scenarios of plant disturbances; from field data on events with similar scenarios; and from task analytic data. A conceptual model to integrate the data was developed and a computer simulation of the model was run, using the SAINT modeling language. Proposed is a quantitative predictive model of operator performance, the Operator Personnel Performance Simulation (OPPS) Model, driven by task requirements, information presentation, and system dynamics. The model output, a probability distribution of predicted time to correctly complete safety-related operator actions, provides data for objective evaluation of quantitative design criteria

  20. Railway safety climate: a study on organizational development.

    Science.gov (United States)

    Cheng, Yung-Hsiang

    2017-09-07

    The safety climate of an organization is considered a leading indicator of potential risk for railway organizations. This study adopts the perceptual measurement-individual attribute approach to investigate the safety climate of a railway organization. The railway safety climate attributes are evaluated from the perspective of railway system staff. We identify four safety climate dimensions from exploratory factor analysis, namely safety communication, safety training, safety management and subjectively evaluated safety performance. Analytical results indicate that the safety climate differs at vertical and horizontal organizational levels. This study contributes to the literature by providing empirical evidence of the multilevel safety climate in a railway organization, presents possible causes of the differences under various cultural contexts and differentiates between safety climate scales for diverse workgroups within the railway organization. This information can be used to improve the safety sustainability of railway organizations and to conduct safety supervisions for the government.

  1. Development of Realistic Safety Analysis Technology for CANDU Reactors

    International Nuclear Information System (INIS)

    Park, Joo Hwan; Rhee, B. W.; Rho, G. H.

    2010-04-01

    The following 3 research items have been studied to develop and establish the realistic safety analysis and the associated technologies for a CANDU reactor. At the first, WIMS-CANDU which is physics cell code for a CANDU has been improved and validated against the physics criticality experiment data transferred through the international cooperation programs. Also an improved physics model to take into account the pressure tube creep was developed and utilized to assess the effects of the pressure tube creep of 0%, 2.5% and 5% diametral increase of pressure tube on core physics parameters. Secondly, the interfacing module between physics and thermal-hydraulics codes has been developed to provide the enhancement of reliability and convenience of the calculation results of the physics parameters such as power coefficient which was calculated by independent code systems. Finally, the important parameters related to the complex heat transfer mechanisms in the crept pressure tubes were identified to find how to improve the existing fuel channel models. One of the important parameters such as the oxidation model of Zr-steam reaction was identified, implemented and verified with the experimental data of the high pressure and temperature fuel channel and its model was utilized for CFD analysis of the crept pressure tube effect on the reactor safety. The results were also provided to validate the CATNENA models of the crept pressure tube and the effects of the pressure tube creep on the blowdown and post-blowdown phase during LOCA was assessed. The results of this study can be used to assess the uncertainty analysis of coolant void reactivity and the effects of the creep deformed pressure tubes on physics/TH/safety issues. Also, those results will be used to improve the current design and operational safety analysis codes, and to technically support the related issues to resolve their problems

  2. Latest developments on safety analysis methodologies at the Juzbado plant

    International Nuclear Information System (INIS)

    Zurron-Cifuentes, Oscar; Ortiz-Trujillo, Diego; Blanco-Fernandez, Luis A.

    2010-01-01

    Over the last few years the Juzbado Plant has developed and implemented several analysis methodologies to cope with specific issues regarding safety management. This paper describes the three most outstanding of them, so as to say, the Integrated Safety Analysis (ISA) project, the adaptation of the MARSSIM methodology for characterization surveys of radioactive contamination spots, and the programme for the Systematic Review of the Operational Conditions of the Safety Systems (SROCSS). Several reasons motivated the decision to implement such methodologies, such as Regulator requirements, operational experience and of course, the strong commitment of ENUSA to maintain the highest standards of nuclear industry on all the safety relevant activities. In this context, since 2004 ENUSA is undertaking the ISA project, which consists on a systematic examination of plant's processes, equipment, structures and personnel activities to ensure that all relevant hazards that could result in unacceptable consequences have been adequately evaluated and the appropriate protective measures have been identified. On the other hand and within the framework of a current programme to ensure the absence of radioactive contamination spots on unintended areas, the MARSSIM methodology is being applied as a tool to conduct the radiation surveys and investigation of potentially contaminated areas. Finally, the SROCSS programme was initiated earlier this year 2009 to assess the actual operating conditions of all the systems with safety relevance, aiming to identify either potential non-conformities or areas for improvement in order to ensure their high performance after years of operation. The following paragraphs describe the key points related to these three methodologies as well as an outline of the results obtained so far. (authors)

  3. Developing safety performance functions incorporating reliability-based risk measures.

    Science.gov (United States)

    Ibrahim, Shewkar El-Bassiouni; Sayed, Tarek

    2011-11-01

    Current geometric design guides provide deterministic standards where the safety margin of the design output is generally unknown and there is little knowledge of the safety implications of deviating from these standards. Several studies have advocated probabilistic geometric design where reliability analysis can be used to account for the uncertainty in the design parameters and to provide a risk measure of the implication of deviation from design standards. However, there is currently no link between measures of design reliability and the quantification of safety using collision frequency. The analysis presented in this paper attempts to bridge this gap by incorporating a reliability-based quantitative risk measure such as the probability of non-compliance (P(nc)) in safety performance functions (SPFs). Establishing this link will allow admitting reliability-based design into traditional benefit-cost analysis and should lead to a wider application of the reliability technique in road design. The present application is concerned with the design of horizontal curves, where the limit state function is defined in terms of the available (supply) and stopping (demand) sight distances. A comprehensive collision and geometric design database of two-lane rural highways is used to investigate the effect of the probability of non-compliance on safety. The reliability analysis was carried out using the First Order Reliability Method (FORM). Two Negative Binomial (NB) SPFs were developed to compare models with and without the reliability-based risk measures. It was found that models incorporating the P(nc) provided a better fit to the data set than the traditional (without risk) NB SPFs for total, injury and fatality (I+F) and property damage only (PDO) collisions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Occupational safety and health criteria for responsible development of nanotechnology

    Science.gov (United States)

    Schulte, P. A.; Geraci, C. L.; Murashov, V.; Kuempel, E. D.; Zumwalde, R. D.; Castranova, V.; Hoover, M. D.; Hodson, L.; Martinez, K. F.

    2014-01-01

    Organizations around the world have called for the responsible development of nanotechnology. The goals of this approach are to emphasize the importance of considering and controlling the potential adverse impacts of nanotechnology in order to develop its capabilities and benefits. A primary area of concern is the potential adverse impact on workers, since they are the first people in society who are exposed to the potential hazards of nanotechnology. Occupational safety and health criteria for defining what constitutes responsible development of nanotechnology are needed. This article presents five criterion actions that should be practiced by decision-makers at the business and societal levels—if nanotechnology is to be developed responsibly. These include (1) anticipate, identify, and track potentially hazardous nanomaterials in the workplace; (2) assess workers' exposures to nanomaterials; (3) assess and communicate hazards and risks to workers; (4) manage occupational safety and health risks; and (5) foster the safe development of nanotechnology and realization of its societal and commercial benefits. All these criteria are necessary for responsible development to occur. Since it is early in the commercialization of nanotechnology, there are still many unknowns and concerns about nanomaterials. Therefore, it is prudent to treat them as potentially hazardous until sufficient toxicology, and exposure data are gathered for nanomaterial-specific hazard and risk assessments. In this emergent period, it is necessary to be clear about the extent of uncertainty and the need for prudent actions.

  5. Safety culture indicators for NPP: international trends and development status in Korea

    International Nuclear Information System (INIS)

    Choi, Y. S.; Ko, J. D.; Choi, K. S.; Jung, Y. H.

    2004-01-01

    Safety culture has been recognized as important to achieve high level of nuclear safety, as several recent events that have occurred in advanced countries were found to have important implications for safety culture. Under the recognition, implementation-focused and practical methods to foster safety culture have become necessary. Development of safety culture indicators for assessing the level of safety culture and identifying some deficiencies is being conducted. This paper examines the regulatory positions of major nuclear power countries on licensee's safety culture, introduces the development status of Korean Safety Culture Indicators and presents its future direction

  6. [Evaluating training programs on occupational health and safety: questionnaire development].

    Science.gov (United States)

    Zhou, Xiao-Yan; Wang, Zhi-Ming; Wang, Mian-Zhen

    2006-03-01

    To develop a questionnaire to evaluate the quality of training programs on occupational health and safety. A questionnaire comprising five subscales and 21 items was developed. The reliability and validity of the questionnaire was tested. Final validation of the questionnaire was undertaken in 700 workers in an oil refining company. The Cronbach's alpha coefficients of the five subscales ranged from 0.6194 to 0.6611. The subscale-scale Pearson correlation coefficients ranged from 0.568 to 0.834 . The theta coefficients of the five subscales were greater than 0.7. The factor loadings of the five subscales in the principal component analysis ranged from 0.731 to 0.855. Use of the questionnaire in the 700 workers produced a good discriminability, with excellent, good, fair and poor comprising 22.2%, 31.2%, 32.4% and 14.1 respectively. Given the fact that 18.7% of workers had never been trained and 29.7% of workers got one-off training only, the training program scored an average of 57.2. The questionnaire is suitable to be used in evaluating the quality of training programs on occupational health and safety. The oil refining company needs to improve training for their workers on occupational health and safety.

  7. Development and assessment of best estimate integrated safety analysis code

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Bub Dong; Lee, Young Jin; Hwang, Moon Kyu (and others)

    2007-03-15

    Improvement of the integrated safety analysis code MARS3.0 has been carried out and a multi-D safety analysis application system has been established. Iterative matrix solver and parallel processing algorithm have been introduced, and a LINUX version has been generated to enable MARS to run in cluster PCs. MARS variables and sub-routines have been reformed and modularised to simplify code maintenance. Model uncertainty analyses have been performed for THTF, FLECHT, NEPTUN, and LOFT experiments as well as APR1400 plant. Participations in international cooperation research projects such as OECD BEMUSE, SETH, PKL, BFBT, and TMI-2 have been actively pursued as part of code assessment efforts. The assessment, evaluation and experimental data obtained through international cooperation projects have been registered and maintained in the T/H Databank. Multi-D analyses of APR1400 LBLOCA, DVI Break, SLB, and SGTR have been carried out as a part of application efforts in multi-D safety analysis. GUI based 3D input generator has been developed for user convenience. Operation of the MARS Users Group (MUG) was continued and through MUG, the technology has been transferred to 24 organisations. A set of 4 volumes of user manuals has been compiled and the correction reports for the code errors reported during MARS development have been published.

  8. Development and assessment of best estimate integrated safety analysis code

    International Nuclear Information System (INIS)

    Chung, Bub Dong; Lee, Young Jin; Hwang, Moon Kyu

    2007-03-01

    Improvement of the integrated safety analysis code MARS3.0 has been carried out and a multi-D safety analysis application system has been established. Iterative matrix solver and parallel processing algorithm have been introduced, and a LINUX version has been generated to enable MARS to run in cluster PCs. MARS variables and sub-routines have been reformed and modularised to simplify code maintenance. Model uncertainty analyses have been performed for THTF, FLECHT, NEPTUN, and LOFT experiments as well as APR1400 plant. Participations in international cooperation research projects such as OECD BEMUSE, SETH, PKL, BFBT, and TMI-2 have been actively pursued as part of code assessment efforts. The assessment, evaluation and experimental data obtained through international cooperation projects have been registered and maintained in the T/H Databank. Multi-D analyses of APR1400 LBLOCA, DVI Break, SLB, and SGTR have been carried out as a part of application efforts in multi-D safety analysis. GUI based 3D input generator has been developed for user convenience. Operation of the MARS Users Group (MUG) was continued and through MUG, the technology has been transferred to 24 organisations. A set of 4 volumes of user manuals has been compiled and the correction reports for the code errors reported during MARS development have been published

  9. Development of a safety and regulation systems simulation program II

    International Nuclear Information System (INIS)

    1985-05-01

    This report describes the development of a safety and regulation systems simulation program under contract to the Atomic Energy Control Board of Canada. A systems logic interaction simulation (SLISIM) program was developed for the AECB's HP-1000 computer which operates in the interactive simulation (INSIM) program environment. The SLISIM program simulates the spatial neutron dynamics, the regulation of the reactor power and in this version the CANDU-PHW 600 MW(e) computerized shutdown systems' trip parameters. The modular concept and interactive capability of the INSIM environment provides the user with considerable flexibility of the setup and control of the simulation

  10. Workshop on development and view on digital safety system of KNICS

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-05-15

    The contents of this workshop are vision of KNICS, introduction of development of safety system of KNICS, development situation of safety class of PLC, view of software for safety-critical system in PLC, RTOS development by shaping, quality assurance and attestation of PLC, development situation of nuclear reactor system and development situation of ESF-CCS.

  11. Workshop on development and view on digital safety system of KNICS

    International Nuclear Information System (INIS)

    2006-05-01

    The contents of this workshop are vision of KNICS, introduction of development of safety system of KNICS, development situation of safety class of PLC, view of software for safety-critical system in PLC, RTOS development by shaping, quality assurance and attestation of PLC, development situation of nuclear reactor system and development situation of ESF-CCS

  12. Development of design and safety analysis supporting system for casks

    International Nuclear Information System (INIS)

    Ohsono, Katsunari; Higashino, Akira; Endoh, Shuji

    1993-01-01

    Mitsubishi heavy Industries has developed a design and safety analysis supporting system 'CADDIE' (Cask Computer Aided Design, Drawing and Integrated Evaluation System), with the following objectives: (1) Enhancement of efficiency of the design and safety analysis (2) Further advancement of design quality (3) Response to the diversification of design requirements. The features of this system are as follows: (1) The analysis model data common to analyses is established, and it is prepared automatically from the model made by CAD. (2) The input data for the analysis code is available by simple operation of conversation type from the analysis model data. (3) The analysis results are drawn out in diagrams by output generator, so as to facilitate easy observation. (4) The data of material properties, fuel assembly data, etc. required for the analyses are made available as a data base. (J.P.N.)

  13. Application of software engineering to development of reactor safety codes

    International Nuclear Information System (INIS)

    Wilburn, N.P.; Niccoli, L.G.

    1981-01-01

    Software Engineering, which is a systematic methodology by which a large scale software development project is partitioned into manageable pieces, has been applied to the development of LMFBR safety codes. The techniques have been applied extensively in the business and aerospace communities and have provided an answer to the drastically increasing cost of developing and maintaining software. The five phases of software engineering (Survey, Analysis, Design, Implementation, and Testing) were applied in turn to development of these codes, along with Walkthroughs (peer review) at each stage. The application of these techniques has resulted in SUPERIOR SOFTWARE which is well documented, thoroughly tested, easy to modify, easier to use and maintain. The development projects have resulted in lower overall cost. (orig.) [de

  14. Development of reliability-based safety enhancement technology

    International Nuclear Information System (INIS)

    Kim, Kil Yoo; Han, Sang Hoon; Jang, Seung Cherl

    2002-04-01

    This project aims to develop critical technologies and the necessary reliability DB for maximizing the economics in the NPP operation with keeping the safety using the information of the risk (or reliability). For the research goal, firstly the four critical technologies(Risk Informed Tech. Spec. Optimization, Risk Informed Inservice Testing, On-line Maintenance, Maintenance Rule) for RIR and A have been developed. Secondly, KIND (Korea Information System for Nuclear Reliability Data) has been developed. Using KIND, YGN 3,4 and UCN 3,4 component reliability DB have been established. A reactor trip history DB for all NPP in Korea also has been developed and analyzed. Finally, a detailed reliability analysis of RPS/ESFAS for KNSP has been performed. With the result of the analysis, the sensitivity analysis also has been performed to optimize the AOT/STI of tech. spec. A statistical analysis procedure and computer code have been developed for the set point drift analysis

  15. Developing the radiation protection safety culture in the UK.

    Science.gov (United States)

    Cole, P; Hallard, R; Broughton, J; Coates, R; Croft, J; Davies, K; Devine, I; Lewis, C; Marsden, P; Marsh, A; McGeary, R; Riley, P; Rogers, A; Rycraft, H; Shaw, A

    2014-06-01

    In the UK, as elsewhere, there is potential to improve how radiological challenges are addressed through improvement in, or development of, a strong radiation protection (RP) safety culture. In preliminary work in the UK, two areas have been identified as having a strong influence on UK society: the healthcare and nuclear industry sectors. Each has specific challenges, but with many overlapping common factors. Other sectors will benefit from further consideration.In order to make meaningful comparisons between these two principal sectors, this paper is primarily concerned with cultural aspects of RP in the working environment and occupational exposures rather than patient doses.The healthcare sector delivers a large collective dose to patients each year, particularly for diagnostic purposes, which continues to increase. Although patient dose is not the focus, it must be recognised that collective patient dose is inevitably linked to collective occupational exposure, especially in interventional procedures.The nuclear industry faces major challenges as work moves from operations to decommissioning on many sites. This involves restarting work in the plants responsible for the much higher radiation doses of the 1960/70s, but also performing tasks that are considerably more difficult and hazardous than those original performed in these plants.Factors which influence RP safety culture in the workplace are examined, and proposals are considered for a series of actions that may lead to an improvement in RP culture with an associated reduction in dose in many work areas. These actions include methods to improve knowledge and awareness of radiation safety, plus ways to influence management and colleagues in the workplace. The exchange of knowledge about safety culture between the nuclear industry and medical areas may act to develop RP culture in both sectors, and have a wider impact in other sectors where exposures to ionising radiations can occur.

  16. Developing the radiation protection safety culture in the UK

    International Nuclear Information System (INIS)

    Cole, P; Marsh, A; Hallard, R; Broughton, J; Coates, R; Croft, J; Davies, K; Devine, I; Lewis, C; Marsden, P; McGeary, R; Riley, P; Rogers, A; Rycraft, H; Shaw, A

    2014-01-01

    In the UK, as elsewhere, there is potential to improve how radiological challenges are addressed through improvement in, or development of, a strong radiation protection (RP) safety culture. In preliminary work in the UK, two areas have been identified as having a strong influence on UK society: the healthcare and nuclear industry sectors. Each has specific challenges, but with many overlapping common factors. Other sectors will benefit from further consideration. In order to make meaningful comparisons between these two principal sectors, this paper is primarily concerned with cultural aspects of RP in the working environment and occupational exposures rather than patient doses. The healthcare sector delivers a large collective dose to patients each year, particularly for diagnostic purposes, which continues to increase. Although patient dose is not the focus, it must be recognised that collective patient dose is inevitably linked to collective occupational exposure, especially in interventional procedures. The nuclear industry faces major challenges as work moves from operations to decommissioning on many sites. This involves restarting work in the plants responsible for the much higher radiation doses of the 1960/70s, but also performing tasks that are considerably more difficult and hazardous than those original performed in these plants. Factors which influence RP safety culture in the workplace are examined, and proposals are considered for a series of actions that may lead to an improvement in RP culture with an associated reduction in dose in many work areas. These actions include methods to improve knowledge and awareness of radiation safety, plus ways to influence management and colleagues in the workplace. The exchange of knowledge about safety culture between the nuclear industry and medical areas may act to develop RP culture in both sectors, and have a wider impact in other sectors where exposures to ionising radiations can occur. (memorandum)

  17. Foundational development of an advanced nuclear reactor integrated safety code

    International Nuclear Information System (INIS)

    Clarno, Kevin; Lorber, Alfred Abraham; Pryor, Richard J.; Spotz, William F.; Schmidt, Rodney Cannon; Belcourt, Kenneth; Hooper, Russell Warren; Humphries, Larry LaRon

    2010-01-01

    This report describes the activities and results of a Sandia LDRD project whose objective was to develop and demonstrate foundational aspects of a next-generation nuclear reactor safety code that leverages advanced computational technology. The project scope was directed towards the systems-level modeling and simulation of an advanced, sodium cooled fast reactor, but the approach developed has a more general applicability. The major accomplishments of the LDRD are centered around the following two activities. (1) The development and testing of LIME, a Lightweight Integrating Multi-physics Environment for coupling codes that is designed to enable both 'legacy' and 'new' physics codes to be combined and strongly coupled using advanced nonlinear solution methods. (2) The development and initial demonstration of BRISC, a prototype next-generation nuclear reactor integrated safety code. BRISC leverages LIME to tightly couple the physics models in several different codes (written in a variety of languages) into one integrated package for simulating accident scenarios in a liquid sodium cooled 'burner' nuclear reactor. Other activities and accomplishments of the LDRD include (a) further development, application and demonstration of the 'non-linear elimination' strategy to enable physics codes that do not provide residuals to be incorporated into LIME, (b) significant extensions of the RIO CFD code capabilities, (c) complex 3D solid modeling and meshing of major fast reactor components and regions, and (d) an approach for multi-physics coupling across non-conformal mesh interfaces.

  18. Foundational development of an advanced nuclear reactor integrated safety code.

    Energy Technology Data Exchange (ETDEWEB)

    Clarno, Kevin (Oak Ridge National Laboratory, Oak Ridge, TN); Lorber, Alfred Abraham; Pryor, Richard J.; Spotz, William F.; Schmidt, Rodney Cannon; Belcourt, Kenneth (Ktech Corporation, Albuquerque, NM); Hooper, Russell Warren; Humphries, Larry LaRon

    2010-02-01

    This report describes the activities and results of a Sandia LDRD project whose objective was to develop and demonstrate foundational aspects of a next-generation nuclear reactor safety code that leverages advanced computational technology. The project scope was directed towards the systems-level modeling and simulation of an advanced, sodium cooled fast reactor, but the approach developed has a more general applicability. The major accomplishments of the LDRD are centered around the following two activities. (1) The development and testing of LIME, a Lightweight Integrating Multi-physics Environment for coupling codes that is designed to enable both 'legacy' and 'new' physics codes to be combined and strongly coupled using advanced nonlinear solution methods. (2) The development and initial demonstration of BRISC, a prototype next-generation nuclear reactor integrated safety code. BRISC leverages LIME to tightly couple the physics models in several different codes (written in a variety of languages) into one integrated package for simulating accident scenarios in a liquid sodium cooled 'burner' nuclear reactor. Other activities and accomplishments of the LDRD include (a) further development, application and demonstration of the 'non-linear elimination' strategy to enable physics codes that do not provide residuals to be incorporated into LIME, (b) significant extensions of the RIO CFD code capabilities, (c) complex 3D solid modeling and meshing of major fast reactor components and regions, and (d) an approach for multi-physics coupling across non-conformal mesh interfaces.

  19. The development of technologies of safety analysis for LMR ('03)

    International Nuclear Information System (INIS)

    Lee, Y. B.; Suk, S. D.; Chang, W. P.; Kwon, Y. M.; Jeong, H. Y.; Ha, K. W.; Heo, S.

    2004-03-01

    The developmental objectives of the project, 'The development of safety analysis techniques in LMR', are the code development for the subchannel blockage analysis, the code development for the system transient analysis, the code development for the HCDA(Hypothetical Core Disruptive Accident) analysis, the preliminary safety analysis for KALIMER-600 equipped with the components of new concepts, and the establishment of data base. The purpose of the analysis for subchannel blockage in the subassembly of LMR is to represent quantitatively that the maximum damage due to the accident is within the safety criteria. The computational program should be developed to simulate the thermal hydraulic phenomena and to verify the safety of LMR for the accident. For the purpose, the hybrid scheme has been implemented into the MATRA-LMR code based on the upwind scheme to analyze the various flow fields occurred in the subchannel blockage accident. The turbulent mixing models using the CFX code were assessed to compute more precisely the heat transfer between subchannels. Through this assessment, empirical correction factors of 1.7 for the heat conduction, 0.006 for the turbulent mixing coefficient were obtained. The distributed resistance model instead of wire forcing function has been developed to represent the more exact flow field due to wire-wrap. Other models, such as heat conductor model and various turbulent mixing model, have been implemented into the MATRA-LMR. The ORNL THORS 19-Pin FFM-5B tests have been assessed to validate above new models using the improved MATRA-LMR. The results using MATRA-LMR were well agreed with the experimental data. The subchannel blockage accidents which assumed to be occurred at the three locations for the conceptual plant of KALIMER-600 have been analysed according to blockage size using the MATRA-LMR code. The results of calculations for the design basis events which 6 subchannels were blocked showed the margins of the 290 7.dog. C up to the

  20. Development of safety enhancement technology of containment building

    International Nuclear Information System (INIS)

    Seo, Jeong Moon; Choun, Y. S.; Choi, I. K.

    2002-04-01

    This study consists of four research areas, (1) Seismic safety assessment, (2) Aging assessment of a containment building, (3) Prediction of long-term behavior and analysis of a containment building, (4) Performance verification of a containment building. In the seismic safety assessment area, responses of a containment building were monitored and the analysis method was verified. Also performed are the identification of earthquake characteristics and improvement of the seismic fragility analysis method. In the area of aging assessment of a containment building, we developed aging management code SLMS and database. Aging tests were performed for containment building materials and aging models were developed. Techniques for investigation, detection, and evaluation of aging were developed. In the area of prediction of long-term behavior and analysis of a containment building, we developed a non-linear structural analysis code NUCAS and material models. In the area of performance verification of a containment building, we analyzed the crack behavior of a containment wall and the behavior of the containment under internal pressure. We also improved the ISI methods for prestressed containment

  1. Economic Developments on Perceived Safety, Violence, and Economic Benefits

    Directory of Open Access Journals (Sweden)

    Anthony Fabio

    2015-01-01

    Full Text Available Background. Emerging research highlights the promise of community- and policy-level strategies in preventing youth violence. Large-scale economic developments, such as sports and entertainment arenas and casinos, may improve the living conditions, economics, public health, and overall wellbeing of area residents and may influence rates of violence within communities. Objective. To assess the effect of community economic development efforts on neighborhood residents’ perceptions on violence, safety, and economic benefits. Methods. Telephone survey in 2011 using a listed sample of randomly selected numbers in six Pittsburgh neighborhoods. Descriptive analyses examined measures of perceived violence and safety and economic benefit. Responses were compared across neighborhoods using chi-square tests for multiple comparisons. Survey results were compared to census and police data. Results. Residents in neighborhoods with the large-scale economic developments reported more casino-specific and arena-specific economic benefits. However, 42% of participants in the neighborhood with the entertainment arena felt there was an increase in crime, and 29% of respondents from the neighborhood with the casino felt there was an increase. In contrast, crime decreased in both neighborhoods. Conclusions. Large-scale economic developments have a direct influence on the perception of violence, despite actual violence rates.

  2. The need for strategic development of safety sciences.

    Science.gov (United States)

    Busquet, Francois; Hartung, Thomas

    2017-01-01

    The practice of risk assessment and regulation of substances has largely developed as a patchwork of circumstantial additions to a nowadays more or less shared international toolbox. The dominant drivers from the US and Europe have pursued remarkably different approaches in the use of these tools for regulation, i.e., a more risk-based approach in the US and a more precautionary approach in Europe. We argue that there is need for scientific developments not only for the tools but also for their application, i.e., a need for Regulatory Science or, perhaps better, Safety Science. While some of this is emerging on the US side as strategic reports, e.g., from the National Academies, the NIH and the regulatory agencies, especially the EPA and the FDA, such strategic developments beyond technological developments are largely lacking in Europe or have started only recently at EFSA, ECHA or within the flagship project EU-ToxRisk. This article provides a rationale for the creation of a European Safety Sciences Institute (ESSI) based on regulatory and scientific needs, political context and current EU missions. Moreover, the possible modus operandi of ESSI will be described along with possible working formats as well as anticipated main tasks and duties. This mirrors the triple alliance on the American side (US EPA, NIH and FDA) in revamping regulatory sciences. Moreover, this could fit the political agenda of the European Commission for better implementation of existing EU legislation rather than creating new laws.

  3. Development of Audit Calculation Methodology for RIA Safety Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joosuk; Kim, Gwanyoung; Woo, Swengwoong [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2015-05-15

    The interim criteria contain more stringent limits than previous ones. For example, pellet-to-cladding mechanical interaction(PCMI) was introduced as a new failure criteria. And both short-term (e.g. fuel-to coolant interaction, rod burst) and long-term(e.g., fuel rod ballooning, flow blockage) phenomena should be addressed for core coolability assurance. For dose calculations, transient-induced fission gas release has to be accounted additionally. Traditionally, the approved RIA analysis methodologies for licensing application are developed based on conservative approach. But newly introduced safety criteria tend to reduce the margins to the criteria. Thereby, licensees are trying to improve the margins by utilizing a less conservative approach. In this situation, to cope with this trend, a new audit calculation methodology needs to be developed. In this paper, the new methodology, which is currently under developing in KINS, was introduced. For the development of audit calculation methodology of RIA safety analysis based on the realistic evaluation approach, preliminary calculation by utilizing the best estimate code has been done on the initial core of APR1400. Followings are main conclusions. - With the assumption of single full-strength control rod ejection in HZP condition, rod failure due to PCMI is not predicted. - And coolability can be assured in view of entalphy and fuel melting. - But, rod failure due to DNBR is expected, and there is possibility of fuel failure at the rated power conditions also.

  4. Analysis of developed transition road safety barrier systems.

    Science.gov (United States)

    Soltani, Mehrtash; Moghaddam, Taher Baghaee; Karim, Mohamed Rehan; Sulong, N H Ramli

    2013-10-01

    Road safety barriers protect vehicles from roadside hazards by redirecting errant vehicles in a safe manner as well as providing high levels of safety during and after impact. This paper focused on transition safety barrier systems which were located at the point of attachment between a bridge and roadside barriers. The aim of this study was to provide an overview of the behavior of transition systems located at upstream bridge rail with different designs and performance levels. Design factors such as occupant risk and vehicle trajectory for different systems were collected and compared. To achieve this aim a comprehensive database was developed using previous studies. The comparison showed that Test 3-21, which is conducted by impacting a pickup truck with speed of 100 km/h and angle of 25° to transition system, was the most severe test. Occupant impact velocity and ridedown acceleration for heavy vehicles were lower than the amounts for passenger cars and pickup trucks, and in most cases higher occupant lateral impact ridedown acceleration was observed on vehicles subjected to higher levels of damage. The best transition system was selected to give optimum performance which reduced occupant risk factors using the similar crashes in accordance with Test 3-21. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Development of Onsite Transportation Safety Documents for Nevada Test Site

    International Nuclear Information System (INIS)

    Frank Hand; Willard Thomas; Frank Sciacca; Manny Negrete; Susan Kelley

    2008-01-01

    Department of Energy (DOE) Orders require each DOE site to develop onsite transportation safety documents (OTSDs). The Nevada Test Site approach divided all onsite transfers into two groups with each group covered by a standalone OTSD identified as Non-Nuclear and Nuclear. The Non-Nuclear transfers involve all radioactive hazardous material in less than Hazard Category (HC)-3 quantities and all chemically hazardous materials. The Nuclear transfers involve all radioactive material equal to or greater than HC-3 quantities and radioactive material mated with high explosives regardless of quantity. Both OTSDs comply with DOE O 460.1B requirements. The Nuclear OTSD also complies with DOE O 461.1A requirements and includes a DOE-STD-3009 approach to hazard analysis (HA) and accident analysis as needed. All Nuclear OTSD proposed transfers were determined to be non-equivalent and a methodology was developed to determine if 'equivalent safety' to a fully compliant Department of Transportation (DOT) transfer was achieved. For each HA scenario, three hypothetical transfers were evaluated: a DOT-compliant, uncontrolled, and controlled transfer. Equivalent safety is demonstrated when the risk level for each controlled transfer is equal to or less than the corresponding DOT-compliant transfer risk level. In this comparison the typical DOE-STD-3009 risk matrix was modified to reflect transportation requirements. Design basis conditions (DBCs) were developed for each non-equivalent transfer. Initial DBCs were based solely upon the amount of material present. Route-, transfer-, and site-specific conditions were evaluated and the initial DBCs revised as needed. Final DBCs were evaluated for each transfer's packaging and its contents

  6. Developing Measures for Assessing the Causality of Safety Culture in a Petrochemical Industry

    Energy Technology Data Exchange (ETDEWEB)

    Wu, T.-C., E-mail: tcwu@sunrise.hk.edu.t [HungKuang University, Department of Safety, Health and Environmental Engineering (China); Lin, C.-H.; Shiau, S.-Y. [HungKuang University, Institute of Occupational Safety and Hazard Prevention (China)

    2009-12-15

    This paper discusses safety culture in the petrochemical sector and the causes and consequences of safety culture. A sample of 520 responses selected by simple random sampling completed questionnaires for this survey, the return rate was 86.75%. The research instrument comprises four sections: basic information, the safety leadership scale (SLS), the safety climate scale (SCS), and the safety performance scale (SPS). SPSS 12.0, a statistical software package, was used for item analysis, validity analysis, and reliability analysis. Exploratory factor analysis indicated that (1) SLS abstracted three factors such as safety caring, safety controlling, and safety coaching; (2) SCS comprised three factors such as emergency response, safety commitment, and risk perception; and (3) SPS was composed of accident investigation, safety training, safety inspections, and safety motivation. We conclude that the SLS, SCS, and SPS developed in this paper have good construct validity and internal consistency and can serve as the basis for future research.

  7. Developing Measures for Assessing the Causality of Safety Culture in a Petrochemical Industry

    International Nuclear Information System (INIS)

    Wu, T.-C.; Lin, C.-H.; Shiau, S.-Y.

    2009-01-01

    This paper discusses safety culture in the petrochemical sector and the causes and consequences of safety culture. A sample of 520 responses selected by simple random sampling completed questionnaires for this survey, the return rate was 86.75%. The research instrument comprises four sections: basic information, the safety leadership scale (SLS), the safety climate scale (SCS), and the safety performance scale (SPS). SPSS 12.0, a statistical software package, was used for item analysis, validity analysis, and reliability analysis. Exploratory factor analysis indicated that (1) SLS abstracted three factors such as safety caring, safety controlling, and safety coaching; (2) SCS comprised three factors such as emergency response, safety commitment, and risk perception; and (3) SPS was composed of accident investigation, safety training, safety inspections, and safety motivation. We conclude that the SLS, SCS, and SPS developed in this paper have good construct validity and internal consistency and can serve as the basis for future research.

  8. Development of a safety case editor with assessment features

    NARCIS (Netherlands)

    Luo, Y.; Li, Z.; van den Brand, M.G.J.

    2016-01-01

    A safety case is an argumentation for showing confidence in the claimed safety assurance of a system, which should be comprehensible and well-structured. Typically, safety cases are represented in plain text, but the structure of safety cases might become ambiguous and unclear. To address this, the

  9. Future generations of CANDU: advantages and development with passive safety

    International Nuclear Information System (INIS)

    Duffey, R. B.

    2006-01-01

    Atomic Energy of Canada Limited (AECL) advances water reactor and CANDLT technology using an evolutionary development strategy. This strategy ensures that innovations are based firmly on current experience and keeps our development programs focused on one reactor concept, reducing risks, development costs, and product development cycle times. It also assures our customers that our products will never become obsolete or unsupported, and the continuous line of water reactor development is secure and supported into the future. Using the channel reactor advantage of modularity, the subdivided core has the advantage of passive safety by heat removal to the low- pressure moderator. With continuous improvements, the Advanced CANDU Reactor TM (ACR-1000TM) concept will likely remain highly competitive for a number of years and leads naturally to the next phase of CANDU development, namely the Generation IV CANDU -SCWR concept. This is conventional water technology, since supercritical boilers and turbines have been operating for some time in coal-fired power plants. Significant cost, safety, and performance advantages would result from the CANDU-SCWR concept, plus the flexibility of a range of plant sizes suitable for both small and large electric grids, and the ability for co-generation of electric power, process heat, and hydrogen. In CANDU-SCWR, novel developments are included in the primary circuit layout and channel design. The R and D in Canada is integrated with the Generation IV international Forum (GIF) plans, and has started on examining replaceable insulating liners that would ensure channel life, and on providing completely passive reactor decay heat removal directly to the moderator heat sink without forced cooling. In the interests of sustainability, hydrogen production by a CANDU- SCWR is also be included as part of the system requirements, where the methods for hydrogen production will depend on the outlet temperature of the reactor

  10. Development and application of the San Onofre safety monitor

    International Nuclear Information System (INIS)

    Hook, Thomas G.; Lee, Roger J.; Morgan, Thomas A.

    2004-01-01

    Halliburton NUS Corporation (NUS) has developed a risk-based configuration management software tool for use at Southern California Edison's San Onofre Nuclear Generating Station. The software, called the Safety Monitor, calculates an estimate of current plant core damage risk based upon the plant's current operating configuration (e.g., equipment operability, system operating alignments). All data is entered and displayed in a format easily understood by plant personnel. The plant hopes to use this tool to ensure that risk is minimized during plant operations and to identify situations in which current Technical Specifications can be optimized. Plant configuration data and out-of-service time data is also automatically collected. (author)

  11. Development of IAEA description of passive safety and subsequent thoughts

    Energy Technology Data Exchange (ETDEWEB)

    Lang, P M [USDOE, Washington, DC (United States)

    1996-12-01

    The description of passive components and systems published by the IAEA in its TECDOC-626 was developed in the course of a Technical Committee Meeting held in Sweden and two subsequent Consultants Meetings held in Vienna. This description is reviewed and discussed in terms of the philosophies behind it, alternatives considered, problems encountered, and conclusions drawn. Also discussed is an Appendix to the TECDOC, which illustrates the spectrum of possibilities from passive to active by describing four typical categories of passivity. Subsequent thoughts on passive safety include a discussion of its advantages and disadvantages, concluding with a summary of current views and problems with it. (author). 8 refs.

  12. Multilevel Safety Climate and Safety Performance in the Construction Industry: Development and Validation of a Top-Down Mechanism

    Directory of Open Access Journals (Sweden)

    Ran Gao

    2016-11-01

    Full Text Available The character of construction projects exposes front-line workers to dangers and accidents. Safety climate has been confirmed to be a predictor of safety performance in the construction industry. This study aims to explore the underlying mechanisms of the relationship between multilevel safety climate and safety performance. An integrated model was developed to study how particular safety climate factors of one level affect those of other levels, and then affect safety performance from the top down. A questionnaire survey was administered on six construction sites in Vietnam. A total of 1030 valid questionnaires were collected from this survey. Approximately half of the data were used to conduct exploratory factor analysis (EFA and the remaining data were submitted to structural equation modeling (SEM. Top management commitment (TMC and supervisors’ expectation (SE were identified as factors to represent organizational safety climate (OSC and supervisor safety climate (SSC, respectively, and coworkers’ caring and communication (CCC and coworkers’ role models (CRM were identified as factors to denote coworker safety climate (CSC. SEM results show that OSC factor is positively related to SSC factor and CSC factors significantly. SSC factor could partially mediate the relationship between OSC factor and CSC factors, as well as the relationship between OSC factor and safety performance. CSC factors partially mediate the relationship between OSC factor and safety performance, and the relationship between SSC factor and safety performance. The findings imply that a positive safety culture should be established both at the organizational level and the group level. Efforts from all top management, supervisors, and coworkers should be provided to improve safety performance in the construction industry.

  13. Multilevel Safety Climate and Safety Performance in the Construction Industry: Development and Validation of a Top-Down Mechanism.

    Science.gov (United States)

    Gao, Ran; Chan, Albert P C; Utama, Wahyudi P; Zahoor, Hafiz

    2016-11-08

    The character of construction projects exposes front-line workers to dangers and accidents. Safety climate has been confirmed to be a predictor of safety performance in the construction industry. This study aims to explore the underlying mechanisms of the relationship between multilevel safety climate and safety performance. An integrated model was developed to study how particular safety climate factors of one level affect those of other levels, and then affect safety performance from the top down. A questionnaire survey was administered on six construction sites in Vietnam. A total of 1030 valid questionnaires were collected from this survey. Approximately half of the data were used to conduct exploratory factor analysis (EFA) and the remaining data were submitted to structural equation modeling (SEM). Top management commitment (TMC) and supervisors' expectation (SE) were identified as factors to represent organizational safety climate (OSC) and supervisor safety climate (SSC), respectively, and coworkers' caring and communication (CCC) and coworkers' role models (CRM) were identified as factors to denote coworker safety climate (CSC). SEM results show that OSC factor is positively related to SSC factor and CSC factors significantly. SSC factor could partially mediate the relationship between OSC factor and CSC factors, as well as the relationship between OSC factor and safety performance. CSC factors partially mediate the relationship between OSC factor and safety performance, and the relationship between SSC factor and safety performance. The findings imply that a positive safety culture should be established both at the organizational level and the group level. Efforts from all top management, supervisors, and coworkers should be provided to improve safety performance in the construction industry.

  14. Calculating the cost of research and Development in nuclear and radiation safety

    International Nuclear Information System (INIS)

    Matsulevich, N.Je.; Nosovs'ka, A.A.

    2010-01-01

    Methodological support assessing the cost of research and development in the area of nuclear and radiation safety regulation is considered. Basic methodological recommendations for determining labor expenditures for research and development in nuclear and radiation safety are provided.

  15. Role of management in the development of safety culture at the operating organization

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, W [International Atomic Energy Agency, Vienna (Austria)

    1997-09-01

    Role of management in the development of safety culture at the operating organization to offer practical suggestions to assist in the development or improvement of a progressive safety culture. 2 figs.

  16. Role of management in the development of safety culture at the operating organization

    International Nuclear Information System (INIS)

    Zhong, W.

    1997-01-01

    Role of management in the development of safety culture at the operating organization to offer practical suggestions to assist in the development or improvement of a progressive safety culture. 2 figs

  17. Nuclear Safeguards Infrastructure Development and Integration with Safety and Security

    International Nuclear Information System (INIS)

    Kovacic, Donald N.; Raffo-Caiado, Ana Claudia; McClelland-Kerr, John; Van sickle, Matthew; Bissani, Mo

    2009-01-01

    Faced with increasing global energy demands, many developing countries are considering building their first nuclear power plant. As a country embarks upon or expands its nuclear power program, it should consider how it will address the 19 issues laid out in the International Atomic Energy Agency (IAEA) document Milestones in Development of a National Infrastructure for Nuclear Power. One of those issues specifically addresses the international nonproliferation treaties and commitments and the implementation of safeguards to prevent diversion of nuclear material from peaceful purposes to nuclear weapons. Given the many legislative, economic, financial, environmental, operational, and other considerations preoccupying their planners, it is often difficult for countries to focus on developing the core strengths needed for effective safeguards implementation. Typically, these countries either have no nuclear experience or it is limited to the operation of research reactors used for radioisotope development and scientific research. As a result, their capacity to apply safeguards and manage fuel operations for a nuclear power program is limited. This paper argues that to address the safeguards issue effectively, a holistic approach must be taken to integrate safeguards with the other IAEA issues including safety and security - sometimes referred to as the '3S' concept. Taking a holistic approach means that a country must consider safeguards within the context of its entire nuclear power program, including operations best practices, safety, and security as well as integration with its larger nonproliferation commitments. The Department of Energy/National Nuclear Security Administration's International Nuclear Safeguards and Engagement Program (INSEP) has been involved in bilateral technical cooperation programs for over 20 years to promote nonproliferation and the peaceful uses of nuclear energy. INSEP is currently spearheading efforts to promote the development of

  18. RAMONA-4B development for SBWR safety studies

    Energy Technology Data Exchange (ETDEWEB)

    Rohatgi, U.S.; Aronson, A.L.; Cheng, H.S.; Khan, H.J.; Mallen, A.N.

    1993-12-31

    The Simplified Boiling Water Reactor (SBWR) is a revolutionary design of a boiling-water reactor. The reactor is based on passive safety systems such as natural circulation, gravity flow, pressurized gas, and condensation. SBWR has no active systems, and the flow in the vessel is by natural circulation. There is a large chimney section above the core to provide a buoyancy head for natural circulation. The reactor can be shut down by either of four systems; namely, scram, Fine Motion Control Rod Drive (FMCRD), Alternate Rod Insertion (ARI), and Standby Liquid Control System (SLCS). The safety injection is by gravity drain from the Gravity Driven Cooling System (GDCS) and Suppression Pool (SP). The heat sink is through two types of heat exchangers submerged in the tank of water. These heat exchangers are the Isolation Condenser (IC) and the Passive Containment Cooling System (PCCS). The RAMONA-4B code has been developed to simulate the normal operation, reactivity transients, and to address the instability issues for SBWR. The code has a three-dimensional neutron kinetics coupled to multiple parallel-channel thermal-hydraulics. The two-phase thermal hydraulics is based on a nonhomogeneous nonequilibrium drift-flux formulation. It employs an explicit integration to solve all state equations (except for neutron kinetics) in order to predict the instability without numerical damping. The objective of this project is to develop a Sun SPARC and IBM RISC 6000 based RAMONA-4B code for applications to SBWR safety analyses, in particular for stability and ATWS studies.

  19. RAMONA-4B development for SBWR safety studies

    International Nuclear Information System (INIS)

    Rohatgi, U.S.; Aronson, A.L.; Cheng, H.S.; Khan, H.J.; Mallen, A.N.

    1993-01-01

    The Simplified Boiling Water Reactor (SBWR) is a revolutionary design of a boiling-water reactor. The reactor is based on passive safety systems such as natural circulation, gravity flow, pressurized gas, and condensation. SBWR has no active systems, and the flow in the vessel is by natural circulation. There is a large chimney section above the core to provide a buoyancy head for natural circulation. The reactor can be shut down by either of four systems; namely, scram, Fine Motion Control Rod Drive (FMCRD), Alternate Rod Insertion (ARI), and Standby Liquid Control System (SLCS). The safety injection is by gravity drain from the Gravity Driven Cooling System (GDCS) and Suppression Pool (SP). The heat sink is through two types of heat exchangers submerged in the tank of water. These heat exchangers are the Isolation Condenser (IC) and the Passive Containment Cooling System (PCCS). The RAMONA-4B code has been developed to simulate the normal operation, reactivity transients, and to address the instability issues for SBWR. The code has a three-dimensional neutron kinetics coupled to multiple parallel-channel thermal-hydraulics. The two-phase thermal hydraulics is based on a nonhomogeneous nonequilibrium drift-flux formulation. It employs an explicit integration to solve all state equations (except for neutron kinetics) in order to predict the instability without numerical damping. The objective of this project is to develop a Sun SPARC and IBM RISC 6000 based RAMONA-4B code for applications to SBWR safety analyses, in particular for stability and ATWS studies

  20. Developments related to the National Nuclear Safety Authority of Romania

    International Nuclear Information System (INIS)

    Baciu, Florin

    1998-01-01

    The contribution presents the status of the National Commission for Nuclear Activity Control (CNCAN) as indicated by the provisions of a Romanian Government Decision of May 1998. As specified in the art.3 the main tasks of the Commission are the following: to issue authorization and exercise permits of activities in nuclear field; to supervise the applications of the provisions stipulated by the law concerning development in safety conditions of nuclear activities; to develop instructions as well as nuclear safety regulations to ensure the quality assurance and functioning in safety conditions of the nuclear facilities and plants, the protection against nuclear radiation of the professionally exposed personnel, of the population, of the environment and of the material goods, the physical protection, the records, preservation and transport of radioactive material and of fissionable materials as well as the management of radioactive waste; organizes expert and is responsible for the state control concerning the integrated application of the law provisions in the field of quality constructions in which nuclear installations of national interest are located, during all the phases and for all the components of the quality system in this field; issues specialty and information documentation specific to its own activity, provides the information of the public through official publication, official statements to the press and other specific form of information; carries out any other tasks provided by law in the field of regulations and control of nuclear activity. Author presents also the CNCAN staff number evolution, the new structure, the staff distribution at headquarters, local agencies and national radiation monitoring network. Finally, the author discusses the legal provisions related to management manual procedures

  1. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  2. Conclusions and Recommendations of the IAEA International Conference on Topical Issues in Nuclear Safety: Ensuring Safety for Sustainable Nuclear Development

    International Nuclear Information System (INIS)

    El-Shanawany, Mamdouh

    2011-01-01

    Over 200 participants from 33 countries and three international organizations came and actively participated and contributed to focused discussions and the success of the conference. The following points summarize the key conclusions and recommendations of the conference with respect to nuclear safety. 1. The nuclear safety approach is based on the philosophy developed in the 60's: defense in depth principles and deterministic criteria. When properly applied and completed by probabilistic analyses and operational experience feedback, it continues to be a successful approach. However, guarding against the risk of accidents requires constant vigilance and high technical competence and a never ending fight against complacency. In this context, having a strong leadership with a commitment to continuous improvement and a vision of sustained excellence is a key element of nuclear safety. Continuous improvement in safety also should be pursued through scientific research and operational experience feedback. 2. An accident anywhere is of concern to all Member States. Therefore, it is in the interest of all Member States to share and collaborate on safety matters. Participation of all Member States in international nuclear safety instruments and conventions, including liability for nuclear damage, is considered beneficial to global safety. The Convention on Nuclear Safety, the Joint Convention, international cooperation through IAEA and other organizations, bilateral or multilateral arrangements are important elements for establishing networks for sharing and transferring knowledge. It is acknowledged that the IAEA's Safety Fundamentals and Safety Requirements provide a sound foundation for high level nuclear safety. IAEA Safety Standards should be the basis for the establishment and maintenance of safety infrastructure. The IAEA's peer reviews and services such as IRRS, OSART, Site Evaluation and Reactor Safety Reviews provide also a valuable platform for sharing

  3. Main Conclusions and Recommendations of International Conference on Topical Issues in Nuclear Installation Safety: Ensuring Safety for Sustainable Nuclear Development

    International Nuclear Information System (INIS)

    El-Shanawany, Mamdouh

    2011-01-01

    Over 200 participants from 33 countries and three international organizations came and actively participated and contributed to focused discussions and the success of the conference. The following points summarize the key conclusions and recommendations of the conference with respect to nuclear safety. 1. The nuclear safety approach is based on the philosophy developed in the 60's: defense in depth principles and deterministic criteria. When properly applied and completed by probabilistic analyses and operational experience feedback, it continues to be a successful approach. However, guarding against the risk of accidents requires constant vigilance and high technical competence and a never ending fight against complacency. In this context, having a strong leadership with a commitment to continuous improvement and a vision of sustained excellence is a key element of nuclear safety. Continuous improvement in safety also should be pursued through scientific research and operational experience feedback. 2. An accident anywhere is of concern to all Member States. Therefore, it is in the interest of all Member States to share and collaborate on safety matters. Participation of all Member States in international nuclear safety instruments and conventions, including liability for nuclear damage, is considered beneficial to global safety. The Convention on Nuclear Safety, the Joint Convention, international cooperation through IAEA and other organizations, bilateral or multilateral arrangements are important elements for establishing networks for sharing and transferring knowledge. It is acknowledged that the IAEA's Safety Fundamentals and Safety Requirements provide a sound foundation for high level nuclear safety. IAEA Safety Standards should be the basis for the establishment and maintenance of safety infrastructure. The IAEA's peer reviews and services such as IRRS, OSART, Site Evaluation and Reactor Safety Reviews provide also a valuable platform for sharing

  4. Development of safety culture - A Chinese traditional cultural perspective

    International Nuclear Information System (INIS)

    Zhou Weihong . E-mail zhouwh@lanps.com

    2002-01-01

    Living in a social community, the culture of an enterprise is certainly under the influence of that society. Safety culture of nuclear utilities is the core of the enterprise culture. As a formal expression as defined in INSAG 3 and 4 by IAEA, it as a matter of fact originated from the summing up of the experiences of western nuclear industry, particularly after such epoch-making accidents of Three Miles Island and Chernobyl. In view of the geographical culture theory, whether or not this conception of western industrial culture will be absorbed and assimilated by Chinese Nuclear Industry is a challenging issue. This is because, on the one hand, Nuclear Power is comparatively speaking a newly developing industry in China and, on the other hand, China has enjoyed an uninterrupted history of traditional culture over five thousand years. In other words, whether the new and alien values will conflict with or be constructively assimilated by our traditional mindset is a critical question to be answered in any development program of safety culture. (author)

  5. HTGR Dust Safety Issues and Needs for Research and Development

    Energy Technology Data Exchange (ETDEWEB)

    Paul W. Humrickhouse

    2011-06-01

    This report presents a summary of high temperature gas-cooled reactor dust safety issues. It draws upon a literature review and the proceedings of the Very High Temperature Reactor Dust Assessment Meeting held in Rockville, MD in March 2011 to identify and prioritize the phenomena and issues that characterize the effect of carbonaceous dust on high temperature reactor safety. It reflects the work and input of approximately 40 participants from the U.S. Department of Energy and its National Labs, the U.S. Nuclear Regulatory Commission, industry, academia, and international nuclear research organizations on the topics of dust generation and characterization, transport, fission product interactions, and chemical reactions. The meeting was organized by the Idaho National Laboratory under the auspices of the Next Generation Nuclear Plant Project, with support from the U.S. Nuclear Regulatory Commission. Information gleaned from the report and related meetings will be used to enhance the fuel, graphite, and methods technical program plans that guide research and development under the Next Generation Nuclear Plant Project. Based on meeting discussions and presentations, major research and development needs include: generating adsorption isotherms for fission products that display an affinity for dust, investigating the formation and properties of carbonaceous crust on the inside of high temperature reactor coolant pipes, and confirming the predominant source of dust as abrasion between fuel spheres and the fuel handling system.

  6. Development of a safety analysis code for molten salt reactors

    International Nuclear Information System (INIS)

    Zhang Dalin; Qiu Suizheng; Su Guanghui

    2009-01-01

    The molten salt reactor (MSR) well suited to fulfill the criteria defined by the Generation IV International Forum (GIF) is presently revisited all around the world because of different attractive features of current renewed relevance. The MSRs are characterized by using the fluid-fuel, so that their technologies are fundamentally different from those used in the conventional solid-fuel reactors. In this work, in particular, the attention is focused on the safety characteristic analysis of the MSRs, in which a point kinetic model considering the flow effects of the fuel salt is established for the MSRs and calculated by developing a microcomputer code coupling with a simplified heat transfer model in the core. The founded models and developed code are applied to analyze the safety characteristics of the molten salt actinide recycler and transmuter system (MOSART) by simulating three types of basic transient conditions including the unprotected loss of flow, unprotected overcooling accident and unprotected transient overpower. Some reasonable results are obtained for the MOSART, which show that the MOSART conceptual design is an inherently stable reactor design. The present study provides some valuable information for the research and design of the new generation MSRs.

  7. Development of Regulatory Audit Core Safety Code : COREDAX

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chae Yong; Jo, Jong Chull; Roh, Byung Hwan [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of); Lee, Jae Jun; Cho, Nam Zin [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    2005-07-01

    Korea Institute of Nuclear Safety (KINS) has developed a core neutronics simulator, COREDAX code, for verifying core safety of SMART-P reactor, which is technically supported by Korea Advanced Institute of Science and Technology (KAIST). The COREDAX code would be used for regulatory audit calculations of 3- dimendional core neutronics. The COREDAX code solves the steady-state and timedependent multi-group neutron diffusion equation in hexagonal geometry as well as rectangular geometry by analytic function expansion nodal (AFEN) method. AFEN method was developed at KAIST, and it was internationally verified that its accuracy is excellent. The COREDAX code is originally programmed based on the AFEN method. Accuracy of the code on the AFEN method was excellent for the hexagonal 2-dimensional problems, but there was a need for improvement for hexagonal-z 3-dimensional problems. Hence, several solution routines of the AFEN method are improved, and finally the advanced AFEN method is created. COREDAX code is based on the advanced AFEN method . The initial version of COREDAX code is to complete a basic framework, performing eigenvalue calculations and kinetics calculations with thermal-hydraulic feedbacks, for audit calculations of steady-state core design and reactivity-induced accidents of SMART-P reactor. This study describes the COREDAX code for hexagonal geometry.

  8. Use and development of probabilistic safety assessment - CSNI WGRISK

    International Nuclear Information System (INIS)

    Siu, Nathan; Monninger, John; Gomez-Cobo, Ana; Kao, Tsu-Mu; Schoen, Gerhard; Gunsell, Lars; Nyman, Ralph; Jelinek, Tomas; Hultquist, Goeran; Rapp, Anders; Eriksson, Stefan; Lantaron, Alfredo; Vojnovic, Djordje; Husarcek, Jan; Kovacs, Zoltan; Versteeg, M.F.; Lopez Morones, Ramon; Lee, Chang-Ju; Fukuda, Mamoru; Burgazzi, Luciano; Caporali, Rino; RoeWEKAMP, Marina; MACSUGA, Geza; Bareith, Attila; Lanore, J.M.; Sorel, Vincent; Virolainen, Reino; Patrik, Milan; Mlady, Ondrej; Raducu, Gheorghe; De Gelder, Pieter; Hendrickx, Isabelle; Lanore, Jeanne-Marie; Murphy, Joseph A.; Shepherd, Charles; Pyy, Pekka T.; Mauny, Elisabeth

    2007-01-01

    The CSNI WGRISK produced a report in July 2002 on 'The Use and Development of Probabilistic Safety Assessment in NEA Member Countries'. This provides a description of the PSA programmes in the member countries at the time that the report was produced. However, there have been significant developments in PSA since 2002. Consequently, a decision was made at the WGRISK meeting in October 2005 to produce an updated version of the report. The aim was to produce an updated, stand alone version of the report that presents an analysis of the position on the use and development of PSA in the WGRISK member countries as of spring 2006. A detailed questionnaire was circulated to WGRISK members and to the IAEA to ascertain the state of the art in PSA use and development at the end of 2006. Detailed responses were prepared by 20 countries totalling several hundred pages of information. After first compilation of information, an updating round was organized by showing to the countries all the answers and the summary made of them by a small group of experts. The process led to some clarifications and more consistency in the report. The collected information was finally analyzed and summarized to reach the conclusions presented in this report. The set of section headings in the report is as follows: Executive summary. 1. Introduction. 2. PSA Framework and Environment. 3. Numerical Safety Criteria. 4. PSA Standards and Guidance. 5. Status and Scope of PSA Programmes. 6. PSA Methodology and Data. 7. PSA Applications. 8. Results and Insights from the PSAs. 9. Future Developments. Appendix A: Overview of the Status of PSA Programmes. Appendix B: Contact information. Appendix C: Questionnaire and Guidance to authors

  9. Evaluation of criteria for developing traffic safety materials for Latinos.

    Science.gov (United States)

    Streit-Kaplan, Erica L; Miara, Christine; Formica, Scott W; Gallagher, Susan Scavo

    2011-03-01

    This quantitative study assessed the validity of guidelines that identified four key characteristics of culturally appropriate Spanish-language traffic safety materials: language, translation, formative evaluation, and credible source material. From a sample of 190, the authors randomly selected 12 Spanish-language educational materials for analysis by 15 experts. Hypotheses included that the experts would rate materials with more of the key characteristics as more effective (likely to affect behavioral change) and rate materials originally developed in Spanish and those that utilized formative evaluation (e.g., pilot tests, focus groups) as more culturally appropriate. Although results revealed a weak association between the number of key characteristics in a material and the rating of its effectiveness, reviewers rated materials originally created in Spanish and those utilizing formative evaluation as significantly more culturally appropriate. The findings and methodology demonstrated important implications for developers and evaluators of any health-related materials for Spanish speakers and other population groups.

  10. Developing an OMERACT Core Outcome Set for Assessing Safety Components in Rheumatology Trials: The OMERACT Safety Working Group.

    Science.gov (United States)

    Klokker, Louise; Tugwell, Peter; Furst, Daniel E; Devoe, Dan; Williamson, Paula; Terwee, Caroline B; Suarez-Almazor, Maria E; Strand, Vibeke; Woodworth, Thasia; Leong, Amye L; Goel, Niti; Boers, Maarten; Brooks, Peter M; Simon, Lee S; Christensen, Robin

    2017-12-01

    Failure to report harmful outcomes in clinical research can introduce bias favoring a potentially harmful intervention. While core outcome sets (COS) are available for benefits in randomized controlled trials in many rheumatic conditions, less attention has been paid to safety in such COS. The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 emphasizes the importance of measuring harms. The Safety Working Group was reestablished at the OMERACT 2016 with the objective to develop a COS for assessing safety components in trials across rheumatologic conditions. The safety issue has previously been discussed at OMERACT, but without a consistent approach to ensure harms were included in COS. Our methods include (1) identifying harmful outcomes in trials of interventions studied in patients with rheumatic diseases by a systematic literature review, (2) identifying components of safety that should be measured in such trials by use of a patient-driven approach including qualitative data collection and statistical organization of data, and (3) developing a COS through consensus processes including everyone involved. Members of OMERACT including patients, clinicians, researchers, methodologists, and industry representatives reached consensus on the need to continue the efforts on developing a COS for safety in rheumatology trials. There was a general agreement about the need to identify safety-related outcomes that are meaningful to patients, framed in terms that patients consider relevant so that they will be able to make informed decisions. The OMERACT Safety Working Group will advance the work previously done within OMERACT using a new patient-driven approach.

  11. Safety

    International Nuclear Information System (INIS)

    2001-01-01

    This annual report of the Senior Inspector for the Nuclear Safety, analyses the nuclear safety at EDF for the year 1999 and proposes twelve subjects of consideration to progress. Five technical documents are also provided and discussed concerning the nuclear power plants maintenance and safety (thermal fatigue, vibration fatigue, assisted control and instrumentation of the N4 bearing, 1300 MW reactors containment and time of life of power plants). (A.L.B.)

  12. Analysis of international approaches which are used at development of theoperational safety performance indicators

    International Nuclear Information System (INIS)

    Lyigots'kij, O.Yi.; Nosovs'kij, A.V.; Chemeris, Yi.O.

    2009-01-01

    Description of international approaches and experience of the use of theoperational safety performance indicators system is provided for estimationof current status and making a decision on corrections in the operationpractice. The state of development of the operational safety performanceindicators system by the operating organization is overviewed. Thepossibility of application of international approaches during development ofthe integral safety performance indicators system is analyzed. Aims and tasksof future researches are formulated in relation to development of theintegral safety performance indicators system.

  13. Developing Expert Teams with a Strong Safety Culture

    Science.gov (United States)

    Rogers, David G.

    2010-01-01

    Would you like to lead a world renowned team that draws out all the talents and expertise of its members and consistently out performs all others in the industry? Ever wonder why so many organizations fail to truly learn from past mistakes only to repeat the same ones at a later date? Are you a program/project manager or team member in a high-risk organization where the decisions made often carry the highest of consequences? Leadership, communication, team building, critical decision-making and continuous team improvement skills and behaviors are mere talking points without the attitudes, commitment and strategies necessary to make them the very fabric of a team. Developing Expert Teams with a Strong Safety Culture, will provide you with proven knowledge and strategies to take your team soaring to heights you may have not thought possible. A myriad of teams have applied these strategies and techniques within their organization team environments: military and commercial aviation, astronaut flight crews, Shuttle flight controllers, members of the Space Shuttle Program Mission Management Team, air traffic controllers, nuclear power control teams, surgical teams, and the fire service report having spectacular success. Many industry leaders are beginning to realize that although the circumstances and environments of these teams may differ greatly to their own, the core elements, governing principles and dynamics involved in managing and building a stellar safety conscious team remain identical.

  14. Modeling the Relationship between Safety Climate and Safety Performance in a Developing Construction Industry: A Cross-Cultural Validation Study.

    Science.gov (United States)

    Zahoor, Hafiz; Chan, Albert P C; Utama, Wahyudi P; Gao, Ran; Zafar, Irfan

    2017-03-28

    This study attempts to validate a safety performance (SP) measurement model in the cross-cultural setting of a developing country. In addition, it highlights the variations in investigating the relationship between safety climate (SC) factors and SP indicators. The data were collected from forty under-construction multi-storey building projects in Pakistan. Based on the results of exploratory factor analysis, a SP measurement model was hypothesized. It was tested and validated by conducting confirmatory factor analysis on calibration and validation sub-samples respectively. The study confirmed the significant positive impact of SC on safety compliance and safety participation , and negative impact on number of self-reported accidents/injuries . However, number of near-misses could not be retained in the final SP model because it attained a lower standardized path coefficient value. Moreover, instead of safety participation , safety compliance established a stronger impact on SP. The study uncovered safety enforcement and promotion as a novel SC factor, whereas safety rules and work practices was identified as the most neglected factor. The study contributed to the body of knowledge by unveiling the deviations in existing dimensions of SC and SP. The refined model is expected to concisely measure the SP in the Pakistani construction industry, however, caution must be exercised while generalizing the study results to other developing countries.

  15. Development of a safety decision-making scenario to measure worker safety in agriculture.

    Science.gov (United States)

    Mosher, G A; Keren, N; Freeman, S A; Hurburgh, C R

    2014-04-01

    Human factors play an important role in the management of occupational safety, especially in high-hazard workplaces such as commercial grain-handling facilities. Employee decision-making patterns represent an essential component of the safety system within a work environment. This research describes the process used to create a safety decision-making scenario to measure the process that grain-handling employees used to make choices in a safety-related work task. A sample of 160 employees completed safety decision-making simulations based on a hypothetical but realistic scenario in a grain-handling environment. Their choices and the information they used to make their choices were recorded. Although the employees emphasized safety information in their decision-making process, not all of their choices were safe choices. Factors influencing their choices are discussed, and implications for industry, management, and workers are shared.

  16. Technical co-operation for nuclear safety in developing countries

    International Nuclear Information System (INIS)

    Flakus, F.N.; Giuliani, P.

    1984-01-01

    The Agency's programme on technical co-operation for nuclear safety is, largely, responsive in character and the Agency's response is tailored to needs identified by developing countries. However, the Agency's assistance alone is not sufficient: technical co-operation can only be successful and is most effective when there is also a strong input from the counterpart body participating in a particular project. The commitment of national governments is fundamental to success. Technical co-operation is most fruitful if the Agency's assistance capabilities and the recipient country's co-operation capabilities match. Co-operation activities mostly take the form of single projects hosted by individual institutions within a single country; regional and inter-regional projects are also important

  17. MRI Evaluation and Safety in the Developing Brain

    Science.gov (United States)

    Tocchio, Shannon; Kline-Fath, Beth; Kanal, Emanuel; Schmithorst, Vincent J.; Panigrahy, Ashok

    2015-01-01

    Magnetic resonance imaging (MRI) evaluation of the developing brain has dramatically increased over the last decade. Faster acquisitions and the development of advanced MRI sequences such as magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), perfusion imaging, functional MR imaging (fMRI), and susceptibility weighted imaging (SWI), as well as the use of higher magnetic field strengths has made MRI an invaluable tool for detailed evaluation of the developing brain. This article will provide an overview of the use and challenges associated with 1.5T and 3T static magnetic fields for evaluation of the developing brain. This review will also summarize the advantages, clinical challenges and safety concerns specifically related to MRI in the fetus and newborn, including the implications of increased magnetic field strength, logistics related to transporting and monitoring of neonates during scanning, sedation considerations and a discussion of current technologies such as MRI-conditional neonatal incubators and dedicated small-foot print neonatal intensive care unit (NICU) scanners. PMID:25743582

  18. 75 FR 56112 - Integrated Food Safety System Online Collaboration Development-Cooperative Agreement With the...

    Science.gov (United States)

    2010-09-15

    ... FDA to meet the White House Food Safety Working Group recommendation that the Federal government... development of an integrated food safety system, and the development and implementation of a sustainable model... levels. NCFPD also has past experience directly supporting the White House Food Safety Working Group...

  19. WP-Cave - assessment of feasibility, safety and development potential

    International Nuclear Information System (INIS)

    1989-09-01

    According to SKB R and D-programme 1986, alternative disposal methods will be investigated to provide a basis for selecting a site and a repository system for the Swedish spent nuclear fuel. The present report is a comparison between the WP-Cave and the reference concept KBS-3. The comparison has resulted in the following conclusions: - Both concepts are judged to be able to provide adequate safety. - A utilization of the potential of the WP-Cave requires, however, extensive development in areas where the current state of knowledge and available data are incomplete. - The higher temperatures in the WP-Cave lead to greater uncertainty as to long-term performance. Reducing this uncertainty would require many yaers of research and substantial resources. - Both repositories, including the barriers they incorporate, could be built with a normal adaption of available technology. -It is not possible to say today whether it would be simpler to find suitable sites for one design or the other. - The WP-Cave is considerably more expensive. A future research direction based on a concentrated emplacement of spent fuel along the lines of the WP-Cave is therefore judged to entail greater uncertainty as regards the possibilities of achieving acceptable safety and to require greater resources for research and development, at the same time as the costs of building the repository would be higher. The studies of the WP-Cave as an integral system should therfore be discontinued. Certain barrier designs in the WP-Cave could also be utulized in repository designs with lower temperature, for example the reduction potential of the steel canisters and the hydraulic cage's diversion of groundwater. Studies within these areas are being conducted within SKB and should continue

  20. 77 FR 36606 - Pipeline Safety: Government/Industry Pipeline Research and Development Forum, Public Meeting

    Science.gov (United States)

    2012-06-19

    ...: Threat Prevention --Working Group 2: Leak Detection/Mitigation & Storage --Working Group 3: Anomaly... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID PHMSA-2012-0146] Pipeline Safety: Government/Industry Pipeline Research and Development Forum, Public...

  1. Development and application of nuclear safety goals in Japan. Lessons learnt from the case of 2003 draft safety goals

    International Nuclear Information System (INIS)

    Sugawara, Shin-etsu; Inamura, Tomoaki

    2016-01-01

    The Nuclear Safety Commission in Japan offered a detailed draft of nuclear safety goals to the public in 2003, though its position was ambiguous in nuclear safety regulation. This report shows the circumstances behind the development and application of 2003 draft safety goals based on our interviews with the experts who had been involved in making the draft. According to our interviews, they had intention to utilize safety goals for improving risk management of regulatory authority and nuclear energy industry, such as ameliorating deterministic regulations, accumulating experience of risk assessment and management, promoting related research, and communicating risks with general public. In practice, however, safety goals had functioned as a tool for emphasizing an assertion that 'nuclear power plants had already been safe enough'. We identified the following four major impediments to utilizing safety goals; 1) lack of sharing overall recognition of the importance of establishing safety goals among nuclear community, 2) excessive emphasis of internal event risks which leads to an inferior priority to tackle with the issue of external events risks, 3) adverse effect of 'tunnel-visioned incrementalism', that is, nuclear energy industrial entities are attracted their foci too much on what they have been told to do by regulators or local governments, and, 4) negative attitude to disclose the outcomes of risk assessment for fear of societal reactions. To encourage upcoming safety goals and risk management, this report provides the following points for overcoming these problems; 1) sharing insights on the reasons why nuclear community set up safety goals, 2) introducing the concept of adaptive risk management for maintaining questioning attitude, 3) conducting a periodic review of goal attainment level and also safety goals themselves from the eyes of a detached observer, and, 4) rebuilding relationship with society beginning with arguments with local stakeholders over

  2. Atypical E2f functions are critical for pancreas polyploidization

    NARCIS (Netherlands)

    Matondo, Ramadhan B; Moreno, Eva; Toussaint, Mathilda J M; Tooten, Peter C J; van Essen, Saskia C; van Liere, Elsbeth A; Youssef, Sameh A; Bongiovanni, Laura; de Bruin, Alain

    2018-01-01

    The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of

  3. Development and Validation of a Safety Attitude Scale for Coal Miners in China

    Directory of Open Access Journals (Sweden)

    Xiang Wu

    2017-11-01

    Full Text Available Safety attitude is of vital importance to accident prevention, and the high accident rate in the coal mining industry makes it urgent to undertake research on coal miners’ safety attitude. However, the current literature still lacks a valid and reliable safety attitude measurement scale for coal miners, which stands as a barrier against their safety attitude improvement. In this study, a scale is developed that can be used to measure coal miners’ safety attitude. The preliminary scale was based on an extended literature review. Empirical data were then collected from 725 coal miners using the preliminary scale. Both exploratory and confirmatory factor analyses were undertaken to validate and improve the scale. The final scale, which consists of 17 items, contains four dimensions: management safety commitment, team safety climate, fatalism and work pressure. Results show that this safety attitude scale can effectively measure the safety attitude of coal miners, showing high psychological measurement validity. This paper contributes to the occupational safety research by developing the factor structure and indicator system of coal miners’ safety attitude, thus providing more profound interpretation of this crucial construct in the safety research domain. The measurement scale serves as an important tool for safety attitude benchmarking among different coal mining enterprises and, thus, can boost the overall safety improvement of the whole industry. These findings can facilitate improvement of both theories and practices related to occupational safety attitude.

  4. KAERI software safety guideline for developing safety-critical software in digital instrumentation and control system of nuclear power plant

    International Nuclear Information System (INIS)

    Lee, Jang Soo; Kim, Jang Yeol; Eum, Heung Seop.

    1997-07-01

    Recently, the safety planning for safety-critical software systems is being recognized as the most important phase in the software life cycle, and being developed new regulatory positions and standards by the regulatory and the standardization organization. The requirements for software important to safety of nuclear reactor are described in such positions and standards. Most of them are describing mandatory requirements, what shall be done, for the safety-critical software. The developers of such a software. However, there have been a lot of controversial factors on whether the work practices satisfy the regulatory requirements, and to justify the safety of such a system developed by the work practices, between the licenser and the licensee. We believe it is caused by the reason that there is a gap between the mandatory requirements (What) and the work practices (How). We have developed a guidance to fill such gap, which can be useful for both licenser and licensee to conduct a justification of the safety in the planning phase of developing the software for nuclear reactor protection systems. (author). 67 refs., 13 tabs., 2 figs

  5. KAERI software safety guideline for developing safety-critical software in digital instrumentation and control system of nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jang Soo; Kim, Jang Yeol; Eum, Heung Seop

    1997-07-01

    Recently, the safety planning for safety-critical software systems is being recognized as the most important phase in the software life cycle, and being developed new regulatory positions and standards by the regulatory and the standardization organization. The requirements for software important to safety of nuclear reactor are described in such positions and standards. Most of them are describing mandatory requirements, what shall be done, for the safety-critical software. The developers of such a software. However, there have been a lot of controversial factors on whether the work practices satisfy the regulatory requirements, and to justify the safety of such a system developed by the work practices, between the licenser and the licensee. We believe it is caused by the reason that there is a gap between the mandatory requirements (What) and the work practices (How). We have developed a guidance to fill such gap, which can be useful for both licenser and licensee to conduct a justification of the safety in the planning phase of developing the software for nuclear reactor protection systems. (author). 67 refs., 13 tabs., 2 figs.

  6. Airline Safety Management: The development of a proactive safety mechanism model for the evolution of safety management system

    OpenAIRE

    Hsu, Yueh-Ling

    2004-01-01

    The systemic origins of many accidents have led to heightened interest in the way in which organisations identify and manage risks within the airline industry. The activities which are thought to represent the term "organisational accident", "safety culture" and "proactive approach" are documented and seek to explain the fact that airlines differ in their willingness and ability to conduct safety management. However, an important but yet relatively undefined task in the airline...

  7. The development of safety cases for healthcare services: Practical experiences, opportunities and challenges

    International Nuclear Information System (INIS)

    Sujan, Mark; Spurgeon, Peter; Cooke, Matthew; Weale, Andy; Debenham, Philip; Cross, Steve

    2015-01-01

    There has been growing interest in the concept of safety cases for medical devices and health information technology, but questions remain about how safety cases can be developed and used meaningfully in the safety management of healthcare services and processes. The paper presents two examples of the development and use of safety cases at a service level in healthcare. These first practical experiences at the service level suggest that safety cases might be a useful tool to support service improvement and communication of safety in healthcare. The paper argues that safety cases might be helpful in supporting healthcare organisations with the adoption of proactive and rigorous safety management practices. However, it is also important to consider the different level of maturity of safety management and regulatory oversight in healthcare. Adaptations to the purpose and use of safety cases might be required, complemented by the provision of education to both practitioners and regulators. - Highlights: • Empirical description of safety case development at service level in healthcare. • Safety cases can support adoption of proactive and rigorous safety management. • Adaptation to purpose and use of safety cases might be required in healthcare. • Education should be provided to practitioners and regulators

  8. Guidelines for PWR safety research and development at NUCLEBRAS - Brazil

    International Nuclear Information System (INIS)

    Pinheiro, R.B.

    1980-06-01

    NUCLEBRAS research into different areas of pressurized light-water reactor technology, is one of the aims of its Research and Development Center, Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), in Belo Horizonte. The main effort of the center is now directed to give technical support to the industrial activities of the Nuclear Program, and to carry out R and D work in strainght connection with these activities. As a consequence few work on safety research is actualy being performed, although the number of activities in this field increases steadily, not as a function but strong related to the development of our industrial program. Basic training and qualification of personnel at CDTN for different research and development activities of NUCLEBRAS has high priority. This is covered either by agreements with national institutions (e.g. universities) or using the various possibilities offered by special agreements and cooperation programs with research centers and other institutions, not only but mainly in Germany, F.R. (Author) [pt

  9. Methodology development for statistical evaluation of reactor safety analyses

    International Nuclear Information System (INIS)

    Mazumdar, M.; Marshall, J.A.; Chay, S.C.; Gay, R.

    1976-07-01

    In February 1975, Westinghouse Electric Corporation, under contract to Electric Power Research Institute, started a one-year program to develop methodology for statistical evaluation of nuclear-safety-related engineering analyses. The objectives of the program were to develop an understanding of the relative efficiencies of various computational methods which can be used to compute probability distributions of output variables due to input parameter uncertainties in analyses of design basis events for nuclear reactors and to develop methods for obtaining reasonably accurate estimates of these probability distributions at an economically feasible level. A series of tasks was set up to accomplish these objectives. Two of the tasks were to investigate the relative efficiencies and accuracies of various Monte Carlo and analytical techniques for obtaining such estimates for a simple thermal-hydraulic problem whose output variable of interest is given in a closed-form relationship of the input variables and to repeat the above study on a thermal-hydraulic problem in which the relationship between the predicted variable and the inputs is described by a short-running computer program. The purpose of the report presented is to document the results of the investigations completed under these tasks, giving the rationale for choices of techniques and problems, and to present interim conclusions

  10. Development of a safety parameter supervision system for Angra-1

    International Nuclear Information System (INIS)

    Silva, R.A. da; Thome Filho, Z.D.; Schirru, R.; Martinez, A.S.; Oliveira, L.F.S. de

    1986-01-01

    The Safety Parameter Supervision System (SSPS) which is a computerized system for monitoring essential parameters in real time, determining the safety status and emergency procedures for returning normal reactor operation, in case of an anomaly occurrence, is presented. The SSPS consists of three sub-systems: Integrated parameter monitoring system which gives to operators an integrated vision of values of a parameter set, able to detect any deviation of normal reactor operation; safety critical function system which evaluates safety status in terms of a safety critical function set appointed in advance, and in case of violation of any critical function, it initiates the adequate emergency procedure to return normal operation; and safety parameter computer system which carries out the arquirement of analogic and digital control signals of nuclear power plant. (M.C.K.) [pt

  11. Development of Broadband Nuclear Safety Data Network (B-NSDN)

    International Nuclear Information System (INIS)

    Son, Gwang Seop; Kim, Dong Hoon; Park, Gi Yong

    2011-01-01

    Recently as introducing digital safety system in nuclear power plant, more data transmission capacity is required. Bandwidth of existing communication network is about a few Mbps. Thus data transmission quantity in recently digital safety system is beyond existing communication network's capacity. In this paper, new protocol that is suitable for safety system communication network is designed. FPGA based communication system is implemented. As result of test, effective bandwidth of B-NSDN is about 20Mbps

  12. Safety and effective developing nuclear power to realize green and low-carbon development

    Directory of Open Access Journals (Sweden)

    Qi-Zhen Ye

    2016-03-01

    Full Text Available This paper analyzes the role of nuclear power of China's energy structure and industry system. Comparing with other renewable energy the nuclear power chain has very low greenhouse gas emission, so it will play more important role in China's low-carbon economy. The paper also discussed the necessity of nuclear power development to achieve emission reduction, energy structure adjustment, nuclear power safety, environmental protection, enhancement of nuclear power technology, nuclear waste treatment, and disposal, as well as nuclear power plant decommissioning. Based on the safety record and situation of the existing power plants in China, the current status of the development of world nuclear power technology, and the features of the independently designed advanced power plants in China, this paper aims to demonstrate the safety of nuclear power. A nuclear power plant will not cause harm either to the environment and nor to the public according to the real data of radioactivity release, which are obtained from an operational nuclear plant. The development of nuclear power technology can enhance the safety of nuclear power. Further, this paper discusses issues related to the nuclear fuel cycle, the treatment, and disposal strategies of nuclear waste, and the decommissioning of a nuclear power plant, all of which are issues of public concern.

  13. Development of 'health and environmental safety assessment network system (HESANS)'

    International Nuclear Information System (INIS)

    Nakamura, Yuji

    1994-01-01

    With the recent advance of the utilization of nuclear energy in a large scale, social interest is being focussed in the potential risk which the nuclear technology will accompany. Especially after the accidents in Chernobyl and other nuclear facilities, serious anxiety to the utilization of nuclear energy is prevailing among the general public. In order to meet the anxiety and distrust of the population in the use of the nuclear power, the health effect or risk which radioactive materials released into the environment will bring about should be comprehensively and properly evaluated, and then should be widely reported to the population. The development of HESANS code system (Health and Environmental Safety Assessment Network System) was planned to set up such a comprehensive computer code that covers a whole pathway of radioactive material from its release to estimates of derived health effects in the population, including the countermeasures for intervention as well. Though the whole system is not totally completed yet so far, the framework of the system has been concreted together with many sub-systems which compose the main part of the code. This report puts main stress on the objective of the development project and the main frame or the structure of the code system. (author)

  14. Workforce perceptions of hospital safety culture: development and validation of the patient safety climate in healthcare organizations survey.

    Science.gov (United States)

    Singer, Sara; Meterko, Mark; Baker, Laurence; Gaba, David; Falwell, Alyson; Rosen, Amy

    2007-10-01

    To describe the development of an instrument for assessing workforce perceptions of hospital safety culture and to assess its reliability and validity. Primary data collected between March 2004 and May 2005. Personnel from 105 U.S. hospitals completed a 38-item paper and pencil survey. We received 21,496 completed questionnaires, representing a 51 percent response rate. Based on review of existing safety climate surveys, we developed a list of key topics pertinent to maintaining a culture of safety in high-reliability organizations. We developed a draft questionnaire to address these topics and pilot tested it in four preliminary studies of hospital personnel. We modified the questionnaire based on experience and respondent feedback, and distributed the revised version to 42,249 hospital workers. We randomly divided respondents into derivation and validation samples. We applied exploratory factor analysis to responses in the derivation sample. We used those results to create scales in the validation sample, which we subjected to multitrait analysis (MTA). We identified nine constructs, three organizational factors, two unit factors, three individual factors, and one additional factor. Constructs demonstrated substantial convergent and discriminant validity in the MTA. Cronbach's alpha coefficients ranged from 0.50 to 0.89. It is possible to measure key salient features of hospital safety climate using a valid and reliable 38-item survey and appropriate hospital sample sizes. This instrument may be used in further studies to better understand the impact of safety climate on patient safety outcomes.

  15. Developing a Highway Safety Fundamentals Course : Research Project Capsule

    Science.gov (United States)

    2012-10-01

    Although the need for road : safety education was fi rst : recognized in the 1960s, : recently it has become an : increasingly urgent issue. To : fulfi ll the hefty goal set up by : the AASHTO Highway : Safety Strategy (cutting : traffi c fatalities ...

  16. Traffic safety developments in Poland : a research note.

    NARCIS (Netherlands)

    Oppe, S.

    2001-01-01

    Recently there has been an increased interest in traffic safety in Poland. There is a feeling that the rapid growth of traffic should be accompanied by additional efforts to improve traffic safety, in order to stop the corresponding increase in fatalities and serious accidents. To set realistic

  17. Software safety analysis techniques for developing safety critical software in the digital protection system of the LMR

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jang Soo; Cheon, Se Woo; Kim, Chang Hoi; Sim, Yun Sub

    2001-02-01

    This report has described the software safety analysis techniques and the engineering guidelines for developing safety critical software to identify the state of the art in this field and to give the software safety engineer a trail map between the code and standards layer and the design methodology and documents layer. We have surveyed the management aspects of software safety activities during the software lifecycle in order to improve the safety. After identifying the conventional safety analysis techniques for systems, we have surveyed in details the software safety analysis techniques, software FMEA(Failure Mode and Effects Analysis), software HAZOP(Hazard and Operability Analysis), and software FTA(Fault Tree Analysis). We have also surveyed the state of the art in the software reliability assessment techniques. The most important results from the reliability techniques are not the specific probability numbers generated, but the insights into the risk importance of software features. To defend against potential common-mode failures, high quality, defense-in-depth, and diversity are considered to be key elements in digital I and C system design. To minimize the possibility of CMFs and thus increase the plant reliability, we have provided D-in-D and D analysis guidelines.

  18. Software safety analysis techniques for developing safety critical software in the digital protection system of the LMR

    International Nuclear Information System (INIS)

    Lee, Jang Soo; Cheon, Se Woo; Kim, Chang Hoi; Sim, Yun Sub

    2001-02-01

    This report has described the software safety analysis techniques and the engineering guidelines for developing safety critical software to identify the state of the art in this field and to give the software safety engineer a trail map between the code and standards layer and the design methodology and documents layer. We have surveyed the management aspects of software safety activities during the software lifecycle in order to improve the safety. After identifying the conventional safety analysis techniques for systems, we have surveyed in details the software safety analysis techniques, software FMEA(Failure Mode and Effects Analysis), software HAZOP(Hazard and Operability Analysis), and software FTA(Fault Tree Analysis). We have also surveyed the state of the art in the software reliability assessment techniques. The most important results from the reliability techniques are not the specific probability numbers generated, but the insights into the risk importance of software features. To defend against potential common-mode failures, high quality, defense-in-depth, and diversity are considered to be key elements in digital I and C system design. To minimize the possibility of CMFs and thus increase the plant reliability, we have provided D-in-D and D analysis guidelines

  19. NS [Nuclear Safety] update. Current safety and security activities and developments taking place in the Department of Nuclear Safety and Security. Issue no. 4, June 2007

    International Nuclear Information System (INIS)

    2007-04-01

    This newsletter contains information on the Centre for Advanced Safety Assessment Tools (CASAT), the new strategy for the recovery of radioactive sources, the Technical Support Organization Conference and a message form the Director of the Division of Nuclear Installation Safety. To improve the efficiency of safety assessment methods, ensure transparency in their validation and application and establish an excellent knowledge base and training programmes, the IAEA's Centre for Advanced Safety Assessment Tools (CASAT) has therefore been formed. The Centre addresses the need for continuous technical support mechanisms for safety assessment methods. It provides support to Member States to enhance their safety assessment capabilities for present and future generations of nuclear systems, with a special focus on countries with a developing nuclear technology and nuclear safety infrastructure. It serves as a consolidated repository of relevant safety analysis knowledge, provides for focused training including advanced analytical simulations, and supports collaboration on safety assessment projects among Member States. The resources provided through CASAT include codes, models, databases, verification and validation information, analytical procedures and guides. The main purpose of the recently established Radioactive Source Technical Coordination Group (RSTCG) is to facilitate the technical coordination of activities of the IAEA related to the control and management of radioactive sources through the development of common approaches in technical matters and to advise the management of the relevant Divisions. It is the task of the RSTCG to provide the programme managers of the participating divisions/sections with a common opinion/advice on technical issues related to the control and management of radioactive sources. The RSTCG members obtain, inter alia from programme managers, information on all relevant project proposals, and share relevant materials in due time to

  20. Development and Application of Level 2 Probabilistic Safety Assessment for Nuclear Power Plants. Specific Safety Guide

    International Nuclear Information System (INIS)

    2010-01-01

    The objective of this Safety Guide is to provide recommendations for meeting the IAEA safety requirements in performing or managing a level 2 probabilistic safety assessment (PSA) project for a nuclear power plant; thus it complements the Safety Guide on level 1 PSA. One of the aims of this Safety Guide is to promote a standard framework, standard terms and a standard set of documents for level 2 PSAs to facilitate regulatory and external peer review of their results. It describes all elements of the level 2 PSA that need to be carried out if the starting point is a fully comprehensive level 1 PSA. Contents: 1. Introduction; 2. PSA project management and organization; 3. Identification of design aspects important to severe accidents and acquisition of information; 4. Interface with level 1 PSA: Grouping of sequences; 5. Accident progression and containment analysis; 6. Source terms for severe accidents; 7. Documentation of the analysis: Presentation and interpretation of results; 8. Use and applications of the PSA; Annex I: Example of a typical schedule for a level 2 PSA; Annex II: Computer codes for simulation of severe accidents; Annex III: Sample outline of documentation for a level 2 PSA study.

  1. DEVELOPING SAFETY INDICATORS ON THE BASIS OF THE ICAO RECOMMENDATIONS

    Directory of Open Access Journals (Sweden)

    V. D. Sharov

    2014-01-01

    Full Text Available The article offers direct use of the recommendations of SMM ICAO Doc.9859, 3rd ed. 2013, for calculation the target and alert levels of safety indicators. Examples of calculation based on data of 2011 and monitoring of the current indicators during 2012 are presented. Safety indicators for airlines in terms of “numbers of incidents per 1000 flight hours” could be calculated on the basis of the state values through the «coefficient of conformity».

  2. Safety and effective developing nuclear power to realize green and low-carbon development

    OpenAIRE

    Ye, Qi-Zhen

    2016-01-01

    This paper analyzes the role of nuclear power of China's energy structure and industry system. Comparing with other renewable energy the nuclear power chain has very low greenhouse gas emission, so it will play more important role in China's low-carbon economy. The paper also discussed the necessity of nuclear power development to achieve emission reduction, energy structure adjustment, nuclear power safety, environmental protection, enhancement of nuclear power technology, nuclear waste trea...

  3. Development of several data bases related to reactor safety research including probabilistic safety assessment and incident analysis at JAERI

    International Nuclear Information System (INIS)

    Kobayashi, Kensuke; Oikawa, Tetsukuni; Watanabe, Norio; Izumi, Fumio; Higuchi, Suminori

    1986-01-01

    Presented are several databases developed at JAERI for reactor safety research including probabilistic safety assessment and incident analysis. First described are the recent developments of the databases such as 1) the component failure rate database, 2) the OECD/NEA/IRS information retrieval system, 3) the nuclear power plant database and so on. Then several issues are discussed referring mostly to the operation of the database (data input and transcoding) and to the retrieval and utilization of the information. Finally, emphasis is given to the increasing role which artifitial intelligence techniques such as natural language treatment and expert systems may play in improving the future capabilities of the databases. (author)

  4. Development of the KINS Safety Culture Maturity Model for Self and Independent Assessment

    International Nuclear Information System (INIS)

    Sheen, C.; Choi, Y.S.

    2016-01-01

    Safety culture of an organization is cultivated and affected not only by societal and regulatory environment of the organization, but by its philosophies, policies, events and activities experienced in the process of accomplishing its mission. The safety culture would be continuously changed by the interactions between its members along with time as an organic entity. In order to perform a systematic self- or independent assessment of safety culture, a safety culture assessment model (SCAM) properly reflecting cultural characteristics should be necessary. In addition, a SCAM should be helpful not only to establish correct directions, goals, and strategies for safety culture development, but should anticipating obstacles against safety culture development in the implementation process derived from the assessment. In practical terms, a SCAM should be useful for deriving effective guidelines and implementing of corrective action programs for the evaluated organization. Korea Institute of Nuclear Safety (KINS) performed a research project for six years to develop a SCAM satisfying the above prerequisites for self- and independent assessment. The KINS SCAM was developed based on the five stage safety culture maturity model proposed by Professor Patrick Hudson and was modified into four stages to reflect existing safety culture assessment experiences at Korean nuclear power plants. In order to define the change mechanism of safety culture for development and reversion, the change model proposed by Prochaska and DiClemente was introduced into KINS SCAM and developed into the Spiral Change Model.

  5. The Development of Laboratory Safety Questionnaire for Middle School Science Teachers

    Science.gov (United States)

    Akpullukcu, Simge; Cavas, Bulent

    2017-01-01

    The purpose of this paper is to develop a "valid and reliable laboratory safety questionnaire" which could be used to identify science teachers' understanding about laboratory safety issues during their science laboratory activities. The questionnaire was developed from a literature review and prior instruments developed on laboratory…

  6. Patient involvement in patient safety: Protocol for developing an intervention using patient reports of organisational safety and patient incident reporting

    Directory of Open Access Journals (Sweden)

    Armitage Gerry

    2011-05-01

    Full Text Available Abstract Background Patients have the potential to provide a rich source of information on both organisational aspects of safety and patient safety incidents. This project aims to develop two patient safety interventions to promote organisational learning about safety - a patient measure of organisational safety (PMOS, and a patient incident reporting tool (PIRT - to help the NHS prevent patient safety incidents by learning more about when and why they occur. Methods To develop the PMOS 1 literature will be reviewed to identify similar measures and key contributory factors to error; 2 four patient focus groups will ascertain practicality and feasibility; 3 25 patient interviews will elicit approximately 60 items across 10 domains; 4 10 patient and clinician interviews will test acceptability and understanding. Qualitative data will be analysed using thematic content analysis. To develop the PIRT 1 individual and then combined patient and clinician focus groups will provide guidance for the development of three potential reporting tools; 2 nine wards across three hospital directorates will pilot each of the tools for three months. The best performing tool will be identified from the frequency, volume and quality of reports. The validity of both measures will be tested. 300 patients will be asked to complete the PMOS and PIRT during their stay in hospital. A sub-sample (N = 50 will complete the PMOS again one week later. Health professionals in participating wards will also be asked to complete the AHRQ safety culture questionnaire. Case notes for all patients will be reviewed. The psychometric properties of the PMOS will be assessed and a final valid and reliable version developed. Concurrent validity for the PIRT will be assessed by comparing reported incidents with those identified from case note review and the existing staff reporting scheme. In a subsequent study these tools will be used to provide information to wards/units about their

  7. Development of a quality assurance safety assessment database for near surface radioactive waste disposal

    International Nuclear Information System (INIS)

    Park, J. W.; Kim, C. L.; Park, J. B.; Lee, E. Y.; Lee, Y. M.; Kang, C. H.; Zhou, W.; Kozak, M. W.

    2003-01-01

    A quality assurance safety assessment database, called QUARK (QUality Assurance program for Radioactive waste management in Korea), has been developed to manage both analysis information and parameter database for safety assessment of Low- and Intermediate-Level radioactive Waste (LILW) disposal facility in Korea. QUARK is such a tool that serves QA purposes for managing safety assessment information properly and securely. In QUARK, the information is organized and linked to maximize the integrity of information and traceability. QUARK provides guidance to conduct safety assessment analysis, from scenario generation to result analysis, and provides a window to inspect and trace previous safety assessment analysis and parameter values. QUARK also provides default database for safety assessment staff who construct input data files using SAGE(Safety Assessment Groundwater Evaluation), a safety assessment computer code

  8. Development of safety factors to be used for evaluation of cracked nuclear components

    International Nuclear Information System (INIS)

    Brickstad, B.; Bergman, M.

    1996-10-01

    A modified concept for safety evaluation is introduced which separately accounts for the failure mechanisms fracture and plastic collapse. For application on nuclear components a set of safety factors are also proposed that retain the safety margins expressed in ASME, section III and XI. By performing comparative studies of the acceptance levels for surface cracks in pipes and a pressure vessel, it is shown that some of the anomalies connected with the old safety procedures are removed. It is the authors belief that the outlined safety evaluation procedure has the capability of treating cracks in a consistent way and that the procedure together with the proposed safety factors fulfill the basic safety requirements for nuclear components. Hopefully, it is possible in the near future to develop a probabilistic safety assessment procedure in Sweden, which enables a systematic treatment of uncertainties in the involved data. 14 refs

  9. Binary Decision Tree Development for Probabilistic Safety Assessment Applications

    International Nuclear Information System (INIS)

    Simic, Z.; Banov, R.; Mikulicic, V.

    2008-01-01

    The aim of this article is to describe state of the development for the relatively new approach in the probabilistic safety analysis (PSA). This approach is based on the application of binary decision diagrams (BDD) representation for the logical function on the quantitative and qualitative analysis of complex systems that are presented by fault trees and event trees in the PSA applied for the nuclear power plants risk determination. Even BDD approach offers full solution comparing to the partial one from the conventional quantification approach there are still problems to be solved before new approach could be fully implemented. Major problem with full application of BDD is difficulty of getting any solution for the PSA models of certain complexity. This paper is comparing two approaches in PSA quantification. Major focus of the paper is description of in-house developed BDD application with implementation of the original algorithms. Resulting number of nodes required to represent the BDD is extremely sensitive to the chosen order of variables (i.e., basic events in PSA). The problem of finding an optimal order of variables that form the BDD falls under the class of NP-complete complexity. This paper presents an original approach to the problem of finding the initial order of variables utilized for the BDD construction by various dynamical reordering schemes. Main advantage of this approach compared to the known methods of finding the initial order is with better results in respect to the required working memory and time needed to finish the BDD construction. Developed method is compared against results from well known methods such as depth-first, breadth-first search procedures. Described method may be applied in finding of an initial order for fault trees/event trees being created from basic events by means of logical operations (e.g. negation, and, or, exclusive or). With some testing models a significant reduction of used memory has been achieved, sometimes

  10. The development of safety assessment technology for the radwaste disposal

    International Nuclear Information System (INIS)

    Han, Kyong Won; Cho, Won Jin; Lee, Han Soo; Lee, Jai Wan; Park, Chung Kyun; Lee, Myun Joo; Cho, Young Hwan; Choi, Heui Joo; Lee, Youn Myoung; Park, Hee Sung

    1989-02-01

    This report is composed of three parts. In part I, an improved radwaste disposal safety assessment code named SADROCM, was developed by upgrading the existing SADROC. A numerical approach was adopted for the simulation of diffusion into rock pore and advection in the fracture. Also quantification of resaturation time in repository was obtained by introducing theoretical resaturation model and groundwater flow model. In radiation dose model the calculated dose by existing model was compared with that by LIMCAL code. Part II resulted in several findings. Regarding the leaching of radionuclide, two steps were observed. It was identified that in the initial step, radionuclide leaching occurred at the surface of solidified waste, and then leaching proceeded by dissolution and diffusion of radionuclide from inside of the solidified waste.The results of the sorption experiments on Cs, Co, Sr for the rock samples from four regions, showed that Kd value of F-site quartz-porphery was the lowest, and that of B-site Rhyolitic tuff the highest. E-site granite, M-site granite gneiss showed medium sorption capacities. The Kd values of each radionuclide were in the following order: Cs > Co > Sr . For the radionuclide migration through fractured rock, examination of hydraulic dispersion model and channeling model was carried out to simulate the dispersion phenomena through the fractured rock. In part III, optimum model was established which allows mathematical prediction of the container corrosion rate and leach rate.Based on this model, the equations were obtained to predict corrosion rate and radionuclide leach rate. A good agreement of these equations and existing experimental data was considered to be an indication that it can be used effectively for the estimation of long-term leaching. (Author)

  11. Lessons learned - development of the tritium facilities 5480.23 safety analysis report and technical safety requirements

    International Nuclear Information System (INIS)

    Cappucci, A.J. Jr.; Bowman, M.E.; Goff, L.

    1997-01-01

    A review was performed which identified open-quotes Lessons Learnedclose quotes from the development of the 5480.23 Tritium Safety Analysis Report (SAR) and the Technical Safety Requirements (TSR) for the Tritium Facilities (TF). The open-quotes Lessons Learnedclose quotes were based on an evaluation of the use of the SRS procedures, processes, and work practices which contributed to the success or lack thereof. This review also identified recommendations and suggestions for improving the development of SARs and TSRs at SRS. The 5480.23 SAR describes the site for the TF, the various process systems in the process buildings, a complete hazards and accident analysis of the most significant hazards affecting the nearby offsite population, and the selection of safety systems, structures, and components to protect both the public and site workers. It also provides descriptions of important programs and processes which add defense in depth to public and worker protection

  12. Developing guidance in the nuclear criticality safety assessment for fuel cycle facilities

    International Nuclear Information System (INIS)

    Galet, C.; Evo, S.

    2012-01-01

    In this poster IRSN (Institute for radiation protection and nuclear safety) presents its safety guides whose purpose is to transmit the safety assessment know-how to any 'junior' staff or even to give a view of the safety approach on the overall risks to any staff member. IRSN has written a first version of such a safety guide for fuel cycle facilities and laboratories. It is organized into several chapters: some refer to types of assessments, others concern the types of risks. Currently, this guide contains 13 chapters and each chapter consists of three parts. In parallel to the development of criticality chapter of this guide, the IRSN criticality department has developed a nuclear criticality safety guide. It follows the structure of the three parts fore-mentioned, but it presents a more detailed first part and integrates, in the third part, the experience feedback collected on nuclear facilities. The nuclear criticality safety guide is online on the IRSN's web site

  13. Safety report content and development for test loop facility on MARIA reactor

    International Nuclear Information System (INIS)

    Konechko, A.; Shumskij, A.M.; Mikul'ahin, V.E.

    1982-01-01

    A 600 kW test loop facility for investigatin.o safety problems is realized on MARIA reactor in Poland together with USSR organizations. Safety reports have been developed in two steps at the designstage. The 1st report being essentially a preliminary safety analysis was developed within the scope of the feasibility study. At the engineering design stage the preliminary test loop facility safety report had been prepared considering measures excluding the possibility of the MARIA reactor damage. The test loop facility safety report is fulfilled for normal, transient and emergency operation regimes. Separate safety basing for each group of experiments will be prepared. The report presents the test loop facility safety criteria coordinated by the nuclear safety comission. They contains the preliminary reports on the test loop facility safety. At the final stage of construction and at thecommitioning stage the start-up safety report will be developed which after required correction and adding up the putting into operation data will turn into operation safety report [ru

  14. Development of Manitoba Hydro's public water safety around dams management guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, Dave; McPhail, Gord; Murphy, Shayla; Schellenberg, Gord [KGS Acres, Winnipeg, (Canada); Read, Nick [Manitoba Hydro, Winnipeg, (Canada)

    2010-07-01

    Several drowning fatalities and safety incidents have occurred around dams in Ontario, Manitoba and other jurisdictions in Canada. Following these incidents, Manitoba Hydro implemented several measures to improve public safety around its dams with the development of a warning signs manual. Manitoba Hydro found that a standard centralized approach to the process of improving public safety is better for ensuring compliance and consistency, even though they have safety measures in place. This paper described the process that Manitoba Hydro has followed in developing a formal set of public water safety around dams (PWSD) guidelines and a program for implementing these guidelines. This program was developed with the intent of providing a high standard of public protection and continuous improvement and monitoring on par with the effect spent on similar dam safety type programs. This paper focused on the development of the pilot PWSD management plan for Pine Falls generating station in order to test the effectiveness and usability of the guidelines.

  15. Development of an FPGA-based controller for safety critical application

    International Nuclear Information System (INIS)

    Xing, A.; De Grosbois, J.; Sklyar, V.; Archer, P.; Awwal, A.

    2011-01-01

    In implementing safety functions, Field Programmable Gate Arrays (FPGA) technology offers a distinct combination of benefits and advantages over microprocessor-based systems. FPGAs can be designed such that the final product is purely hardware, without any overhead runtime software, bringing the design closer to a conventional hardware-based solution. On the other hand, FPGAs can implement more complex safety logic that would generally require microprocessor-based safety systems. There are now qualified FPGA-based platforms available on the market with a credible use history in safety applications in nuclear power plants. Atomic Energy of Canada (AECL), in collaboration with RPC Radiy, has initiated a development program to define a vigorous FPGA engineering process suitable for implementing safety critical functions at the application development level. This paper provides an update on the FPGA development program along with the proposed design model using function block diagrams for the development of safety controllers in CANDU applications. (author)

  16. DEVELOPMENT OF RISK-BASED AND TECHNOLOGY-INDEPENDENT SAFETY CRITERIA FOR GENERATION IV SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    William E. Kastenberg; Edward Blandford; Lance Kim

    2009-03-31

    This project has developed quantitative safety goals for Generation IV (Gen IV) nuclear energy systems. These safety goals are risk based and technology independent. The foundations for a new approach to risk analysis has been developed, along with a new operational definition of risk. This project has furthered the current state-of-the-art by developing quantitative safety goals for both Gen IV reactors and for the overall Gen IV nuclear fuel cycle. The risk analysis approach developed will quantify performance measures, characterize uncertainty, and address a more comprehensive view of safety as it relates to the overall system. Appropriate safety criteria are necessary to manage risk in a prudent and cost-effective manner. This study is also important for government agencies responsible for managing, reviewing, and for approving advanced reactor systems because they are charged with assuring the health and safety of the public.

  17. DEVELOPMENT OF RISK-BASED AND TECHNOLOGY-INDEPENDENT SAFETY CRITERIA FOR GENERATION IV SYSTEMS

    International Nuclear Information System (INIS)

    Kastenberg, William E.; Blandford, Edward; Kim, Lance

    2009-01-01

    This project has developed quantitative safety goals for Generation IV (Gen IV) nuclear energy systems. These safety goals are risk based and technology independent. The foundations for a new approach to risk analysis has been developed, along with a new operational definition of risk. This project has furthered the current state-of-the-art by developing quantitative safety goals for both Gen IV reactors and for the overall Gen IV nuclear fuel cycle. The risk analysis approach developed will quantify performance measures, characterize uncertainty, and address a more comprehensive view of safety as it relates to the overall system. Appropriate safety criteria are necessary to manage risk in a prudent and cost-effective manner. This study is also important for government agencies responsible for managing, reviewing, and for approving advanced reactor systems because they are charged with assuring the health and safety of the public

  18. A Systematic Analysis of Functional Safety Certification Practices in Industrial Robot Software Development

    Directory of Open Access Journals (Sweden)

    Tong Xie

    2017-01-01

    Full Text Available For decades, industry robotics have delivered on the promise of speed, efficiency and productivity. The last several years have seen a sharp resurgence in the orders of industrial robots in China, and the areas addressed within industrial robotics has extended into safety-critical domains. However, safety standards have not yet been implemented widely in academia and engineering applications, particularly in robot software development. This paper presents a systematic analysis of functional safety certification practices in software development for the safety-critical software of industrial robots, to identify the safety certification practices used for the development of industrial robots in China and how these practices comply with the safety standard requirements. Reviewing from Chinese academic papers, our research shows that safety standards are barely used in software development of industrial robot. The majority of the papers propose various solutions to achieve safety, but only about two thirds of the papers refer to non-standardized approaches that mainly address the systematic level rather than the software development level. In addition, our research shows that with the development of artificial intelligent, an emerging field is still on the quest for standardized and suitable approaches to develop safety-critical software.

  19. Development of the evaluation methods in reactor safety analyses and core characteristics

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    In order to support the safety reviews by NRA on reactor safety design including the phenomena with multiple failures, the computer codes are developed and the safety evaluations with analyses are performed in the areas of thermal hydraulics and core characteristics evaluation. In the code preparation of safety analyses, the TRACE and RELAP5 code were prepared to conduct the safety analyses of LOCA and beyond design basis accidents with multiple failures. In the core physics code preparation, the functions of sensitivity and uncertainty analysis were incorporated in the lattice physics code CASMO-4. The verification of improved CASMO-4 /SIMULATE-3 was continued by using core physics data. (author)

  20. Development and Psychometric Analysis of a Nurses’ Attitudes and Skills Safety Scale: Initial Results

    Science.gov (United States)

    Armstrong, Gail E.; Dietrich, Mary; Norman, Linda; Barnsteiner, Jane; Mion, Lorraine

    2016-01-01

    Health care organizations have incorporated updated safety principles in the analysis of errors and in norms and standards. Yet no research exists that assesses bedside nurses’ perceived skills or attitudes toward updated safety concepts. The aims of this study were to develop a scale assessing nurses’ perceived skills and attitudes toward updated safety concepts, determine content validity, and examine internal consistency of the scale and subscales. Understanding nurses’ perceived skills and attitudes about safety concepts can be used in targeting strategies to enhance their safety practices. PMID:27479518

  1. Development and Psychometric Analysis of a Nurses' Attitudes and Skills Safety Scale: Initial Results.

    Science.gov (United States)

    Armstrong, Gail E; Dietrich, Mary; Norman, Linda; Barnsteiner, Jane; Mion, Lorraine

    Health care organizations have incorporated updated safety principles in the analysis of errors and in norms and standards. Yet no research exists that assesses bedside nurses' perceived skills or attitudes toward updated safety concepts. The aims of this study were to develop a scale assessing nurses' perceived skills and attitudes toward updated safety concepts, determine content validity, and examine internal consistency of the scale and subscales. Understanding nurses' perceived skills and attitudes about safety concepts can be used in targeting strategies to enhance their safety practices.

  2. Progress in the development of methodology for fusion safety systems studies

    International Nuclear Information System (INIS)

    Ho, S.K.; Cambi, G.; Ciattaglia, S.; Fujii-e, Y.; Seki, Y.

    1994-01-01

    The development of fusion safety systems-study methodology, including the aspects of schematic classification of overall fusion safety system, qualitative assessment of fusion system for identification of critical accident scenarios, quantitative analysis of accident consequences and risk for safety design evaluation, and system-level analysis of accident consequences and risk for design optimization, by a consortium of international efforts is presented. The potential application of this methodology into reactor design studies will facilitate the systematic assessment of safety performance of reactor designs and enhance the impacts of safety considerations on the selection of design configurations

  3. System safety engineering in the development of advanced surface transportation vehicles

    Science.gov (United States)

    Arnzen, H. E.

    1971-01-01

    Applications of system safety engineering to the development of advanced surface transportation vehicles are described. As a pertinent example, the paper describes a safety engineering efforts tailored to the particular design and test requirements of the Tracked Air Cushion Research Vehicle (TACRV). The test results obtained from this unique research vehicle provide significant design data directly applicable to the development of future tracked air cushion vehicles that will carry passengers in comfort and safety at speeds up to 300 miles per hour.

  4. Fuel cycle safety research. Role and development in future

    International Nuclear Information System (INIS)

    Matsumoto, Shiro

    2005-01-01

    The report stresses important roles played by risk informed methodology in chemical process safety problems as encountered in fuel cycle facility such as a reprocessing plant. Abnormal situation management is a safety issue - The lesson learned from the pesticide manufacturing facility in Bhopal, India. Little attention has been given to understanding the issues regarding performance during normal versus abnormal situation. The first step is in abnormal situation management is to define what really is abnormal. The second step is to ensure that everyone understands the difference between normal and abnormal, and the root causes of abnormal events. The third step is to be aware of current practices that support abnormal situation management, and the procedures, practices, and techniques used to respond to abnormal conditions. Dynamic simulation will become to useful techniques for abnormal situation management as well as probabilistic safety assessment for process facilities including nuclear fuel cycle. (S. Ohno)

  5. Integrated safety case development for deep geological repositories

    International Nuclear Information System (INIS)

    Kawamura, Hideki; McKinley, Ian G.

    2008-01-01

    The paper will illustrate an 'integrated safety case', which involves combining both pre-closure and post-closure safety arguments from the point of view of a repository implementer, who must also ensure that projects are practical, acceptable and economic. The post-closure safety case is based on the performance of a number of barriers, which are established during construction, operation and closure. Such barriers must be confirmed using quality assured methods, supported, as required, by inspection and monitoring. The requirement for integrated assessment means that even the final process to end institutional control and transfer any liabilities from the implementer needs to be considered at present, even though this will undoubtedly be refined and tailored to the site characteristics over the many decades that will pass before this occurs. To illustrate the practical application of this approach, assessment of variants for remote-handled emplacement of the EBS for disposal of HLW in Japan will be discussed. (author)

  6. Development of the Continued Improvement System for Nuclear Safety Culture

    International Nuclear Information System (INIS)

    Park, H. C.; Park, H. G.; Park, Y. W.; Park, J. Y.

    2016-01-01

    It has been found that almost 80 % of the incidents and accidents occurred recently, such as the Fukushima Daiichi disaster and Domestic SBO accident etc. were analyzed to be caused from human errors. (IAEA NES NG-G-2.1) Which strongly claims the importance of the safety culture system. Accordingly, it should be away from a cursory approach like one-off field survey or Snap shop which were being conducted at present for the continued improvement of safety culture. This study introduces an analytical methodology which approaches the generic form of the safety both consciously and unconsciously expressed with behavior, thoughts, and attitude etc. This study was implemented only for open materials such as Inspection report, incidents and accidents reports, QA documents because of the limitation in accessibility to data. More effective use with securing operational data will be possible in future

  7. Development of the Continued Improvement System for Nuclear Safety Culture

    Energy Technology Data Exchange (ETDEWEB)

    Park, H. C.; Park, H. G.; Park, Y. W.; Park, J. Y. [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    It has been found that almost 80 % of the incidents and accidents occurred recently, such as the Fukushima Daiichi disaster and Domestic SBO accident etc. were analyzed to be caused from human errors. (IAEA NES NG-G-2.1) Which strongly claims the importance of the safety culture system. Accordingly, it should be away from a cursory approach like one-off field survey or Snap shop which were being conducted at present for the continued improvement of safety culture. This study introduces an analytical methodology which approaches the generic form of the safety both consciously and unconsciously expressed with behavior, thoughts, and attitude etc. This study was implemented only for open materials such as Inspection report, incidents and accidents reports, QA documents because of the limitation in accessibility to data. More effective use with securing operational data will be possible in future.

  8. The quantifying of road safety developments. Paper presented at the International Conference 'Road Safety in Europe', Birmingham, September 9-11, 1996.

    NARCIS (Netherlands)

    Koornstra, M.J.

    1996-01-01

    The evaluation of the effectiveness of road safety policies and measures must be based on quantative information in road safety developments and the relevant variables that influence that development. However, the concept of road safety itself is not well defined theoretically and quantatively. This

  9. Development of Large-Scale Spacecraft Fire Safety Experiments

    DEFF Research Database (Denmark)

    Ruff, Gary A.; Urban, David L.; Fernandez-Pello, A. Carlos

    2013-01-01

    exploration missions outside of low-earth orbit and accordingly, more complex in terms of operations, logistics, and safety. This will increase the challenge of ensuring a fire-safe environment for the crew throughout the mission. Based on our fundamental uncertainty of the behavior of fires in low...... of the spacecraft fire safety risk. The activity of this project is supported by an international topical team of fire experts from other space agencies who conduct research that is integrated into the overall experiment design. The large-scale space flight experiment will be conducted in an Orbital Sciences...

  10. Development of Strategic Technology Road map for Establishing Safety Infrastructure of Fusion Energy

    International Nuclear Information System (INIS)

    Han, B. S.; Cho, S. H.; Kam, S. C.; Kim, K. T.

    2009-01-01

    The Korean Government established an 'Act for the Promotion of Fusion Energy Development (APFED)' and formulated a 'Strategy Promotion Plan for Fusion Energy Development.' KINS has carried out a safety review of KSTAR (Korea Superconducting Tokamak Advanced Research), for which an application for use was received in 2002 and the license was issued in August 2007. With respect to the APFED, 'Atomic Energy Acts (AEAs)' shall apply in the fusion safety regulation. However the AEAs are not applicable because they aim for dealing with nuclear energy. In this regard, this study was planned to establish safety infrastructure for fusion energy and to develop technologies necessary for verifying the safety. The purpose of this study is to develop a 'Strategic Technology Roadmap (STR) for establishing safety infrastructure of the fusion energy', which displays the content and development schedule and strategy for developing the laws, safety goals and principles, and safety standards applicable for fusion safety regulation, and core technology required for safety regulation of fusion facilities

  11. Cultivating and Development — 30 Years Practice of Safety Culture in China

    International Nuclear Information System (INIS)

    Hu, L.; Zhang, Y.; Zhang, W.; Xu, G.

    2016-01-01

    The safety culture has been cultivated and promoted in China since its very beginning by IAEA. The 1st stage—stage of start and exploration—was from 1984 to 2007, in which the international concept of safety culture was imported and studied, with the process of combination and convergence with the positive elements of Chinese traditional culture. The basic ideas, such as the principles and directing ideas for the nuclear safety, were established in China. The 2nd stage — stage of practice and growing — was from 2007 to 2014, where safety culture was promoted by the Government, and the regulatory body NNSA established its basic supervision value based on the safety culture. The Chinese nuclear industry was encouraged to develop their of safety culture in a vivid form of presenting. The 3rd stage — stage of fast development — is from 2014 to now. The Chinese president Xi announce the Chinese Nuclear Safety View in The Hague in March 2014, showing the states position regarding the nuclear safety and safety culture. The policy declaration was issued and the nuclear safety promotion special action was carried out by NNSA. Safety culture is widely accepted and acknowledged by the nuclear and radioactivity relevant industry. (author)

  12. Development of safety evaluation methods and analysis codes applied to the safety regulations for the design and construction stage of fast breeder reactor

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    The purposes of this study are to develop the safety evaluation methods and analysis codes needed in the design and construction stage of fast breeder reactor (FBR). In JFY 2012, the following results are obtained. As for the development of safety evaluation methods needed in the safety examination conducted for the reactor establishment permission, development of the analysis codes, such as core damage analysis code, were carried out following the planned schedule. As for the development of the safety evaluation method needed for the risk informed safety regulation, the quantification technique of the event tree using the Continuous Markov chain Monte Carlo method (CMMC method) were studied. (author)

  13. 75 FR 20009 - Development of NRC's Safety Culture Policy Statement: Cancellation of Public Workshops Scheduled...

    Science.gov (United States)

    2010-04-16

    ... included the development of the safety culture common terminology effort comprised of: (1) Development of a... alignment on the safety culture common terminology effort. The NRC held the first workshop on February 2-4... of individual industry groups, such as, [[Page 20010

  14. Development of safety culture at Kozloduy NPP: The role of the regulatory body

    International Nuclear Information System (INIS)

    Miliovsky, Ventzislav

    2002-01-01

    An evolution is made upon external factor that accompany the development of safety culture at Kozloduy NPP (KNPP). The two basic stages and the major results achieved independently and with external assistance were considered in the process of development of safety culture. The areas in which the regulatory body insists on having active participation were defined. (author)

  15. Developing Probabilistic Safety Performance Margins for Unknown and Underappreciated Risks

    Science.gov (United States)

    Benjamin, Allan; Dezfuli, Homayoon; Everett, Chris

    2015-01-01

    Probabilistic safety requirements currently formulated or proposed for space systems, nuclear reactor systems, nuclear weapon systems, and other types of systems that have a low-probability potential for high-consequence accidents depend on showing that the probability of such accidents is below a specified safety threshold or goal. Verification of compliance depends heavily upon synthetic modeling techniques such as PRA. To determine whether or not a system meets its probabilistic requirements, it is necessary to consider whether there are significant risks that are not fully considered in the PRA either because they are not known at the time or because their importance is not fully understood. The ultimate objective is to establish a reasonable margin to account for the difference between known risks and actual risks in attempting to validate compliance with a probabilistic safety threshold or goal. In this paper, we examine data accumulated over the past 60 years from the space program, from nuclear reactor experience, from aircraft systems, and from human reliability experience to formulate guidelines for estimating probabilistic margins to account for risks that are initially unknown or underappreciated. The formulation includes a review of the safety literature to identify the principal causes of such risks.

  16. Design for sustainable development : environmental management and safety and health

    NARCIS (Netherlands)

    Zwetsloot, G.; Bos, J.

    1998-01-01

    This is a report on the EU's environmental management and audit scheme and its interaction with the management of safety and health. The focus is on the interactions at company and at policy level. To illustrate the relevance of the interactions at company level, the Annex includes five case studies

  17. Developing an Effective Tool for Teaching Teens about Workplace Safety

    Science.gov (United States)

    Miara, Christine; Gallagher, Susan; Bush, Diane; Dewer, Robin

    2003-01-01

    Paid employment is an important feature of adolescent life. Too often, it has negative health consequences, including more than 200,000 workplace injuries to 14 to 17 year olds every year. Training teens about occupational safety is part of an overall strategy to address this problem. When the project described in this article began, there were…

  18. Development of a safety communication and recognition program for construction.

    Science.gov (United States)

    Sparer, Emily H; Herrick, Robert F; Dennerlein, Jack T

    2015-05-01

    Leading-indicator-based (e.g., hazard recognition) incentive programs provide an alternative to controversial lagging-indicator-based (e.g., injury rates) programs. We designed a leading-indicator-based safety communication and recognition program that incentivized safe working conditions. The program was piloted for two months on a commercial construction worksite and then redesigned using qualitative interview and focus group data from management and workers. We then ran the redesigned program for six months on the same worksite. Foremen received detailed weekly feedback from safety inspections, and posters displayed worksite and subcontractor safety scores. In the final program design, the whole site, not individual subcontractors, was the unit of analysis and recognition. This received high levels of acceptance from workers, who noted increased levels of site unity and team-building. This pilot program showed that construction workers value solidarity with others on site, demonstrating the importance of health and safety programs that engage all workers through a reliable and consistent communication infrastructure. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. Confidence in the long-term safety of deep geological repositories. Its development and communication

    International Nuclear Information System (INIS)

    1999-01-01

    The technical aspects of confidence have been the subject of considerable debate, especially the concept of model validation. The safety case that is provided at a particular stage in the planning, construction, operation or closure of a deep geological repository is a part of a broader decision basis that guides the repository-development process. The basic steps for deriving the safety case at various stages of repository development involve: a safety assessment; and the documentation of the safety assessment, a statement of confidence in the safety indicated by the assessment, and the confirmation of the appropriateness of the safety strategy. The approaches to establish confidence in the evaluation of safety should aim to ensure that the decisions taken within the incremental process of repository development are well-founded. Various aspects of confidence in the evaluation of safety, and their integration within a safety case, are presented in detail in the present report. When communicating confidence in the findings of a safety assessment, clarity in the communication of concepts is always required. Consistent with this requirement, key concepts are specifically defined in the main text of the report. (R.P.)

  20. Development of evaluation method for software safety analysis techniques

    International Nuclear Information System (INIS)

    Huang, H.; Tu, W.; Shih, C.; Chen, C.; Yang, W.; Yih, S.; Kuo, C.; Chen, M.

    2006-01-01

    Full text: Full text: Following the massive adoption of digital Instrumentation and Control (I and C) system for nuclear power plant (NPP), various Software Safety Analysis (SSA) techniques are used to evaluate the NPP safety for adopting appropriate digital I and C system, and then to reduce risk to acceptable level. However, each technique has its specific advantage and disadvantage. If the two or more techniques can be complementarily incorporated, the SSA combination would be more acceptable. As a result, if proper evaluation criteria are available, the analyst can then choose appropriate technique combination to perform analysis on the basis of resources. This research evaluated the applicable software safety analysis techniques nowadays, such as, Preliminary Hazard Analysis (PHA), Failure Modes and Effects Analysis (FMEA), Fault Tree Analysis (FTA), Markov chain modeling, Dynamic Flowgraph Methodology (DFM), and simulation-based model analysis; and then determined indexes in view of their characteristics, which include dynamic capability, completeness, achievability, detail, signal/ noise ratio, complexity, and implementation cost. These indexes may help the decision makers and the software safety analysts to choose the best SSA combination arrange their own software safety plan. By this proposed method, the analysts can evaluate various SSA combinations for specific purpose. According to the case study results, the traditional PHA + FMEA + FTA (with failure rate) + Markov chain modeling (without transfer rate) combination is not competitive due to the dilemma for obtaining acceptable software failure rates. However, the systematic architecture of FTA and Markov chain modeling is still valuable for realizing the software fault structure. The system centric techniques, such as DFM and Simulation-based model analysis, show the advantage on dynamic capability, achievability, detail, signal/noise ratio. However, their disadvantage are the completeness complexity

  1. Implementing national nuclear safety plan at the preliminary stage of nuclear power project development

    International Nuclear Information System (INIS)

    Xue Yabin; Cui Shaozhang; Pan Fengguo; Zhang Lizhen; Shi Yonggang

    2014-01-01

    This study discusses the importance of nuclear power project design and engineering methods at the preliminary stage of its development on nuclear power plant's operational safety from the professional view. Specifically, we share our understanding of national nuclear safety plan's requirement on new reactor accident probability, technology, site selection, as well as building and improving nuclear safety culture and strengthening public participation, with a focus on plan's implications on preliminary stage of nuclear power project development. Last, we introduce China Huaneng Group's work on nuclear power project preliminary development and the experience accumulated during the process. By analyzing the siting philosophy of nuclear power plant and the necessity of building nuclear safety culture at the preliminary stage of nuclear power project development, this study explicates how to fully implement the nuclear safety plan's requirements at the preliminary stage of nuclear power project development. (authors)

  2. New Possibilities for development of the internal health and safety organisation

    DEFF Research Database (Denmark)

    Hasle, Peter; Jensen, Per Langå

    2004-01-01

    Research from several countries indicates that the internal health and safety organisation in most companies is placed in an appendix position. A possibility for developing a stronger and more effective health and safety organisation is to introduce learning. This approach has been applied...... in a Danish network project with eleven companies. The results indicate that health and safety managers and safety representatives have difficulties in fulfilling the role as change agents in mastering such a development project. Only three of the eleven companies turned out to be able to implement successful...

  3. Study on the development of safety regulations for geological disposal of high-level radioactive waste

    International Nuclear Information System (INIS)

    Wei Fangxin

    2012-01-01

    The development of regulations under Regulations on Safety Management of Radioactive Waste has become necessary as the issuance of it. The regulations related to geological disposal of high-level radioactive waste can promote the progress of research and development on geological disposal of high-level radioactive waste in China. This paper has present suggestions on development of regulations on geological disposal of high-level radioactive waste by analyzing development of safety regulations on geological disposal of high-level radioactive waste in foreign countries and problems occurred in China and discussed important issues related to the development of safety regulations on geological disposal of high-level radioactive waste. (author)

  4. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  5. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  6. Scale development of safety management system evaluation for the airline industry.

    Science.gov (United States)

    Chen, Ching-Fu; Chen, Shu-Chuan

    2012-07-01

    The airline industry relies on the implementation of Safety Management System (SMS) to integrate safety policies and augment safety performance at both organizational and individual levels. Although there are various degrees of SMS implementation in practice, a comprehensive scale measuring the essential dimensions of SMS is still lacking. This paper thus aims to develop an SMS measurement scale from the perspective of aviation experts and airline managers to evaluate the performance of company's safety management system, by adopting Schwab's (1980) three-stage scale development procedure. The results reveal a five-factor structure consisting of 23 items. The five factors include documentation and commands, safety promotion and training, executive management commitment, emergency preparedness and response plan and safety management policy. The implications of this SMS evaluation scale for practitioners and future research are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Technology development of maintenance optimization and reliability analysis for safety features in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Woon; Choi, Seong Soo; Lee, Dong Gue; Kim, Young Il

    1999-12-01

    The reliability data management system (RDMS) for safety systems of PHWR type plants has been developed and utilized in the reliability analysis of the special safety systems of Wolsong Unit 1,2 with plant overhaul period lengthened. The RDMS is developed for the periodic efficient reliability analysis of the safety systems of Wolsong Unit 1,2. In addition, this system provides the function of analyzing the effects on safety system unavailability if the test period of a test procedure changes as well as the function of optimizing the test periods of safety-related test procedures. The RDMS can be utilized in handling the requests of the regulatory institute actively with regard to the reliability validation of safety systems. (author)

  8. The patient safety climate in healthcare organizations (PSCHO) survey: Short-form development.

    Science.gov (United States)

    Benzer, Justin K; Meterko, Mark; Singer, Sara J

    2017-08-01

    Measures of safety climate are increasingly used to guide safety improvement initiatives. However, cost and respondent burden may limit the use of safety climate surveys. The purpose of this study was to develop a 15- to 20-item safety climate survey based on the Patient Safety Climate in Healthcare Organizations survey, a well-validated 38-item measure of safety climate. The Patient Safety Climate in Healthcare Organizations was administered to all senior managers, all physicians, and a 10% random sample of all other hospital personnel in 69 private sector hospitals and 30 Veterans Health Administration hospitals. Both samples were randomly divided into a derivation sample to identify a short-form subset and a confirmation sample to assess the psychometric properties of the proposed short form. The short form consists of 15 items represented 3 overarching domains in the long-form scale-organization, work unit, and interpersonal. The proposed short form efficiently captures 3 important sources of variance in safety climate: organizational, work-unit, and interpersonal. The short-form development process was a practical method that can be applied to other safety climate surveys. This safety climate short form may increase response rates in studies that involve busy clinicians or repeated measures. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  9. Developing and Testing the Health Care Safety Hotline: A Prototype Consumer Reporting System for Patient Safety Events.

    Science.gov (United States)

    Schneider, Eric C; Ridgely, M Susan; Quigley, Denise D; Hunter, Lauren E; Leuschner, Kristin J; Weingart, Saul N; Weissman, Joel S; Zimmer, Karen P; Giannini, Robert C

    2017-06-01

    This article describes the design, development, and testing of the Health Care Safety Hotline, a prototype consumer reporting system for patient safety events. The prototype was designed and developed with ongoing review by a technical expert panel and feedback obtained during a public comment period. Two health care delivery organizations in one metropolitan area collaborated with the researchers to demonstrate and evaluate the system. The prototype was deployed and elicited information from patients, family members, and caregivers through a website or an 800 phone number. The reports were considered useful and had little overlap with information received by the health care organizations through their usual risk management, customer service, and patient safety monitoring systems. However, the frequency of reporting was lower than anticipated, suggesting that further refinements, including efforts to raise awareness by actively soliciting reports from subjects, might be necessary to substantially increase the volume of useful reports. It is possible that a single technology platform could be built to meet a variety of different patient safety objectives, but it may not be possible to achieve several objectives simultaneously through a single consumer reporting system while also establishing trust with patients, caregivers, and providers.

  10. Influence of Ergonomics on Traffic Safety and Economy Development

    Directory of Open Access Journals (Sweden)

    Teodor Perić

    2004-09-01

    Full Text Available As an interdisciplinary science, ergonomics needs to makethe operating of traffic safer, faster and more reliable, for thesake of higher profitability and generally improved economiceffects. This is achieved by adapting and shaping the workplace,machines, transport means, equipment, physical environment,working process etc. according to experience abouthuman anatomic physica~ sociologica~ intellectual and otherminimal, average or maximal capabilities. Therefore, it is necessaryto analyse ergonomics from the standpoint of better productivenessof humans, greater safety (comfort and security ingeneral.

  11. Presentation on development of safety assessment reports in Romania

    International Nuclear Information System (INIS)

    Goicea, L.

    2002-01-01

    This presentation shows whole steps of Cernavoda 2 NPP licensing and accident management relevant changes considered. There are description of CANDU Safety principles and design criteria, as well as FSAR structured according to NRC Regulatory Guide 1.70, format of presentation of accident analyses, applicable acceptant criteria to analyses and Design Codes, Safety standards and Safety Guides used. The main features of CANDU reactors are presented, including of base design characteristics and describing of structures of CANDU reactors. During the licensing Cernavoda 2 are passed through Site approval, Construction permits of NPP system (1980-1993), Final construction license (1993) and Commissioning license (1995). In the May 1998 the First operating license is issued, based on FSAR Phase 1, Full power probationary report and carried out the requirements related to revising the FSAR and initiating of the Modernization program. To achieve the defense in depth concept are used and implemented the norms and quality standards during all plant stages, as well as selecting the high quality materials. During all plant stages is keeps strictly accomplishment of the quality requirements, and ensures a high level of reliability by using of operating principle and fabrication. In NPP operation is established using of the approved operating concept permitting only the safe condition for reactor operation. In the process of Cernavoda NPP licensing and operating the CSA and CGSB Canadian Standards, ASME and ANSI American Standards, Romanian Norms are implemented. Another useful Codes and Standards are implemented too, as ACI, ASTM, ANSI, AWS and others. In accident analysis for Safety Analysis Report for Cernavoda Unit 1 are involved 37 computer codes, in such areas as Reactor physics, Thermal-hydraulics, Fuel behavior, Fuel channel, Containment, and Fission product release and dose calculation

  12. NPA applications development in the nuclear safety authority framework

    International Nuclear Information System (INIS)

    Maselj, A.; Vojnovic, D.; Gregonc, M.

    1999-01-01

    Due to the present tasks of the SNSA (Slovenian Nuclear Safety Administration) there was a need to gain a tool for analysing the transients of the Krsko Nuclear Power Plant at the SNSA. Combining the RELAP5 code with graphical interface NPA (Nuclear Plant Analyzer), the SNSA management saw an opportunity to have a powerful instrument for analyses and assessments on a user friendly basis and without high costs. The Krsko NPP Analyzer is a joint project of the SNSA and the operator, the Krsko NPP. The RELAP5/Mod2.5 input deck was constructed by the Krsko NPP's experts and their subcontractors. In 1996 the work started with translation of input model from RELAP5/Mod2.5 version to Mod3.2. This was done by Tractebel which combined NPA masks with translated input deck and constructed new dynamic function and interactive commands between graphical MMI (Man Machine Interface) and simulation code. Since Tractebel performed similar activities for the Belgian plants, their experience was used through a transfer of knowledge to the SNSA. After this phase of the project, a user of the NPP Analyzer can run accidents as SBLOCA, Main Steam Line Break, Feed Water Break, SGTR, and many other transients activating and combining interactive commands, starting from a full power operation. This project has not been finished yet. Improvements of the input deck should be done. The Critical Safety Function window will be created. The analyzer will be a helpful tool during the training program for Accident Assessment Group, which will give to the experts basic knowledge of plant operation, its systems, and physical phenomena during a steady state and transients or accidents. Also a new dimension is added to the existing safety evaluations at the SNSA to confirm the requested level of nuclear safety at the Krsko NPP. (author)

  13. Safety

    International Nuclear Information System (INIS)

    Jones, P.M.S.

    1987-01-01

    Aspects of fission reactors are considered - control, heat removal and containment. Brief descriptions of the reactor accidents at the SL-1 reactor (1961), Windscale (1957), Browns Ferry (1975), Three Mile Island (1979) and Chernobyl (1986) are given. The idea of inherently safe reactor designs is discussed. Safety assessment is considered under the headings of preliminary hazard analysis, failure mode analysis, event trees, fault trees, common mode failure and probabalistic risk assessments. These latter can result in a series of risk distributions linked to specific groups of fault sequences and specific consequences. A frequency-consequence diagram is shown. Fatal accident incidence rates in different countries including the United Kingdom for various industries are quoted. The incidence of fatal cancers from occupational exposure to chemicals is tabulated. Human factors and the acceptability of risk are considered. (U.K.)

  14. Trends in food safety standards and regulation implications for developing countries

    OpenAIRE

    Caswell, Julie A.

    2003-01-01

    "Food safety is affected by the decisions of producers, processors, distributors, food service operators, and consumers, as well as by government regulations. In developed countries, the demand for higher levels of food safety has led to the implementation of regulatory programs that address more types of safety-related attributes (such as bovine spongiform encephalopathy (BSE), microbial pathogens, environmental contaminants, and animal drug and pesticide residues) and impose stricter standa...

  15. Key Factors Affecting Construction Safety Performance in Developing Countries: Evidence from Cambodia

    OpenAIRE

    Durdyev, Serdar; Mohamed, Sherif; Lay, Meng Leang; Ismail, Syuhaida

    2017-01-01

    Although proper safety management in construction is of utmost importance; anecdotal evidence suggests that safety is not adequately considered in many developing countries. This paper considers the key variables affecting construction safety performance in Cambodia. Using an empirical questionnaire survey targeting local construction professionals, respondents were invited to rate the level of importance of 30 variables identified from the seminal literature. The data set was subjected to f...

  16. On the Use of Safety Certification Practices in Autonomous Field Robot Software Development

    DEFF Research Database (Denmark)

    Mogensen, Johann Thor Ingibergsson; Schultz, Ulrik Pagh; Kuhrmann, Marco

    2015-01-01

    reactions or performance in malfunctioning systems, and influence industry regarding software development and project management. However, academia seemingly did not reach the same degree of utilisation of standards. This paper presents the findings from a systematic mapping study in which we study...... the state-of-the-art in developing software for safety-critical software for autonomous field robots. The purpose of the study is to identify practices used for the development of autonomous field robots and how these practices relate to available safety standards. Our findings from reviewing 49 papers show...... on the quest for suitable approaches to develop safety-critical software, awaiting appropriate standards for this support....

  17. A report on developing a checklist to assess company plans focused on improving safety awareness, safe behaviour and safety culture: final report

    NARCIS (Netherlands)

    Steijger, N.; Starren, H.; Keus, M.; Gort, J.; Vervoort, M.

    2003-01-01

    This report describes the process of developing a checklist to asses company plans focused on improving safety awareness, safe behaviour and safety culture. These plans are part of a programme initiated by the Ministry of Social Affairs and Employment aiming at improving the safety performance of

  18. Safety research on fusion DEMO in Japan: Toward development of safety strategy of a water-cooled DEMO

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Makoto, E-mail: nakamura.makoto@jaea.go.jp [Japan Atomic Energy Agency, Rokkasho 039-3212, Aomori (Japan); Tobita, Kenji; Someya, Youji; Utoh, Hiroyasu; Sakamoto, Yoshiteru [Japan Atomic Energy Agency, Rokkasho 039-3212, Aomori (Japan); Gulden, Werner [Fusion for Energy, Garching D-85748 (Germany)

    2016-11-01

    Highlights: • This paper reports the current status of a safety research on water-cooled fusion DEMO in Japan. • We report analyses of two transients: (i) complete loss of decay heat removal and (ii) major ex-VV LOCA. • The MELCOR analysis has clarified the temperature histories of the DEMO components in complete loss of decay heat removal. • A strategy to reduce the pressure load to the final barrier confining radioactive materials is proposed against the major ex-VV LOCA. - Abstract: This paper reports the current status of a safety research on water-cooled fusion DEMO in Japan. A basic strategy of development of the safety guidelines is described for DEMO based on a water-cooled solid pebble bed blanket. Clarification of safety features of the DEMO in accident situations is a key issue to develop the guidelines. Recent achievements in understanding of the safety features of the water-cooled DEMO are reported. The MELCOR analysis has clarified the temperature histories of the DEMO components in a complete loss of decay heat removal event. The transient behavior of the first wall temperature is found to be essentially different from that of ITER. The pressure load to the tokamak cooling water system vault (TCWSV) is analyzed based on a simple model equation of the energy conservation. If the amount of the primary coolant is the same as that of Slim-CS, the previous small Japanese DEMO, the discharged water does not damage the TCWSV with the volume and pressure-tightness similar to those of pressurized light water reactors. It is shown that implementation of a pressure suppression system to the small TCWSV is effective to suppress the pressure load to the second confinement barrier.

  19. Analysis of safety information for nuclear power plants and development of source term estimation program

    International Nuclear Information System (INIS)

    Kim, Tae Woon; Choi, Seong Soo; Park, Jin Hee

    1999-12-01

    Current CARE(Computerized Advisory System for Radiological Emergency) in KINS(Korea Institute of Nuclear Safety) has no STES(Source Term Estimation System) which links between SIDS(Safety Information Display System) and FADAS(Following Accident Dose Assessment System). So in this study, STES is under development. STES system is the system that estimates the source term based on the safety information provided by SIDS. Estimated source term is given to FADAS as an input for estimation of environmental effect of radiation. Through this first year project STES for the Kori 3,4 and Younggwang 1,2 has been developed. Since there is no CARE for Wolsong(PHWR) plants yet, CARE for Wolsong is under construction. The safety parameters are selected and the safety information display screens and the alarm logic for plant status change are developed for Wolsong Unit 2 based on the design documents for CANDU plants

  20. Measuring patient safety in a UK dental hospital: development of a dental clinical effectiveness dashboard.

    Science.gov (United States)

    Pemberton, M N; Ashley, M P; Shaw, A; Dickson, S; Saksena, A

    2014-10-01

    Patient safety is an important marker of quality for any healthcare organisation. In 2008, the British Government white paper entitled High quality care for all, resulting from a review led by Lord Darzi, identified patient safety as a key component of quality and discussed how it might be measured, analysed and acted upon. National and local clinically curated metrics were suggested, which could be displayed via a 'clinical dashboard'. This paper explains the development of a clinical effectiveness dashboard focused on patient safety in an English dental hospital and how it has helped us identify relevant patient safety issues in secondary dental care.

  1. Safety culture giving impetus to the development of nuclear power enterprise

    International Nuclear Information System (INIS)

    Zhang Ying

    2011-01-01

    Jiangsu Nuclear Power Corporation (JNPC) have been continuously assimilating excellent nuclear safety culture at home and abroad and improving the plant safety operation and internal management level of corporation since the successful construction of Phase I project and the gradual success of the expansion project. Implemented the 'top management 8 expectations', executed the '3 into 1' (quality, environment and occupational health safety) management system. The culture of 'zero tolerance' has been deeply rooted. The safety culture brings people's heart closer, which is not only accepted by the employees, but also climbs up to a higher level and adds momentum to the scientific development of Tianwan Nuclear Power Station Base. (author)

  2. Development of safety function assessment trees for pressurized heavy water reactor LP/SD operations

    International Nuclear Information System (INIS)

    Yang, Hui Chang; Chung, Chang Hyun; Kim, Ki Yong; Jee, Moon Hak; Sung, Chang Kyoung

    2003-01-01

    The objective of Configuration Risk Management Program(CRMP) is to maintain the safety level by assuring the defense-in-depth of nuclear power plant while the configurations are changed during plant operations, especially for the LP/SD. Such a safety purpose can be achieved by establishing the risk monitoring programs with both quantitative and qualitative features. Generally, the quantitative risk evaluation models, i.e., PRA models are used for the risk evaluation during full power operation, and the qualitative risk evaluation models such as safety function assessment trees are used. Through this study, safety function assessment trees were developed

  3. Agility in Development of Safety-Critical Software: A Conceptual Model

    DEFF Research Database (Denmark)

    Tordrup Heeager, Lise; Nielsen, Peter Axel

    2018-01-01

    Safety-critical information systems are being used increasingly as we see applications in new areas such as personal medical devices, traffic control and detection of pathogens. A current research debate is whether safety-critical systems must be developed with traditional waterfall processes...

  4. Development, Dissemination, and Assessment of a Food Safety Systems Management Curriculum for Agribusiness Students in Armenia

    Science.gov (United States)

    Pokharel, Siroj; Marcy, Joseph E.; Neilan, Angela M.; Cutter, Catherine N.

    2017-01-01

    This study addresses the development, dissemination, and assessment of a Food Safety System Management (FSSM) curriculum offered to college-aged, agribusiness students in Yerevan, Armenia. Prior to beginning the program, demographic data were collected and a paper-based pretest was administered to access the food safety knowledge, behavior, and…

  5. Development of Strategic Goals of Road Safety Management: A Case Study of Montenegro

    Directory of Open Access Journals (Sweden)

    Milenko Čabarkapa

    2016-12-01

    Full Text Available Evaluation of the results of road safety management at the national level is carried out with a number of predefined indicators. These, predefined indicators should be measurable objectives of road safety management. They are set by national road safety strategies. This paper presents the control implementation of the Strategy to improve road safety in Montenegro for the period 2010-2019. The research showed that the five-year objectives of the National Strategy were achieved in the first years and significantly surmounted. This efficiency is achieved for two main reasons: the development of road safety management, and setting an unambitious, easily attainable goal. These findings are indicators that generally and globally set goals of reducing traffic fatalities cannot comprise at the same time national objectives in all countries. In this context, the methodological improvements of setting national strategic objectives established by the evidences on the national traffic safety issue are proposed.

  6. A study on development strategy of atomic safety organization for atomic environment

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Bok; Jeong, Ji Hun; Kim Tae Hee; Lee, Seung Hyuk; Woo, Eun Jung [Konkuk Univ., Seoul (Korea, Republic of)

    2005-02-15

    The objective of this research is to suggest some strategies which can make the safety of atomic power possible and reinforce the nuclear regulatory system. It will contribute to the expansion and settlement of nuclear safety culture by making the public understand well about the safety of nuclear energy, and searching public relations and incentive strategies. In addition, since the nuclear environment is changing rapidly, the necessity of cooperation between the public and the private has veen mostly required. So we need to develop the effective administrative system based on their cooperation. Therefore, it will examine the function of organization established, operation system, and also social network closely connected with the nuclear safety. Moreover, by analyzing the change of regulatory environment and present safety confirmation of nuclear energy, it will devise the new safety confirmation system of nuclear energy.

  7. The development of regulatory expectations for computer-based safety systems for the UK nuclear programme

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, P. J. [HM Nuclear Installations Inspectorate Marine Engineering Submarines Defence Nuclear Safety Regulator Serco Assurance Redgrave Court, Merton Road, Bootle L20 7HS (United Kingdom); Westwood, R.N; Mark, R. T. [FLEET HQ, Leach Building, Whale Island, Portsmouth, PO2 8BY (United Kingdom); Tapping, K. [Serco Assurance,Thomson House, Risley, Warrington, WA3 6GA (United Kingdom)

    2006-07-01

    The Nuclear Installations Inspectorate (NII) of the UK's Health and Safety Executive (HSE) has completed a review of their Safety Assessment Principles (SAPs) for Nuclear Installations recently. During the period of the SAPs review in 2004-2005 the designers of future UK naval reactor plant were optioneering the control and protection systems that might be implemented. Because there was insufficient regulatory guidance available in the naval sector to support this activity the Defence Nuclear Safety Regulator (DNSR) invited the NII to collaborate with the production of a guidance document that provides clarity of regulatory expectations for the production of safety cases for computer based safety systems. A key part of producing regulatory expectations was identifying the relevant extant standards and sector guidance that reflect good practice. The three principal sources of such good practice were: IAEA Safety Guide NS-G-1.1 (Software for Computer Based Systems Important to Safety in Nuclear Power Plants), European Commission consensus document (Common Position of European Nuclear Regulators for the Licensing of Safety Critical Software for Nuclear Reactors) and IEC nuclear sector standards such as IEC60880. A common understanding has been achieved between the NII and DNSR and regulatory guidance developed which will be used by both NII and DNSR in the assessment of computer-based safety systems and in the further development of more detailed joint technical assessment guidance for both regulatory organisations. (authors)

  8. Developing of Radioactive Wastes Management Safety at Baldone Repository Radons

    International Nuclear Information System (INIS)

    Abramenkovs, A.; Abramenkova, G.; Klavins, M.

    2008-01-01

    The near surface radioactive wastes repository Radons near the Baldone city was put in operation in 1962. The safety assessment of repository was performed during 2000-2001 under the PHARE project to evaluate the recommended upgrades of repository. The outline design for new vaults and interim storage for long lived radioactive wastes was elaborated during 2003-2004 years. The Environmental Impact Assessment (EIA) for upgrade of Baldone repository was performed during 2004-2005 years. Additional evaluations of radioactive wastes management safety were performed during 2006 year by the experts of ENRESA, Spain. It was shown, that the additional efforts were spent for improving of radioactive wastes cementation in concrete containers. The results of tritium and Cs 137 leaching studies are presented and discussed. It was shown, that additives can significantly reduce the migration of radionuclides in ground water. The leaching coefficients for tritium and Cs 137 were determined to supply with the necessary data the risk assessment calculations for operation of Baldone repository R adons

  9. A study to develop the domestic functional requirements of the specific safety systems of CANDU

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Man Woong [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of); Lee, Jae Young; Park, Kun Chul [Handong Global Univ., Pohang (Korea, Republic of)] (and others)

    2003-03-15

    The present research has been made to develop and review critically the functional requirements of the specific safety systems of CANDU such as SDS-1, SDS2, ECCS, and containment. Based on R documents for this, a systematic study was made to develop the domestic regulation statements. Also, the conventional laws are carefully reviewed to see the compatibility to CANDU. Also, the safety assessment method for CANDU was studied by reviewing C documents and recommendation of IAEA. Through the present works, the vague policy in the CANDU safety regulation is cleaning up in a systematic form and a new frame to measure the objective risk of nuclear power plants was developed.

  10. Development of the methodology and approaches to validate safety and accident management

    International Nuclear Information System (INIS)

    Asmolov, V.G.

    1997-01-01

    The article compares the development of the methodology and approaches to validate the nuclear power plant safety and accident management in Russia and advanced industrial countries. It demonstrates that the development of methods of safety validation is dialectically related to the accumulation of the knowledge base on processes and events during NPP normal operation, transients and emergencies, including severe accidents. The article describes the Russian severe accident research program (1987-1996), the implementation of which allowed Russia to reach the world level of the safety validation efforts, presents future high-priority study areas. Problems related to possible approaches to the methodological accident management development are discussed. (orig.)

  11. Development of embedded Control System for Control and Safety Rod Drive Mechanisms (CSRDMs) of PFBR

    International Nuclear Information System (INIS)

    Kameswari, K.; Palanisami, K.; Thirugnana Murthy, D.; Murali, N.; Satyamurty, S.A.V.

    2013-01-01

    Prototype Fast Breeder Reactor (PFBR), a 500 MWe, Sodium cooled, fast breeder reactor is nearing completion at Kalpakkam, Tamil Nadu. PFBR has two independent, fast acting and diverse shutdown systems, one with nine Control and Safety Rods (CSRs) and another with three Diverse Safety Rods (DSRs), with independent driving mechanisms called CSRDMs and DSRDMs respectively. This paper deals with the development of Real Time Computer based Control system for controlling nine CSRDMs with model based software development environment - SCADE (Safety Critical Application Development Environment). (author)

  12. A study to develop the domestic functional requirements of the specific safety systems of CANDU

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Man Woong; Lee, Jae Young; Bang, Kwang Hyun [Handong Global Univ., Pohang (Korea, Republic of)] (and others)

    2001-03-15

    The present research has been made to develop and review critically the functional requirements of the specific safety systems of CANDU such as SOS-1, SOS-2, ECCS and containment. Based on R documents for this, a systematic study was made to develop the domestic regulation statements. Also, the conventional laws are carefully reviewed to see the compatibility to CANDU. Also, the safety assessment method for CANDU was studied by reviewing C documents and recommendation of IAEA. Through the present works, the vague policy in the CANDU safety regulation is cleaning up in a systematic form and a new frame to measure the objective risk of nuclear power plants was developed.

  13. Contemporary Approaches to Safety Culture: Lessons from Developing a Regulatory Oversight Approach

    International Nuclear Information System (INIS)

    Goebel, V.; Heppell-Masys, K.

    2016-01-01

    The Canadian Nuclear Safety Commission (CNSC) regulates the use of nuclear energy and materials to protect health, safety, security and the environment, and to implement Canada’s international commitments on the peaceful use of nuclear energy; and to disseminate objective scientific, technical and regulatory information to the public. In the late 1990s, the CNSC conducted research into an Organization and Management (O&M) assessment method. Based on this research the CNSC conducted O&M assessments at all Canadian nuclear power plants and conducted additional assessments of nuclear research and uranium mine and mill operations. The results of these assessments were presented to licencees and used to inform their ongoing actions related to safety culture. Additional safety culture outreach and oversight activities provided licencees with opportunities to develop effective safety culture assessment methods, to share best practices across industry, and to strive for continual improvement of their organizations. Recent changes to the Canadian Standards Association (CSA) management system standard have resulted in the inclusion of requirements associated to safety culture and human performance. Representatives from several sectors of Canada’s nuclear industry, as well as participation from regulators such as the CNSC took part to the development of this consensus standard. Specifically, these requirements focus on monitoring and understanding safety culture, integrating safety into all of the requirements of the management system, committing workers to adhere to the management system and supporting excellence in workers’ performance. The CNSC is currently developing a regulatory document on safety culture which includes key concepts applicable to all licencees and specific requirements related to self-assessment, and additional guidance for nuclear power plants. Developing a regulatory document on safety culture requires consultation and fact finding initiatives at

  14. Recent developments in IFE safety and tritium research and considerations for future nuclear fusion facilities

    International Nuclear Information System (INIS)

    Reyes, Susana; Anklam, Tom; Meier, Wayne; Campbell, Patrick; Babineau, Dave; Becnel, James; Taylor, Craig; Coons, Jim

    2016-01-01

    Highlights: • The safety characteristics and at risk inventories in an IFE facility are discussed. • The primary nuclear hazard is the potential exposure of workers and/or the public to tritium and/or neutronically activated products. • Recent technology developments in tritium processing are key for minimization of inventories. • Initial safety studies indicate that hazards associated to the use of liquid lithium can be appropriately managed. • Simulation of worst-case scenarios indicate that the accident consequences are limited and below the limit for public evacuation. - Abstract: Over the past five years, the fusion energy group at Lawrence Livermore National Laboratory (LLNL) has made significant progress in the area of safety and tritium research for Inertial Fusion Energy (IFE). Focus has been driven towards the minimization of inventories, accident safety, development of safety guidelines and licensing considerations. Recent technology developments in tritium processing and target fill have had a major impact on reduction of tritium inventories in the facility. A safety advantage of inertial fusion energy using indirect-drive targets is that the structural materials surrounding the fusion reactions can be protected from target emissions by a low-pressure chamber fill gas, therefore eliminating plasma-material erosion as a source of activated dust production. An important inherent safety advantage of IFE when compared to other magnetic fusion energy (MFE) concepts that have been proposed to-date (including ITER), is that loss of plasma control events with the potential to damage the first wall, such as disruptions, are non-conceivable, therefore eliminating a number of potential accident initiators and radioactive in-vessel source term generation. In this paper, we present an overview of the safety assessments performed to-date, comparing results to the US DOE Fusion Safety Standards guidelines and the recent lessons-learnt from ITER safety and

  15. Recent developments in IFE safety and tritium research and considerations for future nuclear fusion facilities

    Energy Technology Data Exchange (ETDEWEB)

    Reyes, Susana, E-mail: reyes20@llnl.gov [Lawrence Livermore National Laboratory, Livermore, CA (United States); Anklam, Tom; Meier, Wayne; Campbell, Patrick [Lawrence Livermore National Laboratory, Livermore, CA (United States); Babineau, Dave; Becnel, James [Savannah River National Laboratory, Aiken, SC (United States); Taylor, Craig; Coons, Jim [Los Alamos National Laboratory, Los Alamos, NM (United States)

    2016-11-01

    Highlights: • The safety characteristics and at risk inventories in an IFE facility are discussed. • The primary nuclear hazard is the potential exposure of workers and/or the public to tritium and/or neutronically activated products. • Recent technology developments in tritium processing are key for minimization of inventories. • Initial safety studies indicate that hazards associated to the use of liquid lithium can be appropriately managed. • Simulation of worst-case scenarios indicate that the accident consequences are limited and below the limit for public evacuation. - Abstract: Over the past five years, the fusion energy group at Lawrence Livermore National Laboratory (LLNL) has made significant progress in the area of safety and tritium research for Inertial Fusion Energy (IFE). Focus has been driven towards the minimization of inventories, accident safety, development of safety guidelines and licensing considerations. Recent technology developments in tritium processing and target fill have had a major impact on reduction of tritium inventories in the facility. A safety advantage of inertial fusion energy using indirect-drive targets is that the structural materials surrounding the fusion reactions can be protected from target emissions by a low-pressure chamber fill gas, therefore eliminating plasma-material erosion as a source of activated dust production. An important inherent safety advantage of IFE when compared to other magnetic fusion energy (MFE) concepts that have been proposed to-date (including ITER), is that loss of plasma control events with the potential to damage the first wall, such as disruptions, are non-conceivable, therefore eliminating a number of potential accident initiators and radioactive in-vessel source term generation. In this paper, we present an overview of the safety assessments performed to-date, comparing results to the US DOE Fusion Safety Standards guidelines and the recent lessons-learnt from ITER safety and

  16. Monitoring road safety development at regional level: A case study in the ASEAN region.

    Science.gov (United States)

    Chen, Faan; Wang, Jianjun; Wu, Jiaorong; Chen, Xiaohong; Zegras, P Christopher

    2017-09-01

    Persistent monitoring of progress, evaluating the results of interventions and recalibrating to achieve continuous improvement over time is widely recognized as being crucial towards the successful development of road safety. In the ASEAN (Association of Southeast Asian Nations) region there is a lack of well-resourced teams that contain multidisciplinary safety professionals, and specialists in individual countries, who are able to carry out this work effectively. In this context, not only must the monitoring framework be effective, it must also be easy to use and adapt. This paper provides a case study that can be easily reproduced; based on an updated and refined Road Safety Development Index (RSDI), by means of the RSR (Rank-sum ratio)-based model, for monitoring/reporting road safety development at regional level. The case study was focused on the road safety achievements in eleven Southeast Asian countries; identifying the areas of poor performance, potential problems and delays. These countries are finally grouped into several classes based on an overview of their progress and achievements regarding to road safety. The results allow the policymakers to better understand their own road safety progress toward their desired impact; more importantly, these results enable necessary interventions to be made in a quick and timely manner. Keeping action plans on schedule if things are not progressing as desired. This would avoid 'reinventing the wheel' and trial and error approaches to road safety, making the implementation of action plans more effective. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Road safety in developing countries: The role of research.

    NARCIS (Netherlands)

    Schreuder, D.A.

    1986-01-01

    Road accidents are a continuous burden for all countries, developing and developed alike. There are reasons, however, to pay special attention to developing countries as the situation often seems to be more unfavourable as in developed countries, and as the consequences of road accidents, can be

  18. Key Factors Affecting Construction Safety Performance in Developing Countries: Evidence from Cambodia

    Directory of Open Access Journals (Sweden)

    Serdar Durdyev

    2017-12-01

    Full Text Available Although proper safety management in construction is of utmost importance; anecdotal evidence suggests that safety is not adequately considered in many developing countries. This paper considers the key variables affecting construction safety performance in Cambodia. Using an empirical questionnaire survey targeting local construction professionals, respondents were invited to rate the level of importance of 30 variables identified from the seminal literature. The data set was subjected to factor analysis. Correlations between the variables show that five key factors underlie the challenges facing the local industry; management and organisation, resources, site management, cosmetic and workforce. It is found that the forefront construction professionals (top management and government authorities should take more responsibilities for further improvements in safety performance on project sites. Findings and recommendations of this study may be useful to construction professional who are seeking ways to improve safety records in developing countries.

  19. Development of Safety Grade PLC (POSAFE-Q) and Performance Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Hwoi; Park, Won Man; Choi, Jong Gyun; Lee, Dong Young [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); No, Young Hun; Song, Seung Hwan [POSCON, Seoul (Korea, Republic of)

    2006-07-01

    The safety grade PLC (POSAFE-Q) is being developed in the Korea Nuclear Instrumentation and Control System (KNICS) R and D project. The PLC satisfies Safety Class 1E, Quality Class 1, and Seismic Category I. The software such as the RTOS and firmware are being developed according to the safety critical software life cycle. Especially, the formal method is applied to design the SRS (Software Requirement Spec.) and the SDS (Software Design Specification.) to be error-free. The POSAFE-Q has several modules such as processor module, input and output modules, communication modules, redundant processor module, redundant power modules, etc,. To verify the function and performance, several tests such as CT, IT and ST were performed. And also, the equipment qualification test for environment, EMI and EMC, and seismic ware performed. All tests are satisfied with the requirements and specification for safety grade PLC, and the criteria for safety system in nuclear power plants.

  20. Development of Safety Grade PLC (POSAFE-Q) and Performance Test Results

    International Nuclear Information System (INIS)

    Kim, Chang Hwoi; Park, Won Man; Choi, Jong Gyun; Lee, Dong Young; No, Young Hun; Song, Seung Hwan

    2006-01-01

    The safety grade PLC (POSAFE-Q) is being developed in the Korea Nuclear Instrumentation and Control System (KNICS) R and D project. The PLC satisfies Safety Class 1E, Quality Class 1, and Seismic Category I. The software such as the RTOS and firmware are being developed according to the safety critical software life cycle. Especially, the formal method is applied to design the SRS (Software Requirement Spec.) and the SDS (Software Design Specification.) to be error-free. The POSAFE-Q has several modules such as processor module, input and output modules, communication modules, redundant processor module, redundant power modules, etc,. To verify the function and performance, several tests such as CT, IT and ST were performed. And also, the equipment qualification test for environment, EMI and EMC, and seismic ware performed. All tests are satisfied with the requirements and specification for safety grade PLC, and the criteria for safety system in nuclear power plants

  1. Developing a safety report for an existing conversion facility

    International Nuclear Information System (INIS)

    Carisse, Hess

    2013-01-01

    A review of the process used to meet the regulatory requirements for a Safety Report at an existing conversion facility is described. This paper will cover the establishment of the regulatory criteria, selection of appropriate methodologies, identification of events and modeling of credible events. Once established there is on-going maintenance to deal with design changes and the need for periodic reviews will also be discussed. Challenges in dealing with the various phases, including incorporation of historical licensing documents, and lessons learned are presented. Of specific interest is the failure of the selected methodology to deal with infrastructure issues. One aspect of lessons learned that will be explored is the lack of an available mechanism for sharing information with similar fuel cycle facilities which is compounded by the fact that there are a small number of fuel cycle facilities compared to nuclear power plants. Possible approaches to dealing with this issue are also discussed. (authors)

  2. Status of nuclear safety developments and prospects for the future

    International Nuclear Information System (INIS)

    Birkhofer, A.; Laverie, M.

    1992-01-01

    During the eighties, the emphasis on safety questions progressively shifted from design and construction of plants towards the operation of existing plants. Lessons learned from incidents and accidents in national or foreign plants, experience gained from the operation and maintenance of plants, research and ageing of installations were some of the issues on which, at that time, the nuclear community focused its attention and concern. At the same time, numerous actions, dedicated to the strengthening of defense-in-depth which consists of piling up enough dispositions (or defense lines) to be able to deal with situations even beyond the initial design of plants, were implemented. Despite all these technical precautions to reduce the risk to the public and the environment, the acceptance level decreased in some countries, due to the impact of T.M.T. and Chernobyl, a certain misunderstanding between technicians and the public proceeding from a lack of openness and poor communication

  3. Workplace activities to promote small attempts for safety. Toward development of safety culture in a nuclear power plant

    International Nuclear Information System (INIS)

    Fukui, Hirokazu; Sugiman, Toshio

    2007-01-01

    Activities that could possibly grow into learning activities for developing safety culture were explored by intensive fieldwork in a nuclear power plant depending on Engestroem's activity theory. As a first step to achieve this goal, workers' small attempts that might contribute to nurturing a safety culture were investigated. Eight kinds of activity were observed and interpreted as having the possibility to facilitate small recognition and small practice, i.e., activities including (1) workgroup as community, (2) other workgroups and other departments as community, (3) meeting drawing remarks as mediating artifacts, (4) study session and Off-the-Job-Training as mediating artifact, (5) award as mediating artifact, (6) extended leave as mediating artifact, (7) check sheet as mediating artifact, and (8) skill-transfer system as mediating artifact. (author)

  4. Development of standards and investigation of safety examination items for advancement of safety regulation of fast breeder reactor

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    The purposes of this study are to prepare the fuel technical standard and the structure and materials standard of fast breeder reactors (FBRs), and to develop the requirements in a reactor establishment permission. The objects of this study are mainly the Monju high performance core and a demonstration FBR. In JFY 2012, the following results were obtained. As for the fuel technical standard, the fuel technical standard adapting the examination of integrity of the FBR fuels was prepared based on the information and data obtained in this study. As for the structure and material standard, the investigation of the revised parts of the standard was carried out. And as for the examination of the safety requirements, safety evaluation items for the future FBR plant and the fission products to be considered in a reactor establishment permission were investigated and examined. (author)