The pre-existing population of 5S rRNA effects p53 stabilization during ribosome biogenesis inhibition.

Science.gov (United States)

Onofrillo, Carmine; Galbiati, Alice; Montanaro, Lorenzo; Derenzini, Massimo

2017-01-17

Pre-ribosomal complex RPL5/RPL11/5S rRNA (5S RNP) is considered the central MDM2 inhibitory complex that control p53 stabilization during ribosome biogenesis inhibition. Despite its role is well defined, the dynamic of 5S RNP assembly still requires further characterization. In the present work, we report that MDM2 inhibition is dependent by a pre-existing population of 5S rRNA.

20-Hydroxyecdysone stimulates nuclear accumulation of BmNep1, a nuclear ribosome biogenesis-related protein in the silkworm, Bombyx mori.

Science.gov (United States)

Ji, M-M; Liu, A-Q; Sima, Y-H; Xu, S-Q

2016-10-01

The pathway of communication between endocrine hormones and ribosome biogenesis critical for physiological adaptation is largely unknown. Nucleolar essential protein 1 (Nep1) is an essential gene for ribosome biogenesis and is functionally conserved in many in vertebrate and invertebrate species. In this study, we cloned Bombyx mori Nep1 (BmNep1) due to its high expression in silk glands of silkworms on day 3 of the fifth instar. We found that BmNep1 mRNA and protein levels were upregulated in silk glands during fourth-instar ecdysis and larval-pupal metamorphosis. By immunoprecipitation with the anti-BmNep1 antibody and liquid chromatography-tandem mass spectrometry analyses, it was shown that BmNep1 probably interacts with proteins related to ribosome structure formation. Immunohistochemistry, biochemical fractionation and immunocytochemistry revealed that BmNep1 is localized to the nuclei in Bombyx cells. Using BmN cells originally derived from ovaries, we demonstrated that 20-hydroxyecdysone (20E) induced BmNep1 expression and stimulated nuclear accumulation of BmNep1. Under physiological conditions, BmNep1 was also upregulated in ovaries during larval-pupal metamorphosis. Overall, our results indicate that the endocrine hormone 20E facilitates nuclear accumulation of BmNep1, which is involved in nuclear ribosome biogenesis in Bombyx. © 2016 The Royal Entomological Society.

The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress.

Science.gov (United States)

Sloan, Katherine E; Bohnsack, Markus T; Watkins, Nicholas J

2013-10-17

Several proto-oncogenes and tumor suppressors regulate the production of ribosomes. Ribosome biogenesis is a major consumer of cellular energy, and defects result in p53 activation via repression of mouse double minute 2 (MDM2) homolog by the ribosomal proteins RPL5 and RPL11. Here, we report that RPL5 and RPL11 regulate p53 from the context of a ribosomal subcomplex, the 5S ribonucleoprotein particle (RNP). We provide evidence that the third component of this complex, the 5S rRNA, is critical for p53 regulation. In addition, we show that the 5S RNP is essential for the activation of p53 by p14(ARF), a protein that is activated by oncogene overexpression. Our data show that the abundance of the 5S RNP, and therefore p53 levels, is determined by factors regulating 5S complex formation and ribosome integration, including the tumor suppressor PICT1. The 5S RNP therefore emerges as the critical coordinator of signaling pathways that couple cell proliferation with ribosome production. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Evolutionary Conservation of the Ribosomal Biogenesis Factor Rbm19/Mrd1: Implications for Function

OpenAIRE

Kallberg, Yvonne; Segerstolpe, Åsa; Lackmann, Fredrik; Persson, Bengt; Wieslander, Lars

2012-01-01

Ribosome biogenesis in eukaryotes requires coordinated folding and assembly of a pre-rRNA into sequential pre-rRNA-protein complexes in which chemical modifications and RNA cleavages occur. These processes require many small nucleolar RNAs (snoRNAs) and proteins. Rbm19/Mrd1 is one such protein that is built from multiple RNA-binding domains (RBDs). We find that Rbm19/Mrd1 with five RBDs is present in all branches of the eukaryotic phylogenetic tree, except in animals and Choanoflagellates, th...

Epigenetic up-regulation of ribosome biogenesis and more aggressive phenotype triggered by the lack of the histone demethylase JHDM1B in mammary epithelial cells.

Science.gov (United States)

Galbiati, Alice; Penzo, Marianna; Bacalini, Maria Giulia; Onofrillo, Carmine; Guerrieri, Ania Naila; Garagnani, Paolo; Franceschi, Claudio; Treré, Davide; Montanaro, Lorenzo

2017-06-06

The alterations of ribosome biogenesis and protein synthesis play a direct role in the development of tumors. The accessibility and transcription of ribosomal genes is controlled at several levels, with their epigenetic regulation being one of the most important. Here we explored the JmjC domain-containing histone demethylase 1B (JHDM1B) function in the epigenetic control of rDNA transcription. Since JHDM1B is a negative regulator of gene transcription, we focused on the effects induced by JHDM1B knock-down (KD). We studied the consequences of stable inducible JHDM1B silencing in cell lines derived from transformed and untransformed mammary epithelial cells. In these cellular models, prolonged JHDM1B downregulation triggered a surge of 45S pre-rRNA transcription and processing, associated with a re-modulation of the H3K36me2 levels at rDNA loci and with changes in DNA methylation of specific CpG sites in rDNA genes. We also found that after JHDM1B KD, cells showed a higher ribosome content: which were engaged in mRNA translation. JHDM1B KD and the consequent stimulation of ribosomes biogenesis conferred more aggressive features to the tested cellular models, which acquired a greater clonogenic, staminal and invasive potential. Taken together, these data indicate that the reduction of JHDM1B leads to a more aggressive cellular phenotype in mammary gland cells, by virtue of its negative regulatory activity on ribosome biogenesis.

Rrp12 and the Exportin Crm1 participate in late assembly events in the nucleolus during 40S ribosomal subunit biogenesis.

Science.gov (United States)

Moriggi, Giulia; Nieto, Blanca; Dosil, Mercedes

2014-12-01

During the biogenesis of small ribosomal subunits in eukaryotes, the pre-40S particles formed in the nucleolus are rapidly transported to the cytoplasm. The mechanisms underlying the nuclear export of these particles and its coordination with other biogenesis steps are mostly unknown. Here we show that yeast Rrp12 is required for the exit of pre-40S particles to the cytoplasm and for proper maturation dynamics of upstream 90S pre-ribosomes. Due to this, in vivo elimination of Rrp12 leads to an accumulation of nucleoplasmic 90S to pre-40S transitional particles, abnormal 35S pre-rRNA processing, delayed elimination of processing byproducts, and no export of intermediate pre-40S complexes. The exportin Crm1 is also required for the same pre-ribosome maturation events that involve Rrp12. Thus, in addition to their implication in nuclear export, Rrp12 and Crm1 participate in earlier biosynthetic steps that take place in the nucleolus. Our results indicate that, in the 40S subunit synthesis pathway, the completion of early pre-40S particle assembly, the initiation of byproduct degradation and the priming for nuclear export occur in an integrated manner in late 90S pre-ribosomes.

Two Nucleolar Proteins, GDP1 and OLI2, Function As Ribosome Biogenesis Factors and Are Preferentially Involved in Promotion of Leaf Cell Proliferation without Strongly Affecting Leaf Adaxial–Abaxial Patterning in Arabidopsis thaliana

Directory of Open Access Journals (Sweden)

Koji Kojima

2018-01-01

Full Text Available Leaf abaxial–adaxial patterning is dependent on the mutual repression of leaf polarity genes expressed either adaxially or abaxially. In Arabidopsis thaliana, this process is strongly affected by mutations in ribosomal protein genes and in ribosome biogenesis genes in a sensitized genetic background, such as asymmetric leaves2 (as2. Most ribosome-related mutants by themselves do not show leaf abaxialization, and one of their typical phenotypes is the formation of pointed rather than rounded leaves. In this study, we characterized two ribosome-related mutants to understand how ribosome biogenesis is linked to several aspects of leaf development. Previously, we isolated oligocellula2 (oli2 which exhibits the pointed-leaf phenotype and has a cell proliferation defect. OLI2 encodes a homolog of Nop2 in Saccharomyces cerevisiae, a ribosome biogenesis factor involved in pre-60S subunit maturation. In this study, we found another pointed-leaf mutant that carries a mutation in a gene encoding an uncharacterized protein with a G-patch domain. Similar to oli2, this mutant, named g-patch domain protein1 (gdp1, has a reduced number of leaf cells. In addition, gdp1 oli2 double mutants showed a strong genetic interaction such that they synergistically impaired cell proliferation in leaves and produced markedly larger cells. On the other hand, they showed additive phenotypes when combined with several known ribosomal protein mutants. Furthermore, these mutants have a defect in pre-rRNA processing. GDP1 and OLI2 are strongly expressed in tissues with high cell proliferation activity, and GDP1-GFP and GFP-OLI2 are localized in the nucleolus. These results suggest that OLI2 and GDP1 are involved in ribosome biogenesis. We then examined the effects of gdp1 and oli2 on adaxial–abaxial patterning by crossing them with as2. Interestingly, neither gdp1 nor oli2 strongly enhanced the leaf polarity defect of as2. Similar results were obtained with as2 gdp1 oli2

Interleukin 6 downregulates p53 expression and activity by stimulating ribosome biogenesis: a new pathway connecting inflammation to cancer

Science.gov (United States)

Brighenti, E; Calabrese, C; Liguori, G; Giannone, F A; Trerè, D; Montanaro, L; Derenzini, M

2014-01-01

Chronic inflammation is an established risk factor for the onset of cancer, and the inflammatory cytokine IL-6 has a role in tumorigenesis by enhancing proliferation and hindering apoptosis. As factors stimulating proliferation also downregulate p53 expression by enhancing ribosome biogenesis, we hypothesized that IL-6 may cause similar changes in inflamed tissues, thus activating a mechanism that favors neoplastic transformation. Here, we showed that IL-6 downregulated the expression and activity of p53 in transformed and untransformed human cell lines. This was the consequence of IL-6-dependent stimulation of c-MYC mRNA translation, which was responsible for the upregulation of rRNA transcription. The enhanced rRNA transcription stimulated the MDM2-mediated proteasomal degradation of p53, by reducing the availability of ribosome proteins for MDM2 binding. The p53 downregulation induced the acquisition of cellular phenotypic changes characteristic of epithelial–mesenchymal transition, such as a reduced level of E-cadherin expression, increased cell invasiveness and a decreased response to cytotoxic stresses. We found that these changes also occurred in colon epithelial cells of patients with ulcerative colitis, a very representative example of chronic inflammation at high risk for tumor development. Histochemical and immunohistochemical analysis of colon biopsy samples showed an upregulation of ribosome biogenesis, a reduced expression of p53, together with a focal reduction or absence of E-cadherin expression in chronic colitis in comparison with normal mucosa samples. These changes disappeared after treatment with anti-inflammatory drugs. Taken together, the present results highlight a new mechanism that may link chronic inflammation to cancer, based on p53 downregulation, which is activated by the enhancement of rRNA transcription upon IL-6 exposure. PMID:24531714

Emerging functions of ribosomal proteins in gene-specific transcription and translation

International Nuclear Information System (INIS)

Lindstroem, Mikael S.

2009-01-01

Ribosomal proteins have remained highly conserved during evolution presumably reflecting often critical functions in ribosome biogenesis or mature ribosome function. In addition, several ribosomal proteins possess distinct extra-ribosomal functions in apoptosis, DNA repair and transcription. An increasing number of ribosomal proteins have been shown to modulate the trans-activation function of important regulatory proteins such as NF-κB, p53, c-Myc and nuclear receptors. Furthermore, a subset of ribosomal proteins can bind directly to untranslated regions of mRNA resulting in transcript-specific translational control outside of the ribosome itself. Collectively, these findings suggest that ribosomal proteins may have a wider functional repertoire within the cell than previously thought. The future challenge is to identify and validate these novel functions in the background of an often essential primary function in ribosome biogenesis and cell growth.

New localization and function of calpain-2 in nucleoli of colorectal cancer cells in ribosomal biogenesis: effect of KRAS status.

Science.gov (United States)

Telechea-Fernández, Marcelino; Rodríguez-Fernández, Lucia; García, Concha; Zaragozá, Rosa; Viña, Juan; Cervantes, Andrés; García-Trevijano, Elena R

2018-02-06

Calpain-2 belongs to a family of pleiotropic Cys-proteases with modulatory rather than degradative functions. Calpain (CAPN) overexpression has been controversially correlated with poor prognosis in several cancer types, including colorectal carcinoma (CRC). However, the mechanisms of substrate-recognition, calpain-2 regulation/deregulation and specific functions in CRC remain elusive. Herein, calpain subcellular distribution was studied as a key event for substrate-recognition and consequently, for calpain-mediated function. We describe a new localization for calpain-2 in the nucleoli of CRC cells. Calpain-2 nucleolar distribution resulted dependent on its enzymatic activity and on the mutational status of KRAS. In KRASWT/- cells serum-starvation induced CAPN2 expression, nucleolar accumulation and increased binding to the rDNA-core promoter and intergenic spacer (IGS), concomitant with a reduction in pre-rRNA levels. Depletion of calpain-2 by specific siRNA prevented pre-rRNA down-regulation after serum removal. Conversely, ribosomal biogenesis proceeded in the absence of serum in unresponsive KRASG13D/- cells whose CAPN2 expression, nucleolar localization and rDNA-occupancy remained unchanged during the time-course of serum starvation. We propose here that nucleolar calpain-2 might be a KRAS-dependent sensor to repress ribosomal biogenesis in growth limiting conditions. Under constitutive activation of the pathway commonly found in CRC, calpain-2 is deregulated and tumor cells become insensitive to the extracellular microenvironment.

Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.

Directory of Open Access Journals (Sweden)

Bai-Wei Gu

Full Text Available Dyskeratosis congenita (DC is an inherited bone marrow failure syndrome characterized by the presence of short telomeres at presentation. Mutations in ten different genes, whose products are involved in the telomere maintenance pathway, have been shown to cause DC. The X-linked form is the most common form of the disease and is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for the assembly and stability of telomerase and is also involved in ribosomal RNA (rRNA processing where it converts specific uridines to pseudouridine. DC is thought to result from failure to maintain tissues, like blood, that are renewed by stem cell activity, but research into pathogenic mechanisms has been hampered by the difficulty of obtaining stem cells from patients. We reasoned that induced pluripotent stem (iPS cells from X-linked DC patients may provide information about the mechanisms involved. Here we describe the production of iPS cells from DC patients with DKC1 mutations Q31E, A353V and ΔL37. In addition we constructed "corrected" lines with a copy of the wild type dyskerin cDNA expressed from the AAVS1 safe harbor locus. We show that in iPS cells with DKC1 mutations telomere maintenance is compromised with short telomere lengths and decreased telomerase activity. The degree to which telomere lengths are affected by expression of telomerase during reprograming, or with ectopic expression of wild type dyskerin, is variable. The recurrent mutation A353V shows the most severe effect on telomere maintenance. A353V cells but not Q31E or ΔL37 cells, are refractory to correction by expression of wild type DKC1 cDNA. Because dyskerin is involved in both telomere maintenance and ribosome biogenesis it has been postulated that defective ribosome biogenesis and translation may contribute to the disease phenotype. Evidence from mouse and zebra fish models has supported the involvement of ribosome biogenesis but primary cells

Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.

Science.gov (United States)

Gu, Bai-Wei; Apicella, Marisa; Mills, Jason; Fan, Jian-Meng; Reeves, Dara A; French, Deborah; Podsakoff, Gregory M; Bessler, Monica; Mason, Philip J

2015-01-01

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by the presence of short telomeres at presentation. Mutations in ten different genes, whose products are involved in the telomere maintenance pathway, have been shown to cause DC. The X-linked form is the most common form of the disease and is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for the assembly and stability of telomerase and is also involved in ribosomal RNA (rRNA) processing where it converts specific uridines to pseudouridine. DC is thought to result from failure to maintain tissues, like blood, that are renewed by stem cell activity, but research into pathogenic mechanisms has been hampered by the difficulty of obtaining stem cells from patients. We reasoned that induced pluripotent stem (iPS) cells from X-linked DC patients may provide information about the mechanisms involved. Here we describe the production of iPS cells from DC patients with DKC1 mutations Q31E, A353V and ΔL37. In addition we constructed "corrected" lines with a copy of the wild type dyskerin cDNA expressed from the AAVS1 safe harbor locus. We show that in iPS cells with DKC1 mutations telomere maintenance is compromised with short telomere lengths and decreased telomerase activity. The degree to which telomere lengths are affected by expression of telomerase during reprograming, or with ectopic expression of wild type dyskerin, is variable. The recurrent mutation A353V shows the most severe effect on telomere maintenance. A353V cells but not Q31E or ΔL37 cells, are refractory to correction by expression of wild type DKC1 cDNA. Because dyskerin is involved in both telomere maintenance and ribosome biogenesis it has been postulated that defective ribosome biogenesis and translation may contribute to the disease phenotype. Evidence from mouse and zebra fish models has supported the involvement of ribosome biogenesis but primary cells from human

The importance of ribosome production, and the 5S RNP-MDM2 pathway, in health and disease.

Science.gov (United States)

Pelava, Andria; Schneider, Claudia; Watkins, Nicholas J

2016-08-15

Ribosomes are abundant, large RNA-protein complexes that are the source of all protein synthesis in the cell. The production of ribosomes is an extremely energetically expensive cellular process that has long been linked to human health and disease. More recently, it has been shown that ribosome biogenesis is intimately linked to multiple cellular signalling pathways and that defects in ribosome production can lead to a wide variety of human diseases. Furthermore, changes in ribosome production in response to nutrient levels in the diet lead to metabolic re-programming of the liver. Reduced or abnormal ribosome production in response to cellular stress or mutations in genes encoding factors critical for ribosome biogenesis causes the activation of the tumour suppressor p53, which leads to re-programming of cellular transcription. The ribosomal assembly intermediate 5S RNP (ribonucleoprotein particle), containing RPL5, RPL11 and the 5S rRNA, accumulates when ribosome biogenesis is blocked. The excess 5S RNP binds to murine double minute 2 (MDM2), the main p53-suppressor in the cell, inhibiting its function and leading to p53 activation. Here, we discuss the involvement of ribosome biogenesis in the homoeostasis of p53 in the cell and in human health and disease. © 2016 The Author(s).

Nucleolus Precursor Bodies and Ribosome Biogenesis in Early Mammalian Embryos: Old Theories and New Discoveries.

Science.gov (United States)

Fulka, Helena; Aoki, Fugaku

2016-06-01

In mammals, mature oocytes and early preimplantation embryos contain transcriptionally inactive structures termed nucleolus precursor bodies instead of the typical fibrillo-granular nucleoli. These nuclear organelles are essential and strictly of maternal origin. If they are removed from oocytes, the resulting embryos are unable to replace them and consequently fail to develop. Historically, nucleolus precursor bodies have been perceived as a passive repository site of nucleolar proteins that are required for embryos to form fully functional nucleoli. Recent results, however, contradict this long-standing dogma and show that these organelles are dispensable for nucleologenesis and ribosome biogenesis. In this article, we discuss the possible roles of nucleolus precursor bodies and propose how they might be involved in embryogenesis. Furthermore, we argue that these organelles are essential only shortly after fertilization and suggest that they might actively participate in centromeric chromatin establishment. © 2016 by the Society for the Study of Reproduction, Inc.

p53- and ERK7-dependent ribosome surveillance response regulates Drosophila insulin-like peptide secretion.

Directory of Open Access Journals (Sweden)

Kiran Hasygar

2014-11-01

Full Text Available Insulin-like signalling is a conserved mechanism that coordinates animal growth and metabolism with nutrient status. In Drosophila, insulin-producing median neurosecretory cells (IPCs regulate larval growth by secreting insulin-like peptides (dILPs in a diet-dependent manner. Previous studies have shown that nutrition affects dILP secretion through humoral signals derived from the fat body. Here we uncover a novel mechanism that operates cell autonomously in the IPCs to regulate dILP secretion. We observed that impairment of ribosome biogenesis specifically in the IPCs strongly inhibits dILP secretion, which consequently leads to reduced body size and a delay in larval development. This response is dependent on p53, a known surveillance factor for ribosome biogenesis. A downstream effector of this growth inhibitory response is an atypical MAP kinase ERK7 (ERK8/MAPK15, which is upregulated in the IPCs following impaired ribosome biogenesis as well as starvation. We show that ERK7 is sufficient and essential to inhibit dILP secretion upon impaired ribosome biogenesis, and it acts epistatically to p53. Moreover, we provide evidence that p53 and ERK7 contribute to the inhibition of dILP secretion upon starvation. Thus, we conclude that a cell autonomous ribosome surveillance response, which leads to upregulation of ERK7, inhibits dILP secretion to impede tissue growth under limiting dietary conditions.

In Profile: Models of Ribosome Biogenesis Defects and Regulation of Protein Synthesis

NARCIS (Netherlands)

Essers, P.B.M.

2013-01-01

Ribosomes are the mediators of protein synthesis in the cell and therefore crucial to proper cell function. In addition, ribosomes are highly abundant, with ribosomal RNA making up 80% of the RNA in the cell. A large amount of resources go into maintaining this pool of ribosomes, so ribosome

Early stages in the biogenesis of eukaryotic β-barrel proteins.

Science.gov (United States)

Jores, Tobias; Rapaport, Doron

2017-09-01

The endosymbiotic organelles mitochondria and chloroplasts harbour, similarly to their prokaryotic progenitors, β-barrel proteins in their outer membrane. These proteins are encoded on nuclear DNA, translated on cytosolic ribosomes and imported into their target organelles by a dedicated machinery. Recent studies have provided insights into the import into the organelles and the membrane insertion of these proteins. Although the cytosolic stages of their biogenesis are less well defined, it is speculated that upon their synthesis, chaperones prevent β-barrel proteins from aggregation and keep them in an import-competent conformation. In this Review, we summarize the current knowledge about the biogenesis of β-barrel proteins, focusing on the early stages from the translation on cytosolic ribosomes to the recognition on the surface of the organelle. © 2017 Federation of European Biochemical Societies.

Ribosomal stress induces L11- and p53-dependent apoptosis in mouse pluripotent stem cells.

Science.gov (United States)

Morgado-Palacin, Lucia; Llanos, Susana; Serrano, Manuel

2012-02-01

Ribosome biogenesis is the most demanding energetic process in proliferating cells and it is emerging as a critical sensor of cellular homeostasis. Upon disturbance of ribosome biogenesis, specific free ribosomal proteins, most notably L11, bind and inhibit Mdm2, resulting in activation of the tumor suppressor p53. This pathway has been characterized in somatic and cancer cells, but its function in embryonic pluripotent cells has remained unexplored. Here, we show that treatment with low doses of Actinomycin D or depletion of ribosomal protein L37, two well-established inducers of ribosomal stress, activate p53 in an L11-dependent manner in mouse embryonic stem cells (ESCs) and in induced pluripotent stem cells (iPSCs). Activation of p53 results in transcriptional induction of p53 targets, including p21, Mdm2, Pidd, Puma, Noxa and Bax. Finally, ribosomal stress elicits L11- and p53-dependent apoptosis in ESCs/iPSCs. These results extend to pluripotent cells the functionality of the ribosomal stress pathway and we speculate that this could be a relevant cellular checkpoint during early embryogenesis.

Induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway delays the initiation but fails to eradicate established murine acute myeloid leukemia.

Science.gov (United States)

Jaako, P; Ugale, A; Wahlestedt, M; Velasco-Hernandez, T; Cammenga, J; Lindström, M S; Bryder, D

2017-01-01

Mutations resulting in constitutive activation of signaling pathways that regulate ribosome biogenesis are among the most common genetic events in acute myeloid leukemia (AML). However, whether ribosome biogenesis presents as a therapeutic target to treat AML remains unexplored. Perturbations in ribosome biogenesis trigger the 5S ribonucleoprotein particle (RNP)-Mdm2-p53 ribosomal stress pathway, and induction of this pathway has been shown to have therapeutic efficacy in Myc-driven lymphoma. In the current study we address the physiological and therapeutic role of the 5S RNP-Mdm2-p53 pathway in AML. By utilizing mice that have defective ribosome biogenesis due to downregulation of ribosomal protein S19 (Rps19), we demonstrate that induction of the 5S RNP-Mdm2-p53 pathway significantly delays the initiation of AML. However, even a severe Rps19 deficiency that normally results in acute bone marrow failure has no consistent efficacy on already established disease. Finally, by using mice that harbor a mutation in the Mdm2 gene disrupting its binding to 5S RNP, we show that loss of the 5S RNP-Mdm2-p53 pathway is dispensable for development of AML. Our study suggests that induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway holds limited potential as a single-agent therapy in the treatment of AML.

Myb-binding protein 1a (Mybbp1a) regulates levels and processing of pre-ribosomal RNA.

Science.gov (United States)

Hochstatter, Julia; Hölzel, Michael; Rohrmoser, Michaela; Schermelleh, Lothar; Leonhardt, Heinrich; Keough, Rebecca; Gonda, Thomas J; Imhof, Axel; Eick, Dirk; Längst, Gernot; Németh, Attila

2012-07-13

Ribosomal RNA gene transcription, co-transcriptional processing, and ribosome biogenesis are highly coordinated processes that are tightly regulated during cell growth. In this study we discovered that Mybbp1a is associated with both the RNA polymerase I complex and the ribosome biogenesis machinery. Using a reporter assay that uncouples transcription and RNA processing, we show that Mybbp1a represses rRNA gene transcription. In addition, overexpression of the protein reduces RNA polymerase I loading on endogenous rRNA genes as revealed by chromatin immunoprecipitation experiments. Accordingly, depletion of Mybbp1a results in an accumulation of the rRNA precursor in vivo but surprisingly also causes growth arrest of the cells. This effect can be explained by the observation that the modulation of Mybbp1a protein levels results in defects in pre-rRNA processing within the cell. Therefore, the protein may play a dual role in the rRNA metabolism, potentially linking and coordinating ribosomal DNA transcription and pre-rRNA processing to allow for the efficient synthesis of ribosomes.

Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism

Directory of Open Access Journals (Sweden)

Deborah Chiabrando

2010-01-01

Full Text Available Diamond-Blackfan anemia (DBA is a rare, pure red-cell aplasia that presents during infancy. Approximately 40% of cases are associated with other congenital defects, particularly malformations of the upper limb or craniofacial region. Mutations in the gene coding for the ribosomal protein RPS19 have been identified in 25% of patients with DBA, with resulting impairment of 18S rRNA processing and 40S ribosomal subunit formation. Moreover, mutations in other ribosomal protein coding genes account for about 25% of other DBA cases. Recently, the analysis of mice from which the gene coding for the heme exporter Feline Leukemia Virus subgroup C Receptor (FLVCR1 is deleted suggested that this gene may be involved in the pathogenesis of DBA. FLVCR1-null mice show a phenotype resembling that of DBA patients, including erythroid failure and malformations. Interestingly, some DBA patients have disease linkage to chromosome 1q31, where FLVCR1 is mapped. Moreover, it has been reported that cells from DBA patients express alternatively spliced isoforms of FLVCR1 which encode non-functional proteins. Herein, we review the known roles of RPS19 and FLVCR1 in ribosome function and heme metabolism respectively, and discuss how the deficiency of a ribosomal protein or of a heme exporter may result in the same phenotype.

Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an essential rRNA-binding site.

Science.gov (United States)

Calviño, Fabiola R; Kharde, Satyavati; Ori, Alessandro; Hendricks, Astrid; Wild, Klemens; Kressler, Dieter; Bange, Gert; Hurt, Ed; Beck, Martin; Sinning, Irmgard

2015-04-07

During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11, assembles into a pre-60S particle, where docking relies on RpL11 interacting with helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the pre-60S is not known. Here we report the crystal structure of a ternary symportin Syo1-RpL5-N-RpL11 complex and provide biochemical and structural insights into 5S RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with H84 for binding. Pull-down experiments show that H84 releases RpL11 from the ternary complex, but not in the presence of 5S RNA. Crosslinking mass spectrometry visualizes structural rearrangements on incorporation of 5S RNA into the Syo1-RpL5-RpL11 complex supporting the formation of a pre-5S RNP. Our data underline the dual role of Syo1 in ribosomal protein transport and as an assembly platform for 5S RNP.

The relationship between the nucleolus and cancer: Current evidence and emerging paradigms.

Science.gov (United States)

Orsolic, Ines; Jurada, Deana; Pullen, Nick; Oren, Moshe; Eliopoulos, Aristides G; Volarevic, Sinisa

2016-06-01

The nucleolus is the most prominent nuclear substructure assigned to produce ribosomes; molecular machines that are responsible for carrying out protein synthesis. To meet the increased demand for proteins during cell growth and proliferation the cell must increase protein synthetic capacity by upregulating ribosome biogenesis. While larger nucleolar size and number have been recognized as hallmark features of many tumor types, recent evidence has suggested that, in addition to overproduction of ribosomes, decreased ribosome biogenesis as well as qualitative changes in this process could also contribute to tumor initiation and cancer progression. Furthermore, the nucleolus has become the focus of intense attention for its involvement in processes that are clearly unrelated to ribosome biogenesis such as sensing and responding to endogenous and exogenous stressors, maintenance of genome stability, regulation of cell-cycle progression, cellular senescence, telomere function, chromatin structure, establishment of nuclear architecture, global regulation of gene expression and biogenesis of multiple ribonucleoprotein particles. The fact that dysregulation of many of these fundamental cellular processes may contribute to the malignant phenotype suggests that normal functioning of the nucleolus safeguards against the development of cancer and indicates its potential as a therapeutic approach. Here we review the recent advances made toward understanding these newly-recognized nucleolar functions and their roles in normal and cancer cells, and discuss possible future research directions. Copyright © 2015 Elsevier Ltd. All rights reserved.

5S Ribosomal RNA Is an Essential Component of a Nascent Ribosomal Precursor Complex that Regulates the Hdm2-p53 Checkpoint

Directory of Open Access Journals (Sweden)

Giulio Donati

2013-07-01

Full Text Available Recently, we demonstrated that RPL5 and RPL11 act in a mutually dependent manner to inhibit Hdm2 and stabilize p53 following impaired ribosome biogenesis. Given that RPL5 and RPL11 form a preribosomal complex with noncoding 5S ribosomal RNA (rRNA and the three have been implicated in the p53 response, we reasoned they may be part of an Hdm2-inhibitory complex. Here, we show that small interfering RNAs directed against 5S rRNA have no effect on total or nascent levels of the noncoding rRNA, though they prevent the reported Hdm4 inhibition of p53. To achieve efficient inhibition of 5S rRNA synthesis, we targeted TFIIIA, a specific RNA polymerase III cofactor, which, like depletion of either RPL5 or RPL11, did not induce p53. Instead, 5S rRNA acts in a dependent manner with RPL5 and RPL11 to inhibit Hdm2 and stabilize p53. Moreover, depletion of any one of the three components abolished the binding of the other two to Hdm2, explaining their common dependence. Finally, we demonstrate that the RPL5/RPL11/5S rRNA preribosomal complex is redirected from assembly into nascent 60S ribosomes to Hdm2 inhibition as a consequence of impaired ribosome biogenesis. Thus, the activation of the Hdm2-inhibitory complex is not a passive but a regulated event, whose potential role in tumor suppression has been recently noted.

5S ribosomal RNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint.

Science.gov (United States)

Donati, Giulio; Peddigari, Suresh; Mercer, Carol A; Thomas, George

2013-07-11

Recently, we demonstrated that RPL5 and RPL11 act in a mutually dependent manner to inhibit Hdm2 and stabilize p53 following impaired ribosome biogenesis. Given that RPL5 and RPL11 form a preribosomal complex with noncoding 5S ribosomal RNA (rRNA) and the three have been implicated in the p53 response, we reasoned they may be part of an Hdm2-inhibitory complex. Here, we show that small interfering RNAs directed against 5S rRNA have no effect on total or nascent levels of the noncoding rRNA, though they prevent the reported Hdm4 inhibition of p53. To achieve efficient inhibition of 5S rRNA synthesis, we targeted TFIIIA, a specific RNA polymerase III cofactor, which, like depletion of either RPL5 or RPL11, did not induce p53. Instead, 5S rRNA acts in a dependent manner with RPL5 and RPL11 to inhibit Hdm2 and stabilize p53. Moreover, depletion of any one of the three components abolished the binding of the other two to Hdm2, explaining their common dependence. Finally, we demonstrate that the RPL5/RPL11/5S rRNA preribosomal complex is redirected from assembly into nascent 60S ribosomes to Hdm2 inhibition as a consequence of impaired ribosome biogenesis. Thus, the activation of the Hdm2-inhibitory complex is not a passive but a regulated event, whose potential role in tumor suppression has been recently noted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Conformational Flexibility of Proteins Involved in Ribosome Biogenesis: Investigations via Small Angle X-ray Scattering (SAXS

Directory of Open Access Journals (Sweden)

Dritan Siliqi

2018-02-01

Full Text Available The dynamism of proteins is central to their function, and several proteins have been described as flexible, as consisting of multiple domains joined by flexible linkers, and even as intrinsically disordered. Several techniques exist to study protein structures, but small angle X-ray scattering (SAXS has proven to be particularly powerful for the quantitative analysis of such flexible systems. In the present report, we have used SAXS in combination with X-ray crystallography to highlight their usefulness at characterizing flexible proteins, using as examples two proteins involved in different steps of ribosome biogenesis. The yeast BRCA2 and CDKN1A-interactig protein, Bcp1, is a chaperone for Rpl23 of unknown structure. We showed that it consists of a rigid, slightly elongated protein, with a secondary structure comprising a mixture of alpha helices and beta sheets. As an example of a flexible molecule, we studied the SBDS (Shwachman-Bodian-Diamond Syndrome protein that is involved in the cytoplasmic maturation of the 60S subunit and constitutes the mutated target in the Shwachman-Diamond Syndrome. In solution, this protein coexists in an ensemble of three main conformations, with the N- and C-terminal ends adopting different orientations with respect to the central domain. The structure observed in the protein crystal corresponds to an average of those predicted by the SAXS flexibility analysis.

Defective ribosome assembly in Shwachman-Diamond syndrome.

Science.gov (United States)

Wong, Chi C; Traynor, David; Basse, Nicolas; Kay, Robert R; Warren, Alan J

2011-10-20

Shwachman-Diamond syndrome (SDS), a recessive leukemia predisposition disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, skeletal abnormalities and poor growth, is caused by mutations in the highly conserved SBDS gene. Here, we test the hypothesis that defective ribosome biogenesis underlies the pathogenesis of SDS. We create conditional mutants in the essential SBDS ortholog of the ancient eukaryote Dictyostelium discoideum using temperature-sensitive, self-splicing inteins, showing that mutant cells fail to grow at the restrictive temperature because ribosomal subunit joining is markedly impaired. Remarkably, wild type human SBDS complements the growth and ribosome assembly defects in mutant Dictyostelium cells, but disease-associated human SBDS variants are defective. SBDS directly interacts with the GTPase elongation factor-like 1 (EFL1) on nascent 60S subunits in vivo and together they catalyze eviction of the ribosome antiassociation factor eukaryotic initiation factor 6 (eIF6), a prerequisite for the translational activation of ribosomes. Importantly, lymphoblasts from SDS patients harbor a striking defect in ribosomal subunit joining whose magnitude is inversely proportional to the level of SBDS protein. These findings in Dictyostelium and SDS patient cells provide compelling support for the hypothesis that SDS is a ribosomopathy caused by corruption of an essential cytoplasmic step in 60S subunit maturation.

Site-specific fluorescent labeling of nascent proteins on the translating ribosome.

Science.gov (United States)

Saraogi, Ishu; Zhang, Dawei; Chandrasekaran, Sandhya; Shan, Shu-ou

2011-09-28

As newly synthesized proteins emerge from the ribosome, they interact with a variety of cotranslational cellular machineries that facilitate their proper folding, maturation, and localization. These interactions are essential for proper function of the cell, and the ability to study these events is crucial to understanding cellular protein biogenesis. To this end, we have developed a highly efficient method to generate ribosome-nascent chain complexes (RNCs) site-specifically labeled with a fluorescent dye on the nascent polypeptide. The fluorescent RNC provides real-time, quantitative information on its cotranslational interaction with the signal recognition particle and will be a valuable tool in elucidating the role of the translating ribosome in numerous biochemical pathways.

Hierarchical recruitment of ribosomal proteins and assembly factors remodels nucleolar pre-60S ribosomes.

Science.gov (United States)

Biedka, Stephanie; Micic, Jelena; Wilson, Daniel; Brown, Hailey; Diorio-Toth, Luke; Woolford, John L

2018-04-24

Ribosome biogenesis involves numerous preribosomal RNA (pre-rRNA) processing events to remove internal and external transcribed spacer sequences, ultimately yielding three mature rRNAs. Removal of the internal transcribed spacer 2 spacer RNA is the final step in large subunit pre-rRNA processing and begins with endonucleolytic cleavage at the C 2 site of 27SB pre-rRNA. C 2 cleavage requires the hierarchical recruitment of 11 ribosomal proteins and 14 ribosome assembly factors. However, the function of these proteins in C 2 cleavage remained unclear. In this study, we have performed a detailed analysis of the effects of depleting proteins required for C 2 cleavage and interpreted these results using cryo-electron microscopy structures of assembling 60S subunits. This work revealed that these proteins are required for remodeling of several neighborhoods, including two major functional centers of the 60S subunit, suggesting that these remodeling events form a checkpoint leading to C 2 cleavage. Interestingly, when C 2 cleavage is directly blocked by depleting or inactivating the C 2 endonuclease, assembly progresses through all other subsequent steps. © 2018 Biedka et al.

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.

Directory of Open Access Journals (Sweden)

Satoshi Nakada

Full Text Available External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK, moderate (MO, middle (MI, and strong (ST overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity increased with increasing overload, with increases of 1.8-fold (MO, 2.2-fold (MI, and 2.5-fold (ST, respectively, relative to non-overloaded muscle (NL in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98. The phosphorylated form of p70S6K (a positive regulator of translational efficiency showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO, 17.4-fold (MI, and 18.2-fold (ST, respectively, relative to NL in the WK group. These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size.

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.

Science.gov (United States)

Nakada, Satoshi; Ogasawara, Riki; Kawada, Shigeo; Maekawa, Takahiro; Ishii, Naokata

2016-01-01

External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK), moderate (MO), middle (MI), and strong (ST) overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity) increased with increasing overload, with increases of 1.8-fold (MO), 2.2-fold (MI), and 2.5-fold (ST), respectively, relative to non-overloaded muscle (NL) in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98). The phosphorylated form of p70S6K (a positive regulator of translational efficiency) showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO), 17.4-fold (MI), and 18.2-fold (ST), respectively, relative to NL in the WK group). These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size.

Simulated microgravity, Mars gravity, and 2g hypergravity affect cell cycle regulation, ribosome biogenesis, and epigenetics in Arabidopsis cell cultures.

Science.gov (United States)

Kamal, Khaled Y; Herranz, Raúl; van Loon, Jack J W A; Medina, F Javier

2018-04-23

Gravity is the only component of Earth environment that remained constant throughout the entire process of biological evolution. However, it is still unclear how gravity affects plant growth and development. In this study, an in vitro cell culture of Arabidopsis thaliana was exposed to different altered gravity conditions, namely simulated reduced gravity (simulated microgravity, simulated Mars gravity) and hypergravity (2g), to study changes in cell proliferation, cell growth, and epigenetics. The effects after 3, 14, and 24-hours of exposure were evaluated. The most relevant alterations were found in the 24-hour treatment, being more significant for simulated reduced gravity than hypergravity. Cell proliferation and growth were uncoupled under simulated reduced gravity, similarly, as found in meristematic cells from seedlings grown in real or simulated microgravity. The distribution of cell cycle phases was changed, as well as the levels and gene transcription of the tested cell cycle regulators. Ribosome biogenesis was decreased, according to levels and gene transcription of nucleolar proteins and the number of inactive nucleoli. Furthermore, we found alterations in the epigenetic modifications of chromatin. These results show that altered gravity effects include a serious disturbance of cell proliferation and growth, which are cellular functions essential for normal plant development.

The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage

DEFF Research Database (Denmark)

Larsen, Dorthe H; Hari, Flurina; Clapperton, Julie A

2014-01-01

Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient...... recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1...

Probing the structure of ribosome assembly intermediates in vivo using DMS and hydroxyl radical footprinting.

Science.gov (United States)

Hulscher, Ryan M; Bohon, Jen; Rappé, Mollie C; Gupta, Sayan; D'Mello, Rhijuta; Sullivan, Michael; Ralston, Corie Y; Chance, Mark R; Woodson, Sarah A

2016-07-01

The assembly of the Escherichia coli ribosome has been widely studied and characterized in vitro. Despite this, ribosome biogenesis in living cells is only partly understood because assembly is coupled with transcription, modification and processing of the pre-ribosomal RNA. We present a method for footprinting and isolating pre-rRNA as it is synthesized in E. coli cells. Pre-rRNA synthesis is synchronized by starvation, followed by nutrient upshift. RNA synthesized during outgrowth is metabolically labeled to facilitate isolation of recent transcripts. Combining this technique with two in vivo RNA probing methods, hydroxyl radical and DMS footprinting, allows the structure of nascent RNA to be probed over time. Together, these can be used to determine changes in the structures of ribosome assembly intermediates as they fold in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

Directory of Open Access Journals (Sweden)

Abhishek Ghosh

2014-10-01

Full Text Available The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs from the brain and increased expression of Imp-L2-a secreted factor that binds and inhibits dILP activity-from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis.

The Absence of the Transcription Factor Yrr1p, Identified from Comparative Genome Profiling, Increased Vanillin Tolerance Due to Enhancements of ABC Transporters Expressing, rRNA Processing and Ribosome Biogenesis in Saccharomyces cerevisiae.

Science.gov (United States)

Wang, Xinning; Liang, Zhenzhen; Hou, Jin; Shen, Yu; Bao, Xiaoming

2017-01-01

Enhancing the tolerance of Saccharomyces cerevisiae to inhibitors derived from lignocellulose is conducive to producing biofuel and chemicals using abundant lignocellulosic materials. Vanillin is a major type of phenolic inhibitor in lignocellulose hydrolysates for S. cerevisiae . In the present work, the factors beneficial to vanillin resistance in yeast were identified from the vanillin-resistant strain EMV-8, which was derived from strain NAN-27 by adaptive evolution. We found 450 SNPs and 44 genes with InDels in the vanillin-tolerant strain EMV-8 by comparing the genome sequences of EMV-8 and NAN-27. To investigate the effects of InDels, InDels were deleted in BY4741, respectively. We demonstrated that the deletion of YRR1 improved vanillin tolerance of strain. In the presence of 6 mM vanillin, deleting YRR1 increase the maximum specific growth rate and the vanillin consumption rate by 142 and 51%, respectively. The subsequent transcriptome analysis revealed that deleting YRR1 resulted in changed expression of over 200 genes in the presence of 5 mM vanillin. The most marked changes were the significant up-regulation of the dehydrogenase ADH7 , several ATP-binding cassette (ABC) transporters, and dozens of genes involved in ribosome biogenesis and rRNA processing. Coincidently, the crude enzyme solution of BY4741( yrr1 Δ) exhibited higher NADPH-dependent vanillin reduction activity than control. In addition, overexpressing the ABC transporter genes PDR5, YOR1 , and SNQ2 , as well as the RNA helicase gene DBP2 , increased the vanillin tolerance of strain. Interestingly, unlike the marked changes we mentioned above, under vanillin-free conditions, there are only limited transcriptional differences between wildtype and yrr1 Δ. This indicated that vanillin might act as an effector in Yrr1p-related regulatory processes. The new findings of the relationship between YRR1 and vanillin tolerance, as well as the contribution of rRNA processing and ribosome biogenesis to

Non-canonical ribosomal DNA segments in the human genome, and nucleoli functioning.

Science.gov (United States)

Kupriyanova, Natalia S; Netchvolodov, Kirill K; Sadova, Anastasia A; Cherepanova, Marina D; Ryskov, Alexei P

2015-11-10

Ribosomal DNA (rDNA) in the human genome is represented by tandem repeats of 43 kb nucleotide sequences that form nucleoli organizers (NORs) on each of five pairs of acrocentric chromosomes. RDNA-similar segments of different lengths are also present on (NOR)(-) chromosomes. Many of these segments contain nucleotide substitutions, supplementary microsatellite clusters, and extended deletions. Recently, it was shown that, in addition to ribosome biogenesis, nucleoli exhibit additional functions, such as cell-cycle regulation and response to stresses. In particular, several stress-inducible loci located in the ribosomal intergenic spacer (rIGS) produce stimuli-specific noncoding nucleolus RNAs. By mapping the 5'/3' ends of the rIGS segments scattered throughout (NOR)(-) chromosomes, we discovered that the bonds in the rIGS that were most often susceptible to disruption in the rIGS were adjacent to, or overlapped with stimuli-specific inducible loci. This suggests the interconnection of the two phenomena - nucleoli functioning and the scattering of rDNA-like sequences on (NOR)(-) chromosomes. Copyright © 2015 Elsevier B.V. All rights reserved.

DNA replication stress restricts ribosomal DNA copy number.

Science.gov (United States)

Salim, Devika; Bradford, William D; Freeland, Amy; Cady, Gillian; Wang, Jianmin; Pruitt, Steven C; Gerton, Jennifer L

2017-09-01

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

DNA replication stress restricts ribosomal DNA copy number

Science.gov (United States)

Salim, Devika; Bradford, William D.; Freeland, Amy; Cady, Gillian; Wang, Jianmin

2017-01-01

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number. PMID:28915237

DNA replication stress restricts ribosomal DNA copy number.

Directory of Open Access Journals (Sweden)

Devika Salim

2017-09-01

Full Text Available Ribosomal RNAs (rRNAs in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

RINT-1 interacts with MSP58 within nucleoli and plays a role in ribosomal gene transcription

International Nuclear Information System (INIS)

Yang, Chuan-Pin; Kuo, Yu-Liang; Lee, Yi-Chao; Lee, Kuen-Haur; Chiang, Chi-Wu; Wang, Ju-Ming; Hsu, Che-Chia

2016-01-01

The nucleolus is the cellular site of ribosomal (r)DNA transcription and ribosome biogenesis. The 58-kDa microspherule protein (MSP58) is a nucleolar protein involved in rDNA transcription and cell proliferation. However, regulation of MSP58-mediated rDNA transcription remains unknown. Using a yeast two-hybrid system with MSP58 as bait, we isolated complementary (c)DNA encoding Rad50-interacting protein 1 (RINT-1), as a MSP58-binding protein. RINT-1 was implicated in the cell cycle checkpoint, membrane trafficking, Golgi apparatus and centrosome dynamic integrity, and telomere length control. Both in vitro and in vivo interaction assays showed that MSP58 directly interacts with RINT-1. Interestingly, microscopic studies revealed the co-localization of MSP58, RINT-1, and the upstream binding factor (UBF), a rRNA transcription factor, in the nucleolus. We showed that ectopic expression of MSP58 or RINT-1 resulted in decreased rRNA expression and rDNA promoter activity, whereas knockdown of MSP58 or RINT-1 by siRNA exerted the opposite effect. Coexpression of MSP58 and RINT-1 robustly decreased rRNA synthesis compared to overexpression of either protein alone, whereas depletion of RINT-1 from MSP58-transfected cells enhanced rRNA synthesis. We also found that MSP58, RINT-1, and the UBF were associated with the rDNA promoter using a chromatin immunoprecipitation assay. Because aberrant ribosome biogenesis contributes to neoplastic transformation, our results revealed a novel protein complex involved in the regulation of rRNA gene expression, suggesting a role for MSP58 and RINT-1 in cancer development. - Highlights: • RINT-1 is a novel MSP58-interacting protein. • RINT-1 is a nucleolar protein that suppresses ribosomal RNA gene transcription. • RINT-1 and MSP58 cooperate to suppress ribosomal RNA gene transcription. • RINT-1, MSP58, and UBF form a complex on the rDNA promoter.

Assembly constraints drive co-evolution among ribosomal constituents.

Science.gov (United States)

Mallik, Saurav; Akashi, Hiroshi; Kundu, Sudip

2015-06-23

Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein-RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein-rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a 'proof of concept' that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome

DEFF Research Database (Denmark)

Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

2008-01-01

indicate that pioglitazone therapy restores insulin sensitivity, in part, by a coordinated upregulation of genes involved in mitochondrial OXPHOS and ribosomal protein biosynthesis in muscle in PCOS. These transcriptional effects of pioglitazone may contribute to prevent the onset of type 2 diabetes...... by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp...... Annotator and Pathway Profiler (GenMAPP 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1) revealed a significant upregulation of genes representing mitochondrial oxidative phosphorylation (OXPHOS), ribosomal proteins, mRNA processing reactome, translation factors, and proteasome degradation in PCOS after...

rRNA maturation in yeast cells depleted of large ribosomal subunit proteins.

Directory of Open Access Journals (Sweden)

Gisela Pöll

Full Text Available The structural constituents of the large eukaryotic ribosomal subunit are 3 ribosomal RNAs, namely the 25S, 5.8S and 5S rRNA and about 46 ribosomal proteins (r-proteins. They assemble and mature in a highly dynamic process that involves more than 150 proteins and 70 small RNAs. Ribosome biogenesis starts in the nucleolus, continues in the nucleoplasm and is completed after nucleo-cytoplasmic translocation of the subunits in the cytoplasm. In this work we created 26 yeast strains, each of which conditionally expresses one of the large ribosomal subunit (LSU proteins. In vivo depletion of the analysed LSU r-proteins was lethal and led to destabilisation and degradation of the LSU and/or its precursors. Detailed steady state and metabolic pulse labelling analyses of rRNA precursors in these mutant strains showed that LSU r-proteins can be grouped according to their requirement for efficient progression of different steps of large ribosomal subunit maturation. Comparative analyses of the observed phenotypes and the nature of r-protein-rRNA interactions as predicted by current atomic LSU structure models led us to discuss working hypotheses on i how individual r-proteins control the productive processing of the major 5' end of 5.8S rRNA precursors by exonucleases Rat1p and Xrn1p, and ii the nature of structural characteristics of nascent LSUs that are required for cytoplasmic accumulation of nascent subunits but are nonessential for most of the nuclear LSU pre-rRNA processing events.

Structural Studies of RNA Helicases Involved in Eukaryotic Pre-mRNA Splicing, Ribosome Biogenesis, and Translation Initiation

DEFF Research Database (Denmark)

He, Yangzi

and ligates the neighbouring exons to generate mature mRNAs. Prp43 is an RNA helicase of the DEAH/RHA family. In yeast, once mRNAs are released, Prp43 catalyzes the disassembly of spliceosomes. The 18S, 5.8S and 25S rRNAs are transcribed as a single polycistronic transcript—the 35S pre......-rRNA. It is nucleolytically cleaved and chemically modified to generate mature rRNAs, which assemble with ribosomal proteins to form the ribosome. Prp43 is required for the processing of the 18S rRNA. Using X-ray crystallography, I determined a high resolution structure of Prp43 bound to ADP, the first structure of a DEAH....../RHA helicase. It defined the conserved structural features of all DEAH/RHA helicases, and unveiled a novel nucleotide binding site. Additionally a preliminary low resolution structure of a ternary complex comprising Prp43, a non-hydrolyzable ATP analogue, and a single-stranded RNA, was obtained. The ribosome...

Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients.

Science.gov (United States)

Garçon, Loïc; Ge, Jingping; Manjunath, Shwetha H; Mills, Jason A; Apicella, Marisa; Parikh, Shefali; Sullivan, Lisa M; Podsakoff, Gregory M; Gadue, Paul; French, Deborah L; Mason, Philip J; Bessler, Monica; Weiss, Mitchell J

2013-08-08

Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the "safe harbor" AAVS1 locus alleviated abnormalities in ribosome biogenesis and hematopoiesis. Our studies show that pathological features of DBA are recapitulated by iPSCs, provide a renewable source of cells to model various tissue defects, and demonstrate proof of principle for genetic correction strategies in patient stem cells.

Acrolein preferentially damages nucleolus eliciting ribosomal stress and apoptosis in human cancer cells.

Science.gov (United States)

Wang, Hsiang-Tsui; Chen, Tzu-Ying; Weng, Ching-Wen; Yang, Chun-Hsiang; Tang, Moon-Shong

2016-12-06

Acrolein (Acr) is a potent cytotoxic and DNA damaging agent which is ubiquitous in the environment and abundant in tobacco smoke. Acr is also an active cytotoxic metabolite of the anti-cancer drugs cyclophosphamide and ifosfamide. The mechanisms via which Acr exerts its anti-cancer activity and cytotoxicity are not clear. In this study, we found that Acr induces cytotoxicity and cell death in human cancer cells with different activities of p53. Acr preferentially binds nucleolar ribosomal DNA (rDNA) to form Acr-deoxyguanosine adducts, and induces oxidative damage to both rDNA and ribosomal RNA (rRNA). Acr triggers ribosomal stress responses, inhibits rRNA synthesis, reduces RNA polymerase I binding to the promoter of rRNA gene, disrupts nucleolar integrity, and impairs ribosome biogenesis and polysome formation. Acr causes an increase in MDM2 levels and phosphorylation of MDM2 in A549 and HeLa cells which are p53 active and p53 inactive, respectively. It enhances the binding of ribosomal protein RPL11 to MDM2 and reduces the binding of p53 and E2F-1 to MDM2 resulting in stabilization/activation of p53 in A549 cells and degradation of E2F-1 in A549 and HeLa cells. We propose that Acr induces ribosomal stress which leads to activation of MDM2 and RPL11-MDM2 binding, consequently, activates p53 and enhances E2F-1 degradation, and that taken together these two processes induce apoptosis and cell death.

RINT-1 interacts with MSP58 within nucleoli and plays a role in ribosomal gene transcription.

Science.gov (United States)

Yang, Chuan-Pin; Kuo, Yu-Liang; Lee, Yi-Chao; Lee, Kuen-Haur; Chiang, Chi-Wu; Wang, Ju-Ming; Hsu, Che-Chia; Chang, Wen-Chang; Lin, Ding-Yen

2016-09-16

The nucleolus is the cellular site of ribosomal (r)DNA transcription and ribosome biogenesis. The 58-kDa microspherule protein (MSP58) is a nucleolar protein involved in rDNA transcription and cell proliferation. However, regulation of MSP58-mediated rDNA transcription remains unknown. Using a yeast two-hybrid system with MSP58 as bait, we isolated complementary (c)DNA encoding Rad50-interacting protein 1 (RINT-1), as a MSP58-binding protein. RINT-1 was implicated in the cell cycle checkpoint, membrane trafficking, Golgi apparatus and centrosome dynamic integrity, and telomere length control. Both in vitro and in vivo interaction assays showed that MSP58 directly interacts with RINT-1. Interestingly, microscopic studies revealed the co-localization of MSP58, RINT-1, and the upstream binding factor (UBF), a rRNA transcription factor, in the nucleolus. We showed that ectopic expression of MSP58 or RINT-1 resulted in decreased rRNA expression and rDNA promoter activity, whereas knockdown of MSP58 or RINT-1 by siRNA exerted the opposite effect. Coexpression of MSP58 and RINT-1 robustly decreased rRNA synthesis compared to overexpression of either protein alone, whereas depletion of RINT-1 from MSP58-transfected cells enhanced rRNA synthesis. We also found that MSP58, RINT-1, and the UBF were associated with the rDNA promoter using a chromatin immunoprecipitation assay. Because aberrant ribosome biogenesis contributes to neoplastic transformation, our results revealed a novel protein complex involved in the regulation of rRNA gene expression, suggesting a role for MSP58 and RINT-1 in cancer development. Copyright © 2016 Elsevier Inc. All rights reserved.

Depletion of ribosomal protein L37 occurs in response to DNA damage and activates p53 through the L11/MDM2 pathway.

Science.gov (United States)

Llanos, Susana; Serrano, Manuel

2010-10-01

Perturbation of ribosomal biogenesis has recently emerged as a relevant p53-activating pathway. This pathway can be initiated by depletion of certain ribosomal proteins, which is followed by the binding and inhibition of MDM2 by a different subset of ribosomal proteins that includes L11. Here, we report that depletion of L37 leads to cell cycle arrest in a L11- and p53-dependent manner. DNA damage can initiate ribosomal stress, although little is known about the mechanisms involved. We have found that some genotoxic insults, namely, UV light and cisplatin, lead to proteasomal degradation of L37 in the nucleoplasm and to the ensuing L11-dependent stabilization of p53. Moreover, ectopic L37 overexpression can attenuate the DNA damage response mediated by p53. These results support the concept that DNA damage-induced proteasomal degradation of L37 constitutes a mechanistic link between DNA damage and the ribosomal stress pathway, and is a relevant contributing signaling pathway for the activation of p53 in response to DNA damage.

Resveratrol induces mitochondrial biogenesis in endothelial cells.

Science.gov (United States)

Csiszar, Anna; Labinskyy, Nazar; Pinto, John T; Ballabh, Praveen; Zhang, Hanrui; Losonczy, Gyorgy; Pearson, Kevin; de Cabo, Rafael; Pacher, Pal; Zhang, Cuihua; Ungvari, Zoltan

2009-07-01

Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.

Erythrocyte nanovesicles: Biogenesis, biolo

Directory of Open Access Journals (Sweden)

Gamaleldin I. Harisa

2017-01-01

Full Text Available Nanovesicles (NVs represent a novel transporter for cell signals to modify functions of target cells. Therefore, NVs play many roles in both physiological and pathological processes. This report highlights biogenesis, composition and biological roles of erythrocytes derived nanovesicles (EDNVs. Furthermore, we address utilization of EDNVs as novel drug delivery cargo as well as therapeutic target. EDNVs are lipid bilayer vesicles rich in phospholipids, proteins, lipid raft, and hemoglobin. In vivo EDNVs biogenesis is triggered by an increase of intracellular calcium levels, ATP depletion and under effect of oxidative stress conditions. However, in vitro production of EDNVs can be achieved via hypotonic treatment and extrusion of erythrocyte. NVs can be used as biomarkers for diagnosis, monitoring of therapy and drug delivery system. Many therapeutic agents are suggested to decrease NVs biogenesis.

The AAA-ATPase NVL2 is a component of pre-ribosomal particles that interacts with the DExD/H-box RNA helicase DOB1

International Nuclear Information System (INIS)

Nagahama, Masami; Yamazoe, Takeshi; Hara, Yoshimitsu; Tani, Katsuko; Tsuji, Akihiko; Tagaya, Mitsuo

2006-01-01

Nuclear VCP/p97-like protein 2 (NVL2) is a member of the chaperone-like AAA-ATPase family with two conserved ATP-binding modules. Our previous studies have shown that NVL2 is localized to the nucleolus by interacting with ribosomal protein L5 and may participate in ribosome synthesis, a process involving various non-ribosomal factors including chaperones and RNA helicases. Here, we show that NVL2 is associated with pre-ribosomal particles in the nucleus. Moreover, we used yeast two-hybrid and co-immunoprecipitation assays to identify an NVL2-interacting protein that could yield insights into NVL2 function in ribosome biogenesis. We found that NVL2 interacts with DOB1, a DExD/H-box RNA helicase, whose yeast homologue functions in a late stage of the 60S subunit synthesis. DOB1 can interact with a second ATP-binding module mutant of NVL2, which shows a dominant negative effect on ribosome synthesis. In contrast, it cannot interact with a first ATP-binding module mutant, which does not show the dominant negative effect. When the dominant negative mutant of NVL2 was overexpressed in cells, DOB1 appeared to remain associated with nuclear pre-ribosomal particles. Such accumulation was not observed upon overexpression of wild-type NVL2 or a nondominant-negative mutant. Taken together, our results suggest that NVL2 might regulate the association/dissociation reaction of DOB1 with pre-ribosomal particles by acting as a molecular chaperone

Safeguards Culture

Energy Technology Data Exchange (ETDEWEB)

Frazar, Sarah L.; Mladineo, Stephen V.

2012-07-01

The concepts of nuclear safety and security culture are well established; however, a common understanding of safeguards culture is not internationally recognized. Supported by the National Nuclear Security Administration, the authors prepared this report, an analysis of the concept of safeguards culture, and gauged its value to the safeguards community. The authors explored distinctions between safeguards culture, safeguards compliance, and safeguards performance, and evaluated synergies and differences between safeguards culture and safety/security culture. The report concludes with suggested next steps.

The international safeguards and domestic safeguards and security interface

International Nuclear Information System (INIS)

Whitworth, A.

1996-01-01

The International Safeguards Division, in conjunction with the Office of Safeguards and Security, organized a workshop on the international safeguards/domestic safeguards and security interface that was held in March 1996. The purpose of the workshop was to identify and resolve domestic safeguards and security issues associated with the implementation of International Atomic Energy Agency (IAEA) safeguards in the Department of Energy (DOE) complex. The workshop drew heavily upon lessons learned in the application of IAEA safeguards at storage facilities in oak Ridge, Hanford, and Rocky Flats. It was anticipated that the workshop would facilitate a consistent DOE safeguards and security approach for the implementation of IAEA safeguards in the DOE complex. This paper discusses the issues and resolutions of several issues raised at the workshop that involve primarily the domestic material control and accountability program

Facility Safeguardability Analysis in Support of Safeguards by Design

International Nuclear Information System (INIS)

Wonder, E.F.

2010-01-01

The idea of 'Safeguards-by-Design' (SBD) means designing and incorporating safeguards features into new civil nuclear facilities at the earliest stages in the design process to ensure that the constructed facility is 'safeguardable,' i.e. will meet national and international nuclear safeguards requirements. Earlier consideration of safeguards features has the potential to reduce the need for costly retrofits of the facility and can result in a more efficient and effective safeguards design. A 'Facility Safeguardability Analysis' (FSA) would be a key step in Safeguards-by-Design that would link the safeguards requirements with the 'best practices', 'lessons learned', and design of the safeguards measures for implementing those requirements. The facility designer's nuclear safeguards experts would work closely with other elements of the project design team in performing FSA. The resultant analysis would support discussions and interactions with the national nuclear regulator (i.e. State System of Accounting for and Control of Nuclear Material - SSAC) and the IAEA for development and approval of the proposed safeguards system. FSA would also support the implementation of international safeguards by the IAEA, by providing them with a means to analyse and evaluate the safeguardability of facilities being designed and constructed - i.e. by independently reviewing and validating the FSA as performed by the design team. Development of an FSA methodology is part of a broader U.S. National Nuclear Security Administration program to develop international safeguards-by-design tools and guidance documents for use by facility designers. The NNSA NGSI -sponsored project team is looking, as one element of its work, at how elements of the methodology developed by the Generation IV International Forum's Working Group on Proliferation Resistance and Physical Protection can be adapted to supporting FSA. (author)

Facility Safeguardability Analysis In Support of Safeguards-by-Design

Energy Technology Data Exchange (ETDEWEB)

Philip Casey Durst; Roald Wigeland; Robert Bari; Trond Bjornard; John Hockert; Michael Zentner

2010-07-01

The following report proposes the use of Facility Safeguardability Analysis (FSA) to: i) compare and evaluate nuclear safeguards measures, ii) optimize the prospective facility safeguards approach, iii) objectively and analytically evaluate nuclear facility safeguardability, and iv) evaluate and optimize barriers within the facility and process design to minimize the risk of diversion and theft of nuclear material. As proposed by the authors, Facility Safeguardability Analysis would be used by the Facility Designer and/or Project Design Team during the design and construction of the nuclear facility to evaluate and optimize the facility safeguards approach and design of the safeguards system. Through a process of “Safeguards-by-Design” (SBD), this would be done at the earliest stages of project conceptual design and would involve domestic and international nuclear regulators and authorities, including the International Atomic Energy Agency (IAEA). The benefits of the Safeguards-by-Design approach is that it would clarify at a very early stage the international and domestic safeguards requirements for the Construction Project Team, and the best design and operating practices for meeting these requirements. It would also minimize the risk to the construction project, in terms of cost overruns or delays, which might otherwise occur if the nuclear safeguards measures are not incorporated into the facility design at an early stage. Incorporating nuclear safeguards measures is straight forward for nuclear facilities of existing design, but becomes more challenging with new designs and more complex nuclear facilities. For this reason, the facility designer and Project Design Team require an analytical tool for comparing safeguards measures, options, and approaches, and for evaluating the “safeguardability” of the facility. The report explains how preliminary diversion path analysis and the Proliferation Resistance and Physical Protection (PRPP) evaluation

Safeguards effectiveness criteria and safeguards efficiency

International Nuclear Information System (INIS)

Stein, G.; Canty, M.J.; Knapp, U.; Munch, E.

1983-01-01

A critical examination of current tendencies in quantification, assessment and enhancement of the effectiveness of international safeguards is undertaken. It is suggested that the present narrow and overly technical interpretation of some elements of international safeguards is both impractical and detrimental. A pragmatic, case-bycase approach is called for to implement the provisions of safeguards agreements in a more balanced, efficient way

EURATOM safeguards. Safeguards verifications in reprocessing plants

International Nuclear Information System (INIS)

Heppleston, M.

1999-01-01

This paper provides a brief historical view of the legal basis for EURATOM. The specific application of safeguards to large scale reprocessing plants, from the theoretical model to the practical application of inspection is considered. The challenge to adequately safeguard major commercial reprocessing facilities has led to many novel approaches being developed. These lessons will also benefit other safeguard projects as a result. Good cooperation between the operator and regulator is essential for the satisfactory installation of adequate safeguard controls. The use of modern data processing technology combined with other diverse monitoring techniques has shown that a major industrial scale reprocessing plant can be controlled under international safeguards to provide a high level of assurance [ru

Regulatory RNPs: a novel class of ribonucleoproteins that potentially contribute to ribosome heterogeneity

Directory of Open Access Journals (Sweden)

Aaron R. Poole

2017-09-01

Full Text Available Many ribonucleoproteins (RNPs, which are comprised of noncoding RNA and associated proteins, are involved in essential cellular processes such as translation and pre-mRNA splicing. One class of RNP is the small Cajal body-specific RNP (scaRNP, which contributes to the biogenesis of small nuclear RNPs (snRNPs that are central components of the spliceosome. Three scaRNAs are internally processed, generating stable nucleolus-enriched RNAs of unknown function. Here, we provide data that show that these RNAs become part of RNPs we term regulatory RNPs (regRNPs. Most modifications within rRNA (predominantly pseudouridylation and ribose 2′-O-methylation are conducted by small nucleolar RNPs (snoRNPs, and we provide evidence that the activity of at least some of these snoRNPs is under the control of regRNPs. Because modifications within rRNA can vary in different physiological or pathological situations, rRNA modifications are thought to be the major source of ribosome heterogeneity. Our identification of regRNPs thus provides a potential mechanism for how ribosome heterogeneity may be accomplished. This work also provides additional functional connections between the Cajal body and the nucleolus.

Safeguards by design - The early consideration of safeguards concepts

International Nuclear Information System (INIS)

Killeen, T.; Moran, B.; Pujol, E.

2009-01-01

Full-text: The IAEA Department of Safeguards is in the process of formalizing its approach to long-range strategic planning. As a result of this activity new endeavours are being identified. One of these endeavours is to develop a concept known as Safeguards by Design. Safeguarding nuclear material and facilities can be made more effective and cost efficient by improving the safeguardability of the system. By taking into account design features that facilitate the implementation of international safeguards early in the design phase, a concept known as safeguards by design, the proliferation resistance of the system can be improved. This improvement process requires an understanding by designers and operators of safeguards and its underlying principles. To advance the safeguards by design approach, the IAEA determined that there is a need to develop written guidance. This guidance would help the major stakeholders - the designers, operators, owners, and regulatory bodies - to better understand how a facility could be designed, built and operated in such a way that effective safeguards could be implemented at reduced cost and with minimal burden to facility operations. By enlisting the cooperation of Member States through the support programme structure, the IAEA is working to first develop a document that describes the basic principles of safeguards, and the fundamental design features and measures that facilitate the implementation of international safeguards. Facility-specific guidance will then be developed utilizing the resources, expertise and experience of the IAEA and its Member States. This paper will review the foundation for the development of this task, describe the progress that has been made and outline the path forward. (author)

Contribution of the 'safeguarded' to the development of safeguards

International Nuclear Information System (INIS)

Anderson, A.R.

1977-01-01

The development of an efficient system of international safeguards requires close and detailed interaction between the safeguarding authority and those being safeguarded, i.e. the plant operator and the State System to which he belongs. Such interaction is found in other control systems but the degree of international collaboration involved in safeguards is perhaps unique and it is valuable to review and analyse the contributions which have arisen from prudent management considerations. The familiar ''Blue Book'' (INFCIRC 153) recognizes clearly the need for an effective State's System of accounting for and control of nuclear materials as a necessary pre-requisite for the development and implementation of an effective IAEA system of safeguards. It is therefore helpful to summarize the relevant contributions from the 'safeguarded' in terms of the components of the State's System specified in paragraph 32 of the Blue Book. This paper reviews the continuing contributions stemming from plant and national experience, with particular emphasis on the development of measurement systems and physical inventory procedures relevant to safeguards. Attention is also drawn to those areas where the specific objectives of IAEA Safeguards lead to requirements additional to those required for management purposes. (author)

International safeguards 1979

International Nuclear Information System (INIS)

Fischer, D.

1979-01-01

First, the nature of the nuclear proliferation problem is reviewed. Afterward, the extent to which the risk of further horizontal proliferation of nuclear weapons is being contained by international agreements and by the application of the IAEA's safeguards under these agreements is investigated. The geographical scope of such safeguards, the gaps in safeguards coverage, and the political and technical effectiveness of such safeguards are examined. In conclusion, it is pointed out that IAEA safeguards are the cutting edge of almost every nonproliferation measure that has so far been applied or put forward. Safeguards would also play a part in any international scheme for limiting vertical proliferation. If the cutting edge of safeguards is blunted or if, for one reason or another, safeguards cannot be or are not being applied, the nonproliferation regime will suffer commensurate damage

Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma.

Science.gov (United States)

Grinchuk, Oleg V; Yenamandra, Surya P; Iyer, Ramakrishnan; Singh, Malay; Lee, Hwee Kuan; Lim, Kiat Hon; Chow, Pierce Kah-Hoe; Kuznetsov, Vladamir A

2018-01-01

Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods. We developed a 24-ribosomal gene-based HCC classifier (RGC), which is prognostically significant in both PT and AT. The RGC gene overexpression in PT was associated with a poor prognosis in the training (hazard ratio = 8.2, P = 9.4 × 10 -6 ) and cross-cohort validation (hazard ratio = 2.63, P = 0.004) datasets. The multivariate survival analysis demonstrated the significant and independent prognostic value of the RGC. The RGC displayed a significant prognostic value in AT of the training (hazard ratio = 5.0, P = 0.03) and cross-validation (hazard ratio = 1.9, P = 0.03) HCC groups, confirming the accuracy and robustness of the RGC. Our experimental and bioinformatics analyses suggested a key role for c-MYC in the pro-oncogenic pattern of ribosomal biogenesis co-regulation in PT and AT. Microarray, quantitative RT-PCR and quantitative immunohistochemical studies of the PT showed that DKK1 in PT is the perspective biomarker for poor HCC outcomes. The common co-transcriptional pattern of ribosome biogenesis genes in PT and AT from HCC patients suggests a new scalable prognostic system, as supported by the model of tumor-like metabolic redirection/assimilation in non-malignant AT. The RGC, comprising 24 ribosomal genes, is introduced as a robust and reproducible prognostic model for

Contribution of the ''safeguarded'' to the development of safeguards

International Nuclear Information System (INIS)

Anderson, A.R.

1977-01-01

The development of an efficient system of international safeguards requires close and detailed interaction between the safeguarding authority and those being safeguarded, i.e. the plant operator and the State System to which he belongs. Such interaction is found in other control systems but the degree of international collaboration involved in Safeguards is perhaps unique and it is valuable to review and analyse the contributions which have arisen from prudent management considerations. Management has many reasons to exercise stringent control of nuclear materials stemming from the value and hazardous nature of the materials being used, and the requirements of relevant national legislation. Because systems at a plant and within a State are generally designed to control quantities of nuclear materials within limits smaller than those specified in the I.A.E.A.'s Safeguards objectives, experience at the plant level has contributed significantly to the development of International Safeguards procedures. In making such contributions, plant management and the national authorities have a common objective with that of the I.A.E.A. in developing a Safeguards system which is both technically-effective and cost-effective. The pursuit of this objective requires that implementation of the Safeguards system can be modified in the light of relevant practical experience of plant operators and of the I.A.E.A. The familiar Blue Book (INFCIRC 153) recognises clearly the need for an effective State's System of accounting for and control of nuclear materials as a necessary pre-requisite for the development and implementation of an effective I.A.E.A. system of Safeguards. It is therefore helpful to review the relevant contributions from the 'Safeguarded' in terms of the components of the State's System specified in paragraph 32 of the Blue Book. This paper reviews the continuing contributions stemming from plant and national experience, with particular emphasis on the development of

Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses

OpenAIRE

Iwai Ohbayashi; Munetaka Sugiyama

2018-01-01

The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized p...

Structure of the ribosomal interacting GTPase YjeQ from the enterobacterial species Salmonella typhimurium

International Nuclear Information System (INIS)

Nichols, C. E.; Johnson, C.; Lamb, H. K.; Lockyer, M.; Charles, I. G.; Hawkins, A. R.; Stammers, D. K.

2007-01-01

The X-ray crystal structure of the GTPase YjeQ from S. typhimurium is presented and compared with those of orthologues from T. maritima and B. subtilis. The YjeQ class of P-loop GTPases assist in ribosome biogenesis and also bind to the 30S subunit of mature ribosomes. YjeQ ribosomal binding is GTP-dependent and thought to specifically direct protein synthesis, although the nature of the upstream signal causing this event in vivo is as yet unknown. The attenuating effect of YjeQ mutants on bacterial growth in Escherichia coli makes it a potential target for novel antimicrobial agents. In order to further explore the structure and function of YjeQ, the isolation, crystallization and structure determination of YjeQ from the enterobacterial species Salmonella typhimurium (StYjeQ) is reported. Whilst the overall StYjeQ fold is similar to those of the previously reported Thematoga maritima and Bacillus subtilis orthologues, particularly the GTPase domain, there are larger differences in the three OB folds. Although the zinc-finger secondary structure is conserved, significant sequence differences alter the nature of the external surface in each case and may reflect varying signalling pathways. Therefore, it may be easier to develop YjeQ-specific inhibitors that target the N- and C-terminal regions, disrupting the metabolic connectivity rather than the GTPase activity. The availability of coordinates for StYjeQ will provide a significantly improved basis for threading Gram-negative orthologue sequences and in silico compound-screening studies, with the potential for the development of species-selective drugs

Structure of the ribosomal interacting GTPase YjeQ from the enterobacterial species Salmonella typhimurium

Energy Technology Data Exchange (ETDEWEB)

Nichols, C. E. [Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Johnson, C.; Lamb, H. K. [Institute of Cell and Molecular Biosciences, Catherine Cookson Building, Medical School, Framlington Place, Newcastle University, Newcastle-upon-Tyne NE2 4HH (United Kingdom); Lockyer, M. [Arrow Therapeutics Ltd, Britannia House, Trinity Street, Borough, London SE1 1DA (United Kingdom); Charles, I. G. [The Wolfson Institute for Biomedical Research, The Cruciform Building, University College London, Gower Street, London WC1E 6BT (United Kingdom); Hawkins, A. R. [Institute of Cell and Molecular Biosciences, Catherine Cookson Building, Medical School, Framlington Place, Newcastle University, Newcastle-upon-Tyne NE2 4HH (United Kingdom); Stammers, D. K., E-mail: daves@strubi.ox.ac.uk [Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

2007-11-01

The X-ray crystal structure of the GTPase YjeQ from S. typhimurium is presented and compared with those of orthologues from T. maritima and B. subtilis. The YjeQ class of P-loop GTPases assist in ribosome biogenesis and also bind to the 30S subunit of mature ribosomes. YjeQ ribosomal binding is GTP-dependent and thought to specifically direct protein synthesis, although the nature of the upstream signal causing this event in vivo is as yet unknown. The attenuating effect of YjeQ mutants on bacterial growth in Escherichia coli makes it a potential target for novel antimicrobial agents. In order to further explore the structure and function of YjeQ, the isolation, crystallization and structure determination of YjeQ from the enterobacterial species Salmonella typhimurium (StYjeQ) is reported. Whilst the overall StYjeQ fold is similar to those of the previously reported Thematoga maritima and Bacillus subtilis orthologues, particularly the GTPase domain, there are larger differences in the three OB folds. Although the zinc-finger secondary structure is conserved, significant sequence differences alter the nature of the external surface in each case and may reflect varying signalling pathways. Therefore, it may be easier to develop YjeQ-specific inhibitors that target the N- and C-terminal regions, disrupting the metabolic connectivity rather than the GTPase activity. The availability of coordinates for StYjeQ will provide a significantly improved basis for threading Gram-negative orthologue sequences and in silico compound-screening studies, with the potential for the development of species-selective drugs.

New Partners in Regulation of Gene Expression: The Enhancer of Trithorax and Polycomb Corto Interacts with Methylated Ribosomal Protein L12 Via Its Chromodomain

Science.gov (United States)

Coléno-Costes, Anne; Jang, Suk Min; de Vanssay, Augustin; Rougeot, Julien; Bouceba, Tahar; Randsholt, Neel B.; Gibert, Jean-Michel; Le Crom, Stéphane; Mouchel-Vielh, Emmanuèle

2012-01-01

Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA–seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators. PMID:23071455

Safeguards

International Nuclear Information System (INIS)

Carchon, R.

1998-01-01

Safeguards activities at the Belgian Nuclear Research Centre SCK/CEN answer internal needs, support the Belgian authorities, and support the IAEA. The main objectives of activities concerning safeguards are: (1) to contribute to a prevention of the proliferation of nuclear materials by maintaining an up-to-date expertise in the field of safeguards and providing advice and guidance as well as scientific and technical support to the Belgian authorities and nuclear industry; (2) to improve the qualification and quantification of nuclear materials via nondestructive assay. The main achievements for 1997 are described

Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit.

Science.gov (United States)

He, J; Cooper, H M; Reyes, A; Di Re, M; Kazak, L; Wood, S R; Mao, C C; Fearnley, I M; Walker, J E; Holt, I J

2012-07-01

The bacterial homologue of C4orf14, YqeH, has been linked to assembly of the small ribosomal subunit. Here, recombinant C4orf14 isolated from human cells, co-purified with the small, 28S subunit of the mitochondrial ribosome and the endogenous protein co-fractionated with the 28S subunit in sucrose gradients. Gene silencing of C4orf14 specifically affected components of the small subunit, leading to decreased protein synthesis in the organelle. The GTPase of C4orf14 was critical to its interaction with the 28S subunit, as was GTP. Therefore, we propose that C4orf14, with bound GTP, binds to components of the 28S subunit facilitating its assembly, and GTP hydrolysis acts as the release mechanism. C4orf14 was also found to be associated with human mitochondrial nucleoids, and C4orf14 gene silencing caused mitochondrial DNA depletion. In vitro C4orf14 is capable of binding to DNA. The association of C4orf14 with mitochondrial translation factors and the mitochondrial nucleoid suggests that the 28S subunit is assembled at the mitochondrial nucleoid, enabling the direct transfer of messenger RNA from the nucleoid to the ribosome in the organelle.

crRNA biogenesis

NARCIS (Netherlands)

Charpentier, E.; Oost, van der J.; White, M.

2013-01-01

Mature crRNAs are key elements in CRISPR-Cas defense against genome invaders. These short RNAs are composed of unique repeat/spacer sequences that guide the Cas protein(s) to the cognate invading nucleic acids for their destruction. The biogenesis of mature crRNAs involves highly precise processing

Neuron-Like Networks Between Ribosomal Proteins Within the Ribosome

Science.gov (United States)

Poirot, Olivier; Timsit, Youri

2016-05-01

From brain to the World Wide Web, information-processing networks share common scale invariant properties. Here, we reveal the existence of neural-like networks at a molecular scale within the ribosome. We show that with their extensions, ribosomal proteins form complex assortative interaction networks through which they communicate through tiny interfaces. The analysis of the crystal structures of 50S eubacterial particles reveals that most of these interfaces involve key phylogenetically conserved residues. The systematic observation of interactions between basic and aromatic amino acids at the interfaces and along the extension provides new structural insights that may contribute to decipher the molecular mechanisms of signal transmission within or between the ribosomal proteins. Similar to neurons interacting through “molecular synapses”, ribosomal proteins form a network that suggest an analogy with a simple molecular brain in which the “sensory-proteins” innervate the functional ribosomal sites, while the “inter-proteins” interconnect them into circuits suitable to process the information flow that circulates during protein synthesis. It is likely that these circuits have evolved to coordinate both the complex macromolecular motions and the binding of the multiple factors during translation. This opens new perspectives on nanoscale information transfer and processing.

Comparison of preribosomal RNA processing pathways in yeast, plant and human cells - focus on coordinated action of endo- and exoribonucleases.

Science.gov (United States)

Tomecki, Rafal; Sikorski, Pawel J; Zakrzewska-Placzek, Monika

2017-07-01

Proper regulation of ribosome biosynthesis is mandatory for cellular adaptation, growth and proliferation. Ribosome biogenesis is the most energetically demanding cellular process, which requires tight control. Abnormalities in ribosome production have severe consequences, including developmental defects in plants and genetic diseases (ribosomopathies) in humans. One of the processes occurring during eukaryotic ribosome biogenesis is processing of the ribosomal RNA precursor molecule (pre-rRNA), synthesized by RNA polymerase I, into mature rRNAs. It must not only be accurate but must also be precisely coordinated with other phenomena leading to the synthesis of functional ribosomes: RNA modification, RNA folding, assembly with ribosomal proteins and nucleocytoplasmic RNP export. A multitude of ribosome biogenesis factors ensure that these events take place in a correct temporal order. Among them are endo- and exoribonucleases involved in pre-rRNA processing. Here, we thoroughly present a wide spectrum of ribonucleases participating in rRNA maturation, focusing on their biochemical properties, regulatory mechanisms and substrate specificity. We also discuss cooperation between various ribonucleolytic activities in particular stages of pre-rRNA processing, delineating major similarities and differences between three representative groups of eukaryotes: yeast, plants and humans. © 2017 Federation of European Biochemical Societies.

A Safeguardability Check-List for Safeguards by Design

Energy Technology Data Exchange (ETDEWEB)

Sevini, F. [European Commission - Joint Research Centre, Institute for Transuranium Elements, Nuclear Security Unit, Ispra (Italy); Renda, G. [European Commission, DG Energy, Directorate E ' Nuclear Safeguards' , Unit 4 ' Inspections: reactors, storages and others facilities, Luxembourg (Luxembourg); Sidlova, V. [European Commission - Joint Research Centre, Institute for Transuranium Elements, Nuclear Security Unit, Ispra (Italy)

2011-12-15

Safeguards by design is a complex step-by-step interactive decision process involving various stake-holders and design choices to be made over a certain period of time. The resulting plant design should be a compromise among economical, safety, security and safeguards implementation constraints. Access to technology and equipment, as well as to the nuclear fuel cycle, determines the basic choices that the designer has to make. Once the boundary conditions for a given facility have been fixed, the designer still faces the challenge of setting several design and operational parameters that will require various trade-offs . Concerning safeguards, these can be seen in three groups, i.e. those related to the general design and its intrinsic proliferation resistance; those related to the specific lay-out and planning; those related to the actual safeguards instrumentation, its effectiveness and efficiency. The paper aims at describing a model for a phased, or 'layered' approach to safeguards-by-design, focusing on the example of off-load reactors.

Promoting Safeguards Best Practice through the Asia-Pacific Safeguards Network (APSN)

International Nuclear Information System (INIS)

Floyd, R.; Everton, C.; Lestari, S.

2015-01-01

There is a growing international focus on effective regulatory oversight of nuclear energy across the three pillars of nuclear safety, security and safeguards. Regarding nuclear safeguards, States in the Asia-Pacific region recognize the importance of cooperation and sharing of experiences to ensure that this is implemented to high international standards. For this reason the Asia-Pacific Safeguards Network (APSN) was formed in 2009 - an informal network of departments, agencies and regulatory authorities with safeguards responsibilities from some 15 countries across the Asia-Pacific region. The objective of APSN it to bring States in the region together to develop practical measures for enhancing effective safeguards implementation, through workshops, sharing experiences and other safeguards projects. APSN works closely with the IAEA to achieve these objectives. This paper will outline the role and objectives of APSN and provide examples of how APSN work together to enhance safeguards effectiveness and raise awareness. The paper will also explore how this model of a broad community of States working together on safeguards could enhance implementation and awareness in other regions of the world. (author)

Safeguards activities in Japan

International Nuclear Information System (INIS)

Osabe, Takeshi

1998-01-01

Current Japanese State System for Accountancy and Control (SSAC) has been developing and fully satisfies requirements of both IAEA Safeguards and bilateral partners. However, the public attention on the national and international safeguards activities were increased and the safeguards authorities were required to promote the objective assessment of safeguards implementation to avoid mistrust in safeguards activities which directly influence the public acceptance of nuclear energy in itself. Additionally, since Japan has promoted to complete nuclear fuel cycle including spent fuel reprocessing, enrichment and mixed oxide fuel fabrication this would require further assurance of Japanese non-proliferation commitment. Japan supports the introduction of strengthened safeguards. In this context it is particularly important to strengthen the relationship between national and the IAEA safeguards to contribute actively to the IAEA safeguards in development and utilization of new technologies towards more effective and efficient IAEA safeguards

Reactive Oxygen Species-Mediated Control of Mitochondrial Biogenesis

Directory of Open Access Journals (Sweden)

Edgar D. Yoboue

2012-01-01

Full Text Available Mitochondrial biogenesis is a complex process. It necessitates the contribution of both the nuclear and the mitochondrial genomes and therefore crosstalk between the nucleus and mitochondria. It is now well established that cellular mitochondrial content can vary according to a number of stimuli and physiological states in eukaryotes. The knowledge of the actors and signals regulating the mitochondrial biogenesis is thus of high importance. The cellular redox state has been considered for a long time as a key element in the regulation of various processes. In this paper, we report the involvement of the oxidative stress in the regulation of some actors of mitochondrial biogenesis.

Safeguards resource management

International Nuclear Information System (INIS)

Strait, R.S.

1986-01-01

Protecting nuclear materials is a challenging problem for facility managers. To counter the broad spectrum of potential threats, facility managers rely on diverse safeguards measures, including elements of physical protection, material control and accountability, and human reliability programs. Deciding how to upgrade safeguards systems involves difficult tradeoffs between increased protection and the costs and operational impact of protection measures. Effective allocation of safeguards and security resources requires a prioritization of system upgrades based on a relative measure of upgrade benefits to upgrade costs. Analytical tools are needed to help safeguards managers measure the relative benefits and costs and allocate their limited resources to achieve balanced, cost-effective protection against the full spectrum of threats. This paper presents a conceptual approach and quantitative model that have been developed by Lawrence Livermore National Laboratory to aid safeguards managers. The model is in the preliminary stages of implementation, and an effort is ongoing to make the approach and quantitative model available for general use. The model, which is designed to complement existing nuclear safeguards evaluation tools, incorporates a variety of factors and integrates information on the likelihood of potential threats, safeguards capabilities to defeat threats, and the relative consequences if safeguards fail. The model uses this information to provide an overall measure for comparing safeguards upgrade projects at a facility

Eukaryotic 5S rRNA biogenesis

Science.gov (United States)

Ciganda, Martin; Williams, Noreen

2012-01-01

The ribosome is a large complex containing both protein and RNA which must be assembled in a precise manner to allow proper functioning in the critical role of protein synthesis. 5S rRNA is the smallest of the RNA components of the ribosome, and although it has been studied for decades, we still do not have a clear understanding of its function within the complex ribosome machine. It is the only RNA species that binds ribosomal proteins prior to its assembly into the ribosome. Its transport into the nucleolus requires this interaction. Here we present an overview of some of the key findings concerning the structure and function of 5S rRNA and how its association with specific proteins impacts its localization and function. PMID:21957041

Next Generation Safeguards Initiative Workshop on Enhanced Recruiting for International Safeguards

International Nuclear Information System (INIS)

Pepper, S.E.; Rosenthal, M.D.; Fishbone, L.G.; Occhogrosso, D.M.; Lockwood, D.; Carroll, C.J.; Dreicer, M.; Wallace, R.; Fankhauser, J.

2009-01-01

Brookhaven National Laboratory (BNL) hosted a Workshop on Enhanced Recruiting for International Safeguards October 22 and 23, 2008. The workshop was sponsored by DOE/NA-243 under the Next Generation Safeguards Initiative (NGSI). Placing well-qualified Americans in sufficient number and in key safeguards positions within the International Atomic Energy Agency's (IAEA's) Department of Safeguards is an important U.S. non-proliferation objective. The goal of the NGSI Workshop on Enhanced Recruiting for International Safeguards was to improve U.S. efforts to recruit U.S. citizens for IAEA positions in the Department of Safeguards. The participants considered the specific challenges of recruiting professional staff, safeguards inspectors, and managers. BNL's International Safeguards Project Office invited participants from the U.S. Department of Energy, the IAEA, U.S. national laboratories, private industry, academia, and professional societies who are either experts in international safeguards or who understand the challenges of recruiting for technical positions. A final report for the workshop will be finalized and distributed in early 2009. The main finding of the workshop was the need for an integrated recruitment plan to take into account pools of potential candidates, various government and private agency stakeholders, the needs of the IAEA, and the NGSI human capital development plan. There were numerous findings related to and recommendations for maximizing the placement of U.S. experts in IAEA Safeguards positions. The workshop participants offered many ideas for increasing the pool of candidates and increasing the placement rate. This paper will provide details on these findings and recommendations

Next Generation Safeguards Initiative Workshop on Enhanced Recruiting for International Safeguards

Energy Technology Data Exchange (ETDEWEB)

Pepper,S.E.; Rosenthal, M.D.; Fishbone, L.G.; Occhogrosso, D.M.; Lockwood, D.; Carroll, C.J.; Dreicer, M.; Wallace, R.; Fankhauser, J.

2009-07-12

Brookhaven National Laboratory (BNL) hosted a Workshop on Enhanced Recruiting for International Safeguards October 22 and 23, 2008. The workshop was sponsored by DOE/NA-243 under the Next Generation Safeguards Initiative (NGSI). Placing well-qualified Americans in sufficient number and in key safeguards positions within the International Atomic Energy Agency’s (IAEA’s) Department of Safeguards is an important U.S. non-proliferation objective. The goal of the NGSI Workshop on Enhanced Recruiting for International Safeguards was to improve U.S. efforts to recruit U.S. citizens for IAEA positions in the Department of Safeguards. The participants considered the specific challenges of recruiting professional staff, safeguards inspectors, and managers. BNL’s International Safeguards Project Office invited participants from the U.S. Department of Energy, the IAEA, U.S. national laboratories, private industry, academia, and professional societies who are either experts in international safeguards or who understand the challenges of recruiting for technical positions. A final report for the workshop will be finalized and distributed in early 2009. The main finding of the workshop was the need for an integrated recruitment plan to take into account pools of potential candidates, various government and private agency stakeholders, the needs of the IAEA, and the NGSI human capital development plan. There were numerous findings related to and recommendations for maximizing the placement of U.S. experts in IAEA Safeguards positions. The workshop participants offered many ideas for increasing the pool of candidates and increasing the placement rate. This paper will provide details on these findings and recommendations

Next Generation Safeguards Initiative Workshop on Enhanced Recruiting for International Safeguards

Energy Technology Data Exchange (ETDEWEB)

Pepper,S.; Rosenthal, M.; Fishbone, L.; Occhiogrosso, D.; Carroll, C.; Dreicer, M.; Wallace, R.; Rankhauser, J.

2008-10-22

In 2007, the National Nuclear Security Administration's Office of Nonproliferation and International Security (NA-24) completed a yearlong review of the challenges facing the international safeguards system today and over the next 25 years. The study found that without new investment in international safeguards, the U.S. safeguards technology base, and our ability to support International Atomic Energy Agency (IAEA) safeguards, will continue to erode and soon may be at risk. To reverse this trend, the then U.S. Secretary of Energy, Samuel Bodman, announced at the 2007 IAEA General Conference that the Department of Energy (DOE) would launch the Next Generation Safeguards Initiative (NGSI). He stated 'IAEA safeguards must be robust and capable of addressing proliferation threats. Full confidence in IAEA safeguards is essential for nuclear power to grow safely and securely. To this end, the U.S. Department of Energy will seek to ensure that modern technology, the best scientific expertise, and adequate resources are available to keep pace with expanding IAEA responsibilities.' To meet this goal, the NGSI objectives include the recruitment of international safeguards experts to work at the U.S. national laboratories and to serve at the IAEA's headquarters. Part of the latter effort will involve enhancing our existing efforts to place well-qualified Americans in a sufficient number of key safeguards positions within the IAEA's Department of Safeguards. Accordingly, the International Safeguards Project Office (ISPO) at Brookhaven National Laboratory (BNL) hosted a Workshop on Enhanced Recruiting for International Safeguards (ERIS) on October 22 and 23, 2008. The ISPO used a workshop format developed earlier with Sonalysts, Inc., that was followed at the U.S. Support Program's (USSP's) technology road-mapping sessions. ISPO invited participants from the U.S. DOE, the IAEA, the U.S. national laboratories, private industry, academia, and

A Comprehensive Analysis of Chromoplast Differentiation Reveals Complex Protein Changes Associated with Plastoglobule Biogenesis and Remodeling of Protein Systems in Sweet Orange Flesh1[OPEN

Science.gov (United States)

Wang, Lun; Deng, Xiuxin

2015-01-01

Globular and crystalloid chromoplasts were observed to be region specifically formed in sweet orange (Citrus sinensis) flesh and converted from amyloplasts during fruit maturation, which was associated with the composition of specific carotenoids and the expression of carotenogenic genes. Subsequent isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analyses of purified plastids from the flesh during chromoplast differentiation and senescence identified 1,386 putative plastid-localized proteins, 1,016 of which were quantified by spectral counting. The iTRAQ values reflecting the expression abundance of three identified proteins were validated by immunoblotting. Based on iTRAQ data, chromoplastogenesis appeared to be associated with three major protein expression patterns: (1) marked decrease in abundance of the proteins participating in the translation machinery through ribosome assembly; (2) increase in abundance of the proteins involved in terpenoid biosynthesis (including carotenoids), stress responses (redox, ascorbate, and glutathione), and development; and (3) maintenance of the proteins for signaling and DNA and RNA. Interestingly, a strong increase in abundance of several plastoglobule-localized proteins coincided with the formation of plastoglobules in the chromoplast. The proteomic data also showed that stable functioning of protein import, suppression of ribosome assembly, and accumulation of chromoplast proteases are correlated with the amyloplast-to-chromoplast transition; thus, these processes may play a collective role in chromoplast biogenesis and differentiation. By contrast, the chromoplast senescence process was inferred to be associated with significant increases in stress response and energy supply. In conclusion, this comprehensive proteomic study identified many potentially new plastid-localized proteins and provides insights into the potential developmental and molecular mechanisms underlying chromoplast

Safeguards effectiveness evaluations in safeguards planning

International Nuclear Information System (INIS)

Al-Ayat, R.A.

1987-01-01

This paper describes analytic tools we developed to quantify the effectiveness of safeguards against theft of special nuclear material by insiders. These tools help identify vulnerabilities in existing safeguards, suggest potential improvements, and help assess the benefits of these upgrades prior to implementation. Alone, these tools are not sufficient for safeguards planning, since the cost of implementing all suggested upgrades almost always exceeds the available resources. This paper describes another tool we developed to allow comparsion of benefits of various upgrades to identify those upgrade packages that achieve the greatest improvement in protection for a given cost and to provide a priority ranking among cost-effective packages, thereby helping decision-makers select the upgrades to implement and highlight the mount of residual risk. 5 refs., 3 figs

Nuclear Safeguards Culture

International Nuclear Information System (INIS)

Findlay, T.

2015-01-01

The paper will consider safeguards culture both at the IAEA and among member states. It will do so through the lens of organizational culture theory and taking into account developments in safeguards since the Iraq case of the early 1990s. The study will seek to identify the current characteristics of safeguards culture and how it has evolved since the 93+2 programme was initiated, as well as considering the roles of the most important purveyors of such culture, including member states and their national safeguards authorities, the General Conference and Board of Governors, the Director General, the Secretariat as a whole, the Safeguards Department and the inspectorate. The question of what might be an optimal safeguards culture at the Agency and among member states will be investigated, along with the issue of how such a culture might be engendered or encouraged. (author)

Building safeguards infrastructure

International Nuclear Information System (INIS)

Stevens, Rebecca S.; McClelland-Kerr, John

2009-01-01

Much has been written in recent years about the nuclear renaissance - the rebirth of nuclear power as a clean and safe source of electricity around the world. Those who question the nuclear renaissance often cite the risk of proliferation, accidents or an attack on a facility as concerns, all of which merit serious consideration. The integration of these three areas - sometimes referred to as 3S, for safety, security and safeguards - is essential to supporting the growth of nuclear power, and the infrastructure that supports them should be strengthened. The focus of this paper will be on the role safeguards plays in the 3S concept and how to support the development of the infrastructure necessary to support safeguards. The objective of this paper has been to provide a working definition of safeguards infrastructure, and to discuss xamples of how building safeguards infrastructure is presented in several models. The guidelines outlined in the milestones document provide a clear path for establishing both the safeguards and the related infrastructures needed to support the development of nuclear power. The model employed by the INSEP program of engaging with partner states on safeguards-related topics that are of current interest to the level of nuclear development in that state provides another way of approaching the concept of building safeguards infrastructure. The Next Generation Safeguards Initiative is yet another approach that underscored five principal areas for growth, and the United States commitment to working with partners to promote this growth both at home and abroad.

Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect.

Directory of Open Access Journals (Sweden)

Guido Veit

2016-05-01

Full Text Available The most common cystic fibrosis (CF causing mutation, deletion of phenylalanine 508 (ΔF508 or Phe508del, results in functional expression defect of the CF transmembrane conductance regulator (CFTR at the apical plasma membrane (PM of secretory epithelia, which is attributed to the degradation of the misfolded channel at the endoplasmic reticulum (ER. Deletion of phenylalanine 670 (ΔF670 in the yeast oligomycin resistance 1 gene (YOR1, an ABC transporter of Saccharomyces cerevisiae phenocopies the ΔF508-CFTR folding and trafficking defects. Genome-wide phenotypic (phenomic analysis of the Yor1-ΔF670 biogenesis identified several modifier genes of mRNA processing and translation, which conferred oligomycin resistance to yeast. Silencing of orthologues of these candidate genes enhanced the ΔF508-CFTR functional expression at the apical PM in human CF bronchial epithelia. Although knockdown of RPL12, a component of the ribosomal stalk, attenuated the translational elongation rate, it increased the folding efficiency as well as the conformational stability of the ΔF508-CFTR, manifesting in 3-fold augmented PM density and function of the mutant. Combination of RPL12 knockdown with the corrector drug, VX-809 (lumacaftor restored the mutant function to ~50% of the wild-type channel in primary CFTRΔF508/ΔF508 human bronchial epithelia. These results and the observation that silencing of other ribosomal stalk proteins partially rescue the loss-of-function phenotype of ΔF508-CFTR suggest that the ribosomal stalk modulates the folding efficiency of the mutant and is a potential therapeutic target for correction of the ΔF508-CFTR folding defect.

Safeguards '85

International Nuclear Information System (INIS)

Gruemm, H.

1981-01-01

IAEA safeguards watch over the pledge of those non-nuclear weapon countries, which are signatories to the NPT, to refrain from using nuclear installations for military purposes. At present, some 700 installations are inspected in 50 countries, among them 117 nuclear power plants. Further advancement of these safeguards measures serves to develop new methods and equipment for safeguards inspection, ensure that the growing numbers of new plants are inspected, and achieve complete coverage of the eleven countries not signatories to the NPT. However, the long term effectiveness of safeguards will depend on progress being made in the contractual obligations fur nuclear disarmament and in assuring the continuity of supply to non-nuclear weapon countries by the atomic powers and the supplier countries. (orig.) [de

IAEA safeguards

International Nuclear Information System (INIS)

1985-01-01

IAEA safeguards are a system of technical measures within the framework of international non-proliferation policy entrusted to the IAEA in its Statute and by other treaties. About 98% of the world's nuclear installations outside the nuclear-weapon countries are now under safeguards. This paper gives a review of IAEA activities in this field: objectives, agreements, work and development of staff of the IAEA's Department of Safeguards, instruments and techniques for direct measurement and verification of nuclear material. (author)

Safeguards Implementation Practices Guide on Establishing and Maintaining State Safeguards Infrastructure

International Nuclear Information System (INIS)

2015-01-01

The IAEA implements safeguards pursuant to agreements concluded with States. It is in the interests of both States and the IAEA to cooperate to facilitate the practical implementation of safeguards. Such cooperation is explicitly required under all types of safeguards agreements. Effective cooperation depends upon States and the IAEA sharing a common understanding of their respective rights and obligations. To address this, in 2012 the IAEA published Services Series 21, Guidance for States Implementing Comprehensive Safeguards Agreements and Additional Protocols, which aimed at enhancing understanding of the safeguards obligations of both States and the IAEA and at improving their cooperation in safeguards implementation. States may establish different processes and procedures at the national level, and set up different systems as required to meet their safeguards obligations. Indeed, a variety of approaches are to be expected, owing to such differences as the size and complexity of States’ nuclear programmes and their regulatory framework. The purpose of this Safeguards Implementation Practices (SIP) Guide is to share the experiences and good practices as well as the lessons learned by both States and the IAEA, acquired over the many decades of safeguards implementation. The information contained in the SIP Guides is provided for explanatory purposes and use of the Guides is not mandatory. The descriptions in the SIP Guides have no legal status and are not intended to add to, subtract from, amend or derogate from, in any way, the rights and obligations of the IAEA and the States set forth in The Structure and Content of Agreements between the Agency and States Required in Connection with the Treaty on the Non-Proliferation of Nuclear Weapons (issued as INFCIRC/153 (Corrected)) and Model Protocol Additional to the Agreement(s) between State(s) and the International Atomic Energy Agency for the Application of Safeguards (issued as INFCIRC/540 (Corrected)). This

MiRNA Biogenesis and Intersecting Pathways

DEFF Research Database (Denmark)

Ben Chaabane, Samir

MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Plant miRNAs are critical for plant growth, development and stress response, and are processed in Arabidopsis from primary miRNA transcripts (pri-miRNAs) by the endonuclease activity of the DICER-LIKE1...... questions need to be addressed to establish a valid link, we provide encouraging evidence of the involvement of chromatin remodeling factors FAS1 and FAS2 in miRNA biogenesis. Together, we have expanded our understanding of the intersections between miRNA biogenesis and other pathways....

Safeguards Implementation at KAERI

Energy Technology Data Exchange (ETDEWEB)

Jung, Juang; Lee, Sung Ho; Lee, Byung-Doo; Kim, Hyun-Sook [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-05-15

The main objective of the safeguards implementation activities is to assure that there are no diversions of declared nuclear material and/or no undeclared activity. The purpose of safeguards implementation activities is the assistance facility operators to meet the safeguards criteria set forth by the Atomic Energy Safety Acts and Regulations. In addition, the nuclear material and technology control team has acted as a contact point for domestic and international safeguards inspection activities and for the relevant safeguards cooperation. Domestic inspections were successfully carried out at the KAERI nuclear facilities pursuant to the domestic laws and regulations in parallel with the IAEA safeguards inspections. It is expected that safeguards work will be increased due to the pyro-related facilities such as PRIDE, ACPF and DUPIC, for which the IAEA is making an effort to establish safeguards approach. KAERI will actively cope with the plan of the NSSC by changing its domestic inspection regulations on the accounting and control of nuclear materials.

PLK4 trans-Autoactivation Controls Centriole Biogenesis in Space.

Science.gov (United States)

Lopes, Carla A M; Jana, Swadhin Chandra; Cunha-Ferreira, Inês; Zitouni, Sihem; Bento, Inês; Duarte, Paulo; Gilberto, Samuel; Freixo, Francisco; Guerrero, Adán; Francia, Maria; Lince-Faria, Mariana; Carneiro, Jorge; Bettencourt-Dias, Mónica

2015-10-26

Centrioles are essential for cilia and centrosome assembly. In centriole-containing cells, centrioles always form juxtaposed to pre-existing ones, motivating a century-old debate on centriole biogenesis control. Here, we show that trans-autoactivation of Polo-like kinase 4 (PLK4), the trigger of centriole biogenesis, is a critical event in the spatial control of that process. We demonstrate that centrioles promote PLK4 activation through its recruitment and local accumulation. Though centriole removal reduces the proportion of active PLK4, this is rescued by concentrating PLK4 to the peroxisome lumen. Moreover, while mild overexpression of PLK4 only triggers centriole amplification at the existing centriole, higher PLK4 levels trigger both centriolar and cytoplasmatic (de novo) biogenesis. Hence, centrioles promote their assembly locally and disfavor de novo synthesis. Similar mechanisms enforcing the local concentration and/or activity of other centriole components are likely to contribute to the spatial control of centriole biogenesis under physiological conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Safeguards on nuclear waste

International Nuclear Information System (INIS)

Crawford, D.W.

1995-01-01

Safeguards and security policies within the Department of Energy (DOE) have been implemented in a graded fashion for the protection, control and accountability of nuclear materials. This graded philosophy has meant that safeguards on low-equity nuclear materials, typically considered of low diversion attractiveness such as waste, has been relegated to minimal controls. This philosophy has been and remains today an acceptable approach for the planning and implementation of safeguards on this material. Nuclear waste protection policy and guidance have been issued due to a lack of clear policy and guidance on the identification and implementation of safeguards controls on waste. However, there are issues related to safe-guarding waste that need to be clarified. These issues primarily stem from increased budgetary and resource pressures to remove materials from safeguards. Finally, there may be an unclear understanding, as to the scope and content of vulnerability assessments required prior to terminating safeguards on waste and other discardable materials and where the authority should lie within the Department for making decisions regarding safeguards termination. This paper examines these issues and the technical basis for Departmental policy for terminating safeguards on waste

Safeguarding the atom

International Nuclear Information System (INIS)

Fischer, D.; Szasz, P.

1985-01-01

Safeguards play a key role in verifying the effectiveness of restraints on the spread of nuclear weapons. This book is a study of the safeguards system of the International Atomic Energy Agency, an important element of the non-proliferation regime. It focuses on the politics of safeguards, especially the political problems of the IAEA and of the day-to-day application of safeguards. It contains a critical appraisal and proposals for ways of improving existing procedures and of adapting them to the political and technological changes of recent years. IAEA safeguards represent the world's first and so far only attempt to verify an arms control agreement by systematic on-site inspection, and their applicability to other arms control measures is examined. (author)

Inventory of safeguards software

International Nuclear Information System (INIS)

Suzuki, Mitsutoshi; Horino, Koichi

2009-03-01

The purpose of this survey activity will serve as a basis for determining what needs may exist in this arena for development of next-generation safeguards systems and approaches. 23 software tools are surveyed by JAEA and NMCC. Exchanging information regarding existing software tools for safeguards and discussing about a next R and D program of developing a general-purpose safeguards tool should be beneficial to a safeguards system design and indispensable to evaluate a safeguards system for future nuclear fuel facilities. (author)

The safeguards options study

Energy Technology Data Exchange (ETDEWEB)

Hakkila, E.A.; Mullen, M.F.; Olinger, C.T.; Stanbro, W.D. [Los Alamos National Lab., NM (United States); Olsen, A.P.; Roche, C.T.; Rudolph, R.R. [Argonne National Lab., IL (United States); Bieber, A.M.; Lemley, J. [Brookhaven National Lab., Upton, NY (United States); Filby, E. [Idaho National Engineering Lab., Idaho Falls, ID (United States)] [and others

1995-04-01

The Safeguards Options Study was initiated to aid the International Safeguards Division (ISD) of the DOE Office of Arms Control and Nonproliferation in developing its programs in enhanced international safeguards. The goal was to provide a technical basis for the ISD program in this area. The Safeguards Options Study has been a cooperative effort among ten organizations. These are Argonne National Laboratory, Brookhaven National Laboratory, Idaho National Engineering Laboratory, Lawrence Livermore National Laboratory, Los Alamos National Laboratory, Mound Laboratory, Oak Ridge National Laboratory, Pacific Northwest Laboratories, Sandia National Laboratories, and Special Technologies Laboratory. Much of the Motivation for the Safeguards Options Study is the recognition after the Iraq experience that there are deficiencies in the present approach to international safeguards. While under International Atomic Energy Agency (IAEA) safeguards at their declared facilities, Iraq was able to develop a significant weapons program without being noticed. This is because negotiated safeguards only applied at declared sites. Even so, their nuclear weapons program clearly conflicted with Iraq`s obligations under the Nuclear Nonproliferation Treaty (NPT) as a nonnuclear weapon state.

The safeguards options study

International Nuclear Information System (INIS)

Hakkila, E.A.; Mullen, M.F.; Olinger, C.T.; Stanbro, W.D.; Olsen, A.P.; Roche, C.T.; Rudolph, R.R.; Bieber, A.M.; Lemley, J.; Filby, E.

1995-04-01

The Safeguards Options Study was initiated to aid the International Safeguards Division (ISD) of the DOE Office of Arms Control and Nonproliferation in developing its programs in enhanced international safeguards. The goal was to provide a technical basis for the ISD program in this area. The Safeguards Options Study has been a cooperative effort among ten organizations. These are Argonne National Laboratory, Brookhaven National Laboratory, Idaho National Engineering Laboratory, Lawrence Livermore National Laboratory, Los Alamos National Laboratory, Mound Laboratory, Oak Ridge National Laboratory, Pacific Northwest Laboratories, Sandia National Laboratories, and Special Technologies Laboratory. Much of the Motivation for the Safeguards Options Study is the recognition after the Iraq experience that there are deficiencies in the present approach to international safeguards. While under International Atomic Energy Agency (IAEA) safeguards at their declared facilities, Iraq was able to develop a significant weapons program without being noticed. This is because negotiated safeguards only applied at declared sites. Even so, their nuclear weapons program clearly conflicted with Iraq's obligations under the Nuclear Nonproliferation Treaty (NPT) as a nonnuclear weapon state

Safeguards and nuclear forensics

International Nuclear Information System (INIS)

Gangotra, Suresh

2016-01-01

Nuclear Safeguards is the detection of diversion of significant quantities of nuclear material from peaceful nuclear activities to the manufacture of nuclear weapons, or of other nuclear explosive devices or for purposes unknown, and deterrence of such diversion by early detection. Safeguards implementation involves nuclear material accounting and containment and surveillance measures. The safeguards are implemented in nuclear facilities by the states, or agencies and International Atomic Energy Agency (IAEA). The measures for the safeguards include nuclear material Accounting (NUMAC) and Containment and surveillance systems. In recent times, there have been advances in safeguards like Near Real Time Monitoring (NRTM), Dynamic Nuclear Material Accounting (DNMA), Safeguards-by-Design (SBD), satellite imagery, information from open sources, remote monitoring etc

IAEA safeguards for geological repositories

International Nuclear Information System (INIS)

Moran, B.W.

2005-01-01

In September. 1988, the IAEA held its first formal meeting on the safeguards requirements for the final disposal of spent fuel and nuclear material-bearing waste. The consensus recommendation of the 43 participants from 18 countries at this Advisory Group Meeting was that safeguards should not terminate of spent fuel even after emplacement in, and closure of, a geologic repository.' As a result of this recommendation, the IAEA initiated a series of consultants' meetings and the SAGOR Programme (Programme for the Development of Safeguards for the Final Disposal of Spent Fuel in Geologic Repositories) to develop an approach that would permit IAEA safeguards to verify the non-diversion of spent fuel from a geologic repository. At the end of this process, in December 1997, a second Advisory Group Meeting, endorsed the generic safeguards approach developed by the SAGOR Programme. Using the SAGOR Programme results and consultants' meeting recommendations, the IAEA Department of Safeguards issued a safeguards policy paper stating the requirements for IAEA safeguards at geologic repositories. Following approval of the safeguards policy and the generic safeguards approach, the Geologic Repository Safeguards Experts Group was established to make recommendations on implementing the safeguards approach. This experts' group is currently making recommendations to the IAEA regarding the safeguards activities to be conducted with respect to Finland's repository programme. (author)

Evolution of safeguards systems design

International Nuclear Information System (INIS)

Shipley, J.P.; Christensen, E.L.; Dietz, R.J.

1979-01-01

Safeguards systems play a vital detection and deterrence role in current nonproliferation policy. These safeguards systems have developed over the past three decades through the evolution of three essential components: the safeguards/process interface, safeguards performance criteria, and the technology necessary to support effective safeguards. This paper discusses the background and history of this evolutionary process, its major developments and status, and the future direction of safeguards system design

Measuring Safeguards Culture

International Nuclear Information System (INIS)

Frazar, Sarah L.; Mladineo, Stephen V.

2011-01-01

As the International Atomic Energy Agency (IAEA) implements a State Level Approach to its safeguards verification responsibilities, a number of countries are beginning new nuclear power programs and building new nuclear fuel cycle faculties. The State Level approach is holistic and investigatory in nature, creating a need for transparent, non-discriminatory judgments about a state's nonproliferation posture. In support of this need, the authors previously explored the value of defining and measuring a state's safeguards culture. We argued that a clear definition of safeguards culture and an accompanying set of metrics could be applied to provide an objective evaluation and demonstration of a country's nonproliferation posture. As part of this research, we outlined four high-level metrics that could be used to evaluate a state's nuclear posture. We identified general data points. This paper elaborates on those metrics, further refining the data points to generate a measurable scale of safeguards cultures. We believe that this work could advance the IAEA's goals of implementing a safeguards system that is fully information driven, while strengthening confidence in its safeguards conclusions.

International safeguards

International Nuclear Information System (INIS)

Sanders, B.; Ha Vinh Phuong

1976-01-01

Since the start of the post-war era, international safeguards were considered essential to ensure that nuclear materials should not be diverted to unauthorised uses. In parallel, it was proposed to set up an international atomic energy agency within the United Nations through which international cooperation in nuclear matters would be channelled and controlled. Created in 1957, the IAEA was authorized to administer safeguards in connection with any assistance it provided as well as at the request of Member State and of any party to bilateral or multilateral arrangements in its ambit. Today, there are two international treaties requiring that its parties should accept Agency safeguards unilaterally, the Latin America Tlatelolco Treaty of 1967, and the Treaty on the Non-Proliferation of Nuclear Weapons (NPT), operative since 1970, which requires in particular that non-nuclear weapon states should accept Agency safeguards on its peaceful nuclear activities. Thus while NPT covers peaceful nuclear activities indiscriminately in a country, the Agency's original safeguards system is applied according to specific agreements and to given facilities. A basic conflict has now emerged between commercial interests and the increasing wish that transfer of nuclear equipment and know-how should not result in proliferation of military nuclear capacity; however, serious efforts are currently in progress to ensure universal application of IAEA safeguards and to develop them in step with the uses of nuclear energy. (N.E.A.) [fr

Safeguards resource management

International Nuclear Information System (INIS)

Strait, R.S.

1986-01-01

Protecting nuclear materials is a challenging problem for facility managers. To counter the broad spectrum of potential threats, facility managers rely on diverse safeguards measures, including elements of physical protection, material control and accountability, and human reliability programs. Deciding how to upgrade safeguards systems involves difficult tradeoffs between increased protection and the costs and operational impact of protection measures. Effective allocation of safeguards and security resources requires a prioritization of systems upgrades based on a relative measure of upgrade benefits to upgrade costs. Analytical tools are needed to help safeguards managers measure the relative benefits and cost and allocate their limited resources to achieve balanced, cost-effective protection against the full spectrum of threats. This paper presents a conceptual approach and quantitative model that have been developed by Lawrence Livermore National Laboratory to aid safeguards managers

The evolution of IAEA safeguards

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-11-01

This, second in a new series of booklets dealing with IAEA safeguards is intended for persons professionally interested in the subject as government officials responsible for non-proliferation or management of nuclear facilities, and practitioners of safeguards - the international and national officials charged with implementing IAEA safeguards. It is also aimed at the broader public concerned with the spread of nuclear weapons and interested in nuclear arms control and disarmament. It presents the situation as IAEA safeguards make `quantum jump` into new phase characterized by the IAEA as the `Strengthened Safeguards System`. It includes the historical overview of the International safeguards from 1945-1998; the aims and limitations of IAEA Safeguards; a chapter on how safeguards work in practice; as well as new challenges and opportunities

The evolution of IAEA safeguards

International Nuclear Information System (INIS)

1998-01-01

This, second in a new series of booklets dealing with IAEA safeguards is intended for persons professionally interested in the subject as government officials responsible for non-proliferation or management of nuclear facilities, and practitioners of safeguards - the international and national officials charged with implementing IAEA safeguards. It is also aimed at the broader public concerned with the spread of nuclear weapons and interested in nuclear arms control and disarmament. It presents the situation as IAEA safeguards make 'quantum jump' into new phase characterized by the IAEA as the 'Strengthened Safeguards System'. It includes the historical overview of the International safeguards from 1945-1998; the aims and limitations of IAEA Safeguards; a chapter on how safeguards work in practice; as well as new challenges and opportunities

IAEA Safeguards: Status and prospects

International Nuclear Information System (INIS)

Gruemm, H.

1983-01-01

The IAEA has just celebrated its 25th anniversary, and the first safeguards inspections were performed twenty years ago. Counting only since 1978, some 5100 inspections had been performed up to mid-1982, using a staff which now includes about 130 inspectors. Despite these impressive figures, and the fact that the IAEA has never detected any apparent diversion of nuclear materials, there are increasing public allegations that safeguards lack effectiveness. After briefly reviewing the nature of IAEA safeguards agreements, the paper examines the political and technical objectives of safeguards together with some of the criticisms which have been voiced. Allocation of limited safeguards resources is examined in terms of the sometimes conflicting allocation criteria which are contained in various safeguards documents. The paper argues that the credibility and deterrent effect of IAEA safeguards should not be underestimated. It should be of greater concern that a few States are known to be operating or constructing non-safeguarded nuclear facilities capable of producing weapons-grade nuclear materials. Thus the risk of safeguards would appear to be greatest at exactly the point where safeguards end. (author)

Role of AAA(+)-proteins in peroxisome biogenesis and function.

Science.gov (United States)

Grimm, Immanuel; Erdmann, Ralf; Girzalsky, Wolfgang

2016-05-01

Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.

Measuring Safeguards Culture

Energy Technology Data Exchange (ETDEWEB)

Frazar, Sarah L.; Mladineo, Stephen V.

2011-07-19

As the International Atomic Energy Agency (IAEA) implements a State Level Approach to its safeguards verification responsibilities, a number of countries are beginning new nuclear power programs and building new nuclear fuel cycle faculties. The State Level approach is holistic and investigatory in nature, creating a need for transparent, non-discriminatory judgments about a state's nonproliferation posture. In support of this need, the authors previously explored the value of defining and measuring a state's safeguards culture. We argued that a clear definition of safeguards culture and an accompanying set of metrics could be applied to provide an objective evaluation and demonstration of a country's nonproliferation posture. As part of this research, we outlined four high-level metrics that could be used to evaluate a state's nuclear posture. We identified general data points. This paper elaborates on those metrics, further refining the data points to generate a measurable scale of safeguards cultures. We believe that this work could advance the IAEA's goals of implementing a safeguards system that is fully information driven, while strengthening confidence in its safeguards conclusions.

Perturbation of Ribosome Biogenesis Drives Cells into Senescence through 5S RNP-Mediated p53 Activation

Directory of Open Access Journals (Sweden)

Kazuho Nishimura

2015-03-01

Full Text Available The 5S ribonucleoprotein particle (RNP complex, consisting of RPL11, RPL5, and 5S rRNA, is implicated in p53 regulation under ribotoxic stress. Here, we show that the 5S RNP contributes to p53 activation and promotes cellular senescence in response to oncogenic or replicative stress. Oncogenic stress accelerates rRNA transcription and replicative stress delays rRNA processing, resulting in RPL11 and RPL5 accumulation in the ribosome-free fraction, where they bind MDM2. Experimental upregulation of rRNA transcription or downregulation of rRNA processing, mimicking the nucleolus under oncogenic or replicative stress, respectively, also induces RPL11-mediated p53 activation and cellular senescence. We demonstrate that exogenous expression of certain rRNA-processing factors rescues the processing defect, attenuates p53 accumulation, and increases replicative lifespan. To summarize, the nucleolar-5S RNP-p53 pathway functions as a senescence inducer in response to oncogenic and replicative stresses.

Safeguards document (INFCIRC/153) and the new safeguards system

International Nuclear Information System (INIS)

Haginoya, Tohru

1997-01-01

INFCIRC/153. The NPT covers nuclear weapons and nuclear explosive devices but not other military uses of nuclear materials. The NPT safeguards applies all nuclear materials including undeclared nuclear materials. The protection of commercially sensitive information is important. The new safeguards system. The Model protocol amends INFCIRC/153 (the Protocol prevails). Apply nuclear fuel cycle related activities with no nuclear material. The environmental monitoring is an important measure, but non-weapon countries have no such technology. Impact and benefit from the new system. Simplification of the conventional safeguards. Could possibly define three categories of plutonium. (author)

Los Alamos safeguards program overview and NDA in safeguards

International Nuclear Information System (INIS)

Keepin, G.R.

1988-01-01

Over the years the Los Alamos safeguards program has developed, tested, and implemented a broad range of passive and active nondestructive analysis (NDA) instruments (based on gamma and x-ray detection and neutron counting) that are now widely employed in safeguarding nuclear materials of all forms. Here very briefly, the major categories of gamma ray and neutron based NDA techniques, give some representative examples of NDA instruments currently in use, and cite a few notable instances of state-of-the-art NDA technique development. Historical aspects and a broad overview of the safeguards program are also presented

Nuclear safeguards policy

International Nuclear Information System (INIS)

Anon.

1982-01-01

Claims have been made that Australia's nuclear safeguards policy, announced in 1977, has changed. However, examination of the texts of nuclear safeguards agreements negotiated by Australia shows that the policy has been implemented and adhered to. The purpose of these agreements is to obtain assurance that uranium exported is used exclusively for peaceful purposes. The questions of reprocessing, transfer to third countries and the application of IAEA safeguards are discussed

New safeguards system and JNC's activities in the new safeguards system

International Nuclear Information System (INIS)

Iwanaga, Masayuki

2000-01-01

The Japan Nuclear Fuel Cycle Development Institute (JNC) has been developing the various area of the technology in the nuclear fuel cycle more than 30 years, as the leading organization. Standing on the accumulated experiences through those activities, JNC will construct the new fuel cycle concept based on the principle for safety, environment, economy and nonproliferation. In this process, evaluation of the specific nonproliferation features with the nuclear material control methods taking in to account of the safegurdability might have one of the major importance. On the other hand, recently, in addition to the conventional safeguards (INFCIRC153), an additional protocol (INFCIRC540) which defines the activities that complement the integrity of a member country's declaration has come into effect in several countries, including Japan. IAEA and other international organizations are now discussing the safeguards concept, which integrates the conventional as well as new safeguards measures. In JNC's efforts to construct the new fuel cycle concept, it is necessary to give sufficient consideration to reflect the integrated safeguards concept. In the process of implementing the concept of the new integrated safeguards system, we presume that changes will have to be made in the traditional approach, which mainly deals with nuclear material. It will become necessary to develop a concrete method and approach in order to analyze and evaluate information, and work will have to be undertaken to optimize such a method based on its effects and efficiency. JNC will make contributions to international society by making the best use of its experience and technological infrastructure to reflect further safeguards development program in JNC so that the new IAEA safeguards can be firmly established. Related to this point of view, the following two subjects is to be introduced on the whole; 1. JNC's experiences and expertise of the development of safeguards technology with the fuel

Nuclear safeguards in challenging times [Experts on nuclear safeguards and verification assess the global picture

International Nuclear Information System (INIS)

Park, W.S.; Hillerman, J.

2007-01-01

Meeting at the IAEA's International Safeguards Symposium in October 2006, more than 500 experts from 60-plus countries and organizations addressed current and future challenges related to safeguards concepts, approaches, technologies, and experience. Sessions addressed five main issues driving developments: Current challenges to the safeguards system; Further strengthening safeguards practices and approaches; Improving the collection and analysis of safeguards information; Advances in safeguards techniques and technology; and Future challenges. Every four to five years, the IAEA brings together safeguards experts from all over the world at international symposia. In October 2001, they met in the shadow of 9/11 and the symposium included a special session on the prevention of nuclear terrorism

Safeguards systems analysis research and development and the practice of safeguards at DOE facilities

International Nuclear Information System (INIS)

Zack, N.R.; Thomas, K.E.; Markin, J.T.; Tape, J.W.

1991-01-01

Los Alamos Safeguards Systems Group personnel interact with Department of Energy (DOE) nuclear materials processing facilities in a number of ways. Among them are training courses, formal technical assistance such as developing information management or data analysis software, and informal ad hoc assistance especially in reviewing and commenting on existing facility safeguards technology and procedures. These activities are supported by the DOE Office of Safeguards and Security, DOE Operations Offices, and contractor organizations. Because of the relationships with the Operations Office and facility personnel, the Safeguards Systems Group research and development (R and D) staff have developed an understanding of the needs of the entire complex. Improved safeguards are needed in areas such as materials control activities, accountability procedures and techniques, systems analysis and evaluation methods, and material handling procedures. This paper surveys the generic needs for efficient and cost effective enhancements in safeguards technologies and procedures at DOE facilities, identifies areas where existing safeguards R and D products are being applied or could be applied, and sets a direction for future systems analysis R and D to address practical facility safeguards needs

Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.

Directory of Open Access Journals (Sweden)

Joseph C Sanchez

2017-10-01

Full Text Available A form of dwarfism known as Meier-Gorlin syndrome (MGS is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5. These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45. The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C. We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways-DNA replication and ribosome biogenesis.

Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.

Science.gov (United States)

Sanchez, Joseph C; Kwan, Elizabeth X; Pohl, Thomas J; Amemiya, Haley M; Raghuraman, M K; Brewer, Bonita J

2017-10-01

A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5). These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45). The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C). We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA) locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways-DNA replication and ribosome biogenesis.

5S rRNA and ribosome.

Science.gov (United States)

Gongadze, G M

2011-12-01

5S rRNA is an integral component of the ribosome of all living organisms. It is known that the ribosome without 5S rRNA is functionally inactive. However, the question about the specific role of this RNA in functioning of the translation apparatus is still open. This review presents a brief history of the discovery of 5S rRNA and studies of its origin and localization in the ribosome. The previously expressed hypotheses about the role of this RNA in the functioning of the ribosome are discussed considering the unique location of 5S rRNA in the ribosome and its intermolecular contacts. Based on analysis of the current data on ribosome structure and its functional complexes, the role of 5S rRNA as an intermediary between ribosome functional domains is discussed.

In vitro degradation of ribosomes.

Science.gov (United States)

Mora, G; Rivas, A

1976-12-01

The cytoplasmic ribosomes from Euglena gracilis var. bacillaris are found to be of two types taking into consideration their stability "in vitro". In the group of unstable ribosomes the large subunit is degraded. The other group apparently does not suffer any degradation under the conditions described. However the RNAs extracted from both types of ribosomes are degraded during sucrose density gradients. The degradation of the largest RNA species has been reported previously, but no comment has been made about the stability of the ribosome itself.

IAEA safeguards assessments

International Nuclear Information System (INIS)

Gruemm, H.; Parisick, R.; Pushkarjov, V.; Shea, T.; Brach, E.

1981-01-01

This paper describes the safeguards program administered by the IAEA, which must provide assurance to the international community that agency safeguards have the capacity to deter diversion, if contemplated, to detect diversion, if undertaken, and to provide assurance that no diversions have occurred when none are detected. This assurance to the international community is based upon the capability of the Agency's safeguards program to detect diversion and its complementary effect of deterrance

Safeguards as an evolutionary system

International Nuclear Information System (INIS)

Carlson, J.

1998-01-01

NPT safeguards pursuant to INFCIRC/153 retain a strong emphasis on materials accountancy, and are primarily concerned with verifying nuclear activities as declared by the State - the correctness of States' declarations. This decade, failure to adequately address the possibility of undeclared nuclear activities - the issue of the completeness of States' declarations - has been recognized as a major shortcoming in the safeguards system. Since the 'classical' safeguards system is unable to provide credible assurance of the absence of clandestine nuclear activities, substantial efforts are being made to strengthen the IAEA's capabilities in this regard. Agreement has been reached on a Model Protocol substantially extending the Agency's authority, and good progress has been made in developing the new approaches, technologies and techniques required to ensure this authority is used effectively. Increasingly, safeguards will involve more qualitative judgements. Transparency will be very important - without a clear understanding by Member States of how the Agency goes about its new tasks and reaches its conclusions about the absence of undeclared activities, the safeguards system will not fulfil its vital confidence-building role. A major theme in current safeguards thinking is integration, the rationalization of classical safeguards with the new safeguards strengthening measures. As part of the rationalization process, it is timely to re-assess traditional safeguards implementation practices. One of these is uniformity in the way safeguards activities are implemented in different States. Another is whether the traditional concept of safeguards confidentiality is consistent with the increasing importance of transparency. (author)

Genetic interactions of MAF1 identify a role for Med20 in transcriptional repression of ribosomal protein genes.

Directory of Open Access Journals (Sweden)

Ian M Willis

2008-07-01

Full Text Available Transcriptional repression of ribosomal components and tRNAs is coordinately regulated in response to a wide variety of environmental stresses. Part of this response involves the convergence of different nutritional and stress signaling pathways on Maf1, a protein that is essential for repressing transcription by RNA polymerase (pol III in Saccharomyces cerevisiae. Here we identify the functions buffering yeast cells that are unable to down-regulate transcription by RNA pol III. MAF1 genetic interactions identified in screens of non-essential gene-deletions and conditionally expressed essential genes reveal a highly interconnected network of 64 genes involved in ribosome biogenesis, RNA pol II transcription, tRNA modification, ubiquitin-dependent proteolysis and other processes. A survey of non-essential MAF1 synthetic sick/lethal (SSL genes identified six gene-deletions that are defective in transcriptional repression of ribosomal protein (RP genes following rapamycin treatment. This subset of MAF1 SSL genes included MED20 which encodes a head module subunit of the RNA pol II Mediator complex. Genetic interactions between MAF1 and subunits in each structural module of Mediator were investigated to examine the functional relationship between these transcriptional regulators. Gene expression profiling identified a prominent and highly selective role for Med20 in the repression of RP gene transcription under multiple conditions. In addition, attenuated repression of RP genes by rapamycin was observed in a strain deleted for the Mediator tail module subunit Med16. The data suggest that Mediator and Maf1 function in parallel pathways to negatively regulate RP mRNA and tRNA synthesis.

The potential use of domestic safeguards interior monitors in International Safeguards

International Nuclear Information System (INIS)

Williams, J.D.; Dupree, S.A.; Sonnier, C.S.

1998-01-01

An important future element of International Safeguards instrumentation is expected to be the merging of containment/surveillance and nondestructive assay equipment with domestic physical protection equipment into integrated systems, coupled with remote monitoring. Instrumentation would include interior monitoring and assessment and entry/exit monitoring. Of particular importance is the application of interior monitors in spaces of declared inactivity; for example, in nuclear material storage locations that are entered infrequently. The use of modern interior monitors in International Safeguards offers potential for improving effectiveness and efficiency. Within the context of increased cooperation, one can readily envision increased interaction between International Safeguards and Domestic Safeguards, including increased joint use of State System of Accounting and Control data

Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer

Energy Technology Data Exchange (ETDEWEB)

Yu, Min [Galactophore Department, JingZhou Central Hospital, JingZhou (China); Li, Ruishu, E-mail: liruishu2016@yahoo.com [Forensic Surgery Department, JingZhou Traditional Chinese Medicine Hospital, JingZhou (China); Zhang, Juan [Endocrinology Department, JingZhou Central Hospital, JingZhou (China)

2016-03-18

Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.

Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer

International Nuclear Information System (INIS)

Yu, Min; Li, Ruishu; Zhang, Juan

2016-01-01

Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.

Beyond Human Capital Development: Balanced Safeguards Workforce Metrics and the Next Generation Safeguards Workforce

International Nuclear Information System (INIS)

2014-01-01

Since its establishment in 2008, the Next Generation Safeguards Initiative (NGSI) has achieved a number of objectives under its five pillars: concepts and approaches, policy development and outreach, international nuclear safeguards engagement, technology development, and human capital development (HCD). As a result of these efforts, safeguards has become much more visible as a critical U.S. national security interest across the U.S. Department of Energy (DOE) complex. However, limited budgets have since created challenges in a number of areas. Arguably, one of the more serious challenges involves NGSI's ability to integrate entry-level staff into safeguards projects. Laissez fair management of this issue across the complex can lead to wasteful project implementation and endanger NGSI's long-term sustainability. The authors provide a quantitative analysis of this problem, focusing on the demographics of the current safeguards workforce and compounding pressures to operate cost-effectively, transfer knowledge to the next generation of safeguards professionals, and sustain NGSI safeguards investments.

Ribosomal studies on the 70S ribosome of E.coli by means of neutron scattering

International Nuclear Information System (INIS)

Burkhardt, N.

1997-01-01

Ribosomes are ribonucleo-protein complexes, which catalyse proteinbiosynthesis in all living organisms. Currently, most of the structural models of the prokaryotic 70S ribosome rely on electron microscopy and describe mainly the outer shape of the particle. Neutron scattering can provide information on the internal structure of the ribosome. Parts of the structure can be contrasted for neutrons by means of an isotopic exchange of the naturally occurring hydrogen ( 1 H) for deuterium ( 2 H), allowing direct measurements in situ. Specifically deuterium-labeled ribosomes (E. coli) were prepared and analysed with neutron scattering. The biochemical methods were established and combined to a generally applicable preparation system. This allows labeling of all ribosomal components in any combination. A systematic analysis of the protein and RNA phases resulted in the development of a new model for the 70S ribosome. This model describes not only the outer shape of the particle, but displays also an experimentally determined internal protein-RNA distribution and the border of subunits for the first time (four-phase model; resolution: 50A). Models of the 70S ribosome from other studies were evaluated and ranked according to consistency with the measured scattering data. Applying a new neutron scattering technique of particular sensitivity, the proton-spin contrast-variation, single proteins could be measured and localized. The positions of the proteins S6 and S10 were determined, providing the first coordinates of protein mass centers within the 70S ribosome. (orig.) [de

U.S. safeguards history and the evolution of safeguards research and development

International Nuclear Information System (INIS)

Brenner, L.M.; McDowell, S.C.T.

1989-01-01

In discussing the U.S. safeguards history and the evolution of safeguards research and development, five significant eras are identified. The period ending January 1, 1947, may be called the first era. Safeguards as known today did not exist and the classic military approach of security protection applied. The second era covers the period from 1947 to 1954 (when the Atomic Energy Act was completely rewritten to accommodate the then foreseen Civil uses Program and international cooperation in peaceful uses of nuclear energy), and the first steps were taken by the Atomic Energy Commission to establish material accounting records for all source and fissionable materials on inventory. The third era covers the period 1954 through 1968, which focused on nuclear safeguards in its domestic activities and made major policy changes in its approach to material control and accountability. The fourth era, 1968 to 1972 saw a quantum jump in the recognition and need for a significant safeguards research and development program, answered by the formation of a safeguards technical support organization at Brookhaven National Laboratory and a safeguards Laboratory at Los Alamos Scientific Laboratory for the development and application of non-destructive assay technology. The fifth era had its beginning in 1972 with the burgeoning of international terrorism. The corresponding need for a strong physical protection research and development support program was responded to by the Sandia National Laboratory

Recent advances in safeguards operations

International Nuclear Information System (INIS)

Agu, B.; Iwamoto, H.

1983-01-01

The facilities and nuclear materials under IAEA safeguards have steadily increased in the past few years with consequent increases in the manpower and effort required for the implementation of effective international safeguards. To meet this challenge, various techniques and instruments have been developed with the assistance, support and cooperation of the Member States. Improved NDA equipment now permits accurate verification of plutonium and HEU bearing items; and optical and TV surveillance systems have improved remarkably. Experience in safeguarding nuclear facilities now includes fast-reactor fuel reprocessing and enrichment plants, even though the Hexapartite Safeguards Project is yet to define an agreed approach for safeguarding enrichment plants. The establishment of field offices now enables the IAEA to adequately implement safeguards at important facilities and also with more effective use of manpower. Closer cooperation with Member States via liaison or similar committees makes for effective safeguards implementation and the speedy solution of attendant problems. The technical support programmes from the Member States continue to provide the basis of the recent advances in safeguards techniques and instrumentation. (author)

Detection and Quantification of Ribosome Inhibition by Aminoglycoside Antibiotics in Living Bacteria Using an Orthogonal Ribosome-Controlled Fluorescent Reporter.

Science.gov (United States)

Huang, Shijie; Zhu, Xuechen; Melançon, Charles E

2016-01-15

The ribosome is the quintessential antibacterial drug target, with many structurally and mechanistically distinct classes of antibacterial agents acting by inhibiting ribosome function. Detecting and quantifying ribosome inhibition by small molecules and investigating their binding modes and mechanisms of action are critical to antibacterial drug discovery and development efforts. To develop a ribosome inhibition assay that is operationally simple, yet provides direct information on the drug target and the mechanism of action, we have developed engineered E. coli strains harboring an orthogonal ribosome-controlled green fluorescent protein (GFP) reporter that produce fluorescent signal when the orthogonal ribosome is inhibited. As a proof of concept, we demonstrate that these strains, when coexpressing homogeneous populations of aminoglycoside resistant ribosomes, act as sensitive and quantitative detectors of ribosome inhibition by a set of 12 structurally diverse aminoglycoside antibiotics. We suggest that this strategy can be extended to quantifying ribosome inhibition by other drug classes.

The Canadian safeguards program

International Nuclear Information System (INIS)

Zarecki, C.W.; Smith, R.M.

1981-12-01

In support of the Treaty on the Non-Proliferation of Nuclear Weapons Canada provides technical support to the International Atomic Energy Agency for the development of safeguards relevant to Canadian designed and built nuclear facilities. Some details of this program are discussed, including the philosophy and development of CANDU safeguards systems; the unique equipment developed for these systems; the provision of technical experts; training programs; liaison with other technical organizations; research and development; implementation of safeguards systems at various nuclear facilities; and the anticipated future direction of the safeguards program

IAEA safeguards glossary

International Nuclear Information System (INIS)

1980-01-01

An unambiguous definition and rationalization of many of the terms for the purpose of IAEA safeguards are given, with a view to improving the common understanding of such terms within the international community. The glossary focuses only on safeguards meanings in general, and IAEA meanings in particular, of the terms discussed. Terms belong to the following problems: nuclear and non-nuclear material, nuclear equipment, design of the safeguards approach, nuclear material accountancy, physical standards, sampling, measurements, statistical concepts and others

Implementation of the CNEN's safeguards laboratory

International Nuclear Information System (INIS)

Almeida, S.G. de

1986-01-01

The International Safeguards Agreements between Brazil and others countries has been concluded with the participation of the International Atomic Energy Agency (AIEA), and involve the Physical Protection and Control of Nuclear Material activities, which set up the National Safeguards System. The Safeguards Laboratory was constructed to the implementation and maintenance of this National Safeguards System, under responsability of CNEN's Safeguards Division, in order to carry out measurements of nuclear materials under safeguards. Technical requirements applied to the construction, setting up and operation of the laboratory are showed. The first results refer to the implementation of safeguards methods and techniques, as well as its participation within international scientific and technical co-operation programs in the safeguards area, through of them we wait its credencement by the AIEA as Regional Safeguards Laboratory for every countries of the Latin America. (Author) [pt

IAEA safeguards glossary. 2001 ed

International Nuclear Information System (INIS)

2002-01-01

IAEA safeguards have evolved since their inception in the late 1960s. In 1980 the IAEA published the first IAEA Safeguards Glossary (IAEA/SG/INF/l) with the aim of facilitating understanding of the specialized safeguards terminology within the international community. In 1987 the IAEA published a revised edition of the Glossary (IAEA/SG/INF/l (Rev.l)) which took into account developments in the safeguards area as well as comments received since the first edition appeared. Since 1987, IAEA safeguards have become more effective and efficient, mainly through the series of strengthening measures approved by the IAEA Board of Governors during 1992-1997, the Board's approval, in 1997, of the Model Protocol Additional to the Agreement(s) between State(s) and the International Atomic Energy Agency for the Application of Safeguards (issued as INFCIRC/540 (Corrected)), and the work, begun in 1999, directed towards the development and implementation of integrated safeguards. The IAEA Safeguards Glossary 2001 Edition reflects these developments. Each of the 13 sections of the Glossary addresses a specific subject related to IAEA safeguards. To facilitate understanding. definitions and, where applicable, explanations have been given for each of the terms listed. The terms defined and explained intentionally have not been arranged in alphabetical order, but their sequence within each section corresponds to the internal relationships of the subject treated. The terms are numbered consecutively within each section and an index referring to these numbers has been provided for ease of reference. The terms used have been translated into the official languages of the IAEA, as well as into German and Japanese. The IAEA Safeguards Glossary 2001 Edition has no legal status and is not intended to serve as a basis for adjudicating on problems of definition such as might arise during the negotiation or in the interpretation of safeguards agreements or additional protocols. The IAEA

IAEA safeguards glossary. 2001 ed

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-06-01

IAEA safeguards have evolved since their inception in the late 1960s. In 1980 the IAEA published the first IAEA Safeguards Glossary (IAEA/SG/INF/l) with the aim of facilitating understanding of the specialized safeguards terminology within the international community. In 1987 the IAEA published a revised edition of the Glossary (IAEA/SG/INF/l (Rev.l)) which took into account developments in the safeguards area as well as comments received since the first edition appeared. Since 1987, IAEA safeguards have become more effective and efficient, mainly through the series of strengthening measures approved by the IAEA Board of Governors during 1992-1997, the Board's approval, in 1997, of the Model Protocol Additional to the Agreement(s) between State(s) and the International Atomic Energy Agency for the Application of Safeguards (issued as INFCIRC/540 (Corrected)), and the work, begun in 1999, directed towards the development and implementation of integrated safeguards. The IAEA Safeguards Glossary 2001 Edition reflects these developments. Each of the 13 sections of the Glossary addresses a specific subject related to IAEA safeguards. To facilitate understanding. definitions and, where applicable, explanations have been given for each of the terms listed. The terms defined and explained intentionally have not been arranged in alphabetical order, but their sequence within each section corresponds to the internal relationships of the subject treated. The terms are numbered consecutively within each section and an index referring to these numbers has been provided for ease of reference. The terms used have been translated into the official languages of the IAEA, as well as into German and Japanese. The IAEA Safeguards Glossary 2001 Edition has no legal status and is not intended to serve as a basis for adjudicating on problems of definition such as might arise during the negotiation or in the interpretation of safeguards agreements or additional protocols. The IAEA

IAEA safeguards glossary. 2001 ed

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-06-01

IAEA safeguards have evolved since their inception in the late 1960s. In 1980 the IAEA published the first IAEA Safeguards Glossary (IAEA/SG/INF/l) with the aim of facilitating understanding of the specialized safeguards terminology within the international community. In 1987 the IAEA published a revised edition of the Glossary (IAEA/SG/INF/l (Rev.l)) which took into account developments in the safeguards area as well as comments received since the first edition appeared. Since 1987, IAEA safeguards have become more effective and efficient, mainly through the series of strengthening measures approved by the IAEA Board of Governors during 1992-1997, the Board's approval, in 1997, of the Model Protocol Additional to the Agreement(s) between State(s) and the International Atomic Energy Agency for the Application of Safeguards (issued as INFCIRC/540 (Corrected)), and the work, begun in 1999, directed towards the development and implementation of integrated safeguards. The IAEA Safeguards Glossary 2001 Edition reflects these developments. Each of the 13 sections of the Glossary addresses a specific subject related to IAEA safeguards. To facilitate understanding. definitions and, where applicable, explanations have been given for each of the terms listed. The terms defined and explained intentionally have not been arranged in alphabetical order, but their sequence within each section corresponds to the internal relationships of the subject treated. The terms are numbered consecutively within each section and an index referring to these numbers has been provided for ease of reference. The terms used have been translated into the official languages of the IAEA, as well as into German and Japanese. The IAEA Safeguards Glossary 2001 Edition has no legal status and is not intended to serve as a basis for adjudicating on problems of definition such as might arise during the negotiation or in the interpretation of safeguards agreements or additional protocols. The IAEA

IAEA safeguards glossary. 2001 ed

International Nuclear Information System (INIS)

2002-01-01

IAEA safeguards have evolved since their inception in the late 1960s. In 1980 the IAEA published the first IAEA Safeguards Glossary (IAEA/SG/INF/l) with the aim of facilitating understanding of the specialized safeguards terminology within the international community. In 1987 the IAEA published a revised edition of the Glossary (IAEA/SG/INF/l (Rev.l)) which took into account developments in the safeguards area as well as comments received since the first edition appeared. Since 1987, IAEA safeguards have become more effective and efficient, mainly through the series of strengthening measures approved by the IAEA Board of Governors during 1992-1997, the Board's approval, in 1997, of the Model Protocol Additional to the Agreement(s) between State(s) and the International Atomic Energy Agency for the Application of Safeguards (issued as INFCIRC/540 (Corrected)), and the work, begun in 1999, directed towards the development and implementation of integrated safeguards. The IAEA Safeguards Glossary 2001 Edition reflects these developments. Each of the 13 sections of the Glossary addresses a specific subject related to IAEA safeguards. To facilitate understanding. definitions and, where applicable, explanations have been given for each of the terms listed. The terms defined and explained intentionally have not been arranged in alphabetical order, but their sequence within each section corresponds to the internal relationships of the subject treated. The terms are numbered consecutively within each section and an index referring to these numbers has been provided for ease of reference. The terms used have been translated into the official languages of the IAEA, as well as into German and Japanese. The IAEA Safeguards Glossary 2001 Edition has no legal status and is not intended to serve as a basis for adjudicating on problems of definition such as might arise during the negotiation or in the interpretation of safeguards agreements or additional protocols. The IAEA

The miRNA biogenesis in marine bivalves

Directory of Open Access Journals (Sweden)

Umberto Rosani

2016-03-01

Full Text Available Small non-coding RNAs include powerful regulators of gene expression, transposon mobility and virus activity. Among the various categories, mature microRNAs (miRNAs guide the translational repression and decay of several targeted mRNAs. The biogenesis of miRNAs depends on few gene products, essentially conserved from basal to higher metazoans, whose protein domains allow specific interactions with dsRNA. Here, we report the identification of key genes responsible of the miRNA biogenesis in 32 bivalves, with particular attention to the aquaculture species Mytilus galloprovincialis and Crassostrea gigas. In detail, we have identified and phylogenetically compared eight evolutionary conserved proteins: DROSHA, DGCR8, EXP5, RAN, DICER TARBP2, AGO and PIWI. In mussels, we recognized several other proteins participating in the miRNA biogenesis or in the subsequent RNA silencing. According to digital expression analysis, these genes display low and not inducible expression levels in adult mussels and oysters whereas they are considerably expressed during development. As miRNAs play an important role also in the antiviral responses, knowledge on their production and regulative effects can shed light on essential molecular processes and provide new hints for disease prevention in bivalves.

Nuclear safeguards technology handbook

International Nuclear Information System (INIS)

1977-12-01

The purpose of this handbook is to present to United States industrial organizations the Department of Energy's (DOE) Safeguards Technology Program. The roles and missions for safeguards in the U.S. government and application of the DOE technology program to industry safeguards planning are discussed. A guide to sources and products is included

The ribosome can prevent aggregation of partially folded protein intermediates: studies using the Escherichia coli ribosome.

Directory of Open Access Journals (Sweden)

Bani Kumar Pathak

Full Text Available BACKGROUND: Molecular chaperones that support de novo folding of proteins under non stress condition are classified as chaperone 'foldases' that are distinct from chaperone' holdases' that provide high affinity binding platform for unfolded proteins and prevent their aggregation specifically under stress conditions. Ribosome, the cellular protein synthesis machine can act as a foldase chaperone that can bind unfolded proteins and release them in folding competent state. The peptidyl transferase center (PTC located in the domain V of the 23S rRNA of Escherichia coli ribosome (bDV RNA is the chaperoning center of the ribosome. It has been proposed that via specific interactions between the RNA and refolding proteins, the chaperone provides information for the correct folding of unfolded polypeptide chains. RESULTS: We demonstrate using Escherichia coli ribosome and variants of its domain V RNA that the ribosome can bind to partially folded intermediates of bovine carbonic anhydrase II (BCAII and lysozyme and suppress aggregation during their refolding. Using mutants of domain V RNA we demonstrate that the time for which the chaperone retains the bound protein is an important factor in determining its ability to suppress aggregation and/or support reactivation of protein. CONCLUSION: The ribosome can behave like a 'holdase' chaperone and has the ability to bind and hold back partially folded intermediate states of proteins from participating in the aggregation process. Since the ribosome is an essential organelle that is present in large numbers in all living cells, this ability of the ribosome provides an energetically inexpensive way to suppress cellular aggregation. Further, this ability of the ribosome might also be crucial in the context that the ribosome is one of the first chaperones to be encountered by a large nascent polypeptide chains that have a tendency to form partially folded intermediates immediately following their synthesis.

Perturbation of ribosome biogenesis drives cells into senescence through 5S RNP-mediated p53 activation.

Science.gov (United States)

Nishimura, Kazuho; Kumazawa, Takuya; Kuroda, Takao; Katagiri, Naohiro; Tsuchiya, Mai; Goto, Natsuka; Furumai, Ryohei; Murayama, Akiko; Yanagisawa, Junn; Kimura, Keiji

2015-03-03

The 5S ribonucleoprotein particle (RNP) complex, consisting of RPL11, RPL5, and 5S rRNA, is implicated in p53 regulation under ribotoxic stress. Here, we show that the 5S RNP contributes to p53 activation and promotes cellular senescence in response to oncogenic or replicative stress. Oncogenic stress accelerates rRNA transcription and replicative stress delays rRNA processing, resulting in RPL11 and RPL5 accumulation in the ribosome-free fraction, where they bind MDM2. Experimental upregulation of rRNA transcription or downregulation of rRNA processing, mimicking the nucleolus under oncogenic or replicative stress, respectively, also induces RPL11-mediated p53 activation and cellular senescence. We demonstrate that exogenous expression of certain rRNA-processing factors rescues the processing defect, attenuates p53 accumulation, and increases replicative lifespan. To summarize, the nucleolar-5S RNP-p53 pathway functions as a senescence inducer in response to oncogenic and replicative stresses. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Nuclear safeguards technology handbook

Energy Technology Data Exchange (ETDEWEB)

1977-12-01

The purpose of this handbook is to present to United States industrial organizations the Department of Energy's (DOE) Safeguards Technology Program. The roles and missions for safeguards in the U.S. government and application of the DOE technology program to industry safeguards planning are discussed. A guide to sources and products is included. (LK)

Safeguards Culture: lesson learned

International Nuclear Information System (INIS)

Frazar, S.; Mladineo, S.V.

2010-01-01

After the discovery of Iraq's clandestine nuclear program in 1991, the international community developed new tools for evaluating and demonstrating states' nuclear intentions. The International Atomic Energy Agency (IAEA) developed a more holistic approach toward international safeguards verification to garner more complete information about states' nuclear activities. This approach manifested itself in State Level Evaluations, using information from a variety of sources, including the implementation of integrated safeguards in Member States, to reach a broader conclusion. Those wishing to exhibit strong nonproliferation postures to a more critical international community took steps to demonstrate their nonproliferation 'bona fides'. As these Member States signed and brought into force the Additional Protocol, submitted United Nations Security Council Resolution 1540 reports and strengthened their export control laws, the international community began to consider the emergence of so-called safeguards cultures. Today, safeguards culture can be a useful tool for measuring nonproliferation postures, but so far its impact on the international safeguards regime has been under appreciated. There is no agreed upon definition for safeguards culture nor agreement on how it should be measured.

Minotaur is critical for primary piRNA biogenesis.

Science.gov (United States)

Vagin, Vasily V; Yu, Yang; Jankowska, Anna; Luo, Yicheng; Wasik, Kaja A; Malone, Colin D; Harrison, Emily; Rosebrock, Adam; Wakimoto, Barbara T; Fagegaltier, Delphine; Muerdter, Felix; Hannon, Gregory J

2013-08-01

Piwi proteins and their associated small RNAs are essential for fertility in animals. In part, this is due to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to silence transposon targets and, as such, form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs is encoded within genomic loci, termed piRNA clusters. These give rise to long, single-stranded, primary transcripts that are processed into piRNAs. Despite the biological importance of this pathway, neither the characteristics that define a locus as a source of piRNAs nor the mechanisms that catalyze primary piRNA biogenesis are well understood. We searched an EMS-mutant collection annotated for fertility phenotypes for genes involved in the piRNA pathway. Twenty-seven homozygous sterile strains showed transposon-silencing defects. One of these, which strongly impacted primary piRNA biogenesis, harbored a causal mutation in CG5508, a member of the Drosophila glycerol-3-phosphate O-acetyltransferase (GPAT) family. These enzymes catalyze the first acylation step on the path to the production of phosphatidic acid (PA). Though this pointed strongly to a function for phospholipid signaling in the piRNA pathway, a mutant form of CG5508, which lacks the GPAT active site, still functions in piRNA biogenesis. We have named this new biogenesis factor Minotaur.

Minotaur is critical for primary piRNA biogenesis

Science.gov (United States)

Vagin, Vasily V.; Yu, Yang; Jankowska, Anna; Luo, Yicheng; Wasik, Kaja A.; Malone, Colin D.; Harrison, Emily; Rosebrock, Adam; Wakimoto, Barbara T.; Fagegaltier, Delphine; Muerdter, Felix; Hannon, Gregory J.

2013-01-01

Piwi proteins and their associated small RNAs are essential for fertility in animals. In part, this is due to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to silence transposon targets and, as such, form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs is encoded within genomic loci, termed piRNA clusters. These give rise to long, single-stranded, primary transcripts that are processed into piRNAs. Despite the biological importance of this pathway, neither the characteristics that define a locus as a source of piRNAs nor the mechanisms that catalyze primary piRNA biogenesis are well understood. We searched an EMS-mutant collection annotated for fertility phenotypes for genes involved in the piRNA pathway. Twenty-seven homozygous sterile strains showed transposon-silencing defects. One of these, which strongly impacted primary piRNA biogenesis, harbored a causal mutation in CG5508, a member of the Drosophila glycerol-3-phosphate O-acetyltransferase (GPAT) family. These enzymes catalyze the first acylation step on the path to the production of phosphatidic acid (PA). Though this pointed strongly to a function for phospholipid signaling in the piRNA pathway, a mutant form of CG5508, which lacks the GPAT active site, still functions in piRNA biogenesis. We have named this new biogenesis factor Minotaur. PMID:23788724

Safeguard sleuths

International Nuclear Information System (INIS)

Lowry, D.

1989-01-01

A report of the conference of the European Safeguards Research and Development Association, which tries to prevent the diversion of nuclear materials to military uses is given. Some of the problems encountered by safeguards inspectors are mentioned, such as being able to follow the material through the maze of piping in a reprocessing plant, the linguistic difficulties if the inspector does not speak the operator's language, the difference between precision and accuracy and the necessity of human inspection, containment and surveillance systems. Unexplained outages at a reprocessing plant are always treated as suspicious, as are power failures which prevent normal surveillance. The UK practice of allocating civil fuel temporarily to military use at Harwell also makes safeguard policing more difficult. (UK)

IAEA symposium on international safeguards

International Nuclear Information System (INIS)

1999-01-01

The eighth IAEA Symposium on International Safeguards was organized by the IAEA in cooperation with the Institute of Nuclear Materials Management and the European Safeguards Research and Development Association. It was attended by over 350 specialists and policy makers in the field of nuclear safeguards and verification from more than 50 countries and organizations. The purpose of the Symposium was to foster a broad exchange of information on concepts and technologies related to important developments in the areas of international safeguards and security. For the first time in the history of the symposia, the IAEA is issuing proceedings free of charge to participants on CD-ROM. The twenty-two plenary, technical, and poster sessions featured topics related to technological and policy aspects from national, regional and global perspectives. The theme of the Symposium: Four Decades of Development - Safeguarding into the New Millennium set the stage for the commemoration of a number of significant events in the annals of safeguards. 1997 marked the Fortieth Anniversary of the IAEA, the Thirtieth Anniversary of the Tlatelolco Treaty, and the Twentieth Anniversary of the Department of Safeguards Member State Support Programmes. There were special events and noted presentations featuring these anniversaries and giving the participants an informative retrospective view of safeguards development over the past four decades. The proceedings of this symposium provide the international community with a comprehensive view of where nuclear safeguards and verification stood in 1997 in terms of the growing demands and expectations. The Symposium offered thoughtful perspectives on where safeguards are headed within the broader context of verification issues. As the world of international nuclear verification looks towards the next millennium, the implementation of the expanding and strengthened safeguards system presents formidable challenges

Technology development for safeguards

Energy Technology Data Exchange (ETDEWEB)

Kim, Ho Dong; Kang, H. Y.; Song, D. Y. [and others

2005-04-01

The objective of this project are to establish the safeguards technology of the nuclear proliferation resistance to the facilities which handle with high radioactivity nuclear materials like the spent fuel, to provide the foundation of the technical independency for the establishment of the effective management of domestic spent fuels, and to construct the base of the early introduction of the key technology relating to the back-end nuclear fuel cycle through the development of the safeguards technology of the DFDF of the nuclear non-proliferation. The essential safeguards technologies of the facility such as the measurement and account of nuclear materials and the C/S technology were carried out in this stage (2002-2004). The principal results of this research are the development of error reduction technology of the NDA equipment and a new NDA system for the holdup measurement of process materials, the development of the intelligent surveillance system based on the COM, the evaluation of the safeguardability of the Pyroprocessing facility which is the core process of the nuclear fuel cycle, the derivation of the research and development items which are necessary to satisfy the safeguards criteria of IAEA, and the presentation of the direction of the technology development relating to the future safeguards of Korea. This project is the representative research project in the field of the Korea's safeguards. The safeguards technology and equipment developed while accomplishing this project can be applied to other nuclear fuel cycle facilities as well as DFDF and will be contributed to increase the international confidence in the development of the nuclear fuel cycle facility of Korea and its nuclear transparency.

Genome-wide analysis of effectors of peroxisome biogenesis.

Directory of Open Access Journals (Sweden)

Ramsey A Saleem

2010-08-01

Full Text Available Peroxisomes are intracellular organelles that house a number of diverse metabolic processes, notably those required for beta-oxidation of fatty acids. Peroxisomes biogenesis can be induced by the presence of peroxisome proliferators, including fatty acids, which activate complex cellular programs that underlie the induction process. Here, we used multi-parameter quantitative phenotype analyses of an arrayed mutant collection of yeast cells induced to proliferate peroxisomes, to establish a comprehensive inventory of genes required for peroxisome induction and function. The assays employed include growth in the presence of fatty acids, and confocal imaging and flow cytometry through the induction process. In addition to the classical phenotypes associated with loss of peroxisomal functions, these studies identified 169 genes required for robust signaling, transcription, normal peroxisomal development and morphologies, and transmission of peroxisomes to daughter cells. These gene products are localized throughout the cell, and many have indirect connections to peroxisome function. By integration with extant data sets, we present a total of 211 genes linked to peroxisome biogenesis and highlight the complex networks through which information flows during peroxisome biogenesis and function.

DOE/ABACC safeguards cooperation

International Nuclear Information System (INIS)

Whitaker, J.M.; Toth, P.; Rubio, J.

1995-01-01

In 1994, the US Department of Energy (DOE) and the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC) signed a safeguards cooperation agreement. The agreement provides for cooperation in the areas of nuclear material control, accountancy, verification, and advanced containment and surveillance technologies for international safeguards applications. ABACC is an international safeguards organization responsible for verifying the commitments of a 1991 bilateral agreement between Argentina and Brazil in which both countries agreed to submit all nuclear material in all nuclear activities to a Common System of Accounting and Control of Nuclear Materials (SCCC). DOE provides critical assistance (including equipment and training) through the Office of Nonproliferation and National Security to countries and international organizations to enhance their capabilities to control and verify nuclear material inventories. Specific activities initiated under the safeguards agreement include: (1) active US participation in ABACC's safeguards training courses, (2) joint development of specialized measurement training workshops, (3) characterization of laboratory standards, and (4) development and application of an extensive analytical laboratory comparison program. The results realized from these initial activities have been mutually beneficial in regard to strengthening the application of international safeguards in Argentina and Brazil

Role of ATP in the regulation of cholesterol biogenesis

International Nuclear Information System (INIS)

Subba Rao, G.; Ramasarma, T.

1974-01-01

Intraperitoneal administration of glucose (4oomg/rat) stimulated the biogenesis of sterols in starved rats while citrate or pyruvate (20mg/rat) did not have any effect. ATP (10mg/ rat) administered intraperitoneally stimulated the incorporation of acetate-1- 14 C into sterols but not of mevalonate-2- 14 C into sterols in starved rats. The results indicate that ATP may play a role in regulating cholesterol biogenesis and it is not acting merely as an energy source. (author)

Proliferation Resistance and Safeguards by Design: The Safeguardability Assessment Tool Provided by the INPRO Collaborative Project ''INPRO'' (Proliferation Resistance and Safeguardability Assessment)

International Nuclear Information System (INIS)

Haas, E.; Chang, H.-L.; Phillips, J.R.; Listner, C.

2015-01-01

Since the INPRO Collaborative Project on Proliferation Resistance and Safeguardability Assessment Tools (PROSA) was launched in 2011, Member State experts have worked with the INPRO Section and the IAEA Department of Safeguards to develop a revised methodology for self-assessment of sustainability in the area of proliferation resistance of a nuclear energy system (NES). With the common understanding that there is ''no proliferation resistance without safeguards'' the revised approach emphasizes the evaluation of a new 'User Requirement' for ''safeguardability'', that combines metrics of effective and efficient implementation of IAEA Safeguards including ''Safeguards-by-Design'' principles. The assessment with safeguardability as the key issue has been devised as a linear process evaluating the NES against a ''Basic Principle'' in the area of proliferation resistance, answering fundamental questions related to safeguards: 1) Do a State's legal commitments, policies and practices provide credible assurance of the exclusively peaceful use of the NES, including a legal basis for verification activities by the IAEA? 2) Does design and operation of the NES facilitate the effective and efficient implementation of IAEA safeguards? To answer those questions, a questionnaire approach has been developed that clearly identifies gaps and weaknesses. Gaps include prospects for improvements and needs for research and development. In this context, the PROSA approach assesses the safeguardability of a NES using a layered ''Evaluation Questionnaire'' that defines Evaluation Parameters (EP), EP-related questions, Illustrative Tests and Screening Questions to present and structure the evidence of findings. An integral part of the assessment process is Safeguards-by-Design, the identification of potential diversion, misuse and concealment strategies (coarse diversion path

How safe are nuclear safeguards

International Nuclear Information System (INIS)

Sullivan, E.

1979-01-01

Reports of weaknesses in IAEA safeguards have alarmed the US and since September 1977, US officials have refused to certify that the IAEA can adequately safeguard nuclear material the US exports. For political reasons, the IAEA safeguards system cannot perform an actual policing role or physically protect strategic material. The IAEA can only send out inspectors to verify bookkeeping and install cameras to sound the alarm should a diversion occur. Based on these IAEA reports and on interviews with scientists and US officials, the following serious problems hampering the Agency's safeguards effort can be identified: no foolproof safeguards for commercial reprocessing plants, uranium enrichment facilities, or fast breeder reactors; equipment failure and unreliable instruments; faulty accounting methods; too few well-trained inspectors; restrictions on where inspectors can go; commercial conflicts. Programs by the US, Canada, West Germany, Japan, and developing nations devised to better safeguards are briefly discussed. Some experts question whether international safeguards can be improved quickly enough to successfully deter nuclear weapons proliferation, given the rapid spread of nuclear technology to the third world

Some developments in safeguards techniques

International Nuclear Information System (INIS)

Beets, C.

1977-01-01

The fundamental principles of safeguards and the research and development of safeguards techniques are described. Safeguard accountancy based upon the partition of the fuel cycle into suitable material balance areas will be further improved. Implementation of international safeguards in the European fuel fabrication and reprocessing facilities is described. The effectiveness of a material accounting system depends on the quality of the quantitative data. The allocation of the tasks in the framework of an integrated safeguards is concerned with R and D work only and has no bearing on the allocation of the implementation costs. Bulk measurements, sampling and destructive or non-destructive analysis of samples are described for the determination of batch data. Testing of the safeguards techniques as a keystone in relation to plant instrumentation programmes are still being developed throughout the world. In addition to accountancy and control, it also includes an effective physical security program. The system of international safeguards that prevailed in the sixties has been re-modelled to comply with the new requirements of the Non-Proliferation Treaty and with the growth of nuclear energy

Structure of safeguards systems

International Nuclear Information System (INIS)

Shipley, J.P.

1978-06-01

An effective safeguards system for domestic nuclear fuel cycle facilities consists of several important subsystems that must coordinate their functions with plant management and process control. The safeguards system must not unnecessarily disrupt plant operations, compromise safety requirements, or infringe on employee working conditions. This report describes concepts, which have been developed with the cooperation of the nuclear industry and the safeguards community, for achieving these objectives

Novel technologies for safeguards

International Nuclear Information System (INIS)

Annese, C.; Monteith, A.; Whichello, J.

2009-01-01

Full-text: The International Atomic Energy Agency (IAEA) Novel Technologies Project is providing access to a wider range of methods and instruments, as well as establishing a systematic mechanism to analyse gaps in the inspectorate's technical support capabilities. The project also targets emerging and future inspectorate needs in the areas of verification and the detection of undeclared nuclear activities, materials, and facilities, providing an effective pathway to technologies in support of safeguards implementation. The identification of safeguards-useful nuclear fuel cycle (NFC) indicators and signatures (I and S) is a fundamental sub-task within the Project. It interfaces with other IAEA efforts currently underway to develop future safeguards approaches through undertaking an in-depth review of NFC processes. Primarily, the sub-task aims to identify unique and safeguards-useful 'indicators', which identify the presence of a particular process, and 'signatures', which emanate from that process when it is in operation. The matching of safeguards needs to detection tool capabilities facilitates the identification of gaps where no current method or instrument exists. The Project has already identified several promising technologies based on atmospheric gas sampling and analysis, laser spectrometry and optically stimulated luminescence. Instruments based on these technologies are presently being developed through support programme tasks with Member States. This paper discusses the IAEA's project, Novel Technologies for the Detection of Undeclared Nuclear Activities, Materials and Facilities and its goal to develop improved methods and instruments. The paper also describes the method that has been devised within the Project to identify safeguards-useful NFC I and S and to determine how the sub-task interfaces with other IAEA efforts to establish emerging safeguards approaches. As with all safeguards-targeted research and development (R and D), the IAEA depends

The Agency's Safeguards System (1965)

International Nuclear Information System (INIS)

1965-01-01

On 28 September 1965 the Board of Governors approved the Agency's revised safeguards system which is set forth in this document for the information of all Members. For ease of reference the revised system may be cited as 'The Agency's Safeguards System (1965)' to distinguish it from the original system - 'The Agency's Safeguards System (1961)'- and from the original system as extended to large reactor facilities - 'The Agency's Safeguards System (1961, as Extended in 1964)'

A ribosome without RNA

Directory of Open Access Journals (Sweden)

Harold S Bernhardt

2015-11-01

Full Text Available It was Francis Crick who first asked why the ribosome contains so much RNA, and discussed the implications of this for the direct flow of genetic information from DNA to protein. Remarkable advances in our understanding of the ribosome and protein synthesis, including the recent publication of two mammalian mitochondrial ribosome structures, have shed new light on this intriguing aspect of evolution in molecular biology. We examine here whether RNA is indispensable for coded protein synthesis, or whether an all-protein ‘ribosome’ (or ‘synthosome’ might be possible, with a protein enzyme catalyzing peptide synthesis, and release factor-like protein adaptors able to read a message composed of deoxyribonucleotides. We also compare the RNA world hypothesis with the alternative ‘proteins first’ hypothesis in terms of their different understandings of the evolution of the ribosome, and whether this might have been preceded by an ancestral form of nonribosomal peptide synthesis catalyzed by protein enzymes.

Roles of Transcriptional and Translational Control Mechanisms in Regulation of Ribosomal Protein Synthesis in Escherichia coli.

Science.gov (United States)

Burgos, Hector L; O'Connor, Kevin; Sanchez-Vazquez, Patricia; Gourse, Richard L

2017-11-01

Bacterial ribosome biogenesis is tightly regulated to match nutritional conditions and to prevent formation of defective ribosomal particles. In Escherichia coli , most ribosomal protein (r-protein) synthesis is coordinated with rRNA synthesis by a translational feedback mechanism: when r-proteins exceed rRNAs, specific r-proteins bind to their own mRNAs and inhibit expression of the operon. It was recently discovered that the second messenger nucleotide guanosine tetra and pentaphosphate (ppGpp), which directly regulates rRNA promoters, is also capable of regulating many r-protein promoters. To examine the relative contributions of the translational and transcriptional control mechanisms to the regulation of r-protein synthesis, we devised a reporter system that enabled us to genetically separate the cis -acting sequences responsible for the two mechanisms and to quantify their relative contributions to regulation under the same conditions. We show that the synthesis of r-proteins from the S20 and S10 operons is regulated by ppGpp following shifts in nutritional conditions, but most of the effect of ppGpp required the 5' region of the r-protein mRNA containing the target site for translational feedback regulation and not the promoter. These results suggest that most regulation of the S20 and S10 operons by ppGpp following nutritional shifts is indirect and occurs in response to changes in rRNA synthesis. In contrast, we found that the promoters for the S20 operon were regulated during outgrowth, likely in response to increasing nucleoside triphosphate (NTP) levels. Thus, r-protein synthesis is dynamic, with different mechanisms acting at different times. IMPORTANCE Bacterial cells have evolved complex and seemingly redundant strategies to regulate many high-energy-consuming processes. In E. coli , synthesis of ribosomal components is tightly regulated with respect to nutritional conditions by mechanisms that act at both the transcription and translation steps. In

The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1.

Directory of Open Access Journals (Sweden)

Monique N O'Leary

Full Text Available Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibility that heterogenous populations of ribosomes are unique to yeast. Here, we examine the roles of the mammalian Rpl22, finding that Rpl22(-/- mice have only subtle phenotypes with no significant translation defects. We find that in the Rpl22(-/- mouse there is a compensatory increase in Rpl22-like1 (Rpl22l1 expression and incorporation into ribosomes. Consistent with the hypothesis that either ribosomal protein can support translation, knockdown of Rpl22l1 impairs growth of cells lacking Rpl22. Mechanistically, Rpl22 regulates Rpl22l1 directly by binding to an internal hairpin structure and repressing its expression. We propose that ribosome specificity may exist in mammals, providing evidence that one ribosomal protein can influence composition of the ribosome by regulating its own paralog.

Synthetic peptides and ribosomal proteins as substrate for 60S ribosomal protein kinase from yeast cells

DEFF Research Database (Denmark)

Grankowski, N; Gasior, E; Issinger, O G

1993-01-01

Kinetic studies on the 60S protein kinase were conducted with synthetic peptides and ribosomal proteins as substrate. Peptide RRREEESDDD proved to be the best synthetic substrate for this enzyme. The peptide has a sequence of amino acids which most closely resembles the structure of potential...... phosphorylation sites in natural substrates, i.e., acidic ribosomal proteins. The superiority of certain kinetic parameters for 60S kinase obtained with the native whole 80S ribosomes over those of the isolated fraction of acidic ribosomal proteins indicates that the affinity of 60S kinase to the specific protein...

Safeguards for geological repositories

International Nuclear Information System (INIS)

Fattah, A.

2000-01-01

Direct disposal of spent nuclear fuel in geological repositories is a recognised option for closing nuclear fuel cycles. Geological repositories are at present in stages of development in a number of countries and are expected to be built and operated early next century. A State usually has an obligation to safely store any nuclear material, which is considered unsuitable to re-enter the nuclear fuel cycle, isolated from the biosphere. In conjunction with this, physical protection has to be accounted for to prevent inadvertent access to such material. In addition to these two criteria - which are fully under the State's jurisdiction - a third criterion reflecting international non-proliferation commitments needs to be addressed. Under comprehensive safeguards agreements a State concedes verification of nuclear material for safeguards purposes to the IAEA. The Agency can thus provide assurance to the international community that such nuclear material has been used for peaceful purposes only as declared by the State. It must be emphasised that all three criteria mentioned constitute a 'unit'. None can be sacrificed for the sake of the other, but compromises may have to be sought in order to make their combination as effective as possible. Based on comprehensive safeguards agreements signed and ratified by the State, safeguards can be terminated only when the material has been consumed or diluted in such a way that it can no longer be utilised for any nuclear activities or has become practicably irrecoverable. As such safeguards for nuclear material in geological repositories have to be continued even after the repository has been back-filled and sealed. The effective application of safeguards must assure continuity-of-knowledge that the nuclear material in the repository has not been diverted for an unknown purpose. The nuclear material disposed in a geological repository may eventually have a higher and long term proliferation risk because the inventory is

Strengthening regional safeguards

International Nuclear Information System (INIS)

Palhares, L.; Almeida, G.; Mafra, O.

1996-01-01

Nuclear cooperation between Argentina and Brazil has been growing since the early 1980's and as it grew, so did cooperation with the US Department of Energy (DOE). The Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC) was formed in December 1991 to operate the Common System of Accounting and Control of Nuclear Materials (SCCC). In April 1994, ABACC and the DOE signed an Agreement of Cooperation in nuclear material safeguards. This cooperation has included training safeguards inspectors, exchanging nuclear material measurement and containment and surveillance technology, characterizing reference materials, and studying enrichment plant safeguards. The goal of the collaboration is to exchange technology, evaluate new technology in Latin American nuclear facilities, and strengthen regional safeguards. This paper describes the history of the cooperation, its recent activities, and future projects. The cooperation is strongly supported by all three governments: the Republics of Argentina and Brazil and the United States

Recent advances in IAEA safeguards systems analysis

International Nuclear Information System (INIS)

Bahm, W.; Ermakov, S.; Kaniewski, J.; Lovett, J.; Pushkarjov, V.; Rosenthal, M.D.

1983-01-01

Efficient implementation of effective safeguards, the objective of the IAEA's Department of Safeguards, would be unthinkable without carrying out systematic studies on many different problems related to technical and other aspects of safeguards. The System Studies Section of the Department concentrates its efforts on such studies with the purpose of elaborating concepts, criteria, approaches and rules for the implementation of safeguards. In particular, the Section elaborates concepts and approaches for applying safeguards at the complex facilities that are expected to enter under safeguards in the future, develops approaches and rules in the areas where the Agency is still gaining experience, and assists in the implementation of safeguards whenever problems requiring non-routine solutions arise. This paper presents examples of the present activities of the System Studies Section: development of guidelines for use by facility designers in order to make safeguards easier and more effective, studies on near-real-time material accountancy, preparation of safeguards approaches for specific facility types, preparation of model inspection activity lists for different facility types and alternative safeguards approaches and preparation of safeguards policy papers containing the rules and regulations to be followed in the design and implementation of safeguards. (author)

Nuclear safeguards research and development

Science.gov (United States)

Henry, C. N.

1981-11-01

The status of a nuclear safeguard research and development program is presented. Topics include nondestructive assay technology development and applications, international safeguards, training courses, technology transfer, analytical chemistry methods for fissionable materials safeguards, the Department of Energy Computer Security Technical Center, and operational security.

Implementation of Safeguards in Thailand

International Nuclear Information System (INIS)

Rueanngoen, A.; Changkrueng, K.; Srijittawa, L.; Mungpayaban, H.; Wititteeranon, A.

2015-01-01

Thailand is a non-nuclear weapon state. The non-nuclear activities are mainly medical, agricultural, and industrial. Therefore, Thailand ratified the Nuclear Non-Proliferation Treaty (NPT) since 1972 and has been entry into force of the Comprehensive Safeguards Agreement (INFCIRC 241) since 1974. Based on the INFCIRC 153, Thailand established a system of accounting for and control of all nuclear material subject to safeguards under the Agreement. In order to ensure the peaceful use of nuclear in Thailand the Nuclear-Non- Proliferation Center of Office of Atoms for Peace (NPC, OAP) was established to act as State level Safeguards. NPC is responsible for keeping records and providing information under requirement of Comprehensive Safeguards Agreement. In addition, the strengthening of cooperation and good coordination between Thailand and IAEA are indeed important and necessary to implementation safeguards in country. Based on the report of IAEA safeguards statement, there is no indication of the diversion of nuclear materials or misuse of the facility or the items in Thailand. Up to present, nuclear activities in Thailand are peaceful without diversion of using. This paper reviews the current status of the implementation Safeguards in Thailand. (author)

IAEA safeguard system

International Nuclear Information System (INIS)

Pontes, B.C.

1987-01-01

The intents of IAEA safeguards, analysing into the IAEA statutes, are presented. The different types of safeguard agreements; the measurements of accounting, containment and caution used by the operator and; the information to be provided and the verification to be developed by IAEA are described. (M.C.K.) [pt

Mitochondrial biogenesis in the pulmonary vasculature during inhalation lung injury and fibrosis

Science.gov (United States)

Cell survival and injury repair is facilitated by mitochondrial biogenesis; however, the role of this process in lung repair is unknown. We evaluated mitochondrial biogenesis in the mouse lung in two injuries that cause acute inflammation and in two that cause chronic inflammatio...

Current technical issues in international safeguards

International Nuclear Information System (INIS)

Bennett, C.A.

1977-01-01

Safeguards systems, and the associated need for technical and systems development, reflect changing conditions and concerns associated with the nuclear fuel cycle and the safety and security of nuclear materials and facilities. In particular, the implementation of international safeguards has led to the recognition of certain technical issues, both old and new, which are in need of resolution. These are: 1. The grading of nuclear materials and facilities with respect to their relative safeguards significance. 2. The extension and upgrading of safeguards techniques to maintain adequate protection in view of constantly increasing amounts of material to be safeguarded. 3. The balance between safeguards mechanisms based on physical protection and material accounting, and the role of surveillance and containment in each case. 4. The role of information systems as a basis for both analytical feedback and the determination of the factors affecting system effectiveness and their interrelationship. 5. A determination of the degree to which the overall technical effectiveness of international inspection activities can be quantified. Each of these technical issues must be considered in light of the specific objectives of international safeguards, which differ from domestic safeguards in terms of the level of the threat, the safeguards mechanisms available, and the diversion strategies assumed. Their resolution in this international context is essential if the effectiveness and viability of international safeguards are to be maintained

Mitochondrial iron-sulfur cluster biogenesis from molecular understanding to clinical disease

Science.gov (United States)

Alfadhel, Majid; Nashabat, Marwan; Ali, Qais Abu; Hundallah, Khalid

2017-01-01

Iron–sulfur clusters (ISCs) are known to play a major role in various protein functions. Located in the mitochondria, cytosol, endoplasmic reticulum and nucleus, they contribute to various core cellular functions. Until recently, only a few human diseases related to mitochondrial ISC biogenesis defects have been described. Such diseases include Friedreich ataxia, combined oxidative phosphorylation deficiency 19, infantile complex II/III deficiency defect, hereditary myopathy with lactic acidosis and mitochondrial muscle myopathy, lipoic acid biosynthesis defects, multiple mitochondrial dysfunctions syndromes and non ketotic hyperglycinemia due to glutaredoxin 5 gene defect. Disorders of mitochondrial import, export and translation, including sideroblastic anemia with ataxia, EVEN-PLUS syndrome and mitochondrial complex I deficiency due to nucleotide-binding protein-like protein gene defect, have also been implicated in ISC biogenesis defects. With advances in next generation sequencing technologies, more disorders related to ISC biogenesis defects are expected to be elucidated. In this article, we aim to shed the light on mitochondrial ISC biogenesis, related proteins and their function, pathophysiology, clinical phenotypes of related disorders, diagnostic approach, and future implications. PMID:28064324

Safeguarding the Plutonium Fuel Cycle

International Nuclear Information System (INIS)

Johnson, S.J.; Lockwood, D.

2013-01-01

In developing a Safeguards Approach for a plutonium process facility, two general diversion and misuse scenarios must be addressed: 1) Unreported batches of undeclared nuclear material being processed through the plant and bypassing the accountancy measurement points, and 2) The operator removing plutonium at a rate that cannot be detected with confidence due to measurement uncertainties. This paper will look at the implementation of international safeguards at plutonium fuel cycle facilities in light of past lessons learned and current safeguards approaches. It will then discuss technical areas which are currently being addressed as future tools to improve on the efficiency of safeguards implementation, while maintaining its effectiveness. The discussion of new improvements will include: safeguards by design (SBD), process monitoring (PM), measurement and monitoring equipment, and data management. The paper is illustrated with the implementation of international safeguards at the Rokkasho Reprocessing Plant in Japan and its accountancy structure is detailed. The paper is followed by the slides of the presentation

Safeguards agreements - Their legal and conceptual basis

International Nuclear Information System (INIS)

Sanders, B.; Rainer, R.H.

1977-01-01

The application of Agency safeguards requires treaty arrangements (Safeguards Agreements) between the State or States concerned and the Agency. The authority for the Agency to conclude such agreements and to implement them is provided for in the Agency's Statute. On the basis of the statutory provisions safeguards principles and procedures have been elaborated. These have been laid down in: The Agency's Safeguards System 1965, extended in 1966 and 1968; and the basis for negotiating safeguards agreements with NNWS pursuant to NPT. The verification of the undertaking by the State concerned not to use items subject to safeguards for purposes contrary to the terms of the agreement is ensured through the application of various safeguards measures. Containment and surveillance measures are expected to play an increasingly important role. One of the specific features of NPT Safeguards Agreements is the establishment of national systems of accounting and control of nuclear material. The majority of the agreements concluded under the non-NPT safeguards agreements implement obligations undertaken under co-operation agreements between States for peaceful uses of nuclear energy. These agreements naturally reflect approaches adopted by the parties, in particular regarding the circumstances under which safeguards should be applied. Thus, the concepts used in the non-NPT safeguards agreements and the Safeguards System document, which is incorporated in these agreements by reference, are in continuous evolution. The Agency's Safeguards System document (INFCIRC/66/Rev.2) continues to be supplemented in practical application and through explicit decision by the Board. The non-NPT safeguards agreements contain, besides technical safeguards provisions from this document, and further provision for notification, inventories and financial matters, legal and political provisions such as sanctions in the case of non-compliance, and privileges and immunities. The paper discusses the

IAEA safeguards for the 21st century

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-07-01

The publication includes the lectures held during the seminar on IAEA safeguards for the 21st century. The topics covered are as follows: the nuclear non-proliferation regime; Legal instruments related to the application of safeguards; multilateral nuclear export controls; physical protection and its role in nuclear non-proliferation; the evolution of safeguards; basis for the strengthening of safeguards; information required from states, including 'small quantities protocol'; processing and evaluation of new information for strengthened safeguards; additional physical access and new technologies for strengthened safeguards; equipping the IAEA Inspectorate with new skills; achievements to date the strengthened safeguards; complement ofregional non-proliferation arrangements in international nuclear verification; promotion of transparency through Korean experience; and the future prospects of safeguards.

Sequence Classification: 893067 [

Lifescience Database Archive (English)

Full Text Available tuent of 66S pre-ribosomal particles, involved in 60S ribosomal subunit biogenesis; localizes to both nucleolus and cytoplasm; Nop15p || http://www.ncbi.nlm.nih.gov/protein/6324219 ...

Safeguards systems parameters

International Nuclear Information System (INIS)

Avenhaus, R.; Heil, J.

1979-01-01

In this paper analyses are made of the values of those parameters that characterize the present safeguards system that is applied to a national fuel cycle; those values have to be fixed quantitatively so that all actions of the safeguards authority are specified precisely. The analysis starts by introducing three categories of quantities: The design parameters (number of MBAs, inventory frequency, variance of MUF, verification effort and false-alarm probability) describe those quantities whose values have to be specified before the safeguards system can be implemented. The performance criteria (probability of detection, expected detection time, goal quantity) measure the effectiveness of a safeguards system; and the standards (threshold amount and critical time) characterize the magnitude of the proliferation problem. The means by which the values of the individual design parameters can be determined with the help of the performance criteria; which qualitative arguments can narrow down the arbitrariness of the choice of values of the remaining parameters; and which parameter values have to be fixed more or less arbitrarily, are investigated. As a result of these considerations, which include the optimal allocation of a given inspection effort, the problem of analysing the structure of the safeguards system is reduced to an evaluation of the interplay of only a few parameters, essentially the quality of the measurement system (variance of MUF), verification effort, false-alarm probability, goal quantity and probability of detection

Licensee safeguards contingency plans

International Nuclear Information System (INIS)

Anon.

1978-01-01

The Nuclear Regulatory Commission is amending its regulations to require that licensees authorized to operate a nuclear reactor (other than certain research and test reactors), and those authorized to possess strategic quantities of plutonium, uranium-233, or uranium-235 develop and implement acceptable plans for responding to threats, thefts, and industrial sabotage of licensed nuclear materials and facilities. The plans will provide a structured, orderly, and timely response to safeguards contingencies and will be an important segment of NRC's contingency planning programs. Licensee safeguards contingency plans will result in organizing licensee's safeguards resources in such a way that, in the unlikely event of a safeguards contingency, the responding participants will be identified, their several responsibilities specified, and their responses coordinated

Safeguards challenges of Fast Breeder Reactor

International Nuclear Information System (INIS)

Ko, H. S.

2010-01-01

Although the safeguards system of Sodium Fast Reactor (SFR) seems similar to that of Light Water Reactor (LWR), it was raised safeguards challenges of SFR that resulted from the visual opacity of liquid sodium, chemical reactivity of sodium and other characteristics of fast reactor. As it is the basic concept stage of the safeguards of SFR in Korea, this study tried to analyze the latest similar study of safeguards issues of the Fast Breeder Reactor (FBR) at Joyo and Monju in Japan. For this reason, this study is to introduce some potential safeguards challenges of Fast Breeder Reactor. With this analysis, future study could be to address the safeguards challenges of SFR in Korea

The next generation safeguards initiative

International Nuclear Information System (INIS)

Tobey, William

2008-01-01

NGSI or the Next Generation Safeguards Initiative is designed to revitalize the U.S. safeguards technical base, as well as invest in human resources, and to mobilize our primary asset - the U.S. National Laboratories - as well as industry and academia to restore capabilities. While NGSI is a U.S. effort it is intended to serve as a catalyst for a much broader commitment to international safeguards in partnership with the IAEA and other countries. Initiatives over the last years include such as the Proliferation Security Initiative, UN Security Council Resolution 1540, the Global Initiative to Combat Nuclear Terrorism, and initiatives of the G-8 and NSG to discourage the spread of enrichment and reprocessing. NGSI augments this agenda by providing a means to strengthen the technical and political underpinnings of IAEA safeguards. Priorities and envisioned activities under NGSI are the following. (1) Cooperation with IAEA and others to promote universal adoption of safeguards agreements and the Additional Protocol including greater information sharing between member states and the IAEA, investigation of weaponization and procurement activities, and options to strengthen the state-level approach to safeguards. (2) NGSI anticipates the deployment of new types of reactors and fuel cycle facilities, as well as the need to use limited safeguards resources effectively and efficiently, especially in plants that pose the largest burden specifically complex, bulk-handling facilities. (3) NGSI will encourage a generational improvement in current safeguards technologies including improvement of precision and speed of nuclear measurements, performance of real-time process monitoring and surveillance in unattended mode, enabling in-field, pre-screening and analysis of nuclear and environmental samples, and collection, integration, analysis and archiving safeguards-relevant information from all available sources.(4) NGSI will address human capital management. Training and

Safeguards can not operate alone

International Nuclear Information System (INIS)

Martikka, E.; Honkamaa, T.; Haemaelaeinen, M.; Okko, O.

2013-01-01

There are around 20 new states which are planning to use nuclear energy in the near future. Globally there are several nuclear power plants under construction and they will be bigger than ever. Also new type of nuclear facility, final disposal facility for spent nuclear fuel, will be constructed and in operation in Finland and Sweden in ca. 10 years time. It is evident that the nuclear world is changing much and quickly. After the Additional Protocol, safeguards are no longer only about accounting and control of nuclear materials, but also about verifying that there are no undeclared nuclear materials and activities in the state. It is not possible or effective anymore to implement safeguards without taking into account of the nuclear safety and security. The safeguards should not be isolated. The synergy between safeguards, security and safety exist, when implementing nationally that there are no undeclared nuclear materials or activities. In safeguards we could not do our duties effectively if we ignore some of those other S's. Safeguards by Design process does not work properly if only international safeguards and security requirements has been taken into account, it urges all 3S to be taken care at the same time. Safeguards should operate also with other synergetic regimes and organisations like CTBTO, Fissile Material Cut-off, disarmament, export control, border control,... The paper is followed by the slides of the presentation

IAEA safeguards for the 21st century

International Nuclear Information System (INIS)

1999-01-01

The publication includes the lectures held during the seminar on IAEA safeguards for the 21st century. The topics covered are as follows: the nuclear non-proliferation regime; Legal instruments related to the application of safeguards; multilateral nuclear export controls; physical protection and its role in nuclear non-proliferation; the evolution of safeguards; basis for the strengthening of safeguards; information required from states, including 'small quantities protocol'; processing and evaluation of new information for strengthened safeguards; additional physical access and new technologies for strengthened safeguards; equipping the IAEA Inspectorate with new skills; achievements to date the strengthened safeguards; complement of regional non-proliferation arrangements in international nuclear verification; promotion of transparency through Korean experience; and the future prospects of safeguards

Application of safeguards procedures

International Nuclear Information System (INIS)

1977-01-01

The earliest applications of safeguards procedures took place in a political and technical climate far different from that of today. In the early 1960's there was a fear of the proliferation possibilities which could arise as more and more countries acquired nuclear power plants. Today nuclear power is being produced in some 20 countries without resulting in nuclear weapons proliferation. The export of equipment and technology for the nuclear fuel cycle, however, has become the subject of current concern. In view of these developments, it is not surprising that techniques in the application of safeguards have also changed. In order to appreciate the nature of these changes, it is important to be aware of the original general attitude towards the technical problems of safeguards applications. Originally, the common attitude was that the objectives of safeguards were self-evident and the methods, while in need of development, were known at least in outline. Today, it has become evident that before a safeguards procedure can be applied, the objectives must first be carefully defined, and the criteria against which success in meeting those objectives can be measured must also be developed. In line with this change, a significant part of the effort of the safeguards inspectorate is concerned with work preliminary and subsequent to the actual inspection work in the field. Over the last two years, for example, a considerable part of the work of experienced safeguards staff has been spent in analysing the possibilities of diverting material at each facility to be safeguarded. These analyses are carried out in depth by a 'facility officer' and are subjected to constructive criticism by teams composed of staff responsible for similar types of facilities as well as other technical experts. The analyses consider the measures currently considered practicable, to meet the diversion possibilities and where necessary list the development work needed to overcome any present

Safeguards by Design Challenge

Energy Technology Data Exchange (ETDEWEB)

Alwin, Jennifer Louise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2016-09-13

The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA’s limited budget. Dose to workers should always be as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).

Safeguards by Design Challenge

International Nuclear Information System (INIS)

Alwin, Jennifer Louise

2016-01-01

The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA's limited budget. Dose to workers should always be as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).

IAEA safeguards approaches and goals

International Nuclear Information System (INIS)

Khlebnikov, Nikolai

2001-01-01

IAEA safeguards provide a technical means of verifying that political obligations undertaken by States party to international agreements relating to the peaceful uses of nuclear energy are being honored. The Agency assures the international community that States party to Safeguards Agreements are complying with their undertaking not to use facilities and divert nuclear materials from peaceful uses to the manufacture of nuclear explosive devices. The task of IAEA safeguards can be summed up as to detect diversion of nuclear materials committed to peaceful uses of nuclear energy, or the misuse of equipment or facilities subject to certain safeguards agreements, and to deter such diversion or misuse through the risk of early detection. This lecture concentrates on the factors the Agency takes into account in designing and implementing safeguards approaches at facilities. (author)

Addressing Safeguards Challenges for the Future

Energy Technology Data Exchange (ETDEWEB)

Majali, Raed; Yim, Man-Sung [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2015-10-15

IAEA safeguard system is considered the corner stone of the international nuclear nonproliferation regime. Effective implementation of this legal instrument enables the IAEA to draw a conclusion with a high degree of confidence on the peaceful use of nuclear material and activities in the state. This paper aims to provide an opportunity to address various challenges encountered by IAEA. Strengthening safeguards system for verification is one of the most urgent challenges facing the IAEA. The IAEA should be able to provide credible assurance not only about declared use of nuclear material and facilities but also about the absence of undeclared material and activities. Implementation of IAEA safeguards continue to play a vital role within the nuclear non-proliferation regime. IAEA must move towards more enhanced safeguards system that is driven by the full use of all the safeguards available relevant information. Safeguards system must be responsive to evolving challenges and continue innovation through efficient implementations of more effective safeguards.

Structure of Ribosomal Silencing Factor Bound to Mycobacterium tuberculosis Ribosome.

Science.gov (United States)

Li, Xiaojun; Sun, Qingan; Jiang, Cai; Yang, Kailu; Hung, Li-Wei; Zhang, Junjie; Sacchettini, James C

2015-10-06

The ribosomal silencing factor RsfS slows cell growth by inhibiting protein synthesis during periods of diminished nutrient availability. The crystal structure of Mycobacterium tuberculosis (Mtb) RsfS, together with the cryo-electron microscopy (EM) structure of the large subunit 50S of Mtb ribosome, reveals how inhibition of protein synthesis by RsfS occurs. RsfS binds to the 50S at L14, which, when occupied, blocks the association of the small subunit 30S. Although Mtb RsfS is a dimer in solution, only a single subunit binds to 50S. The overlap between the dimer interface and the L14 binding interface confirms that the RsfS dimer must first dissociate to a monomer in order to bind to L14. RsfS interacts primarily through electrostatic and hydrogen bonding to L14. The EM structure shows extended rRNA density that it is not found in the Escherichia coli ribosome, the most striking of these being the extended RNA helix of H54a. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nuclear safeguards

International Nuclear Information System (INIS)

Estrampres, J.

2010-01-01

Close cooperation with the Ministry of Industry with representation from the UNESA Safeguards Group, has meant that, after almost two years of intense meetings and negotiations, Spain has a specific plant to plant agreement for the application of Safeguards under this new method. This is an agreement which aims to be a benchmark for all other EU countries, as the IAEA tends to apply a generic agreement that, in many cases, majority interferes in the nuclear power plants own processes. (Author).

Implementing Safeguards-by-Design

International Nuclear Information System (INIS)

Bjornard, Trond; Bean, Robert; Durst, Phillip Casey; Hockert, John; Morgan, James

2010-01-01

Excerpt Safeguards-by-Design (SBD) is an approach to the design and construction of nuclear facilities whereby safeguards are designed-in from the very beginning. It is a systematic and structured approach for fully integrating international and national safeguards (MC and A), physical security, and other proliferation barriers into the design and construction process for nuclear facilities. SBD is primarily a project management or project coordination challenge, and this report focuses on that aspect of SBD. The present report continues the work begun in 2008 and focuses specifically on the design process, or project management and coordination - the planning, definition, organization, coordination, scheduling and interaction of activities of the safeguards experts and stakeholders as they participate in the design and construction of a nuclear facility. It delineates the steps in a nuclear facility design and construction project, in order to provide the project context within which the safeguards design activities take place, describes the involvement of safeguards experts in the design process, the nature of their analyses, interactions and decisions, as well as describing the documents created and how they are used. Designing and constructing a nuclear facility is an extremely complex undertaking. The stakeholders in an actual project are many - owner, operator, State regulators, nuclear facility primary contractor, subcontractors (e.g. instrument suppliers), architect engineers, project management team, safeguards, safety and security experts, in addition to the IAEA and its team. The purpose of the present report is to provide a common basis for discussions amongst stakeholders to collaboratively develop a SBD approach that will be both practically useful and mutually beneficial. The principal conclusions from the present study are: (1) In the short term, the successful implementation of SBD is principally a project management problem. (2) Life-cycle cost

Implementing The Safeguards-By-Design Process

International Nuclear Information System (INIS)

Whitaker, J. Michael; McGinnis, Brent; Laughter, Mark D.; Morgan, Jim; Bjornard, Trond; Bean, Robert; Durst, Phillip; Hockert, John; DeMuth, Scott; Lockwood, Dunbar

2010-01-01

The Safeguards-by-Design (SBD) approach incorporates safeguards into the design and construction of nuclear facilities at the very beginning of the design process. It is a systematic and structured approach for fully integrating international and national safeguards for material control and accountability (MC and A), physical protection, and other proliferation barriers into the design and construction process for nuclear facilities. Implementing SBD is primarily a project management or project coordination challenge. This paper focuses specifically on the design process; the planning, definition, organization, coordination, scheduling and interaction of the safeguards experts and stakeholders as they participate in the design and construction of a nuclear facility. It delineates the steps in a nuclear facility design and construction project in order to provide the project context within which the safeguards design activities take place, describes the involvement of the safeguards experts in the design process, the nature of their analyses, interactions and decisions, and describes the documents created and how they are used. This report highlights the project context of safeguards activities, and identifies the safeguards community (nuclear facility operator, designer/builder, state regulator, SSAC and IAEA) must accomplish in order to implement SBD within the project.

Optimizing IAEA Safeguards

International Nuclear Information System (INIS)

Varjoranta, Tero

2016-01-01

IAEA safeguards make a vital contribution to international security. Through safeguards, the IAEA deters the spread of nuclear weapons and provides credible assurance that States are honouring their international obligations to use nuclear material only for peaceful purposes. Its independent verification work allows the IAEA to facilitate building international confidence and strengthening collective security for all.

Ribosomal studies on the 70S ribosome of E.coli by means of neutron scattering; Strukturuntersuchungen am 70S-Ribosom von E.coli unter Anwendung von Neutronenstreuung

Energy Technology Data Exchange (ETDEWEB)

Burkhardt, N. [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Werkstofforschung

1997-12-31

Ribosomes are ribonucleo-protein complexes, which catalyse proteinbiosynthesis in all living organisms. Currently, most of the structural models of the prokaryotic 70S ribosome rely on electron microscopy and describe mainly the outer shape of the particle. Neutron scattering can provide information on the internal structure of the ribosome. Parts of the structure can be contrasted for neutrons by means of an isotopic exchange of the naturally occurring hydrogen ({sup 1}H) for deuterium ({sup 2}H), allowing direct measurements in situ. Specifically deuterium-labeled ribosomes (E. coli) were prepared and analysed with neutron scattering. The biochemical methods were established and combined to a generally applicable preparation system. This allows labeling of all ribosomal components in any combination. A systematic analysis of the protein and RNA phases resulted in the development of a new model for the 70S ribosome. This model describes not only the outer shape of the particle, but displays also an experimentally determined internal protein-RNA distribution and the border of subunits for the first time (four-phase model; resolution: 50A). Models of the 70S ribosome from other studies were evaluated and ranked according to consistency with the measured scattering data. Applying a new neutron scattering technique of particular sensitivity, the proton-spin contrast-variation, single proteins could be measured and localized. The positions of the proteins S6 and S10 were determined, providing the first coordinates of protein mass centers within the 70S ribosome. (orig.) [Deutsch] Ribosomen sind Ribonukleinsaeure-Protein Komplexe, die in allen lebenden Organismen die Proteinbiosynthese katalysieren. Strukturmodelle fuer das prokaryontische 70S-Ribosom beruhen derzeit vorwiegend auf elektronenmikroskopischen Untersuchungen und beschreiben im wesentlichen die aeussere Oberflaeche des Partikels. Informationen ueber die innere Struktur des Ribosoms koennen Messungen mit

Ribosomal studies on the 70S ribosome of E.coli by means of neutron scattering; Strukturuntersuchungen am 70S-Ribosom von E.coli unter Anwendung von Neutronenstreuung

Energy Technology Data Exchange (ETDEWEB)

Burkhardt, N [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Werkstofforschung

1998-12-31

Ribosomes are ribonucleo-protein complexes, which catalyse proteinbiosynthesis in all living organisms. Currently, most of the structural models of the prokaryotic 70S ribosome rely on electron microscopy and describe mainly the outer shape of the particle. Neutron scattering can provide information on the internal structure of the ribosome. Parts of the structure can be contrasted for neutrons by means of an isotopic exchange of the naturally occurring hydrogen ({sup 1}H) for deuterium ({sup 2}H), allowing direct measurements in situ. Specifically deuterium-labeled ribosomes (E. coli) were prepared and analysed with neutron scattering. The biochemical methods were established and combined to a generally applicable preparation system. This allows labeling of all ribosomal components in any combination. A systematic analysis of the protein and RNA phases resulted in the development of a new model for the 70S ribosome. This model describes not only the outer shape of the particle, but displays also an experimentally determined internal protein-RNA distribution and the border of subunits for the first time (four-phase model; resolution: 50A). Models of the 70S ribosome from other studies were evaluated and ranked according to consistency with the measured scattering data. Applying a new neutron scattering technique of particular sensitivity, the proton-spin contrast-variation, single proteins could be measured and localized. The positions of the proteins S6 and S10 were determined, providing the first coordinates of protein mass centers within the 70S ribosome. (orig.) [Deutsch] Ribosomen sind Ribonukleinsaeure-Protein Komplexe, die in allen lebenden Organismen die Proteinbiosynthese katalysieren. Strukturmodelle fuer das prokaryontische 70S-Ribosom beruhen derzeit vorwiegend auf elektronenmikroskopischen Untersuchungen und beschreiben im wesentlichen die aeussere Oberflaeche des Partikels. Informationen ueber die innere Struktur des Ribosoms koennen Messungen mit

IAEA safeguards in new nuclear facilities

Energy Technology Data Exchange (ETDEWEB)

Catton, A. [International Atomic Energy Agency, Vienna (Austria); Durbin, K. [United States Department of Energy, Washington, D.C. (United States); Hamilton, A. [International Atomic Energy Agency, Vienna (Austria); Martikka, E. [STUK, Helsinki (Finland); Poirier, S.; Sprinkle, J. K.; Stevens, R. [International Atomic Energy Agency, Vienna (Austria); Whitlock, J. [Atomic Energy of Canada Limited, Chalk River, ON (Canada)

2014-07-01

The inclusion of international safeguards early in the design of nuclear facilities offers an opportunity to reduce project risk. It also has the potential to minimize the impact of safeguards activities on facility operations. Safeguards by design (SBD) encourages stakeholders to become familiar with the requirements of their safeguards agreements and to decide when and how they will fulfil those requirements. As one example, modular reactors are at a design stage where SBD can have a useful impact. Modular reactors might be turnkey projects where the operator takes ownership after commissioning. This comes with a legal obligation to comply with International Atomic Energy Agency (IAEA) safeguards requirements. Some of the newcomer countries entering the reactor market have little experience with IAEA safeguards and the associated non-proliferation obligations. To reduce delays or cost increments, one can embed safeguards considerations in the bid and design phases of the project, along with the safety and security considerations. SBD does not introduce any new requirements - it is a process whereby facility designers facilitate the implementation of the existing safeguards requirements. In short, safeguards experts share their expertise with the designers and vice versa. Once all parties understand the fundamentals of all of the operational constraints, they are better able to decide how best to address them. This presentation will provide an overview of SBD activities. (author)

Differential Stoichiometry among Core Ribosomal Proteins

Directory of Open Access Journals (Sweden)

Nikolai Slavov

2015-11-01

Full Text Available Understanding the regulation and structure of ribosomes is essential to understanding protein synthesis and its dysregulation in disease. While ribosomes are believed to have a fixed stoichiometry among their core ribosomal proteins (RPs, some experiments suggest a more variable composition. Testing such variability requires direct and precise quantification of RPs. We used mass spectrometry to directly quantify RPs across monosomes and polysomes of mouse embryonic stem cells (ESC and budding yeast. Our data show that the stoichiometry among core RPs in wild-type yeast cells and ESC depends both on the growth conditions and on the number of ribosomes bound per mRNA. Furthermore, we find that the fitness of cells with a deleted RP-gene is inversely proportional to the enrichment of the corresponding RP in polysomes. Together, our findings support the existence of ribosomes with distinct protein composition and physiological function.

Selenium supplementation induces mitochondrial biogenesis in trophoblasts

Czech Academy of Sciences Publication Activity Database

Khera, A.; Dong, L. F.; Holland, O.; Vanderlelie, J.; Pasdar, E.A.; Neužil, Jiří; Perkins, A.V.

2015-01-01

Roč. 36, č. 8 (2015), s. 363-369 ISSN 0143-4004 Institutional support: RVO:86652036 Keywords : Selenium * Reactive oxygen species * Mitochondrial biogenesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.972, year: 2015

Safeguard Vulnerability Analysis Program (SVAP)

International Nuclear Information System (INIS)

Gilman, F.M.; Dittmore, M.H.; Orvis, W.J.; Wahler, P.S.

1980-01-01

This report gives an overview of the Safeguard Vulnerability Analysis Program (SVAP) developed at Lawrence Livermore National Laboratory. SVAP was designed as an automated method of analyzing the safeguard systems at nuclear facilities for vulnerabilities relating to the theft or diversion of nuclear materials. SVAP addresses one class of safeguard threat: theft or diversion of nuclear materials by nonviolent insiders, acting individually or in collusion. SVAP is a user-oriented tool which uses an interactive input medium for preprocessing the large amounts of safeguards data. Its output includes concise summary data as well as detailed vulnerability information

Mitochondrial Biogenesis in Diverse Cauliflower Cultivars under Mild and Severe Drought. Impaired Coordination of Selected Transcript and Proteomic Responses, and Regulation of Various Multifunctional Proteins

Directory of Open Access Journals (Sweden)

Michał Rurek

2018-04-01

Full Text Available Mitochondrial responses under drought within Brassica genus are poorly understood. The main goal of this study was to investigate mitochondrial biogenesis of three cauliflower (Brassica oleracea var. botrytis cultivars with varying drought tolerance. Diverse quantitative changes (decreases in abundance mostly in the mitochondrial proteome were assessed by two-dimensional gel electrophoresis (2D PAGE coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS. Respiratory (e.g., complex II, IV (CII, CIV and ATP synthase subunits, transporter (including diverse porin isoforms and matrix multifunctional proteins (e.g., components of RNA editing machinery were diversely affected in their abundance under two drought levels. Western immunoassays showed additional cultivar-specific responses of selected mitochondrial proteins. Dehydrin-related tryptic peptides (found in several 2D spots immunopositive with dehydrin-specific antisera highlighted the relevance of mitochondrial dehydrin-like proteins for the drought response. The abundance of selected mRNAs participating in drought response was also determined. We conclude that mitochondrial biogenesis was strongly, but diversely affected in various cauliflower cultivars, and associated with drought tolerance at the proteomic and functional levels. However, discussed alternative oxidase (AOX regulation at the RNA and protein level were largely uncoordinated due to the altered availability of transcripts for translation, mRNA/ribosome interactions, and/or miRNA impact on transcript abundance and translation.

Mitochondrial Biogenesis in Diverse Cauliflower Cultivars under Mild and Severe Drought. Impaired Coordination of Selected Transcript and Proteomic Responses, and Regulation of Various Multifunctional Proteins

Science.gov (United States)

Rurek, Michał; Czołpińska, Magdalena; Staszak, Aleksandra Maria; Nowak, Witold; Krzesiński, Włodzimierz; Spiżewski, Tomasz

2018-01-01

Mitochondrial responses under drought within Brassica genus are poorly understood. The main goal of this study was to investigate mitochondrial biogenesis of three cauliflower (Brassica oleracea var. botrytis) cultivars with varying drought tolerance. Diverse quantitative changes (decreases in abundance mostly) in the mitochondrial proteome were assessed by two-dimensional gel electrophoresis (2D PAGE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Respiratory (e.g., complex II, IV (CII, CIV) and ATP synthase subunits), transporter (including diverse porin isoforms) and matrix multifunctional proteins (e.g., components of RNA editing machinery) were diversely affected in their abundance under two drought levels. Western immunoassays showed additional cultivar-specific responses of selected mitochondrial proteins. Dehydrin-related tryptic peptides (found in several 2D spots) immunopositive with dehydrin-specific antisera highlighted the relevance of mitochondrial dehydrin-like proteins for the drought response. The abundance of selected mRNAs participating in drought response was also determined. We conclude that mitochondrial biogenesis was strongly, but diversely affected in various cauliflower cultivars, and associated with drought tolerance at the proteomic and functional levels. However, discussed alternative oxidase (AOX) regulation at the RNA and protein level were largely uncoordinated due to the altered availability of transcripts for translation, mRNA/ribosome interactions, and/or miRNA impact on transcript abundance and translation. PMID:29642585

Nuclear safeguards: a perspective

International Nuclear Information System (INIS)

Walske, C.

1975-01-01

Safeguards, both international and domestic, are discussed from the industrial viewpoint. Anti-criminal measures are considered in more detail. Areas of anti-criminal safeguards which need improvement are pointed out; they include communications, recovery force, and accounting

The Safeguards Analytical Laboratory (SAL) in the Agency's safeguards measurement system activity in 1990

International Nuclear Information System (INIS)

Bagliano, G.; Cappis, J.; Deron, S.; Parus, J.L.

1991-05-01

The IAEA applies Safeguards at the request of a Member State to whole or part of its nuclear materials. The verification of nuclear material accountability still constitutes the fundamental method of control, although sealing and surveillance procedures play an important complementary and increasing role in Safeguards. A small fraction of samples must still be analyzed at independent analytical laboratories using conventional Destructive Analytical (DA) methods of highest accuracy in order to verify that small potential biases in the declarations of the State are not masking protracted diversions of significant quantities of fissile materials. The Safeguards Analytical Laboratory (SAL) is operated by the Agency's Laboratories at Seibersdorf to provide to the Department of Safeguards and its inspectors such off-site Analytical Services, in collaboration with the Network of Analytical Laboratories (NWAL) of the Agency. In the last years SAL and the Safeguards DA Services have become more directly involved in the qualification and utilization of on-site analytical instrumentation such as K-edge X-Ray absorptiometers and quadrupole mass spectrometers. The nature and the origin of the samples analyzed, the measurements usually requested by the IAEA inspectors, the methods and the analytical techniques available at SAL and at the Network of Analytical Laboratories (NWAL) with the performances achieved during the past years are described and discussed in several documents. This report gives an evaluation compared with 1989 of the volume and the quality of the analyses reported in 1990 by SAL and by the NWAL in reply to requests of IAEA Safeguards inspectors. The reports summarizes also on-site DA developments and support provided by SAL to the Division of Safeguards Operation and special training courses to the IAEA Safeguards inspectors. 55 refs, 7 figs, 15 tabs

Reactor safeguards

CERN Document Server

Russell, Charles R

1962-01-01

Reactor Safeguards provides information for all who are interested in the subject of reactor safeguards. Much of the material is descriptive although some sections are written for the engineer or physicist directly concerned with hazards analysis or site selection problems. The book opens with an introductory chapter on radiation hazards, the construction of nuclear reactors, safety issues, and the operation of nuclear reactors. This is followed by separate chapters that discuss radioactive materials, reactor kinetics, control and safety systems, containment, safety features for water reactor

Control of ribosome formation in rat heart

International Nuclear Information System (INIS)

Russo, L.A.

1987-01-01

Diabetes of 9 days duration produced a 17% diminution in the rate of total protein synthesis in rat hearts perfused as Langendorff preparations supplied with glucose, plasma levels of amino acids, and 400 μU/ml insulin. This reduction was attributable to a decrease in efficiency of protein synthesis and total RNA content. Total messenger RNA content decreased in diabetic hearts in proportion to the reduction in total RNA. Diabetes also resulted in diminished ribosome content as reflected by the induction in total RNA. Ribosome production was investigated by monitoring incorporation of [ 3 H]phenylalanine into the proteins of cytoplasmic ribosomes. Rates of ribosome formation in diabetic hearts were as fast as control rates in the presence of insulin, and were faster than control rates in the absence of the hormone. These results indicated that ribosome content fell in diabetic hearts despite unchanged or faster rates of ribosome formation

Cryo-EM structure of the archaeal 50S ribosomal subunit in complex with initiation factor 6 and implications for ribosome evolution

DEFF Research Database (Denmark)

Greber, Basil J; Boehringer, Daniel; Godinic-Mikulcic, Vlatka

2012-01-01

additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter...... between this archaeal ribosome and eukaryotic ribosomes but are mostly absent in bacteria and in some archaeal lineages. Furthermore, the structure reveals that, in spite of highly divergent evolutionary trajectories of the ribosomal particle and the acquisition of novel functions of IF6 in eukaryotes......, the molecular binding of IF6 on the ribosome is conserved between eukaryotes and archaea. The structure also provides a snapshot of the reductive evolution of the archaeal ribosome and offers new insights into the evolution of the translation system in archaea....

Combined SAFE/SNAP approach to safeguards evaluation

International Nuclear Information System (INIS)

Engi, D.; Chapman, L.D.; Grant, F.H.; Polito, J.

1980-01-01

The scope of a safeguards evaluation model can efficiently address one of two issues: (1) global safeguards effectiveness or (2) vulnerability analysis for individual scenarios. The Safeguards Automated Facility Evaluation (SAFE) focuses on the first issue, while the Safeguards Network Analysis Procedure (SNAP) is directed towards the second. A combined SAFE/SNAP approach to the problem of safeguards evaluation is described and illustrated through an example. 4 refs

Building safeguards infrastructure

International Nuclear Information System (INIS)

McClelland-Kerr, J.; Stevens, J.

2010-01-01

Much has been written in recent years about the nuclear renaissance - the rebirth of nuclear power as a clean and safe source of electricity around the world. Those who question the nuclear renaissance often cite the risk of proliferation, accidents or an attack on a facility as concerns, all of which merit serious consideration. The integration of three areas - sometimes referred to as 3S, for safety, security and safeguards - is essential to supporting the clean and safe growth of nuclear power, and the infrastructure that supports these three areas should be robust. The focus of this paper will be on the development of the infrastructure necessary to support safeguards, and the integration of safeguards infrastructure with other elements critical to ensuring nuclear energy security

Overview of the Facility Safeguardability Analysis (FSA) Process

Energy Technology Data Exchange (ETDEWEB)

Bari, Robert A.; Hockert, John; Wonder, Edward F.; Johnson, Scott J.; Wigeland, Roald; Zentner, Michael D.

2012-08-01

Executive Summary The safeguards system of the International Atomic Energy Agency (IAEA) is intended to provide the international community with credible assurance that a State is fulfilling its safeguards obligations. Effective and cost-efficient IAEA safeguards at the facility level are, and will remain, an important element of IAEA safeguards as those safeguards evolve towards a “State-Level approach.” The Safeguards by Design (SBD) concept can facilitate the implementation of these effective and cost-efficient facility-level safeguards (Bjornard, et al. 2009a, 2009b; IAEA, 1998; Wonder & Hockert, 2011). This report, sponsored by the National Nuclear Security Administration’s Office of Nuclear Safeguards and Security, introduces a methodology intended to ensure that the diverse approaches to Safeguards by Design can be effectively integrated and consistently used to cost effectively enhance the application of international safeguards.

Regulation of chloroplast biogenesis: the immutans mutant of Arabidopsis

Energy Technology Data Exchange (ETDEWEB)

Rodermel, Steven

2015-11-16

The immutans (im) variegation mutant of Arabidopsis is an ideal model to gain insight into factors that control chloroplast biogenesis. im defines the gene for PTOX, a plastoquinol terminal oxidase that participates in control of thylakoid redox. Here, we report that the im defect can be suppressed during the late stages of plant development by gigantea (gi2), which defines the gene for GIGANTEA (GI), a central component of the circadian clock that plays a poorly-understood role in diverse plant developmental processes. imgi2 mutants are late-flowering and display other well-known phenotypes associated with gi2, such as starch accumulation and resistance to oxidative stress. We show that the restoration of chloroplast biogenesis in imgi2 is caused by a developmental-specific de-repression of cytokinin signaling that involves crosstalk with signaling pathways mediated by gibberellin (GA) and SPINDLY (SPY), a GA response inhibitor. Suppression of the plastid defect in imgi2 is likely caused by a relaxation of excitation pressures in developing plastids by factors contributed by gi2, including enhanced rates of photosynthesis and increased resistance to oxidative stress. Interestingly, the suppression phenotype of imgi can be mimicked by crossing im with the starch accumulation mutant, sex1, perhaps because sex1 utilizes pathways similar to gi. We conclude that our studies provide a direct genetic linkage between GIGANTEA and chloroplast biogenesis, and we construct a model of interactions between signaling pathways mediated by gi, GA, SPY, cytokinins, and sex1 that are required for chloroplast biogenesis.

Kinetic pathway of 40S ribosomal subunit recruitment to hepatitis C virus internal ribosome entry site.

Science.gov (United States)

Fuchs, Gabriele; Petrov, Alexey N; Marceau, Caleb D; Popov, Lauren M; Chen, Jin; O'Leary, Seán E; Wang, Richard; Carette, Jan E; Sarnow, Peter; Puglisi, Joseph D

2015-01-13

Translation initiation can occur by multiple pathways. To delineate these pathways by single-molecule methods, fluorescently labeled ribosomal subunits are required. Here, we labeled human 40S ribosomal subunits with a fluorescent SNAP-tag at ribosomal protein eS25 (RPS25). The resulting ribosomal subunits could be specifically labeled in living cells and in vitro. Using single-molecule Förster resonance energy transfer (FRET) between RPS25 and domain II of the hepatitis C virus (HCV) internal ribosome entry site (IRES), we measured the rates of 40S subunit arrival to the HCV IRES. Our data support a single-step model of HCV IRES recruitment to 40S subunits, irreversible on the initiation time scale. We furthermore demonstrated that after binding, the 40S:HCV IRES complex is conformationally dynamic, undergoing slow large-scale rearrangements. Addition of translation extracts suppresses these fluctuations, funneling the complex into a single conformation on the 80S assembly pathway. These findings show that 40S:HCV IRES complex formation is accompanied by dynamic conformational rearrangements that may be modulated by initiation factors.

Crystallization of ribosomes from Thermus thermophilus

International Nuclear Information System (INIS)

Karpova, E.A.; Serdyuk, I.N.; Tarkhovskii, Yu.S.; Orlova, E.V.; Borovyagin, V.L.

1987-01-01

An understanding of the molecular bases of the process of protein biosynthesis on the ribosome requires a knowledge of its structure with high three-dimensional resolution involving the method of x-ray crystallographic analysis. The authors report on the production of crystals of the 70S ribosomes from a new source - the highly thermophilic bacterium Thermus thermophilus. Ribosomes for crystallization were obtained from Th. thermophilus strain HB8 by two washings in buffer with high ionic strength. The ribosome preparation was investigated for homogeneity by the method of high-speed sedimentation in a buffer containing 15 mM MgCl 2 , 50 mM NH 4 Cl, and 10 MM Tris-HCl, pH 7.5. Analysis showed that the preparation if homogeneous. The same preparation was investigated for intactness of ribosomal RNA by the method of gel electrophoresis in 2.75% acrylamide 0.5% agarose gel in a buffer containing 30 mM Tris, 30 mM NaH 2 PO 4 , 10 mM EDTA, 1-2% SDS, and 6 M urea. Analysis showed that the preparation possesses intact 16S and 23S RNA. The latter did not degrade, at least in a week of exposure of the ribosomes in buffer solution at 5 0 C. The ribosome preparation had no appreciable RNase activity, which was verified by incubating 4.5 micrograms of ribosomes with 3 micrograms of 14 C-labeled 16S rRna (50 0 C, 90 min) in a buffer containing 10 mM MgCl 2 , 100 mM NH 4 Cl, and 10 mM Tris-HCl, pH/sub 20 0 / 7.5. The incubated nonhydrolyzed RNA was precipitated with 5% trichloroacetic acid and applied on a GF/C filter. The radioactivity was determined in a toluene scintillator on an LS-100C counter

Mitochondrial Cytochrome c Oxidase Biogenesis Is Regulated by the Redox State of a Heme-Binding Translational Activator.

Science.gov (United States)

Soto, Iliana C; Barrientos, Antoni

2016-02-20

Mitochondrial cytochrome c oxidase (COX), the last enzyme of the respiratory chain, catalyzes the reduction of oxygen to water and therefore is essential for cell function and viability. COX is a multimeric complex, whose biogenesis is extensively regulated. One type of control targets cytochrome c oxidase subunit 1 (Cox1), a key COX enzymatic core subunit translated on mitochondrial ribosomes. In Saccharomyces cerevisiae, Cox1 synthesis and COX assembly are coordinated through a negative feedback regulatory loop. This coordination is mediated by Mss51, a heme-sensing COX1 mRNA-specific processing factor and translational activator that is also a Cox1 chaperone. In this study, we investigated whether Mss51 hemylation and Mss51-mediated Cox1 synthesis are both modulated by the reduction-oxidation (redox) environment. We report that Cox1 synthesis is attenuated under oxidative stress conditions and have identified one of the underlying mechanisms. We show that in vitro and in vivo exposure to hydrogen peroxide induces the formation of a disulfide bond in Mss51 involving CPX motif heme-coordinating cysteines. Mss51 oxidation results in a heme ligand switch, thereby lowering heme-binding affinity and promoting its release. We demonstrate that in addition to affecting Mss51-dependent heme sensing, oxidative stress compromises Mss51 roles in COX1 mRNA processing and translation. H2O2-induced downregulation of mitochondrial translation has so far not been reported. We show that high H2O2 concentrations induce a global attenuation effect, but milder concentrations specifically affect COX1 mRNA processing and translation in an Mss51-dependent manner. The redox environment modulates Mss51 functions, which are essential for regulation of COX biogenesis and aerobic energy production.

Safeguards instrumentation: a computer-based catalog

International Nuclear Information System (INIS)

Fishbone, L.G.; Keisch, B.

1981-08-01

The information contained in this catalog is needed to provide a data base for safeguards studies and to help establish criteria and procedures for international safeguards for nuclear materials and facilities. The catalog primarily presents information on new safeguards equipment. It also describes entire safeguards systems for certain facilities, but it does not describe the inspection procedures. Because IAEA safeguards do not include physical security, devices for physical protection (as opposed to containment and surveillance) are not included. An attempt has been made to list capital costs, annual maintenance costs, replacement costs, and useful lifetime for the equipment. For equipment which is commercially available, representative sources have been listed whenever available

Safeguards instrumentation: a computer-based catalog

Energy Technology Data Exchange (ETDEWEB)

Fishbone, L.G.; Keisch, B.

1981-08-01

The information contained in this catalog is needed to provide a data base for safeguards studies and to help establish criteria and procedures for international safeguards for nuclear materials and facilities. The catalog primarily presents information on new safeguards equipment. It also describes entire safeguards systems for certain facilities, but it does not describe the inspection procedures. Because IAEA safeguards do not include physical security, devices for physical protection (as opposed to containment and surveillance) are not included. An attempt has been made to list capital costs, annual maintenance costs, replacement costs, and useful lifetime for the equipment. For equipment which is commercially available, representative sources have been listed whenever available.

Setting priorities for safeguards upgrades

International Nuclear Information System (INIS)

Al-Ayat, R.A.; Judd, B.R.; Patenaude, C.J.; Sicherman, A.

1987-01-01

This paper describes an analytic approach and a computer program for setting priorities among safeguards upgrades. The approach provides safeguards decision makers with a systematic method for allocating their limited upgrade resources. The priorities are set based on the upgrades cost and their contribution to safeguards effectiveness. Safeguards effectiveness is measured by the probability of defeat for a spectrum of potential insider and outsider adversaries. The computer program, MI$ER, can be used alone or as a companion to ET and SAVI, programs designed to evaluate safeguards effectiveness against insider and outsider threats, respectively. Setting the priority required judgments about the relative importance (threat likelihoods and consequences) of insider and outsider threats. Although these judgments are inherently subjective, MI$ER can analyze the sensitivity of the upgrade priorities to these weights and determine whether or not they are critical to the priority ranking. MI$ER produces tabular and graphical results for comparing benefits and identifying the most cost-effective upgrades for a given expenditure. This framework provides decision makers with an explicit and consistent analysis to support their upgrades decisions and to allocate the safeguards resources in a cost-effective manner

Nuclear safeguards implementations in Taiwan

International Nuclear Information System (INIS)

Hou, R-H.; Chang, C-K.; Lin, C-R.; Gone, J-K.; Chen, W-L.; Yao, D.

2006-01-01

Full text: Now with six Nuclear Power Plant (NPP) units in operation, two Advanced Boiling Water Reactor (ABWR) units under construction, and other peaceful applications of nuclear and radiation technology expanding in great pace, the Atomic Energy Council (AEC) has been focused on reactor safety regulation, radiation protection, radioactive waste administration, environmental monitoring and R and D for technology development and other civilian nuclear applications. Despite Taiwan's departure from the United Nations and therefore its family member International Atomic Energy Agency (IAEA) in 1971, Taiwan remains its commitment to the Treaty on the Non-Proliferation of Nuclear Weapons (NPT). To date, Taiwan is still part of the international nuclear safeguards system and accepts IAEA's inspections in accordance with its regulations on nuclear safeguards. In 1998, Taiwan further agreed, through exchange of letters between the AEC and IAEA, to implementation of the measures provided for in the model Protocol Additional to its safeguards agreement. In this paper, we will introduce Taiwan's nuclear safeguards history and describe some highlights of safeguards implementation in recent years, such as complementary accesses, transparency visits, remote monitoring inspections, unannounced inspections, facility attachment termination for the decommissioned facilities, and annual safeguards implementation meeting with IAEA

DNAJC21 Mutations Link a Cancer-Prone Bone Marrow Failure Syndrome to Corruption in 60S Ribosome Subunit Maturation.

Science.gov (United States)

Tummala, Hemanth; Walne, Amanda J; Williams, Mike; Bockett, Nicholas; Collopy, Laura; Cardoso, Shirleny; Ellison, Alicia; Wynn, Rob; Leblanc, Thierry; Fitzgibbon, Jude; Kelsell, David P; van Heel, David A; Payne, Elspeth; Plagnol, Vincent; Dokal, Inderjeet; Vulliamy, Tom

2016-07-07

A substantial number of individuals with bone marrow failure (BMF) present with one or more extra-hematopoietic abnormality. This suggests a constitutional or inherited basis, and yet many of them do not fit the diagnostic criteria of the known BMF syndromes. Through exome sequencing, we have now identified a subgroup of these individuals, defined by germline biallelic mutations in DNAJC21 (DNAJ homolog subfamily C member 21). They present with global BMF, and one individual developed a hematological cancer (acute myeloid leukemia) in childhood. We show that the encoded protein associates with rRNA and plays a highly conserved role in the maturation of the 60S ribosomal subunit. Lymphoblastoid cells obtained from an affected individual exhibit increased sensitivity to the transcriptional inhibitor actinomycin D and reduced amounts of rRNA. Characterization of mutations revealed impairment in interactions with cofactors (PA2G4, HSPA8, and ZNF622) involved in 60S maturation. DNAJC21 deficiency resulted in cytoplasmic accumulation of the 60S nuclear export factor PA2G4, aberrant ribosome profiles, and increased cell death. Collectively, these findings demonstrate that mutations in DNAJC21 cause a cancer-prone BMF syndrome due to corruption of early nuclear rRNA biogenesis and late cytoplasmic maturation of the 60S subunit. Copyright © 2016. Published by Elsevier Inc.

Cryo-EM Structure of the Archaeal 50S Ribosomal Subunit in Complex with Initiation Factor 6 and Implications for Ribosome Evolution

Science.gov (United States)

Greber, Basil J.; Boehringer, Daniel; Godinic-Mikulcic, Vlatka; Crnkovic, Ana; Ibba, Michael; Weygand-Durasevic, Ivana; Ban, Nenad

2013-01-01

Translation of mRNA into proteins by the ribosome is universally conserved in all cellular life. The composition and complexity of the translation machinery differ markedly between the three domains of life. Organisms from the domain Archaea show an intermediate level of complexity, sharing several additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter thermautotrophicus in complex with archaeal IF6 at 6.6 Å resolution using cryo-electron microscopy (EM). The structure provides detailed architectural insights into the 50S ribosomal subunit from a methanogenic archaeon through identification of the rRNA expansion segments and ribosomal proteins that are shared between this archaeal ribosome and eukaryotic ribosomes but are mostly absent in bacteria and in some archaeal lineages. Furthermore, the structure reveals that, in spite of highly divergent evolutionary trajectories of the ribosomal particle and the acquisition of novel functions of IF6 in eukaryotes, the molecular binding of IF6 on the ribosome is conserved between eukaryotes and archaea. The structure also provides a snapshot of the reductive evolution of the archaeal ribosome and offers new insights into the evolution of the translation system in archaea. PMID:22306461

Safeguards and Non-destructive Assay

International Nuclear Information System (INIS)

Carchon, R.; Bruggeman, M.

2001-01-01

SCK-CEN's programme on safeguards and non-destructive assay includes: (1) various activities to assure nuclear materials accountancy; (2) contributes to the implementation of Integrated Safeguards measures in Belgium and to assist the IAEA through the Belgian Support Programme; (3) renders services to internal and external customers in the field of safeguards; (4) improves passive neutron coincidence counting techniques for waste assay and safeguards verification measurements by R and D on correlation algorithms implemented via software or dedicated hardware; (5) improves gamma assay techniques for waste assay by implementing advanced scanning techniques and different correlation algorithms; and (6) develops numerical calibration techniques. Major achievements in these areas in 2000 are reported

Symposium on International Safeguards: Preparing for Future Verification Challenges

International Nuclear Information System (INIS)

2010-01-01

The purpose of the symposium is to foster dialogue and information exchange involving Member States, the nuclear industry and members of the broader nuclear non-proliferation community to prepare for future verification challenges. Topics addressed during the 2010 symposium include the following: - Supporting the global nuclear non-proliferation regime: Building support for strengthening international safeguards; Enhancing confidence in compliance with safeguards obligations; Legal authority as a means to enhance effectiveness and efficiency; Verification roles in support of arms control and disarmament. - Building collaboration and partnerships with other international forums: Other verification and non-proliferation regimes; Synergies between safety, security and safeguards regimes. - Improving cooperation between IAEA and States for safeguards implementation: Strengthening State systems for meeting safeguards obligations; Enhancing safeguards effectiveness and efficiency through greater cooperation; Lessons learned: recommendations for enhancing integrated safeguards implementation. - Addressing safeguards challenges in an increasingly interconnected world: Non-State actors and covert trade networks; Globalization of nuclear information and technology. - Preparing for the global nuclear expansion and increasing safeguards workload: Furthering implementation of the State-level concept and integrated safeguards; Information-driven safeguards; Remote data-driven safeguards inspections; Safeguards in States without comprehensive safeguards agreements. - Safeguarding advanced nuclear facilities and innovative fuel cycles: Proliferation resistance; Safeguards by design; Safeguards approaches for advanced facilities. - Advanced technologies and methodologies: For verifying nuclear material and activities; For detecting undeclared nuclear material and activities; For information collection, analysis and integration. - Enhancing the development and use of safeguards

Ribosomal history reveals origins of modern protein synthesis.

Directory of Open Access Journals (Sweden)

Ajith Harish

Full Text Available The origin and evolution of the ribosome is central to our understanding of the cellular world. Most hypotheses posit that the ribosome originated in the peptidyl transferase center of the large ribosomal subunit. However, these proposals do not link protein synthesis to RNA recognition and do not use a phylogenetic comparative framework to study ribosomal evolution. Here we infer evolution of the structural components of the ribosome. Phylogenetic methods widely used in morphometrics are applied directly to RNA structures of thousands of molecules and to a census of protein structures in hundreds of genomes. We find that components of the small subunit involved in ribosomal processivity evolved earlier than the catalytic peptidyl transferase center responsible for protein synthesis. Remarkably, subunit RNA and proteins coevolved, starting with interactions between the oldest proteins (S12 and S17 and the oldest substructure (the ribosomal ratchet in the small subunit and ending with the rise of a modern multi-subunit ribosome. Ancestral ribonucleoprotein components show similarities to in vitro evolved RNA replicase ribozymes and protein structures in extant replication machinery. Our study therefore provides important clues about the chicken-or-egg dilemma associated with the central dogma of molecular biology by showing that ribosomal history is driven by the gradual structural accretion of protein and RNA structures. Most importantly, results suggest that functionally important and conserved regions of the ribosome were recruited and could be relics of an ancient ribonucleoprotein world.

Safeguards agreements - their legal and conceptual basis

International Nuclear Information System (INIS)

Sanders, B.; Rainer, R.

1977-01-01

The application of Agency safeguards requires treaty arrangements (''Safeguards Agreements'') between the State or States concerned and the Agency. The authority for the Agency to conclude such agreements and to implement them is provided for in the Agency's Statute (Articles II, III A.5 and XII). On the basis of the statutory provisions safeguards principles and procedures have been elaborated. These have been laid down in: (a) The Agency's Safeguards System 1965, extended in 1966 and 1968 (INFCIRC/66/Rev.2); and (b) The basis for negotiating safeguards agreements with NNWS pursuant to NPT (INFCIRC/153). The verification of the undertaking by the State concerned not to use items subject to safeguards for purposes contrary to the terms of the agreement is verified through the application of various safeguards measures (design review, records, reports and inspection). Containment and surveillance measures are expected to play an increasingly important role. NPT Safeguards Agreements foresee as one of their specific features the establishment of national systems of accounting and control of nuclear material. The majority of the agreements concluded under document INFCIRC/66/Rev.2 - i.e. the non-NPT safeguards agreements - implement obligations undertaken under co-operation agreements between States for peaceful uses of nuclear energy. These agreements naturally reflect approaches adopted by the parties, in particular as to the circumstances under which safeguards should be applied. Thus, the concepts used in the non-NPT safeguards agreements and the safeguards system of document INFCIRC/66/Rev.2 which is incorporated in these agreements by reference are in continuous evolution. Document INFCIRC/66/Rev.2 continues to be supplemented in practical application and through explicit decision by the Board. The non-NPT safeguards agreements contain, besides technical safeguards provisions from document INFCIRC/66/Rev.2, and further provision for notification, inventories

Safeguards Strategy in Physical Protection System for Nuclear Installation

International Nuclear Information System (INIS)

Ade lndra B; Kasturi; Tatang Eryadi

2004-01-01

Safeguards strategy is directed at efforts of eliminating theft of nuclear materials and sabotage of nuclear installation. For achieving the above objective, it is necessary to set up safeguards strategy in physical protection of nuclear materials and installation. The safeguards strategy starts from anticipated security condition, list of thefts, planning referred to as safeguards planning. Safeguards planning are implemented in safeguards implementation, followed up then by evaluation. Results of evaluation are equipped with results of safeguards survey already developed. Safeguards' planning is made from these results and serve as guidelines for next safeguards implementation and is repeated to form a safeguard cycle. One safeguard cycle is made on a periodical basis, at least annually. (author)

On the Spatial Organization of mRNA, Plasmids, and Ribosomes in a Bacterial Host Overexpressing Membrane Proteins.

Directory of Open Access Journals (Sweden)

Lieke A van Gijtenbeek

2016-12-01

Full Text Available By using fluorescence imaging, we provide a time-resolved single-cell view on coupled defects in transcription, translation, and growth during expression of heterologous membrane proteins in Lactococcus lactis. Transcripts encoding poorly produced membrane proteins accumulate in mRNA-dense bodies at the cell poles, whereas transcripts of a well-expressed homologous membrane protein show membrane-proximal localization in a translation-dependent fashion. The presence of the aberrant polar mRNA foci correlates with cessation of cell division, which is restored once these bodies are cleared. In addition, activation of the heat-shock response and a loss of nucleoid-occluded ribosomes are observed. We show that the presence of a native-like N-terminal domain is key to SRP-dependent membrane localization and successful production of membrane proteins. The work presented gives new insights and detailed understanding of aberrant membrane protein biogenesis, which can be used for strategies to optimize membrane protein production.

Safeguards technology: present posture and future impact

International Nuclear Information System (INIS)

Keepin, G.R.

1976-01-01

With widespread and growing concern over the issues of nuclear safeguards, international nuclear trade and nuclear weapons proliferation, the full development of the world's nuclear energy potential could well depend on how effectively the strategic nuclear materials that fuel nuclear power are controlled and safeguarded. The broad U.S. program in nuclear safeguards and security is directed toward a balanced safeguards system incorporating the two major components of physical security and materials control. The current posture of modern safeguards technology, its impact on plant operations, and the key role it must play in the implementation of stringent cost-effective safeguards systems in facilities throughout the nuclear fuel cycle are outlined

A view to the new safeguards system

International Nuclear Information System (INIS)

Tsuboi, Hiroshi

2000-01-01

The Additional Protocol to the Safeguards Agreement between Japan and the IAEA entered into force on 16 December 1999. An initial declaration of the expanded information will be provided to the IAEA by next June in accordance with the Additional Protocol. In Japan the new integrated safeguards system, which strengthens the effectiveness and improves efficiency of IAEA Safeguards, is considered to be very important issue. The establishment of a permanent and universal safeguards system including application of safeguards in Nuclear Weapon States also is an important issue from the view-point of not only non-proliferation but also nuclear disarmament. Safeguards are expected to have an increasingly important role. (author)

Ribosomal Antibiotics: Contemporary Challenges

Directory of Open Access Journals (Sweden)

Tamar Auerbach-Nevo

2016-06-01

Full Text Available Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.

Safeguards training at Pacific Northwest Laboratory

International Nuclear Information System (INIS)

Dickman, D.A.

1986-10-01

Safeguarding our country's nuclear materials against theft or diversion is extremely important due to their significantly strategic value. In addition, nuclear materials also have an extremely high monetary value. The term ''safeguards'' is defined as an integrated system of physical protection, accountability, and material control measures designed to deter, prevent, detect, and respond to unauthorized possession and use of special nuclear materials. An aggressive Safeguards program, therefore, employs both good security measures and a strong material control and accountability system. For effective internal control of nuclear materials, having people qualified in the many aspects of safeguards and accountability is essential. At Pacific Northwest Laboratory (PNL), this goal is accomplished through a Laboratory-wide Safeguards Awareness Program. All PNL staff members receive a level of Safeguards training appropriate to their particular function within the Laboratory. This paper presents an overview of the unique training opportunities this topic provides and how the training goals are accomplished through the various training courses given to the staff members

The evolution of safeguards

International Nuclear Information System (INIS)

Heinonen, O.

1999-01-01

The Agency's safeguards system has demonstrated a flexibility capable of responding to the verification demands of its Member States. It is capable of safeguarding nuclear materials, facilities, equipment and non-nuclear material. The Agency is in the process of strengthening safeguards in its verification of declared activities. Since the early 1990's the Board of Governors took up the issue of strengthening measures such as inspections at undeclared locations, the early provision of design information, a system of universal reporting on nuclear material and certain nuclear-related equipment and non-nuclear material. Following the Agency's 'Programme 93+2', a major step forward was the adoption by the Board of Governors of the Additional Protocol in May 1997. This included important strengthened safeguards measures based on greater access to information and locations. A number of member states have already indicated their willingness to participate in this system by signing the Additional Protocol and this is now in the early stages of implementation for a few states. (author)

Safeguards on nuclear materials

International Nuclear Information System (INIS)

Cisar, V.; Keselica, M.; Bezak, S.

2001-01-01

The article describes the implementation of IAEA safeguards for nuclear materials in the Czech and Slovak Republics, the establishment and development of the State System of Accounting for and Control of Nuclear Material (SSAC) at the levels of the state regulatory body and of the operator, particularly at the Dukovany nuclear power plant. A brief overview of the historical development is given. Attention is concentrated on the basic concepts and legal regulation accepted by the Czech and Slovak Republics in accordance with the new approach to create a complete legislative package in the area of nuclear energy uses. The basic intention is to demonstrate the functions of the entire system, including safeguards information processing and technical support of the system. Perspectives of the Integrated Safeguards System are highlighted. The possible ways for approximation of the two national systems to the Safeguards System within the EU (EURATOM) are outlined, and the necessary regulatory and operators' roles in this process are described. (author)

Effect of primary and secondary radicals on chain breaks in ribosomal RNA in E. coli ribosomes

International Nuclear Information System (INIS)

Singh, H.; Bishop, J.

1984-01-01

It has been shown previously that, in dilute aerated solutions, ribosomes are inactivated by OH radicals and by secondary radicals produced from added alcohols (Singh and Vadasz 1983 a). In de-aerated solutions, both radicalH and e - sub(aq) also inactivate ribosomes (Singh and Vadasz 1983 b). The results of these studies and other on different systems (Adams et al. 1973, Aldrich and Cundall 1969, Dewey and Stein 1970, Masuda et al. 1971, Nabben et al. 1982, 1983, Samuni et al. 1980, Singh and Singh 1982) have shown that damage to biological systems occurs by diverse mechanisms. One of these mechanisms involves chain breaks in RNA (Pollard and Weller 1967). The purpose of this study was to determine which of the primary and secondary radicals cause chain breaks in ribosomal RNA (rRNA) within the ribosomes. (author)

Defining and Measuring Safeguards Culture

International Nuclear Information System (INIS)

Frazar, Sarah L.; Mladineo, Stephen V.

2010-01-01

In light of the shift toward State Level Evaluations and information driven safeguards, this paper offers a refined definition of safeguards culture and a set of metrics for measuring the extent to which a safeguards culture exists in a state. Where the IAEA is able to use the definition and metrics to come to a positive conclusion about the country, it may help reduce the burden on the Agency and the state.

IAEA Safeguards Information System (ISIS)

International Nuclear Information System (INIS)

1984-10-01

Publication of this technical document should serve for better understanding of the technical and functional features of the IAEA Safeguards Information System (ISIS) within the Agency, as well as in the National Systems of accounting for and control of nuclear material. It will also serve as a foundation for further development and improvement of the design and modifications of the Safeguards Information System and its services as a function of Safeguards implementation

The basis for the strengthening of safeguards

International Nuclear Information System (INIS)

Goldschmidt, P.

1999-01-01

For the past 30 years, the International Atomic Energy Agency's safeguards system has contributed to the international non-proliferation regime, by providing, inter alia, assurances regarding the peaceful uses of declared nuclear material. However, the discovery of a clandestine nuclear weapons programme in Iraq in 1991 drew world-wide attention to the need to strengthen the system to address the absence of undeclared nuclear material and activities. Efforts to strengthen the IAEA's safeguards system began in 1991 and culminated in 1997 when the IAEA's Board of Governors approved a Model Protocol Additional to IAEA Safeguards Agreements which greatly expands the legal basis and scope of IAEA safeguards. Within this strengthened system it is expected that the IAEA be able to provide assurance not only of the absence of diversion of declared nuclear material but also on the absence of undeclared nuclear material and activities. This is to be done within a safeguards system that uses an optimal combination of all safeguards measures available, thereby achieving maximum effectiveness and efficiency within the available resources. This paper will summarize the evolution of the safeguards system, describe strengthened safeguards, report on the status of implementing the strengthening measures, and outline plans for integrating all available safeguards measures. (author)

Information-Driven Safeguards: A Country Officer's Perspective

International Nuclear Information System (INIS)

Gyane, E.

2010-01-01

Since the transition from 'traditional' to strengthened safeguards, the evaluation and analysis of information has played an increasingly important role in the Agency's safeguards activities. During the State evaluation process, the Agency utilizes all available information for drawing credible safeguards conclusions. Besides State declared information and data gathered during inspections, a large number of information sources are reviewed for any indications of safeguards relevance. The State level approach - in contrast to the facility-based approach under traditional safeguards - considers the acquisition paths available to a State and adjusts safeguards intensity accordingly. An additional protocol widens the information base available to the Agency for analysis and evaluation and it extends the Agency's access rights in the field. The use of information for determining safeguards activities is often referred to as 'information-driven safeguards'. Country officers are inspectors in the Department of Safeguards Operations Divisions who are responsible for States and thus form the base of the Agency's information chain. The information-driven safeguards approach has led to a significant change in the role of inspector country officers: While the verification of declared nuclear material remains the cornerstone of the IAEA Safeguards System, country officers are now not only expected to be knowledgeable about the inspection-related aspects in their countries. They also need to act on information on their States coming from a variety of sources on an ongoing basis, in order to identify proliferation indicators at an early stage. Country officers thus analyse developments in their States as well as their States' relations with other States. They review scientific literature for research that could potentially be of safeguards relevance. They observe their States' nuclear facilities from satellite imagery. They evaluate reports on nuclear trade between their States

International inspection activity impacts upon DOE safeguards requirements

International Nuclear Information System (INIS)

Zack, N.R.

1995-01-01

The US has placed certain special nuclear materials declared excess to their strategic needs under international safeguards through the International Atomic Energy Agency (IAEA). This Presidential initiative has obligated materials at several Department of Energy (DOE) facilities for these safeguards activities to demonstrate the willingness of the US to ban production or use of nuclear materials outside of international safeguards. However, IAEA inspection activities generally tend to be intrusive in nature and are not consistent with several domestic safeguards procedures implemented to reduce worker radiation exposures and increase the cost-effectiveness and efficiency of accounting for and storing of special nuclear materials. To help identify and provide workable solutions to these concerns, the Office of Safeguards and Security has conducted a program to determine possible changes to the DOE safeguards and security requirements designed to help facilities under international safeguards inspections more easily comply with domestic safeguards goals during international inspection activities. This paper will discuss the impact of international inspection activities on facility safeguards operations and departmental safeguards procedures and policies

Cholesterol in myelin biogenesis and hypomyelinating disorders.

Science.gov (United States)

Saher, Gesine; Stumpf, Sina Kristin

2015-08-01

The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids. Copyright © 2015 Elsevier B.V. All rights reserved.

Safeguards management inspection procedures

International Nuclear Information System (INIS)

Barth, M.J.; Dunn, D.R.

1984-08-01

The objective of this inspection module is to independently assess the contributions of licensee management to overall safeguards systems performance. The inspector accomplishes this objective by comparing the licensee's safeguards management to both the 10 CFR, parts 70 and 73, requirements and to generally accepted management practices. The vehicle by which this comparison is to be made consists of assessment questions and key issues which point the inspector to areas of primary concern to the NRC and which raise additional issues for the purpose of exposing management ineffectiveness. Further insight into management effectiveness is obtained through those assessment questions specifically directed toward the licensee's safeguards system performance. If the quality of the safeguards is poor, then the inspector should strongly suspect that management's role is ineffective and should attempt to determine management's influence (or lack thereof) on the underlying safeguards deficiencies. (The converse is not necessarily true, however.) The assessment questions in essence provide an opportunity for the inspector to identify, to single out, and to probe further, questionable management practices. Specific issues, circumstances, and concerns which point to questionable or inappropriate practices should be explicitly identified and referenced against the CFR and the assessment questions. The inspection report should also explain why the inspector feels certain management practices are poor, counter to the CFR, and/or point to ineffecive management. Concurrent with documenting the inspection results, the inspector should provide recommendations for alleviating observed management practices that are detrimental to effective safeguards. The recommendations could include: specific changes in the practices of the licensee, followup procedures on the part of NRC, and proposed license changes

Safeguards approach for conditioning facility for spent fuel

International Nuclear Information System (INIS)

Younkin, J.M.; Barham, M.; Moran, B.W.

1999-01-01

A safeguards approach has been developed for conditioning facilities associated with the final disposal of spent fuel in geologic repositories. The proposed approach is based on a generic conditioning facility incorporating common features of conditioning facility designs currently proposed. The generic facility includes a hot cell for consolidation of spent fuel pins and repackaging of spent fuel items such as assemblies and cans of pins. The consolidation process introduces safeguards concerns which have not previously been addressed in traditional safeguards approaches. In developing the safeguards approach, diversion of spent fuel was assessed in terms of potential target items, operational activities performed on the items, containment of the items, and concealment activities performed on the items. The combination of these factors defines the potential diversion pathways. Diversion pathways were identified for spent fuel pellets, pins, assemblies, canisters, and casks. Diversion activities provide for opportunities of detection along the diversion paths. Potential detection methods were identified at several levels of diversion activities. Detection methods can be implemented through safeguards measures. Safeguards measures were proposed for each of the primary safeguards techniques of design information verification (DIV), containment and surveillance (C/S), and material accountancy. Potential safeguards approaches were developed by selection of appropriate combinations of safeguards measures. For all candidate safeguards approaches, DIV is a fundamental component. Variations in the approaches are mainly in the degree of C/S measures and in the types and numbers of material accountancy verification measures. The candidate safeguards approaches were evaluated toward the goal of determining a model safeguards approach. This model approach is based on the integrated application of selected safeguards measures to use International Atomic Energy Agency resources

The international safeguards profession

International Nuclear Information System (INIS)

Sanders, K.E.

1986-01-01

The International Atomic Energy Agency has established a staff of safeguards professionals who are responsible for carrying out on-site inspections to determine compliance with international safeguards agreements. By IAEA Statute, the paramount consideration in recruiting IAEA staff is to secure employees of the highest standards of efficiency, technical competence, and integrity. An analysis of the distribution of professionals in the IAEA Department of Safeguards has revealed some interesting observations regarding the distribution of grade levels, age, time in service, gender, and geographical origin. Following several earlier studies performed by contractors for ACDA, U.S. efforts have been undertaken to attract and better prepare candidates for working at the IAEA

Combined SAFE/SNAP approach to safeguards evaluation

International Nuclear Information System (INIS)

Engi, D.; Chapman, L.D.; Grant, F.H.; Polito, J.

1980-01-01

Generally, the scope of a safeguards evaluation model can efficiently address one of two issues, (1) global safeguards effectiveness, or (2) vulnerability analysis for individual scenarios. The Safeguards Automated Facility Evaluation (SAFE) focuses on (1) while the Safeguards Network Analysis Procedure (SNAP) is directed at (2). SAFE addresses (1) in that it considers the entire facility, i.e., the composite system of hardware and human components, in one global analysis. SNAP addresses (2) by providing a safeguards modeling symbology sufficiently flexible to represent quite complex scenarios from the standpoint of hardware interfaces while also accounting for a rich variety of human decision making. A combined SAFE/SNAP approach to the problem of safeguards evaluation is described and illustrated through an example

Cholesterol and myelin biogenesis.

Science.gov (United States)

Saher, Gesine; Simons, Mikael

2010-01-01

Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

State-wide performance criteria for international safeguards

International Nuclear Information System (INIS)

Budlong-Sylvester, K.W.; Pilat, Joseph F.; Stanbro, W.D.

2001-01-01

Traditionally, the International Atomic Energy Agency (IAEA) has relied upon prescriptive criteria to guide safeguards implementation. The prospect of replacing prescriptive safeguards criteria with more flexible performance criteria would constitute a structural change in safeguards and raises several important questions. Performance criteria imply that while safeguards goals will be fixed, the means of attaining those goals will not be explicitly prescribed. What would the performance objectives be under such a system? How would they be formulated? How would performance be linked to higher level safeguards objectives? How would safeguards performance be measured State-wide? The implementation of safeguards under performance criteria would also signal a dramatic change in the manner the Agency does business. A higher degree of flexibility could, in principle, produce greater effectiveness and efficiency, but would come with a need for increased Agency responsibility in practice. To the extent that reliance on prescriptive criteria decreases, the burden of justifying actions and ensuring their transparency will rise. Would there need to be limits to safeguards implementation? What would be the basis for setting such limits? This paper addresses these and other issues and questions relating to both the formulation and the implementation of performance-based criteria.

The IAEA safeguards information system

International Nuclear Information System (INIS)

Gmelin, W.R.; Parsick, R.

1976-01-01

The IAEA safeguards under the Non-Proliferation Treaty is meant to follow the model agreement developed by the Safeguards Committee in 1970 and formulated in document INFCIRC/153, which contains provisions that Member States, having concluded Safeguards Agreements with the Agency, should provide design information and reports on initial inventories, changes in the inventories and material balances in respect of each nuclear facility and material balance area for all nuclear materials subject to safeguards. The Agency, on the other hand, should establish and maintain an accountancy system which would provide the data on the location and the movements of all nuclear material subject to safeguards on the basis of the reported information and information obtained during inspections in order to support the Agency's verification activities in the field, to enable the preparation of safeguards statements and to adjust the inspection intensity. Following these requirements, a computer-based information system has been developed and is being implemented and used routinely for input manipulations and queries on a limited scale. This information system comprises two main parts: Part 1 for processing the information as provided by the States, and Part 2 (still under development) for processing the inspection data obtained during verification. This paper describes the characteristics of the Agency information system for processing data under the Non-Proliferation Treaty as well as recent operational experience. (author)

Introduction to nuclear material safeguards

International Nuclear Information System (INIS)

Kuroi, Hideo

1986-01-01

This article is aimed at outlining the nuclear material safeguards. The International Atomic Energy Agency (IAEA) was established in 1957 and safeguards inspection was started in 1962. It is stressed that any damage resulting from nuclear proliferation would be triggered by a human intentional act. Various measures have been taken by international societies and nations, of which the safeguards are the only means which relay mainly on technical procedures. There are two modes of diversing nuclear materials to military purposes. One would be done by national intension while the other by indivisulas or expert groups, i.e., sub-national intention. IAEA is responsible for the prevention of diversification by nations, for which the international safeguards are being used. Measures against the latter mode of diversification are called nuclear protection, for which each nation is responsible. The aim of the safeguards under the Nonproliferation Treaty is to detect the diversification of a significant amount of nuclear materials from non-military purposes to production of nuclear explosion devices such as atomic weapons or to unidentified uses. Major technical methods used for the safeguards include various destructive and non-destructive tests as well as containment and monitoring techniques. System techniques are to be employed for automatic containment and monitoring procedures. Appropriate nuclear protection system techniques should also be developed. (Nogami, K.)

Next Generation Safeguards Initiative: 2010 and Beyond

International Nuclear Information System (INIS)

Whitney, J.M.; LaMontagne, S.; Sunshine, A.; Lockwood, D.; Peranteau, D.; Dupuy, G.

2010-01-01

Strengthening the international safeguards system is a key element of the U.S. non-proliferation policy agenda as evidenced by President Obama's call for more 'resources and authority to strengthen international inspections' in his April 2009 Prague speech. Through programs such as the recently-launched Next Generation Safeguards Initiative (NGSI) and the long standing U.S. Program of Technical Assistance to IAEA Safeguards, the United States is working to implement this vision. The U.S. Department of Energy's National Nuclear Security Administration launched NGSI in 2008 to develop the policies, concepts, technologies, expertise, and international safeguards infrastructure necessary to strengthen and sustain the international safeguards system as it evolves to meet new challenges. Following a successful 2009, NGSI has made significant progress toward these goals in 2010. NGSI has recently completed a number of policy studies on advanced safeguards concepts and sponsored several workshops, including a second international meeting on Harmonization of International Safeguards Infrastructure Development in Vienna. The program is also continuing multi-year projects to investigate advanced non-destructive assay techniques, enhance recruitment and training efforts, and strengthen international cooperation on safeguards. In December 2010, NGSI will host the Third Annual International Meeting on International Safeguards in Washington, DC, which will draw together key stakeholders from government, the nuclear industry, and the IAEA to further develop and promote a common understanding of Safeguards by Design principles and goals, and to identify opportunities for practical application of the concept. This paper presents a review of NGSI program activities in 2010 and previews plans for upcoming activities. (author)

Integrated Safeguards Information System for Japan (ISIS-J) - Strengthening SSAC for Enhancing Confidence in Compliance with Safeguards Obligations -

International Nuclear Information System (INIS)

Iso, S.; Nishiyama, N.; Kumakura, S.; Takizawa, K.; Yoshida, H.; Kobayashi, I.; Kikuchi, M.; Kimura, N.; Matsubara, T.; Yatsu, S.

2010-01-01

IAEA has stated the importance of enhancing cooperation with SSAC. Therefore, Japan has developed the Integrated Safeguards Information System for enhancing confidence in compliance with the national obligation under the safeguards agreement and the additional protocol. Japan already established the National System including national inspections with NDA and DA verification functions and evaluation of data obtained from national inspections and has maintained the National System of safeguards as a SSAC in accordance with the safeguards agreement. Nuclear Material Control Center (NMCC) is engaged in national safeguards activities as designated organization of national inspectorate and information treatment including safeguards data analysis. Recently, purpose of IAEA's safeguards activities may shift to detection of proliferation based on plausible proliferation paths from detection of diversion by certain material accountancy measures. Major safeguards activities of IAEA have changed from quantitative aspects to qualitative them. As supplements for declining the quantitative measures such as the activities based on the safeguards criteria the IAEA would expect the SSAC functions for maintaining the activities of quantitative manners. Japan believes that the State's responsibility for enhancing cooperation between the National System and the IAEA must assure the confidence level of correctness and completeness of the State declarations with accurate and precise accountability as findings from SSAC. Japan has started the development of the strengthened and autonomous national system namely the Integrated safeguards Information System for Japan (ISIS-J) in order to fulfil our responsibility. Japan would seek to improve quality of information including nuclear material accounting data as well as expanded declaration relevant to nuclear activities in Japan, and to increase abilities for explaining safeguards relevant events in Japan. The enhanced findings could include

Nucleolar remodeling in nuclear transfer embryos

DEFF Research Database (Denmark)

Laurincik, Jozef; Maddox-Hyttel, Poul

2007-01-01

Transcription of the ribosomal RNA (rRNA) genes occurs in the nucleolus and results in ribosome biogenesis. The rRNA gene activation and the associated nucleolus formation may be used as a marker for the activation of the embryonic genome in mammalian embryos and, thus serve to evaluate the devel......Transcription of the ribosomal RNA (rRNA) genes occurs in the nucleolus and results in ribosome biogenesis. The rRNA gene activation and the associated nucleolus formation may be used as a marker for the activation of the embryonic genome in mammalian embryos and, thus serve to evaluate...... nucleoli are not apparent until the 5th cell cycle, whereas in somatic cell nuclear transfer embryos the functional nucleoli emerge already during the 3rd cell cycle. Intergeneric reconstructed embryos produced by the fusion of bovine differentiated somatic cell to a nonactivated ovine cytoplast fail...

Network adaptable information systems for safeguard applications

International Nuclear Information System (INIS)

Rodriguez, C.; Burczyk, L.; Chare, P.; Wagner, H.

1996-01-01

While containment and surveillance systems designed for nuclear safeguards have greatly improved through advances in computer, sensor, and microprocessor technologies, the authors recognize the need to continue the advancement of these systems to provide more standardized solutions for safeguards applications of the future. The benefits to be gained from the use of standardized technologies are becoming evident as safeguard activities are increasing world-wide while funding of these activities is becoming more limited. The EURATOM Safeguards Directorate and Los Alamos National Laboratory are developing and testing advanced monitoring technologies coupled with the most efficient solutions for the safeguards applications of the future

IAEA safeguards - a 1988 perspective

International Nuclear Information System (INIS)

Jennekens, J.

1988-01-01

The problem of IAEA safeguards as regards its perspectives for 1988 is discussed. The necessity of balancing between safeguards measures required for the timely detection of nuclear material diversion to military purposes and measures to prove the absence of diversion is stated. Accurately working safeguards system aimed at the provision of nondiversion can include, as an accompanying component, any deterrence element required. Such a system will be more expensive than any other altrenatives but it will undoubtly be more suitable and accepatble

Safeguards in the Slovak Republic

International Nuclear Information System (INIS)

Vaclav, J.

2010-01-01

The former Czechoslovakia acceded to the Non-Proliferation Treaty in 1968. Based on requirements of the Safeguard Agreement the State System of Accounting for and Control of nuclear material has been established. After dissolution of Czechoslovakia the Slovak Republic succeeded to the Safeguards Agreement. As a regulator the Nuclear Regulatory Authority of the Slovak Republic (UJD) has been constituted. After European Union (EU) accession EU legislation became valid in the Slovak republic. Atomic Law No. 541/2004 Coll. on Peaceful Use of Nuclear Energy adopts this legislation. In the frame of strengthening the IAEA safeguards an implementation of the Protocol Additional became actual. The Protocol Additional was signed by the government of the Slovak Republic in September 1999. On 1 December 2005 safeguards agreement INFCIRC/193 including the relevant Additional Protocol entered into force. As an instrument supporting non-proliferation of nuclear weapons a control of export/import of nuclear material, nuclear related and dual-use material following the EC regulation 428/2009 of 5 May 2009 setting up a Community regime for the control of exports, transfer, brokering and transit of dual use items. The execution of accountancy and control of nuclear material inspection activities has been considerably influenced by the implementation of integrated safeguards, implemented in the Slovak Republic on 1 September 2009. The aim of mentioned integrated safeguards regime is to decrease the amount and difficulty of inspections. At the same time the possibility of accountancy and control of nuclear material inspections announced 24 hours in advance took effect. The execution of Protocol Additional inspections remains the same. Additionally to international safeguards system UJD has kept the national safeguards system which observes all nuclear material on the territory of the Slovak Republic. The government of the Slovak Republic plays active role within activities of the NSG

Microprocessor Activity Controls Differential miRNA Biogenesis In Vivo

Directory of Open Access Journals (Sweden)

Thomas Conrad

2014-10-01

Full Text Available In miRNA biogenesis, pri-miRNA transcripts are converted into pre-miRNA hairpins. The in vivo properties of this process remain enigmatic. Here, we determine in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. On the basis of differential processing efficiencies, we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression.

Achieving the Benefits of Safeguards by Design

International Nuclear Information System (INIS)

Bjornard, Trond; Bean, Robert; Hebditch, David; Morgan, Jim; Meppen, Bruce; DeMuth, Scott; Ehinger, Michael; Hockert, John

2008-01-01

The overarching driver for developing a formalized process to achieve safeguards by design is to support the global growth of nuclear power while reducing 'nuclear security' risks. This paper discusses an institutional approach to the design process for a nuclear facility, for designing proliferation resistance, international safeguards and U.S. national safeguards and security into new nuclear facilities. In the United States, the need exists to develop a simple, concise, formalized, and integrated approach for incorporating international safeguards and other non-proliferation considerations into the facility design process. An effective and efficient design process is one which clearly defines the functional requirements at the beginning of the project and provides for the execution of the project to achieve a reasonable balance among competing objectives in a cost effective manner. Safeguards by Design is defined as 'the integration of international and national safeguards, physical security and non-proliferation features as full and equal partners in the design process of a nuclear energy system or facility,' with the objective to achieve facilities that are intrinsically more robust while being less expensive to safeguard and protect. This Safeguards by Design process has been developed such that it: (sm b ullet) Provides improved safeguards, security, and stronger proliferation barriers, while reducing the life cycle costs to the operator and regulatory agencies, (sm b ullet) Can be translated to any international context as a model for nuclear facility design, (sm b ullet) Fosters a culture change to ensure the treatment of 'nuclear security' considerations as 'full and equal' partners in the design process, (sm b ullet) Provides a useful tool for the project manager responsible for the design, construction, and start-up of nuclear facilities, and (sm b ullet) Addresses the key integration activities necessary to efficiently incorporate International Atomic

Crosstalk between the nucleolus and the DNA damage response.

Science.gov (United States)

Ogawa, L M; Baserga, S J

2017-02-28

Nucleolar function and the cellular response to DNA damage have long been studied as distinct disciplines. New research and a new appreciation for proteins holding multiple functional roles, however, is beginning to change the way we think about the crosstalk among distinct cellular processes. Here, we focus on the crosstalk between the DNA damage response and the nucleolus, including a comprehensive review of the literature that reveals a role for conventional DNA repair proteins in ribosome biogenesis, and conversely, ribosome biogenesis proteins in DNA repair. Furthermore, with recent advances in nucleolar proteomics and a growing list of proteins that localize to the nucleolus, it is likely that we will continue to identify new DNA repair proteins with a nucleolar-specific role. Given the importance of ribosome biogenesis and DNA repair in essential cellular processes and the role that they play in diverse pathologies, continued elucidation of the overlap between these two disciplines will be essential to the advancement of both fields and to the development of novel therapeutics.

Mitochondrial cytochrome c biogenesis: no longer an enigma.

Science.gov (United States)

Babbitt, Shalon E; Sutherland, Molly C; San Francisco, Brian; Mendez, Deanna L; Kranz, Robert G

2015-08-01

Cytochromes c (cyt c) and c1 are heme proteins that are essential for aerobic respiration. Release of cyt c from mitochondria is an important signal in apoptosis initiation. Biogenesis of c-type cytochromes involves covalent attachment of heme to two cysteines (at a conserved CXXCH sequence) in the apocytochrome. Heme attachment is catalyzed in most mitochondria by holocytochrome c synthase (HCCS), which is also necessary for the import of apocytochrome c (apocyt c). Thus, HCCS affects cellular levels of cyt c, impacting mitochondrial physiology and cell death. Here, we review the mechanisms of HCCS function and the roles of heme and residues in the CXXCH motif. Additionally, we consider concepts emerging within the two prokaryotic cytochrome c biogenesis pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pickering safeguards: a preliminary analysis

International Nuclear Information System (INIS)

Todd, J.L.; Hodgkinson, J.G.

1977-05-01

A summary is presented of thoughts relative to a systems approach for implementing international safeguards. Included is a preliminary analysis of the Pickering Generating Station followed by a suggested safeguards system for the facility

Overcoming Safeguards Challenges

International Nuclear Information System (INIS)

Henriques, Sasha

2011-01-01

The focus of the 2010 IAEA International Safeguards Symposium was how best, from a technical perspective, to prepare for future verification challenges during this time of change. By bringing together the leading experts in the field from across the world, this symposium provided an opportunity for stakeholders to explore possible solutions in support of the IAEA's nuclear verification mission, and to identify areas where the different stakeholders in the safeguards business can help address these challenges

Nucleolar Proteome Analysis and Proteasomal Activity Assays Reveal a Link between Nucleolus and 26S Proteasome in A. thaliana

Science.gov (United States)

Montacié, Charlotte; Durut, Nathalie; Opsomer, Alison; Palm, Denise; Comella, Pascale; Picart, Claire; Carpentier, Marie-Christine; Pontvianne, Frederic; Carapito, Christine; Schleiff, Enrico; Sáez-Vásquez, Julio

2017-01-01

In all eukaryotic cells, the nucleolus is functionally and structurally linked to rRNA synthesis and ribosome biogenesis. This compartment contains as well factors involved in other cellular activities, but the functional interconnection between non-ribosomal activities and the nucleolus (structure and function) still remains an open question. Here, we report a novel mass spectrometry analysis of isolated nucleoli from Arabidopsis thaliana plants using the FANoS (Fluorescence Assisted Nucleolus Sorting) strategy. We identified many ribosome biogenesis factors (RBF) and proteins non-related with ribosome biogenesis, in agreement with the recognized multi-functionality of the nucleolus. Interestingly, we found that 26S proteasome subunits localize in the nucleolus and demonstrated that proteasome activity and nucleolus organization are intimately linked to each other. Proteasome subunits form discrete foci in the disorganized nucleolus of nuc1.2 plants. Nuc1.2 protein extracts display reduced proteasome activity in vitro compared to WT protein extracts. Remarkably, proteasome activity in nuc1.2 is similar to proteasome activity in WT plants treated with proteasome inhibitors (MG132 or ALLN). Finally, we show that MG132 treatment induces disruption of nucleolar structures in WT but not in nuc1.2 plants. Altogether, our data suggest a functional interconnection between nucleolus structure and proteasome activity. PMID:29104584

Safeguarding arms control

International Nuclear Information System (INIS)

Flanagan, S.J.

1988-01-01

This essay reviews the evolution of various safeguards concepts associated with U.S. Soviet arms control negotiations over the past twenty-five years. It explore in some detail the origins, nature, and effectiveness of the safeguards packages associated with six agreements: the Limited Test Ban Treaty (1963), the SALT I Interim Agreement (1972), the Anti-Ballistic Missile (ABM) Treaty (1972), the Threshold Test Ban Treaty (1974), the Peaceful Nuclear Explosions Treaty (1976) and the SALT II Treaty (1979). Finally, the implications of this historical record for developing future nuclear and conventional arms control accords and for shoring up existing pacts, such as the ABM Treaty, are assessed with a view towards practicable prescriptions for Western policymakers. The treaty eliminating intermediate-range nuclear forces (INF) incorporates several verification safeguards, and it is very likely that analogous measures would be attached to any accord constraining conventional forces in Europe

Safeguards Export-Import Training: Adapting to Changes in the Department of Safeguards Over 6 Years of Experience

International Nuclear Information System (INIS)

Chatelus, R.; ); Crete, J.-M.; Schot, P.-M.; Hushbeck, E.C.; Heine, P.

2015-01-01

Safeguards relevant information encompasses information available to the Agency in exercising its rights and fulfiling its obligations under relevant safeguards agreement(s). It includes information relating to nuclear or nuclear related trade like international transfers of nuclear material, or export (or import upon request by the Agency) of specified equipment described in annex 2 of the Additional Protocol. It may also include information provided by States on a voluntary basis. In 2005, the General Conference (see GC(49)/RES/13) encouraged the provision of information on procurement enquiries, export denials and other nuclear related information. Objectively and independently assessing this information and combining it with other Safeguards data and knowledge requires relevant expertise and well defined processes. Since 2008, the bi-annual Export-Import (EXIM) Training Workshop, jointly run by the IAEA Department of Safeguards and the U.S. Department of Energy, enables SG staff to develop competencies required for collecting, processing and drawing objective conclusions in this area. Over the years, more than 150 SG staff have been exposed to technical information on relevant non-nuclear material and equipment, trade data from different origins, analytical processes, and exercises to use this knowledge in realistic safeguards work scenarios. The EXIM training has also been an opportunity to develop analytical best practices and explore how this analytical work finds it place in the verification process. The paper describes the background and purpose of the EXIM training, how it helps Safeguards to independently collect and analyze relevant trade information to fulfil its obligations. It also touches on the lessons learned from six years of training experience, observing how the Department of Safeguards develops and implements structured processes to collect, process and evaluate safeguards relevant trade information, in order to establish findings and draw

Optimizing the IAEA safeguards system

International Nuclear Information System (INIS)

Drobysz, Sonia; Sitt, Bernard

2011-09-01

During the 2010 Non-Proliferation Treaty Review Conference, States parties recognized that the Additional Protocol (AP) provides increased confidence about the absence of undeclared nuclear material and activities in a State as a whole. They agreed in action 28 of the final document to encourage 'all States parties that have not yet done so to conclude and bring into force an AP as soon as possible and to implement them provisionally pending their entry into force'. Today, 109 out of 189 States parties to the NPT have brought an AP in force. The remaining outliers have not yet done so for three types of reasons: they do not clearly understand what the AP entails; when they do, they refuse to accept new non-proliferation obligations either on the ground of lack of progress in the realm of disarmament, or simply because they are not ready to bear the burden of additional safeguards measures. Strong incentives are thus needed in order to facilitate universalization of the AP. While external incentives would help make the AP a de facto norm and encourage its conclusion by reducing the deplored imbalanced implementation of non-proliferation and disarmament obligations, internal incentives developed by the Agency and its member States can also play an important role. In this respect, NPT States parties recommended in action 32 of the Review Conference final document 'that IAEA safeguards should be assessed and evaluated regularly. Decisions adopted by the IAEA policy bodies aimed at further strengthening the effectiveness and improving the efficiency of IAEA safeguards should be supported and implemented'. The safeguards system should therefore be optimized: the most effective use of safeguards measures as well as safeguards human, financial and technical resources would indeed help enhance the acceptability and even attractiveness of the AP. Optimization can be attractive for States committed to a stronger verification regime independently from other claims, but still

The European Safeguards Research and Development Association Addresses Safeguards and Nonproliferation

International Nuclear Information System (INIS)

Janssens-Maenhout, Greet; Kusumi, R.; Daures, Pascal A.; Janssens, Willem; Dickman, Deborah A.

2010-01-01

The renaissance of efforts to expand the use of nuclear energy requires the parallel development of a renewed and more sophisticated work force. Growth in the nuclear sector with high standard of safety, safeguards and security requires skilled staff for design, operations, inspections etc. High-quality nuclear technology educational programs are diminished from past years, and the ability of universities to attract students and to meet future staffing requirements of the nuclear industry is becoming seriously compromised. Thus, education and training in nuclear engineering and sciences is one of the cornerstones for the nuclear sector. Teaching in the nuclear field still seems strongly influenced by national history but it is time to strengthen resources and collaborate. Moreover with the current nuclear security threats it becomes critical that nuclear technology experts master the basic principles not only of safety, but also of nuclear safeguards, nonproliferation and nuclear security. In Europe the European Nuclear Education Network (ENEN) Association has established the certificate 'European Master of Science in Nuclear Engineering (EMSNE)' as the classic nuclear engineering program covering reactor operation and nuclear safety. However, it does not include courses on nonproliferation, safeguards, or dual-use technologies. The lack of education in nuclear safeguards was tackled by the European Safeguards Research and Development Association (ESARDA), through development and implementation of safeguards course modules. Since 2005 the ESARDA Working Group, called the Training and Knowledge Management Working Group, (TKMWG) has worked with the Joint Research Centre (JRC) in Ispra, Italy to organize a Nuclear Safeguards and Nonproliferation course. This five-day course is held each spring at the JRC, and continues to show increasing interest as evidenced by the positive responses of international lecturers and students. The standard set of lectures covers a broad

Safeguards Network Analysis Procedure (SNAP): overview

International Nuclear Information System (INIS)

Chapman, L.D; Engi, D.

1979-08-01

Nuclear safeguards systems provide physical protection and control of nuclear materials. The Safeguards Network Analysis Procedure (SNAP) provides a convenient and standard analysis methodology for the evaluation of physical protection system effectiveness. This is achieved through a standard set of symbols which characterize the various elements of safeguards systems and an analysis program to execute simulation models built using the SNAP symbology. The outputs provided by the SNAP simulation program supplements the safeguards analyst's evaluative capabilities and supports the evaluation of existing sites as well as alternative design possibilities. This paper describes the SNAP modeling technique and provides an example illustrating its use

Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients

OpenAIRE

Gu, Bai-Wei; Apicella, Marisa; Mills, Jason; Fan, Jian-Meng; Reeves, Dara A.; French, Deborah; Podsakoff, Gregory M.; Bessler, Monica; Mason, Philip J.

2015-01-01

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by the presence of short telomeres at presentation. Mutations in ten different genes, whose products are involved in the telomere maintenance pathway, have been shown to cause DC. The X-linked form is the most common form of the disease and is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for the assembly and stability of telomerase and is also involved in ribosom...

Nuclear safeguards technology 1986

International Nuclear Information System (INIS)

1987-01-01

This publication presents the results of the sixth in a series of international symposia on nuclear material safeguards. Development efforts related to safeguards for reprocessing plants constituted over twenty per cent of the programme. Other papers present results of over four years of field testing of near real time material accountancy at a plant in Japan, and results for a lesser period of time at a plant in Scotland. Papers reporting work on destructive and non-destructive measurement procedures or equipment constituted another thirty per cent of the programme, more if measurements in reprocessing and poster presentations are included. In honour of the tenth anniversary of the founding of the Safeguards Analytical Laboratory, two sessions were devoted to a review of destructive analytical measurement procedures. Some subjects received only minor attention during the Symposium. The statistical theory of random sampling, safeguards for uranium enrichment plants, material accountancy systems and several other topics appear only incidentally in the programme, but primarily because there are few remaining problems, not because there is little remaining interest

IAEA symposium on international safeguards. Extended synopses

International Nuclear Information System (INIS)

1997-10-01

The most important subjects treated in 188 papers presented by the participants from member state and IAEA Safeguards Inspectors at the Symposium were as follows: implementation of IAEA safeguards; national support programs to the IAEA safeguards; experiences in application of safeguard monitoring devices; improved methods for verification of plutonium; highly enriched uranium; surveillance of spent fuel storage facilities, reprocessing plants, fuel fabrication plants; excess weapon grade plutonium and other fissile materials

AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74

Energy Technology Data Exchange (ETDEWEB)

Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami, E-mail: nagahama@my-pharm.ac.jp

2015-11-20

Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used a proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.

AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74

International Nuclear Information System (INIS)

Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami

2015-01-01

Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used a proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.

Safeguards training at Pacific Northwest Laboratory

International Nuclear Information System (INIS)

Dickman, D.A.

1988-01-01

In recent years considerable attention has been given to upgrading security education programs at facilities across the country. At Pacific Northwest Laboratory (PNL), a Laboratory-wide Safeguard Awareness Training Program has been established in order to raise the cognizance of the entire staff with regard to safeguards issues and concerns. This aggressive safeguards program involves a strong interface of physical security measure and material control and accountability systems. Within PNL, four distinct audiences were defined and a needs assessment analysis performed for each to determine specific training requirements. The target audiences identified were: material balance area (MBA) custodians, managers of material balance areas, material handlers, and new employees. Five safeguards training courses were created to meet the needs of those audiences. This paper discusses the development of the Safeguards Awareness Program at PNL and its benefits to the Laboratory

Safeguards Guidance Document for Designers of Commercial Nuclear Facilities: International Nuclear Safeguards Requirements and Practices For Uranium Enrichment Plants

Energy Technology Data Exchange (ETDEWEB)

Robert Bean; Casey Durst

2009-10-01

This report is the second in a series of guidelines on international safeguards requirements and practices, prepared expressly for the designers of nuclear facilities. The first document in this series is the description of generic international nuclear safeguards requirements pertaining to all types of facilities. These requirements should be understood and considered at the earliest stages of facility design as part of a new process called “Safeguards-by-Design.” This will help eliminate the costly retrofit of facilities that has occurred in the past to accommodate nuclear safeguards verification activities. The following summarizes the requirements for international nuclear safeguards implementation at enrichment plants, prepared under the Safeguards by Design project, and funded by the U.S. Department of Energy (DOE) National Nuclear Security Administration (NNSA), Office of NA-243. The purpose of this is to provide designers of nuclear facilities around the world with a simplified set of design requirements and the most common practices for meeting them. The foundation for these requirements is the international safeguards agreement between the country and the International Atomic Energy Agency (IAEA), pursuant to the Treaty on the Non-proliferation of Nuclear Weapons (NPT). Relevant safeguards requirements are also cited from the Safeguards Criteria for inspecting enrichment plants, found in the IAEA Safeguards Manual, Part SMC-8. IAEA definitions and terms are based on the IAEA Safeguards Glossary, published in 2002. The most current specification for safeguards measurement accuracy is found in the IAEA document STR-327, “International Target Values 2000 for Measurement Uncertainties in Safeguarding Nuclear Materials,” published in 2001. For this guide to be easier for the designer to use, the requirements have been restated in plainer language per expert interpretation using the source documents noted. The safeguards agreement is fundamentally a

NPT safeguards and the peaceful use of nuclear energy

International Nuclear Information System (INIS)

Kyd, D.R.

1993-10-01

Origin of safeguards system and of comprehensive safeguards agreements, assurance given by IAEA safeguards, penalties and sanctions in case of breach of a safeguards agreement, recent experiences with Iraq, South Africa and DPRK as well as limits of the safeguards system are described

IAEA safeguards: Challenges and opportunities

International Nuclear Information System (INIS)

1993-01-01

The history of the IAEA safeguards regime is described. New challenges and opportunities are discussed in connection with the discovery in Iraq of a clandestine nuclear weapons development programme, the difficulties experienced in the implementation of the safeguards agreement with the Democratic People's Republic of Korea, the conclusion of a comprehensive safeguards agreement with Argentina, Brazil and the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials, recent developments in South Africa, the emergence of newly independent States that made up the former USSR. 2 figs

Integrated safeguards and facility design and operations

International Nuclear Information System (INIS)

Tape, J.W.; Coulter, C.A.; Markin, J.T.; Thomas, K.E.

1987-01-01

The integration of safeguards functions to deter or detect unauthorized actions by an insider requires the careful communication and management of safeguards-relevant information on a timely basis. The traditional separation of safeguards functions into physical protection, materials control, and materials accounting often inhibits important information flows. Redefining the major safeguards functions as authorization, enforcement, and verification, and careful attention to management of information from acquisition to organization, to analysis, to decision making can result in effective safeguards integration. The careful inclusion of these ideas in facility designs and operations will lead to cost-effective safeguards systems. The safeguards authorization function defines, for example, personnel access requirements, processing activities, and materials movements/locations that are permitted to accomplish the mission of the facility. Minimizing the number of authorized personnel, limiting the processing flexibility, and maintaining up-to-date flow sheets will facilitate the detection of unauthorized activities. Enforcement of the authorized activities can be achieved in part through the use of barriers, access control systems, process sensors, and health and safety information. Consideration of safeguards requirements during facility design can improve the enforcement function. Verification includes the familiar materials accounting activities as well as auditing and testing of the other functions

Improving the Transparency of IAEA Safeguards Reporting

International Nuclear Information System (INIS)

Toomey, Christopher; Hayman, Aaron M.; Wyse, Evan T.; Odlaug, Christopher S.

2011-01-01

In 2008, the Standing Advisory Group on Safeguards Implementation (SAGSI) indicated that the International Atomic Energy Agency's (IAEA) Safeguards Implementation Report (SIR) has not kept pace with the evolution of safeguards and provided the IAEA with a set of recommendations for improvement. The SIR is the primary mechanism for providing an overview of safeguards implementation in a given year and reporting on the annual safeguards findings and conclusions drawn by the Secretariat. As the IAEA transitions to State-level safeguards approaches, SIR reporting must adapt to reflect these evolutionary changes. This evolved report will better reflect the IAEA's transition to a more qualitative and information-driven approach, based upon State-as-a-whole considerations. This paper applies SAGSI's recommendations to the development of multiple models for an evolved SIR and finds that an SIR repurposed as a 'safeguards portal' could significantly enhance information delivery, clarity, and transparency. In addition, this paper finds that the 'portal concept' also appears to have value as a standardized information presentation and analysis platform for use by Country Officers, for continuity of knowledge purposes, and the IAEA Secretariat in the safeguards conclusion process. Accompanying this paper is a fully functional prototype of the 'portal' concept, built using commercial software and IAEA Annual Report data.

Visualizing Safeguards: Software for Conceptualizing and Communicating Safeguards Data

Energy Technology Data Exchange (ETDEWEB)

Gallucci, N. [Brookhaven National Lab. (BNL), Upton, NY (United States)

2015-07-12

The nuclear programs of states are complex and varied, comprising a wide range of fuel cycles and facilities. Also varied are the types and terms of states’ safeguards agreements with the IAEA, each placing different limits on the inspectorate’s access to these facilities. Such nuances make it difficult to draw policy significance from the ground-level nuclear activities of states, or to attribute ground-level outcomes to the implementation of specific policies or initiatives. While acquiring a firm understanding of these relationships is critical to evaluating and formulating effective policy, doing so requires collecting and synthesizing large bodies of information. Maintaining a comprehensive working knowledge of the facilities comprising even a single state’s nuclear program poses a challenge, yet marrying this information with relevant safeguards and verification information is more challenging still. To facilitate this task, Brookhaven National Laboratory has developed a means of capturing the development, operation, and safeguards history of all the facilities comprising a state’s nuclear program in a single graphic. The resulting visualization offers a useful reference tool to policymakers and analysts alike, providing a chronology of states’ nuclear development and an easily digestible history of verification activities across their fuel cycles.

Inspection technologies -Development of national safeguards technology-

International Nuclear Information System (INIS)

Hong, J. S.; Kim, B. K.; Kwack, E. H.

1996-12-01

17 facility regulations prepared by nuclear facilities according to the Ministerial Notices were evaluated. Safeguards inspection activities under Safeguards are described. Safeguards inspection equipments and operation manuals to be used for national inspection are also described. Safeguards report are produced and submitted to MOST by using the computerized nuclear material accounting system at state level. National inspection support system are developed to produce the on-site information for domestic inspection. Planning and establishment of policy for nuclear control of nuclear materials, international cooperation for nuclear control, CTBT, strengthening of international safeguards system, and the supply of PWRs to North Korea are also described. (author). 43 tabs., 39 figs

Sequence Classification: 891686 [

Lifescience Database Archive (English)

Full Text Available TMB Non-TMH Non-TMB TMB Non-TMB Non-TMB >gi|6320838|ref|NP_010917.1| Constituent of 66S pre-ribosomal partic...les, involved in 60S ribosomal subunit biogenesis; Nop16p || http://www.ncbi.nlm.nih.gov/protein/6320838 ...

Directed proteomic analysis of the human nucleolus

DEFF Research Database (Denmark)

Andersen, Jens S; Lyon, Carol E; Fox, Archa H

2002-01-01

BACKGROUND: The nucleolus is a subnuclear organelle containing the ribosomal RNA gene clusters and ribosome biogenesis factors. Recent studies suggest it may also have roles in RNA transport, RNA modification, and cell cycle regulation. Despite over 150 years of research into nucleoli, many aspec...

IAEA symposium on international safeguards. Extended synopses

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-10-01

The most important subjects treated in 188 papers presented by the participants from member state and IAEA Safeguards Inspectors at the Symposium were as follows: implementation of IAEA safeguards; national support programs to the IAEA safeguards; experiences in application of safeguard monitoring devices; improved methods for verification of plutonium; highly enriched uranium; surveillance of spent fuel storage facilities, reprocessing plants, fuel fabrication plants; excess weapon grade plutonium and other fissile materials Refs, figs, tabs

Tokai Advanced Safeguards Technology Exercise (TASTEX). An experience in international co-operation on safeguards

International Nuclear Information System (INIS)

Fukuda, G.; Koizumi, T.; Higuchi, K.

1983-01-01

TASTEX stands for Tokai Advanced Safeguards Technology Exercise, and was the joint programme of Japan, the United States of America, France and the International Atomic Energy Agency for developing, testing and evaluating advanced safeguards technology to be used in reprocessing facilities. The TASTEX programme, which started early in 1978 and successfully ended in May 1981, consisted of thirteen safeguards-technology-related tasks, from Task A to M. They were classified into four groups from the viewpoints of their usefulness and effectiveness: (1) Tasks technically feasible for international safeguards application in the near future: Tasks E, G, H and part of Task A (underwater CCTV and monitoring cameras); (2) Tasks which can be used in the future if research and development are continued: Tasks F, I, J, C and the other part of Task A (exclusive of the themes shown in (1)); (3) Tasks which may be used in future at the Tokai Reprocessing Facility if research and development are continued: Tasks K and L; and (4) Tasks which are difficult to be used at the Tokai Reprocessing Facility: Tasks B, D and M. The tasks classified under Group (1) are being developed further as part of the JASPAS (Japan Support Programme for Agency's Safeguards) project. (author)

Safeguards and Physics Measurements: Services

International Nuclear Information System (INIS)

Carchon, R.

2000-01-01

SCK-CEN's department of Safeguards and Physics Measurements provides a wide variety of internal and external services including dosimetry, calibration, instrumentation, whole body counting, safeguards and non-destructive analysis. Main developments in these areas in 1999 are described

Safeguards Guidance for Designers of Commercial Nuclear Facilities – International Safeguards Requirements for Uranium Enrichment Plants

Energy Technology Data Exchange (ETDEWEB)

Philip Casey Durst; Scott DeMuth; Brent McGinnis; Michael Whitaker; James Morgan

2010-04-01

For the past two years, the United States National Nuclear Security Administration, Office of International Regimes and Agreements (NA-243), has sponsored the Safeguards-by-Design Project, through which it is hoped new nuclear facilities will be designed and constructed worldwide more amenable to nuclear safeguards. In the course of this project it was recognized that commercial designer/builders of nuclear facilities are not always aware of, or understand, the relevant domestic and international safeguards requirements, especially the latter as implemented by the International Atomic Energy Agency (IAEA). To help commercial designer/builders better understand these requirements, a report was prepared by the Safeguards-by-Design Project Team that articulated and interpreted the international nuclear safeguards requirements for the initial case of uranium enrichment plants. The following paper summarizes the subject report, the specific requirements, where they originate, and the implications for design and construction. It also briefly summarizes the established best design and operating practices that designer/builder/operators have implemented for currently meeting these requirements. In preparing the subject report, it is recognized that the best practices are continually evolving as the designer/builder/operators and IAEA consider even more effective and efficient means for meeting the safeguards requirements and objectives.

Future issues in international safeguards

International Nuclear Information System (INIS)

Hakkila, E.A.; Markin, J.T.; Mullen, M.F.

1991-01-01

The introduction of large bulk-handling facilities into the internationally safeguarded, commercial nuclear fuel cycle, increased concerns for radiation exposure, and the constant level of resources available to the International Atomic Energy Agency (IAEA) are driving new and innovative approaches to international safeguards. Inspector resources have traditionally been allocated on a facility-type basis. Approaches such as randomization of inspections either within a facility or across facilities in a State or the application of a fuel-cycle approach within a State are being considered as means of conserving resources. Large bulk-handling facilities require frequent material balance closures to meet IAEA timeliness goals. Approaches such as near-real-time accounting, running book inventories, and adjusted running book inventories are considered as means to meet these goals. The automated facilities require that safeguards measures also be automated, leading to more reliance on operator-supplied equipment that must be authenticated by the inspectorate. New Non-Proliferation Treaty signatory States with advanced nuclear programs will further drain IAEA resources. Finally, the role of special inspections in IAEA safeguards may be expanded. This paper discusses these issues in terms of increasing safeguards effectiveness and the possible impact on operators. 14 refs

Strengthened safeguards: Present and future challenges

International Nuclear Information System (INIS)

Goldschmidt, Pierre

2001-01-01

Full text: The safeguards system is experiencing what has been seen as a revolution and, in doing so, it is confronting a series of challenges. These can be grouped into three areas. Drawing and maintaining safeguards conclusions - The process by which the safeguards conclusions are derived is based upon the analysis, evaluation and review of all the information available to the Agency. This process is on- going, but the State Evaluation Reports are compiled and reviewed periodically. For States with an additional protocol in force, the absence of indicators of the presence of undeclared nuclear material or activities provides the basis for the safeguards conclusion. Future challenges center on States' expectations of, and reactions to, the results of the evaluation and review process. Designing and implementing integrated safeguards - The conceptual framework of integrated safeguards is being actively pursued. Basic principles have been defined and integrated safeguards approaches have been developed for various types of facilities. Work is also progressing on the design of integrated safeguards approaches for specific States. Complementary access is being successfully implemented, and procedures for the use of unannounced inspections are being developed with the prospect of cost- effectiveness gains. Costs neutrality vs. quality and credibility - The Department faces serious staff and financial challenges. It has succeeded so far in 'doing more' and 'doing better' within a zero-real growth budget, but the scope for further significant efficiency gains is exhausted. There is no capacity to absorb new or unexpected tasks. Difficulties in recruiting and retaining qualified and experienced staff exacerbate the problems and add to costs. The Director General of the IAEA has referred to the need for new initiatives to bridge the budgetary gap; a possible measure is proposed. The tasks of meeting the challenges and demands of strengthened safeguards have been added to

Safeguards culture on 3S interfaces

Energy Technology Data Exchange (ETDEWEB)

Jeong, Yon Hong; Lee, Na Young; Han, Jae-Jun [Korea Institute of Nuclear Non-proliferation and Control, Daejeon (Korea, Republic of)

2015-05-15

But when proliferation of nuclear weapon does happen due to violation of safeguards, the impact would be no smaller compare to the others. Therefore, it should be treated as important as the others. In fact, safeguards culture wasn't issued first time in this paper. However, the past safeguards culture only meant the conception based upon specific purpose. But it should be generalized to extend the target and scope enough to cover any possible misbehavior. The aforementioned NMAC will be a quite meaningful research subject not just for strengthening safeguards culture, but also for the security and safeguards interface. Recognizing the importance of this, the , IAEA has developed a set of technical criteria based on the IAEA implementing guide entitled Use of Nuclear Material Accounting and Control for Nuclear Security Purposes at Facilities(in publication) and a methodology to assess the use of a facility's NMAC system for nuclear security. IAEA has established an expert team to continuously evaluate and apply NMAC systems going forward. In the process of such efforts, the ROK should work to select and apply appropriate features so as to build a more improved safeguards culture and to determine the best practice.

Safeguards culture on 3S interfaces

International Nuclear Information System (INIS)

Jeong, Yon Hong; Lee, Na Young; Han, Jae-Jun

2015-01-01

But when proliferation of nuclear weapon does happen due to violation of safeguards, the impact would be no smaller compare to the others. Therefore, it should be treated as important as the others. In fact, safeguards culture wasn't issued first time in this paper. However, the past safeguards culture only meant the conception based upon specific purpose. But it should be generalized to extend the target and scope enough to cover any possible misbehavior. The aforementioned NMAC will be a quite meaningful research subject not just for strengthening safeguards culture, but also for the security and safeguards interface. Recognizing the importance of this, the , IAEA has developed a set of technical criteria based on the IAEA implementing guide entitled Use of Nuclear Material Accounting and Control for Nuclear Security Purposes at Facilities(in publication) and a methodology to assess the use of a facility's NMAC system for nuclear security. IAEA has established an expert team to continuously evaluate and apply NMAC systems going forward. In the process of such efforts, the ROK should work to select and apply appropriate features so as to build a more improved safeguards culture and to determine the best practice

A Little Customs Glossary for IAEA Safeguards: Customs Procedures and Concepts that Matter for the Implementation of Modern Safeguards

Energy Technology Data Exchange (ETDEWEB)

Chatelus, Renaud [Consultant, Export Control and IAEA Safeguards Specialist, IAEA (International Atomic Energy Agency (IAEA))

2012-06-15

The additional protocols to the IAEA comprehensive safeguards agreements include provisions about the reporting by states of their imports and exports of listed equipment and non-nuclear material, also known as the 'trigger list', as well as nuclear materials. Beyond declarations and their verification, IAEA Safeguards also looks at other Imports and exports as part of its efforts to build confidence on the absence of undeclared nuclear activities or material. In all cases, information about international transfers of interest to Nuclear Safeguards is closely related to export control activities. But, if much has been written about the material and equipment to be declared, neither IAEA Safeguards nor Export control related documents provide much explanation about what exports and imports actually are. In fact, precise legal definitions are to be found generally in national customs regulations and international agreements on customs and trade. Unfortunately, these are not necessarily in line with Safeguards understanding. It is therefore essential that IAEA safeguards comprehends the customs concepts and procedures that are behind Safeguards relevant information.

A Little Customs Glossary for IAEA Safeguards: Customs Procedures and Concepts that Matter for the Implementation of Modern Safeguards

International Nuclear Information System (INIS)

Chatelus, Renaud; )

2012-01-01

The additional protocols to the IAEA comprehensive safeguards agreements include provisions about the reporting by states of their imports and exports of listed equipment and non-nuclear material, also known as the “trigger list”, as well as nuclear materials. Beyond declarations and their verification, IAEA Safeguards also looks at other Imports and exports as part of its efforts to build confidence on the absence of undeclared nuclear activities or material. In all cases, information about international transfers of interest to Nuclear Safeguards is closely related to export control activities. But, if much has been written about the material and equipment to be declared, neither IAEA Safeguards nor Export control related documents provide much explanation about what exports and imports actually are. In fact, precise legal definitions are to be found generally in national customs regulations and international agreements on customs and trade. Unfortunately, these are not necessarily in line with Safeguards understanding. It is therefore essential that IAEA safeguards comprehends the customs concepts and procedures that are behind Safeguards relevant information.

Safeguards and retrievability from waste forms

Energy Technology Data Exchange (ETDEWEB)

Danker, W.

1996-05-01

This report describes issues discussed at a session from the PLutonium Stabilization and Immobilization Workshop related to safeguards and retrievability from waste forms. Throughout the discussion, the group probed the goals of disposition efforts, particularly an understanding of the {open_quotes}spent fuel standard{close_quotes}, since the disposition material form derives from these goals. The group felt strongly that not only the disposition goals but safeguards to meet these goals could affect the material form. Accordingly, the Department was encouraged to explore and apply safeguards as early in the implementation process as possible. It was emphasized that this was particularly true for any planned use of existing facilities. It is much easier to build safeguards approaches into the development of new facilities, than to backfit existing facilities. Accordingly, special safeguards challenges are likely to be encountered, given the cost and schedule advantages offered by use of existing facilities.

Safeguards summary event list (SSEL)

International Nuclear Information System (INIS)

1989-07-01

The Safeguards Summary Event List (SSEL) provides brief summaries of several hundred safeguards-related events involving nuclear material or facilities regulated by the US Nuclear Regulatory Commission (NRC). Because of public interest, also included are events reported involving byproduct material which is exempt from safeguards requirements. Events are described under the categories of bomb-related, intrusion, missing and/or allegedly stolen, transportation, tampering/vandalism, arson, firearms, radiological sabotage, nonradiological sabotage, alcohol and drugs, and miscellaneous. The information contained in the event descriptions is derived primarily from official NRC reporting channels

Safeguards Summary Event List (SSEL)

International Nuclear Information System (INIS)

Fadden, M.; Yardumian, J.

1993-07-01

The Safeguards Summary Event List provides brief summaries of hundreds of safeguards-related events involving nuclear material or facilities regulated by the US Nuclear Regulatory Commission. Events are described under the categories: Bomb-related, Intrusion, Missing/Allegedly Stolen, Transportation-related, Tampering/Vandalism, Arson, Firearms-related, Radiological Sabotage, Non-radiological Sabotage, and Miscellaneous. Because of the public interest, the Miscellaneous category also includes events reported involving source material, byproduct material, and natural uranium, which are exempt from safeguards requirements. Information in the event descriptions was obtained from official NRC sources

Some basic concepts of fast breeder reactor safeguards

International Nuclear Information System (INIS)

Tkharev, E.; Walford, F.J.

1987-04-01

The range of discussion topics of this report is restricted to a few key areas of safeguards importance at Fast Breeder Reactors (FBR) only. The differences between thermal and fast reactors that may have safeguards significance in the case of FBRs are listed. The FBR principles of design are mentioned. The relevant safeguards objectives and criteria are given. The fundamental issues for safeguarding FBR are treated. An outline safeguards approach is presented. Model inspection activities are mentioned. 4 figs

The state-level approach: moving beyond integrated safeguards

International Nuclear Information System (INIS)

Tape, James W.

2008-01-01

The concept of a State-Level Approach (SLA) for international safeguards planning, implementation, and evaluation was contained in the Conceptual Framework for Integrated Safeguards (IS) agreed in 2002. This paper describes briefly the key elements of the SLA, including State-level factors and high-level safeguards objectives, and considers different cases in which application of the SLA methodology could address safeguards for 'suspect' States, 'good' States, and Nuclear Weapons States hosting fuel cycle centers. The continued use and further development of the SLA to customize safeguards for each State, including for States already under IS, is seen as central to effective and efficient safeguards for an expanding nuclear world.

Key Nuclear Verification Priorities: Safeguards and Beyond

International Nuclear Information System (INIS)

Carlson, J.

2010-01-01

In addressing nuclear verification priorities, we should look beyond the current safeguards system. Non-proliferation, which the safeguards system underpins, is not an end in itself, but an essential condition for achieving and maintaining nuclear disarmament. Effective safeguards are essential for advancing disarmament, and safeguards issues, approaches and techniques are directly relevant to the development of future verification missions. The extent to which safeguards challenges are successfully addressed - or otherwise - will impact not only on confidence in the safeguards system, but on the effectiveness of, and confidence in, disarmament verification. To identify the key nuclear verification priorities, we need to consider the objectives of verification, and the challenges to achieving these. The strategic objective of IAEA safeguards might be expressed as: To support the global nuclear non-proliferation regime by: - Providing credible assurance that states are honouring their safeguards commitments - thereby removing a potential motivation to proliferate; and - Early detection of misuse of nuclear material and technology - thereby deterring proliferation by the risk of early detection, enabling timely intervention by the international community. Or to summarise - confidence-building, detection capability, and deterrence. These will also be essential objectives for future verification missions. The challenges to achieving these involve a mix of political, technical and institutional dimensions. Confidence is largely a political matter, reflecting the qualitative judgment of governments. Clearly assessments of detection capability and deterrence have a major impact on confidence. Detection capability is largely thought of as 'technical', but also involves issues of legal authority, as well as institutional issues. Deterrence has both political and institutional aspects - including judgments on risk of detection and risk of enforcement action being taken. The

Key Nuclear Verification Priorities - Safeguards and Beyond

International Nuclear Information System (INIS)

Carlson, J.

2010-01-01

In addressing nuclear verification priorities, we should look beyond the current safeguards system. Non-proliferation, which the safeguards system underpins, is not an end in itself, but an essential condition for achieving and maintaining nuclear disarmament. Effective safeguards are essential for advancing disarmament, and safeguards issues, approaches and techniques are directly relevant to the development of future verification missions. The extent to which safeguards challenges are successfully addressed - or otherwise - will impact not only on confidence in the safeguards system, but on the effectiveness of, and confidence in, disarmament verification. To identify the key nuclear verification priorities, we need to consider the objectives of verification, and the challenges to achieving these. The strategic objective of IAEA safeguards might be expressed as: To support the global nuclear non-proliferation regime by: - Providing credible assurance that states are honouring their safeguards commitments - thereby removing a potential motivation to proliferate; and - Early detection of misuse of nuclear material and technology - thereby deterring proliferation by the risk of early detection, enabling timely intervention by the international community. Or to summarise - confidence-building, detection capability, and deterrence. These will also be essential objectives for future verification missions. The challenges to achieving these involve a mix of political, technical and institutional dimensions. Confidence is largely a political matter, reflecting the qualitative judgment of governments. Clearly assessments of detection capability and deterrence have a major impact on confidence. Detection capability is largely thought of as 'technical', but also involves issues of legal authority, as well as institutional issues. Deterrence has both political and institutional aspects - including judgments on risk of detection and risk of enforcement action being taken. The

IAEA's Safeguards Implementation Practices Guides

International Nuclear Information System (INIS)

Mathews, C.; Sahar, S.; Cisar, V.

2015-01-01

Implementation of IAEA safeguards benefits greatly from effective cooperation among the IAEA, State or regional authorities (SRAs), and operators of facilities and other locations. To improve such cooperation, the IAEA has produced numerous safeguards guidance documents in its Services Series publications. The IAEA also provides assistance, training and advisory services that are based on the published guidance. The foundation of the IAEA's safeguards guidance is the Guidance for States Implementing Comprehensive Safeguards Agreements and Additional Protocols (IAEA Services Series 21) published in March of 2012. The large majority of States have concluded CSAs and therefore will benefit from this guidance. Many States with CSAs also have concluded small quantities protocols (SQPs) to their CSAs. In April of 2013, the IAEA published the Safeguards Implementation Guide for States with SQPs (IAEA Services Series 22). Other guidance focuses on specific topics such as preparing additional protocol declarations and nuclear material accounting. This paper will describe a recent effort to produce a ''Safeguards Implementation Practices'' (SIP) series of guides that will provide additional explanatory information about safeguards implementation, and share the practical experiences and lessons learned of States and the IAEA over the many decades of implementing safeguards. The topics to be addressed in four SIP guides include: 1) Facilitating IAEA Verification Activities; 2) Establishing and Maintaining State Safeguards Infrastructure; 3) Provision of Information to the IAEA; and 4) Collaborative Approaches to Safeguards Implementation. The SIP Guides build upon the content of IAEA Services Series 21. Because the SIP Guides are intended to share implementation practices and lessons learned of States, a number of experienced State experts have participated in the development of the documents, through a joint Member State Support Programme task

Pebble bed modular reactor safeguards: developing new approaches and implementing safeguards by design

Energy Technology Data Exchange (ETDEWEB)

Beyer, Brian David [Los Alamos National Laboratory; Beddingfield, David H [Los Alamos National Laboratory; Durst, Philip [INL; Bean, Robert [INL

2010-01-01

The design of the Pebble Bed Modular Reactor (PBMR) does not fit or seem appropriate to the IAEA safeguards approach under the categories of light water reactor (LWR), on-load refueled reactor (OLR, i.e. CANDU), or Other (prismatic HTGR) because the fuel is in a bulk form, rather than discrete items. Because the nuclear fuel is a collection of nuclear material inserted in tennis-ball sized spheres containing structural and moderating material and a PBMR core will contain a bulk load on the order of 500,000 spheres, it could be classified as a 'Bulk-Fuel Reactor.' Hence, the IAEA should develop unique safeguards criteria. In a multi-lab DOE study, it was found that an optimized blend of: (i) developing techniques to verify the plutonium content in spent fuel pebbles, (ii) improving burn-up computer codes for PBMR spent fuel to provide better understanding of the core and spent fuel makeup, and (iii) utilizing bulk verification techniques for PBMR spent fuel storage bins should be combined with the historic IAEA and South African approaches of containment and surveillance to verify and maintain continuity of knowledge of PBMR fuel. For all of these techniques to work the design of the reactor will need to accommodate safeguards and material accountancy measures to a far greater extent than has thus far been the case. The implementation of Safeguards-by-Design as the PBMR design progresses provides an approach to meets these safeguards and accountancy needs.

Risk analysis of nuclear safeguards regulations

International Nuclear Information System (INIS)

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

1982-06-01

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

SARP-II: Safeguards Accounting and Reports Program, Revised

International Nuclear Information System (INIS)

Kempf, C.R.

1994-01-01

A computer code, SARP (Safeguards Accounting and Reports Program) which will generate and maintain at-facility safeguards accounting records, and generate IAEA safeguards reports based on accounting data input by the user, was completed in 1990 by the Safeguards, Safety, and Nonproliferation Division (formerly the Technical Support Organization) at Brookhaven National Laboratory as a task under the US Program of Technical Support to IAEA safeguards. The code was based on a State System of Accounting for and Control of Nuclear Material (SSAC) for off-load refueled power reactor facilities, with model facility and safeguards accounting regime as described in IAEA Safeguards Publication STR-165. Since 1990, improvements in computing capabilities and comments and suggestions from users engendered revision of the original code. The result is an updated, revised version called SARP-II which is discussed in this report

Anaerobic Copper Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli.

Science.gov (United States)

Tan, Guoqiang; Yang, Jing; Li, Tang; Zhao, Jin; Sun, Shujuan; Li, Xiaokang; Lin, Chuxian; Li, Jianghui; Zhou, Huaibin; Lyu, Jianxin; Ding, Huangen

2017-08-15

While copper is an essential trace element in biology, pollution of groundwater from copper has become a threat to all living organisms. Cellular mechanisms underlying copper toxicity, however, are still not fully understood. Previous studies have shown that iron-sulfur proteins are among the primary targets of copper toxicity in Escherichia coli under aerobic conditions. Here, we report that, under anaerobic conditions, iron-sulfur proteins in E. coli cells are even more susceptible to copper in medium. Whereas addition of 0.2 mM copper(II) chloride to LB (Luria-Bertani) medium has very little or no effect on iron-sulfur proteins in wild-type E. coli cells under aerobic conditions, the same copper treatment largely inactivates iron-sulfur proteins by blocking iron-sulfur cluster biogenesis in the cells under anaerobic conditions. Importantly, proteins that do not have iron-sulfur clusters (e.g., fumarase C and cysteine desulfurase) in E. coli cells are not significantly affected by copper treatment under aerobic or anaerobic conditions, indicating that copper may specifically target iron-sulfur proteins in cells. Additional studies revealed that E. coli cells accumulate more intracellular copper under anaerobic conditions than under aerobic conditions and that the elevated copper content binds to the iron-sulfur cluster assembly proteins IscU and IscA, which effectively inhibits iron-sulfur cluster biogenesis. The results suggest that the copper-mediated inhibition of iron-sulfur proteins does not require oxygen and that iron-sulfur cluster biogenesis is the primary target of anaerobic copper toxicity in cells. IMPORTANCE Copper contamination in groundwater has become a threat to all living organisms. However, cellular mechanisms underlying copper toxicity have not been fully understood up to now. The work described here reveals that iron-sulfur proteins in Escherichia coli cells are much more susceptible to copper in medium under anaerobic conditions than they

Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.

Science.gov (United States)

Bellance, N; Benard, G; Furt, F; Begueret, H; Smolková, K; Passerieux, E; Delage, J P; Baste, J M; Moreau, P; Rossignol, R

2009-12-01

Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.

Video image processing for nuclear safeguards

International Nuclear Information System (INIS)

Rodriguez, C.A.; Howell, J.A.; Menlove, H.O.; Brislawn, C.M.; Bradley, J.N.; Chare, P.; Gorten, J.

1995-01-01

The field of nuclear safeguards has received increasing amounts of public attention since the events of the Iraq-UN conflict over Kuwait, the dismantlement of the former Soviet Union, and more recently, the North Korean resistance to nuclear facility inspections by the International Atomic Energy Agency (IAEA). The role of nuclear safeguards in these and other events relating to the world's nuclear material inventory is to assure safekeeping of these materials and to verify the inventory and use of nuclear materials as reported by states that have signed the nuclear Nonproliferation Treaty throughout the world. Nuclear safeguards are measures prescribed by domestic and international regulatory bodies such as DOE, NRC, IAEA, and EURATOM and implemented by the nuclear facility or the regulatory body. These measures include destructive and non destructive analysis of product materials/process by-products for materials control and accountancy purposes, physical protection for domestic safeguards, and containment and surveillance for international safeguards

Safeguards Automated Facility Evaluation (SAFE) methodology

International Nuclear Information System (INIS)

Chapman, L.D.; Grady, L.M.; Bennett, H.A.; Sasser, D.W.; Engi, D.

1978-08-01

An automated approach to facility safeguards effectiveness evaluation has been developed. This automated process, called Safeguards Automated Facility Evaluation (SAFE), consists of a collection of a continuous stream of operational modules for facility characterization, the selection of critical paths, and the evaluation of safeguards effectiveness along these paths. The technique has been implemented on an interactive computer time-sharing system and makes use of computer graphics for the processing and presentation of information. Using this technique, a comprehensive evaluation of a safeguards system can be provided by systematically varying the parameters that characterize the physical protection components of a facility to reflect the perceived adversary attributes and strategy, environmental conditions, and site operational conditions. The SAFE procedure has broad applications in the nuclear facility safeguards field as well as in the security field in general. Any fixed facility containing valuable materials or components to be protected from theft or sabotage could be analyzed using this same automated evaluation technique

Development of DUPIC safeguards technology

Energy Technology Data Exchange (ETDEWEB)

Kim, H D; Ko, W I; Song, D Y [and others

2000-03-01

During the first phase of R and D program conducted from 1997 to 1999, nuclear material safeguards studies system were performed on the technology development of DUPIC safeguards system such as nuclear material measurement in bulk form and product form, DUPIC fuel reactivity measurement, near-real-time accountancy, and containment and surveillance system for effective and efficient implementation of domestic and international safeguards obligation. For the nuclear material measurement system, the performance test was finished and received IAEA approval, and now is being used in DUPIC Fuel Fabrication Facility(DFDF) for nuclear material accounting and control. Other systems being developed in this study were already installed in DFDF and being under performance test. Those systems developed in this study will make a contribution not only to the effective implementation of DUPIC safeguards, but also to enhance the international confidence build-up in peaceful use of spent fuel material. (author)

A Legal Analysis of Safeguard Measures in the European Community

Directory of Open Access Journals (Sweden)

Guang Ma

2006-12-01

Full Text Available In 2002, the European Community imposed its first safeguard measure since the establishment of the WTO. And in 2003, it introduced two new regulations on safeguard measures, namely the “Council Regulation on a transitional product- specific safeguard mechanism for imports originating in the People's Republic of China” and the “Council Regulation on measures that the Community may take in relation to the combined effect of anti-dumping or anti-subsidy measures with safeguard measures." In this article, the author analyzes these safeguard measures and the European Commission's practice of such measures. By comparing the safeguard laws and their practice, it is the author's intention to clarify whether the safeguard measures in thIn 2002, the European Community imposed its first safeguard measure since the establishment of the WTO. And in 2003, it introduced two new regulations on safeguard measures, namely the "Council Regulation on a transitional product- specific safeguard mechanism for imports originating in the People's Republic of China" and the "Council Regulation on measures that the Community may take in relation to the combined effect of anti-dumping or anti-subsidy measures with safeguard measures." In this article, the author analyzes these safeguard measures and the European Commission's practice of such measures. By comparing the safeguard laws and their practice, it is the author's intention to clarify whether the safeguard measures in the European Community comply with the WTO Agreement on Safeguards. In conclusion, based on the analysis of safeguard measures in the European Community's legal system and their practice in actual cases, it apparent that the European Community is making a serious effort to comply with the standards of the WTO Safeguards Agreement. In certain respects, the European Community has a comparatively higher level of standards than the WTO. Nevertheless, there continue to be challenges to WTO

Guarantying and testing the nuclear safeguards

International Nuclear Information System (INIS)

Turcu, Ilie

2002-01-01

Apparently, the nuclear power will ensure an important share of the world energy demand at least for the next decades because there is no viable alternative in the fan of energy sources neither one complying with the environment preservation requirements. The nuclear energy future depends not only on technical and economical aspects but also on preventing any danger of nuclear safeguards nature. The main international legal instrument which provides concrete commitments for nations in this field is the Nuclear Safeguard Convention. It provides guarantees and testings of the nuclear safeguards over the entire service life of the nuclear power plants. In the two general conferences (of 1999 and 2002) the status and measures adopted in the field of nuclear safeguards by the states adhering to the convention were discussed and reviewed, as well as the issues of financial resources, licensing and the adequate measures in emergency cases. The nuclear safeguards is a major issue among the criteria of integration in UE. Essential for maintaining and endorsing the provisions of nuclear safeguards in Romania are specific research and development activities aiming at integrating the equipment and structures, solving the operation problems of nuclear facilities, studying the behavior of installations in transient regimes, investigating the reliability and probabilistic assessing of nuclear safeguards, examining the phenomenology and simulating severe accidents or human factor behavior. Of major importance appears to be the international cooperation aiming that a permanent exchange of information and experience, dissemination of the best results, solutions and practices. The paper presents the status and trends at the world level, as well as in Romania, underlining the main issues of the strategy in this field and stressing the financial and human resources implied the implementing the nuclear safeguards provisions

Next Generation Safeguards Initiative: Human Capital Development

International Nuclear Information System (INIS)

Scholz, M.; Irola, G.; Glynn, K.

2015-01-01

Since 2008, the Human Capital Development (HCD) subprogramme of the U.S. National Nuclear Security Administration's (NNSA) Next Generation Safeguards Initiative (NGSI) has supported the recruitment, education, training, and retention of the next generation of international safeguards professionals to meet the needs of both the International Atomic Energy Agency (IAEA) and the United States. Specifically, HCD's efforts respond to data indicating that 82% of safeguards experts at U.S. Laboratories will have left the workforce within 15 years. This paper provides an update on the status of the subprogramme since its last presentation at the IAEA Safeguards Symposium in 2010. It highlights strengthened, integrated efforts in the areas of graduate and post-doctoral fellowships, young and midcareer professional support, short safeguards courses, and university engagement. It also discusses lessons learned from the U.S. experience in safeguards education and training as well as the importance of long-range strategies to develop a cohesive, effective, and efficient human capital development approach. (author)

Probing the stiffness of isolated nucleoli by atomic force microscopy.

Science.gov (United States)

Louvet, Emilie; Yoshida, Aiko; Kumeta, Masahiro; Takeyasu, Kunio

2014-04-01

In eukaryotic cells, ribosome biogenesis occurs in the nucleolus, a membraneless nuclear compartment. Noticeably, the nucleolus is also involved in several nuclear functions, such as cell cycle regulation, non-ribosomal ribonucleoprotein complex assembly, aggresome formation and some virus assembly. The most intriguing question about the nucleolus is how such dynamics processes can occur in such a compact compartment. We hypothesized that its structure may be rather flexible. To investigate this, we used atomic force microscopy (AFM) on isolated nucleoli. Surface topography imaging revealed the beaded structure of the nucleolar surface. With the AFM's ability to measure forces, we were able to determine the stiffness of isolated nucleoli. We could establish that the nucleolar stiffness varies upon drastic morphological changes induced by transcription and proteasome inhibition. Furthermore, upon ribosomal proteins and LaminB1 knockdowns, the nucleolar stiffness was increased. This led us to propose a model where the nucleolus has steady-state stiffness dependent on ribosome biogenesis activity and requires LaminB1 for its flexibility.

Safeguards and physics measurements

International Nuclear Information System (INIS)

Carchon, R.

2002-01-01

SCK-CEN's programme on safeguards and physics measurements involves gamma and neutron dosimetry, calibrations and irradiations, electronic support, metrology of various samples including internal contamination of human beings, of waste barrels and of fissile materials, neutron activation analysis, and radioisotope source preparation. The document reports on the main activities and achievements of the sections 'Instrumentation, Calibration and Dosimetry' and 'Safeguards and Nuclear Physics Measurements'

Australian nuclear safeguards

International Nuclear Information System (INIS)

Kerin, J.C.

1988-01-01

The Australian Government considers that allegations made by the West German magazine - Der Spiegel in its January and February 1988 editions, flow from a lack of understanding of the complexities of international trade in nuclear materials, confusion between internal and international flag swaps and failure to comprehend the equivalence principle used in nuclear materials accounting. The Ministerial statement briefly outlines these issues and concludes that there is no evidence that any material subject to Australia's bilateral safeguards agreement has been diverted from peaceful uses or that Australia's safeguard requirements have been breached

IAEA safeguards and classified materials

International Nuclear Information System (INIS)

Pilat, J.F.; Eccleston, G.W.; Fearey, B.L.; Nicholas, N.J.; Tape, J.W.; Kratzer, M.

1997-01-01

The international community in the post-Cold War period has suggested that the International Atomic Energy Agency (IAEA) utilize its expertise in support of the arms control and disarmament process in unprecedented ways. The pledges of the US and Russian presidents to place excess defense materials, some of which are classified, under some type of international inspections raises the prospect of using IAEA safeguards approaches for monitoring classified materials. A traditional safeguards approach, based on nuclear material accountancy, would seem unavoidably to reveal classified information. However, further analysis of the IAEA's safeguards approaches is warranted in order to understand fully the scope and nature of any problems. The issues are complex and difficult, and it is expected that common technical understandings will be essential for their resolution. Accordingly, this paper examines and compares traditional safeguards item accounting of fuel at a nuclear power station (especially spent fuel) with the challenges presented by inspections of classified materials. This analysis is intended to delineate more clearly the problems as well as reveal possible approaches, techniques, and technologies that could allow the adaptation of safeguards to the unprecedented task of inspecting classified materials. It is also hoped that a discussion of these issues can advance ongoing political-technical debates on international inspections of excess classified materials

The standing advisory group on safeguards implementation

International Nuclear Information System (INIS)

Jennekens, J.H.F.

1982-09-01

In 1975 the Director General of the IAEA called together ten persons from member states with nuclear programs at varying stages of development to form the Standing Advisory Group on Safeguards Implementation. The group was later expanded to twelve. The Director General asked the group to evaluate the technical objectives of Agency safeguards, assess the effectiveness and efficiency of specific safeguards operating methods in meeting these technical objectives, advise on techniques to be employed in safeguards operations, and recommend areas where further work is needed. This paper reviews the work of the Standing Advisory Group on Safeguards Implementation since its formation in 1975, summarizes the subjects that have been examined and the advice rendered, and outlines the problem areas requiring further study

Legal instruments related to the application of safeguards

International Nuclear Information System (INIS)

Rames, J.

1999-01-01

This presentation discusses the legal framework of IAEA Safeguards which consists of a number of elements, including agreements calling for verification of nonproliferation undertakings, basic safeguards documents (INFCIRC/66/Rev.2, INFCIRC/153 (Corr..), INFCIRC/540 (Corr.), INFCIRC/9/Rev.2, GC(V)/INF/39), the safeguards agreements themselves, along with the relevant protocols and subsidiary arrangements, and finally the decisions, interpretations and practices of the Boards of Governors. Major differences between the various types of IAEA safeguards agreements are outlined. Procedures involved in the initiation, negotiation, conclusion and amendment of safeguard agreements are described

Reporting of safeguards events

International Nuclear Information System (INIS)

Dwyer, P.A.; Ervin, N.E.

1988-02-01

On June 9, 1987, the Commission published in the Federal Register a final rule revising the reporting requirements for safeguards events. Safeguards events include actual or attempted theft of special nuclear material (SNM); actual or attempted acts or events which interrupt normal operations at power reactors due to unauthorized use of or tampering with machinery, components, or controls; certain threats made against facilities possessing SNM; and safeguards system failures impacting the effectiveness of the system. The revised rule was effective October 8, 1987. On September 14, 1987, the NRC held a workshop in Bethesda, MD, to answer affected licensees' questions on the final rule. This report documents questions discussed at the September 14 meeting, reflects a completed staff review of the answers, and supersedes previous oral comment on the topics covered

Fuel cycle based safeguards

International Nuclear Information System (INIS)

De Montmollin, J.M.; Higinbotham, W.A.; Gupta, D.

1985-07-01

In NPT safeguards the same model approach and absolute-quantity inspection goals are applied at present to all similar facilities, irrespective of the State's fuel cycle. There is a continuing interest and activity on the part of the IAEA in new NPT safeguards approaches that more directly address a State's nuclear activities as a whole. This fuel cycle based safeguards system is expected to a) provide a statement of findings for the entire State rather than only for individual facilities; b) allocate inspection efforts so as to reflect more realistically the different categories of nuclear materials in the different parts of the fuel cycle and c) provide more timely and better coordinated information on the inputs, outputs and inventories of nuclear materials in a State. (orig./RF) [de

Eukaryotic ribosome display with in situ DNA recovery.

Science.gov (United States)

He, Mingyue; Edwards, Bryan M; Kastelic, Damjana; Taussig, Michael J

2012-01-01

Ribosome display is a cell-free display technology for in vitro selection and optimisation of proteins from large diversified libraries. It operates through the formation of stable protein-ribosome-mRNA (PRM) complexes and selection of ligand-binding proteins, followed by DNA recovery from the selected genetic information. Both prokaryotic and eukaryotic ribosome display systems have been developed. In this chapter, we describe the eukaryotic rabbit reticulocyte method in which a distinct in situ single-primer RT-PCR procedure is used to recover DNA from the selected PRM complexes without the need for prior disruption of the ribosome.

10 CFR 72.184 - Safeguards contingency plan.

Science.gov (United States)

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Safeguards contingency plan. 72.184 Section 72.184 Energy... Protection § 72.184 Safeguards contingency plan. (a) The requirements of the licensee's safeguards contingency plan for responding to threats and radiological sabotage must be as defined in appendix C to part...

Safeguards planning in a plant design process

International Nuclear Information System (INIS)

Heinrich, L.A.

1977-01-01

The safeguards efforts for the partitioning fuel cycle are considered. Included in the discussion are the organization of the safeguards study, the development of safeguards criteria, the expression of these criteria as requirements for facility design, and some preliminary details of the implementation of these requirements in facility and process layout

Structure for the decomposition of safeguards responsibilities

International Nuclear Information System (INIS)

Dugan, V.L.; Chapman, L.D.

1977-01-01

A major mission of safeguards is to protect against the use of nuclear materials by adversaries to harm society. A hierarchical structure of safeguards responsibilities and activities to assist in this mission is defined. The structure begins with the definition of international or multi-national safeguards and continues through domestic, regional, and facility safeguards. The facility safeguards is decomposed into physical protection and material control responsibilities. In addition, in-transit safeguards systems are considered. An approach to the definition of performance measures for a set of Generic Adversary Action Sequence Segments (GAASS) is illustrated. These GAASS's begin outside facility boundaries and terminate at some adversary objective which could lead to eventual safeguards risks and societal harm. Societal harm is primarily the result of an adversary who is successful in the theft of special nuclear material or in the sabotage of vital systems which results in the release of material in situ. With the facility safeguards system, GAASS's are defined in terms of authorized and unauthorized adversary access to materials and components, acquisition of material, unauthorized removal of material, and the compromise of vital components. Each GAASS defines a set of ''paths'' (ordered set of physical protection components) and each component provides one or more physical protection ''functions'' (detection, assessment, communication, delay, neutralization). Functional performance is then developed based upon component design features, the environmental factors, and the adversary attributes. An example of this decomposition is presented

Structure for the decomposition of safeguards responsibilities

International Nuclear Information System (INIS)

Dugan, V.L.; Chapman, L.D.

1977-08-01

A major mission of safeguards is to protect against the use of nuclear materials by adversaries to harm society. A hierarchical structure of safeguards responsibilities and activities to assist in this mission is defined. The structure begins with the definition of international or multi-national safeguards and continues through domestic, regional, and facility safeguards. The facility safeguards is decomposed into physical protection and material control responsibilities. In addition, in-transit safeguards systems are considered. An approach to the definition of performance measures for a set of Generic Adversary Action Sequence Segments (GAASS) is illustrated. These GAASS's begin outside facility boundaries and terminate at some adversary objective which could lead to eventual safeguards risks and societal harm. Societal harm is primarily the result of an adversary who is successful in the theft of special nuclear material or in the sabotage of vital systems which results in the release of material in situ. With the facility safeguards system, GAASS's are defined in terms of authorized and unauthorized adversary access to materials and components, acquisition of material, unauthorized removal of material, and the compromise of vital components. Each GAASS defines a set of ''paths'' (ordered set of physical protection components) and each component provides one or more physical protection ''functions'' (detection, assessment, communication, delay, neutralization). Functional performance is then developed based upon component design features, the environmental factors, and the adversary attributes. An example of this decomposition is presented

7 CFR 947.55 - Safeguards.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Safeguards. 947.55 Section 947.55 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... safeguards to prevent shipments pursuant to § 947.54 from entering channels of trade and other outlets for...

Safeguards Envelope Progress FY08

Energy Technology Data Exchange (ETDEWEB)

Robert Bean; Richard Metcalf; Aaron Bevill

2008-09-01

The Safeguards Envelope Project met its milestones by creating a rudimentary safeguards envelope, proving the value of the approach on a small scale, and determining the most appropriate path forward. The Idaho Chemical Processing Plant’s large cache of reprocessing process monitoring data, dubbed UBER Data, was recovered and used in the analysis. A probabilistic Z test was used on a Markov Monte Carlo simulation of expected diversion data when compared with normal operating data. The data regarding a fully transient event in a tank was used to create a simple requirement, representative of a safeguards envelope, whose impact was a decrease in operating efficiency by 1.3% but an increase in material balance period of 26%. This approach is operator, state, and international safeguards friendly and should be applied to future reprocessing plants. Future requirements include tank-to-tank correlations in reprocessing facilities, detailed operations impact studies, simulation inclusion, automated optimization, advanced statistics analysis, and multi-attribute utility analysis.

Safeguards Envelope Progress FY08

International Nuclear Information System (INIS)

Bean, Robert; Metcalf, Richard; Bevill, Aaron

2008-01-01

The Safeguards Envelope Project met its milestones by creating a rudimentary safeguards envelope, proving the value of the approach on a small scale, and determining the most appropriate path forward. The Idaho Chemical Processing Plant's large cache of reprocessing process monitoring data, dubbed UBER Data, was recovered and used in the analysis. A probabilistic Z test was used on a Markov Monte Carlo simulation of expected diversion data when compared with normal operating data. The data regarding a fully transient event in a tank was used to create a simple requirement, representative of a safeguards envelope, whose impact was a decrease in operating efficiency by 1.3% but an increase in material balance period of 26%. This approach is operator, state, and international safeguards friendly and should be applied to future reprocessing plants. Future requirements include tank-to-tank correlations in reprocessing facilities, detailed operations impact studies, simulation inclusion, automated optimization, advanced statistics analysis, and multi-attribute utility analysis

Leveraging physical protection technology for international safeguards applications

International Nuclear Information System (INIS)

Glidewell, Don

2001-01-01

Full text: In an effort to improve the effectiveness, efficiency, and reliability of equipment used for International Safeguards, the European Safeguards Research and Development Association (ESARDA) Reflection Group requested the ESARDA Containment and Surveillance Working Group to investigate the feasibility of employing physical protection technologies for international safeguards applications. The physical protection market has traditionally been much greater than the international safeguards market. Consequently, physical protection technology has been subjected to greater testing and evaluation, and has enjoyed much greater real world experience. The larger market yields economies of scale, and the greater testing and experience should arguably result in improved reliability. This paper will compare requirements for physical protection versus international safeguards equipment, and identify types of physical protection equipment, which have potential for safeguards applications. It will evaluate both Commercial Off-the-Shelf (COTS) and non-COTS equipment. Finally, for selected physical protection equipment, the paper will evaluate the degree of modification that would be needed to make it acceptable for safeguards applications. (author)

Third International Meeting on Next Generation Safeguards: Safeguards-by-Design at Enrichment Facilities

International Nuclear Information System (INIS)

Long, Jon D.; McGinnis, Brent R.; Morgan, James B.; Whitaker, Michael; Lockwood, Dunbar; Shipwash, Jacqueline L.

2011-01-01

The Third International Meeting on Next Generation Safeguards (NGS3) was hosted by the U.S. Department of Energy (DOE)/National Nuclear Security Administration's (NNSA) Office of Nonproliferation and International Security (NIS) in Washington, D.C. on 14-15 December 2010; this meeting focused on the Safeguards-by-Design (SBD) concept. There were approximately 100 participants from 13 countries, comprised of safeguards policy and technical experts from government and industry. Representatives also were present from the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC), the European Atomic Energy Agency (Euratom), and the International Atomic Energy Agency (IAEA). The primary objective of this meeting was to exchange views and provide recommendations on implementation of the SBD concept for four specific nuclear fuel cycle facility types: gas centrifuge enrichment plants (GCEPs), GEN III and GEN IV reactors, aqueous reprocessing plants, and mixed oxide fuel fabrication facilities. The general and facility-specific SBD documents generated from the four working groups, which were circulated for comment among working group participants, are intended to provide a substantive contribution to the IAEA's efforts to publish SBD guidance for these specific types of nuclear facilities in the near future. The IAEA has described the SBD concept as an approach in which 'international safeguards are fully integrated into the design process of a new nuclear facility from the initial planning through design, construction, operation, and decommissioning.' As part of the Next Generation Safeguards Initiative (NGSI), the DOE is working to establish SBD as a global norm through DOE laboratory studies, international workshops, engagement with industry and the IAEA, and setting an example through its use in new nuclear facilities in the United States. This paper describes the discussion topics and final recommendations of the Enrichment Facilities Working

Safeguarding and Protecting the Nuclear Fuel Cycle

International Nuclear Information System (INIS)

Bjornard, Trond; Garcia, Humberto; Desmond, William; Demuth, Scott

2010-01-01

International safeguards as applied by the International Atomic Energy Agency (IAEA) are a vital cornerstone of the global nuclear nonproliferation regime - they protect against the peaceful nuclear fuel cycle becoming the undetected vehicle for nuclear weapons proliferation by States. Likewise, domestic safeguards and nuclear security are essential to combating theft, sabotage, and nuclear terrorism by non-State actors. While current approaches to safeguarding and protecting the nuclear fuel cycle have been very successful, there is significant, active interest to further improve the efficiency and effectiveness of safeguards and security, particularly in light of the anticipated growth of nuclear energy and the increase in the global threat environment. This article will address two recent developments called Safeguards-by-Design and Security-by-Design, which are receiving increasing broad international attention and support. Expected benefits include facilities that are inherently more economical to effectively safeguard and protect. However, the technical measures of safeguards and security alone are not enough - they must continue to be broadly supported by dynamic and adaptive nonproliferation and security regimes. To this end, at the level of the global fuel cycle architecture, 'nonproliferation and security by design' remains a worthy objective that is also the subject of very active, international focus.

International safeguards

International Nuclear Information System (INIS)

Petit, A.

1991-01-01

The IAEA has now 200 Inspectors or so, and Euratom a similar number. People in Vienna are talking about increases of this staff, in the range of a possible doubling in the five years to come, although even an immediate restart of the expansion of nuclear industry, would not materialize significantly within this period. This means that keeping the same safeguarding approach would probably lead to another doubling of such staff in the ten following years, which is completely unrealistic. Such a staff is our of proportion with those of national inspectorates in other fields. The paper analyzes the basic irrealistic dogma which have hindered the progress of international safeguards, and recall the suggestions made since ten years to improve them

Safeguards and physics measurements

Energy Technology Data Exchange (ETDEWEB)

Carchon, R

2002-04-01

SCK-CEN's programme on safeguards and physics measurements involves gamma and neutron dosimetry, calibrations and irradiations, electronic support, metrology of various samples including internal contamination of human beings, of waste barrels and of fissile materials, neutron activation analysis, and radioisotope source preparation. The document reports on the main activities and achievements of the sections 'Instrumentation, Calibration and Dosimetry' and 'Safeguards and Nuclear Physics Measurements'.

Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

Science.gov (United States)

Cerqueira, Fernanda M; Laurindo, Francisco R M; Kowaltowski, Alicia J

2011-03-31

Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis.

Science.gov (United States)

Zitouni, Sihem; Francia, Maria E; Leal, Filipe; Montenegro Gouveia, Susana; Nabais, Catarina; Duarte, Paulo; Gilberto, Samuel; Brito, Daniela; Moyer, Tyler; Kandels-Lewis, Steffi; Ohta, Midori; Kitagawa, Daiju; Holland, Andrew J; Karsenti, Eric; Lorca, Thierry; Lince-Faria, Mariana; Bettencourt-Dias, Mónica

2016-05-09

Centrioles are essential for the assembly of both centrosomes and cilia. Centriole biogenesis occurs once and only once per cell cycle and is temporally coordinated with cell-cycle progression, ensuring the formation of the right number of centrioles at the right time. The formation of new daughter centrioles is guided by a pre-existing, mother centriole. The proximity between mother and daughter centrioles was proposed to restrict new centriole formation until they separate beyond a critical distance. Paradoxically, mother and daughter centrioles overcome this distance in early mitosis, at a time when triggers for centriole biogenesis Polo-like kinase 4 (PLK4) and its substrate STIL are abundant. Here we show that in mitosis, the mitotic kinase CDK1-CyclinB binds STIL and prevents formation of the PLK4-STIL complex and STIL phosphorylation by PLK4, thus inhibiting untimely onset of centriole biogenesis. After CDK1-CyclinB inactivation upon mitotic exit, PLK4 can bind and phosphorylate STIL in G1, allowing pro-centriole assembly in the subsequent S phase. Our work shows that complementary mechanisms, such as mother-daughter centriole proximity and CDK1-CyclinB interaction with centriolar components, ensure that centriole biogenesis occurs once and only once per cell cycle, raising parallels to the cell-cycle regulation of DNA replication and centromere formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Safeguards and security progress report, January-December 1985

International Nuclear Information System (INIS)

1987-03-01

From January to December 1985, the Los Alamos Safeguards and Security Program was involved in the activities described in the first four parts of this report: Safeguards Operations, Security Development and Support, Safeguards Technology Development, and International Support. Part 1 covers efforts of direct assistance to the Department of Energy and Nuclear Regulatory Commission licensee facilities. This assistance includes consultation on materials accounting problems, development and demonstration of specialized techniques and instruments, and comprehensive participation in the design and evaluation of advanced safeguards systems. In addition, a series of training courses in various aspects of safeguards makes the technology more accessible to those who must apply it. Part 2 treats activities aimed at the security of information and computer systems. Our focus this period was on continuing the activities of the Center for Computer Security, which provides the basis for encouraging and disseminating this emerging technology, and on the development and demonstration of secure computer systems. Part 3 describes the broad development efforts essential to continuing improvements in the practice of safeguards. Although these projects are properly classified as developmental, they address recognized problems that commonly occur in operating facilities. Finally, Part 4 covers international safeguards activities, including both support to the International Atomic Energy Agency and bilateral exchanges. Enrichment plant safeguards and international safeguards for reprocessing plants required a significant portion of our resources. All of these efforts are beginning to provide substantial returns on our investment in technology transfer, not only in raising the level of safeguards effectiveness but also in our benefiting from field experiences in operating environments

Safeguards and security progress report, January-December 1985

Energy Technology Data Exchange (ETDEWEB)

1987-03-01

From January to December 1985, the Los Alamos Safeguards and Security Program was involved in the activities described in the first four parts of this report: Safeguards Operations, Security Development and Support, Safeguards Technology Development, and International Support. Part 1 covers efforts of direct assistance to the Department of Energy and Nuclear Regulatory Commission licensee facilities. This assistance includes consultation on materials accounting problems, development and demonstration of specialized techniques and instruments, and comprehensive participation in the design and evaluation of advanced safeguards systems. In addition, a series of training courses in various aspects of safeguards makes the technology more accessible to those who must apply it. Part 2 treats activities aimed at the security of information and computer systems. Our focus this period was on continuing the activities of the Center for Computer Security, which provides the basis for encouraging and disseminating this emerging technology, and on the development and demonstration of secure computer systems. Part 3 describes the broad development efforts essential to continuing improvements in the practice of safeguards. Although these projects are properly classified as developmental, they address recognized problems that commonly occur in operating facilities. Finally, Part 4 covers international safeguards activities, including both support to the International Atomic Energy Agency and bilateral exchanges. Enrichment plant safeguards and international safeguards for reprocessing plants required a significant portion of our resources. All of these efforts are beginning to provide substantial returns on our investment in technology transfer, not only in raising the level of safeguards effectiveness but also in our benefiting from field experiences in operating environments.

Safeguards and Security progress report, January--December 1989

Energy Technology Data Exchange (ETDEWEB)

Smith, D.B.; Jaramillo, G.R. (comps.)

1990-11-01

From January to December 1989, the Los Alamos Safeguards and Security Research and Development (R D) program carried out the activities described in the first four parts of this report: Science and Technology Base Development, Basic Systems Design, Onsite Test and Evaluation and Facility Support, and International Safeguards. For the most part, these activities were sponsored by the Department of Energy's Office of Safeguards and Security. Part 1 covers development of the basic technology essential to continuing improvements in the practice of safeguards and security. It includes our computer security R D and the activities of the DOE Center for Computer Security, which provides the basis for encouraging and disseminating this important technology. Part 2 treats activities aimed at developing methods for designing and evaluating safeguards systems, with special emphasis on the integration of the several subsystems into a real safeguards system. Part 3 describes efforts of direct assistance to the DOE and its contractors and includes consultation on materials control and accounting problems, development and demonstration of specialized techniques and instruments, and comprehensive participation in the design and demonstration of advanced safeguards systems. Part 3 also reports a series of training courses in various aspects of safeguards that makes the technology more accessible to those who must apply it. Finally, Part 4 covers international safeguards activities, including both support to the International Atomic Energy Agency and bilateral exchanges. Part 5 reports several safeguards-related activities that have sponsors other than the DOE/OSS. 87 refs., 52 figs.

The voluntary safeguards offer of the United States

International Nuclear Information System (INIS)

Houck, F.S.

1985-01-01

During negotiations of the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) concerns were expressed by non-nuclear-weapon States that their acceptance of Agency safeguards would put them at a disadvantage vis-a-vis the nuclear-weapon States. To allay these concerns, the United States and the United Kingdom in December 1967 made voluntary offers to accept Agency safeguards on their peaceful nuclear activities. Subsequently, France made a voluntary offer, the safeguards agreement for which was approved by the IAEA Board of Governors in February 1978, with a view to encouraging acceptance of Agency safeguards by additional States. More recently, in February 1985 the Board approved the safeguards agreement for the voluntary offer of the USSR, made inter alia to encourage further acceptance of Agency safeguards. These safeguards agreements with nuclear-weapon-States have two important features in common: Namely, they result from voluntary offers to accept safeguards rather than from multilateral or bilateral undertakings, and they give the Agency the right but generally not an obligation to apply its safeguards. The agreements differ in certain respects, the most noteworthy of which is the scope of the nuclear activities covered by each offer. The agreements of the United States and United Kingdom are the broadest, covering all peaceful nuclear activities in each country. The safeguards agreement for the US voluntary offer has been in force since December 1980. Now is an appropriate time to review the experience with the agreement's implementation during its first four years, as well as its history and salient features

International safeguards for reprocessing plants. Final report

International Nuclear Information System (INIS)

Kratzer, M.; Scheinman, L.; Sievering, N.; Wonder, E.; Lipman, D.; Immerman, W.; Elliott, J.M.; Crane, F.

1981-04-01

Proliferation risks inherent in reprocessing show the need to employ technically effective safeguards which can detect, with a high degree of assurance and on a timely basis, the diversion of significant quantities of fissionable material. A balance must be struck between what is technically feasible and effective and what is institutionally acceptable. Purpose of this report is to examine the several technical approaches to safeguards in light of their prospective acceptability. This study defines the economic, political and institutional nature of the safeguards problem; surveys generically alternative technical approaches to international safeguards including their effectiveness and relative development; characterizes the institutional implications and uncertainties associated with the acceptance and implementation of each technical alternative; and integrates these assessments into a set of overall judgments on feasible directions for reprocessing plant safeguards systems

International safeguards for reprocessing plants. Final report

Energy Technology Data Exchange (ETDEWEB)

Kratzer, M.; Scheinman, L.; Sievering, N.; Wonder, E.; Lipman, D.; Immerman, W.; Elliott, J.M.; Crane, F.

1981-04-01

Proliferation risks inherent in reprocessing show the need to employ technically effective safeguards which can detect, with a high degree of assurance and on a timely basis, the diversion of significant quantities of fissionable material. A balance must be struck between what is technically feasible and effective and what is institutionally acceptable. Purpose of this report is to examine the several technical approaches to safeguards in light of their prospective acceptability. This study defines the economic, political and institutional nature of the safeguards problem; surveys generically alternative technical approaches to international safeguards including their effectiveness and relative development; characterizes the institutional implications and uncertainties associated with the acceptance and implementation of each technical alternative; and integrates these assessments into a set of overall judgments on feasible directions for reprocessing plant safeguards systems.

Agreement reached on integrated safeguards in European Union

International Nuclear Information System (INIS)

2010-01-01

Full text: The International Atomic Energy Agency (IAEA), in cooperation with the European Commission, has reached agreement on arrangements to implement 'integrated safeguards' in all non-nuclear-weapon States of the European Union with significant nuclear activities. 'This important milestone is the result of the constructive common efforts of all parties concerned. It is a clear signal of the importance attributed by the EU and its Member States, as well as the IAEA, to the reinforcement of the nuclear non-proliferation regime,' said Andris Piebalgs, Member of the European Commission in charge of Energy. 'Once we have sufficient confidence that a State' s nuclear activities are purely peaceful, we can apply safeguards measures in a less prescriptive, more customised manner. This reduces the inspection burden on the State and the inspection effort of the IAEA, while enabling the IAEA to maintain the conclusion that all nuclear material has remained in peaceful activities,' said Olli Heinonen, Deputy Director General and Head of IAEA Safeguards Department. Background The Nuclear Non-Proliferation Treaty (NPT) is the main international Treaty prohibiting the spread of nuclear weapons. It entrusts the IAEA to verify that nuclear material is not diverted to nuclear weapons or other nuclear explosive devices through the application of 'safeguards'. IAEA safeguards include comprehensive safeguards agreements and additional protocols that enable the IAEA to conclude that all nuclear material has remained in peaceful activities in a State. Integrated Safeguards refers to the optimum combination of all safeguards measures available to the Agency under comprehensive safeguards agreements and additional protocols to achieve maximum effectiveness and efficiency in meeting the Agency ' s safeguards obligations. In the European Union, nuclear safeguards are implemented on the basis of the Euratom Treaty and trilateral agreements between Euratom, its Member States and the IAEA

The future of IAEA safeguards: challenges and responses

International Nuclear Information System (INIS)

Pilat, Joseph F.; Budlong-Sylvester, Kory W.

2011-01-01

For nearly two decades, the International Atomic Energy Agency (lAEA) has been transforming its safeguards system to address the challenges posed by undeclared nuclear programs, the associated revelation of an extensive non-State nuclear procurement network and other issues, including past limits to its verification mandate and the burden of noncompliance issues. Implementing the new measures, including those in the Additional Protocol, and integrating new and old safeguards measures, remains a work in progress. Implementation is complicated by factors including the limited teclmological tools that are available to address such issues as safeguarding bulk handling facilities, detection of undeclared facilities/activities, especially related to enrichment, etc. As this process continues, new challenges are arising, including the demands of expanding nuclear power production worldwide, so-called safeguards by design for a new generation of facilities, the possible IAEA role in a fissile material cutoff treaty and other elements of the arms control and disarmament agenda, the possible role in 'rollback' cases, etc. There is no doubt safeguards will need to evolve in the future, as they have over the last decades. In order for the evolutionary path to proceed, there will inter alia be a need to identify technological gaps, especially with respect to undeclared facilities, and ensure they are filled by adapting old safeguards technologies, by developing and introducing new and novel safeguards teclmologies and/or by developing new procedures and protocols. Safeguards will also need to respond to anticipated emerging threats and to future, unanticipated threats. This will require strategic planning and cooperation among Member States and with the Agency. This paper will address challenges to IAEA safeguards and the technological possibilities and R and D strategies needed to meet those challenges in the context of the forty-year evolution of safeguards, including the

Legal instruments related to the application of safeguards

International Nuclear Information System (INIS)

Rockwood, Laura

2001-01-01

The legal framework of IAEA safeguards consists of a number of elements, not at all of which are documents. These elements include the Statute of the IAEA; treaties and supply agreements calling for verification of nonproliferation undertakings; the basic safeguards documents, the safeguards agreements themselves, along with the relevant protocols and subsidiary arrangements; and finally, the decisions, interpretations and practices of the Board of Governors. After a discussion of these elements the major differences between the various types of IAEA safeguards agreements are outlined. Finally the procedures involved in the initiation, negotiation, conclusion and amendment of safeguards agreements are described. (author)

Safeguards Culture: Analogies from Safety Culture and Security Culture

International Nuclear Information System (INIS)

Naito, K.

2013-01-01

The terminology of 'safeguards culture' has been used loosely by safeguards experts as an essential element for establishing an organizational environment of stakeholders for the effective and efficient implementation of international safeguards. However, unlike the other two triplet brothers/ sisters of 3S's (Safety, Security, Safeguards), there is no formally established definition of safeguards culture. In the case of safety culture, INSAG (the International Nuclear Safety Advisory Group) has extensively dealt with its concept, elaborating its definition and key characteristics, and published its report, INSAG-4, as the IAEA Safety Series 75. On the other hand, security culture has also been defined by AdSec (the Advisory Group on Nuclear Security). In this paper, a provisional definition of safeguards culture is made on the analogies of safety culture and security culture, and an effort is made to describe essential elements of safeguards culture. It is proposed for SAGSI (the Standing Advisory Group on Safeguards Implementation) to formally consider the definition of safeguards culture and its characteristics. The paper is followed by the slides of the presentation. (author)

Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide.

Science.gov (United States)

Shi, Zhen; Fujii, Kotaro; Kovary, Kyle M; Genuth, Naomi R; Röst, Hannes L; Teruel, Mary N; Barna, Maria

2017-07-06

Emerging studies have linked the ribosome to more selective control of gene regulation. However, an outstanding question is whether ribosome heterogeneity at the level of core ribosomal proteins (RPs) exists and enables ribosomes to preferentially translate specific mRNAs genome-wide. Here, we measured the absolute abundance of RPs in translating ribosomes and profiled transcripts that are enriched or depleted from select subsets of ribosomes within embryonic stem cells. We find that heterogeneity in RP composition endows ribosomes with differential selectivity for translating subpools of transcripts, including those controlling metabolism, cell cycle, and development. As an example, mRNAs enriched in binding to RPL10A/uL1-containing ribosomes are shown to require RPL10A/uL1 for their efficient translation. Within several of these transcripts, this level of regulation is mediated, at least in part, by internal ribosome entry sites. Together, these results reveal a critical functional link between ribosome heterogeneity and the post-transcriptional circuitry of gene expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Safeguards Summary Event List (SSEL)

International Nuclear Information System (INIS)

1991-07-01

The Safeguards Summary Event List (SSEL) provides brief summaries of several hundred safeguards-related events involving nuclear material or facilities regulated by the US Nuclear Regulatory Commission (NRC). Because of public interest, the Miscellaneous category includes a few events which involve either source material, byproduct material, or natural uranium which are exempt from safeguards requirements. Events are described under the categories of bomb-related, intrusion, missing and/or allegedly stolen, transportation, tampering/vandalism, arson, firearms, radiological sabotage, nonradiological sabotage, pre-1990 alcohol and drugs (involving reactor operators, security force members, or management persons), and miscellaneous. The information contained in the event descriptions is derived primarily from official NRC reporting channels

Some reflections on nuclear safeguards

International Nuclear Information System (INIS)

Campbell, Ross.

1981-01-01

The author doubts whether, in view of the 1976 policy of requiring adherence to the Non-Proliferation Treaty or equivalent IAEA safeguards, Canada still needs the 1974 policy of bilateral safeguards on technology as well as material. The opinion is expressed that bilateral safeguards create difficulties for the IAEA, and are resented by some potential customers. Much better, if it were achievable, would be a code agreed by a convention of vendors and customers alike, to include sanctions against transgressors. The author expresses confidence in the IAEA, but perceives a need for more men and money. Also needed are better instruments to account for materials

Design and evaluation of an integrated safeguards system: principles

International Nuclear Information System (INIS)

Markin, J.T.; Coulter, C.A.; Gutmacher, R.G.; Whitty, W.J.

1984-01-01

An integrated safeguards system is defined as a collection of safeguards activities in which system components are coordinated to meet safeguards objectives efficiently within constraints imposed by safeguards resources, facility operations, potential adversaries, and regulatory requirements. This paper describes principles for designing and evaluating an integrated safeguards system that consists of four parts: a problem definition phase that specifies resources and constraints composing the problem boundary values, a system analysis/synthesis phase that describes how to select and integrate safeguards activities for efficient attainment of system objectives, a system evaluation/optimization phase that defines measures of safeguards performance and develops methods for evaluating them, and a decision-making phase that develops principles for selecting admissible designs and preference-ordering designs

Effect of sodium fluoride on the amount of polyribosomes, single ribosomes and ribosomal subunits in a cellular slime mold, Dictyostelium discoideum

Energy Technology Data Exchange (ETDEWEB)

Sameshima, M; Ito, K; Iwabuchi, M

1972-01-01

In the slime mold, Dictyostelium discoideum, when the rate of protein synthesis was decreased by NaF, free 80-S ribosomes accumulated at the expense of polyribosomes, while 60-S and 40-S ribosomal subunits remained almost constant. The same level of ribosomal subunits was also maintained in cells after incubation with cycloheximide or at the stationary phase of growth.

International safeguards problem

International Nuclear Information System (INIS)

Scheinman, L.; Curtis, H.B.

1977-01-01

To recognize the limitations of safeguards as a barrier to nuclear proliferation is not to deny their essential role in the effort to contain that problem. Without a safeguards system, international nuclear commerce and development would not, indeed could not, be what they are today. The problems evoked in the discussion of the spread of sensitive nuclear technology underscore the importance of ensuring that activities do not outpace our ability to control them. To sustain a global nuclear economy requires a readiness to live within the constraints that such an economy requires. Enhanced safeguards and strengthened national commitments to facilitate their application are key elements of those constraints. So also may be a prepardness by many nations to forego explicitly national control over all facets of the nuclear fuel cycle while still sharing fully and equally in the benefits of the peaceful atom. The challenge of the coming years will be to craft mechanisms and institutions enabling the continued growth of peaceful nuclear activity without further impairing international security. The constraints that such an outcome entails are not limited to nations lacking sophisticated nuclear technology; they apply to the most advanced nuclear nations as well--partly through adherence to the safeguards system that these countries call upon others to adopt, and partly through greater willingness to entertain solutions that may involve greater international involvement in, and control over, their own peaceful nuclear productive activities. With time, the relative incompatibility of nuclear energy with full national sovereignty, and the far-sighted wisdom of the Baruch Plan, are becoming increasingly clear. 1 table, 10 references

Pumping up the volume - vacuole biogenesis in Arabidopsis thaliana.

Science.gov (United States)

Krüger, Falco; Schumacher, Karin

2017-07-08

Plant architecture follows the need to collect CO 2, solar energy, water and mineral nutrients via large surface areas. It is by the presence of a central vacuole that fills much of the cell volume that plants manage to grow at low metabolic cost. In addition vacuoles buffer the fluctuating supply of essential nutrients and help to detoxify the cytosol when plants are challenged by harmful molecules. Despite their large size and multiple important functions, our knowledge of vacuole biogenesis and the machinery underlying their amazing dynamics is still fragmentary. In this review, we try to reconcile past and present models for vacuole biogenesis with the current knowledge of multiple parallel vacuolar trafficking pathways and the molecular machineries driving membrane fusion and organelle shape. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perfluorooctanoic acid stimulated mitochondrial biogenesis and gene transcription in rats

International Nuclear Information System (INIS)

Walters, M.W.; Bjork, J.A.; Wallace, K.B.

2009-01-01

Perfluorooctanoic acid (PFOA), used in the production of non-stick surface compounds, exhibits a worldwide distribution in the serum of humans and wildlife. In rodents PFOA transactivates PPARα and PPARγ nuclear receptors and increases mitochondrial DNA (mtDNA) copy number, which may be critical to the altered metabolic state of affected animals. A key regulator of mitochondrial biogenesis and transcription of mitochondrial genes is the PPARγ coactivator-1α (Pgc-1α) protein. The purpose of this study was to determine if Pgc-1α is implicated in the stimulation of mitochondrial biogenesis that occurs following the treatment of rats with PFOA. Livers from adult male Sprague-Dawley rats that received a 30 mg/kg daily oral dose of PFOA for 28 days were used for all experiments. Analysis of mitochondrial replication and transcription was performed by real time PCR, and proteins were detected using western blotting. PFOA treatment caused a transcriptional activation of the mitochondrial biogenesis pathway leading to a doubling of mtDNA copy number. Further, transcription of OXPHOS genes encoded by mtDNA was 3-4 times greater than that of nuclear encoded genes, suggestive of a preferential induction of mtDNA transcription. Western blot analysis revealed an increase in Pgc-1α, unchanged Tfam and decreased Cox II and Cox IV subunit protein expression. We conclude that PFOA treatment in rats induces mitochondrial biogenesis at the transcriptional level with a preferential stimulation of mtDNA transcription and that this occurs by way of activation of the Pgc-1α pathway. Implication of the Pgc-1α pathway is consistent with PPARγ transactivation by PFOA and reveals new understanding and possibly new critical targets for assessing or averting the associated metabolic disease.

77 FR 38033 - WTO Agricultural Safeguard Trigger Levels

Science.gov (United States)

2012-06-26

... DEPARTMENT OF AGRICULTURE Foreign Agricultural Service WTO Agricultural Safeguard Trigger Levels... and trigger levels for safeguard measures provided for in the World Trade Organization (WTO) Agreement... measures under the safeguard provisions of the WTO [[Page 38034

The Department of Safeguards Quality Management System

International Nuclear Information System (INIS)

Konecni, S.

2015-01-01

The International Atomic Energy Agency (IAEA) Department of Safeguards quality management system (QMS) provides the framework for all activities that support the Agency's commitment to providing soundly-based safeguards conclusions regarding the peaceful use of nuclear material. The focus of the QMS is to enhance the effectiveness and efficiency of safeguards implementation through defined, documented processes, routine oversight and continual improvement initiatives. In accordance with QMS principles, the high-level business processes representing the Department's activities are defined in procedures, guidelines and policies that are maintained in the Safeguards Document Manager. These processes form the basis for Department operations for drawing safeguards conclusions regarding State's compliance with their safeguards obligations. Oversight is provided through internal quality audits. These audits are targeted at processes selected by Senior Management with a focus on procedure compliance as well as customer expectations. Best practices and areas for improvement are assessed through continual improvement. Noncompliance and conditions that are adverse to quality are identified and analyzed in the Condition Report System. Root cause analysis and the implementation actions to eliminate the cause reduce the chance of condition recurrence. Through continual process improvement, processes are measured and analyzed to reduce process and administration waste. The improved processes improve efficiency while providing the desired results. Within the scope of the QMS, these tools support the performance of Departmental processes so that Safeguards products achieve the intended purpose. This paper describes how the various elements of the Department's QMS support safeguards implementation. (author)

A Portrait of Ribosomal DNA Contacts with Hi-C Reveals 5S and 45S rDNA Anchoring Points in the Folded Human Genome.

Science.gov (United States)

Yu, Shoukai; Lemos, Bernardo

2016-12-31

Ribosomal RNAs (rRNAs) account for >60% of all RNAs in eukaryotic cells and are encoded in the ribosomal DNA (rDNA) arrays. The rRNAs are produced from two sets of loci: the 5S rDNA array resides exclusively on human chromosome 1, whereas the 45S rDNA array resides on the short arm of five human acrocentric chromosomes. The 45S rDNA gives origin to the nucleolus, the nuclear organelle that is the site of ribosome biogenesis. Intriguingly, 5S and 45S rDNA arrays exhibit correlated copy number variation in lymphoblastoid cells (LCLs). Here we examined the genomic architecture and repeat content of the 5S and 45S rDNA arrays in multiple human genome assemblies (including PacBio MHAP assembly) and ascertained contacts between the rDNA arrays and the rest of the genome using Hi-C datasets from two human cell lines (erythroleukemia K562 and lymphoblastoid cells). Our analyses revealed that 5S and 45S arrays each have thousands of contacts in the folded genome, with rDNA-associated regions and genes dispersed across all chromosomes. The rDNA contact map displayed conserved and disparate features between two cell lines, and pointed to specific chromosomes, genomic regions, and genes with evidence of spatial proximity to the rDNA arrays; the data also showed a lack of direct physical interaction between the 5S and 45S rDNA arrays. Finally, the analysis identified an intriguing organization in the 5S array with Alu and 5S elements adjacent to one another and organized in opposite orientation along the array. Portraits of genome folding centered on the ribosomal DNA array could help understand the emergence of concerted variation, the control of 5S and 45S expression, as well as provide insights into an organelle that contributes to the spatial localization of human chromosomes during interphase. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

International safeguards data management system

International Nuclear Information System (INIS)

Argentesi, F.; Costantini, L.; Franklin, M.; Dondi, M.G.

1981-01-01

The data base management system ''ISADAM'' (i.e. International Safeguards Data Management System) described in this report is intended to facilitate the safeguards authority in making efficient and effective use of accounting reports. ISADAM has been developed using the ADABAS data base management system and is implemented on the JRC-Ispra computer. The evaluation of safeguards declarations focuses on three main objectives: - the requirement of syntactical consistency with the legal conventions of data recording for safeguards accountancy; - the requirement of accounting evidence that there is no material unaccounted for (MUF); - the requirement of semantic consistency with the technological characteristics of the plant and the processing plans of the operator. Section 2 describes in more detail the facilities which ISADAM makes available to a safeguards inspector. Section 3 describes how the MUF variance computation is derived from models of measurement error propagation. Many features of the ISADAM system are automatically provided by ADABAS. The exceptions to this are the utility software designed to: - screen plant declarations before loading into the data base, - prepare variance summary files designed to support real-time computation of MUF and variance of MUF, - provide analyses in response to user requests in interactive or batch mode. Section 4 describes the structure and functions of this software which have been developed by JRC-Ispra

Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy.

Science.gov (United States)

Fischer, Niels; Konevega, Andrey L; Wintermeyer, Wolfgang; Rodnina, Marina V; Stark, Holger

2010-07-15

The translocation step of protein synthesis entails large-scale rearrangements of the ribosome-transfer RNA (tRNA) complex. Here we have followed tRNA movement through the ribosome during translocation by time-resolved single-particle electron cryomicroscopy (cryo-EM). Unbiased computational sorting of cryo-EM images yielded 50 distinct three-dimensional reconstructions, showing the tRNAs in classical, hybrid and various novel intermediate states that provide trajectories and kinetic information about tRNA movement through the ribosome. The structures indicate how tRNA movement is coupled with global and local conformational changes of the ribosome, in particular of the head and body of the small ribosomal subunit, and show that dynamic interactions between tRNAs and ribosomal residues confine the path of the tRNAs through the ribosome. The temperature dependence of ribosome dynamics reveals a surprisingly flat energy landscape of conformational variations at physiological temperature. The ribosome functions as a Brownian machine that couples spontaneous conformational changes driven by thermal energy to directed movement.

Safeguards for the atom

Energy Technology Data Exchange (ETDEWEB)

NONE

1959-10-15

Concern over the destructive potentialities of nuclear energy has grown all over the world. In fact, it was this concern, coupled with an awareness of the equally great potentialities for peaceful prosperity, that led to the establishment of the International Atomic Energy Agency. That nuclear energy should be used solely for peaceful purposes is an ideal to which all people would subscribe. Realization of this ideal, however, is dependent on many complex factors which are outside the scope of the Agency. In its own limited sphere, however, the Agency has the responsibility to ensure that in its efforts to promote the peaceful uses it does not in any way increase the potentiality of military use. The possibility of military application is not the only danger that the Agency must guard against, it has a further function arising from the nature of the materials needed in atomic energy work. Since the basic materials are radioactive and since all ionizing radiation is potentially dangerous, the Agency must ensure that in helping its Member States to develop the peaceful uses of atomic energy it does not increase the hazards of nuclear radiation or radioactive contamination. It must establish standards of safe practice for activities carried out under its auspices or with its assistance. Since the safeguards will have two distinct objectives, a distinction can be made between those which will be designed to prevent the diversion of Agency assistance to military use and those against health and safety hazards. So far as the health and safety measures are concerned, a good deal of work has already been done in determining the standards of safe practice which will be the basis for the relevant rules. The Agency has published the first in its series of safety manuals, 'Safe Handling of Radioisotopes', which deals with such standards. Safeguards against the diversion or loss of nuclear materials and facilities are more difficult to devise. It is not considered feasible for

Safeguards for the atom

International Nuclear Information System (INIS)

1959-01-01

Concern over the destructive potentialities of nuclear energy has grown all over the world. In fact, it was this concern, coupled with an awareness of the equally great potentialities for peaceful prosperity, that led to the establishment of the International Atomic Energy Agency. That nuclear energy should be used solely for peaceful purposes is an ideal to which all people would subscribe. Realization of this ideal, however, is dependent on many complex factors which are outside the scope of the Agency. In its own limited sphere, however, the Agency has the responsibility to ensure that in its efforts to promote the peaceful uses it does not in any way increase the potentiality of military use. The possibility of military application is not the only danger that the Agency must guard against, it has a further function arising from the nature of the materials needed in atomic energy work. Since the basic materials are radioactive and since all ionizing radiation is potentially dangerous, the Agency must ensure that in helping its Member States to develop the peaceful uses of atomic energy it does not increase the hazards of nuclear radiation or radioactive contamination. It must establish standards of safe practice for activities carried out under its auspices or with its assistance. Since the safeguards will have two distinct objectives, a distinction can be made between those which will be designed to prevent the diversion of Agency assistance to military use and those against health and safety hazards. So far as the health and safety measures are concerned, a good deal of work has already been done in determining the standards of safe practice which will be the basis for the relevant rules. The Agency has published the first in its series of safety manuals, 'Safe Handling of Radioisotopes', which deals with such standards. Safeguards against the diversion or loss of nuclear materials and facilities are more difficult to devise. It is not considered feasible for

C. elegans nucleostemin is required for larval growth and germline stem cell division.

Directory of Open Access Journals (Sweden)

Michelle M Kudron

2008-08-01

Full Text Available The nucleolus has shown to be integral for many processes related to cell growth and proliferation. Stem cells in particular are likely to depend upon nucleolus-based processes to remain in a proliferative state. A highly conserved nucleolar factor named nucleostemin is proposed to be a critical link between nucleolar function and stem-cell-specific processes. Currently, it is unclear whether nucleostemin modulates proliferation by affecting ribosome biogenesis or by another nucleolus-based activity that is specific to stem cells and/or highly proliferating cells. Here, we investigate nucleostemin (nst-1 in the nematode C. elegans, which enables us to examine nst-1 function during both proliferation and differentiation in vivo. Like mammalian nucleostemin, the NST-1 protein is localized to the nucleolus and the nucleoplasm; however, its expression is found in both differentiated and proliferating cells. Global loss of C. elegans nucleostemin (nst-1 leads to a larval arrest phenotype due to a growth defect in the soma, while loss of nst-1 specifically in the germ line causes germline stem cells to undergo a cell cycle arrest. nst-1 mutants exhibit reduced levels of rRNAs, suggesting defects in ribosome biogenesis. However, NST-1 is generally not present in regions of the nucleolus where rRNA transcription and processing occurs, so this reduction is likely secondary to a different defect in ribosome biogenesis. Transgenic studies indicate that NST-1 requires its N-terminal domain for stable expression and both its G1 GTPase and intermediate domains for proper germ line function. Our data support a role for C. elegans nucleostemin in cell growth and proliferation by promoting ribosome biogenesis.

Computer-based safeguards information and accounting system

International Nuclear Information System (INIS)

1977-01-01

Acquiring, processing and analysing information about inventories and flow of nuclear materials are essential parts of IAEA safeguards. Safeguards information originates from several sources. The information to be provided is specified in the various safeguards agreements between the States and the IAEA, including both NPT agreements and safeguards trilateral agreements. Most of the safeguards information currently received by the IAEA is contained in accounting reports from the States party to the NPT. Within the frame of the material balance concept of NPT, three types of reports are provided to the IAEA by the States: Physical Inventory Listings (PIL); Inventory Change Reports (ICR); Material Balance Reports (MBR). In addition, facility design information is reported when NPT safeguards are applied and whenever there is a change in the facility or its operation. Based on this data, an accounting system is used to make available such information as the book inventories of nuclear material as a function of time, material balance evaluations, and analysis of shipments versus receipts of nuclear material. A second source of NPT safeguards information is the inspection activities carried out in the field as a necessary counterpart for verification of the data presented by the States in their accounting reports. The processing of inspection reports and other inspection data is carried out by the present system in a provisional manner until a new system, which is under development is available. The major effort currently is directed not to computer processing but toward developing and applying uniform inspection procedures and information requirements. A third source of NPT safeguards information is advanced notifications and notifications of transfer of source materials before the starting point of safeguards. Since, however, the States are not completely aware of the need and requirement to provide these data, this is a point to be emphasized in future workshops and

Work Group 1: Future Directions for International Safeguards

International Nuclear Information System (INIS)

Casterton, J.; Meylemans, P.

2013-01-01

The State-Level Concept (SLC) is a holistic approach to safeguards implementation, applicable to all States with safeguards agreements. It is based on a comprehensive and continuous State evaluation and a State level approach for each State, including a specific combination of safeguards measures. It is executed through an annual implementation plan. The SLC has the value of considering the State as a whole. It provides the opportunity to take State-specific factors into account through all stages of safeguards implementation. The implementation of the SLC permits the IAEA to be responsive to all kinds of changes arising from continuous analysis. As a result the safeguards conclusions remain soundly based and up-to-date. The SLC is implemented by the IAEA as a continuous process involving three major components: establishing knowledge about the State and drawing conclusions, determining the specific State level approach, and planning and implementing safeguards activities. The major products that emerge from this process are the State level approach, the annual implementation plan that is the basis for implementing safeguards activities in a State on an annual basis, and the safeguards conclusions, which are set out in the Safeguards Implementation Report on an annual basis. A better cooperation between IAEA and SSAC (State Systems of Accounting for and Control of nuclear material), RSAC (Regional State Systems of Accounting for and Control of nuclear material is important for developing and implementing SLC. The paper is followed by the slides of the presentation. (A.C.)

Safeguards technology development for spent fuel storage and disposal

International Nuclear Information System (INIS)

Sanders, K.E.

1991-01-01

This paper reports on facilities for monitored retrievable storage and geologic repository that will be operating in the US by 1998 and 2010 respectively. The international safeguards approach for these facilities will be determined broadly by the Safeguards Agreement and the IAEA Safeguards Criteria (currently available for 1991-1995) and defined specifically in the General Subsidiary Arrangements and Specific Facility Attachments negotiated under the US/IAEA Safeguards Agreement. Design information for these facilities types, as it is conceptualized, will be essential input to the safeguards approach. Unique design and operating features will translate into equally unique challenges to the application of international safeguards. The development and use of new safeguards technologies offers the greatest potential for improving safeguards. The development and use of new safeguards technologies offers the greatest potential for improving safeguards by enabling efficient and effective application with regard to the operator's interest, US policies, and the IAEA's statutorial obligations. Advanced unattended or remote measurement, authentication of operator's measurement, authentication of operator's measurement data, and integration of monitoring and containment/surveillance potentially are among the most fruitful areas of technology development. During the next year, a long range program plan for international safeguard technology development for monitored retrievable storage and geologic repository will be developed by the International Branch in close coordination with the Office of Civilian Radioactive Waste Management. This presentation preliminarily identifies elements of this long range program

Societal risk approach to safeguards design and evaluation

International Nuclear Information System (INIS)

Bennett, C.A.; Murphey, W.M.; Sherr, T.S.

1975-06-01

There has been much discussion and public debate concerning the effectiveness of the national system of safeguards against malevolent acts involving nuclear materials. Useful dialogue on this subject has been hampered by the lack of well-defined objectives, system parameters and boundary conditions as a framework for communication. This study provides such a framework. Expressing the safeguards objective in terms of societal risk represents a change in focus, rather than intent, from the earlier view of safeguards as a system for protecting nuclear material against theft or diversion. The study defines both the safeguards problem and the safeguards system in terms that can be related to the general safeguards objective. It is axiomatic that the first step to an effective solution is a careful definition of the problem. The significant and immediate value of this study lies in the rigorous definition and systematic organization of recognized elements into a coherent and comprehensive pattern. Although the title specifically addresses design and evaluation, the framework provided by the study will be a useful management tool for safeguards implementation and administration as well. (U.S.)

Safeguards and security progress report, January-December 1984

Energy Technology Data Exchange (ETDEWEB)

Smith, D.B. (comp.)

1986-01-01

From January to December 1984, the Los Alamos Safeguards and Security Program was involved in the activities described in the first four parts of this report: Nuclear Facility Support, Security Development and Support, Safeguards Technology Development, and International Safeguards. Part 1 covers efforts of direct assistance to the Department of Energy (DOE) and Nuclear Regulatory Commission (NRC) licensee facilities. Part 2 treats activities aimed at the security of information and computer systems. was Part 3 describes the broad development efforts essential to continuing improvements in the practice of safeguards. Although these projects are properly classified as developmental, they address recognized problems that commonly occur in operating facilities. Finally, Part 4 covers international safeguards activities, including both support to the International Atomic Energy Agency and bilateral exchanges. Enrichment plant safeguards, especially those concerning the Gas Centrifuge Enrichment Plant, required a significant portion of our resources. These efforts are beginning to provide substantial returns on our investment in technology transfer, not only in raising the level of safeguards effectiveness but also in benefiting from field experiences in operating environments.

Safeguards and security progress report, January-December 1984

International Nuclear Information System (INIS)

Smith, D.B.

1986-01-01

From January to December 1984, the Los Alamos Safeguards and Security Program was involved in the activities described in the first four parts of this report: Nuclear Facility Support, Security Development and Support, Safeguards Technology Development, and International Safeguards. Part 1 covers efforts of direct assistance to the Department of Energy (DOE) and Nuclear Regulatory Commission (NRC) licensee facilities. Part 2 treats activities aimed at the security of information and computer systems. was Part 3 describes the broad development efforts essential to continuing improvements in the practice of safeguards. Although these projects are properly classified as developmental, they address recognized problems that commonly occur in operating facilities. Finally, Part 4 covers international safeguards activities, including both support to the International Atomic Energy Agency and bilateral exchanges. Enrichment plant safeguards, especially those concerning the Gas Centrifuge Enrichment Plant, required a significant portion of our resources. These efforts are beginning to provide substantial returns on our investment in technology transfer, not only in raising the level of safeguards effectiveness but also in benefiting from field experiences in operating environments

Non-proliferation and international safeguards. [Booklet by IAEA

Energy Technology Data Exchange (ETDEWEB)

1978-01-01

This booklet consists of 13 separate, brief analyses related to the subject title, namely: The International Scope of IAEA Safeguards; Application of Safeguards Procedures; Computer-Based Safeguards Information and Accounting System; IAEA Training Activities Related to State Systems of Nuclear Materials Accountancy and Control; Surveillance and Containment Measures to Support IAEA Safeguards; International Plutonium Management; Safeguards for Reprocessing and Enrichment Plants; Non-Destructive Assay: Instruments and Techniques for Agency Safeguards; The Safeguards Analytical Laboratory: Its Functions and Analytical Facilities; Resolution of the UN General Assembly on the Treaty on the Non-Proliferation of Nuclear Weapons of 12 June 1968; The Treaty on the Non-Proliferation of Nuclear Weapons; Final Declaration of the Review Conference of the Parties to the Treaty on the Non-Proliferation of Nuclear Weapons, May 1975; Resolutions on the IAEA's Work in the Field of the Peaceful Uses of Atomic Energy, adopted by the UN General Assembly on 8 and 12 December, 1977; and a Map on the NPT situation in the world (with explanations).

Prospects for regional safeguards systems - State-level Approach

International Nuclear Information System (INIS)

Peixoto, O.J.M.

2013-01-01

The increased co-operation with Regional Safeguard's System (RSAC) is a relevant tool for strengthening effectiveness and improving the efficiency of the international safeguard. The new safeguards system that emerges from the application of the Additional Protocol (INFCIRC/540) and the full use of State-level Concept is a challenge and an opportunity for effectively incorporate RSAC into the international safeguards scheme. The challenge is to determine how the co-operation and coordination will be implemented on this new safeguards scheme. This paper presents some discussions and prospects on the issues to be faced by RSAC and IAEA during the implementation of State-level Approach (SLA) using all information available. It is also discussed how different levels of co-operation could be achieved when SLA is applied by IAEA safeguards. The paper is followed by the slides of the presentation. (authors)

Design and evaluation of an integrated safeguards system: principles

International Nuclear Information System (INIS)

Markin, J.T.; Coulter, C.A.; Gutmacher, R.G.; Whitty, W.J.

1984-07-01

An integrated safeguards system is defined as a collection of safeguards activities in which system components are coordinated to meet safeguards objectives efficiently within constraints imposed by safeguards resources, facility operations, potential adversaries, and regulatory requirements. This paper describes principles for designing and evaluating an integrated safeguards system that consists of four parts: (1) a problem definition phase that specifies resources and constraints composing the problem boundary values; (2) a system analysis/synthesis phase that describes how to select and integrate safeguards activities for efficient attainment of system objectives; (3) a system evaluation/optimization phase that defines measures of safeguards performance and develops methods for evaluating them; and (4) a decision-making phase that develops principles for selecting admissible designs and preference-ordering designs. 6 references, 4 figures, 5 tables

The Phosphorylation of Ribosomal Protein in Lemna minor

Science.gov (United States)

Trewavas, A.

1973-01-01

Sterile cultures of Lemna minor have been labeled with 32P1, and the ribosomal proteins have been examined for radioactivity. In relatively short term labeling a radioactive protein was found which ran as a single component in both urea/acetic acid and sodium lauryl sulfate gel electrophoresis. Acid hydrolysis of the labeled protein permitted the isolation of serine phosphate. After labeling to equilibrium with 32P1, calculation indicated only 0.6 to 0.75 atom of this protein phosphorus per ribosome. The phosphorylated protein is found in both polysomes and “derived” monomers and appears to be located in the ribosomal small subunit. Its apparent molecular weight is 42,000. Addition of growth-inhibiting concentrations of abscisic acid does not alter the apparent degree of labeling of this protein in 5 hours, but after 24 hours of treatment the total protein phosphorus was reduced from 0.75 atom of phosphorus per ribosome to 0.36 atom of phosphorus per ribosome. PMID:16658405

The International Atomic Energy Agency's safeguards system

International Nuclear Information System (INIS)

Wagner, W.

2000-01-01

A system of international safeguards has been established to provide assurance that nuclear materials in civilian use are not diverted from their peaceful purpose. The safeguards system is administered by the International Atomic Energy Agency/Department of Safeguards and devolves from treaties and other international agreements. Inspectors from the Agency verify reports from States about nuclear facilities by audits, observation, and measurements. (author)

Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

Directory of Open Access Journals (Sweden)

Fernanda M Cerqueira

2011-03-01

Full Text Available Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR. Since treatment of mice with dinitrophenol (DNP promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

Mice with a Mutation in the Mdm2 Gene That Interferes with MDM2/Ribosomal Protein Binding Develop a Defect in Erythropoiesis.

Directory of Open Access Journals (Sweden)

Takuya Kamio

Full Text Available MDM2, an E3 ubiquitin ligase, is an important negative regulator of tumor suppressor p53. In turn the Mdm2 gene is a transcriptional target of p53, forming a negative feedback loop that is important in cell cycle control. It has recently become apparent that the ubiquitination of p53 by MDM2 can be inhibited when certain ribosomal proteins, including RPL5 and RPL11, bind to MDM2. This inhibition, and the resulting increase in p53 levels has been proposed to be responsible for the red cell aplasia seen in Diamond-Blackfan anemia (DBA and in 5q- myelodysplastic syndrome (MDS. DBA and 5q- MDS are associated with inherited (DBA or acquired (5q- MDS haploinsufficiency of ribosomal proteins. A mutation in Mdm2 causing a C305F amino acid substitution blocks the binding of ribosomal proteins. Mice harboring this mutation (Mdm2C305F, retain a normal p53 response to DNA damage, but lack the p53 response to perturbations in ribosome biogenesis. While studying the interaction between RP haploinsufficiency and the Mdm2C305F mutation we noticed that Mdm2C305F homozygous mice had altered hematopoiesis. These mice developed a mild macrocytic anemia with reticulocytosis. In the bone marrow (BM, these mice showed a significant decrease in Ter119hi cells compared to wild type (WT littermates, while no decrease in the number of mature erythroid cells (Ter119hiCD71low was found in the spleen, which showed compensated bone marrow hematopoiesis. In methylcellulose cultures, BFU-E colonies from the mutant mice were slightly reduced in number and there was a significant reduction in CFU-E colony numbers in mutant mice compared with WT controls (p < 0.01. This erythropoietic defect was abrogated by concomitant p53 deficiency (Trp53ko/ko. Further investigation revealed that in Mdm2C305F animals, there was a decrease in Lin-Sca-1+c-Kit+ (LSK cells, accompanied by significant decreases in multipotent progenitor (MPP cells (p < 0.01. Competitive BM repopulation experiments

A computational investigation on the connection between dynamics properties of ribosomal proteins and ribosome assembly.

Directory of Open Access Journals (Sweden)

Brittany Burton

Full Text Available Assembly of the ribosome from its protein and RNA constituents has been studied extensively over the past 50 years, and experimental evidence suggests that prokaryotic ribosomal proteins undergo conformational changes during assembly. However, to date, no studies have attempted to elucidate these conformational changes. The present work utilizes computational methods to analyze protein dynamics and to investigate the linkage between dynamics and binding of these proteins during the assembly of the ribosome. Ribosomal proteins are known to be positively charged and we find the percentage of positive residues in r-proteins to be about twice that of the average protein: Lys+Arg is 18.7% for E. coli and 21.2% for T. thermophilus. Also, positive residues constitute a large proportion of RNA contacting residues: 39% for E. coli and 46% for T. thermophilus. This affirms the known importance of charge-charge interactions in the assembly of the ribosome. We studied the dynamics of three primary proteins from E. coli and T. thermophilus 30S subunits that bind early in the assembly (S15, S17, and S20 with atomic molecular dynamic simulations, followed by a study of all r-proteins using elastic network models. Molecular dynamics simulations show that solvent-exposed proteins (S15 and S17 tend to adopt more stable solution conformations than an RNA-embedded protein (S20. We also find protein residues that contact the 16S rRNA are generally more mobile in comparison with the other residues. This is because there is a larger proportion of contacting residues located in flexible loop regions. By the use of elastic network models, which are computationally more efficient, we show that this trend holds for most of the 30S r-proteins.

Phosphorylation of acidic ribosomal proteins from rabbit reticulocytes by a ribosome-associated casein kinase

DEFF Research Database (Denmark)

Issinger, O G

1977-01-01

Two acidic proteins from 80-S ribosomes were isolated and purified to homogeneity. The purified acidic proteins could be phosphorylated by casein kinase using [gamma-32P]ATP and [gamma-32P]GTP as a phosphoryl donor. The proteins became phosphorylated in situ, too. Sodium dodecyl sulfate polyacryl......Two acidic proteins from 80-S ribosomes were isolated and purified to homogeneity. The purified acidic proteins could be phosphorylated by casein kinase using [gamma-32P]ATP and [gamma-32P]GTP as a phosphoryl donor. The proteins became phosphorylated in situ, too. Sodium dodecyl sulfate...

Future directions for international safeguards - ESARDA WG on integrated safeguards

International Nuclear Information System (INIS)

Rezniczek, A.

2013-01-01

Reducing IAEA inspection effort does not mean that the overall safeguards effort will be reduced. There will be compensation and additional effort spent by states and SSACs (State Systems of Accounting and Control). State and/or regional authorities take very serious their responsibilities to safeguard the nuclear material. Enhanced cooperation between all players should be more seriously considered by the IAEA. A more effective implementation of the principle 'one job - one person' and sub-delegation of verification tasks should be taken into account for future evolution. At present, the state level approach is still based on a bottom up approach and not developed top down. The basis is still an aggregation of the facility specific safeguards approaches with some minor adjustments by state specific factors. The touchstone for a true state level approach would be a top-down development process with the result that safeguards effort spent in a state is no longer strongly correlated to the amount and quality of nuclear material in that state. The limitation of the Physical Model is that only the technical aspects are reflected. To actually perform a proliferation, the technical capability is a necessary but insufficient condition. Besides the pure technical capabilities, one has to consider the feasibility for a state to actually implement a proliferation action in its given environment. Factors to be considered are for example institutional factors, ownership of facilities and social and political structures in the state. The help a purely technical assessment can provide is also limited in cases where states have a well developed fuel cycle and thus have at their disposal all required technical capabilities. The paper is followed by the slides of the presentation. (authors)

On the control of ribosomal protein biosynthesis in Escherichia coli

International Nuclear Information System (INIS)

Pichon, J.; Marvaldi, J.; Coeroli, C.; Cozzone, A.; Marchis-Mouren, G.

1977-01-01

The rate of individual ribosomal protein synthesis relative to total protein synthesis has been determined in Escherichia coli rel + and rel - cells, under valyl-tRNA deprivation. These strains have a temperature-sensitive valyl-tRNA synthetase. Starvation was obtained following transfer of the cells to non-permissive temperature. Ribosomal proteins were obtained by treatment of either total lysates of freeze-thawed lysozyme spheroplasts or ammonium sulphate precipitate of ribosomes, with acetic acid. Differential labelling of the ribosomal proteins was observed in both strains: proteins from the rel + strain appear more labelled than those from the rel - strain, the rate of labelling of individual proteins being about the same in both strains. Moreover ribosomal proteins were found as stable during starvation as total protein. It is thus concluded that in starving cells individual ribosomal proteins are not synthesized at equal rates. This indicates that the synthesis of ribosomal proteins is not only under the control of the rel gene

IAEA safeguards: some pros and cons

International Nuclear Information System (INIS)

Kelly, P.

1986-01-01

The author gives a personal view of the International Atomic Energy Agency's (IAEA) safeguards. The IAEA safeguards system is described (including containment, surveillance and inspection), and the limitations and strengths of the system are examined. (U.K.)

AFCI Safeguards Enhancement Study: Technology Development Roadmap

Energy Technology Data Exchange (ETDEWEB)

Smith, Leon E.; Dougan, A.; Tobin, Stephen; Cipiti, B.; Ehinger, Michael H.; Bakel, A. J.; Bean, Robert; Grate, Jay W.; Santi, P.; Bryan, Steven; Kinlaw, M. T.; Schwantes, Jon M.; Burr, Tom; Lehn, Scott A.; Tolk, K.; Chichester, David; Menlove, H.; Vo, D.; Duckworth, Douglas C.; Merkle, P.; Wang, T. F.; Duran, F.; Nakae, L.; Warren, Glen A.; Friedrich, S.; Rabin, M.

2008-12-31

The Advanced Fuel Cycle Initiative (AFCI) Safeguards Campaign aims to develop safeguards technologies and processes that will significantly reduce the risk of proliferation in the U.S. nuclear fuel cycle of tomorrow. The Safeguards Enhancement Study was chartered with identifying promising research and development (R&D) directions over timescales both near-term and long-term, and under safeguards oversight both domestic and international. This technology development roadmap documents recognized gaps and needs in the safeguarding of nuclear fuel cycles, and outlines corresponding performance targets for each of those needs. Drawing on the collective expertise of technologists and user-representatives, a list of over 30 technologies that have the potential to meet those needs was developed, along with brief summaries of each candidate technology. Each summary describes the potential impact of that technology, key research questions to be addressed, and prospective development milestones that could lead to a definitive viability or performance assessment. Important programmatic linkages between U.S. agencies and offices are also described, reflecting the emergence of several safeguards R&D programs in the U.S. and the reinvigoration of nuclear fuel cycles across the globe.

The IAEA's safeguards systems. Ready for the 21st century

International Nuclear Information System (INIS)

1998-01-01

The publication reviews the IAEA's safeguards system, answering the following questions: What is being done to halt the further spread of nuclear weapons? Why are IAEA Safeguards important? what assurances do safeguards seek to provide? How are safeguards agreements implemented? What specific challenges have there been for IAEA verification? Can the IAEA prevent the diversion of declared Material? How has the safeguards system been strengthened? How much do safeguards cost? What is the future of IAEA verification? (author)

The IAEA's safeguards system. Ready for the 21st century

International Nuclear Information System (INIS)

1997-09-01

The publication reviews the IAEA's safeguards system, answering the following questions: What is being done to halt the further spread of nuclear weapons? Why are IAEA Safeguards important? What assurances do safeguards seek to provide? How are safeguards agreements implemented? What specific challenges have there been for IAEA verification? Can the IAEA prevent the diversion of declared Material? How has the safeguards system been strengthened? How much do safeguards cost? What is the future of IAEA verification?

Canada and international safeguards. Verifying nuclear non-proliferation

International Nuclear Information System (INIS)

1990-01-01

The Non-Proliferation Treaty (NPT) came into force in 1970 and now has about 140 signatory nations. By creating legal barriers against proliferation and by promoting an international non-proliferation ethic, the NPT has promoted international peace and security. A key ingredient has been the confidence generated through verification by IAEA safeguards. By the end of 1988 IAEA safeguards agreements had been concluded with about 100 countries, including Canada. Over 500 nuclear facilities worldwide are under safeguards or contain safeguarded nuclear material. The existence of this credible and effective safeguards system makes international trade in nuclear equipment and materials possible, monitoring the transfer of nuclear technology to developing countries as well as between industrial countries. Canada is committed to non-proliferation and IAEA safeguards. Canadian non-proliferation policy is among the strictest in the world, even though opportunities have been lost to sell Canadian technology abroad as a result

Middle term prospects for Japan's safeguards

International Nuclear Information System (INIS)

Ogawa, T.

2001-01-01

Japan has responded to IAEA requirements on reinforced safeguard regulations. The IAEA additional protocol entered in force in Japan on December 1999. Japan submitted a preliminary information report to IAEA on June 2000 after joint works with the Nuclear Material Control Center (NMCC) of Japan. The first annual report was submitted to IAEA on May 2001. Another activity for the additional protocol is complementary accesses. The total 36 accesses to facilities have been done from November 2000 to September 2001. Procedures of access to managements are under discussion. MEXT (Ministry of Education, Culture, Sports, Science and Technology) has been constructing the Rokkasho Safeguards On-Site Laboratory from 1997, and the Rokkasho Safeguards Center from 2000. The Design Information Verification (DIV) is now ongoing. Much more personal resources will be needed for future inspections. Therefore, the budget for safeguards is increasing in contrast to the flat base budget for the total atomic energy. As for future activity, a MOX (Mixed Oxide Fuels) fuel processing plant is one of the issues for discussion. The construction of the MOX processing plant is supposed to begin on around 2004. The conclusion of additional protocol will be given by IAEA until end of 2002. Shift to integrated safeguards are under discussions by MEXT, NMCC and utilities of Japan parallel with IAEA. Key issues of discussion are cost saving for safeguards, development of personal resources for inspectors and the role of NMCC. (Y. Tanaka)

IAEA safeguards: Staying ahead of the game

International Nuclear Information System (INIS)

2007-07-01

What are nuclear safeguards and why are they important? Answers are provided in the booklet, describing and explaining the fundamentals of the IAEA safeguards system and its role as a key element of international security, and addressing the system's implementation, costs, requirements, resources and historical development, with an emphasis on trends and strengthening measures over the past 10-15 years. Topics discussed include the safeguards State evaluation process and and the key requirements of the safeguards system including information sources (open source information, commercial satellite imagery and nuclear trade related information) and the state of the art equipment, techniques and technology (unattended and remote monitoring equipment, environmental sampling, etc.)

Developing a simulation for border safeguarding

CSIR Research Space (South Africa)

Van Rooyen, S

2011-09-01

Full Text Available Border safeguarding is the defence of territorial integrity and sovereignty, and this is a joint responsibility of the military and the police. Military doctrine for conventional warfare is not sufficient for Border Safeguarding operations due...

Concept for fuel-cycle based safeguards

International Nuclear Information System (INIS)

deMontmollin, J.M.; Higinbotham, W.A.; Gupta, D.

1985-01-01

Although the guidelines for NPT safeguards specify that the State's fuel cycle and degree of international independence are to be taken into account, the same model approach and absolute-quantity inspection goals are applied to all similar facilities, irrespective of the State's fuel cycle, and the findings are reported in those terms. A concept whereby safeguards might more effectively and efficiently accomplish the purposes of NPT safeguards is explored. The principal features are: (1) division of the fuel cycle into three zones, each containing material having a different degree of significance for safeguards; (2) closing a verified material balance around each zone, supplementing the present MBA balances for more sensitive facilities and replacing them for others; (3) maintenance by the IAEA of a current book inventory for each facility by means of immediate, abbreviated reporting of interfacility transfers; (4) near real-time analysis of material flow patterns through the fuel cycle; and (5) a periodic statement of the findings for the entire State that takes the form that there is assurance that all nuclear materials under safeguards are accounted for to some stated degree of uncertainty

Safeguards and security progress report, January-December 1983

Energy Technology Data Exchange (ETDEWEB)

Smith, D.B. (comp.)

1984-09-01

From January to December 1983, the Los Alamos Safeguards and Security Program was involved in the activities described in the first four parts of this report: Nuclear Facility Support, Security Development and Support, Safeguards Technology Development, and International Safeguards. Part 1 covers efforts of direct assistance to the Department of Energy (DOE) and Nuclear Regulatory Commission (NRC) licensee facilities. This assistance includes consultation on materials accounting problems, development of specialized techniques and instruments, and comprehensive participation in the design and implementation of advanced safeguards systems. In addition, a series of training courses in various aspects of safeguards makes the technology more accessible to those who must apply it. Part 2 treats activities aimed at the security of information and computer systems. Our focus this peiod was on continuing the activities of the Computer Security Center, which provides the basis for encouraging and disseminating this emerging technology, and on the development and demonstration of secure computer systems. Part 3 describes the broad development efforts essential to continuing improvements in the practice of safeguards. Although these projects are properly classified as developmental, they address recognized problems that commonly occur in operating facilities. Finally, Part 4 covers international safeguards activities, including both support to the International Atomic Energy Agency and bilateral exchanges. Enrichment plant safeguards, especially those concerning the Gas Centrifuge Enrichment Plant, required a significant portion of our resources. These efforts are beginning to provide substantial returns on our investment in technology transfer, not only in raising the level of safeguards effectiveness but also in our benefiting from field experiences in operating environments.

Points for Improvement in Mexican Legislation on Safeguards

International Nuclear Information System (INIS)

Maciel Sánchez, S.; Carreño Padilla, A. L.

2015-01-01

The main goal of this paper is to underline the specific points needed still to be improved on safeguards in the Mexican legal framework. The problem: Mexico proposed the Tlatelolco Treaty which was before the TNP. So the Mexican legislation on safeguards should to be one of the best around the world, but there are still points to be improved, such as a specific regulation on the topic. Justification: Remembering that the exact sciences need of the law in order to be applied in a desirable way. I mean, the safeguards could be well conceived and well worked from the physics and mathematics point of view, but in order to be followed in any country, it is necessary the right legal framework. Hypothesis: What has Mexico now in its legislation on safeguards and what remains to be done (what is pending in the Mexican legal scope of the safeguards)? Objectives: – To propose legal solutions to correct the weakness of the Mexican legal framework on Safeguards; taking into account my own experience drafting the Mexican regulation on safeguards from 2008 for the Mexican Government in my nuclear law firm “Martínez and Maciel”. – To propose a legal framework on safeguards for Mexico as it is understood by the IAEA. – To update the legal frame work on safeguards in Mexico linking it to the Back end of the spent fuel. (Considering that sooner or later the Mexican Government will have to define its politic on this topic). (author)

Safeguards and security progress report, January-December 1983

International Nuclear Information System (INIS)

Smith, D.B.

1984-09-01

From January to December 1983, the Los Alamos Safeguards and Security Program was involved in the activities described in the first four parts of this report: Nuclear Facility Support, Security Development and Support, Safeguards Technology Development, and International Safeguards. Part 1 covers efforts of direct assistance to the Department of Energy (DOE) and Nuclear Regulatory Commission (NRC) licensee facilities. This assistance includes consultation on materials accounting problems, development of specialized techniques and instruments, and comprehensive participation in the design and implementation of advanced safeguards systems. In addition, a series of training courses in various aspects of safeguards makes the technology more accessible to those who must apply it. Part 2 treats activities aimed at the security of information and computer systems. Our focus this peiod was on continuing the activities of the Computer Security Center, which provides the basis for encouraging and disseminating this emerging technology, and on the development and demonstration of secure computer systems. Part 3 describes the broad development efforts essential to continuing improvements in the practice of safeguards. Although these projects are properly classified as developmental, they address recognized problems that commonly occur in operating facilities. Finally, Part 4 covers international safeguards activities, including both support to the International Atomic Energy Agency and bilateral exchanges. Enrichment plant safeguards, especially those concerning the Gas Centrifuge Enrichment Plant, required a significant portion of our resources. These efforts are beginning to provide substantial returns on our investment in technology transfer, not only in raising the level of safeguards effectiveness but also in our benefiting from field experiences in operating environments

The Concept of Goals-Driven Safeguards

International Nuclear Information System (INIS)

Wigeland, R.; Bjornard, T.; Castle, B.

2009-01-01

The IAEA, NRC, and DOE regulations and requirements for safeguarding nuclear material and facilities have been reviewed and each organization's purpose, objectives, and scope are discussed in this report. Current safeguards approaches are re-examined considering technological advancements and how these developments are changing safeguards approaches used by these organizations. Additionally, the physical protection approaches required by the IAEA, NRC, and DOE were reviewed and the respective goals, objectives, and requirements are identified and summarized in this report. From these, a brief comparison is presented showing the high-level similarities among these regulatory organizations' approaches to physical protection. The regulatory documents used in this paper have been assembled into a convenient reference library called the Nuclear Safeguards and Security Reference Library. The index of that library is included in this report, and DVDs containing the full library are available.

IAEA safeguards for the Fissile Materials Disposition Project

International Nuclear Information System (INIS)

Close, D.A.

1995-06-01

This document is an overview of International Atomic Energy Agency (IAEA) safeguards and the basic requirements or elements of an IAEA safeguards regime. The primary objective of IAEA safeguards is the timely detection of the diversion of a significant quantity of material and the timely detection of undeclared activities. The two important components of IAEA safeguards to accomplish their primary objective are nuclear material accountancy and containment and surveillance. This overview provides guidance to the Fissile Materials Disposition Project for IAEA inspection requirements. IAEA requirements, DOE Orders, and Nuclear Regulatory Commission regulations will be used as the basis for designing a safeguards and security system for the facilities recommended by the Fissile Materials Disposition Project

Safeguards-By-Design: Guidance and Tools for Stakeholders

Energy Technology Data Exchange (ETDEWEB)

Mark Schanfein; Shirley Johnson

2012-02-01

Effective implementation of the Safeguards-by-Design (SBD) approach can help meet the challenges of global nuclear energy growth, by designing facilities that have improved safeguardability and reduced safeguards-related life cycle costs. The ultimate goal of SBD is to implement effective and efficient safeguards that reduce the burden to both the facility operator and the International Atomic Energy Agency. Since 2008, the National Nuclear Security Administration's Next Generation Safeguards Initiative's Safeguards By Design Project has initiated multiple studies and workshops with industry and regulatory stakeholders, including the IAEA, to develop relevant documents to support the implementation of SBD. These 'Good Practices Guides' describe facility and process design features that will facilitate implementation of effective nuclear material safeguards starting in the earliest phases of design through to final design. These guides, which are in their final editorial stages, start at a high level and then narrow down to specific nuclear fuel cycle facilities such as Light Water Reactors, Generation III/IV Reactors, High Temperature Gas Cooled Reactors, and Gas Centrifuge Enrichment Plants. Most recently, NGSI has begun development of a facility safeguardability assessment toolkit to assist the designer. This paper will review the current status of these efforts, provide some examples of these documents, and show some standard IAEA Unattended Instrumentation that is permanently installed in nuclear facilities for monitoring.

Safeguards-By-Design: Guidance and Tools for Stakeholders

International Nuclear Information System (INIS)

Schanfein, Mark; Johnson, Shirley

2012-01-01

Effective implementation of the Safeguards-by-Design (SBD) approach can help meet the challenges of global nuclear energy growth, by designing facilities that have improved safeguardability and reduced safeguards-related life cycle costs. The ultimate goal of SBD is to implement effective and efficient safeguards that reduce the burden to both the facility operator and the International Atomic Energy Agency. Since 2008, the National Nuclear Security Administration's Next Generation Safeguards Initiative's Safeguards By Design Project has initiated multiple studies and workshops with industry and regulatory stakeholders, including the IAEA, to develop relevant documents to support the implementation of SBD. These 'Good Practices Guides' describe facility and process design features that will facilitate implementation of effective nuclear material safeguards starting in the earliest phases of design through to final design. These guides, which are in their final editorial stages, start at a high level and then narrow down to specific nuclear fuel cycle facilities such as Light Water Reactors, Generation III/IV Reactors, High Temperature Gas Cooled Reactors, and Gas Centrifuge Enrichment Plants. Most recently, NGSI has begun development of a facility safeguardability assessment toolkit to assist the designer. This paper will review the current status of these efforts, provide some examples of these documents, and show some standard IAEA Unattended Instrumentation that is permanently installed in nuclear facilities for monitoring.

IAEA Safeguards: Past, Present, and Future

Energy Technology Data Exchange (ETDEWEB)

Santi, Peter A. [Los Alamos National Laboratory; Hypes, Philip A. [Los Alamos National Laboratory

2012-06-14

This talk will present an overview of the International Atomic Energy Agency with a specific focus on its international safeguards mission and activities. The talk will first present a brief history of the IAEA and discuss its current governing structure. It will then focus on the Safeguards Department and its role in providing assurance that nuclear materials are being used for peaceful purposes. It will then look at how the IAEA is currently evolving the way in which it executes its safeguards mission with a focus on the idea of a state-level approach.

Safeguards at NRC licensed facilities: Are we doing enough

International Nuclear Information System (INIS)

Asselstine, J.K.

1986-01-01

Safeguards at the Nuclear Regulatory Commission (NRC) facilities are discussed in this paper. The NRC is pursuing a number of initiatives in the safeguards area. The Commission is conducting a reassessment of its safeguards design basis threat statements to consider the possible implications of an explosive-laden vehicle for U.S. nuclear safeguards and to examine the comparability of safeguards features at NRC-licensed and DOE facilities. The Commission is also completing action on measures to protect against the sabotage threat from an insider at NRC-licensed facilities, and is examining the potential safety implications of safeguards measures. Finally, the NRC has developed measures to reduce the theft potential for high-enriched uranium

Introduction of designated organization to safeguards implementation in Japan

International Nuclear Information System (INIS)

Terada, Hiromi; Akiba, Mitsunori; Ando, Hisataka; Okazaki, Shuji; Irikura, Masatoshi; Kurihara, Hiroyoshi

2000-01-01

With domestic application of the IAEA new measures (program 93+2) for strengthening the effectiveness and improving the efficiency of the safeguards system, the Nuclear Regulation Laws was amended for implementation of the new measures based upon the Additional Protocol, and also the new Designated Organization System was introduced to the SSAC (States' System of Accounting for and Control of Nuclear Materials) for safeguards implementation in Japan since beginning of January 2000. On the basis of accumulated experiences of the state safeguards implementation for more than 20 years and then established standardization of the inspection procedures, the Japan's Government is able to utilize the expertise of private organizations for the safeguards implementation. Any capable organizations can be designated by the Government as the Designated Organization for all or a part of safeguards implementations on behalf of the Government. According to the amended Law, the Prime Minister can make the Designated Organization implement safeguards implementations that are defined firstly as safeguards inspections which can be done along the Government instructions without any discussions and decisions, secondarily as destructive analysis of safeguards samples, and thirdly as technical research on advanced safeguards measures. The amendment of the Law was approved by the National Diet on June 9th 1999 and entered into force on December 16th 1999. The Additional Protocol also entered into force in Japan at the same time. The NMCC (Nuclear Material Control Center) was designated as the Organization on December 27th 1999 and started the safeguards implementation in January 7th 2000. In order to prepare for the Designated Organization, the NMCC rearranged the organizational system and kept capable human resources enough for the safeguards implementations. Also the NMCC carried out many programs of education and training for the inspectors. Furthermore, manuals and criteria for the

IAEA safeguards technical manual

International Nuclear Information System (INIS)

1982-03-01

Part F of the Safeguards Technical Manual is being issued in three volumes. Volume 1 was published in 1977 and revised slightly in 1979. Volume 1 discusses basic probability concepts, statistical inference, models and measurement errors, estimation of measurement variances, and calibration. These topics of general interest in a number of application areas, are presented with examples drawn from nuclear materials safeguards. The final two chapters in Volume 1 deal with problem areas unique to safeguards: calculating the variance of MUF and of D respectively. Volume 2 continues where Volume 1 left off with a presentation of topics of specific interest to Agency safeguards. These topics include inspection planning from a design and effectiveness evaluation viewpoint, on-facility site inspection activities, variables data analysis as applied to inspection data, preparation of inspection reports with respect to statistical aspects of the inspection, and the distribution of inspection samples to more than one analytical laboratory. Volume 3 covers generally the same material as Volumes 1 and 2 but with much greater unity and cohesiveness. Further, the cook-book style of the previous two volumes has been replaced by one that makes use of equations and formulas as opposed to computational steps, and that also provides the bases for the statistical procedures discussed. Hopefully, this will help minimize the frequency of misapplications of the techniques

International seminar on safeguards information reporting and processing. Extended synopses

International Nuclear Information System (INIS)

1998-01-01

Review of the safeguards of information technology, its current developments and status of safeguards in Member States are described concerning especially the role of domestic safeguards in cooperation with IAEA Safeguards. A Number of reports is dealing with declarations provided to the IAEA pursuant to Protocols Additional to Safeguard agreements. The Information Section of the IAEA Safeguards Information Technology Division is responsible for the data entry, loading and quality control od State supplied declarations. A software system is used to process information which should be readily accessible and usable in implementation of the strengthened safeguards system. Experiences in combating illegal trafficking of nuclear materials in a number of countries are included

Adipose tissue conditioned media support macrophage lipid-droplet biogenesis by interfering with autophagic flux.

Science.gov (United States)

Bechor, Sapir; Nachmias, Dikla; Elia, Natalie; Haim, Yulia; Vatarescu, Maayan; Leikin-Frenkel, Alicia; Gericke, Martin; Tarnovscki, Tanya; Las, Guy; Rudich, Assaf

2017-09-01

Obesity promotes the biogenesis of adipose tissue (AT) foam cells (FC), which contribute to AT insulin resistance. Autophagy, an evolutionarily-conserved house-keeping process, was implicated in cellular lipid handling by either feeding and/or degrading lipid-droplets (LDs). We hypothesized that beyond phagocytosis of dead adipocytes, AT-FC biogenesis is supported by the AT microenvironment by regulating autophagy. Non-polarized ("M0") RAW264.7 macrophages exposed to AT conditioned media (AT-CM) exhibited a markedly enhanced LDs biogenesis rate compared to control cells (8.3 Vs 0.3 LDs/cells/h, p<0.005). Autophagic flux was decreased by AT-CM, and fluorescently following autophagosomes over time revealed ~20% decline in new autophagic vesicles' formation rate, and 60-70% decrease in autophagosomal growth rate, without marked alternations in the acidic lysosomal compartment. Suppressing autophagy by either targeting autophagosome formation (pharmacologically, with 3-methyladenine or genetically, with Atg12±Atg7-siRNA), decreased the rate of LD formation induced by oleic acid. Conversely, interfering with late autophago-lysosomal function, either pharmacologically with bafilomycin-A1, chloroquine or leupeptin, enhanced LD formation in macrophages without affecting LD degradation rate. Similarly enhanced LD biogenesis rate was induced by siRNA targeting Lamp-1 or the V-ATPase. Collectively, we propose that secreted products from AT interrupt late autophagosome maturation in macrophages, supporting enhanced LDs biogenesis and AT-FC formation, thereby contributing to AT dysfunction in obesity. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

From safeguards to treaty verification and the future

International Nuclear Information System (INIS)

Harry, J.

1997-01-01

Changes in safeguards techniques and changes in the context in which it has to be applied have led to a continuous evolution of safeguards. Nuclear material accountancy and its verification is still the basis of safeguards. But also other, less technical, tools are developed for the future. Will safeguards not become an idle story but continue to lay effectively and efficiently a concrete foundation for international trust and peace, there is a need for more investment in new methods and techniques to allow safeguards to keep pace with the developments, both politically and technically. Safeguards serves the international community by enhancing the mutual trust that leads to national security. That also enabled the rapid growth of international co-operation on the applications of nuclear energy. But international security is based on confidence. It is not a priori the technique that creates that sphere of confidence, the human and political interactions are at least equally important. In different cultures there are marked differences in behaviour and such differences can be easily misinterpreted. Therefore also the new safeguards has to be equally objectively established and critically executed under the close attention of all parties concerned

Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium.

Directory of Open Access Journals (Sweden)

Boa Kim

Full Text Available Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs using in vitro and in vivo complementary studies.Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2 for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (ΔΨm. Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta and muscle feed (femoral artery arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds.Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function.

Inspection methods for safeguards systems at nuclear facilities

International Nuclear Information System (INIS)

Minichino, C.; Richard, E.W.

1981-01-01

A project team at Lawrence Livermore National Laboratory has been developing inspection procedures and training materials for the NRC inspectors of safeguards systems at licensed nuclear facilities. This paper describes (1) procedures developed for inspecting for compliance with the Code of Federal Regulations, (2) training materials for safeguards inspectors on technical topics related to safeguards systems, such as computer surety, alarm systems, sampling techniques, and power supplies, and (3) an inspector-oriented methodology for evaluating the overall effectiveness of safeguards systems

The Role of Exportin-5 in MicroRNA Biogenesis and Cancer

Directory of Open Access Journals (Sweden)

Ke Wu

2018-04-01

Full Text Available MicroRNAs (miRNAs are conserved small non-coding RNAs that play an important role in the regulation of gene expression and participate in a variety of biological processes. The biogenesis of miRNAs is tightly controlled at multiple steps, such as transcription of miRNA genes, processing by Drosha and Dicer, and transportation of precursor miRNAs (pre-miRNAs from the nucleus to the cytoplasm by exportin-5 (XPO5. Given the critical role of nuclear export of pre-miRNAs in miRNA biogenesis, any alterations of XPO5, resulting from either genetic mutation, epigenetic change, abnormal expression level or posttranslational modification, could affect miRNA expression and thus have profound effects on tumorigenesis. Importantly, XPO5 phosphorylation by ERK kinase and its cis/trans isomerization by the prolyl isomerase Pin1 impair XPO5′s nucleo-to-cytoplasmic transport ability of pre-miRNAs, leading to downregulation of mature miRNAs in hepatocellular carcinoma. In this review, we focus on how XPO5 transports pre-miRNAs in the cells and summarize the dysregulation of XPO5 in human tumors. Keywords: Exportin-5, MicroRNA, Biogenesis, Dysregulation, Cancer

Safeguarding uranium enrichment facilities. Review and analysis of the status of safeguards technology for uranium enrichment facilities

International Nuclear Information System (INIS)

1977-09-01

The objective of this paper is to examine critically the diversion potential at uranium enrichment facilities and to outline a basic safeguards strategy which counters all identified hazards as completely as possible yet with a minimum of non-essential redundancy. Where existing technology does not appear to be adequate for effective safeguards, the limitations are examined, and suggestions for further R and D effort are made. Parts of this report are generally applicable to all currently known enrichment processes, while other parts are specifically directed toward facilities based on the gas centrifuge process. It is hoped that additional sections discussing a safeguards strategy for gas diffusion facilities can be added later. It should be emphasized that this is a technical report, and does not reflect any legal positions. The safeguards strategy and subsequent inspection procedures are intended as guidelines, not as negotiating positions

Strengthening IAEA Safeguards for Research Reactors

Energy Technology Data Exchange (ETDEWEB)

Reid, Bruce D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Anzelon, George A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Budlong-Sylvester, Kory [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2016-09-01

During their December 10-11, 2013, workshop in Grenoble France, which focused on the history and future of safeguarding research reactors, the United States, France and the United Kingdom (UK) agreed to conduct a joint study exploring ways to strengthen the IAEA’s safeguards approach for declared research reactors. This decision was prompted by concerns about: 1) historical cases of non-compliance involving misuse (including the use of non-nuclear materials for production of neutron generators for weapons) and diversion that were discovered, in many cases, long after the violations took place and as part of broader pattern of undeclared activities in half a dozen countries; 2) the fact that, under the Safeguards Criteria, the IAEA inspects some reactors (e.g., those with power levels under 25 MWt) less than once per year; 3) the long-standing precedent of States using heavy water research reactors (HWRR) to produce plutonium for weapons programs; 4) the use of HEU fuel in some research reactors; and 5) various technical characteristics common to some types of research reactors that could provide an opportunity for potential proliferators to misuse the facility or divert material with low probability of detection by the IAEA. In some research reactors it is difficult to detect diversion or undeclared irradiation. In addition, infrastructure associated with research reactors could pose a safeguards challenge. To strengthen the effectiveness of safeguards at the State level, this paper advocates that the IAEA consider ways to focus additional attention and broaden its safeguards toolbox for research reactors. This increase in focus on the research reactors could begin with the recognition that the research reactor (of any size) could be a common path element on a large number of technically plausible pathways that must be considered when performing acquisition pathway analysis (APA) for developing a State Level Approach (SLA) and Annual Implementation Plan (AIP). To

Psychology of nuclear safeguards

Energy Technology Data Exchange (ETDEWEB)

Parker, L [Manchester Univ. (UK)

1978-08-17

it is argued that it is unreasonable to expect the Non-Proliferation Treaty to prevent the diversion of nuclear materials from peaceful purposes to nuclear weapons, which it was designed to do. However it is considered that although prevention cannot be guaranteed it is possible to deter such diversions. The question of publicity is examined since any safeguards system is judged exclusively on what is seen to be their failures and safeguard authorities will be tempted to conceal any diversion.

IAEA safeguards information system

International Nuclear Information System (INIS)

Nardi, J.

1984-01-01

The basic concepts, structure, and operation of the Agency Safeguards Information System is discussed with respect to its role in accomplishing the overall objectives of safeguards. The basis and purposes of the Agency's information system, the structure and flow of information within the Agency's system, the relationship of the components is the Agency system, the requirements of Member States in respect of their reporting to the Agency, and the relationship of accounting data vis-a-vis facility and inspection data are described

The primary structures of ribosomal proteins S14 and S16 from the archaebacterium Halobacterium marismortui. Comparison with eubacterial and eukaryotic ribosomal proteins.

Science.gov (United States)

Kimura, J; Kimura, M

1987-09-05

The amino acid sequences of two ribosomal proteins, S14 and S16, from the archaebacterium Halobacterium marismortui have been determined. Sequence data were obtained by the manual and solid-phase sequencing of peptides derived from enzymatic digestions with trypsin, chymotrypsin, pepsin, and Staphylococcus aureus protease as well as by chemical cleavage with cyanogen bromide. Proteins S14 and S16 contain 109 and 126 amino acid residues and have Mr values of 11,964 and 13,515, respectively. Comparison of the sequences with those of ribosomal proteins from other organisms demonstrates that S14 has a significant homology with the rat liver ribosomal protein S11 (36% identity) as well as with the Escherichia coli ribosomal protein S17 (37%), and that S16 is related to the yeast ribosomal protein YS22 (40%) and proteins S8 from E. coli (28%) and Bacillus stearothermophilus (30%). A comparison of the amino acid residues in the homologous regions of halophilic and nonhalophilic ribosomal proteins reveals that halophilic proteins have more glutamic acids, asparatic acids, prolines, and alanines, and less lysines, arginines, and isoleucines than their nonhalophilic counterparts. These amino acid substitutions probably contribute to the structural stability of halophilic ribosomal proteins.

Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants

International Nuclear Information System (INIS)

Perez-de-Arce, Karen; Foncea, Rocio; Leighton, Federico

2005-01-01

It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-κB activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy

The present status of IAEA safeguards on nuclear fuel cycle facilities

International Nuclear Information System (INIS)

1978-11-01

The present IAEA approach to safeguarding various types of nuclear facilities is examined. The IAEA safeguards objectives, criteria and specific techniques are addressed, with reference e.g. to concepts like timely detection, quantities of safeguards significance, and conversion times. Material accountancy and containment and surveillance as basic features of IAEA safeguards verification are discussed. Safeguards measures for specific facility types are considered and corresponding levels of IAEA safeguards experience are assessed. Outlines of expected IAEA safeguard approaches to large bulk handling facilities are discussed. The evolutionary nature of safeguards based on experience and research and development is mentioned

Development of nuclear materials accounting for international safeguards

International Nuclear Information System (INIS)

Markin, J.T.; Augustson, R.H.; Eccleston, G.W.; Hakkila, E.A.

1991-01-01

This paper reports that nuclear materials accountancy was introduced as a primary safeguards measure in international safeguards at the inception of the EURATOM safeguards directorate in 1959 and in IAEA safeguards in 1961 with the issuance of INFCIRC 26. As measurement technology evolved and safeguarded facilities increased in both number and size, measurement methodology requirements increased as reflected in INFCIRC 66 (Rev 2.) in 1968 and later in INFCIRC 153 in 1972. Early measurements relied heavily on chemical analysis, but in the 1960s the measurements evolved more and more toward nondestructive assay. Future nuclear materials accountancy systems will increase in complexity, driven by larger and more complex facilities; more stringent health, safety, and environmental considerations; and unattended automation in facility operations

Training to raise staff awareness about safeguarding children.

Science.gov (United States)

Fleming, Jane

2015-04-01

To improve outcomes for children and young people health organisations are required to train all staff in children's safeguarding. This creates difficulties for large complex organisations where most staff provide services to the adult population. Heart of England NHS Foundation Trust is a large acute and community trust that had difficulties in engaging staff in children's safeguarding training. Compliance rates for clinical staff who were trained in children's safeguarding were low and needed to be addressed. This article sets out why safeguarding training is important for all staff and how the trust achieved staff engagement and improved compliance rates. To evaluate, maintain and develop safeguarding knowledge, understanding, skills, attitude and behaviour further resources are planned to allow access to learning resources in a variety of formats.

Hypoxic stress-induced changes in ribosomes of maize seedling roots

International Nuclear Information System (INIS)

Bailey-Serres, J.; Freeling, M.

1990-01-01

The hypoxic stress response of Zea mays L. seedling roots involves regulation of gene expression at transcriptional and posttranscriptional levels. We investigated the effect of hypoxia on the translational machinery of seedling roots. The levels of monoribosomes and ribosomal subunits increased dramatically within 1 hour of stress. Prolonged hypoxia resulted in continued accumulation of nontranslating ribosomes, as well as increased levels of small polyribosomes. The return of seedlings to normal aerobic conditions resulted in recovery of normal polyribosome levels. Comparison of ribosomal proteins from control and hypoxic roots revealed differences in quantity and electrophoretic mobility. In vivo labeling of roots with [ 35 S]methionine revealed variations in newly synthesized ribosomal proteins. In vivo labeling of roots with [ 32 P]orthophosphate revealed a major reduction in the phosphorylation of a 31 kilodalton ribosomal protein in hypoxic stressed roots. In vitro phosphorylation of ribosomal proteins by endogenous kinases was used to probe for differences in ribosome structure and composition. The patterns of in vitro kinased phosphoproteins of ribosomes from control and hypoxic roots were not identical. Variation in phosphoproteins of polyribosomes from control and hypoxic roots, as well as among polyribosomes from hypoxic roots were observed. These results indicate that modification of the translational machinery occurs in response to hypoxic stress

Ribosomes slide on lysine-encoding homopolymeric A stretches

Science.gov (United States)

Koutmou, Kristin S; Schuller, Anthony P; Brunelle, Julie L; Radhakrishnan, Aditya; Djuranovic, Sergej; Green, Rachel

2015-01-01

Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant. Here we show that mRNAs encoding iterated lysine codons, AAA or AAG, differentially impact protein synthesis: insertion of iterated AAA codons into an ORF diminishes protein expression more than insertion of synonymous AAG codons. Kinetic studies in E. coli reveal that differential protein production results from pausing on consecutive AAA-lysines followed by ribosome sliding on homopolymeric A sequence. Translation in a cell-free expression system demonstrates that diminished output from AAA-codon-containing reporters results from premature translation termination on out of frame stop codons following ribosome sliding. In eukaryotes, these premature termination events target the mRNAs for Nonsense-Mediated-Decay (NMD). The finding that ribosomes slide on homopolymeric A sequences explains bioinformatic analyses indicating that consecutive AAA codons are under-represented in gene-coding sequences. Ribosome ‘sliding’ represents an unexpected type of ribosome movement possible during translation. DOI: http://dx.doi.org/10.7554/eLife.05534.001 PMID:25695637

Safeguards Workforce Repatriation, Retention and Utilization

Energy Technology Data Exchange (ETDEWEB)

Gallucci, Nicholas [Brookhaven National Lab. (BNL), Upton, NY (United States); Poe, Sarah [Brookhaven National Lab. (BNL), Upton, NY (United States)

2015-10-01

Brookhaven National Laboratory was tasked by NA-241 to assess the transition of former IAEA employees back to the United States, investigating the rate of retention and overall smoothness of the repatriation process among returning safeguards professionals. Upon conducting several phone interviews, study authors found that the repatriation process went smoothly for the vast majority and that workforce retention was high. However, several respondents expressed irritation over the minimal extent to which their safeguards expertise had been leveraged in their current positions. This sentiment was pervasive enough to prompt a follow-on study focusing on questions relating to the utilization rather than the retention of safeguards professionals. A second, web-based survey was conducted, soliciting responses from a larger sample pool. Results suggest that the safeguards workforce may be oversaturated, and that young professionals returning to the United States from Agency positions may soon encounter difficulties finding jobs in the field.

Handbook of nuclear data for safeguards

International Nuclear Information System (INIS)

Lammer, M.; Schwerer, O.

1991-06-01

This handbook contains nuclear data needed by safeguards users for their work. It was initiated by an IAEA working group, and the contents were defined by the relies to a questionnaire sent to safeguards specialists. This is a preliminary edition of the handbook for distribution to safeguards and nuclear data experts for review. The present edition of the handbook contains the following basic nuclear data: actinides: nuclear decay data, thermal neutron cross sections and resonance integrals, prompt neutron data, delayed neutron data; fission products: nuclear decay data, thermal neutron capture cross sections and resonance integrals; fission product yields. Also included are appendices that summarize the data requested by safeguards users, and that present a number of questions to them and to data experts on the data contained in this preliminary issue and about additional data for possible inclusion in future editions and updates of the handbook

International seminar on safeguards information reporting and processing. Extended synopses

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-12-31

Review of the safeguards of information technology, its current developments and status of safeguards in Member States are described concerning especially the role of domestic safeguards in cooperation with IAEA Safeguards. A Number of reports is dealing with declarations provided to the IAEA pursuant to Protocols Additional to Safeguard agreements. The Information Section of the IAEA Safeguards Information Technology Division is responsible for the data entry, loading and quality control od State supplied declarations. A software system is used to process information which should be readily accessible and usable in implementation of the strengthened safeguards system. Experiences in combating illegal trafficking of nuclear materials in a number of countries are included Refs, figs, 1 tab

Integrating virtual reality applications in nuclear safeguards

International Nuclear Information System (INIS)

Barletta, Michael; Crete, Jean-Maurice; Pickett, Susan

2011-01-01

Virtual reality (VR) tools have already been developed and deployed in the nuclear industry, including in nuclear power plant construction, project management, equipment and system design, and training. Recognized as powerful tools for, inter alia, integration of data, simulation of activities, design of facilities, validation of concepts and mission planning, their application in nuclear safeguards is still very limited. However, VR tools may eventually offer transformative potential for evolving the future safeguards system to be more fully information-driven. The paper focuses especially on applications in the area of training that have been underway in the Department of Safeguards of the International Atomic Energy Agency. It also outlines future applications envisioned for safeguards information and knowledge management, and information-analytic collaboration. The paper identifies some technical and programmatic pre-requisites for realizing the integrative potential of VR technologies. If developed with an orientation to integrating applications through compatible platforms, software, and models, virtual reality tools offer the long-term potential of becoming a real 'game changer,' enabling a qualitative leap in the efficiency and effectiveness of nuclear safeguards. The IAEA invites Member States, industry, and academia to make proposals as to how such integrating potential in the use of virtual reality technology for nuclear safeguards could be realized. (author)

Germ Plasm Biogenesis--An Oskar-Centric Perspective.

Science.gov (United States)

Lehmann, Ruth

2016-01-01

Germ granules are the hallmark of all germ cells. These membrane-less, electron-dense structures were first observed over 100 years ago. Today, their role in regulating and processing transcripts critical for the establishment, maintenance, and protection of germ cells is well established, and pathways outlining the biochemical mechanisms and physical properties associated with their biogenesis are emerging. © 2016 Elsevier Inc. All rights reserved.

The Unexplored Mechanisms and Regulatory Functions of Ribosomal Translocation

Science.gov (United States)

Alejo, Jose Luis

In every cell, protein synthesis is carried out by the ribosome, a complex macromolecular RNA-protein assembly. Decades of structural and kinetic studies have increased our understanding of ribosome initiation, decoding, translocation and termination. Yet, the underlying mechanism of these fundamental processes has yet to be fully delineated. Hence, the molecular basis of regulation remains obscure. Here, single-molecule fluorescence methods are applied to decipher the mechanism and regulatory roles of the multi-step process of directional substrate translocation on the ribosome that accompanies every round of protein synthesis. In Chapter 1, single-molecule fluorescence resonance energy transfer (smFRET) is introduced as a tool for studying bacterial ribosome translocation. Chapter 2 details the experimental methods. In Chapter 3, the elongation factor G(EF-G)-catalyzed movement of substrates through the ribosome is examined from several perspectives or signals reporting on various degrees of freedom of ribosome dynamics. Two ribosomal states interconvert in the presence of EF-G(GDP), displaying novel head domain motions, until relocking takes place. In Chapter 4, in order to test if the mentioned fluctuations leading to relocking are correlated to the engagement of the P-site by the peptidyl-tRNA, the translocation of miscoded tRNAs is studied. Severe defects in the relocking stages of translocation reveal the correlation between this new stage of translocation and P-site tRNA engagement.

Transit Matching for International Safeguards

International Nuclear Information System (INIS)

Gilligan, K.; Whitaker, M.; Oakberg, J.

2015-01-01

In 2013 the U.S. Department of Energy / National Nuclear Security Administration Office of Non-proliferation and International Security (NIS) supported a study of the International Atomic Energy Agency's (IAEA) processes and procedures for ensuring that shipments of nuclear material correspond to (match) their receipts (i.e., transit matching). Under Comprehensive Safeguards Agreements, Member States are obliged to declare such information within certain time frames. Nuclear weapons states voluntarily declare such information under INFCIRC/207. This study was funded by the NIS Next Generation Safeguards Initiative (NGSI) Concepts and Approaches program. Oak Ridge National Laboratory led the research, which included collaboration with the U.S. Nuclear Regulatory Commission, the U.S. Nuclear Material Management and Safeguards System (NMMSS), and the IAEA Section for Declared Information Analysis within the Department of Safeguards. The project studied the current transit matching methodologies, identified current challenges (e.g., level of effort and timeliness), and suggested improvements. This paper presents the recommendations that resulted from the study and discussions with IAEA staff. In particular, it includes a recommendation to collaboratively develop a set of best reporting practices for nuclear weapons states under INFCIRC/207. (author)

Integrated safeguards: Australian views and experience

International Nuclear Information System (INIS)

Carlson, J.; Bragin, V.; Leslie, R.

2001-01-01

Full text: Australia has had a pioneering role in assisting the IAEA to develop the procedures and methods for strengthened safeguards, both before and after the conclusion of Australia's additional protocol. Australia played a key role in the negotiation of the model additional protocol, and made ratification a high priority in order to encourage early ratification by other States. Australia was the first State to ratify an additional protocol, on 10 December 1997, and was the first State in which the IAEA exercised complementary access and managed access under an additional protocol. Australia has undergone three full cycles of evaluation under strengthened safeguards measures, enabling the Agency to conclude it was appropriate to commence implementation of integrated safeguards. In January 2001 Australia became the first State in which integrated safeguards are being applied. As such, Australia's experience will be of interest to other States as they consult with the IAEA on the modalities for the introduction of integrated safeguards in their jurisdictions. The purpose of the paper is to outline Australia's experience with strengthened safeguards and Australia's views on the implementation of integrated safeguards. Australia has five Material Balance Areas (MBAs), the principal one covering the 10 MWt research reactor at Lucas Heights and the associated inventory of fresh and irradiated HEU fuel. Under classical safeguards, generally Australia was subject to annual Physical Inventory Verifications (PIVs) for the four MBAs at Lucas Heights, plus quarterly interim inspections, making a total of four inspections a year (PIVs for the different MBAs were conducted concurrently with each other or with interim inspections in other MBAs), although there was a period when the fresh fuel inventory exceeded one SQ, requiring monthly inspections. Under strengthened safeguards, this pattern of four inspections a year was maintained, with the addition of complementary

Societal risk approach to safeguards design and evaluation

International Nuclear Information System (INIS)

Murphey, W.M.; Sherr, T.S.; Bennett, C.A.

1975-01-01

A comprehensive rationale for safeguards design and evaluation, and a framework for continuing systematic assessment of the system's effectiveness and efficient allocation of available safeguards resources for balanced protection, were developed. The societal risk approach employed considers the likelihood of successful destructive acts involving nuclear materials or facilities and the magnitude of the effects on society. The safeguards problem is described in terms of events affecting societal risk and adversary actions. Structure of the safeguards system and the evaluation of its adequacy are discussed. Adversary characteristics are also discussed

Comprehensive safeguards evaluation methods and societal risk analysis

International Nuclear Information System (INIS)

Richardson, J.M.

1982-03-01

Essential capabilities of an integrated evaluation methodology for analyzing safeguards systems are discussed. Such a methodology must be conceptually meaningful, technically defensible, discriminating and consistent. A decompostion of safeguards systems by function is mentioned as a possible starting point for methodology development. The application of a societal risk equation to safeguards systems analysis is addressed. Conceptual problems with this approach are discussed. Technical difficulties in applying this equation to safeguards systems are illustrated through the use of confidence intervals, information content, hypothesis testing and ranking and selection procedures

Some problems relating to application of safeguards in the future

International Nuclear Information System (INIS)

Tolchenkov, D.L.

1983-01-01

By the end of this century there will have been a considerable increase in the amount of nuclear material and the number of facilities subject to IAEA safeguards. The IAEA will therefore be faced with problems due to the increased volume of safeguards activity, the application of safeguards to new types of facility and to large facilities, the optimization of the existing IAEA safeguards system and so on. The authors analyse the potential growth in the IAEA's safeguards activities up to the year 2000 and consider how to optimize methods for the application of safeguards, taking into account a number of factors relating to a State's nuclear activity, the application of full-scope IAEA safeguards etc. On the basis of a hypothetical model of the nuclear fuel cycle that allows for the factors considered as part of the International Nuclear Fuel Cycle Evaluation (INFCE), the authors assess the possible risk of diversion as a function of a full-scope safeguards effort. They also examine possible conceptual approaches to safeguarding large-scale facilities such as fuel reprocessing and uranium enrichment plants. (author)