Regulatory alerts for dietary supplements in Canada and the United States, 2005-13.

Science.gov (United States)

Abe, Andrew M; Hein, Darren J; Gregory, Philip J

2015-06-01

Dietary supplement regulatory alerts published by the Food and Drug Administration (FDA) and Health Canada were evaluated and characterized. FDA MedWatch and Health Canada websites were reviewed to identify regulatory alerts regarding dietary supplements from January 1, 2005, through December 31, 2013. Alerts were analyzed to identify product characteristics that may be predictive of product quality issues and potential patient harm. A total of 1560 dietary supplement-related regulatory alerts were identified. Of those, 1287 (83%) were identified through Health Canada, and 273 (18%) were identified through FDA MedWatch. The country of origin of dietary supplements associated with regulatory alerts was not provided in most regulatory alerts; however, when their origin was provided, the United States was the most common. Dietary supplements intended for sexual enhancement were the subject of 33% of all regulatory alerts identified. Products purchased online were the most likely to be associated with a regulatory alert. Dietary supplements intended for sexual enhancement, weight loss, and bodybuilding or athletic performance appeared to pose the greatest risk for patient harm due to product contamination with a pharmaceutical such as a phosphodiesterase-5 inhibitor or sibutramine. Analysis of Canadian and U.S. regulatory alerts concerning dietary supplements revealed that more than 80% of the composite alerts were issued by Health Canada. The most common intended uses of supplements for which alerts were issued were sexual enhancement, weight loss, and bodybuilding or athletic performance. The most common reason for alerts was the presence of a pharmaceutical contaminant. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

77 FR 17569 - United States-Canada Regulatory Cooperation Council (RCC)-Transportation-Dangerous Goods Working...

Science.gov (United States)

2012-03-26

... identified in the Joint Action Plan, the Transportation--Dangerous Goods Working Group led by senior...)-- Transportation--Dangerous Goods Working Group AGENCY: Pipeline and Hazardous Materials Safety Administration...--Dangerous Goods Working Group, of the United States-Canada Regulatory Cooperation Council (RCC). Comments...

The influence of regulatory fit and interactivity on brand satisfaction and trust in E-health marketing inside 3D virtual worlds (Second Life).

Science.gov (United States)

Jin, Seung-A Annie; Lee, Kwan Min

2010-12-01

Interactive three-dimensional (3D) virtual environments like Second Life have great potential as venues for effective e-health marketing and e-brand management. Drawing from regulatory focus and interactivity literatures, this study examined the effects of the regulatory fit that consumers experience in interactive e-health marketing on their brand satisfaction and brand trust. The results of a two-group comparison experiment conducted within Second Life revealed that consumers in the regulatory fit condition show greater brand satisfaction and brand trust than those in the regulatory misfit condition, thus confirming the persuasive influence of regulatory fit in e-brand management inside 3D virtual worlds. In addition, a structural equation modeling analysis demonstrated the mediating role of consumers' perceived interactivity in explaining the processional link between regulatory fit and brand evaluation. Theoretical contributions and managerial implications of these findings are discussed.

Adaptation of Tri-molecular fluorescence complementation allows assaying of regulatory Csr RNA-protein interactions in bacteria.

Science.gov (United States)

Gelderman, Grant; Sivakumar, Anusha; Lipp, Sarah; Contreras, Lydia

2015-02-01

sRNAs play a significant role in controlling and regulating cellular metabolism. One of the more interesting aspects of certain sRNAs is their ability to make global changes in the cell by interacting with regulatory proteins. In this work, we demonstrate the use of an in vivo Tri-molecular Fluorescence Complementation assay to detect and visualize the central regulatory sRNA-protein interaction of the Carbon Storage Regulatory system in E. coli. The Carbon Storage Regulator consists primarily of an RNA binding protein, CsrA, that alters the activity of mRNA targets and of an sRNA, CsrB, that modulates the activity of CsrA. We describe the construction of a fluorescence complementation system that detects the interactions between CsrB and CsrA. Additionally, we demonstrate that the intensity of the fluorescence of this system is able to detect changes in the affinity of the CsrB-CsrA interaction, as caused by mutations in the protein sequence of CsrA. While previous methods have adopted this technique to study mRNA or RNA localization, this is the first attempt to use this technique to study the sRNA-protein interaction directly in bacteria. This method presents a potentially powerful tool to study complex bacterial RNA protein interactions in vivo. © 2014 Wiley Periodicals, Inc.

Extra-regulatory impact tests and analyses of the structural evaluation test unit

International Nuclear Information System (INIS)

Ludwigsen, J.S.; Ammerman, D.J.

1995-01-01

The structural evaluation test unit is roughly equivalent to a 1/3 scale model of a high level waste rail cask. The test unit was designed to just meet the requirements of NRC Regulatory Guide 7.6 when subjected to a 9 m (30 ft) free drop resulting in an impact velocity of 13.4 m/s (30 mph) onto an unyielding target in the end-on orientation. The test unit was then subjected to impacts with higher velocities to determine the amount of built-in conservatism in this design approach. Test impacts of 13.4, 20.1 and 26.8 m/s (30, 45, and 60 mph) were performed. This paper will describe the design, testing, and comparison of measured strains and deformations to the equivalent analytical predictions

Regulatory approaches in the United States of America for safe management and disposal of long-lived radionuclides

International Nuclear Information System (INIS)

Greeves, J.T.; Bell, M.J.; Nelson, R.A.

1998-01-01

Regulation of the safe management and disposal of commercial, man-made, long-lived radioactive wastes in the United States is the responsibility of the US Nuclear Regulatory Commission (NRC). In some instances, state regulatory authorities have entered into agreements with the NRC to exercise regulatory authority over management and disposal of low-level radioactive wastes and uranium mill tailings within their borders. The legal and regulatory framework employed to achieve safe management and disposal of long-lived radioactive wastes in the US regulatory system is quite detailed, and in many cases the requirements are considerably prescriptive. The NRC has undertaken an initiative to move in the direction of adopting risk-informed, performance-based and risk-informed, less-prescriptive regulations. The current status and future direction of the legal and regulatory framework for management and disposal of commercial long-lived radioactive waste in the US is described. (author)

Data Science and Political Economy: Application to Financial Regulatory Structure

Directory of Open Access Journals (Sweden)

Sharyn O'Halloran

2016-11-01

Full Text Available The development of computational data science techniques in natural language processing and machine learning algorithms to analyze large and complex textual information opens new avenues for studying the interaction between economics and politics. We apply these techniques to analyze the design of financial regulatory structure in the United States since 1950. The analysis focuses on the delegation of discretionary authority to regulatory agencies in promulgating, implementing, and enforcing financial sector laws and overseeing compliance with them. Combining traditional studies with the new machine learning approaches enables us to go beyond the limitations of both methods and offer a more precise interpretation of the determinants of financial regulatory structure.

Exploring the impact of permitting and local regulatory processes on residential solar prices in the United States

International Nuclear Information System (INIS)

Burkhardt, Jesse; Wiser, Ryan; Darghouth, Naïm; Dong, C.G.; Huneycutt, Joshua

2015-01-01

This article statistically isolates the impacts of city-level permitting and other local regulatory processes on residential PV prices in the United States. We combine data from two “scoring” mechanisms that independently capture local regulatory process efficiency with the largest dataset of installed PV prices in the United States. We find that variations in local permitting procedures can lead to differences in average residential PV prices of approximately $0.18/W between the jurisdictions with the least-favorable and most-favorable permitting procedures. Between jurisdictions with scores across the middle 90% of the range (i.e., 5th percentile to 95th percentile), the difference is $0.14/W, equivalent to a $700 (2.2%) difference in system costs for a typical 5-kW residential PV installation. When considering variations not only in permitting practices, but also in other local regulatory procedures, price differences grow to $0.64–$0.93/W between the least-favorable and most-favorable jurisdictions. Between jurisdictions with scores across the middle 90% of the range, the difference is equivalent to a price impact of at least $2500 (8%) for a typical 5-kW residential PV installation. These results highlight the magnitude of cost reduction that might be expected from streamlining local regulatory regimes. - Highlights: • We show local regulatory processes meaningfully affect U.S. residential PV prices. • We use regression analysis and two mechanisms for “scoring” regulatory efficiency. • Local permitting procedure variations can produce PV price differences of $0.18/W. • Broader regulatory variations can produce PV price differences of $0.64–$0.93/W. • The results suggest the cost-reduction potential of streamlining local regulations

Conformance to Regulatory Guide 1.97 Slurry Power Station, Unit Nos. 1 and 2 (Docket Nos. 50-280 and 50-281)

International Nuclear Information System (INIS)

Stoffel, J.W.

1985-09-01

This EG and G Idaho, Inc., report reviews the submittals for Regulatory Guide 1.97, Revision 3, for Unit Nos. 1 and 2 of the Surry Power Station and identifies areas of nonconformance to the regulatory guide. Exceptions to Regulatory Guide 1.97 are evaluated and those areas where sufficient basis for acceptability is not provided are identified

A regulatory view of containment integrity in the United Kingdom

International Nuclear Information System (INIS)

Bradford, P.M.; Patchett, C.M.

1994-01-01

This paper reviews the approach of HM Nuclear Installations Inspectorate (NII) to containment integrity in the United Kingdom (UK). NII is that part of the regulatory authority, the Health and Safety Executive (HSE), which administers the UK's nuclear site licensing system. A major part of the licensing process lies in the assessment of licensees' submissions for new and existing plant. The purpose of this paper is to: briefly review our revised Safety Assessment Principles, describe our assessment and inspection activities on the primary containment building of the Sizewell B PWR which is progressing to full power operation in 1994 and, to indicate our views on the possible directions for future research into containment design and performance. (author). 5 refs

National legislative and regulatory activities: Armenia, Brazil, Canada, France, Georgia, Greece, India, Ireland, Japan, Lithuania, Switzerland, Ukraine, United Arab Emirates, United States

International Nuclear Information System (INIS)

Anon.

2012-01-01

Armenia: Nuclear safety and radiological protection (Initiation of process relating to the life extension of nuclear power plant unit 2). Brazil: General legislation (Authorisation for the construction of nuclear submarines). Canada: Environmental protection (Changes to the federal environmental assessment law). France: Radioactive waste management (Changes to the National Plan for Management of Radioactive Materials and Waste). Georgia: Nuclear safety and radiological protection (New law on nuclear and radiation safety). Greece: Nuclear safety (Presidential decree on nuclear safety transposing European Council directive into national legislation); Emergency preparedness and response (Establishment of national plan for nuclear, radiological, biological and chemical threats). India: Licensing and regulatory infrastructure (Pending invitation for the IAEA's Integrated Regulatory Review Services to conduct a peer review); Liability and compensation (Committee on Subordinate Legislation Report on the Civil Liability for Nuclear Damage Rules, 2011). Ireland: Nuclear safety and radiological protection (Adoption of revised regulations regarding radiological protection). Japan: Nuclear Regulation Authority Act (Structure, Functions, New Nuclear Emergency Preparedness System). Lithuania: General legislation (New laws affecting Visaginas nuclear power plant project implementation); Licensing and regulatory infrastructure (Revised rules for issuing licenses and permits); Nuclear security (Revised physical protection requirements, New rules for the preparation of security plans); Radioactive waste management (Revised Rules of Procedure of Submission of Data on Activities Involving Radioactive Waste Disposal to the European Commission). Switzerland: General legislation (Draft energy strategy open for public comment until January 2013). Ukraine: Radioactive waste management (New law on development of a central repository); General legislation (Law providing for the location

Conformance to Regulatory Guide 1.97, Perry Nuclear Power Plant, Unit Nos. 1 and 2 (Docket Nos. 50-440 and 50-441)

International Nuclear Information System (INIS)

Udy, A.C.

1985-03-01

This EG and G Idaho, Inc., report provides a review of the submittals for Regulatory Guide 1.97, Revision 2, for the Perry Nuclear Power Plant, Unit Nos. 1 and 2. Any exception to the guidelines of Regulatory Guide 1.97 are evaluated

Conformance to Regulatory Guide 1.97, Joseph M. Farley Nuclear Plant, Unit Nos. 1 and 2 (Docket No. 50-348 and 50-364)

International Nuclear Information System (INIS)

Stoffel, J.W.

1985-05-01

This EG and G Idaho, Inc., report reviews the submittals for Regulatory Guide 1.97 for Unit Nos. 1 and 2 of the Joseph M. Farley Nuclear Plant and identifies areas of nonconformance to the regulatory guide. Exceptions to Regulatory Guide 1.97 are evaluated and those areas where sufficient basis for acceptability is not provided are identified

Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.

Science.gov (United States)

Du, Meijun; Yuan, Tiezheng; Schilter, Kala F; Dittmar, Rachel L; Mackinnon, Alexander; Huang, Xiaoyi; Tschannen, Michael; Worthey, Elizabeth; Jacob, Howard; Xia, Shu; Gao, Jianzhong; Tillmans, Lori; Lu, Yan; Liu, Pengyuan; Thibodeau, Stephen N; Wang, Liang

2015-01-01

Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Interaction between adipose tissue-derived mesenchymal stem cells and regulatory T-cells

OpenAIRE

Engela, Anja; Baan, Carla; Peeters, Anna; Weimar, Willem; Hoogduijn, Martin

2013-01-01

textabstractMesenchymal stem cells (MSCs) exhibit immunosuppressive capabilities, which have evoked interest in their application as cell therapy in transplant patients. So far it has been unclear whether allogeneic MSCs and host regulatory T-cells (Tregs) functionally influence each other. We investigated the interaction between both cell types using perirenal adipose tissue-derived MSCs (ASCs) from kidney donors and Tregs from blood bank donors or kidney recipients 6 months after transplant...

The enforcement program of the nuclear regulatory commission in the United States

International Nuclear Information System (INIS)

Thornburg, H.D.

1977-01-01

The enforcement program of the United States Nuclear Regulatory Commission consists of a clearly spelled out, evenly applied program of deterrents which escalate according to the nature of the offense and the past history of the licensee's noncompliances. Ninety-eight percent of all enforcement actions are normally handled by the five Regional offices. Only one percent of noncompliances have been classed as violations where significant safety consequences occurred. A strong and timely enforcement program is essential to insure that licensees fulfill their obligations to protect the public and the environment. (Auth.) [fr

Scientific and Regulatory Perspectives in Herbal and Dietary Supplement Associated Hepatotoxicity in the United States

Directory of Open Access Journals (Sweden)

Mark I. Avigan

2016-03-01

Full Text Available In the United States (US, the risk of hepatotoxicity linked to the widespread use of certain herbal products has gained increased attention among regulatory scientists. Based on current US law, all dietary supplements sold domestically, including botanical supplements, are regulated by the Food and Drug Administration (FDA as a special category of foods. Under this designation, regulatory scientists do not routinely evaluate the efficacy of these products prior to their marketing, despite the content variability and phytochemical complexity that often characterizes them. Nonetheless, there has been notable progress in the development of advanced scientific methods to qualitatively and quantitatively measure ingredients and screen for contaminants and adulterants in botanical products when hepatotoxicity is recognized.

A regulatory view of containment integrity in the United Kingdom

Energy Technology Data Exchange (ETDEWEB)

Bradford, P M; Patchett, C M [Health and Safety Executive, Bootle (United Kingdom). Nuclear Installations Inspectorate

1994-12-31

This paper reviews the approach of HM Nuclear Installations Inspectorate (NII) to containment integrity in the United Kingdom (UK). NII is that part of the regulatory authority, the Health and Safety Executive (HSE), which administers the UK`s nuclear site licensing system. A major part of the licensing process lies in the assessment of licensees` submissions for new and existing plant. The purpose of this paper is to: briefly review our revised Safety Assessment Principles, describe our assessment and inspection activities on the primary containment building of the Sizewell B PWR which is progressing to full power operation in 1994 and, to indicate our views on the possible directions for future research into containment design and performance. (author). 5 refs.

Reactor aging research. United States Nuclear Regulatory Commission

International Nuclear Information System (INIS)

Vassilaros, M.G.

1998-01-01

The reactor ageing research activities in USA described, are focused on the research of reactor vessel integrity, including regulatory issues and technical aspects. Current emphasis are described for fracture analysis, embrittlement research, inspection capabilities, validation od annealing rule, revision of regulatory guide

Virginia Power's regulatory reduction program

International Nuclear Information System (INIS)

Miller, G.D.

1996-01-01

Virginia Power has two nuclear plants, North Anna and Surry Power Stations, which have two units each for a total of four nuclear units. In 1992, the Nuclear Regulatory Commission solicited comments from the nuclear industry to obtain their ideas for reducing the regulatory burden on nuclear facilities. Pursuant to the new regulatory climate, Virginia Power developed an internal program to evaluate and assess the regulatory and self-imposed requirements to which they were committed, and to pursue regulatory relief or internal changes where possible and appropriate. The criteria were that public safety must be maintained, and savings must be significant. Up to the date of the conference, over US$22 million of one-time saving had been effected, and US$2.75 million in annual savings

Conformance to Regulatory Guide 1.97, Shearon Harris Nuclear Power Plant, Unit Nos. 1 and 2 (Docket Nos. 50-400 and 50-401)

International Nuclear Information System (INIS)

Stoffel, J.W.

1985-09-01

This EG and G Idaho, Inc. report reviews the submittals for Regulatory Guide 1.97, Revision 3, for Unit Nos. 1 and 2 of the Shearon Harris Nuclear Power Plant and identifies areas of nonconformance to the regulatory guide. Exceptions to Regulatory Guide 1.97 are evaluated and those areas where sufficient basis for acceptability is not provided are identified. 7 refs

Orientation-dependent interaction between Drosophila insulators is a property of this class of regulatory elements.

Science.gov (United States)

Kyrchanova, Olga; Chetverina, Darya; Maksimenko, Oksana; Kullyev, Andrey; Georgiev, Pavel

2008-12-01

Insulators are defined as a class of regulatory elements that delimit independent transcriptional domains within eukaryotic genomes. According to previous data, an interaction (pairing) between some Drosophila insulators can support distant activation of a promoter by an enhancer. Here, we have demonstrated that pairs of well-studied insulators such as scs-scs, scs'-scs', 1A2-1A2 and Wari-Wari support distant activation of the white promoter by the yeast GAL4 activator in an orientation-dependent manner. The same is true for the efficiency of the enhancer that stimulates white expression in the eyes. In all insulator pairs tested, stimulation of the white gene was stronger when insulators were inserted between the eye enhancer or GAL4 and the white promoter in opposite orientations relative to each other. As shown previously, Zw5, Su(Hw) and dCTCF proteins are required for the functioning of different insulators that do not interact with each other. Here, strong functional interactions have been revealed between DNA fragments containing binding sites for either Zw5 or Su(Hw) or dCTCF protein but not between heterologous binding sites [Zw5-Su(Hw), dCTCF-Su(Hw), or dCTCF-Zw5]. These results suggest that insulator proteins can support selective interactions between distant regulatory elements.

TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks.

Science.gov (United States)

Lepoivre, Cyrille; Bergon, Aurélie; Lopez, Fabrice; Perumal, Narayanan B; Nguyen, Catherine; Imbert, Jean; Puthier, Denis

2012-01-31

Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions. Furthermore, given the intrinsic complexity of the data, the development of new tools offering integrated and meaningful visualizations of molecular interactions is necessary to help users drawing new hypotheses without being overwhelmed by the density of the subsequent graph. We extend the previously developed TranscriptomeBrowser database with a set of tables containing 1,594,978 human and mouse molecular interactions. The database includes: (i) predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices), (ii) potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments, (iii) regulatory interactions curated from the literature, (iv) predicted post-transcriptional regulation by micro-RNA, (v) protein kinase-substrate interactions and (vi) physical protein-protein interactions. In order to easily retrieve and efficiently analyze these interactions, we developed In-teractomeBrowser, a graph-based knowledge browser that comes as a plug-in for Transcriptome-Browser. The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list by providing a context-specific display of putative regulatory and physical interactions. To achieve this, InteractomeBrowser relies on a "cell compartments-based layout" that makes use of a subset of the Gene Ontology to map gene products onto relevant cell compartments. This layout is particularly powerful for visual integration of heterogeneous biological information

Regulatory approaches to, and practice of, PSA in Finland, France, Spain, Sweden, Switzerland, the United Kingdom, and the United States of America

International Nuclear Information System (INIS)

Baier, M.; Schaefer, A.

2005-01-01

Performing level-1 probabilistic safety analyses (PSA) is the established standard in most countries using nuclear power. In addition, level-2 PSA has become more and more widespread over the past few years. However, regulatory requirements and practice differ from country to country, especially with respect to level-2 analyses. In an effort to determine these differences more precisely, the ISaR Institute for Safety and Reliability, on behalf of VGB PowerTech Service GmbH, conducted a study of these seven countries: Finland, France, Spain, Sweden, Switzerland, the United Kingdom, and the United States. The study focused on level-2 PSA carried out by plant operators within the framework of periodic safety reviews. The findings of the study are based on extensive interviews of at least one expert each on the operators' and the authorities' side for each of the seven countries. Points taken into account in particular included the criteria imposed by regulators on PSA carried out by operators; the rank of PSA within the regulatory framework; the required versus the actual scopes of analysis; the objectives and uses of PSA; reviews of the analyses; the methods employed. (orig.)

A regulatory view of the seismic assessment of existing nuclear structures in the United Kingdom

International Nuclear Information System (INIS)

Inkester, J.E.

2001-01-01

The paper describes the background to the seismic assessment of existing nuclear structures in the United Kingdom. Nuclear installations in this country were not designed specifically to resist earthquakes until the nineteen-seventies, although older plants were robustly constructed. The seismic capability of these older installations is now being evaluated as part of the periodic safety reviews which nuclear licensees are required to carry out. The regulatory requirements which set the framework for these studies are explained. The licensees' processes of hazard appraisal and examination of the response of the structure are briefly summarized. Regulatory views on some of the criteria used to judge the adequacy of safety are discussed. Finally the paper provides some comments on future initiatives and possible areas of development. (author)

Project management with regulatory constraints: Return to service of San Onofre Unit 1

International Nuclear Information System (INIS)

Hosmer, J.

1986-01-01

Station acceptance of the RTS work was completed in early November, 1984. The unit completed a successful integrated leak rate test, hot function test, and 200 hour warranty run in December, 1984 six weeks ahead of the CPUC mandate. Capital expenditures, although greater than the initial forecast, were two million dollars less than the 37.5 million dollar CPUC cap. The unit has run essentially trouble-free at current rated power until the current 1985 outage. Strategies and lessons learned that contributed to a successful RTS (e.g., all regulatory and economic constraints were met) included the use of numerous brainstorm sessions between SCE, Bechtel, and other consultants; innovative state of the art technical criterion (e.g., realistic versus overly conservative engineering); and budget and schedule contingencies consistent with the known and unknown risks

Regulatory difficulties in a developing country

International Nuclear Information System (INIS)

Jacobs, W.R. Jr.

1978-01-01

The regulatory agency assigned the task of regulating the initial entry into the field of nuclear power generation by a developing country has a very difficult job. Based on the authors' experience during the start-up and initial operation of Ko-Ri Unit I, the first power reactor in the Republic of Korea, observations on regulatory difficulties and recommendations for improved regulatory effectiveness are offered. The problem areas can be loosely grouped into three general categories: (1) Lack of adequate technical knowledge which is the basis for all effective regulation; (2) Difficulties with understanding and utilization of the required regulatory documentation; (3) Failure to establish the proper regulatory environment. Examples are cited from actual experience during the Ko-Ri Unit I start-up to demonstrate the impact that regulatory activities can have on a plant construction and testing programme. The problems encountered are not unique to developing countries but also exist in the United States of America. Recommendations are offered which should be beneficial to either newly formed regulatory agencies or agencies wishing to improve their abilities and effectiveness. These include: (1) Additional training of regulatory inspectors in plant operations; (2) Additional experience gained by participation in regulatory activities in other countries; (3) Increased attention given to regulatory documents, especially plant technical specifications; (4) Establishment of formal lines of communication between the utility and the regulatory agency; (5) Clear definition of regulatory responsibilities to avoid areas of overlapping jurisdiction; (6) Active participation by the regulatory staff very early in the project. It is hoped that these and other recommendations offered will greatly improve regulatory effectiveness and at the same time demonstrate that when the decision is made to 'go nuclear', a strong commitment must be made to develop and support a technically

Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

Science.gov (United States)

Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

2014-01-01

Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

Mutational robustness of gene regulatory networks.

Directory of Open Access Journals (Sweden)

Aalt D J van Dijk

Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.

TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks

Directory of Open Access Journals (Sweden)

Lepoivre Cyrille

2012-01-01

Full Text Available Abstract Background Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions. Furthermore, given the intrinsic complexity of the data, the development of new tools offering integrated and meaningful visualizations of molecular interactions is necessary to help users drawing new hypotheses without being overwhelmed by the density of the subsequent graph. Results We extend the previously developed TranscriptomeBrowser database with a set of tables containing 1,594,978 human and mouse molecular interactions. The database includes: (i predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices, (ii potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments, (iii regulatory interactions curated from the literature, (iv predicted post-transcriptional regulation by micro-RNA, (v protein kinase-substrate interactions and (vi physical protein-protein interactions. In order to easily retrieve and efficiently analyze these interactions, we developed In-teractomeBrowser, a graph-based knowledge browser that comes as a plug-in for Transcriptome-Browser. The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list by providing a context-specific display of putative regulatory and physical interactions. To achieve this, InteractomeBrowser relies on a "cell compartments-based layout" that makes use of a subset of the Gene Ontology to map gene products onto relevant cell compartments. This layout is particularly powerful for visual integration

Decree 328/003. Is approve the organizational structure reformulation project of the regulatory unit of Unit 006 Energy and water services of subsection 02 Presidency of the Republic

International Nuclear Information System (INIS)

2003-01-01

This decree approve the organizational structure project of The regulatory energy and water services ( URSEA). This unit is responsible for monitoring the activities related to electricity, gas, drinking water, sanitation and oil, fuel and other hydrocarbon derivatives

Conformance to Regulatory Guide 1.97 Browns Ferry Nuclear Plant, Unit Nos. 1, 2 and 3 (Docket Nos. 50-259, 50-260, and 50-296)

International Nuclear Information System (INIS)

Udy, A.C.

1985-07-01

This EG and G Idaho, Inc., report reviews the submittals for Regulatory Guide 1.97, Revision 3, for Unit Nos. 1, 2 and 3 of the Browns Ferry Nuclear Plant and identifies areas of nonconformance to the regulatory guide. Exceptions to Regulatory Guide 1.97 are evaluated and those areas where sufficient basis for acceptability is not provided are identified

Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - United Kingdom

International Nuclear Information System (INIS)

2003-01-01

This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining Regime; 3. Radioactive Substances; 4. Nuclear Installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response); 5. Trade in Nuclear Materials and Equipment; 6. Radiation Protection; 7. Radioactive Waste Management; 8. Non-Proliferation and Physical Protection; 9. Transport; 10. Nuclear Third Party Liability; II. Institutional Framework: 1. Regulatory and Supervisory Authorities (Department of Trade and Industry - DTI; Secretary of State for Environment, Food and Rural Affairs and the Secretary of State for Health; Secretary of State for Transport; Secretary of State for Education); 2. Advisory Bodies (Medical Research Council - MRC; Nuclear Safety Advisory Committee; Radioactive Waste Management Advisory Committee); 3. Public and Semi-Public Agencies (United Kingdom Atomic Energy Authority - UKAEA; Health and Safety Commission and Executive - HSC/HSE; National Radiological Protection Board - NRPB; Environment Agencies; British Nuclear Fuels plc. - BNFL; Amersham International plc.; The National Nuclear Corporation Ltd. - NNC; United Kingdom Nirex Ltd.; Magnox Electric plc.; British Energy Generation Ltd.; Scottish Electricity Generator Companies; British Energy Generation Ltd.; Regional Electricity Companies in England and Wales)

Establishing Policy Foundations and Regulatory Systems to Enhance Nursing Practice in the United Arab Emirates.

Science.gov (United States)

Brownie, Sharon M; Hunter, Lyndal H; Aqtash, Salah; Day, Gary E

2015-01-01

In 2009, the United Arab Emirates (UAE) established a Nursing and Midwifery Council with a mandate to develop standards for the registration and regulation of nursing and midwifery and to strengthen the nursing and midwifery workforce. Priorities included workforce Emiratization and the development of regulatory standards to support advanced and speciality nursing practice and new models of care-particularly for the management of noncommunicable diseases. This article provides background, context for, and best practice inputs to the effort to provide one unified framework of nursing regulation and licensure across the whole of the UAE. This article is intended for nurse leaders, policy makers, and regulators who are reviewing or developing nursing regulatory processes and advancing nursing workforce capacity building activities; and nurse educators and nurses wishing to work in the UAE. © The Author(s) 2015.

Exploring overlapping functional units with various structure in protein interaction networks.

Directory of Open Access Journals (Sweden)

Xiao-Fei Zhang

Full Text Available Revealing functional units in protein-protein interaction (PPI networks are important for understanding cellular functional organization. Current algorithms for identifying functional units mainly focus on cohesive protein complexes which have more internal interactions than external interactions. Most of these approaches do not handle overlaps among complexes since they usually allow a protein to belong to only one complex. Moreover, recent studies have shown that other non-cohesive structural functional units beyond complexes also exist in PPI networks. Thus previous algorithms that just focus on non-overlapping cohesive complexes are not able to present the biological reality fully. Here, we develop a new regularized sparse random graph model (RSRGM to explore overlapping and various structural functional units in PPI networks. RSRGM is principally dominated by two model parameters. One is used to define the functional units as groups of proteins that have similar patterns of connections to others, which allows RSRGM to detect non-cohesive structural functional units. The other one is used to represent the degree of proteins belonging to the units, which supports a protein belonging to more than one revealed unit. We also propose a regularizer to control the smoothness between the estimators of these two parameters. Experimental results on four S. cerevisiae PPI networks show that the performance of RSRGM on detecting cohesive complexes and overlapping complexes is superior to that of previous competing algorithms. Moreover, RSRGM has the ability to discover biological significant functional units besides complexes.

Medical revalidation as professional regulatory reform: Challenging the power of enforceable trust in the United Kingdom.

Science.gov (United States)

Spendlove, Zoey

2018-05-01

For more than two decades, international healthcare crises and ensuing political debates have led to increasing professional governance and regulatory policy reform. Governance and policy reforms, commonly representing a shift from embodied trust in professionals to state enforceable trust, have challenged professional power and self-regulatory privileges. However, controversy remains as to whether such policies do actually shift the balance of power and what the resulting effects of policy introduction would be. This paper explores the roll-out and operationalisation of revalidation as medical regulatory reform within a United Kingdom National Health Service hospital from 2012 to 2013, and its impact upon professional power. Revalidation policy was subject to the existing governance and management structures of the organisation, resulting in the formal policy process being shaped at the local level. This paper explores how the disorganised nature of the organisation hindered rather than facilitated robust processes of professional governance and regulation, fostering formalistic rather than genuine professional engagement with the policy process. Formalistic engagement seemingly assisted the medical profession in retaining self-regulatory privileges whilst maintaining professional power over the policy process. The paper concludes by challenging the concept of state enforceable trust and the theorisation that professional groups are effectively regulated and controlled by means of national and organisational objectives, such as revalidation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Robustness in Regulatory Interaction Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic and Genetic

Science.gov (United States)

Demongeot, Jacques; Ben Amor, Hedi; Elena, Adrien; Gillois, Pierre; Noual, Mathilde; Sené, Sylvain

2009-01-01

Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability). We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode) of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression). We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime) or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control. PMID:20057955

Robustness in Regulatory Interaction Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic and Genetic

Directory of Open Access Journals (Sweden)

Sylvain Sené

2009-10-01

Full Text Available Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability. We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression. We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control.

Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.

Science.gov (United States)

Yu, Bowen; Doraiswamy, Harish; Chen, Xi; Miraldi, Emily; Arrieta-Ortiz, Mario Luis; Hafemeister, Christoph; Madar, Aviv; Bonneau, Richard; Silva, Cláudio T

2014-12-01

Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).

Preservation and Implementation of Decommissioning Lessons Learned in the United States Nuclear Regulatory Commission

International Nuclear Information System (INIS)

Rodriguez, Rafael L.

2008-01-01

Over the past several years, the United States Nuclear Regulatory Commission (NRC) has actively worked to capture and preserve lessons learned from the decommissioning of nuclear facilities. More recently, NRC has involved industry groups, the Organization of Agreement States (OAS), and the Department of Energy (DOE) in the effort to develop approaches to capture, preserve and disseminate decommissioning lessons learned. This paper discusses the accomplishments of the working group, some lessons learned by the NRC in the recent past, and how NRC will incorporate these lessons learned into its regulatory framework. This should help ensure that the design and operation of current and future nuclear facilities will result in less environmental impact and more efficient decommissioning. In summary, the NRC will continue capturing today's experience in decommissioning so that future facilities can take advantage of lessons learned from today's decommissioning projects. NRC, both individually and collectively with industry groups, OAS, and DOE, is aggressively working on the preservation and implementation of decommissioning lessons learned. The joint effort has helped to ensure the lessons from the whole spectrum of decommissioning facilities (i.e., reactor, fuel cycle, and material facilities) are better understood, thus maximizing the amount of knowledge and best practices obtained from decommissioning activities. Anticipated regulatory activities at the NRC will make sure that the knowledge gained from today's decommissioning projects is preserved and implemented to benefit the nuclear facilities that will decommission in the future

Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

Energy Technology Data Exchange (ETDEWEB)

Matsushita, Y., E-mail: kurita@cs.tut.ac.jp; Murakawa, T., E-mail: kurita@cs.tut.ac.jp; Shimamura, K., E-mail: kurita@cs.tut.ac.jp; Oishi, M., E-mail: kurita@cs.tut.ac.jp; Ohyama, T., E-mail: kurita@cs.tut.ac.jp; Kurita, N., E-mail: kurita@cs.tut.ac.jp [Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580 (Japan)

2015-02-27

The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

International Nuclear Information System (INIS)

Matsushita, Y.; Murakawa, T.; Shimamura, K.; Oishi, M.; Ohyama, T.; Kurita, N.

2015-01-01

The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA

National legislative and regulatory activities

International Nuclear Information System (INIS)

2014-01-01

This section of the Bulletin presents a summary of the recent national legislative and regulatory activities sorted by country and topic: - Algeria: Nuclear security. - France: Radioactive waste management; Nuclear safety and radiological protection; General legislation; International co-operation. - Germany: International trade. - Indonesia: Nuclear security, General legislation. - Ireland: Nuclear safety and radiological protection; General legislation. - Lithuania: Nuclear security; Nuclear safety and radiological protection. - Slovak Republic: International co-operation; Liability and compensation; Environmental protection. - Switzerland: Radioactive waste management. - United Arab Emirates: Liability and compensation. - United States: Radioactive waste management; Licensing and regulatory infrastructure

Competitive Electricity Market Regulation in the United States: A Primer

Energy Technology Data Exchange (ETDEWEB)

Flores-Espino, Francisco [National Renewable Energy Lab. (NREL), Golden, CO (United States); Tian, Tian [National Renewable Energy Lab. (NREL), Golden, CO (United States); Chernyakhovskiy, Ilya [National Renewable Energy Lab. (NREL), Golden, CO (United States); Chernyakhovskiy, Ilya [National Renewable Energy Lab. (NREL), Golden, CO (United States); Miller, Mackay [National Grid, Warwick (United Kingdom)

2016-12-01

The electricity system in the United States is a complex mechanism where different technologies, jurisdictions and regulatory designs interact. Today, two major models for electricity commercialization operate in the United States. One is the regulated monopoly model, in which vertically integrated electricity providers are regulated by state commissions. The other is the competitive model, in which power producers can openly access transmission infrastructure and participate in wholesale electricity markets. This paper describes the origins, evolution, and current status of the regulations that enable competitive markets in the United States.

Nurse-Patient Communication Interactions in the Intensive Care Unit

Science.gov (United States)

Happ, Mary Beth; Garrett, Kathryn; Thomas, Dana DiVirgilio; Tate, Judith; George, Elisabeth; Houze, Martin; Radtke, Jill; Sereika, Susan

2011-01-01

Background The inability to speak during critical illness is a source of distress for patients, yet nurse-patient communication in the intensive care unit has not been systematically studied or measured. Objectives To describe communication interactions, methods, and assistive techniques between nurses and nonspeaking critically ill patients in the intensive care unit. Methods Descriptive observational study of the nonintervention/usual care cohort from a larger clinical trial of nurse-patient communication in a medical and a cardiothoracic surgical intensive care unit. Videorecorded interactions between 10 randomly selected nurses (5 per unit) and a convenience sample of 30 critically ill adults (15 per unit) who were awake, responsive, and unable to speak because of respiratory tract intubation were rated for frequency, success, quality, communication methods, and assistive communication techniques. Patients self-rated ease of communication. Results Nurses initiated most (86.2%) of the communication exchanges. Mean rate of completed communication exchange was 2.62 exchanges per minute. The most common positive nurse act was making eye contact with the patient. Although communication exchanges were generally (>70%) successful, more than one-third (37.7%) of communications about pain were unsuccessful. Patients rated 40% of the communication sessions with nurses as somewhat difficult to extremely difficult. Assistive communication strategies were uncommon, with little to no use of assistive communication materials (eg, writing supplies, alphabet or word boards). Conclusions Study results highlight specific areas for improvement in communication between nurses and nonspeaking patients in the intensive care unit, particularly in communication about pain and in the use of assistive communication strategies and communication materials. PMID:21362711

Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in the United States. Preliminary background report

Energy Technology Data Exchange (ETDEWEB)

Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

1980-01-01

This report is one of a series of preliminary reports describing the laws and regulatory programs of the United States and each of the 50 states affecting the siting and operation of energy generating facilities likely to be used in Integrated Community Energy Systems (ICES). Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES. This report describes laws and regulatory programs in the United States. Subsequent reports will (1) describe public utility rate regulatory procedures and practices as they might affect an ICES, (2) analyze each of the aforementioned regulatory programs to identify impediments to the development of ICES, and (3) recommend potential changes in legislation and regulatory practices and procedures to overcome such impediments.

Standardization of nuclear power plants in the United States: recent regulatory developments

International Nuclear Information System (INIS)

Cowan, B.Z.; Tourtellotte, J.R.

1992-01-01

On April 18, 1989, the United States (U.S.) Nuclear Regulatory Commission (NRC) amended the regulations governing the process for licensing nuclear power plants in the United States to provide for issuance of early site permits, standard design certifications and combined construction permits and operating licenses for nuclear power reactors. The new regulations are designed to achieve early resolution of licensing issues and facilitate standardization of nuclear power plants in the United States. The program for design standardization is central to efforts mounted by the U.S. government and industry to ensure that there will be a next generation of nuclear power facilities in the U.S. The most significant changes are provisions for certification of standard designs and for issuance prior to start of construction of combined licenses which incorporate a construction permit and an operating license with conditions. Such certifications and combined licenses must contain tests, inspections and analyses, and acceptance criteria, which are necessary and sufficient to provide reasonable assurance that the facility has been constructed and will operate in accordance with the combined license. A number of significant implementation issues have arisen. In addition a major court case brought by several anti-nuclear groups is pending, challenging NRC authority to issue combined licenses. It is the goal of the U.S. nuclear industry to have the first of the next generation of standardized nuclear power plants ordered, licensed, constructed and on-line by the year 2000. (author)

The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

Science.gov (United States)

Molzon, J A; Giaquinto, A; Lindstrom, L; Tominaga, T; Ward, M; Doerr, P; Hunt, L; Rago, L

2011-04-01

The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.

National legislative and regulatory activities

International Nuclear Information System (INIS)

2012-01-01

This section gathers the following national legislative and regulatory activities sorted by country: Bulgaria: General legislation; Czech Republic: General legislation; France: General legislation, Regulatory infrastructure and activity; Germany: General legislation; India: Liability and compensation, Organisation and structure; Ireland: Radiation protection, General legislation; Korea (Republic of): Organisation and structure; Lithuania: Regulatory infrastructure and activity, Radioactive waste management, Radiation protection, international cooperation, Nuclear safety; Poland: General legislation; Romania: Environmental protection; Russian Federation: Radioactive waste management; Slovenia: Nuclear safety; Spain: Liability and compensation, Nuclear security; Sweden: Nuclear safety; Turkey: Radiation protection, Regulatory infrastructure and activity, Nuclear safety, Liability and compensation; United States: General legislation

Functional and topological characteristics of mammalian regulatory domains

Science.gov (United States)

Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

2014-01-01

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

Regulatory responses to over-the-counter codeine analgesic misuse in Australia, New Zealand and the United Kingdom.

Science.gov (United States)

Tobin, Claire L; Dobbin, Malcolm; McAvoy, Brian

2013-10-01

Analysis of the policy response by Australia's National Drugs and Poisons Schedule Committee (NDPSC) and comparison with recommendations by expert advisory committees in New Zealand and the United Kingdom. Analysis of public policy documents of relevant regulatory authorities was conducted. Data were extracted regarding changes to over-the-counter (OTC) codeine analgesic scheduling, indications, maximum unit dose, maximum daily dose, maximum pack size, warning labels, consumer medicine information and advertising. Where available, public submissions and other issues considered by the committees and rationale for their recommendations were recorded and thematically analysed. Expert advisory committees in Australia, NZ and the UK defined the policy problem of OTC codeine misuse and harm as small relative to total use and responded by restricting availability. Pharmacist supervision was required at the point-of-sale and pack sizes were reduced to short-term use. Comparison with recommendations by expert advisory committees in NZ and the UK suggests the NDPSC's actions in response to OTC codeine misuse were appropriate given the available evidence of misuse and harm, but highlights opportunities to utilise additional regulatory levers. Framing policy problems as matters of public health in the context of limited evidence may support decision makers to implement cautionary incremental policy change. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

Regulatory Lessons for Internet Traffic Management from Japan, the European Union, and the United States: Toward Equity, Neutrality and Transparency

Directory of Open Access Journals (Sweden)

John Harris Stevenson

2010-01-01

Full Text Available As network neutrality has been one of the most contentious Internet public policy issues of the past decade, this article provides a comparative overview of events, policies, and legislation surrounding Internet traffic management practises (ITMPs (e.g., network neutrality in Japan, the European Union, the United States, and Canada. Using the frame provided by Richard Rose of “hybrid lessons”to create a policy synthesis, the paper details the telecom policy environment, Internet Service provider competition, legislative jurisdiction, remedies for ITMPs, consumer transparency, and adherence to privacy protection in each country. The analysis focuses on Canada’s first significant regulatory effort to address network neutrality, which came during the Canadian Radio-television and Telecommunications Commission 2009 process on Internet traffic management. This paper presents a brief overview of the Canadian regulatory environment and the specific questions which were the subject of the CRTC review. Employing Richard Rose’s methods for comparative public policy analysis, we offer a number of regulatory “lessons” from Japan, the European Union, and the United States based on their experiences with traffic management issues. Applying these lessons to the Canadian context, we make several specific policy recommendations, among them that competition be encouraged within the Internet service provider space, that network management practises be reasonable and limited, and that ISPs provide full disclosure of network management policies and practises.

The Regulatory Independence of FANR

International Nuclear Information System (INIS)

ALNuaimi, Fatema; Choi, Kwang Shik

2012-01-01

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

The Regulatory Independence of FANR

Energy Technology Data Exchange (ETDEWEB)

ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2012-05-15

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

Organization of nuclear regulatory activities

International Nuclear Information System (INIS)

Blidaru, Valentin

2008-01-01

facilities; - Accident analyses; - Criticality calculations; - Licensing process for TRIGA research reactor; - Application of RESP code for CANDU type power reactors. The main tasks, objectives and methodologies applied by the Regulatory Authority are presented. The main nuclear facilities to which specific regulatory approaches are applied are: - Cernavoda Nuclear Power Plant Unit 1; - Cernavoda NPP Unit 2; - TRIGA Research reactor; - WWR-S research reactor (in conservation); - Specific installations related to the nuclear safety area of licensing, namely; - devices as C-2, C-5, C-6, by the TRIGA research reactor; - criticality aspects relating to transportation and storage of the fresh and spent fuels; - CANDU6 fuel plant; - dry storage facilities for spent fuel. The second half of the paper deals with specific aspects concerning the TRIGA research reactors. There are described the regulatory approaches and the licensing process, it is given a presentation of the configuration of the reactor, the operation of replacing the HEU fuel by LEU fuel, operation and applications of the reactor and finally specific aspects of the licensing process. These aspects concern the following issues: - reactivity accidents; - core interaction; - fuel temperature; prompt negative temperature coefficient. The regulatory approach for further licensing process deals with the following aspects: - nuclear safety documentation assessment for the reactor and each experimental device; - the operational licence to be issued for the whole nuclear unit; - technical nuclear safety documentation to be revised by the licensee and additional safety assessment to be performed for the reactor itself and also for the experimental devices in order to establish the concordance with the design changes (conversion to LEU from HEU fuel, 6 control rods in the reactor control system); - technical limits and conditions to be well established according to the tests conclusions or independent calculations and safety

Mapping out the regulatory environment and its interaction with land and property markets

International Nuclear Information System (INIS)

Adams, David

2008-01-01

The purpose of this paper is to explain how the regulatory environment created by planning and building regulations interacts with land and property markets. Since this regulatory environment operates as a form of intervention within property markets in general and the development process in particular, it is essential first to understand the nature, structure and operation of land and property markets. These are covered in the first section. The second section identifies the aims and components of the planning system and building regulations. From this basis, four broad types of policy intervention are reviewed in the third section. These cover policies that seek to shape, regulate or stimulate market activity, and those that aim to build state or market capacity to produce desired outcomes. The final section uses the private residential development process as a case study to explore the extent to which state intervention can influence producer-consumer relationships in one important market sector. The paper argues that effective intervention in land and property markets requires the creation of a broad range of policy tools and their appropriate deployment to suit particular market circumstances. (author)

Nuclear Regulatory Legislation

International Nuclear Information System (INIS)

1989-08-01

This compilation of statutes and material pertaining to nuclear regulatory legislation through the 100th Congress, 2nd Session, has been prepared by the Office of the General Counsel, US Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document. Persons using this document are placed on notice that it may not be used as an authoritative citation in lieu of the primary legislative sources. Furthermore, while every effort has been made to ensure the completeness and accuracy of this material, neither the United States Government, the Nuclear Regulatory Commission, nor any of their employees makes any expressed or implied warranty or assumes liability for the accuracy or completeness of the material presented in this compilation

Team structure and regulatory focus: the impact of regulatory fit on team dynamic.

Science.gov (United States)

Dimotakis, Nikolaos; Davison, Robert B; Hollenbeck, John R

2012-03-01

We report a within-teams experiment testing the effects of fit between team structure and regulatory task demands on task performance and satisfaction through average team member positive affect and helping behaviors. We used a completely crossed repeated-observations design in which 21 teams enacted 2 tasks with different regulatory focus characteristics (prevention and promotion) in 2 organizational structures (functional and divisional), resulting in 84 observations. Results suggested that salient regulatory demands inherent in the task interacted with structure to determine objective and subjective team-level outcomes, such that functional structures were best suited to (i.e., had best fit with) tasks with a prevention regulatory focus and divisional structures were best suited to tasks with a promotion regulatory focus. This contingency finding integrates regulatory focus and structural contingency theories, and extends them to the team level with implications for models of performance, satisfaction, and team dynamics.

Proceedings of the specialists' meeting on regulatory inspection practices in nuclear power plants

International Nuclear Information System (INIS)

1977-01-01

The sessions and contributions of this conference are dealing with: the general problems of regulatory inspection of nuclear power plants and overall national practices (in Canada, France, Germany, Italy, Spain, the United States), specific problems and practical experience of regulatory inspection during site study, evaluation, design, manufacturing and construction of nuclear plants (in Finland, Germany, Spain, Sweden, Great-Britain, United States), quality insurance issues, pressure component regulations, specific problems and practical experience of regulatory inspection during commissioning (in Spain, Sweden, Great-Britain and United States), specific problems and practical experience of regulatory inspection during operation (in Spain, Great-Britain, Unites States, Italy and Sweden), special aspects of regulatory inspection (notably public information issues in Sweden and in Great-Britain, inspection of nuclear fuel transportation in Spain, enforcement programme in the USA)

United States nuclear regulatory commission program for inspection of decommissioning nuclear power plants

International Nuclear Information System (INIS)

Harris, P.W.

2001-01-01

The United States Nuclear Regulatory Commission (USNRC or Commission) has been inspecting decommissioning commercial nuclear power plants in the United States (U.S.) since the first such facility permanently shutdown in September 1967. Decommissioning inspections have principally focused on the safe storage and maintenance of spent reactor fuel; occupational radiation exposure; environmental radiological releases; the dismantlement and decontamination of structures, systems, and components identified to contain or potentially contain licensed radioactive material; and the performance of final radiological survey of the site and remaining structures to support termination of the USNRC-issued operating license. Over the last 5 years, USNRC inspection effort in these areas has been assessed and found to provide reasonable confidence that decommissioning can be conducted safely and in accordance with Commission rules and regulations. Recently, the staff has achieved a better understanding of the risks associated with particular decommissioning accidents 1 and plans to apply these insights to amendments proposed to enhance decommissioning rules and regulations. The probabilities, scenarios, and conclusions resulting from this effort are being assessed as to their applicability to the inspection of decommissioning commercial power reactors. (author)

United States nuclear regulatory commission program for inspection of decommissioning nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Harris, P.W. [U.S. Nuclear Regulatory Commission, Washington, DC (United States)

2001-07-01

The United States Nuclear Regulatory Commission (USNRC or Commission) has been inspecting decommissioning commercial nuclear power plants in the United States (U.S.) since the first such facility permanently shutdown in September 1967. Decommissioning inspections have principally focused on the safe storage and maintenance of spent reactor fuel; occupational radiation exposure; environmental radiological releases; the dismantlement and decontamination of structures, systems, and components identified to contain or potentially contain licensed radioactive material; and the performance of final radiological survey of the site and remaining structures to support termination of the USNRC-issued operating license. Over the last 5 years, USNRC inspection effort in these areas has been assessed and found to provide reasonable confidence that decommissioning can be conducted safely and in accordance with Commission rules and regulations. Recently, the staff has achieved a better understanding of the risks associated with particular decommissioning accidents 1 and plans to apply these insights to amendments proposed to enhance decommissioning rules and regulations. The probabilities, scenarios, and conclusions resulting from this effort are being assessed as to their applicability to the inspection of decommissioning commercial power reactors. (author)

On-Demand Interactive Simulation-Centered Training for Small Unit Tactics

National Research Council Canada - National Science Library

Munro, Allen

2003-01-01

Training on small unit infantry tactics in both the context of present-day infantry operations and in Objective Force Warrior contexts may benefit from the use of interactive graphics with behavioral...

National legislative and regulatory activities

International Nuclear Information System (INIS)

2016-01-01

This section treats of the following National legislative and regulatory activities: 1 - France: General legislation, regulations and instruments; Nuclear trade (including non-proliferation); International co-operation; 2 - India: Licensing and regulatory infrastructure; Liability and compensation; 3 - Ireland: Nuclear safety and radiological protection (including nuclear emergency planning); Transport of radioactive material; Nuclear trade (including non-proliferation); 4 - Lithuania: Licensing and regulatory infrastructure; Nuclear safety and radiological protection (including nuclear emergency planning); Radioactive waste management; 5 - Luxembourg: Nuclear safety and radiological protection (including nuclear emergency planning); 6 - Slovak Republic: International co-operation; General legislation, regulations and instruments; 7 - Spain: Radioactive materials (including physical protection); Radioactive waste management; 8 - United States: Licensing and regulatory infrastructure

HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets.

Science.gov (United States)

De Kumar, Bony; Parker, Hugo J; Paulson, Ariel; Parrish, Mark E; Pushel, Irina; Singh, Narendra Pratap; Zhang, Ying; Slaughter, Brian D; Unruh, Jay R; Florens, Laurence; Zeitlinger, Julia; Krumlauf, Robb

2017-09-01

Hoxa1 has diverse functional roles in differentiation and development. We identify and characterize properties of regions bound by HOXA1 on a genome-wide basis in differentiating mouse ES cells. HOXA1-bound regions are enriched for clusters of consensus binding motifs for HOX, PBX, and MEIS, and many display co-occupancy of PBX and MEIS. PBX and MEIS are members of the TALE family and genome-wide analysis of multiple TALE members (PBX, MEIS, TGIF, PREP1, and PREP2) shows that nearly all HOXA1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins define distinct classes of HOXA1 targets, which may create functional diversity. Transgenic reporter assays in zebrafish confirm enhancer activities for many HOXA1-bound regions and the importance of HOX-PBX and TGIF motifs for their regulation. Proteomic analyses show that HOXA1 physically interacts on chromatin with PBX, MEIS, and PREP family members, but not with TGIF, suggesting that TGIF may have an independent input into HOXA1-bound regions. Therefore, TALE proteins appear to represent a wide repertoire of HOX cofactors, which may coregulate enhancers through distinct mechanisms. We also discover extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes, indicating that the specificity of HOXA1 during development may be regulated though a complex cross-regulatory network of HOXA1 and TALE proteins. This study provides new insight into a regulatory network involving combinatorial interactions between HOXA1 and TALE proteins. © 2017 De Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

Tuning the hybridization bandgap by meta-molecules with in-unit interaction

Energy Technology Data Exchange (ETDEWEB)

Chen, Yongqiang; Li, Yunhui, E-mail: liyunhui@tongji.edu.cn; Wu, Qian; Jiang, Haitao; Zhang, Yewen; Chen, Hong [Key Laboratory of Advanced Micro-Structured Materials, Ministry of Education, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China)

2015-09-07

In this paper, we demonstrate that the hybridization bandgap (HBG) can be tuned conveniently by deep subwavelength meta-molecules with in-unit interaction. Spontaneous-emission-cancellation-like (SEC-like) effect is realized in a meta-molecule by introducing the destructive interference of two detuned meta-atoms. The meta-atoms consisting of subwavelength zero-index-metamaterial-based resonators are side-coupled to a microstrip. Compared to conventional HBG configurations, the presence of in-unit interaction between meta-atoms provides more flexibility in tuning the bandgap properties, keeping the device volume almost unchanged. Both numerical simulations and microwave experiments confirm that the width, depth, and spectrum shape of HBG can be tuned by simply introducing SEC-like interaction into the meta-molecule. Due to these features, our design may be promising to be applied in microwave or optics communications systems with strict limitation of device volume and flexible bandgap properties.

Interactions of severe accident research and regulatory positions (ISARRP)

International Nuclear Information System (INIS)

Sehgal, B.R.

2001-12-01

The work Programme of the ISARRP Project was divided into several work packages. The work was conducted in the form of presentations and discussions, held during several meetings whose character was that of workshops. Short reports were prepared by the partners assigned to each task. Work Package 1: Critical review of the SA phenomenological research. The objective of this work package was to consider the progress made world-wide in research on the resolution of the outstanding phenomenological issues posed by severe accidents. Work Package 2: Relevance of severe accident research to SAMG requirements and implementation. The objective of this work package was to relate the progress made in the resolution of the SA issues to the practical matter of what results are required or have been used for the management of severe accidents. Clearly, the SAMG is the most important avenue employed by the regulatory organizations to assure themselves of the safe (from public perspective) performance of a nuclear plant in a postulated severe accident event. Work Package 3: Relevance of severe accident research to PSA and the risk informed regulatory approach. The objectives of this work package is to relate the results obtained by the severe accident research to the requirements of a PSA and of the new trend of employing the risk informed approach in promulgating regulations. Clearly a PSA identifies vulnerabilities in the knowledge base, however, their importance is decidedly plant specific. Nevertheless the uncertainties in the phenomenology or in resolution of issues lead to uncertainties in the PSA conclusions and in the adoption of the risk informed approach. Work Package 4: Questionnaire and the evaluation of responses to the questions. The purpose of this work package is to solicit the views of the regulatory organizations towards the results of the SA research and the benefits they have derived from it in terms of regulatory actions, or in the confidence they have gained

Interactions of severe accident research and regulatory positions (ISARRP)

Energy Technology Data Exchange (ETDEWEB)

Sehgal, B.R. (comp.) [Royal Inst. of Tech., Stockholm (Sweden). Nuclear Power Safety

2001-12-01

The work Programme of the ISARRP Project was divided into several work packages. The work was conducted in the form of presentations and discussions, held during several meetings whose character was that of workshops. Short reports were prepared by the partners assigned to each task. Work Package 1: Critical review of the SA phenomenological research. The objective of this work package was to consider the progress made world-wide in research on the resolution of the outstanding phenomenological issues posed by severe accidents. Work Package 2: Relevance of severe accident research to SAMG requirements and implementation. The objective of this work package was to relate the progress made in the resolution of the SA issues to the practical matter of what results are required or have been used for the management of severe accidents. Clearly, the SAMG is the most important avenue employed by the regulatory organizations to assure themselves of the safe (from public perspective) performance of a nuclear plant in a postulated severe accident event. Work Package 3: Relevance of severe accident research to PSA and the risk informed regulatory approach. The objectives of this work package is to relate the results obtained by the severe accident research to the requirements of a PSA and of the new trend of employing the risk informed approach in promulgating regulations. Clearly a PSA identifies vulnerabilities in the knowledge base, however, their importance is decidedly plant specific. Nevertheless the uncertainties in the phenomenology or in resolution of issues lead to uncertainties in the PSA conclusions and in the adoption of the risk informed approach. Work Package 4: Questionnaire and the evaluation of responses to the questions. The purpose of this work package is to solicit the views of the regulatory organizations towards the results of the SA research and the benefits they have derived from it in terms of regulatory actions, or in the confidence they have gained

Regulatory practices - United States example

International Nuclear Information System (INIS)

Shapar, M.

1976-01-01

In 1954, the Atomic Energy Act of 1946 was revised to do away with the federal state monopoly in this field and to enable private industry to develop nuclear power. This evolution led the federal authorities to give the Atomic Energy Commission the powers to control the design, licensing and operation of nuclear reactors. These powers were constantly strengthened and are now exercised by the Nuclear Regulatory Commission (NRC). Since its creation in 1975, the Commission has amended the regulations on licensing of nuclear reactors in the light of experience acquired so as to shorten the duration of this procedure. These amendments concern the standardization of nuclear power plants, limited work authorizations, the methods for issuing licenses. The objective of the Commission aim to make the licensing procedure for nuclear power plants simpler and more efficient and hence, less costly, while ensuring that a very high level for safety standards and environmental protection is maintained. (NEA) [fr

Food Reformulation, Responsive Regulation, and “Regulatory Scaffolding”: Strengthening Performance of Salt Reduction Programs in Australia and the United Kingdom

Directory of Open Access Journals (Sweden)

Roger Magnusson

2015-06-01

Full Text Available Strategies to reduce excess salt consumption play an important role in preventing cardiovascular disease, which is the largest contributor to global mortality from non-communicable diseases. In many countries, voluntary food reformulation programs seek to reduce salt levels across selected product categories, guided by aspirational targets to be achieved progressively over time. This paper evaluates the industry-led salt reduction programs that operate in the United Kingdom and Australia. Drawing on theoretical concepts from the field of regulatory studies, we propose a step-wise or “responsive” approach that introduces regulatory “scaffolds” to progressively increase levels of government oversight and control in response to industry inaction or under-performance. Our model makes full use of the food industry’s willingness to reduce salt levels in products to meet reformulation targets, but recognizes that governments remain accountable for addressing major diet-related health risks. Creative regulatory strategies can assist governments to fulfill their public health obligations, including in circumstances where there are political barriers to direct, statutory regulation of the food industry.

Using the interactive distance learning broadcast format for international audiences

International Nuclear Information System (INIS)

Callan, C.; Hylko, J.M.

1997-01-01

Since 1989, the National Environmental Technology Network (NETN) has been broadcasting interactive presentations on topics of national and international concern. Each interactive presentation covers such topics as decommissioning, environmental risk management, radioactive waste management, waste minimization, and total quality management. Course materials are provided to the attendees which feature case studies, legal and regulatory issues, and the application of existing and new technologies. The interactive presentations are broadcast by satellite and videotaped, allowing employees to participate who do not have convenient access to traditional classroom training resources. Over 8,000 professionals and students in the United States and several foreign countries have participated in the distance learning broadcast format, thus providing a proven and cost-effective method for managing educational and facility resources effectively. A case study is presented depicting why training, if neglected, can result in costly errors, and how the distance learning broadcast format can be expanded to assist regulatory officials, and even the local populace, in making cost-effective decisions. (author)

A Regulatory Network Analysis of Orphan Genes in Arabidopsis Thaliana

Science.gov (United States)

Singh, Pramesh; Chen, Tianlong; Arendsee, Zebulun; Wurtele, Eve S.; Bassler, Kevin E.

Orphan genes, which are genes unique to each particular species, have recently drawn significant attention for their potential usefulness for organismal robustness. Their origin and regulatory interaction patterns remain largely undiscovered. Recently, methods that use the context likelihood of relatedness to infer a network followed by modularity maximizing community detection algorithms on the inferred network to find the functional structure of regulatory networks were shown to be effective. We apply improved versions of these methods to gene expression data from Arabidopsis thaliana, identify groups (clusters) of interacting genes with related patterns of expression and analyze the structure within those groups. Focusing on clusters that contain orphan genes, we compare the identified clusters to gene ontology (GO) terms, regulons, and pathway designations and analyze their hierarchical structure. We predict new regulatory interactions and unravel the structure of the regulatory interaction patterns of orphan genes. Work supported by the NSF through Grants DMR-1507371 and IOS-1546858.

Specific problems and practical experience of regulatory inspection during commissioning in the United Kingdom

International Nuclear Information System (INIS)

Lewis, G.

1977-01-01

The commissioning of nine Magnox and two Advanced Gas-cooled Reactor Nuclear Power Plants in the United Kingdom during the last sixteen years under the regulatory control of the Nuclear Installations Inspectorate of the Health and Safety Executive has been based on a Stage Approval Philosophy starting with proof-testing of the primary gas circuit and concluding with tests on the reactor at full power. The practical experience gained during this period has enabled the Nuclear Installations Inspectorate to rationalise the procedures and test requirements without comporomising safety standards. The Operating Rules and Maintenance Schedules are approved for commissioning and during this period are reviewed for their adequacy for future power operation of the plant. The organisation, documentation, test procedures and the commissioning programme used for the Advanced Gas-cooled Reactors are briefly explained. (author)

United States Nuclear Regulatory Commission information digest: 1997 edition. Volume 9

International Nuclear Information System (INIS)

1997-05-01

The Nuclear Regulatory Commission Information Digest (digest) provides a summary of information about the US Nuclear Regulatory Commission (NRC), NRC's regulatory responsibilities, NRC licensed activities, and general information on domestic and world-wide nuclear energy. The digest, published annually, is a compilation of nuclear- and NRC-related data and is designed to provide a quick reference to major facts about the agency and the industry it regulates. In general, the data cover 1975 through 1996, with exceptions noted. Information on generating capacity and average capacity factor for operating US commercial nuclear power reactors is obtained from monthly operating reports that are submitted directly to the NRC by the licensee. This information is reviewed by the NRC for consistency only and no independent validation and/or verification is performed

Court-agency interaction in environmental policymaking: the cases of the Nuclear Regulatory Commission and the Environmental Protection Agency

International Nuclear Information System (INIS)

Thomas, L.W.

1981-01-01

This study examines the increasingly active participation of courts in the administrative process as well as agency responses to court-imposed policy shifts. More specifically, it is an investigation of the interaction between the federal courts, primarily the Supreme Court and the District of Columbia Court of Appeals, and two federal regulatory agencies, the Nuclar Regulatory Commission and the Environmental Protection Agency. There are five objectives to the study. The first is to examine the natura of court-agency interaction and to determine the extent to which patterns of judicial review of administrative actions can be discerned. The second is to examine the effect of court orders on agency programs and policies. The third is to assess the anticipatory dimension of court-agency relations. The fourth is to inquire into the recurring dimension of court-agency interaction and to determine its effect on subsequent court decisions. The last is to assess the institutional capacity of courts to deal with scientific and technological issues. This study indicates that judicial review has a substantial effect on the NRC's and the EPA's decision-making activities. Few, if any, recent major policy decisions of the two agencies have not been scrutinized closely by federal appellate courts. During the past decade, the courts have blocked policy initiative on numerous occasions and have been the primary source of change in others. In addition, the mere anticipation of judicial review was found to be a factor motivating the two agencies to make reasoned decisions

Review of nuclear regulatory activities associated with safety culture and the management of safety in the United Kingdom

International Nuclear Information System (INIS)

Woodhouse, P.A.

1995-01-01

This paper describes some of the key regulatory activities which have taken place in the United Kingdom in recent years in the areas of safety culture and management of safety. It explains how the UK's nuclear licensing regime, regulated and enforced by the Nuclear Installations Inspectorate, (NII), provides the framework for a viable safety management system and identifies a management of safety model which a NII Task Force has developed. It finally identifies further work which is being undertaken by the NII. (author). 4 refs, 2 figs

Revisiting interaction specificity reveals neuronal and adipocyte Munc18 membrane fusion regulatory proteins differ in their binding interactions with partner SNARE Syntaxins.

Directory of Open Access Journals (Sweden)

Michelle P Christie

Full Text Available The efficient delivery of cellular cargo relies on the fusion of cargo-carrying vesicles with the correct membrane at the correct time. These spatiotemporal fusion events occur when SNARE proteins on the vesicle interact with cognate SNARE proteins on the target membrane. Regulatory Munc18 proteins are thought to contribute to SNARE interaction specificity through interaction with the SNARE protein Syntaxin. Neuronal Munc18a interacts with Syntaxin1 but not Syntaxin4, and adipocyte Munc18c interacts with Syntaxin4 but not Syntaxin1. Here we show that this accepted view of specificity needs revision. We find that Munc18c interacts with both Syntaxin4 and Syntaxin1, and appears to bind "non-cognate" Syntaxin1 a little more tightly than Syntaxin4. Munc18a binds Syntaxin1 and Syntaxin4, though it interacts with its cognate Syntaxin1 much more tightly. We also observed that when bound to non-cognate Munc18c, Syntaxin1 captures its neuronal SNARE partners SNAP25 and VAMP2, and Munc18c can bind to pre-formed neuronal SNARE ternary complex. These findings reveal that Munc18a and Munc18c bind Syntaxins differently. Munc18c relies principally on the Syntaxin N-peptide interaction for binding Syntaxin4 or Syntaxin1, whereas Munc18a can bind Syntaxin1 tightly whether or not the Syntaxin1 N-peptide is present. We conclude that Munc18a and Munc18c differ in their binding interactions with Syntaxins: Munc18a has two tight binding modes/sites for Syntaxins as defined previously but Munc18c has just one that requires the N-peptide. These results indicate that the interactions between Munc18 and Syntaxin proteins, and the consequences for in vivo function, are more complex than can be accounted for by binding specificity alone.

Genome-Wide Mapping of Transcriptional Regulation and Metabolism Describes Information-Processing Units in Escherichia coli

Directory of Open Access Journals (Sweden)

Daniela Ledezma-Tejeida

2017-08-01

Full Text Available In the face of changes in their environment, bacteria adjust gene expression levels and produce appropriate responses. The individual layers of this process have been widely studied: the transcriptional regulatory network describes the regulatory interactions that produce changes in the metabolic network, both of which are coordinated by the signaling network, but the interplay between them has never been described in a systematic fashion. Here, we formalize the process of detection and processing of environmental information mediated by individual transcription factors (TFs, utilizing a concept termed genetic sensory response units (GENSOR units, which are composed of four components: (1 a signal, (2 signal transduction, (3 genetic switch, and (4 a response. We used experimentally validated data sets from two databases to assemble a GENSOR unit for each of the 189 local TFs of Escherichia coli K-12 contained in the RegulonDB database. Further analysis suggested that feedback is a common occurrence in signal processing, and there is a gradient of functional complexity in the response mediated by each TF, as opposed to a one regulator/one pathway rule. Finally, we provide examples of other GENSOR unit applications, such as hypothesis generation, detailed description of cellular decision making, and elucidation of indirect regulatory mechanisms.

Nuclear Regulatory Commission issuances, March 1975

International Nuclear Information System (INIS)

1975-04-01

Reactor licensing actions taken by the Nuclear Regulatory Commission, the Atomic Safety and Licensing Appeal Board and the Atomic Safety and Licensing Boards for March 1975 are presented. Action was included for the following reactors: Big Rock Point Nuclear Plant; West Valley Reprocessing Plant; Limerick Generating Station, Units 1 and 2; Midland Plants, Units 1 and 2; Wolf Creek Generating Station, Unit 1; Monticello Nuclear Generating Plant, Unit 1; Douglas Point Nuclear Generating Station, Units 1 and 2; Seabrook Station, Units 1 and 2; Vermont Yankee Nuclear Power Station; and WPPSS Hanford Units 1 and 4. (U.S.)

Modeling disease risk through analysis of physical interactions between genetic variants within chromatin regulatory circuitry.

Science.gov (United States)

Corradin, Olivia; Cohen, Andrea J; Luppino, Jennifer M; Bayles, Ian M; Schumacher, Fredrick R; Scacheri, Peter C

2016-11-01

SNPs associated with disease susceptibility often reside in enhancer clusters, or super-enhancers. Constituents of these enhancer clusters cooperate to regulate target genes and often extend beyond the linkage disequilibrium (LD) blocks containing risk SNPs identified in genome-wide association studies (GWAS). We identified 'outside variants', defined as SNPs in weak LD with GWAS risk SNPs that physically interact with risk SNPs as part of a target gene's regulatory circuitry. These outside variants further explain variation in target gene expression beyond that explained by GWAS-associated SNPs. Additionally, the clinical risk associated with GWAS SNPs is considerably modified by the genotype of outside variants. Collectively, these findings suggest a potential model in which outside variants and GWAS SNPs that physically interact in 3D chromatin collude to influence target transcript levels as well as clinical risk. This model offers an additional hypothesis for the source of missing heritability for complex traits.

The dynamics of the transnational food chain regulatory governance

DEFF Research Database (Denmark)

Chatzopoulou, Sevasti

2015-01-01

dynamics of the interactions among public and private actors operate within the transnational food standards setting process. The study identifies the groups of interdependent actors (public and private) that interact within the transnational food chain regulatory process and develop public...... in detail how these interactions operate empirically on specific regulations. Practical implications – The paper offers an integrative thorough understanding of the food chain regulatory standard setting process, relevant for academics, policy makers, the industry, and society. Originality/value – The paper...

Low-income minority fathers' control strategies and children's regulatory skills

Science.gov (United States)

Malin, Jenessa L.; Cabrera, Natasha J.; Karberg, Elizabeth; Aldoney, Daniela; Rowe, Meredith

2015-01-01

The current study explored the bidirectional association of children's individual characteristics, fathers' control strategies at 24-months and children's regulatory skills at pre-kindergarten (pre-K). Using a sample of low-income minority families with 2-year-olds from the Early Head Start Evaluation Research Program (n = 71) we assessed the association between child gender and vocabulary skills, fathers' control strategies at 24-months (e.g., regulatory behavior and regulatory language), and children's sustained attention and emotion regulation at pre-kindergarten. There were three main findings. First, fathers' overwhelmingly use commands (e.g., do that) to promote compliance in their 24-month old children. Second, children's vocabulary skills predict fathers' regulatory behaviors during a father-child interaction, whereas children's gender predicts fathers' regulatory language during an interaction. Third, controlling for maternal supportiveness, fathers' regulatory behaviors at 24-months predict children's sustained attention at pre-kindergarten whereas fathers' regulatory language at 24-months predicts children's emotion regulation at pre-kindergarten. Our findings highlight the importance of examining paternal contributions to children's regulatory skills. PMID:25798496

The interplay between regulatory focus and temporal distance in the health context.

Science.gov (United States)

Berezowska, Aleksandra; Fischer, Arnout R H; van Trijp, Hans C M

2018-02-01

This study identifies how the interaction between temporal distance, regulatory focus, and framing of health outcomes affects individuals' intention to adopt a personalized nutrition service. A 2 (temporal distance: immediate health outcomes vs. delayed health outcomes) × 2 (regulatory focus: prevention vs. promotion) × 2 (health outcome framing: illness prevention vs. health promotion) full-factorial between-subjects design. In two experiments with samples of 236 and 242 students, regulatory focus was manipulated by asking participants to describe which academic outcomes they want to either achieve or prevent and how they aim to do this. Temporal distance and health outcome framing were manipulated by modifying descriptions of personalized nutrition services. To study the process through which temporal distance, regulatory focus, and health outcome framing affect adoption intention, measures of perceived privacy risk and perceived personalization benefit were included as mediators. The interaction between temporal distance and regulatory focus had a significant effect on adoption intention, perceived privacy risk, and perceived personalization benefit. For prevention-focused individuals' adoption intention was higher, perceived personalization benefit was higher, and perceived privacy risk was lower when health outcomes were immediate instead of delayed. These effects were not significant for promotion-focused individuals. Health outcome framing affected the interaction between temporal distance and regulatory focus, but only in Study 1. Only perceived personalization benefit served as a mediator. Tailoring temporal distance to individuals' regulatory focus increases adoption intention for personalized nutrition advice. Statement of contribution What is already known on this subject? Intention to adopt dietary recommendations results from a cognitive decision-making process. Regulatory focus and temporal distance are relevant for the adoption of dietary

Legal and Regulatory Barriers to Reverse Innovation.

Science.gov (United States)

Rowthorn, Virginia; Plum, Alexander J; Zervos, John

Reverse innovation, or the importation of new, affordable, and efficacious models to high-income countries from the developing world, has emerged as a way to improve the health care system in the United States. Reverse innovation has been identified as a key emerging trend in global health systems in part because low-resourced settings are particularly good laboratories for low-cost/high-impact innovations that are developed out of necessity. A difficult question receiving scant attention is that of legal and regulatory barriers. The objective of this paper is to understand and elucidate the legal barriers faced by innovators bringing health interventions to the United States. Semistructured qualitative interviews were conducted with 9 key informants who have directly participated in the introduction of global health care approaches to the United States health system. A purposive sampling scheme was employed to identify participants. Phone interviews were conducted over one week in July 2016 with each participant and lasted an average of 35 minutes each. Purely legal barriers included questions surrounding tort liability, standard of care, and concerns around patient-administered self-care. Regulatory burdens included issues of international medical licensure, reimbursement, and task shifting and scope of work challenges among nonprofessionals (e.g. community health workers). Finally, perceived (i.e. not realized or experienced) legal and regulatory barriers to innovative modalities served as disincentives to bringing products or services developed outside of the United States to the United States market. Conflicting interests within the health care system, safety concerns, and little value placed on low-cost interventions inhibit innovation. Legal and regulatory barriers rank among, and contribute to, an anti-innovation atmosphere in healthcare for domestic and reverse innovators alike. Reverse innovation should be fostered through the thoughtful development of

Quantitative inference of dynamic regulatory pathways via microarray data

Directory of Open Access Journals (Sweden)

Chen Bor-Sen

2005-03-01

Full Text Available Abstract Background The cellular signaling pathway (network is one of the main topics of organismic investigations. The intracellular interactions between genes in a signaling pathway are considered as the foundation of functional genomics. Thus, what genes and how much they influence each other through transcriptional binding or physical interactions are essential problems. Under the synchronous measures of gene expression via a microarray chip, an amount of dynamic information is embedded and remains to be discovered. Using a systematically dynamic modeling approach, we explore the causal relationship among genes in cellular signaling pathways from the system biology approach. Results In this study, a second-order dynamic model is developed to describe the regulatory mechanism of a target gene from the upstream causality point of view. From the expression profile and dynamic model of a target gene, we can estimate its upstream regulatory function. According to this upstream regulatory function, we would deduce the upstream regulatory genes with their regulatory abilities and activation delays, and then link up a regulatory pathway. Iteratively, these regulatory genes are considered as target genes to trace back their upstream regulatory genes. Then we could construct the regulatory pathway (or network to the genome wide. In short, we can infer the genetic regulatory pathways from gene-expression profiles quantitatively, which can confirm some doubted paths or seek some unknown paths in a regulatory pathway (network. Finally, the proposed approach is validated by randomly reshuffling the time order of microarray data. Conclusion We focus our algorithm on the inference of regulatory abilities of the identified causal genes, and how much delay before they regulate the downstream genes. With this information, a regulatory pathway would be built up using microarray data. In the present study, two signaling pathways, i.e. circadian regulatory

The Regulatory Framework for Privacy and Security

Science.gov (United States)

Hiller, Janine S.

The internet enables the easy collection of massive amounts of personally identifiable information. Unregulated data collection causes distrust and conflicts with widely accepted principles of privacy. The regulatory framework in the United States for ensuring privacy and security in the online environment consists of federal, state, and self-regulatory elements. New laws have been passed to address technological and internet practices that conflict with privacy protecting policies. The United States and the European Union approaches to privacy differ significantly, and the global internet environment will likely cause regulators to face the challenge of balancing privacy interests with data collection for many years to come.

Current insights into the molecular systems pharmacology of lncRNA-miRNA regulatory interactions and implications in cancer translational medicine

Directory of Open Access Journals (Sweden)

Sujit Nair

2016-04-01

Full Text Available In recent times, the role(s of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in the pathogenesis of various cancers has received great attention. Indeed, there is also a growing recognition of regulatory RNA cross-talk, i.e., lncRNA-miRNA interactions, that may modulate various events in carcinogenesis and progression to metastasis. This review summarizes current evidence in the literature of lncRNA-miRNA interactions in various cancers such as breast, liver, stomach, lung, prostate, bladder, colorectal, blood, brain, skin, kidney, cervical, laryngeal, gall bladder, and bone. Further, the potential prognostic and theragnostic clinical applications of lncRNA-miRNA interactions in cancer are discussed along with an overview of noncoding RNA (ncRNA-based studies that were presented at the American Society of Clinical Oncology (ASCO 2015. Interestingly, the last decade has seen tremendous innovation, as well as increase in complexity, of the cancer biological network(s from mRNA- to miRNA- and lncRNA-based networks. Thus, biological networks devoted to understanding regulatory interactions between these ncRNAs would be the next frontier in better elucidating the contributions of lncRNA-miRNA interactions in cancer. Herein, a cancer biological network of lncRNA-miRNA interactions is presented wherein “edges” connect interacting lncRNA-miRNA pairs, with each ncRNA serving as a discrete “node” of the network. In conclusion, the untapped potential of lncRNA-miRNA interactions in terms of its diagnostic, prognostic and therapeutic potential as targets for clinically actionable intervention as well as biomarker validation in discovery pipelines remains to be explored. Future research will likely harness this potential so as to take us closer to the goal of “precision” and “personalized medicine” which is tailor-made to the unique needs of each cancer patient, and is clearly the way forward going into the future.

Impacts of different regulatory regimes in the unitization of production; Impactos dos diferentes regimes regulatorios na individualizacao da producao

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Vinicius Farias; Moreira, Robson Prates [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil)

2012-07-01

The unitization process is required in most regulatory models around the world when it identifies that a reservoir straddles to out of the contracted area. This procedure aims to ensure a greater exploitation of petroleum. In Brazil is no different; however there are still many ambiguities in this process. The introduction of new tax regimes in the country broadened the doubts, as we may have a reservoir straddling between concession, production sharing, assignment of rights areas and areas not yet contracted. The objective of the present paper is to explore the uncertainties that must be addressed by the oil and gas sector in order to ensure low legal, regulatory and fiscal risks in the oil industry. The main topics discussed are the rules for production allocation, reserves and expenditures, the ANP and PPSA roles' conflicts, restriction of parties' rights, adjustment of contractual rules and also mitigate or eliminate economic, financial and fiscal uncertainties. This article does not propose solutions to all lacks raised. (author)

Uncovering packaging features of co-regulated modules based on human protein interaction and transcriptional regulatory networks

Directory of Open Access Journals (Sweden)

He Weiming

2010-07-01

Full Text Available Abstract Background Network co-regulated modules are believed to have the functionality of packaging multiple biological entities, and can thus be assumed to coordinate many biological functions in their network neighbouring regions. Results Here, we weighted edges of a human protein interaction network and a transcriptional regulatory network to construct an integrated network, and introduce a probabilistic model and a bipartite graph framework to exploit human co-regulated modules and uncover their specific features in packaging different biological entities (genes, protein complexes or metabolic pathways. Finally, we identified 96 human co-regulated modules based on this method, and evaluate its effectiveness by comparing it with four other methods. Conclusions Dysfunctions in co-regulated interactions often occur in the development of cancer. Therefore, we focussed on an example co-regulated module and found that it could integrate a number of cancer-related genes. This was extended to causal dysfunctions of some complexes maintained by several physically interacting proteins, thus coordinating several metabolic pathways that directly underlie cancer.

Developing regulatory approaches

International Nuclear Information System (INIS)

Axelsson, Lars

2012-01-01

Lars Axelsson presented SSM progress on oversight of LMfS/SC since the Chester 1 Workshop in 2007. Current SSM approaches for safety culture oversight include targeted safety management and safety culture inspections, compliance inspections which cover aspects of safety management/safety culture and multi-disciplinary team inspections. Examples of themes for targeted inspections include management of ambiguous operational situations or other weak signals, understanding of and attitudes to Human Performance tools, the Safety Department's role and authority and Leadership for safety. All regulatory activities provide inputs for the SSM yearly safety evaluation of each licensee. A form has been developed to capture safety culture observations from inspections and other interactions with licensees. Analysis will be performed to identify patterns and provide information to support planning of specific Safety Culture activities. Training has been developed for regulatory staff to enhance the quality of regulatory interventions on safety culture. This includes a half-day seminar to provide an overview of safety culture, and a workshop which provides more in-depth discussion on cultural issues and how to capture those during regulatory activities. Future plans include guidance for inspectors, and informal seminars on safety culture with licensees

Low-income, minority fathers' control strategies and their children's regulatory skills.

Science.gov (United States)

Malin, Jenessa L; Cabrera, Natasha J; Karberg, Elizabeth; Aldoney, Daniela; Rowe, Meredith L

2014-01-01

The current study explored the bidirectional association of children's individual characteristics, fathers' control strategies at 24 months, and children's regulatory skills at prekindergarten (pre-K). Using a sample of low-income, minority families with 2-year-olds from the Early Head Start Research and Evaluation Project (n = 71), we assessed the association between child gender and vocabulary skills, fathers' control strategies at 24 months (e.g., regulatory behavior and regulatory language), and children's sustained attention and emotion regulation at prekindergarten. There were three main findings. First, fathers overwhelmingly used commands (e.g., "Do that.") to promote compliance in their 24-month-old children. Second, children's vocabulary skills predicted fathers' regulatory behaviors during a father-child interaction whereas children's gender predicted fathers' regulatory language during an interaction. Third, controlling for maternal supportiveness, fathers' regulatory behaviors at 24 months predicted children's sustained attention at pre-K whereas fathers' regulatory language at 24 months predicted children's emotion regulation at pre-K. Our findings highlight the importance of examining paternal contributions to children's regulatory skills. © 2014 Michigan Association for Infant Mental Health.

Performance-Based (Risk-Informed) Regulation: A Regulatory Perspective

International Nuclear Information System (INIS)

Kadambi, N. Prasad

2005-01-01

Performance-based regulation (PBR) has been mandated at the national level in the United States and at the agency level, where appropriate, at the U.S. Nuclear Regulatory Commission (USNRC). Guidance has been developed that implements the USNRC's definitions of PBR and other such conceptual regulatory improvements. This paper describes why PBR is important, what constitutes PBR in the context of direction provided at the USNRC, and how PBR can be implemented using a five-step process. The process steps articulate questions to be posed by the analyst regarding various aspects of a regulatory issue so that a suitably performance-based resolution can be developed. A regulatory alternative thus developed can be included among other options to be considered as part of the regulatory decision-making process

Network perturbation by recurrent regulatory variants in cancer.

Directory of Open Access Journals (Sweden)

Kiwon Jang

2017-03-01

Full Text Available Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes.

Regulatory aspects of NPP safety

International Nuclear Information System (INIS)

Kastchiev, G.

1999-01-01

Extensive review of the NPP Safety is presented including tasks of Ministry of Health, Ministry of Internal Affairs, Ministry of Environment and Waters, Ministry of Defense in the field of national system for monitoring the nuclear power. In the frame of national nuclear safety legislation Bulgaria is in the process of approximation of the national legislation to that of EC. Detailed analysis of the status of regulatory body, its functions, organisation structure, responsibilities and future tasks is included. Basis for establishing the system of regulatory inspections and safety enforcement as well as intensification of inspections is described. Assessment of safety modifications is concerned with complex program for reconstruction of Units 1-4 of Kozloduy NPP, as well as for modernisation of Units 5 and 6. Qualification and licensing of the NPP personnel, Year 2000 problem, priorities and the need of international assistance are mentioned

Decisions by regulatory agencies: are they evidence-based?

Directory of Open Access Journals (Sweden)

Furberg Curt D

2007-04-01

Full Text Available Abstract Contradictory statements about the non-steroidal anti-inflammatory drugs from the European Medicines Agency and the United States Food and Drug Administration have raised questions about whether regulatory decisions are evidence-based. For the selective COX-2 inhibitors, there are clear contraindications and warnings in Europe, but only a vaguely worded Black Box warning in the United States. All the non-selective agents are given an almost "clean bill of health" in Europe, while all of them are judged to have a similar risk-benefit ratio as celecoxib in the United States. The regulatory agencies have failed to recognize the clinical trial evidence that the risk of cardiovascular events varies substantially among the non-selective agents, with diclofenac carrying the highest risk of harm.

Regulatory application of seismic experience data for nuclear power plants in the United States

Energy Technology Data Exchange (ETDEWEB)

Chen, Pei-Ying [Nuclear Regulatory Commission, Washington, DC (United States)

1997-03-01

On the basis of its review and evaluation (Reference 3) of the SQUG GIP (Reference 2) and on the basis of the differences between current seismic qualification requirements and the criteria and procedures provided in the GIP, the NRC staff does not consider the USI A-46 methodology given in the GIP to be a `seismic qualification` procedure. Rather, the staff considers the GIP methodology to be a seismic adequacy verification procedure, which was developed on the basis of generic equipment earthquake experience data, supplemented by generic equipment test data. The implementation of the GIP approach for USI A-46 plants provides safety enhancement, in certain aspects, beyond the original licensing bases. Therefore, the GIP methodology is an acceptable evaluation method, for USI A-46 plants only, to verify the seismic adequacy of the safe-shutdown equipment installed in the NPPs in the United States. With the new development in the experience-based approach for seismic qualification of equipment currently underway in the U.S. nuclear industry, there is a potential for future regulatory application of an experience-based approach as a seismic qualification method for certain selected equipment installed in NPPs in the United States. However, industry`s use of the experience-based approach will be dependent on the submittal and staff approval of this approach. (J.P.N.)

Long-range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP.

Science.gov (United States)

Aguirre, Luis A; Alonso, M Eva; Badía-Careaga, Claudio; Rollán, Isabel; Arias, Cristina; Fernández-Miñán, Ana; López-Jiménez, Elena; Aránega, Amelia; Gómez-Skarmeta, José Luis; Franco, Diego; Manzanares, Miguel

2015-04-17

Recent genome-wide association studies have uncovered genomic loci that underlie an increased risk for atrial fibrillation, the major cardiac arrhythmia in humans. The most significant locus is located in a gene desert at 4q25, approximately 170 kilobases upstream of PITX2, which codes for a transcription factor involved in embryonic left-right asymmetry and cardiac development. However, how this genomic region functionally and structurally relates to PITX2 and atrial fibrillation is unknown. To characterise its function, we tested genomic fragments from 4q25 for transcriptional activity in a mouse atrial cardiomyocyte cell line and in transgenic mouse embryos, identifying a non-tissue-specific potentiator regulatory element. Chromosome conformation capture revealed that this region physically interacts with the promoter of the cardiac specific isoform of Pitx2. Surprisingly, this regulatory region also interacts with the promoter of the next neighbouring gene, Enpep, which we show to be expressed in regions of the developing mouse heart essential for cardiac electrical activity. Our data suggest that de-regulation of both PITX2 and ENPEP could contribute to an increased risk of atrial fibrillation in carriers of disease-associated variants, and show the challenges that we face in the functional analysis of genome-wide disease associations.

Interactions between tetrathiafulvalene units in dimeric structures – the influence of cyclic cores

Directory of Open Access Journals (Sweden)

Huixin Jiang

2015-06-01

Full Text Available A selection of cyclic and acyclic acetylenic scaffolds bearing two tetrathiafulvalene (TTF units was prepared by different metal-catalyzed coupling reactions. The bridge separating the two TTF units was systematically changed from linearly conjugated ethyne, butadiyne and tetraethynylethene (trans-substituted units to a cross-conjugated tetraethynylethene unit, placed in either acyclic or cyclic arrangements. The cyclic structures correspond to so-called radiaannulenes having both endo- and exocyclic double bonds. Interactions between two redox-active TTF units in these molecules were investigated by cyclic voltammetry, UV–vis–NIR and EPR absorption spectroscopical methods of the electrochemically generated oxidized species. The electron-accepting properties of the acetylenic cores were also investigated electrochemically.

Review of Technical Studies in the United States in Support of Burnup Credit Regulatory Guidance

International Nuclear Information System (INIS)

Wagner, John C.; Parks, Cecil V.; Mueller, Don; Gauld, Ian C.

2010-01-01

Taking credit for the reduction in reactivity associated with fuel depletion can enable more cost-effective, higher-density storage, transport, disposal, and reprocessing of spent nuclear fuel (SNF) while maintaining sufficient subcritical margin to establish an adequate safety basis. Consequently, there continues to be considerable interest in the United States (U.S.), as well as internationally, in the increased use of burnup credit in SNF operations, particularly related to storage, transport, and disposal of commercial SNF. This interest has motivated numerous technical studies related to the application of burnup credit, both domestically and internationally, as well as the design of SNF storage, transport and disposal systems that rely on burnup credit for maintaining subcriticality. Responding to industry requests and needs, the U.S. Nuclear Regulatory Commission (NRC) initiated a burnup credit research program in 1999, with support from the Oak Ridge National Laboratory (ORNL), to develop regulatory guidance and the supporting technical bases for allowing and expanding the use of burnup credit in pressurized-water reactor SNF storage and transport applications. Although this NRC research program has not been continuous since its inception, considerable progress has been achieved in many key areas in terms of increased understanding of relevant phenomena and issues, availability of relevant information and data, and subsequently updated regulatory guidance for expanded use of burnup credit. This paper reviews technical studies performed by ORNL for the U.S. NRC burnup credit research program. Examples of topics include reactivity effects associated with reactor operating characteristics, fuel assembly characteristics, burnable absorbers, control rods, spatial burnup distributions, cooling time, and assembly misloading; methods and data for validation of isotopic composition predictions; methods and data for validation of criticality calculations; and

A regulatory perspective of the role of construction in revitalizing the United States nuclear industry

International Nuclear Information System (INIS)

Stello, V. Jr.

1983-01-01

Technical and managerial experience in nuclear power plant construction is presented from the perspective of the United States Nuclear Regulatory Commission (NRC). In the context of actions that would contribute to revitalizing the nuclear industry in the United States of America, greater effectiveness of utility management during construction is proposed. The reasons why management effectiveness is so important are developed beginning with summaries of defects that were built into several US plants under construction. The root causes of these significant defects were management failures. In terms of benefits, effective management is important because of its effects on nuclear safety, project construction costs, and future reliability of the plant after commissioning. Actions that would enhance good management include emphasizing the inseparable nature of production and quality, that quality cannot be inspected into a plant, and that a strong construction management staff and exchanges of experience and information are essential. Techniques that have been used successfully in construction management are discussed. NRC and industry initiatives are in progress to improve management responsibility and learning from experience. Projects include Owner's Certification, assessments of licensee performance, fostering good practices across the industry, and improving the NRC inspection programme. Revitalization will not be easy, but it is achievable. (author)

A regulatory perspective on the abuse potential evaluation of novel stimulant drugs in the United States.

Science.gov (United States)

Calderon, Silvia N; Klein, Michael

2014-12-01

In the United States of America (USA), the abuse potential assessment of a drug is performed as part of the safety evaluation of a drug under development, and to evaluate if the drug needs to be subject to controls that would minimize the abuse of the drug once on the market. The assessment of the abuse potential of new drugs consists of a scientific and medical evaluation of all data related to abuse of the drug. This paper describes the regulatory framework for evaluating the abuse potential of new drugs, in general, including novel stimulants. The role of the United States Food and Drug Administration (FDA) in the evaluation of the abuse potential of drugs, and its role in drug control are also discussed. A definition of abuse potential, an overview of the currently accepted approaches to evaluating the abuse potential of a drug, as well as a description of the criteria that applies when recommending a specific level of control (i.e., a Schedule) for a drug under the Controlled Substances Act (CSA). This article is part of the Special Issue entitled 'CNS Stimulants'. Published by Elsevier Ltd.

Oxidative stress and maternal obesity: feto-placental unit interaction.

Science.gov (United States)

Malti, N; Merzouk, H; Merzouk, S A; Loukidi, B; Karaouzene, N; Malti, A; Narce, M

2014-06-01

To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. Maternal, fetal and placental triglyceride levels were increased in obese group compared to control. Maternal malondialdehyde, carbonyl proteins, nitric oxide and superoxide anion levels were high while reduced glutathione concentrations and superoxide dismutase activity were low in obesity. In the placenta and in newborns of these obese mothers, variations of redox balance were also observed indicating high oxidative stress. Maternal and placental interaction constituted a strong predictor of fetal redox variations in obese pregnancies. Maternal obesity compromised placental metabolism and antioxidant status which strongly impacted fetal redox balance. Oxidative stress may be one of the key downstream mediators that initiate programming of the offspring. Maternal obesity is associated with metabolic alterations and dysregulation of redox balance in the mother-placenta - fetus unit. These perturbations could lead to maternal and fetal complications and should be carefully considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

The United States nuclear regulatory commission license renewal process

International Nuclear Information System (INIS)

Holian, B.E.

2009-01-01

The United States (U.S.) Nuclear Regulatory Commission (NRC) license renewal process establishes the technical and administrative requirements for the renewal of operating power plant licenses. Reactor ope-rating licenses were originally issued for 40 years and are allowed to be renewed. The review process for license renewal applications (L.R.A.) provides continued assurance that the level of safety provided by an applicant's current licensing basis is maintained for the period of extended operation. The license renewal review focuses on passive, long-lived structures and components of the plant that are subject to the effects of aging. The applicant must demonstrate that programs are in place to manage those aging effects. The review also verifies that analyses based on the current operating term have been evaluated and shown to be valid for the period of extended operation. The NRC has renewed the licenses for 52 reactors at 30 plant sites. Each applicant requested, and was granted, an extension of 20 years. Applications to renew the licenses of 20 additional reactors at 13 plant sites are under review. As license renewal is voluntary, the decision to seek license renewal and the timing of the application is made by the licensee. However, the NRC expects that, over time, essentially all U.S. operating reactors will request license renewal. In 2009, the U.S. has 4 plants that enter their 41. year of ope-ration. The U.S. Nuclear Industry has expressed interest in 'life beyond 60', that is, requesting approval of a second renewal period. U.S. regulations allow for subsequent license renewals. The NRC is working with the U.S. Department of Energy (DOE) on research related to light water reactor sustainability. (author)

The legal, regulatory and safety basis for opening WIPP

International Nuclear Information System (INIS)

Dials, G.E.

1997-01-01

Current laws in the United States of America direct the U.S. Department of Energy (DOE) to site, design, operate, and decommission a deep geological repository for safe disposal of transuranic radioactive waste (TRUW) at the Waste Isolation Pilot Plant (WIPP) site. In 1993, the DOE established the Carlsbad Area Office (CAO) to integrate the nation's management of TRUW and to open the WIPP site for safe disposal of TRUW in compliance with applicable laws and regulations. The CAO submitted the final Compliance Certification Application (CCA) in 1996, and is on schedule to open WIPP in November 1997, about three years earlier than scheduled before the establishment of the CAO. The performance assessment (PA) embodied in the CCA demonstrates that WIPP meets the EPA's regulatory requirements for radioactive releases for the 10,000 year regulatory period in both the undisturbed and disturbed (human intrusion) scenarios. Detailed planning, compliance-based research and development (R and D), teamwork among project participants and early and open iterative interactions with the regulators, oversight groups and other interested parties in the certification/permitting process are key components of the progress in the safe disposal of long-lived radioactive wastes. (author)

United States Nuclear Regulatory Commission staff practice and procedure digest

International Nuclear Information System (INIS)

1990-03-01

This document contains procedures for review by US Nuclear Regulatory Commission for reviewing and deciding on matters pertaining to nuclear power plant licensing. Also, contained within the document are decisions the Commission has made between July 1972 to September 1989. (F.S.D.)

Identification and Functional Analysis of Gene Regulatory Sequences Interacting with Colorectal Tumor Suppressors

DEFF Research Database (Denmark)

Dahlgaard, Katja; Troelsen, Jesper

2018-01-01

Several tumor suppressors possess gene regulatory activity. Here, we describe how promoter and promoter/enhancer reporter assays can be used to characterize a colorectal tumor suppressor proteins’ gene regulatory activity of possible target genes. In the first part, a bioinformatic approach...... of the quick and efficient In-Fusion cloning method, and how to carry out transient transfections of Caco-2 colon cancer cells with the produced luciferase reporter plasmids using polyethyleneimine (PEI). A plan describing how to set up and carry out the luciferase expression assay is presented. The luciferase...... to identify relevant gene regulatory regions of potential target genes is presented. In the second part, it is demonstrated how to prepare and carry out the functional assay. We explain how to clone the bioinformatically identified gene regulatory regions into luciferase reporter plasmids by the use...

Regulatory agencies and regulatory risk

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2008-01-01

The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

Organisation and experience of the regulatory review in the United Kingdom

International Nuclear Information System (INIS)

Gausden, R.; Woods, P.B.

1979-01-01

Regulatory requirements and stages of the review in the UK are outlined. The organisation, management and working procedures of the Inspectorate are described and the effort and timescale which have been found necessary for a satisfactory safety review is discussed. A number of problem areas in the review situation have been identified from experience and these are discussed and possible solutions proposed. They include the importance of early review of generic aspects of systems which are being considered for licensing, the place of safety principles and of detailed engineering assessment in the review process, the independence of the regulatory group's activities in its study of major technical issues and the use which should be made of outside expertise. (auth.)

Regulatory Risk Management of Advanced Nuclear Power Plants

International Nuclear Information System (INIS)

George, Glenn R.

2002-01-01

Regulatory risk reflects both the likelihood of adverse outcomes during regulatory interactions and the severity of those outcomes. In the arena of advanced nuclear power plant licensing and construction, such adverse outcomes may include, for example, required design changes and construction delays. These, in turn, could significantly affect the economics of the plant and the generation portfolio in which it will operate. In this paper, the author addresses these issues through the lens of risk management. The paper considers various tools and techniques of regulatory risk management, including design diversity and hedging strategies. The effectiveness of alternate approaches is weighed and recommendations are made in several regulatory contexts. (author)

Inference of Transcription Regulatory Network in Low Phytic Acid Soybean Seeds

Directory of Open Access Journals (Sweden)

Neelam Redekar

2017-11-01

Full Text Available A dominant loss of function mutation in myo-inositol phosphate synthase (MIPS gene and recessive loss of function mutations in two multidrug resistant protein type-ABC transporter genes not only reduce the seed phytic acid levels in soybean, but also affect the pathways associated with seed development, ultimately resulting in low emergence. To understand the regulatory mechanisms and identify key genes that intervene in the seed development process in low phytic acid crops, we performed computational inference of gene regulatory networks in low and normal phytic acid soybeans using a time course transcriptomic data and multiple network inference algorithms. We identified a set of putative candidate transcription factors and their regulatory interactions with genes that have functions in myo-inositol biosynthesis, auxin-ABA signaling, and seed dormancy. We evaluated the performance of our unsupervised network inference method by comparing the predicted regulatory network with published regulatory interactions in Arabidopsis. Some contrasting regulatory interactions were observed in low phytic acid mutants compared to non-mutant lines. These findings provide important hypotheses on expression regulation of myo-inositol metabolism and phytohormone signaling in developing low phytic acid soybeans. The computational pipeline used for unsupervised network learning in this study is provided as open source software and is freely available at https://lilabatvt.github.io/LPANetwork/.

The benefits of interpersonal regulatory fit for individual goal pursuit.

NARCIS (Netherlands)

Righetti, F.; Finkenauer, C.; Rusbult, C. E.

2011-01-01

The present work examines whether individual goal pursuit is influenced by advice and suggestions from interaction partners whose regulatory orientation is perceived to fit (vs. not fit) the individual's orientation. We sought to investigate whether such interpersonal regulatory fit yields

Regulatory viewpoint on nuclear fuel quality assurance

International Nuclear Information System (INIS)

Tripp, L.E.

1976-01-01

Considerations of the importance of fuel quality and performance to nuclear safety, ''as low reasonably achievable'' release of radioactive materials in reactor effluents, and past fuel performance problems demonstrate the need for strong regulatory input, review and inspection of nuclear fuel quality assurance programs at all levels. Such a regulatory program is being applied in the United States of America by the US Nuclear Regulatory Commission. Quality assurance requirements are contained within government regulations. Guidance on acceptable methods of implementing portions of the quality assurance program is contained within Regulatory Guides and other NRC documents. Fuel supplier quality assurance program descriptions are reviewed as a part of the reactor licensing process. Inspections of reactor licensee control of their fuel vendors as well as direct inspections of fuel vendor quality assurance programs are conducted on a regularly scheduled basis. (author)

Assessing and managing regulatory risk in renewable energy: Contrasts between Canada and the United States

International Nuclear Information System (INIS)

Holburn, Guy L.F.

2012-01-01

Abstact: A challenge for energy firms when considering new investments is to balance expected financial gains against potential risks. However, while investment opportunities in different jurisdictions are often straightforward to identify, the policy or regulatory risks for investors are more difficult to accurately ascertain. Here, I provide a novel conceptual framework for how firms can assess regulatory risk that focuses on the institutional processes governing policy-making. Risks are lower – and policies will subsequently be more stable – in jurisdictions where regulatory agencies have greater autonomy from politicians and where policies are formulated through more ‘rigid’ policy-making processes. The contrasting development patterns of renewable energy policies in Ontario and Texas offer support for the framework. I further develop strategies for how firms can successfully manage regulatory risks in different types of environment. - Highlights: ► The paper provides a conceptual framework for how firms can assess regulatory risk. ► Risks are lower when regulators have greater autonomy from elected politicians. ► Risks are lower when policy-making processes are more ‘rigid’. ► Firms can strategically mitigate regulatory risk in different types of environment.

Access to the decision-making process: opportunities for public involvement in the facility decommissioning process of the United States Nuclear Regulatory Commission

International Nuclear Information System (INIS)

Cameron, F.X.

1996-01-01

This paper discusses recent initiatives taken by the United States Nuclear Regulatory Commission NRC) to effectively involve the public in decommissioning decisions. Initiatives discussed include the Commission's rulemaking to establish the radiological criteria for decommissioning, as well as public involvement methods that have been used on a site-by-site basis. As un example of public involvement, the NRC is currently in the process of developing generic rules on the radiological criteria for the decontamination and decommissioning of NRC-licensed sites. Not only was this proposed rule developed through an extensive and novel approach for public involvement, but it also establishes the basic provisions that will govern public involvement in future NRC decisions on the decommissioning of individual sites. The aim is to provide the public with timely information about all phases of the NRC staff to express concerns and make recommendations. Th NRC recognizes the value and the necessity of effective public involvement in its regulatory activities and has initiated a number of changes to its regulatory program to accomplish this. From the NRC's perspective, it is much easier and less costly to incorporate these mechanisms for public involvement into the regulatory program early in the process, rather than try to add them after considerable public controversy on an action has already been generated. The historical antecedents for initiatives mentioned, as well as 'lessons learned' from prior experience are also discussed. (author)

Results of regulatory impact survey of industrial and medical materials licensees of the Office of Nuclear Material Safety and Safeguards

International Nuclear Information System (INIS)

Lach, D.; Melber, B.; Brichoux, J.; Hattrup, M.; Conger, R.; Hughes, K.

1995-06-01

This report presents the findings of a regulatory impact survey of nuclear materials licensees of the United States Nuclear Regulatory Commission (NRC). Commissioners of the NRC directed staff to provide the Commission with first hand information from licensees that could be used to improve the overall regulatory program. A self-administered, mail-out survey questionnaire was used to collect data from a sample of licensees who had interaction with the NRC during the previous 12 months. A total of 371 respondents of the 589 who were sent questionnaires returned completed surveys, for a response rate of 63%. The body of the report presents the findings of the survey including a brief introduction to the approach used, followed by survey findings regarding regulations, policies and regulatory guidance; experience with licensing applications, renewals and amendments; inspections; reporting requirements; and enforcement actions. The appendices of the report include a copy of the survey as administered to licensees, a fuller description of the survey design and data collection methods, and detailed graphic material describing survey responses

Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 2: Appendices

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 2 contains copies of the documents which established the relationship between NRC, DOE, USEC, and DOL (Dept of Labor) required to facilitate regulatory oversight transition.

Regulatory Oversight Program, July 1, 1993 - March 3, 1997. Volume 2: Appendices

International Nuclear Information System (INIS)

1997-01-01

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 2 contains copies of the documents which established the relationship between NRC, DOE, USEC, and DOL (Dept of Labor) required to facilitate regulatory oversight transition

National legislative and regulatory activities

International Nuclear Information System (INIS)

2014-01-01

This section treats of the following activities sorted by country: 1 - Belarus: International cooperation, Organisation and structure, Licensing and regulatory infrastructure, Nuclear safety and radiological protection; 2 - France: Nuclear safety and radiological protection, Radioactive waste management, Environmental protection, Liability and compensation, International co-operation; 3 - Hungary: General legislation, Radioactive waste management, Nuclear security; 4 - Ireland: Nuclear safety and radiological protection (including emergency planning); 5 - Lithuania: Licensing and regulatory infrastructure; 6 - Moldova: Nuclear safety and radiological protection; 7 - Portugal: Radioactive waste management, Nuclear safety and radiological protection; 8 - Slovak Republic: Radioactive waste management, Liability and compensation; 9 - Spain: Radioactive waste management; 10 - Ukraine: Radioactive waste management; 11 - United Kingdom: Organisation and structure

Intramolecular dynamics within the N-Cap-SH3-SH2 regulatory unit of the c-Abl tyrosine kinase reveal targeting to the cellular membrane.

Science.gov (United States)

de Oliveira, Guilherme A P; Pereira, Elen G; Ferretti, Giulia D S; Valente, Ana Paula; Cordeiro, Yraima; Silva, Jerson L

2013-09-27

c-Abl is a key regulator of cell signaling and is under strict control via intramolecular interactions. In this study, we address changes in the intramolecular dynamics coupling within the c-Abl regulatory unit by presenting its N-terminal segment (N-Cap) with an alternative function in the cell as c-Abl becomes activated. Using small angle x-ray scattering, nuclear magnetic resonance, and confocal microscopy, we demonstrate that the N-Cap and the Src homology (SH) 3 domain acquire μs-ms motions upon N-Cap association with the SH2-L domain, revealing a stabilizing synergy between these segments. The N-Cap-myristoyl tether likely triggers the protein to anchor to the membrane because of these flip-flop dynamics, which occur in the μs-ms time range. This segment not only presents the myristate during c-Abl inhibition but may also trigger protein localization inside the cell in a functional and stability-dependent mechanism that is lost in Bcr-Abl(+) cells, which underlie chronic myeloid leukemia. This loss of intramolecular dynamics and binding to the cellular membrane is a potential therapeutic target.

Self-sustained oscillations of complex genomic regulatory networks

International Nuclear Information System (INIS)

Ye Weiming; Huang Xiaodong; Huang Xuhui; Li Pengfei; Xia Qinzhi; Hu Gang

2010-01-01

Recently, self-sustained oscillations in complex networks consisting of non-oscillatory nodes have attracted great interest in diverse natural and social fields. Oscillatory genomic regulatory networks are one of the most typical examples of this kind. Given an oscillatory genomic network, it is important to reveal the central structure generating the oscillation. However, if the network consists of large numbers of genes and interactions, the oscillation generator is deeply hidden in the complicated interactions. We apply the dominant phase-advanced driving path method proposed in Qian et al. (2010) to reduce complex genomic regulatory networks to one-dimensional and unidirectionally linked network graphs where negative regulatory loops are explored to play as the central generators of the oscillations, and oscillation propagation pathways in the complex networks are clearly shown by tree branches radiating from the loops. Based on the above understanding we can control oscillations of genomic networks with high efficiency.

NRC regulatory information conference: Proceedings

International Nuclear Information System (INIS)

1989-09-01

This volume of the report provides the proceedings from the Nuclear Regulatory Commission (NRC) Regulatory Information Conference that was held at the Mayflower Hotel, Washington, DC, on April 18, 19, and 20, 1989. This conference was held by the NRC and chaired by Dr. Thomas E. Mosley, Director, Office of Nuclear Reactor Regulations (NRR) and coordinated by S. Singh Bajwa, Chief, Technical Assistance Management Section, NRR. There were approximately 550 participants from nine countries at the conference. The countries represented were Canada, England, Italy, Japan, Mexico, Spain, Taiwan, Yugoslavia, and the United States. The NRC staff discussed with nuclear industry its regulatory philosophy and approach and the bases on which they have been established. Furthermore, the NRC staff discussed several initiatives that have been implemented recently and their bases as well as NRC's expectations for new initiatives to further improve safety. The figures contained in Appendix A to the volume correspond to the slides that were shown during the presentations. Volume 2 of this report contains the formal papers that were distributed at the beginning of the Regulatory Information Conference and other information about the conference

A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.

Directory of Open Access Journals (Sweden)

Jayson Gutiérrez

2009-09-01

Full Text Available The way in which the information contained in genotypes is translated into complex phenotypic traits (i.e. embryonic expression patterns depends on its decoding by a multilayered hierarchy of biomolecular systems (regulatory networks. Each layer of this hierarchy displays its own regulatory schemes (i.e. operational rules such as +/- feedback and associated control parameters, resulting in characteristic variational constraints. This process can be conceptualized as a mapping issue, and in the context of highly-dimensional genotype-phenotype mappings (GPMs epistatic events have been shown to be ubiquitous, manifested in non-linear correspondences between changes in the genotype and their phenotypic effects. In this study I concentrate on epistatic phenomena pervading levels of biological organization above the genetic material, more specifically the realm of molecular networks. At this level, systems approaches to studying GPMs are specially suitable to shed light on the mechanistic basis of epistatic phenomena. To this aim, I constructed and analyzed ensembles of highly-modular (fully interconnected networks with distinctive topologies, each displaying dynamic behaviors that were categorized as either arbitrary or functional according to early patterning processes in the Drosophila embryo. Spatio-temporal expression trajectories in virtual syncytial embryos were simulated via reaction-diffusion models. My in silico mutational experiments show that: 1 the average fitness decay tendency to successively accumulated mutations in ensembles of functional networks indicates the prevalence of positive epistasis, whereas in ensembles of arbitrary networks negative epistasis is the dominant tendency; and 2 the evaluation of epistatic coefficients of diverse interaction orders indicates that, both positive and negative epistasis are more prevalent in functional networks than in arbitrary ones. Overall, I conclude that the phenotypic and fitness effects of

Overlapping positive and negative regulatory domains of the human β-interferon gene

International Nuclear Information System (INIS)

Goodbourn, S.; Maniatis, T.

1988-01-01

Virus of poly(I) x poly(C) induction of human β-interferon gene expression requires a 40-base-pair DNA sequence designated the interferon gene regulatory element (IRE). Previous studies have shown that the IRE contains both positive and negative regulatory DNA sequences. To localize these sequences and study their interactions, the authors have examined the effects of a large number of single-base mutations within the IRE on β-interferon gene regulation. They find that the IRE consists of two genetically separable positive regulatory domains and an overlapping negative control sequence. They propose that the β-interferon gene is switched off in uninduced cells by a repressor that blocks the interaction between one of the two positive regulatory sequences and a specific transcription factor. Induction would then lead to inactivation or displacement of the repressor and binding of transcription factors to both positive regulatory domains

Improvement of Regulatory Framework for Long-Term Operation and Ageing Management of NPPs

International Nuclear Information System (INIS)

Kostenko, S.P.

2015-01-01

The regulatory framework for long-term operation and ageing management of NPP units in Ukraine was reviewed and deficiencies were identified. The procedure for improving regulatory framework for long-term operation and ageing management is presented. It takes into consideration IAEA recommendations and international practices, as well as experience obtained in long-term operation efforts for Rivne NPP-1, 2 and South Ukraine NPP-1. The paper demonstrates interrelations between standards and technical documents on long-term operation and ageing management. The information is presented regarding the current state of regulatory and legal documentation development and industry-specific standards on long-term operation and ageing management of NPP units in Ukraine

Classroom Interaction in Regular and Special Education Middle Primary Classrooms in the United Arab Emirates

Science.gov (United States)

Dukmak, Samir

2010-01-01

Samir Dukmak is an assistant professor in the Department of Special Education in the Faculty of Education at the United Arab Emirates University. The research reported in this article investigated the frequency, types of and reasons for student-initiated interactions in both regular and special education classrooms in the United Arab Emirates…

Regulatory approach to NPP ageing in Bulgaria

International Nuclear Information System (INIS)

Vassilev, D.

2000-01-01

In this contribution summary information of Kozloduy NPP units is presented. The nuclear legislation, regulatory approach for managing safety aspects on NPP ageing, short term programme, complex programme PRG'97 ant other aspects of ageing management are discussed

Sparsity in Model Gene Regulatory Networks

International Nuclear Information System (INIS)

Zagorski, M.

2011-01-01

We propose a gene regulatory network model which incorporates the microscopic interactions between genes and transcription factors. In particular the gene's expression level is determined by deterministic synchronous dynamics with contribution from excitatory interactions. We study the structure of networks that have a particular '' function '' and are subject to the natural selection pressure. The question of network robustness against point mutations is addressed, and we conclude that only a small part of connections defined as '' essential '' for cell's existence is fragile. Additionally, the obtained networks are sparse with narrow in-degree and broad out-degree, properties well known from experimental study of biological regulatory networks. Furthermore, during sampling procedure we observe that significantly different genotypes can emerge under mutation-selection balance. All the preceding features hold for the model parameters which lay in the experimentally relevant range. (author)

Simultaneous genome-wide inference of physical, genetic, regulatory, and functional pathway components.

Directory of Open Access Journals (Sweden)

Christopher Y Park

2010-11-01

Full Text Available Biomolecular pathways are built from diverse types of pairwise interactions, ranging from physical protein-protein interactions and modifications to indirect regulatory relationships. One goal of systems biology is to bridge three aspects of this complexity: the growing body of high-throughput data assaying these interactions; the specific interactions in which individual genes participate; and the genome-wide patterns of interactions in a system of interest. Here, we describe methodology for simultaneously predicting specific types of biomolecular interactions using high-throughput genomic data. This results in a comprehensive compendium of whole-genome networks for yeast, derived from ∼3,500 experimental conditions and describing 30 interaction types, which range from general (e.g. physical or regulatory to specific (e.g. phosphorylation or transcriptional regulation. We used these networks to investigate molecular pathways in carbon metabolism and cellular transport, proposing a novel connection between glycogen breakdown and glucose utilization supported by recent publications. Additionally, 14 specific predicted interactions in DNA topological change and protein biosynthesis were experimentally validated. We analyzed the systems-level network features within all interactomes, verifying the presence of small-world properties and enrichment for recurring network motifs. This compendium of physical, synthetic, regulatory, and functional interaction networks has been made publicly available through an interactive web interface for investigators to utilize in future research at http://function.princeton.edu/bioweaver/.

The regulatory mechanism in the U.S. lessons learned

International Nuclear Information System (INIS)

Roberts, T.M.

1987-01-01

The U.S. Nuclear Regulatory Commission is responsible for the regulation of the commercial uses of nuclear power in the United States in order to protect the public health and safety. The NRC has undertaken a number of initiatives to incorporate the experience gained from the over 25 years of commercial nuclear power plant operation. These initiatives are aimed at improving the regulatory structure currently in place by providing for a more predictable and stable regulatory environment and by more efficiently and effectively focusing the activities of utilities on the safe operation of their facilities. (author)

The waste isolation pilot plant regulatory compliance program

International Nuclear Information System (INIS)

Mewhinney, J.A.; Kehrman, R.F.

1996-01-01

The passage of the WIPP Land Withdrawal Act of 1992 (LWA) marked a turning point for the Waste Isolation Pilot Plant (WIPP) program. It established a Congressional mandate to open the WIPP in as short a time as possible, thereby initiating the process of addressing this nation's transuranic (TRU) waste problem. The DOE responded to the LWA by shifting the priority at the WIPP from scientific investigations to regulatory compliance and the completion of prerequisites for the initiation of operations. Regulatory compliance activities have taken four main focuses: (1) preparing regulatory submittals; (2) aggressive schedules; (3) regulator interface; and (4) public interactions

76 FR 82323 - Design, Inspection, and Testing Criteria for Air Filtration and Adsorption Units

Science.gov (United States)

2011-12-30

... Filtration and Adsorption Units AGENCY: Nuclear Regulatory Commission. ACTION: Draft regulatory guide... for Air Filtration and Adsorption Units of Postaccident Engineered-Safety-Feature Atmosphere Cleanup... testing of air filtration and iodine adsorption units of engineered-safety-feature (ESF) atmosphere...

The impact of gene expression variation on the robustness and evolvability of a developmental gene regulatory network.

Directory of Open Access Journals (Sweden)

David A Garfield

2013-10-01

Full Text Available Regulatory interactions buffer development against genetic and environmental perturbations, but adaptation requires phenotypes to change. We investigated the relationship between robustness and evolvability within the gene regulatory network underlying development of the larval skeleton in the sea urchin Strongylocentrotus purpuratus. We find extensive variation in gene expression in this network throughout development in a natural population, some of which has a heritable genetic basis. Switch-like regulatory interactions predominate during early development, buffer expression variation, and may promote the accumulation of cryptic genetic variation affecting early stages. Regulatory interactions during later development are typically more sensitive (linear, allowing variation in expression to affect downstream target genes. Variation in skeletal morphology is associated primarily with expression variation of a few, primarily structural, genes at terminal positions within the network. These results indicate that the position and properties of gene interactions within a network can have important evolutionary consequences independent of their immediate regulatory role.

Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

Directory of Open Access Journals (Sweden)

Guo Zheng

2006-01-01

Full Text Available Abstract Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network to address the underlying regulations of genes that can span any unit(s of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex

A review from the regulatory position of the control of occupational exposure associated with the first 20 years of the United Kingdom commercial nuclear power programme

International Nuclear Information System (INIS)

Emmerson, B.W.

1980-01-01

The control of occupational exposure received at commercial nuclear generating plants in the United Kingdom has been subject to regulatory requirements embodied in site licence conditions since 1959, and at commercial fuel production and reprocessing plants since 1971. The paper indicates the main radiological control objectives which have applied, reviews the statutory measures introduced for their achievement and indicates some of the administrative arrangements made by site operators in order to comply. The principal sources of occupational exposure associated with each stage of the fuel cycle are identified and exposure data since licensed operations commenced are reviewed. The effectiveness of the United Kingdom site licensing procedure in ensuring adequate radiological control procedures, including the minimisation of occupational exposure, is examined in relation to the relevant ICRP recommendations and against the background of the first 20 years of commercial nuclear power production. The impact on these procedures of more recently introduced legislation relating to health and safety at all places of employment in the United Kingdom is discussed. The paper considers the changes in current regulatory procedures that may result from the introduction of ICRP-26 and the recommendations of ICRP Committee 2, and concludes with a review of the more important problems facing the licensee and the Nuclear Inspectorate with regard to the implementation of future radiological control procedures. (H.K.)

United States Nuclear Regulatory Commission staff practice and procedure digest

International Nuclear Information System (INIS)

1991-02-01

This Revision 9 of the fifth edition of the NRC Staff Practice and Procedure Digest contains a digest of a number of Commission, Atomic Safety and Licensing Appeal Board, and Atomic Safety and Licensing Board decisions issued during the period from July 1, 1972 to September 30, 1990 interpreting the NRC's Rules of Practice in 10 CFR Part 2. This Revision 9 replaces in part earlier editions and revisions and includes appropriate changes reflecting the amendments to the Rules of Practice effective through September 30, 1990. This edition of the Digest was prepared by attorneys from Aspen Systems Corporation pursuant to Contract number 18-89-346. Persons using this Digest are placed on notice that it may not be used as an authoritative citation in support of any position before the Commission or any of its adjudicatory tribunals. Persons using this Digest are also placed on notice that it is intended for use only as an initial research tool, that it may, and likely does, contain errors, including errors in analysis and interpretation of decisions, and that the user should not rely on the Digest analyses and interpretations but must read, analyze and rely on the user's own analysis of the actual Commission, Appeal Board and Licensing Board decisions cited. Further, neither the United States, the Nuclear Regulatory Commission, Aspen Systems Corporation, nor any of their employees makes any expressed or implied warranty or assumes liability or responsibility for the accuracy, completeness or usefulness of any material presented in the Digest. The Digest is roughly structured in accordance with the chronological sequence of the nuclear facility licensing process as set forth in Appendix A to 10 CFR Part 2. Those decisions which did not fit into that structure are dealt with in a section on general matters. Where appropriate, particular decisions are indexed under more than one heading. (JF)

Regulatory Oversight Program, July 1, 1993 - March 3, 1997. Volume 1

International Nuclear Information System (INIS)

1997-09-01

On July 1, 1993, a Regulatory Oversight (RO) organization was established within the United States Department of Energy (DOE), Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the RO program was to ensure continued plant safety, safeguards and security while the Paducah and Portsmouth gaseous diffusion plants (GDPs) transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). These activities were performed under the authority of the lease agreement between DOE and USEC until NRC issued a Certificate of Compliance or approved a Compliance Plan pursuant to Section 1701 of the Atomic Energy Act of 1954, as amended, and assumed regulatory responsibility. This report chronicles the formal development, operation and key activities of the RO organization from its beginning in July 1993, until the turnover of the regulatory oversight responsibility to the NRC on March 3, 1997. Through its evolution to closure, the RO program was a formal, proceduralized effort designed to provide consistent regulation and to facilitate transition to NRC. The RO Program was also a first-of-a-kind program for DOE. The process, experience, and lessons learned summarized herein should be useful as a model for transition of other DOE facilities to privatization or external regulation

Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 1

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-09-01

On July 1, 1993, a Regulatory Oversight (RO) organization was established within the United States Department of Energy (DOE), Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the RO program was to ensure continued plant safety, safeguards and security while the Paducah and Portsmouth gaseous diffusion plants (GDPs) transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). These activities were performed under the authority of the lease agreement between DOE and USEC until NRC issued a Certificate of Compliance or approved a Compliance Plan pursuant to Section 1701 of the Atomic Energy Act of 1954, as amended, and assumed regulatory responsibility. This report chronicles the formal development, operation and key activities of the RO organization from its beginning in July 1993, until the turnover of the regulatory oversight responsibility to the NRC on March 3, 1997. Through its evolution to closure, the RO program was a formal, proceduralized effort designed to provide consistent regulation and to facilitate transition to NRC. The RO Program was also a first-of-a-kind program for DOE. The process, experience, and lessons learned summarized herein should be useful as a model for transition of other DOE facilities to privatization or external regulation.

Regulatory analysis for the resolution of Generic Issue 130: Essential service water system failures at multi-unit sites

International Nuclear Information System (INIS)

Leung, V.; Basdekas, D.; Mazetis, G.

1991-06-01

The essential service water system (ESWS) is required to provide cooling in nuclear power plants during normal operation and accident conditions. The ESWS typically supports component cooling water heat exchangers, containment spray heat exchangers, high-pressure injection pump oil coolers, emergency diesel generators, and auxiliary building ventilation coolers. Failure of the ESWS function could lead to severe consequences. This report presents the regulatory analysis for GI-130, ''Essential Service Water System Failures at Multi-Unit Sites.'' The risk reduction estimates, cost/benefit analyses, and other insights gained during this effort have shown that implementation of the recommendations will significantly reduce risk and that these improvements are warranted in accordance with the backfit rule, 10 CFR 50.109(a)(3). 19 refs., 16 tabs

A unified architecture of transcriptional regulatory elements

DEFF Research Database (Denmark)

Andersson, Robin; Sandelin, Albin Gustav; Danko, Charles G.

2015-01-01

Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However...... and enhancers are considered a single class of functional element, with a unified architecture for transcription initiation. The context of interacting regulatory elements and the surrounding sequences determine local transcriptional output as well as the enhancer and promoter activities of individual elements....

75 FR 6404 - Regulatory Site Visit Training Program

Science.gov (United States)

2010-02-09

... review efficiency and quality, and the quality of its regulatory efforts and interactions, by providing... tissue establishments. The visits may include packaging facilities, quality control and pathology...

High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

Science.gov (United States)

Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

2007-01-01

Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

Hormesis in Regulatory risk assessment - Science and Science Policy.

Science.gov (United States)

Gray, George

2011-01-01

This brief commentary will argue that whether hormesis is considered in regulatory risk assessment is a matter less of science than of science policy. I will first discuss the distinction between science and science policy and their roles in regulatory risk assessment. Then I will focus on factors that influence science policy, especially as it relates to the conduct of risk assessments to inform regulatory decisions, with a focus on the U.S. Environmental Protection Agency (EPA). The key questions will then be how does hormesis interact with current concepts of science and science policy for risk assessment? Finally, I look ahead to factors that may increase, or decrease, the likelihood of hormesis being incorporated into regulatory risk assessment.

Crystal structure of the regulatory subunit of archaeal initiation factor 2B (aIF2B) from hyperthermophilic archaeon Pyrococcus horikoshii OT3: a proposed structure of the regulatory subcomplex of eukaryotic IF2B

International Nuclear Information System (INIS)

Kakuta, Yoshimitsu; Tahara, Maino; Maetani, Shigehiro; Yao, Min; Tanaka, Isao; Kimura, Makoto

2004-01-01

Eukaryotic translation initiation factor 2B (eIF2B) is the guanine-nucleotide exchange factor for eukaryotic initiation factor 2 (eIF2). eIF2B is a heteropentameric protein composed of α-ε subunits. The α, β, and δ subunits form a regulatory subcomplex, while the γ and ε form a catalytic subcomplex. Archaea possess homologues of α, β, and δ subunits of eIF2B. Here, we report the three-dimensional structure of an archaeal regulatory subunit (aIF2Bα) from the hyperthermophilic archaeon Pyrococcus horikoshii OT3 determined by X-ray crystallography at 2.2 A resolution. aIF2Bα consists of two subdomains, an N-domain (residues 1-95) and a C-domain (residues 96-276), connected by a long α-helix (α5: 78-106). The N-domain contains a five helix bundle structure, while the C-domain folds into the α/β structure, thus showing similarity to D-ribose-5-phosphate isomerase structure. The presence of two molecules in the crystallographic asymmetric unit and the gel filtration analysis suggest a dimeric structure of aIF2Bα in solution, interacting with each other by C-domains. Furthermore, the crystallographic 3-fold symmetry generates a homohexameric structure of aIF2Bα; the interaction is primarily mediated by the long α-helix at the N-domains. This structure suggests an architecture of the three subunits, α, β, and δ, in the regulatory subcomplex within eIF2B

Crisis, criticism, change: Regulatory reform in the wake of nuclear accidents

International Nuclear Information System (INIS)

Sexton, Kimberly A.; )

2015-01-01

Accidents are a forcing function for change in the nuclear industry. While these events can shed light on needed technical safety reforms, they can also shine a light on needed regulatory system reforms. The TEPCO Fukushima Daiichi nuclear power plant (NPP) accident in Japan is the most recent example of this phenomenon, but it is not the only one. In the wake of the three major accidents that have occurred in the nuclear power industry - Three Mile Island (TMI) in the United States; Chernobyl in Ukraine, in the former Soviet Union; and the Fukushima Daiichi NPP accident in Japan - a commission or committee of experts issued a report (or reports) with harsh criticism of the countries' regulatory system. And each of these accidents prompted changes in the respective regulatory systems. In looking at these responses, however, one must ask if this crisis, criticism, change approach is working and whether regulatory bodies around the world should instead undertake their own systematic reviews, un-prompted by crisis, to better ensure safety. This article will attempt to analyse the issue of regulatory reform in the wake of nuclear accidents by first providing a background in nuclear regulatory systems, looking to international and national legal frameworks. Next, the article will detail a cross-section of current regulatory systems around the world. Following that, the article will analyse the before and after of the regulatory systems in the United States, the Soviet Union and Japan in relation to the TMI, Chernobyl and Fukushima accidents. Finally, taking all this together, the article will address some of the international and national efforts to define exactly what makes a good regulator and provide conclusions on regulatory reform in the wake of nuclear accidents. (author)

Use of risk information in regulatory reviews

International Nuclear Information System (INIS)

Sagar, B.; Benke, R.; Mohanty, S.

2004-01-01

The regulatory framework for licensing any high-level waste repository at Yucca Mountain in the United States, calls for appropriate use of risk information to ensure operational safety during the pre-closure period and long-term safety during the post-closure period. This paper focuses on the post-closure period. Regulations in the Code of Federal Regulations (CFR), Title 10, Part 63, apply to any repository at Yucca Mountain and envision use of probabilistic methods to develop quantitative risk information. Accumulated engineering and scientific experience at Yucca Mountain and analog sites and quantitative risk information from studies conducted by the implementer, regulator, and others are combined to formulate 'risk insights,' which are then used to plan and execute regulatory reviews. The U.S. Nuclear Regulatory Commission (NRC) and the Center for Nuclear Waste Regulatory Analyses (CNWRA) recently consolidated the knowledge gained during several g ears and developed such risk insights for the potential repository at Yucca Mountain. This paper discusses the types of risk information used to generate risk insights and how the risk insights will be used in regulatory reviews. A companion paper presents more details on sensitivity analysis methods used to generate risk information. (authors)

Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 3

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 3 contains copies of two reports that document the DOE/ORO regulatory oversight inspection and enforcement history for each gaseous diffusion plant site. Each report provides a formal mechanism by which DOE/ORO could communicate the inspection and enforcement history to NRC. The reports encompass the inspection activities that occurred during July 1, 1993 through March 2, 1997.

The transcriptional regulatory network of Corynebacterium jeikeium K411 and its interaction with metabolic routes contributing to human body odor formation.

Science.gov (United States)

Barzantny, Helena; Schröder, Jasmin; Strotmeier, Jasmin; Fredrich, Eugenie; Brune, Iris; Tauch, Andreas

2012-06-15

Lipophilic corynebacteria are involved in the generation of volatile odorous products in the process of human body odor formation by degrading skin lipids and specific odor precursors. Therefore, these bacteria represent appropriate model systems for the cosmetic industry to examine axillary malodor formation on the molecular level. To understand the transcriptional control of metabolic pathways involved in this process, the transcriptional regulatory network of the lipophilic axilla isolate Corynebacterium jeikeium K411 was reconstructed from the complete genome sequence. This bioinformatic approach detected a gene-regulatory repertoire of 83 candidate proteins, including 56 DNA-binding transcriptional regulators, nine two-component systems, nine sigma factors, and nine regulators with diverse physiological functions. Furthermore, a cross-genome comparison among selected corynebacterial species of the taxonomic cluster 3 revealed a common gene-regulatory repertoire of 44 transcriptional regulators, including the MarR-like regulator Jk0257, which is exclusively encoded in the genomes of this taxonomical subline. The current network reconstruction comprises 48 transcriptional regulators and 674 gene-regulatory interactions that were assigned to five interconnected functional modules. Most genes involved in lipid degradation are under the combined control of the global cAMP-sensing transcriptional regulator GlxR and the LuxR-family regulator RamA, probably reflecting the essential role of lipid degradation in C. jeikeium. This study provides the first genome-scale in silico analysis of the transcriptional regulation of metabolism in a lipophilic bacterium involved in the formation of human body odor. Copyright © 2012 Elsevier B.V. All rights reserved.

CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation1,2

Science.gov (United States)

Thauland, Timothy J.; Koguchi, Yoshinobu; Dustin, Michael L.; Parker, David C.

2014-01-01

Regulatory T cells (Tregs) are essential for tolerance to self and environmental antigens, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naïve CD4 T cell-DC interactions. Here, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs. We use supported planar bilayers to show that Tregs dramatically slow down, but maintain a highly polarized and motile phenotype after recognizing antigen in the absence of costimulation. These motile cells are characterized by distinct accumulations of LFA-1-ICAM-1 in the lamella and TCR-MHC in the uropod, consistent with a motile immunological synapse or ‘kinapse’. However, in the presence of high, but not low, concentrations of CD80, Tregs form stationary, symmetrical synapses. Using blocking antibodies, we show that, while CTLA-4 is required for CD80 downmodulation, CD28-CD80 interactions are critical for modulating Treg motility in the presence of antigen. Together, these results support the hypothesis that Tregs are tuned to alter their motility depending on costimulatory signals. PMID:25355918

76 FR 76168 - Regulatory Site Visit Training Program

Science.gov (United States)

2011-12-06

... quality of its regulatory efforts and interactions, by providing CBER staff with a better understanding of... may include the following: (1) Packaging facilities, (2) quality control and pathology/toxicology...

76 FR 4919 - Regulatory Site Visit Training Program

Science.gov (United States)

2011-01-27

... quality of its regulatory efforts and interactions, by providing CBER staff with a better understanding of... may include the following: (1) Packaging facilities, (2) quality control and pathology/toxicology...

Why do interracial interactions impair executive function? A resource depletion account.

Science.gov (United States)

Richeson, Jennifer A; Trawalter, Sophie

2005-06-01

Three studies investigated the veracity of a resource depletion account of the impairment of inhibitory task performance after interracial contact. White individuals engaged in either an interracial or same-race interaction, then completed an ostensibly unrelated Stroop color-naming test. In each study, the self-regulatory demands of the interaction were either increased (Study 1) or decreased (Studies 2 and 3). Results revealed that increasing the self-regulatory demands of an interracial interaction led to greater Stroop interference compared with control, whereas reducing self-regulatory demands led to less Stroop interference. Manipulating self-regulatory demands did not affect Stroop performance after same-race interactions. Taken together, the present studies point to resource depletion as the likely mechanism underlying the impairment of cognitive functioning after interracial dyadic interactions.

Information transmission in genetic regulatory networks: a review

International Nuclear Information System (INIS)

Tkacik, Gasper; Walczak, Aleksandra M

2011-01-01

Genetic regulatory networks enable cells to respond to changes in internal and external conditions by dynamically coordinating their gene expression profiles. Our ability to make quantitative measurements in these biochemical circuits has deepened our understanding of what kinds of computations genetic regulatory networks can perform, and with what reliability. These advances have motivated researchers to look for connections between the architecture and function of genetic regulatory networks. Transmitting information between a network's inputs and outputs has been proposed as one such possible measure of function, relevant in certain biological contexts. Here we summarize recent developments in the application of information theory to gene regulatory networks. We first review basic concepts in information theory necessary for understanding recent work. We then discuss the functional complexity of gene regulation, which arises from the molecular nature of the regulatory interactions. We end by reviewing some experiments that support the view that genetic networks responsible for early development of multicellular organisms might be maximizing transmitted 'positional information'. (topical review)

Interaction of the Yersinia pestis type III regulatory proteins LcrG and LcrV occurs at a hydrophobic interface

Directory of Open Access Journals (Sweden)

Nilles Matthew L

2002-06-01

Full Text Available Abstract Background Secretion of anti-host proteins by Yersinia pestis via a type III mechanism is not constitutive. The process is tightly regulated and secretion occurs only after an appropriate signal is received. The interaction of LcrG and LcrV has been demonstrated to play a pivotal role in secretion control. Previous work has shown that when LcrG is incapable of interacting with LcrV, secretion of anti-host proteins is prevented. Therefore, an understanding of how LcrG interacts with LcrV is required to evaluate how this interaction regulates the type III secretion system of Y. pestis. Additionally, information about structure-function relationships within LcrG is necessary to fully understand the role of this key regulatory protein. Results In this study we demonstrate that the N-terminus of LcrG is required for interaction with LcrV. The interaction likely occurs within a predicted amphipathic coiled-coil domain within LcrG. Our results demonstrate that the hydrophobic face of the putative helix is required for LcrV interaction. Additionally, we demonstrate that the LcrG homolog, PcrG, is incapable of blocking type III secretion in Y. pestis. A genetic selection was utilized to obtain a PcrG variant capable of blocking secretion. This PcrG variant allowed us to locate a region of LcrG involved in secretion blocking. Conclusion Our results demonstrate that LcrG interacts with LcrV via hydrophobic interactions located in the N-terminus of LcrG within a predicted coiled-coil motif. We also obtained preliminary evidence that the secretion blocking activity of LcrG is located between amino acids 39 and 53.

International nuclear safety experts conclude IAEA peer review of China's regulatory system

International Nuclear Information System (INIS)

2010-01-01

Full text: An international team of senior experts on nuclear safety regulation today completed a two-week International Atomic Energy Agency (IAEA) review of the governmental and regulatory framework for nuclear safety in the People's Republic of China. The team identified good practices within the system and gave advice on areas for future improvements. The IAEA has conveyed the team's main conclusions to the Government of the People's Republic of China. The final report will be submitted to China by Autumn 2010. At the request of Chinese authorities, the IAEA assembled a team of 22 experts to conduct an Integrated Regulatory Review Service (IRRS) mission. This mission is a peer review based on the IAEA Safety Standards . It is not an inspection, nor an audit. The experts came from 15 different countries: Australia, Canada, the Czech Republic, Finland, France, Hungary, Japan, Pakistan, the Republic of Korea, Slovenia, South Africa, Sweden, the United Kingdom, Ukraine and the United States. Mike Weightman, the United Kingdom's Head of Nuclear Directorate, HSE and HM Chief Inspector of Nuclear Installations said: ''I was honoured and pleased to lead such a team of senior regulatory experts from around the world, and I was impressed by their commitment, experience and hard work to provide their best advice possible. We had very constructive interactions with the Chinese authority to maximize the beneficial impact of the mission.'' The scope of the mission included the regulation of nuclear and radiation safety of the facilities and activities regulated by the Ministry of Environmental Protection (MEP) National Nuclear Safety Administration (NNSA). The mission was conducted from 18 to 30 July, mainly in Beijing. To observe Chinese regulatory activities, the IRRS team visited several nuclear facilities, including a nuclear power plant, a manufacturer of safety components for nuclear power plants, a research reactor, a fuel cycle facility, a waste management facility

Interaction mode between catalytic and regulatory subunits in glucosidase II involved in ER glycoprotein quality control.

Science.gov (United States)

Satoh, Tadashi; Toshimori, Takayasu; Noda, Masanori; Uchiyama, Susumu; Kato, Koichi

2016-11-01

The glycoside hydrolase family 31 (GH31) α-glucosidases play vital roles in catabolic and regulated degradation, including the α-subunit of glucosidase II (GIIα), which catalyzes trimming of the terminal glucose residues of N-glycan in glycoprotein processing coupled with quality control in the endoplasmic reticulum (ER). Among the known GH31 enzymes, only GIIα functions with its binding partner, regulatory β-subunit (GIIβ), which harbors a lectin domain for substrate recognition. Although the structural data have been reported for GIIα and the GIIβ lectin domain, the interaction mode between GIIα and GIIβ remains unknown. Here, we determined the structure of a complex formed between GIIα and the GIIα-binding domain of GIIβ, thereby providing a structural basis underlying the functional extension of this unique GH31 enzyme. © 2016 The Protein Society.

Self-discrepancy and regulatory fit in avatar-based exergames.

Science.gov (United States)

Jin, Seung-A Annie

2012-12-01

Drawing from Higgins's self-discrepancy theory and regulatory focus theory, this study examined the use of activated selves and regulatory foci in health games. Utilizing the Wii's avatar-creating and exergaming features, a 2 (activated self: actual self versus ideal self) x 2 (regulatory focus: promotion versus prevention) x 2 (efficacy appeals: self-efficacy versus response-efficacy) between-subjects experiment tested the interactions of activated selves, regulatory foci, and efficacy appeals on low-calorie dieting intentions after health game playing. Results from an experiment with 156 participants demonstrated that a fit between regulatory focus and efficacy appeals induced greater dieting intentions when the actual self was activated while the opposite effect occurred when the ideal self was activated. Theoretical contributions to basic and applied social psychology as well as managerial implications for consumer behavior research are considered.

Characterization of noncoding regulatory DNA in the human genome.

Science.gov (United States)

Elkon, Ran; Agami, Reuven

2017-08-08

Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

Transcription regulatory networks analysis using CAGE

KAUST Repository

Tegnér, Jesper N.

2009-10-01

Mapping out cellular networks in general and transcriptional networks in particular has proved to be a bottle-neck hampering our understanding of biological processes. Integrative approaches fusing computational and experimental technologies for decoding transcriptional networks at a high level of resolution is therefore of uttermost importance. Yet, this is challenging since the control of gene expression in eukaryotes is a complex multi-level process influenced by several epigenetic factors and the fine interplay between regulatory proteins and the promoter structure governing the combinatorial regulation of gene expression. In this chapter we review how the CAGE data can be integrated with other measurements such as expression, physical interactions and computational prediction of regulatory motifs, which together can provide a genome-wide picture of eukaryotic transcriptional regulatory networks at a new level of resolution. © 2010 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

Regulatory Promotion of Emergent CCS Technology

Energy Technology Data Exchange (ETDEWEB)

Davies, Lincoln; Uchitel, Kirsten; Johnson, David

2014-01-01

Despite the growing inevitability of climate change and the attendant need for mitigation strategies, carbon capture and sequestration (CCS) has yet to gain much traction in the United States. Recent regulatory proposals by the U.S. Environmental Protection Agency (EPA), limited in scope to new-build power plants, represent the only significant policy initiative intended to mandate diffusion of CCS technology. Phase I of this Project assessed barriers to CCS deployment as prioritized by the CCS community. That research concluded that there were four primary barriers: (1) cost, (2) lack of a carbon price, (3) liability, and (4) lack of a comprehensive regulatory regime. Phase II of this Project, as presented in this Report, assesses potential regulatory models for CCS and examines where those models address the hurdles to diffusing CCS technology identified in Phase I. It concludes (1) that a CCS-specific but flexible standard, such as a technology performance standard or a very particular type of market-based regulation, likely will promote CCS diffusion, and (2) that these policies cannot work alone, but rather, should be combined with other measures, such as liability limits and a comprehensive CCS regulatory regime.

Reactivation of nuclear power plant construction projects. Plant status, policy issues and regulatory options

International Nuclear Information System (INIS)

Spangler, M.B.

1986-07-01

Prior to the TMI-2 accident on March 28, 1979, four nuclear power plant units that had previously been issued a construction permit were cancelled, principally because of reduced projections of regional power demand. Since that time, an additional 31 units with CPs have been cancelled and eight units deferred. On December 23, 1985 one of the deferred units (Limerick-2) was reactivated and construction resumed. The primary objective of this policy study is to identify the principal issues requiring office-level consideration in the event of reactivation of the construction of one or more of the nuclear power plants falling into two categories: (1) LWR units issued a construction permit whose construction has been cancelled, and (2) LWR units whose construction has been deferred. The study scope is limited to identifying regulatory issues or questions deserving analysis rather than providing, at this time, answers or recommended actions. Five tasks are addressed: a tabulation and discussion of the status of all cancelled and deferred LWR units; and identification of potential safety and environmental issues; an identification of regulatory or policy issues and needed information to determine the desirability of revising certain rules and policies; and identification of regulatory options and decision criteria; and an identification of decision considerations in determining staff requirements and organizational coordination of LWR reactivation policy and implementation efforts. 41 refs

rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks.

Science.gov (United States)

Guo, Liyuan; Wang, Jing

2018-01-04

Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element-target gene pairs (E-G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Synthetic tetracycline-inducible regulatory networks: computer-aided design of dynamic phenotypes

Directory of Open Access Journals (Sweden)

Kaznessis Yiannis N

2007-01-01

Full Text Available Abstract Background Tightly regulated gene networks, precisely controlling the expression of protein molecules, have received considerable interest by the biomedical community due to their promising applications. Among the most well studied inducible transcription systems are the tetracycline regulatory expression systems based on the tetracycline resistance operon of Escherichia coli, Tet-Off (tTA and Tet-On (rtTA. Despite their initial success and improved designs, limitations still persist, such as low inducer sensitivity. Instead of looking at these networks statically, and simply changing or mutating the promoter and operator regions with trial and error, a systematic investigation of the dynamic behavior of the network can result in rational design of regulatory gene expression systems. Sophisticated algorithms can accurately capture the dynamical behavior of gene networks. With computer aided design, we aim to improve the synthesis of regulatory networks and propose new designs that enable tighter control of expression. Results In this paper we engineer novel networks by recombining existing genes or part of genes. We synthesize four novel regulatory networks based on the Tet-Off and Tet-On systems. We model all the known individual biomolecular interactions involved in transcription, translation, regulation and induction. With multiple time-scale stochastic-discrete and stochastic-continuous models we accurately capture the transient and steady state dynamics of these networks. Important biomolecular interactions are identified and the strength of the interactions engineered to satisfy design criteria. A set of clear design rules is developed and appropriate mutants of regulatory proteins and operator sites are proposed. Conclusion The complexity of biomolecular interactions is accurately captured through computer simulations. Computer simulations allow us to look into the molecular level, portray the dynamic behavior of gene regulatory

Scientific underpinnings of biotechnology regulatory frameworks.

Science.gov (United States)

Gleim, Savannah; Smyth, Stuart J

2018-05-25

Part of what is presently missing at domestic regulatory levels (and that is important at the international level as well) is a detailed understanding of what the rules of, and for, regulation should be, who the actors, stakeholders and major decision makers are and finally, how to get agreement about the rules. Greater insights into the system of rules that underpin regulatory frameworks for agri-food and biotechnology products in genetically modified (GM) crop- adopting nations will provide value by clarifying the evidence used to commercialize these technologies. This article examines the public documents available from Canada, the United States, the European Union and the Organisation for Economic Cooperation and Development regarding the development of regulatory risk assessment frameworks for products of biotechnology to determine what science grounds these frameworks. The documentation used to provide the initial structure to the existing regulatory frameworks identifies the linkages, connections and relationships that exist between science, risk assessment and regulatory policy. The relationship between risk and regulation has never been more critical to the commercialization of innovative agricultural products. Documenting the role of science-based risk assessment in regulations and how this has changed over the 20 years of experience in regulating GM crops will identify changes in the risk/regulation relationship. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks

Science.gov (United States)

Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E.; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A.; Kellis, Manolis

2012-01-01

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein–protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level. PMID:22456606

Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks.

Science.gov (United States)

Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A; Kellis, Manolis

2012-07-01

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein-protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level.

Nuclear Regulatory Commission Information Digest: 1993 edition

International Nuclear Information System (INIS)

1993-03-01

The Nuclear Regulatory Commission Information Digest (digest) provides a summary of information about the U.S. Nuclear Regulatory Commission (NRC), NRC's regulatory responsibilities, the activities NRC licenses, and general information on domestic and worldwide nuclear energy. The digest, published annually, is a compilation of nuclear- and NRC-related data and is designed to provide a quick reference to major facts about the agency and the industry it regulates. In general, the data cover 1975 through 1992, with exceptions noted. Information on generating capacity and average capacity factor for operating U.S. commercial nuclear power reactors is obtained from monthly operating reports that are submitted directly to the NRC by the licensee. This information is reviewed by the NRC for consistency only and no independent validation and/or verification is performed. Comments and/or suggestions on the data presented are welcomed and should be directed to Karen Olive, United States Nuclear Regulatory Commission, Office of the Controller, Division of Budget and Analysis, Washington, D.C. 20555. For detailed and complete information about tables and figures, refer to the source publications

Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases

Directory of Open Access Journals (Sweden)

Min Kyung Sung

2014-12-01

Full Text Available Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE data: type 2 diabetes mellitus (DM, hypertension (HT, and coronary artery disease (CAD. We showed that epistatic single-nucleotide polymorphisms (SNPs were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012, which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE. Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.

78 FR 44193 - Introduction to the Unified Agenda of Federal Regulatory and Deregulatory Actions

Science.gov (United States)

2013-07-23

... the United States Federal Mediation and Conciliation Service Financial Stability Oversight Council... Flexibility Analysis, actions selected for periodic review under section 610(c) of the Regulatory Flexibility... know what action it will take next. Regulatory Flexibility Analysis Required--whether an analysis is...

Global transcriptional regulatory network for Escherichia coli robustly connects gene expression to transcription factor activities

Science.gov (United States)

Fang, Xin; Sastry, Anand; Mih, Nathan; Kim, Donghyuk; Tan, Justin; Lloyd, Colton J.; Gao, Ye; Yang, Laurence; Palsson, Bernhard O.

2017-01-01

Transcriptional regulatory networks (TRNs) have been studied intensely for >25 y. Yet, even for the Escherichia coli TRN—probably the best characterized TRN—several questions remain. Here, we address three questions: (i) How complete is our knowledge of the E. coli TRN; (ii) how well can we predict gene expression using this TRN; and (iii) how robust is our understanding of the TRN? First, we reconstructed a high-confidence TRN (hiTRN) consisting of 147 transcription factors (TFs) regulating 1,538 transcription units (TUs) encoding 1,764 genes. The 3,797 high-confidence regulatory interactions were collected from published, validated chromatin immunoprecipitation (ChIP) data and RegulonDB. For 21 different TF knockouts, up to 63% of the differentially expressed genes in the hiTRN were traced to the knocked-out TF through regulatory cascades. Second, we trained supervised machine learning algorithms to predict the expression of 1,364 TUs given TF activities using 441 samples. The algorithms accurately predicted condition-specific expression for 86% (1,174 of 1,364) of the TUs, while 193 TUs (14%) were predicted better than random TRNs. Third, we identified 10 regulatory modules whose definitions were robust against changes to the TRN or expression compendium. Using surrogate variable analysis, we also identified three unmodeled factors that systematically influenced gene expression. Our computational workflow comprehensively characterizes the predictive capabilities and systems-level functions of an organism’s TRN from disparate data types. PMID:28874552

DOE regulatory reform initiative vitrified mixed waste

International Nuclear Information System (INIS)

Carroll, S.J.; Holtzscheiter, E.W.

1997-01-01

The US Department of Energy (DOE) is charged with responsibly managing the largest volume of mixed waste in the United States. This responsibility includes managing waste in compliance with all applicable Federal and State laws and regulations, and in a cost-effective, environmentally responsible manner. Managing certain treated mixed wastes in Resource Conservation and Recovery Act (RCRA) permitted storage and disposal units (specifically those mixed wastes that pose low risks from the hazardous component) is unlikely to provide additional protection to human health and the environment beyond that afforded by managing these wastes in storage and disposal units subject to requirements for radiological control. In October, 1995, the DOE submitted a regulatory reform proposal to the Environmental Protection Agency (EPA) relating to vitrified mixed waste forms. The technical proposal supports a regulatory strategy that would allow vitrified mixed waste forms treated through a permit or other environmental compliance mechanism to be granted an exemption from RCRA hazardous waste regulation, after treatment, based upon the inherent destruction and immobilization capabilities of vitrification technology. The vitrified waste form will meet, or exceed the performance criteria of the Environmental Assessment (EA) glass that has been accepted as an international standard for immobilizing radioactive waste components and the LDR treatment standards for inorganics and metals for controlling hazardous constituents. The proposal further provides that vitrified mixed waste would be responsibly managed under the Atomic Energy Act (AEA) while reducing overall costs. Full regulatory authority by the EPA or a State would be maintained until an acceptable vitrified mixed waste form, protective of human health and the environment, is produced

10 CFR 20.1005 - Units of radioactivity.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Units of radioactivity. 20.1005 Section 20.1005 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION General Provisions § 20.1005 Units of radioactivity. For the purposes of this part, activity is expressed in the special unit of...

Regulatory approaches to obesity prevention: A systematic overview of current laws addressing diet-related risk factors in the European Union and the United States.

Science.gov (United States)

Sisnowski, Jana; Handsley, Elizabeth; Street, Jackie M

2015-06-01

High prevalence of overweight and obesity remains a significant international public health problem. Law has been identified as a tool for obesity prevention and selected high-profile measures have been reported. However, the nature and extent of enacted legislation internationally are unclear. This research provides an overview of regulatory approaches enacted in the United States, the European Union, and EU Member States since 2004. To this end, relevant databases of primary and secondary legislation were systematically searched to identify and explore laws addressing dietary risk factors for obesity. Across jurisdictions, current regulatory approaches to obesity prevention are limited in reach and scope. Target groups are rarely the general population, but instead sub-populations in government-supported settings. Consumer information provision is preferred over taxation and marketing restrictions other than the regulation of health and nutrition claims. In the EU in particular, product reformulation with industry consent has also emerged as a popular small-scale measure. While consistent and widespread use of law is lacking, governments have employed a range of regulatory measures in the name of obesity prevention, indicating that there is, in principle, political will. Results from this study may serve as a starting point for future research and policy development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In silico analysis of cis-acting regulatory elements in 5' regulatory regions of sucrose transporter gene families in rice (Oryza sativa Japonica) and Arabidopsis thaliana.

Science.gov (United States)

Ibraheem, Omodele; Botha, Christiaan E J; Bradley, Graeme

2010-12-01

The regulation of gene expression involves a multifarious regulatory system. Each gene contains a unique combination of cis-acting regulatory sequence elements in the 5' regulatory region that determines its temporal and spatial expression. Cis-acting regulatory elements are essential transcriptional gene regulatory units; they control many biological processes and stress responses. Thus a full understanding of the transcriptional gene regulation system will depend on successful functional analyses of cis-acting elements. Cis-acting regulatory elements present within the 5' regulatory region of the sucrose transporter gene families in rice (Oryza sativa Japonica cultivar-group) and Arabidopsis thaliana, were identified using a bioinformatics approach. The possible cis-acting regulatory elements were predicted by scanning 1.5kbp of 5' regulatory regions of the sucrose transporter genes translational start sites, using Plant CARE, PLACE and Genomatix Matinspector professional databases. Several cis-acting regulatory elements that are associated with plant development, plant hormonal regulation and stress response were identified, and were present in varying frequencies within the 1.5kbp of 5' regulatory region, among which are; A-box, RY, CAT, Pyrimidine-box, Sucrose-box, ABRE, ARF, ERE, GARE, Me-JA, ARE, DRE, GA-motif, GATA, GT-1, MYC, MYB, W-box, and I-box. This result reveals the probable cis-acting regulatory elements that possibly are involved in the expression and regulation of sucrose transporter gene families in rice and Arabidopsis thaliana during cellular development or environmental stress conditions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins.

Science.gov (United States)

Zhang, Mingce; Robinson, Tanya O; Duverger, Alexandra; Kutsch, Olaf; Heath, Sonya L; Cron, Randy Q

2018-03-01

During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently represent the largest subpopulation of CD4 T cell subsets, implying relative resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture system. This suppression was mediated in part via multiple inhibitory surface proteins expressed on Tregs. Antibody blockade of CTLA-4, PD-1, and GARP on Tregs resulted in increased HIV-1 DNA integration and mRNA expression in neighboring CD4 T cells. Moreover, antibody blockade of Tregs inhibitory proteins resulted in increased HIV-1 LTR transcription in co-cultured CD4 T cells. Thus, Tregs inhibit HIV-1 infection of other CD4 T cell subsets via interactions with inhibitory cell surface proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

78 FR 49553 - Three Mile Island, Unit 2; Post Shutdown Decommissioning Activities Report

Science.gov (United States)

2013-08-14

... NUCLEAR REGULATORY COMMISSION [Docket No. 50-320; NRC-2013-0183] Three Mile Island, Unit 2; Post Shutdown Decommissioning Activities Report AGENCY: Nuclear Regulatory Commission. ACTION: Notice of receipt... Shutdown Decommissioning Activity Report (PSDAR) for Three Mile Island, Unit 2 (TMI-2). The PSDAR provides...

USNRC regulatory guidance for engineered safety feature air cleaning systems

International Nuclear Information System (INIS)

Bellamy, R.R.

1991-01-01

The need for clear, technically appropriate, and easily implementable guidance for the design, testing, and maintenance of nuclear air cleaning systems has long been recognized. Numerous industry consensus standards have been issued and revised over the last 30 years. Guidance has also been published by the US Nuclear Regulatory Commission in the form of regulations, regulatory guides, standard review plans, NUREG documents, and information notices. This paper will summarize the latest revisions to these documents and emphasize Regulatory Guide 1.52, Design, Testing, and Maintenance Criteria for Post-Accident Engineered-Safety-Feature Atmosphere Cleanup System Air Filtration and Adsorption Units of Light-Water-Cooled Nuclear Power Plants, which was last revised in 1978. The USNRC has undertaken a project to revise this regulatory guide, and the status of that revision is highlighted

Senescence-associated barley NAC (NAM, ATAF1,2, CUC) transcription factor interacts with radical-induced cell death 1 through a disordered regulatory domain

DEFF Research Database (Denmark)

Kjaersgaard, Trine; Jensen, Michael K; Christiansen, Michael W

2011-01-01

as a transcriptional activator suggesting that an involvement of HvNAC013 and HvNAC005 in senescence will be different. HvNAC013 interacted with barley radical-induced cell death 1 (RCD1) via the very C-terminal part of its TRD, outside of the region containing the LP motif. No significant secondary structure...... (NAM, ATAF1,2, CUC) TF family are up-regulated during senescence in barley (Hordeum vulgare). Both HvNAC005 and HvNAC013 bound the conserved NAC DNA target sequence. Computational and biophysical analyses showed that both proteins are intrinsically disordered in their large C-terminal domains, which...... was induced in the HvNAC013 TRD upon interaction with RCD1. RCD1 also interacted with regions dominated by intrinsic disorder in TFs of the MYB and basic helix-loop-helix families. We propose that RCD1 is a regulatory protein capable of interacting with many different TFs by exploiting their intrinsic...

Aquaporin Protein-Protein Interactions

Directory of Open Access Journals (Sweden)

Jennifer Virginia Roche

2017-10-01

Full Text Available Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently regulated by gating or trafficking, allowing for the cell to control membrane permeability in a specific manner. Protein–protein interactions play crucial roles in both regulatory processes and also mediate alternative functions such as cell adhesion. In this review, we summarize recent knowledge about aquaporin protein–protein interactions; dividing the interactions into three types: (1 interactions between aquaporin tetramers; (2 interactions between aquaporin monomers within a tetramer (hetero-tetramerization; and (3 transient interactions with regulatory proteins. We particularly focus on the structural aspects of the interactions, discussing the small differences within a conserved overall fold that allow for aquaporins to be differentially regulated in an organism-, tissue- and trigger-specific manner. A deep knowledge about these differences is needed to fully understand aquaporin function and regulation in many physiological processes, and may enable design of compounds targeting specific aquaporins for treatment of human disease.

CMRegNet-An interspecies reference database for corynebacterial and mycobacterial regulatory networks

DEFF Research Database (Denmark)

Abreu, Vinicius A C; Almeida, Sintia; Tiwari, Sandeep

2015-01-01

gene regulatory network can lead to various practical applications, creating a greater understanding of how organisms control their cellular behavior. DESCRIPTION: In this work, we present a new database, CMRegNet for the gene regulatory networks of Corynebacterium glutamicum ATCC 13032......Net to date the most comprehensive database of regulatory interactions of CMNR bacteria. The content of CMRegNet is publicly available online via a web interface found at http://lgcm.icb.ufmg.br/cmregnet ....

Romania - NPP PLiM Between Regulatory Requirement / Oversight and Operator Safety / Financial Interest

International Nuclear Information System (INIS)

Goicea, Lucian

2012-01-01

Cernavoda Unit 1 PLiM started in the first third of its design life, to develop as regulatory requirements of the components of standards and programmes and to benefit by earlier implementation of the measures for achieving maximum operating life. CNCAN regulatory present approach on the utility PLiM combines the regulatory requirements on management system, ageing management provisions of periodic safety review, detailed technical requirements of ageing programmes and different techniques focusing only on safety issues. (author)

The Interaction of Motivation, Self-Regulatory Strategies, and Autonomous Learning Behavior in Different Learner Groups

Science.gov (United States)

Kormos, Judit; Csizér, Kata

2014-01-01

Autonomous learning and effective self-regulatory strategies are increasingly important in foreign language learning; without these, students might not be able to exploit learning opportunities outside language classrooms. This study investigated the influence of motivational factors and self-regulatory strategies on autonomous learning behavior.…

As to achieve regulatory action, regulatory approaches

International Nuclear Information System (INIS)

Cid, R.; Encinas, D.

2014-01-01

The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

Age specific interactions between smoking and radon among United States uranium miners

International Nuclear Information System (INIS)

Steenland, K.

1994-01-01

United States uranium miners who smoked have death rates from lung cancer that are intermediate between the rates predicted by the additive and multiplicative models (on a ratio scale) across all age groups. Age specific patterns of interaction have not been thoroughly examined, and most analyses have been internal ones in which there was no truly non-exposed group. Here age specific death rates of lung cancer among ever smoking uranium miners have been examined for conformity with the additive and multiplicative models. The multiplicative model fits well for the youngest and oldest categories, but poorly for the middle age ranges. In the middle age range, predicted rates under the multiplicative model were quite high, surpassing the corresponding United States death rates for all causes combined. (Author)

Breeding and regulatory opportunities and constraints for developing broccoli cultivars adapted to organic agriculture

NARCIS (Netherlands)

Renaud, E.N.C.

2014-01-01

This thesis is about the regulatory and technical challenges to the organic seed and breeding sector. This study specifically explored the mutual influence of the regulatory environment for organic seed sector development in the United States (US), Europe Union (EU) and Mexico, and the extent to

77 FR 13258 - Biotechnology Regulatory Services; Changes Regarding the Solicitation of Public Comment for...

Science.gov (United States)

2012-03-06

...] Biotechnology Regulatory Services; Changes Regarding the Solicitation of Public Comment for Petitions for..., Chief of Staff, Biotechnology Regulatory Services, APHIS, 4700 River Road Unit 147, Riverdale, MD 20737... process changes APHIS is making to our petition process, go to http://www.aphis.usda.gov/biotechnology/pet...

Activities of Nuclear Regulatory Authority and safety of nuclear facilities in the Slovak Republic in 1993

International Nuclear Information System (INIS)

1994-04-01

A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (NRA SR) in 1993 is presented. These activities are reported under the headings: (1) Introduction; (2) Regulatory activities at nuclear power plants units in operation; (2.1) Nuclear power plant SEP-EBO V-1; (4) Selected operation events and safety assessment in NPP SEP-EBO V-1; (2.2) Safety assessment of NPP SEP-EBO V-2; (3) Results of regulatory activities at the decommissioning of NPP A-1; (4) Regulatory activities at units under construction SEP-EMO - NPP Mochovce; (5) Further regulatory activities. (5.1) Preparation of designated personnel; (5.2) Inspection and accountancy of nuclear material; (5.3) Security provisions; (5.4) Accounted items and double use items; (5.5) Problem of radioactive wastes; (6.1) International co-operation activities of NRA; (6.2) Emergency planning; (6.3) International activities for quality enhancement of national supervision; (7) Conclusion [sk

Identifying time-delayed gene regulatory networks via an evolvable hierarchical recurrent neural network.

Science.gov (United States)

Kordmahalleh, Mina Moradi; Sefidmazgi, Mohammad Gorji; Harrison, Scott H; Homaifar, Abdollah

2017-01-01

The modeling of genetic interactions within a cell is crucial for a basic understanding of physiology and for applied areas such as drug design. Interactions in gene regulatory networks (GRNs) include effects of transcription factors, repressors, small metabolites, and microRNA species. In addition, the effects of regulatory interactions are not always simultaneous, but can occur after a finite time delay, or as a combined outcome of simultaneous and time delayed interactions. Powerful biotechnologies have been rapidly and successfully measuring levels of genetic expression to illuminate different states of biological systems. This has led to an ensuing challenge to improve the identification of specific regulatory mechanisms through regulatory network reconstructions. Solutions to this challenge will ultimately help to spur forward efforts based on the usage of regulatory network reconstructions in systems biology applications. We have developed a hierarchical recurrent neural network (HRNN) that identifies time-delayed gene interactions using time-course data. A customized genetic algorithm (GA) was used to optimize hierarchical connectivity of regulatory genes and a target gene. The proposed design provides a non-fully connected network with the flexibility of using recurrent connections inside the network. These features and the non-linearity of the HRNN facilitate the process of identifying temporal patterns of a GRN. Our HRNN method was implemented with the Python language. It was first evaluated on simulated data representing linear and nonlinear time-delayed gene-gene interaction models across a range of network sizes and variances of noise. We then further demonstrated the capability of our method in reconstructing GRNs of the Saccharomyces cerevisiae synthetic network for in vivo benchmarking of reverse-engineering and modeling approaches (IRMA). We compared the performance of our method to TD-ARACNE, HCC-CLINDE, TSNI and ebdbNet across different network

Feasibility for the medium efficiency filter as a postfilter in the air cleaning unit

International Nuclear Information System (INIS)

Lim, H. S.; Jung, D. Y.; Byun, S. C.; Kim, S. H.

2002-01-01

The Air Cleaning Unit (ACU) is provided in a nuclear facility to filter the radioactive materials in gaseous effluents released from the facility during normal operation and during a postulated accident. The Air Cleaning Unit (ACU) consists of pre-HEPA filters, charcoal adsorber, post HEPA filters, fans, etc. The charcoal filters keep on-site dose and off-site effluents ALARA, consistent with regulatory requirements. The function of HEPA filter downstream of charcoal(carbon) adsorber in ACU is to catch potential radioactive carbon dust and to be a backup in the event of failure of upstream HEPA. Previous Regulatory Guide use only post HEPA filter of charcoal adsorber downstream but the Regulatory Guide of current revisions allows use of 95% dust spot efficiency filters in lieu of HEPA at the downstream of the carbon adsorber. In this paper is described that the background information of filters, Current Regulatory Guide of revised by the United States Nuclear Regulatory Commission and the feasibility for the medium efficiency filter as a carbon adsorber post filter in the Air Cleaning Unit

Interprofessional intensive care unit team interactions and medical crises: a qualitative study.

Science.gov (United States)

Piquette, Dominique; Reeves, Scott; Leblanc, Vicki R

2009-05-01

Research has suggested that interprofessional collaboration could improve patient outcomes in the intensive care unit (ICU). Maintaining optimal interprofessional interactions in a setting where unpredictable medical crises occur periodically is however challenging. Our study aimed to investigate the perceptions of ICU health care professionals regarding how acute medical crises affect their team interactions. We conducted 25 semi-structured interviews of ICU nurses, staff physicians, and respiratory therapists. All interviews were audio-taped and transcribed, and the analysis was undertaken using an inductive thematic approach. Our data indicated that the nature of interprofessional interactions changed as teams passed through three key temporal periods around medical crises. During the "pre-crisis period", interactions were based on the mutual respect of each other's expertise. During the "crisis period", hierarchical interactions were expected and a certain lack of civility was tolerated. During the "post-crisis period", divergent perceptions emerged amongst health professionals. Post-crisis team dispersion left the nurses with questions and emotions not expressed by other team members. Nurses believed that systematic interprofessional feedback sessions held immediately after a crisis could address some of their needs. Further research is needed to establish the possible benefits of strategies addressing ICU health care professionals' specific needs for interprofessional feedback after a medical crisis.

RMOD: a tool for regulatory motif detection in signaling network.

Directory of Open Access Journals (Sweden)

Jinki Kim

Full Text Available Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.

Creating a safety culture in the regulatory authority: The Cuban experience

International Nuclear Information System (INIS)

Ferro Fernandez, R.; Guillen Campos, A.

2002-01-01

The Cuban regulatory authority has been working during several years for the fostering and development of a high Safety Culture level in nuclear activities in the country. As starting point to achieve this objective the assessment of the Safety Culture level in the regulatory authority performance was considered an important issue. For this purpose a preliminary diagnosis was carried out by means of a national survey that allowed identifying some areas of the regulatory activity that required improvements in order to achieve a higher Safety Culture and to immediately implement appropriate actions. Two of the most important actions undertaken were: the statement of the regulatory authority Safety Policy which governs and determines the performance of this organization and its staff and also the implementation of a new interaction practice at top level between the regulatory authority and the utilities of the nuclear sector through the Annual Regulatory Conference. The present paper summarizes these two introduced practices into the Cuban regulatory activity. (author)

Regulatory Approaches for Adding Capacity to Existing Hydropower Facilities

Energy Technology Data Exchange (ETDEWEB)

Levine, Aaron L. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Curtis, Taylor L. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kazerooni, Borna [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

2017-10-24

In 2015, hydroelectric generation accounted for more than 6 percent of total net electricity generation in the United States and 46 percent of electricity generation from all renewables. The United States has considerable hydroelectric potential beyond what is already being developed. Nearly 7 GW of this potential is found by adding capacity to existing hydropower facilities. To optimize the value of hydroelectric generation, the U.S. Department of Energy's Hydropower Vision Study highlights the importance of adding capacity to existing facilities. This report provides strategic approaches and considerations for Federal Energy Regulatory Commission licensed and exempt hydropower facilities seeking to increase generation capacity, which may include increases from efficiency upgrades. The regulatory approaches reviewed for this report include capacity and non-capacity amendments, adding capacity during relicensing, and adding capacity when converting a license to a 10-MW exemption.

European regulatory framework for person carrier robots

NARCIS (Netherlands)

Fosch Villaronga, E.; Roig, A.

The aim of this paper is to establish the grounds for a future regulatory framework for Person Carrier Robots, which includes legal and ethical aspects. Current industrial standards focus on physical human–robot interaction, i.e. on the prevention of harm. Current robot technology nonetheless

Regulatory issues of digital instrumentation and control system in Lungmen project

International Nuclear Information System (INIS)

Chuang, C.F.; Chou, H.P.

2004-01-01

The Lungmen Nuclear Power Station (LNPS) is currently under construction in Taiwan, which consists of 2 advanced boiling water reactor (ABWR) units. The instrumentation and control (IC) systems of the LNPS are based on the state-of-the-art modernized fully integrated digital design. These IC systems possess many advantages and distinguished features comparing to traditional analog IC systems, they enjoy set-point stability, self-diagnostic and automatic testing ability, fault tolerance and avoidance, low power requirements, data handling and storage capability, as well as enhanced human-machine interfaces. This paper presents regulatory overviews, regulatory requirements, current major regulatory issues, as well as the areas of regulatory concerns and the lessons learned on the digital IC systems in the Lungmen Project

Regulatory aspects of the enforcement policy applied to teletherapy equipment obsolescence (1995-2002)

International Nuclear Information System (INIS)

Truppa, Walter A.; Rey, Hugo L.; Rojas, Carlos A.

2004-01-01

The paper describes the way in which the Nuclear Regulatory Authority (ARN) has implemented an 'enforcement' policy for the services of radiotherapy that operated obsolete cobalt therapy units. Without doubt one of the greater advances has been the simulation and planning of the treatment, indispensable tools in a system of quality in radiotherapy where the equipment acquires a preponderant paper. In Argentina the distribution of equipment was inhomogeneous, and within it coexisted, as primary and unique units, great amount with a technology today already obsolete. The Nuclear Regulatory Authority (ARN) took a strong regulatory attitude directed to change or to retire many of the units, as its characteristics of design and antiquity did not fulfill the criteria of radiological security established in the norms (optimization of the dose, distances source to skin, yield in surface, adequate maintenance, etc.). On this matter a policy was applied to impose within suitable terms, the change of the obsolete equipment for this practice, particularly those distances source to skin minor than 80 cm. As result of the applied coercive measures at this moment, 28 equipment of cobalt therapy in advanced degree of obsolescence were retired by regulatory decision. Part of these equipment were replaced by their owners by more modern equipment whose operation adjusts to the requirements of the radiological security norm, whereas the majority was replaced by linear accelerators. At the moment there are 86 of cobalt therapy units and 52 accelerators operating in our country, against 104 and 32 respectively, that operated in 1995. (author)

Inferring regulatory networks from expression data using tree-based methods.

Directory of Open Access Journals (Sweden)

Vân Anh Huynh-Thu

2010-09-01

Full Text Available One of the pressing open problems of computational systems biology is the elucidation of the topology of genetic regulatory networks (GRNs using high throughput genomic data, in particular microarray gene expression data. The Dialogue for Reverse Engineering Assessments and Methods (DREAM challenge aims to evaluate the success of GRN inference algorithms on benchmarks of simulated data. In this article, we present GENIE3, a new algorithm for the inference of GRNs that was best performer in the DREAM4 In Silico Multifactorial challenge. GENIE3 decomposes the prediction of a regulatory network between p genes into p different regression problems. In each of the regression problems, the expression pattern of one of the genes (target gene is predicted from the expression patterns of all the other genes (input genes, using tree-based ensemble methods Random Forests or Extra-Trees. The importance of an input gene in the prediction of the target gene expression pattern is taken as an indication of a putative regulatory link. Putative regulatory links are then aggregated over all genes to provide a ranking of interactions from which the whole network is reconstructed. In addition to performing well on the DREAM4 In Silico Multifactorial challenge simulated data, we show that GENIE3 compares favorably with existing algorithms to decipher the genetic regulatory network of Escherichia coli. It doesn't make any assumption about the nature of gene regulation, can deal with combinatorial and non-linear interactions, produces directed GRNs, and is fast and scalable. In conclusion, we propose a new algorithm for GRN inference that performs well on both synthetic and real gene expression data. The algorithm, based on feature selection with tree-based ensemble methods, is simple and generic, making it adaptable to other types of genomic data and interactions.

Nuclear Regulatory Commission Issuances, August 1981

International Nuclear Information System (INIS)

1981-01-01

Contents include: Issuances of the Nuclear Regulatory Commission--Metropolitan Edison Company (Three Mile Island Nuclear Station, Unit No. 1), Metropolitan Edison Company, et al. (Three Mile Island Nuclear Station, Unit 1), Westinghouse Electric Corp. (Export of LEU to the Philippines); Issuances of Atomic Safety and Licensing Appeal Boards--Duke Power Company (Amendment to Materials License SNM-1773--Transportation of Spent Fuel from Oconee Nuclear Station for Storage at McGuire Nuclear Station); Issuances of the Atomic Safety Licensing Boards--Commonwealth Edison Company (Byron Station, Units 1 and 2), Dairyland Power Cooperative (La Crosse Boiling Water Reactor, Operating License and Show Cause), Florida Power and Light Company (St. Lucie Plant, Unit No. 2), Florida Power and Light Company (Turkey Point Nuclear Generating, Units 3 and 4), Metropolitan Edison Company (Three Mile Island Nuclear Station, Unit 1) Pacific Gas and Electric Company (Diablo Canyon Nuclear Power Plant, Units 1 and 2), The Regents of the University of California (UCLA Research Reactor), The Toledo Edison Company, et al. (Davis-Besse Nuclear Power Station, Units 2 and 3: Terminiation of Proceedings); Issuances of the Directors Denial--Florida Power and Light Company

Interactional and Categorial Practices in the Strange Case of the United Nathans Weapons Inspections

DEFF Research Database (Denmark)

McIlvenny, Paul

-conducts’. In this paper, the interactional practices of a prefigurative protest demonstration are examined. Video recordings were made of a creative, peaceful event called “United Nathans Weapons Inspections” in February 2003. The paper draws upon Mitchell Dean’s analytics of government in order to undertake an analytics...... of protest by uncovering how fields of visibility, forms of knowledge, technologies and apparatuses, and subjectivities and identities are negotiated and accomplished collaboratively in social interaction. The paper explores some of the tools and methods that are well suited to investigating the situated...... work by which subjectivation is morally accomplished in social interaction. The paper shows how CA and MCA can help trace the interactional, embodied and categorial practices that are endogenous to conducting the conduct of others and the self, and thus which constitute or contest the rationalities...

Interacting effects of maternal responsiveness, infant regulatory problems and dopamine D4 receptor gene in the development of dysregulation during childhood: A longitudinal analysis.

Science.gov (United States)

Poustka, Luise; Zohsel, Katrin; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Schmid, Brigitte; Trautmann-Villalba, Patricia; Hohmann, Sarah; Becker, Katja; Esser, Günter; Schmidt, Martin H; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred

2015-11-01

Recent longitudinal studies have indicated that affective and behavioral dysregulation in childhood is associated with an increased risk for various negative outcomes in later life. However, few studies to date have examined early mechanisms preceding dysregulation during early childhood. Aim of this study was to elucidate early mechanisms relating to dysregulation in later life using data from an epidemiological cohort study on the long-term outcome of early risk factors from birth to adulthood. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness was evaluated by trained raters. Infant regulatory problems were assessed on the basis of a parent interview and direct observation by trained raters. At age 8 and 11 years, 290 children (139 males) were rated on the Child Behavior Checklist (CBCL). Additionally, participants were genotyped for the dopamine D4 receptor (DRD4) exon 3 VNTR polymorphism. A significant three-way interaction between maternal responsiveness, DRD4 genotype and infant regulatory problems was detected predicting the CBCL-dysregulation profile (CBCL-DP). Carriers of the DRD4 7r allele with regulatory problems at age 3 months showed significantly more behavior problems associated with the CBCL-DP during childhood when exposed to less maternal responsiveness. In contrast, no effect of maternal responsiveness was observed in DRD4 7r carriers without infant regulatory problems and in non-carriers of the DRD4 7r allele. This prospective longitudinal study extends earlier findings regarding the association of the CBCL-DP with early parenting and later psychopathology, introducing both DRD4 genotype and infant regulatory problems as important moderators. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genomic analysis of the hierarchical structure of regulatory networks

Science.gov (United States)

Yu, Haiyuan; Gerstein, Mark

2006-01-01

A fundamental question in biology is how the cell uses transcription factors (TFs) to coordinate the expression of thousands of genes in response to various stimuli. The relationships between TFs and their target genes can be modeled in terms of directed regulatory networks. These relationships, in turn, can be readily compared with commonplace “chain-of-command” structures in social networks, which have characteristic hierarchical layouts. Here, we develop algorithms for identifying generalized hierarchies (allowing for various loop structures) and use these approaches to illuminate extensive pyramid-shaped hierarchical structures existing in the regulatory networks of representative prokaryotes (Escherichia coli) and eukaryotes (Saccharomyces cerevisiae), with most TFs at the bottom levels and only a few master TFs on top. These masters are situated near the center of the protein–protein interaction network, a different type of network from the regulatory one, and they receive most of the input for the whole regulatory hierarchy through protein interactions. Moreover, they have maximal influence over other genes, in terms of affecting expression-level changes. Surprisingly, however, TFs at the bottom of the regulatory hierarchy are more essential to the viability of the cell. Finally, one might think master TFs achieve their wide influence through directly regulating many targets, but TFs with most direct targets are in the middle of the hierarchy. We find, in fact, that these midlevel TFs are “control bottlenecks” in the hierarchy, and this great degree of control for “middle managers” has parallels in efficient social structures in various corporate and governmental settings. PMID:17003135

US Nuclear Regulatory Commission, 1984 annual report. Volume 1

International Nuclear Information System (INIS)

1985-01-01

This is the 10th annual report of the US Nuclear Regulatory Commission (NRC). This report covers the major activities, events, decisions and planning that took place during fiscal year 1984 (October 1983 through September 1984) within the NRC or involving the NRC. Information is presented concerning 1984 highlights and planning for 1985; reactor regulation; cleanup at Three Mile Island Unit 2; operational experience; nuclear materials; safeguards; waste management; inspection, enforcement, quality assurance, and emergency preparedness; cooperation with the States; international programs; nuclear regulatory research; proceedings and litigation; and management and communication

Emotion: The Self-regulatory Sense.

Science.gov (United States)

Peil, Katherine T

2014-03-01

While emotion is a central component of human health and well-being, traditional approaches to understanding its biological function have been wanting. A dynamic systems model, however, broadly redefines and recasts emotion as a primary sensory system-perhaps the first sensory system to have emerged, serving the ancient autopoietic function of "self-regulation." Drawing upon molecular biology and revelations from the field of epigenetics, the model suggests that human emotional perceptions provide an ongoing stream of "self-relevant" sensory information concerning optimally adaptive states between the organism and its immediate environment, along with coupled behavioral corrections that honor a universal self-regulatory logic, one still encoded within cellular signaling and immune functions. Exemplified by the fundamental molecular circuitry of sensorimotor control in the E coli bacterium, the model suggests that the hedonic (affective) categories emerge directly from positive and negative feedback processes, their good/bad binary appraisals relating to dual self-regulatory behavioral regimes-evolutionary purposes, through which organisms actively participate in natural selection, and through which humans can interpret optimal or deficit states of balanced being and becoming. The self-regulatory sensory paradigm transcends anthropomorphism, unites divergent theoretical perspectives and isolated bodies of literature, while challenging time-honored assumptions. While suppressive regulatory strategies abound, it suggests that emotions are better understood as regulating us, providing a service crucial to all semantic language, learning systems, evaluative decision-making, and fundamental to optimal physical, mental, and social health.

Emotion: The Self-regulatory Sense

Science.gov (United States)

2014-01-01

While emotion is a central component of human health and well-being, traditional approaches to understanding its biological function have been wanting. A dynamic systems model, however, broadly redefines and recasts emotion as a primary sensory system—perhaps the first sensory system to have emerged, serving the ancient autopoietic function of “self-regulation.” Drawing upon molecular biology and revelations from the field of epigenetics, the model suggests that human emotional perceptions provide an ongoing stream of “self-relevant” sensory information concerning optimally adaptive states between the organism and its immediate environment, along with coupled behavioral corrections that honor a universal self-regulatory logic, one still encoded within cellular signaling and immune functions. Exemplified by the fundamental molecular circuitry of sensorimotor control in the E coli bacterium, the model suggests that the hedonic (affective) categories emerge directly from positive and negative feedback processes, their good/bad binary appraisals relating to dual self-regulatory behavioral regimes—evolutionary purposes, through which organisms actively participate in natural selection, and through which humans can interpret optimal or deficit states of balanced being and becoming. The self-regulatory sensory paradigm transcends anthropomorphism, unites divergent theoretical perspectives and isolated bodies of literature, while challenging time-honored assumptions. While suppressive regulatory strategies abound, it suggests that emotions are better understood as regulating us, providing a service crucial to all semantic language, learning systems, evaluative decision-making, and fundamental to optimal physical, mental, and social health. PMID:24808986

Analytical Chemistry in the Regulatory Science of Medical Devices.

Science.gov (United States)

Wang, Yi; Guan, Allan; Wickramasekara, Samanthi; Phillips, K Scott

2018-06-12

In the United States, regulatory science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all Food and Drug Administration-regulated products. Good regulatory science facilitates consumer access to innovative medical devices that are safe and effective throughout the Total Product Life Cycle (TPLC). Because the need to measure things is fundamental to the regulatory science of medical devices, analytical chemistry plays an important role, contributing to medical device technology in two ways: It can be an integral part of an innovative medical device (e.g., diagnostic devices), and it can be used to support medical device development throughout the TPLC. In this review, we focus on analytical chemistry as a tool for the regulatory science of medical devices. We highlight recent progress in companion diagnostics, medical devices on chips for preclinical testing, mass spectrometry for postmarket monitoring, and detection/characterization of bacterial biofilm to prevent infections.

Facing regulatory challenges of on-line hemodiafiltration.

Science.gov (United States)

Kümmerle, Wolfgang

2011-01-01

On-line hemodiafiltration (on-line HDF) is the result of a vision that triggered multifarious changes in very different areas. Driven by the idea to offer better medical treatment for renal patients, technological innovations were developed and established that also constituted new challenges in the field of regulatory affairs. The existing regulations predominantly addressed the quality and safety of those products needed to perform dialysis treatment which were supplied by industrial manufacturers. However, the complexity of treatment system required for the provision of on-line fluids demanded a holistic approach encompassing all components involved. Hence, focus was placed not only on single products, but much more on their interfacing, and the clinical infrastructure, in particular, had to undergo substantial changes. The overall understanding of the interaction between such factors, quite different in their nature, was crucial to overcome the arising regulatory obstacles. This essay describes the evolution of the on-line HDF procedure from the regulatory point of view. A simplified diagram demonstrates the path taken from the former regulatory understanding to the realization of necessary changes. That achievement was only possible through 'management of preview' and consequent promotion of technical and medical innovations as well as regulatory re-evaluations. Copyright © 2011 S. Karger AG, Basel.

End of FY10 report - used fuel disposition technical bases and lessons learned : legal and regulatory framework for high-level waste disposition in the United States.

Energy Technology Data Exchange (ETDEWEB)

Weiner, Ruth F.; Blink, James A. (Lawrence Livermore National Laboratory, Livermore, CA); Rechard, Robert Paul; Perry, Frank (Los Alamos National Laboratory, Los Alamos, NM); Jenkins-Smith, Hank C. (University of Oklahoma, Norman, OK); Carter, Joe (Savannah River Nuclear Solutions, Aiken, SC); Nutt, Mark (Argonne National Laboratory, Argonne, IL); Cotton, Tom (Complex Systems Group, Washington DC)

2010-09-01

This report examines the current policy, legal, and regulatory framework pertaining to used nuclear fuel and high level waste management in the United States. The goal is to identify potential changes that if made could add flexibility and possibly improve the chances of successfully implementing technical aspects of a nuclear waste policy. Experience suggests that the regulatory framework should be established prior to initiating future repository development. Concerning specifics of the regulatory framework, reasonable expectation as the standard of proof was successfully implemented and could be retained in the future; yet, the current classification system for radioactive waste, including hazardous constituents, warrants reexamination. Whether or not consideration of multiple sites are considered simultaneously in the future, inclusion of mechanisms such as deliberate use of performance assessment to manage site characterization would be wise. Because of experience gained here and abroad, diversity of geologic media is not particularly necessary as a criterion in site selection guidelines for multiple sites. Stepwise development of the repository program that includes flexibility also warrants serious consideration. Furthermore, integration of the waste management system from storage, transportation, and disposition, should be examined and would be facilitated by integration of the legal and regulatory framework. Finally, in order to enhance acceptability of future repository development, the national policy should be cognizant of those policy and technical attributes that enhance initial acceptance, and those policy and technical attributes that maintain and broaden credibility.

The regulatory function in radioactive waste management

International Nuclear Information System (INIS)

Duncan, A.; Pescatore, C.

2008-01-01

Allan Duncan, expert to NEA and former Chief Inspector for Pollution (United Kingdom), elaborated on the regulatory function in the domain of radioactive waste management. The preparation of a document and a brochure on the subject has been one of the main tasks of the Regulators' Forum since its creation in 2001. He stressed that management of NORM waste was generally subject to different standards than similar radioactive waste from a nuclear source, for no obvious reason than that of public perception. He also pointed out the large number of 'regulatory bodies' involved in the regulation of radioactive waste management facilities and particularly geological disposal facilities, and their links to the Government. He gave the example of the United Kingdom. He stressed the fact that, since there will not be continuous control, licensing of geological disposal is an act of trust in the regulatory system. A. Duncan gave the position of two Commissions in England on deep geological disposal. The UK Sustainable Development Commission says, 'it is impossible to guarantee safety over long-term disposal of (nuclear) waste' which implies that nuclear fission power should be shut down; CoRWM, the Committee on Radioactive Waste Management, recommends instead geological disposal for existing wastes as a broadly acceptable solution. As a concluding remark A. Duncan focused the attention on the general question of what current society needs to do in order to meet its obligations to future generations with respect to disposal of long-lived wastes. (authors)

Causality analysis detects the regulatory role of maternal effect genes in the early Drosophila embryo

Directory of Open Access Journals (Sweden)

Zara Ghodsi

2017-03-01

Full Text Available In developmental studies, inferring regulatory interactions of segmentation genetic network play a vital role in unveiling the mechanism of pattern formation. As such, there exists an opportune demand for theoretical developments and new mathematical models which can result in a more accurate illustration of this genetic network. Accordingly, this paper seeks to extract the meaningful regulatory role of the maternal effect genes using a variety of causality detection techniques and to explore whether these methods can suggest a new analytical view to the gene regulatory networks. We evaluate the use of three different powerful and widely-used models representing time and frequency domain Granger causality and convergent cross mapping technique with the results being thoroughly evaluated for statistical significance. Our findings show that the regulatory role of maternal effect genes is detectable in different time classes and thereby the method is applicable to infer the possible regulatory interactions present among the other genes of this network.

Considering public confidence in developing regulatory programs

International Nuclear Information System (INIS)

Collins, S.J.

2001-01-01

In the area of public trust and in any investment, planning and strategy are important. While it is accepted in the United States that an essential part of our mission is to leverage our resources to improving Public Confidence this performance goal must be planned for, managed and measured. Similar to our premier performance goal of Maintaining Safety, a strategy must be developed and integrated with our external stake holders but with internal regulatory staff as well. In order to do that, business is to be conducted in an open environment, the basis for regulatory decisions has to be available through public documents and public meetings, communication must be done in clear and consistent terms. (N.C.)

76 FR 40754 - Duke Energy Carolinas, LLC Catawba Nuclear Station, Units 1 and 2; McGuire Nuclear Station, Units...

Science.gov (United States)

2011-07-11

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0100; Docket Nos. 50-413 and 50-414; Docket Nos. 50-369 and 50-370; Docket Nos. 50-269, 50-270, And 50-287] Duke Energy Carolinas, LLC Catawba Nuclear Station, Units 1 and 2; McGuire Nuclear Station, Units 1 and 2; Oconee Nuclear Station, Units 1, 2, and 3; Notice...

Splicing Regulatory Elements and mRNA-abundance of dlg1 and capt, Genetically Interacting with dFMRP in Drosophila Brain

Directory of Open Access Journals (Sweden)

Maria Petrova

2014-09-01

Full Text Available To further understand the molecular and cellular mechanisms underlying the disease, we used the Drososphila FraX model and investigated a not well studied role of Drosophila Fragile X Mental Retardation Protein (dFMRP in alternative splicing of neuronal mRNAs to which it binds via a G-quartet sequence. By means of qRT-PCR we established the relative abundance of some isoforms of the gene dlg1, resulting from alternative exon skipping nearby a G-quartet and an exonic ESE-sequence, both acting as exonic splicing enhancers. We also investigated the relative mRNA-abundance of all capt-isoforms and the pre-mRNAs of both genes. We proposed a possible involvement of dFMRP in alternative splicing of genes, interacting with dfmr1. In the absence of dFMRP in larval and pupal brains, we found a change in the mRNA-level of one of the studied isoforms of dlg1 and of its pre-mRNA.We also established previously reported splicing regulatory elements and predicted computationally novel hexamere sequences in the exonic/intronic ends of both genes with p upative regulatory roles in alternative splicing.

Development of regulatory guidance for risk-informing digital system reviews

International Nuclear Information System (INIS)

Arndt, S. A.

2006-01-01

In 1995, the U.S. Nuclear Regulatory Commission (NRC) issued the Probabilistic Risk Assessment (PRA) Policy Statement, which encourages the increased use of PRA and associated analyses in all regulatory matters to the extent supported by the state-of-the-art in PRA and the data. This policy applies, in part, to the review of digital systems, which offer the potential to improve plant safety and reliability through such features as increased hardware reliability and stability and improved failure detection capability. However, there are presently no universally accepted methods for modeling digital systems in current-generation PRAs. Further, there are ongoing debates among the PRA technical community regarding the level of detail that any digital system reliability model must have to adequately model the complex system interactions that can contribute to digital system failure modes. Moreover, for PRA modeling of digital reactor protection and control systems, direct interactions between system components and indirect interactions through controlled/supervised plant processes may necessitate the use of dynamic PRA methodologies. This situation has led the NRC to consider developing performance based rather than prescriptive regulatory guidance in this area. This paper will discuss the development of this guidance and some preliminary concepts. (authors)

The regulatory approach to the assessment of containment structures in the United Kingdom, with reference to the proposed Sizewell 'B' project

International Nuclear Information System (INIS)

Todd, I.W.

1988-01-01

The regulation of nuclear installations in the United Kingdom is carried out by means of a licensing system which is administered on behalf of the Health and Safety Executive (HSE) by HM Nuclear Installations Inspectorate. A major part of this process lies in the assessment of an installation's designs and safety case, which must be submitted to the Inspectorate before a licence may be granted. This paper describes the work carried out in assessing the design proposed for the containment structure of the United Kingdom's first PWR, Sizewell 'B'. The roles of the Inspectorate's Safety Assessment Principles, and the engineering judgement of the individual assessor, are discussed. The reasons behind the Inspectorate's decision to commission independent design studies of the structure are explained, and the results of these studies are presented in outline. Views are also expressed upon the validation of analytical results, quality assurance, and further work planned by the Inspectorate in this field. The paper concludes that it is the flexibility and discretion allowed by the above approach which represents the principal strength of the UK's system of regulatory assessment. (author)

Self-regulatory failure and intimate partner violence perpetration.

Science.gov (United States)

Finkel, Eli J; DeWall, C Nathan; Slotter, Erica B; Oaten, Megan; Foshee, Vangie A

2009-09-01

Five studies tested the hypothesis that self-regulatory failure is an important predictor of intimate partner violence (IPV) perpetration. Study 1 participants were far more likely to experience a violent impulse during conflictual interaction with their romantic partner than they were to enact a violent behavior, suggesting that self-regulatory processes help individuals refrain from perpetrating IPV when they experience a violent impulse. Study 2 participants high in dispositional self-control were less likely to perpetrate IPV, in both cross-sectional and residualized-lagged analyses, than were participants low in dispositional self-control. Study 3 participants verbalized more IPV-related cognitions if they responded immediately to partner provocations than if they responded after a 10-s delay. Study 4 participants whose self-regulatory resources were experimentally depleted were more violent in response to partner provocation (but not when unprovoked) than were nondepleted participants. Finally, Study 5 participants whose self-regulatory resources were experimentally bolstered via a 2-week training regimen exhibited less violent inclinations than did participants whose self-regulatory resources had not been bolstered. These findings hint at the power of incorporating self-regulation dynamics into predictive models of IPV perpetration. (c) 2009 APA, all rights reserved).

Systems interaction and single failure criterion

International Nuclear Information System (INIS)

1981-01-01

This report documents the results of a six-month study to evaluate the ongoing research programs of the U.S. Nuclear Regulatory Commission (NRC) and U.S. commercial nuclear station owners which address the safety significance of systems interaction and the regulatory adequacy of the single failure criterion. The evaluation of system interactions provided is the initial phase of a more detailed study leading to the development and application of methodology for quantifying the relative safety of operating nuclear plants. (Auth.)

Applications of pharmacogenomics in regulatory science: a product life cycle review.

Science.gov (United States)

Tan-Koi, W C; Leow, P C; Teo, Y Y

2018-05-22

With rapid developments of pharmacogenomics (PGx) and regulatory science, it is important to understand the current PGx integration in product life cycle, impact on clinical practice thus far and opportunities ahead. We conducted a cross-sectional review on PGx-related regulatory documents and implementation guidelines in the United States and Europe. Our review found that although PGx-related guidance in both markets span across the entire product life cycle, the scope of implementation guidelines varies across two continents. Approximately one-third of Food and Drug Administration (FDA)-approved drugs with PGx information in drug labels and half of the European labels posted on PharmGKB website contain recommendations on genetic testing. The drugs affected 19 and 15 World Health Organization Anatomical Therapeutic Chemical drug classes (fourth level) in the United States and Europe, respectively, with protein kinase inhibitors (13 drugs in the United States and 16 drugs in Europe) being most prevalent. Topics of emerging interest were novel technologies, adaptive design in clinical trial and sample collection.

A High-Level Petri Net Framework for Genetic Regulatory Networks

Directory of Open Access Journals (Sweden)

Banks Richard

2007-12-01

Full Text Available To understand the function of genetic regulatory networks in the development of cellular systems, we must not only realise the individual network entities, but also the manner by which they interact. Multi-valued networks are a promising qualitative approach for modelling such genetic regulatory networks, however, at present they have limited formal analysis techniques and tools. We present a flexible formal framework for modelling and analysing multi-valued genetic regulatory networks using high-level Petri nets and logic minimization techniques. We demonstrate our approach with a detailed case study in which part of the genetic regulatory network responsible for the carbon starvation stress response in Escherichia coli is modelled and analysed. We then compare and contrast this multivalued model to a corresponding Boolean model and consider their formal relationship.

Impact of regulatory science on global public health

Directory of Open Access Journals (Sweden)

Meghal Patel

2012-07-01

Full Text Available Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies.

Impact of regulatory science on global public health.

Science.gov (United States)

Patel, Meghal; Miller, Margaret Ann

2012-07-01

Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies. Copyright © 2012. Published by Elsevier B.V.

Interaction between adipose tissue-derived mesenchymal stem cells and regulatory T-cells

NARCIS (Netherlands)

A.U. Engela (Anja); C.C. Baan (Carla); A. Peeters (Anna); W. Weimar (Willem); M.J. Hoogduijn (Martin)

2013-01-01

textabstractMesenchymal stem cells (MSCs) exhibit immunosuppressive capabilities, which have evoked interest in their application as cell therapy in transplant patients. So far it has been unclear whether allogeneic MSCs and host regulatory T-cells (Tregs) functionally influence each other. We

The regulatory framework for safe decommissioning of nuclear power plants in Korea

International Nuclear Information System (INIS)

Sangmyeon Ahn; Jungjoon Lee; Chanwoo Jeong; Kyungwoo Choi

2013-01-01

We are having 23 units of nuclear power plants in operation and 5 units of nuclear power plants under construction in Korea as of September 2012. However, we don't have any experience on shutdown permanently and decommissioning of nuclear power plants. There are only two research reactors being decommissioned since 1997. It is realized that improvement of the regulatory framework for decommissioning of nuclear facilities has been emphasized constantly from the point of view of IAEA's safety standards. It is also known that IAEA will prepare the safety requirement on decommissioning of facilities; its title is the Safe Decommissioning of Facilities, General Safety Requirement Part 6. According to the result of IAEA's Integrated Regulatory Review Service (IRRS) mission to Korea in 2011, it was recommended that the regulatory framework should require decommissioning plans for nuclear installations to be constructed and operated and these plans should be updated periodically. In addition, after the Fukushima nuclear disaster in Japan in March of 2011, preparedness for early decommissioning caused by an unexpected severe accident became important issues and concerns. In this respect, it is acknowledged that the regulatory framework for decommissioning of nuclear facilities in Korea need to be improved. First of all, we focus on identifying the current status and relevant issues of regulatory framework for decommissioning of nuclear power plants compared to the IAEA's safety standards in order to achieve our goal. And then the plan is established for improvement of regulatory framework for decommissioning of nuclear power plants in Korea. It is expected that if the things will go forward as planned, the revised regulatory framework for decommissioning could enhance the safety regime on the decommissioning of nuclear power plants in Korea in light of international standards. (authors)

Detailed regulatory mechanism of the interaction between ZO-1 PDZ2 and connexin43 revealed by MD simulations.

Directory of Open Access Journals (Sweden)

Fei Xiao

Full Text Available The gap junction protein connexin43 (Cx43 binds to the second PDZ domain of Zonula occludens-1 (ZO-1 through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9 and Ser (-10 of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9 significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation.

Status of development and licensing support for advanced liquid metal reactors in the United States

Energy Technology Data Exchange (ETDEWEB)

Pedersen, D R [Argonne National Laboratory, Argonne, IL (United States); Gyorey, G [General Electric, San Jose, CA (United States)

1991-07-01

The cornerstones of the United States Advanced Liquid Metal Cooled Reactor (ALMR) program sponsored by the Department of Energy are: the ALMR plant design program at General Electric based on the PRISM (Power Reactor Innovative Small Module) concept, and the Integral Fast Reactor program (IFR) at Argonne National Laboratory (ANL). The goal of the U.S. program is to produce a standard, commercial ALMR, including the associated fuel cycle. The paper addresses the status of the IFR program, the ALMR program and the interaction of the ALMR program with the regulatory environment. (author)

Status of development and licensing support for advanced liquid metal reactors in the United States

International Nuclear Information System (INIS)

Pedersen, D.R.; Gyorey, G.

1991-01-01

The cornerstones of the United States Advanced Liquid Metal Cooled Reactor (ALMR) program sponsored by the Department of Energy are: the ALMR plant design program at General Electric based on the PRISM (Power Reactor Innovative Small Module) concept, and the Integral Fast Reactor program (IFR) at Argonne National Laboratory (ANL). The goal of the US program is to produce a standard, commercial ALMR, including the associated fuel cycle. The paper addresses the status of the IFR program, the ALMR program and the interaction of the ALMR program with the regulatory environment

Status of development and licensing support for advanced liquid metal reactors in the United States

International Nuclear Information System (INIS)

Pedersen, D.R.; Gyorey, G.

1991-01-01

The cornerstones of the United States Advanced Liquid Metal Cooled Reactor (ALMR) program sponsored by the Department of Energy are: the ALMR plant design program at General Electric based on the PRISM (Power Reactor Innovative Small Module) concept, and the Integral Fast Reactor program (IFR) at Argonne National Laboratory (ANL). The goal of the U.S. program is to produce a standard, commercial ALMR, including the associated fuel cycle. The paper addresses the status of the IFR program, the ALMR program and the interaction of the ALMR program with the regulatory environment. (author)

Nuclear Regulatory Commission Issuances, September 1981

International Nuclear Information System (INIS)

1981-01-01

Contents include: Issuances of the Nuclear Regulatory Commission--Commonwealth Edison Company (Dresden Nuclear Power Station, Unit 1), Consolidated Edison Company of New York (Indian Point, Unit 2), Metropolitan Edison Company, et al. (Three Mile Island Nuclear Station, Unit 1), Pacific Gas and Electric Company (Diablo Canyon Nuclear Power Plant, Units 1 and 2), Pacific Gas and Electric Company (Diablo Canyon Nuclear Power Plant, Units 1 and 2), Power Authority of the State of New York (Indian Point, Unit 3), Texas Utilities Generating Company, et al. (Comanche Peak Steam Electric Station, Units 1 and 2); Issuances of Atomic Safety and Licensing Appeal Boards--Pacific Gas and Electric Company (Diablo Canyon Nuclear Power Plant, Units 1 and 2), Philadelphia Electric Company, et al. (Peach Bottom Atomic Power Statin, Units 2 and 3), Metropolitan Edison Company, et al. (Three Mile Island Nuclear Statin, Unit No. 2), Public Service Electric and Gas Company (Hope Creek Generating Station, Units 1 and 2), The Toledo Edison Company, et al. (Davis-Besse Nuclear Power Station, Units 2 and 3); Issuances of the Atomic Safety Licensing Boards--Cleveland Electric Illuminating Company, et al. (Perry Nuclear Power Plant, Units 1 and 2), Commonwealth Edison Company (Dresden Station, Units 2 and 3), Houston Lighting and Power Company (Allens Creek Nuclear Generating Station, Unit 1), Southern California Edison Company, et al. (San Onofre Nuclear Generating Station, Units 2 and 3), Texas Utilities Generating Company, et al. (Comanche Peak Steam Electric Station, Units 1 and 2), Texas Utilities Generating Company, et al

National legislative and regulatory activities

International Nuclear Information System (INIS)

2015-01-01

This section treats of the following National legislative and regulatory activities: 1 - Canada: Liability and compensation; 2 - France: Liability and compensation; Nuclear safety and radiological protection; 3 - Greece: Organisation and structure; 4 - Hungary: General legislation; 5 - India: Liability and compensation; 6 - Japan: Liability and compensation; 7 - Korea: Liability and compensation; 8 - Lithuania: General legislation; Transport of radioactive material; 9 - Slovak Republic: International co-operation; Liability and compensation; 10 - Slovenia: General legislation; 11 - Switzerland: Liability and compensation; 12 - United States: Radioactive waste management

Object-Based Attention on Social Units: Visual Selection of Hands Performing a Social Interaction.

Science.gov (United States)

Yin, Jun; Xu, Haokui; Duan, Jipeng; Shen, Mowei

2018-05-01

Traditionally, objects of attention are characterized either as full-fledged entities or either as elements grouped by Gestalt principles. Because humans appear to use social groups as units to explain social activities, we proposed that a socially defined group, according to social interaction information, would also be a possible object of attentional selection. This hypothesis was examined using displays with and without handshaking interactions. Results demonstrated that object-based attention, which was measured by an object-specific attentional advantage (i.e., shorter response times to targets on a single object), was extended to two hands performing a handshake but not to hands that did not perform meaningful social interactions, even when they did perform handshake-like actions. This finding cannot be attributed to the familiarity of the frequent co-occurrence of two handshaking hands. Hence, object-based attention can select a grouped object whose parts are connected within a meaningful social interaction. This finding implies that object-based attention is constrained by top-down information.

Safeguards inventory and process monitoring regulatory comparison

Energy Technology Data Exchange (ETDEWEB)

Cavaluzzi, Jack M. [Texas A & M Univ., College Station, TX (United States); Gibbs, Philip W. [Brookhaven National Lab. (BNL), Upton, NY (United States)

2013-06-27

Detecting the theft or diversion of the relatively small amount of fissile material needed to make a nuclear weapon given the normal operating capacity of many of today’s running nuclear production facilities is a difficult task. As throughput increases, the ability of the Material Control and Accountability (MC&A) Program to detect the material loss decreases because the statistical measurement uncertainty also increases. The challenge faced is the ability of current accounting, measurement, and material control programs to detect small yet significant losses under some regulatory approaches can decrease to the point where it is extremely low if not practically non-existent at normal operating capacities. Adding concern to this topic is that there are variations among regulatory bodies as far as what is considered a Significant Quantity (SQ). Some research suggests that thresholds should be lower than those found in any current regulation which if adopted would make meeting detection goals even more difficult. This paper reviews and compares the current regulatory requirements for the MA elements related to physical inventory, uncertainty of the Inventory Difference (ID), and Process Monitoring (PM) in the United States Department of Energy (DOE) and Nuclear Regulatory Commission (NRC), Rosatom of the Russian Federation and the Chinese Atomic Energy Agency (CAEA) of China. The comparison looks at how the regulatory requirements for the implementation of various MA elements perform across a range of operating capacities in example facilities.

Assessment of regulatory effectiveness. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-09-01

This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

Regulatory networks and connected components of the neutral space. A look at functional islands

Science.gov (United States)

Boldhaus, G.; Klemm, K.

2010-09-01

The functioning of a living cell is largely determined by the structure of its regulatory network, comprising non-linear interactions between regulatory genes. An important factor for the stability and evolvability of such regulatory systems is neutrality - typically a large number of alternative network structures give rise to the necessary dynamics. Here we study the discretized regulatory dynamics of the yeast cell cycle [Li et al., PNAS, 2004] and the set of networks capable of reproducing it, which we call functional. Among these, the empirical yeast wildtype network is close to optimal with respect to sparse wiring. Under point mutations, which establish or delete single interactions, the neutral space of functional networks is fragmented into ≈ 4.7 × 108 components. One of the smaller ones contains the wildtype network. On average, functional networks reachable from the wildtype by mutations are sparser, have higher noise resilience and fewer fixed point attractors as compared with networks outside of this wildtype component.

A guide to approaching regulatory considerations for lentiviral-mediated gene therapies.

Science.gov (United States)

White, Michael; Whittaker, Roger; Stoll, Elizabeth Ann

2017-06-12

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well-characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is non-pathogenic and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations, and how they are administered in the United Kingdom, although many of the principles will be similar for other regions including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarises the extant regulatory guidance for gene therapies, categorised as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy.

RegTransBase - A Database Of Regulatory Sequences and Interactionsin a Wide Range of Prokaryotic Genomes

Energy Technology Data Exchange (ETDEWEB)

Kazakov, Alexei E.; Cipriano, Michael J.; Novichkov, Pavel S.; Minovitsky, Simon; Vinogradov, Dmitry V.; Arkin, Adam; Mironov, AndreyA.; Gelfand, Mikhail S.; Dubchak, Inna

2006-07-01

RegTransBase, a manually curated database of regulatoryinteractions in prokaryotes, captures the knowledge in publishedscientific literature using a controlled vocabulary. Although a number ofdatabases describing interactions between regulatory proteins and theirbinding sites are currently being maintained, they focus mostly on themodel organisms Escherichia coli and Bacillus subtilis, or are entirelycomputationally derived. RegTransBase describes a large number ofregulatory interactions reported in many organisms and contains varioustypes of experimental data, in particular: the activation or repressionof transcription by an identified direct regulator; determining thetranscriptional regulatory function of a protein (or RNA) directlybinding to DNA (RNA); mapping or prediction of binding site for aregulatory protein; characterization of regulatory mutations. Currently,the RegTransBase content is derived from about 3000 relevant articlesdescribing over 7000 experiments in relation to 128 microbes. It containsdata on the regulation of about 7500 genes and evidence for 6500interactions with 650 regulators. RegTransBase also contains manuallycreated position weight matrices (PWM) that can be used to identifycandidate regulatory sites in over 60 species. RegTransBase is availableat http://regtransbase.lbl.gov.

Interaction of the regulatory subunit of the cAMP-dependent protein kinase with PATZ1 (ZNF278)

International Nuclear Information System (INIS)

Yang, Weng-Lang; Ravatn, Roald; Kudoh, Kazuya; Alabanza, Leah; Chin, Khew-Voon

2010-01-01

The effects of cAMP in cell are predominantly mediated by the cAMP-dependent protein kinase (PKA), which is composed of two genetically distinct subunits, catalytic (C) and regulatory (R), forming a tetrameric holoenzyme R 2 C 2 . The only known function for the R subunit is that of inhibiting the activity of the C subunit kinase. It has been shown that overexpression of RIα, but not the C subunit kinase, is associated with neoplastic transformation. In addition, it has also been demonstrated that mutation in the RIα, but not the C subunit is associated with increased resistance to the DNA-damaging anticancer drug cisplatin, thus suggesting that the RIα subunit of PKA may have functions independent of the kinase. We show here that the RIα subunit interacts with a BTB/POZ domain zinc-finger transcription factor, PATZ1 (ZNF278), and co-expression with RIα results in its sequestration in the cytoplasm. The cytoplasmic/nuclear translocation is inducible by cAMP. C-terminus deletion abolishes PATZ1 interaction with RIα and results in its localization in the nucleus. PATZ1 transactivates the cMyc promoter and the presence of cAMP and co-expression with RIα modulates its transactivation. Moreover, PATZ1 is aberrantly expressed in cancer. Taken together, our results showed a potentially novel mechanism of cAMP signaling mediated through the interaction of RIα with PATZ1 that is independent of the kinase activity of PKA, and the aberrant expression of PATZ1 in cancer point to its role in cell growth regulation.

Quality assurance evolution at Laguna Verde Nuclear Power Plant Unit 1 and 2, regulatory aspects

International Nuclear Information System (INIS)

Leon Martinez, Cenobia

1996-01-01

Quality Assurance (QA) in Mexico started with the construction of the Laguna Verde Nuclear Power Plant. The Nuclear Regulatory Body, based in the adopted regulation, required the use of Quality Assurance in the design, construction and operation of the Plant. This paper describes the evolution of QA from its beginnings, through its developing phase up to this time, and shows the role of the Regulatory Body, which has participated actively in the implantation of QA in a properly manner, enforcing the utility in avoiding deviations and non-compliancies with the established regulation. (author)

A regulatory view of the seismic re-evaluation of existing nuclear power plants in the United Kingdom

International Nuclear Information System (INIS)

Inkester, J.E.; Bradford, P.M.

1995-01-01

The paper describes the background to the seismic re-evaluation of existing nuclear power plants in the United Kingdom. Nuclear installations in this country were not designed specifically to resist earthquakes until the nineteen-seventies, although older plants were robustly constructed. The seismic capability of these older installations is now being evaluated as part of the periodic safety reviews which nuclear licensees are required to carry out. The regulatory requirements which set the framework for these studies are explained and the approaches being adopted by the licensees for their assessment of the seismic capability of existing plants are outlined. The process of hazard appraisal is reported together with a general overview of UK seismicity. The paper then discusses the methodologies used to evaluate the response of plant to the hazard. Various other types of nuclear installation besides power plants are subject to licensing in the UK and the application of seismic evaluation to some of these is briefly described. Finally the paper provides some comments on future initiatives and possible areas of development. (author)

Instream sand and gravel mining: Environmental issues and regulatory process in the United States

Science.gov (United States)

Meador, M.R.; Layher, A.O.

1998-01-01

Sand and gravel are widely used throughout the U.S. construction industry, but their extraction can significantly affect the physical, chemical, and biological characteristics of mined streams. Fisheries biologists often find themselves involved in the complex environmental and regulatory issues related to instream sand and gravel mining. This paper provides an overview of information presented in a symposium held at the 1997 midyear meeting of the Southern Division of the American Fisheries Society in San Antonio, Texas, to discuss environmental issues and regulatory procedures related to instream mining. Conclusions from the symposium suggest that complex physicochemical and biotic responses to disturbance such as channel incision and alteration of riparian vegetation ultimately determine the effects of instream mining. An understanding of geomorphic processes can provide insight into the effects of mining operations on stream function, and multidisciplinary empirical studies are needed to determine the relative effects of mining versus other natural and human-induced stream alterations. Mining regulations often result in a confusing regulatory process complicated, for example, by the role of the U.S. Army Corps of Engineers, which has undergone numerous changes and remains unclear. Dialogue among scientists, miners, and regulators can provide an important first step toward developing a plan that integrates biology and politics to protect aquatic resources.

Selected review of regulatory standards and licensing issues for nuclear power plants

International Nuclear Information System (INIS)

Stevenson, J.D.; Thomas, F.A.

1982-11-01

This report presents a compilation and description of current foreign regulatory standards and licensing issues in the areas of interest associated with Siting, Structural Engineering, Metallurgy and Materials, and Mechanical Engineering. In addition, summary comparisons of the requirements of both the US and foreign nuclear power plant regulatory standards are provided. The selected foreign countries surveyed include Canada, France, Japan, Sweden, United Kingdom of Great Britain and Northern Ireland, and the Federal Republic of Germany

A regulatory perspective on design and performance requirements for engineered systems in high-level waste

International Nuclear Information System (INIS)

Bernero, R.M.

1992-01-01

For engineered systems, this paper gives an overview of some of the current activities at the U.S. Nuclear Regulatory Commission (NRC), with the intent of elucidating how the regulatory process works in the management of high-level waste (HLW). Throughout the waste management cycle, starting with packaging and transportation, and continuing to final closure of a repository, these activities are directed at taking advantage of the prelicensing consultation period, a period in which the NRC, DOE and others can interact in ways that will reduce regulatory, technical and institutional uncertainties, and open the path to development and construction of a deep geologic repository for permanent disposal of HLW. Needed interactions in the HLW program are highlighted. Examples of HLW regulatory activities are given in discussions of a multipurpose-cask concept and of current NRC work on the meaning of the term substantially complete containment

Proceedings of the CSNI specialists meeting on fuel-coolant interactions

Energy Technology Data Exchange (ETDEWEB)

None

1994-03-01

A specialists meeting on fuel-coolant interactions was held in Santa Barbara, CA from January 5-7, 1993. The meeting was sponsored by the United States Nuclear Regulatory Commission in collaboration with the Committee on the Safety of Nuclear Installation (CSNI) of the OECD Nuclear Energy Agency (NEA) and the University of California at Santa Barbara. The objectives of the meeting are to cross-fertilize on-going work, provide opportunities for mutual check points, seek to focus the technical issues on matters of practical significance and re-evaluate both the objectives as well as path of future research. Individual papers have been cataloged separately.

Proceedings of the CSNI specialists meeting on fuel-coolant interactions

International Nuclear Information System (INIS)

1994-03-01

A specialists meeting on fuel-coolant interactions was held in Santa Barbara, CA from January 5--7, 1993. The meeting was sponsored by the United States Nuclear Regulatory Commission in collaboration with the Committee on the Safety of Nuclear Installation (CSNI) of the OECD Nuclear Energy Agency (NEA) and the University of California at Santa Barbara. The objectives of the meeting are to cross-fertilize on-going work, provide opportunities for mutual check points, seek to focus the technical issues on matters of practical significance and re-evaluate both the objectives as well as path of future research. Individual papers have been cataloged separately

SELF-REGULATORY ABILITIES IN PROFESSIONAL ACTIVITY

Directory of Open Access Journals (Sweden)

G V Ozhiganova

2016-12-01

Full Text Available The self-regulation is considered by the author as a general ability of the person. The levels of self-regulation relating to any professional activity, and corresponding to these levels self-regulatory capacities are distinguished: 1 psychophysiological - the ability for self-regulation of emotional and psycho- physiological states; 2 socio-psychological - the ability for self-regulation in the process of social interaction; 3 psychological (the ability to regulate activities; the capacity for personal self-control;spiritual - the highest capacity for self-regulation due to the higher values and meanings of existence. Self-regulation at the highest spiritual level is considered in this research in connection with the actualization of higher self-regulatory capacities, leading to self-realization of the person including professional activity. Processes, levels, components of self-regulation, associated with different conditions of professional activities (for example, in extreme situations, as well as with different types of professions (teachers, sales managers, etc. are described. A particular attention is given to self- regulation in the teaching activities: levels, techniques of teachers’ self-regulatory skills are presented; the importance of teachers’ personal self-regulation is emphasized, because it determines self-development, self-improvement and self-fulfillment in their chosen profession, and is associated with the manifestation of higher self-regulatory capacities. It is noted that in the process of professional activities different levels and types of self-regulation are demanded. The self-regulation in professional activities is carried out due to various self-regulatory capabilities - from simple to complex, including the highest.

Regulatory Considerations for Gene Therapy Products in the US, EU, and Japan.

Science.gov (United States)

Halioua-Haubold, Celine-Lea; Peyer, James G; Smith, James A; Arshad, Zeeshaan; Scholz, Matthew; Brindley, David A; MacLaren, Robert E

2017-12-01

Developers of gene therapy products (GTPs) must adhere to additional regulation beyond that of traditional small-molecule therapeutics, due to the unique mechanism-of-action of GTPs and the subsequent novel risks arisen. We have provided herein a summary of the regulatory structure under which GTPs fall in the United States, the European Union, and Japan, and a comprehensive overview of the regulatory guidance applicable to the developer of GTP. Understanding the regulatory requirements for seeking GTP market approval in these major jurisdictions is crucial for an effective and expedient path to market. The novel challenges facing GTP developers is highlighted by a case study of alipogene tiparvovec (Glybera).

Nuclear Regulatory Commission Issuances, May 81

International Nuclear Information System (INIS)

1981-05-01

Contents: Issuances of the Nuclear Regulatory Commission--Consolidated Edison Company of New York, Inc. (Indian Point, Unit No. 2), Power Authority of the State of New York (Indian Point, No. 3 Nuclear Power Plant), Pacific Gas and Electric Company (Diablo Canyon Nuclear Power Plant, Units 1 and 2), Statement of Policy on Conduct of Licensing Proceedings, Uranium Mill Licensing Requirements; Issuances of Atomic Safety and Licensing Appeal Boards--Houston Lighting and Power Company, et al. (South Texas Project, Units 1 and 2), Metropolitan Edison Company, et al. (Three Mile Island Nuclear Station, Unit No. 2), Pennsylvania Power and Light Company and Allegheny Electric Cooperative, Inc. (Susquehanna Steam Electric Station, Units 1 and 2), Philadelphia Electric Company et al. (Peach Bottom Atomic Power Station, Units 2 and 3), Public Service Electric and Gas Company (Hope Creek Generating Station, Units 1 and 2); Issuances of the Atomic Safety and Licensing Boards--Duke Power Company (William B. McGuire Nuclear Station, Units 1 and 2), Florida Light and Power Company (Turkey Point Nuclear Generating, Units 3 and 4), Illinois Power Company, et al. (Clinton Power Station, Units 1 and 2), Sacramento Municipal Utility District (Rancho Seco Nuclear Generating Station); Issuances of the Directors Denial--Commonwealth Edison Company (Byron Station, Units 1 and 2), Consolidated Edison Company of New York, Inc. (Indian Point Unit No. 2), Gulf States Utilities Company (River Bend Station Units 1 and 2), Petition to Suspend All Operating Licenses for Pressurized Water Reactors (River Bend Station Units 1 and 2), Portland General Electric Company (Trojan Nuclear

Regulatory focus moderates the social performance of individuals who conceal a stigmatized identity

NARCIS (Netherlands)

Newheiser, Anna-Kaisa; Barreto, Manuela; Ellemers, Naomi; Derks, Belle; Scheepers, Daan

2015-01-01

People often choose to hide a stigmatized identity to avoid bias. However, hiding stigma can disrupt social interactions. We considered whether regulatory focus qualifies the social effects of hiding stigma by examining interactions in which stigmatized participants concealed a devalued identity

Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses.

Directory of Open Access Journals (Sweden)

Jumpei Ito

2017-07-01

Full Text Available Human endogenous retroviruses (HERVs and other long terminal repeat (LTR-type retrotransposons (HERV/LTRs have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs. Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified "HERV/LTR-shared regulatory element (HSRE," defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG, embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2, hematopoietic TFs (e.g., SPI1 (PU1, GATA1/2, and TAL1, and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/. This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into

The Prevalence of Potential Drug Interactions Among Critically Ill Elderly Patients in the Intensive Care Unit (ICU

Directory of Open Access Journals (Sweden)

Hossein Rafiei

2012-01-01

Full Text Available Objectives: The aim of the research was to determine prevalence of potential drug interactions among elderly patients in the Shahid Bahonar ICU in Kerman. Methods & Materials: In this cross sectional study, data about all elderly patients who were admitted in the intensive care unit from 1/4/2009 to 1/4/2010 were retrieved from medical records and evaluated with regard to the number and type of drug interactions, the number of drugs administered, age, sex, length of stay in the ICU, and the number of doctors prescribing medications of medications administered. The extent and number of drug interactions were investigated based on the reference textbook Drug Interaction Facts and in order to analyze the data collected, using SPSS 18 and according to study goals, a descriptive test, Pierson's correlation test, an independent T-test and a one-way ANOVA were used. Results: In total, 77 types of drugs and 394 drugs were prescribed with a mean of 5.6(SD=1.5 drugs per patient. A total of 108 potential drug interactions were found related to drugs prescribed during the first twenty-four hours. In terms of the type of drug interactions, delayed, moderate and possible types comprised the highest proportion of drug interactions. The four major interactions were between cimetidine and methadone, furosemide and amikacine, phenytoin and dopamine, and heparin and aspirin. The results of Pierson's correlation test were inicative of a positive correlation between the number of potential drug interactions and that of the drugs prescribed (r=0.563, P<0.05. Results of a one-way ANOVA showed that the mean number of potential drug interaction were significantly higher in those who died than in other patients (P<0.05. Conclusion: Elderly patients who are admitted to the intensive care unit are at a high risk of developing drug interactions and better care must be taken by medical team members.

Small RNA-Controlled Gene Regulatory Networks in Pseudomonas putida

DEFF Research Database (Denmark)

Bojanovic, Klara

evolved numerous mechanisms to controlgene expression in response to specific environmental signals. In addition to two-component systems, small regulatory RNAs (sRNAs) have emerged as major regulators of gene expression. The majority of sRNAs bind to mRNA and regulate their expression. They often have...... multiple targets and are incorporated into large regulatory networks and the RNA chaper one Hfq in many cases facilitates interactions between sRNAs and their targets. Some sRNAs also act by binding to protein targets and sequestering their function. In this PhD thesis we investigated the transcriptional....... Detailed insights into the mechanisms through which P. putida responds to different stress conditions and increased understanding of bacterial adaptation in natural and industrial settings were gained. Additionally, we identified genome-wide transcription start sites, andmany regulatory RNA elements...

77 FR 60481 - Design, Inspection, and Testing Criteria for Air Filtration and Adsorption Units of Post-Accident...

Science.gov (United States)

2012-10-03

... filtration and iodine adsorption units of ESF atmosphere cleanup systems in light-water-cooled nuclear power... Filtration and Adsorption Units of Post-Accident Engineered-Safety-Feature Atmosphere Cleanup Systems in Light-Water-Cooled Nuclear Power Plants AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide...

United States Nuclear Regulatory Commission research program on core debris/concrete interactions and ex-vessel fission-product release

International Nuclear Information System (INIS)

Burson, S.B.

1987-01-01

The study of core debris/concrete interaction phenomena has been a significant element of the NRC's Severe Accident Research Program for a number of years. The CORCON and VANESA codes used to predict the consequences of high-temperature debris attack on concrete and fission-product aerosol release are state-of-the-art computational tools. The major thrust of current NRC sponsored research focuses on the refinement, verification, and validation of these codes. An overview of the analytical and experimental aspects of the NRC research program is presented

Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer

Directory of Open Access Journals (Sweden)

Matloob Khushi

2014-11-01

Full Text Available Chromatin factors interact with each other in a cell and sequence-specific manner in order to regulate transcription and a wealth of publically available datasets exists describing the genomic locations of these interactions. Our recently published BiSA (Binding Sites Analyser database contains transcription factor binding locations and epigenetic modifications collected from published studies and provides tools to analyse stored and imported data. Using BiSA we investigated the overlapping cis-regulatory role of estrogen receptor alpha (ERα and progesterone receptor (PR in the T-47D breast cancer cell line. We found that ERα binding sites overlap with a subset of PR binding sites. To investigate further, we re-analysed raw data to remove any biases introduced by the use of distinct tools in the original publications. We identified 22,152 PR and 18,560 ERα binding sites (<5% false discovery rate with 4,358 overlapping regions among the two datasets. BiSA statistical analysis revealed a non-significant overall overlap correlation between the two factors, suggesting that ERα and PR are not partner factors and do not require each other for binding to occur. However, Monte Carlo simulation by Binary Interval Search (BITS, Relevant Distance, Absolute Distance, Jaccard and Projection tests by Genometricorr revealed a statistically significant spatial correlation of binding regions on chromosome between the two factors. Motif analysis revealed that the shared binding regions were enriched with binding motifs for ERα, PR and a number of other transcription and pioneer factors. Some of these factors are known to co-locate with ERα and PR binding. Therefore spatially close proximity of ERα binding sites with PR binding sites suggests that ERα and PR, in general function independently at the molecular level, but that their activities converge on a specific subset of transcriptional targets.

Seismic soil-structure-equipment interaction analysis of unit 5/6, Kozloduy NPP

Energy Technology Data Exchange (ETDEWEB)

Kostov, M [Bulgarian Academy of Sciences, Central Laboratory for Seismic Mechanics and Earthquake Engineering, Sofia (Bulgaria)

1995-07-01

This research project is aimed to analyse problems of soil-structure-equipment interaction under seismic excitation in case of Kozloduy NPP. Reevaluation and upgrading of Kozloduy NPP has started after 1977 Vrancea earthquake. New Safe Shutdown Earthquake (SSE) level was defined, upgrading most of structural equipment was performed, seismic instrumentation was installed. New investigations were initiated after 1990 IAEA mission visited the site. A comprehensive site confirmation project was started with a subsequent structural and equipment reevaluation and upgrading. This work deals with Units 5 and 6 of WWER-1000 type only.

An overview of the corrective action management unit and temporary unit regulations

International Nuclear Information System (INIS)

Green, D.R.; Corathers, L.; Coalgate, J.

1995-01-01

In February 1993, the US Environmental Protection Agency (EPA) promulgated the corrective action management unit (CAMU) and temporary unit (TU) regulations as 40 CFR Part 264, Subpart S. These regulations are intended to foster the selection of protective and cost-effective remedies for the restoration of sites contaminated by hazardous substances, hazardous wastes, and hazardous waste constituents by removing certain regulatory impediments to implementing those remedies, most notably those of the land disposal restrictions (LDRs). This paper provides a brief overview of the CAMU and TU regulations

Soil-structure interaction in nuclear power plants: a comparison of methods

International Nuclear Information System (INIS)

Wight, L.H.

1976-06-01

We performed an extensive parametric survey to analyze the differences between two methods of calculating soil-structure interaction. One method involves discretizing the soil-structure system and solving for the complete response with the LUSH computer code. The other method solves for the lumped mass structural response with Whitman soil springs. Twelve soil-structure interaction problems are solved by each of these methods. Representative results are presented and discussed. The debate within the nuclear industry in the United States over the relative merits of various methods of calculating soil-structure interaction has intensified over the last three years. The debate is largely the result of the U.S. Nuclear Regulatory Commission's position generally favoring the finite element approach. Certain sectors of the industry claim that this ruling is without technical basis, that it requires unnecessary expense, and that it inhibits the judgment of the analyst. We have addressed each of these points through lumped mass and finite element calculations on a set of twelve soil-structure interaction problems. The results of these calculations indicate some of the consequences of the choice of method

Sheep skeletal muscle transcriptome analysis reveals muscle growth regulatory lncRNAs.

Science.gov (United States)

Chao, Tianle; Ji, Zhibin; Hou, Lei; Wang, Jin; Zhang, Chunlan; Wang, Guizhi; Wang, Jianmin

2018-01-01

As widely distributed domestic animals, sheep are an important species and the source of mutton. In this study, we aimed to evaluate the regulatory lncRNAs associated with muscle growth and development between high production mutton sheep (Dorper sheep and Qianhua Mutton Merino sheep) and low production mutton sheep (Small-tailed Han sheep). In total, 39 lncRNAs were found to be differentially expressed. Using co-expression analysis and functional annotation, 1,206 co-expression interactions were found between 32 lncRNAs and 369 genes, and 29 of these lncRNAs were found to be associated with muscle development, metabolism, cell proliferation and apoptosis. lncRNA-mRNA interactions revealed 6 lncRNAs as hub lncRNAs. Moreover, three lncRNAs and their associated co-expressed genes were demonstrated by cis-regulatory gene analyses, and we also found a potential regulatory relationship between the pseudogene lncRNA LOC101121401 and its parent gene FTH1. This study provides a genome-wide resolution of lncRNA and mRNA regulation in muscles from mutton sheep.

[Neuronal and hormonal regulatory mechanisms of tears production and secretion].

Science.gov (United States)

Mrugacz, Małgorzata; Zywalewska, Nella; Bakunowicz-Lazarczyk, Alina

2005-01-01

The ocular surface, tear film, lacrimal glands act as a functional unit to preserve the quality of the refractive surface of the eye, and to resist injury and protect the eye against bodily and environmental conditions. Homeostasis of this functional unit involves neuronal and hormonal regulatory mechanisms. The eye appears to be a target organ for sex hormones particulary the androgen, as they modulate the immune system and trophic functions of the lacrimal and Meibomian glands.

Regulatory activities

International Nuclear Information System (INIS)

2001-01-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

Heart morphogenesis gene regulatory networks revealed by temporal expression analysis.

Science.gov (United States)

Hill, Jonathon T; Demarest, Bradley; Gorsi, Bushra; Smith, Megan; Yost, H Joseph

2017-10-01

During embryogenesis the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq timecourse in zebrafish from 30 hpf to 72 hpf and identified 5861 genes with altered expression. We clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis. This approach predicted hundreds of regulatory interactions and found batteries enriched in specific cell and tissue types, indicating that the approach can be used to narrow the search for novel genetic markers and regulatory interactions. Subsequent analyses confirmed the GRN using two mutants, Tbx5 and nkx2-5 , and identified sets of duplicated zebrafish genes that do not show temporal subfunctionalization. This dataset provides an essential resource for future studies on the genetic/epigenetic pathways implicated in congenital heart defects and the mechanisms of cardiac transcriptional regulation. © 2017. Published by The Company of Biologists Ltd.

Overcoming regulatory and economic challenges facing pharmacogenomics.

Science.gov (United States)

Cohen, Joshua P

2012-09-15

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place. Copyright © 2012 Elsevier B.V. All rights reserved.

Regulatory experiences from the spent fuel disposal step-wise implementation

International Nuclear Information System (INIS)

Heinonen, Jussi

2016-01-01

How to ensure regulatory readiness in different steps? Criteria for decision making: • Up-to-date safety requirements; • What is enough in this licensing step? Review strategy: • What is relevant in this licensing step?; • How to address (top-down or bottom-up review, own analysis, inspection)?Expertise: • Strategy for developing regulatory competences and resources; • Adapted to licensing step in question. Interaction with applicant: • important for mutual understanding; • Address main safety questions during pre-licensing – no surprises!

Interaction of the regulatory subunit of the cAMP-dependent protein kinase with PATZ1 (ZNF278)

Energy Technology Data Exchange (ETDEWEB)

Yang, Weng-Lang [Long Island Jewish Medical Center, North Shore University Hospital, Manhasset, NY 11030 (United States); Ravatn, Roald [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Kudoh, Kazuya [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama (Japan); Alabanza, Leah [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States)

2010-01-15

The effects of cAMP in cell are predominantly mediated by the cAMP-dependent protein kinase (PKA), which is composed of two genetically distinct subunits, catalytic (C) and regulatory (R), forming a tetrameric holoenzyme R{sub 2}C{sub 2}. The only known function for the R subunit is that of inhibiting the activity of the C subunit kinase. It has been shown that overexpression of RI{alpha}, but not the C subunit kinase, is associated with neoplastic transformation. In addition, it has also been demonstrated that mutation in the RI{alpha}, but not the C subunit is associated with increased resistance to the DNA-damaging anticancer drug cisplatin, thus suggesting that the RI{alpha} subunit of PKA may have functions independent of the kinase. We show here that the RI{alpha} subunit interacts with a BTB/POZ domain zinc-finger transcription factor, PATZ1 (ZNF278), and co-expression with RI{alpha} results in its sequestration in the cytoplasm. The cytoplasmic/nuclear translocation is inducible by cAMP. C-terminus deletion abolishes PATZ1 interaction with RI{alpha} and results in its localization in the nucleus. PATZ1 transactivates the cMyc promoter and the presence of cAMP and co-expression with RI{alpha} modulates its transactivation. Moreover, PATZ1 is aberrantly expressed in cancer. Taken together, our results showed a potentially novel mechanism of cAMP signaling mediated through the interaction of RI{alpha} with PATZ1 that is independent of the kinase activity of PKA, and the aberrant expression of PATZ1 in cancer point to its role in cell growth regulation.

Reconstructing gene regulatory networks from knock-out data using Gaussian Noise Model and Pearson Correlation Coefficient.

Science.gov (United States)

Mohamed Salleh, Faridah Hani; Arif, Shereena Mohd; Zainudin, Suhaila; Firdaus-Raih, Mohd

2015-12-01

A gene regulatory network (GRN) is a large and complex network consisting of interacting elements that, over time, affect each other's state. The dynamics of complex gene regulatory processes are difficult to understand using intuitive approaches alone. To overcome this problem, we propose an algorithm for inferring the regulatory interactions from knock-out data using a Gaussian model combines with Pearson Correlation Coefficient (PCC). There are several problems relating to GRN construction that have been outlined in this paper. We demonstrated the ability of our proposed method to (1) predict the presence of regulatory interactions between genes, (2) their directionality and (3) their states (activation or suppression). The algorithm was applied to network sizes of 10 and 50 genes from DREAM3 datasets and network sizes of 10 from DREAM4 datasets. The predicted networks were evaluated based on AUROC and AUPR. We discovered that high false positive values were generated by our GRN prediction methods because the indirect regulations have been wrongly predicted as true relationships. We achieved satisfactory results as the majority of sub-networks achieved AUROC values above 0.5. Copyright © 2015 Elsevier Ltd. All rights reserved.

Competent authority regulatory control of the transport of radioactive material

International Nuclear Information System (INIS)

1987-04-01

The purpose of this guide is to assist competent authorities in regulating the transport of radioactive materials and to assist users of transport regulations in their interactions with competent authorities. The guide should assist specifically those countries which are establishing their regulatory framework and further assist countries with established procedures to harmonize their application and implementation of the IAEA Regulations. This guide specifically covers various aspects of the competent authority implementation of the IAEA Regulations for the Safe Transport of Radioactive Material. In addition, physical protection and safeguards control of the transport of nuclear materials as well as third party liability aspects are briefly discussed. This is because they have to be taken into account in overall transport regulatory activities, especially when establishing the regulatory framework

AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA.

Science.gov (United States)

Götz, Frank; Roske, Yvette; Schulz, Maike Svenja; Autenrieth, Karolin; Bertinetti, Daniela; Faelber, Katja; Zühlke, Kerstin; Kreuchwig, Annika; Kennedy, Eileen J; Krause, Gerd; Daumke, Oliver; Herberg, Friedrich W; Heinemann, Udo; Klussmann, Enno

2016-07-01

A-kinase anchoring proteins (AKAPs) interact with the dimerization/docking (D/D) domains of regulatory subunits of the ubiquitous protein kinase A (PKA). AKAPs tether PKA to defined cellular compartments establishing distinct pools to increase the specificity of PKA signalling. Here, we elucidated the structure of an extended PKA-binding domain of AKAP18β bound to the D/D domain of the regulatory RIIα subunits of PKA. We identified three hydrophilic anchor points in AKAP18β outside the core PKA-binding domain, which mediate contacts with the D/D domain. Such anchor points are conserved within AKAPs that bind regulatory RII subunits of PKA. We derived a different set of anchor points in AKAPs binding regulatory RI subunits of PKA. In vitro and cell-based experiments confirm the relevance of these sites for the interaction of RII subunits with AKAP18 and of RI subunits with the RI-specific smAKAP. Thus we report a novel mechanism governing interactions of AKAPs with PKA. The sequence specificity of each AKAP around the anchor points and the requirement of these points for the tight binding of PKA allow the development of selective inhibitors to unequivocally ascribe cellular functions to the AKAP18-PKA and other AKAP-PKA interactions. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

National legislative and regulatory activities

International Nuclear Information System (INIS)

Anon.

2011-01-01

This chapter of Nuclear Law Bulletin gathers some documents about national legislative and regulatory activities: - Belgium: Amendment of the Act on classification and security clearances, certifications and security notifications; Czech Republic: Resolution of the government of the Czech Republic on the time schedule of preparatory works for enlarging the nuclear power plant Temelin; Finland: Temporary Amendment to the Nuclear Liability Act; Ireland: Merchant Shipping Act; Romania: Emergency Ordinance on the identification, designation and protection of critical infrastructures; Emergency Ordinance on the control regime of dual-use items; Amendment to the Act on the safe conduct of nuclear activities; Nuclear safety norms on design and construction of nuclear power plants and nuclear safety norms on siting of nuclear power plants; United Kingdom: Establishment of the Office for Nuclear Regulation; United States: Waste Confidence Decision and Rule Update; Response to recent events in Japan

Fisheries regulatory regimes and resilience to climate change.

Science.gov (United States)

Ojea, Elena; Pearlman, Isaac; Gaines, Steven D; Lester, Sarah E

2017-05-01

Climate change is already producing ecological, social, and economic impacts on fisheries, and these effects are expected to increase in frequency and magnitude in the future. Fisheries governance and regulations can alter socio-ecological resilience to climate change impacts via harvest control rules and incentives driving fisher behavior, yet there are no syntheses or conceptual frameworks for examining how institutions and their regulatory approaches can alter fisheries resilience to climate change. We identify nine key climate resilience criteria for fisheries socio-ecological systems (SES), defining resilience as the ability of the coupled system of interacting social and ecological components (i.e., the SES) to absorb change while avoiding transformation into a different undesirable state. We then evaluate the capacity of four fisheries regulatory systems that vary in their degree of property rights, including open access, limited entry, and two types of rights-based management, to increase or inhibit resilience. Our exploratory assessment of evidence in the literature suggests that these regulatory regimes vary widely in their ability to promote resilient fisheries, with rights-based approaches appearing to offer more resilience benefits in many cases, but detailed characteristics of the regulatory instruments are fundamental.

Managing carbon regulatory risk in utility resource planning: Current practices in the Western United States

International Nuclear Information System (INIS)

Barbose, Galen; Wiser, Ryan; Phadke, Amol; Goldman, Charles

2008-01-01

Concerns about global climate change have substantially increased the likelihood that future policy will seek to minimize carbon dioxide emissions. As such, even today, electric utilities are making resource planning and investment decisions that consider the possible implications of these future carbon regulations. In this article, we examine the manner in which utilities assess the financial risks associated with future carbon regulations within their long-term resource plans. We base our analysis on a review of the most recent resource plans filed by 15 electric utilities in the Western United States. Virtually all of these utilities made some effort to quantitatively evaluate the potential cost of future carbon regulations when analyzing alternate supply- and demand-side resource options for meeting customer load. Even without federal climate regulation in the US, the prospect of that regulation is already having an impact on utility decision-making and resource choices. That said, the methods and assumptions used by utilities to analyze carbon regulatory risk, and the impact of that analysis on their choice of a particular resource strategy, vary considerably, revealing a number of opportunities for analytic improvement. Though our review focuses on a subset of US electric utilities, this work holds implications for all electric utilities and energy policymakers who are seeking to minimize the compliance costs associated with future carbon regulations

On the role of sparseness in the evolution of modularity in gene regulatory networks.

Science.gov (United States)

Espinosa-Soto, Carlos

2018-05-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

First generation TREN dendrimers functionalized with naphthyl and/or dansyl units. Ground and excited state electronic interactions and protonation effects.

Science.gov (United States)

Passaniti, Paolo; Maestri, Mauro; Ceroni, Paola; Bergamini, Giacomo; Vögtle, Fritz; Fakhrnabavi, Hassan; Lukin, Oleg

2007-04-01

We report the photophysical properties (absorption and emission spectra, quantum yield, and lifetime) of five dendrimers of first generation based on a TREN (tris(2-aminoethyl)amine) skeleton functionalized at the periphery with naphthyl and/or 5-dimethylamino-1-naphthalenesulfonamide (hereafter called dansyl) chromophores. Each dendrimer comprises one tertiary amine unit in the core and three branches carrying a sulfonimido unit at the periphery, each one substituted by two identical or different moieties. In particular, TD6 and TN6 contain dansyl (D) or naphthyl (N) units, respectively, while TD3B3, TN3B3 and TN3D3 contain dansyl, naphthyl or benzyl (B) units at the periphery. The spectroscopic behaviour of these dendrimers has been investigated in acetonitrile solution and compared with that of reference compounds. For all dendrimers the absorption bands are red shifted compared to those of monomeric naphthyl and dansyl reference compounds. Moreover, the intense naphthyl and dansyl fluorescence is greatly quenched because of strong interactions between the two aromatic moieties linked by a sulfonimido unit. Protonation of the amine units of the dendrimers by addition of CF(3)SO(3)H (triflic) acid causes a decrease in intensity of the luminescence and a change in the shape of the emission bands. The shapes of the titration curves depend on the dendrimer, but in any case the effect of acid can be fully reversed by successive addition of base (tributylamine). The obtained results reveal that among the intradendrimer interactions the most important one is that taking place (via mesomeric interaction) between the various chromophores and a pair of sulfonimido groups.

Application of Regulatory Focus Theory to Search Advertising.

Science.gov (United States)

Mowle, Elyse N; Georgia, Emily J; Doss, Brian D; Updegraff, John A

The purpose of this paper is to test the utility of regulatory focus theory principles in a real-world setting; specifically, Internet hosted text advertisements. Effect of compatibility of the ad text with the regulatory focus of the consumer was examined. Advertisements were created using Google AdWords. Data were collected for the number of views and clicks each ad received. Effect of regulatory fit was measured using logistic regression. Logistic regression analyses demonstrated that there was a strong main effect for keyword, such that users were almost six times as likely to click on a promotion advertisement as a prevention advertisement, as well as a main effect for compatibility, such that users were twice as likely to click on an advertisement with content that was consistent with their keyword. Finally, there was a strong interaction of these two variables, such that the effect of consistent advertisements was stronger for promotion searches than for prevention searches. The effect of ad compatibility had medium to large effect sizes, suggesting that individuals' state may have more influence on advertising response than do individuals' traits (e.g. personality traits). Measurement of regulatory fit was limited by the constraints of Google AdWords. The results of this study provide a possible framework for ad creation for Internet advertisers. This paper is the first study to demonstrate the utility of regulatory focus theory in online advertising.

Regulatory focus, self-efficacy and outcome expectations as drivers of motivation to consume healthy food products

DEFF Research Database (Denmark)

Tudoran, Ana Alina; Scholderer, Joachim; Brunsø, Karen

2012-01-01

In this paper we apply the principle of RegulatoryFocus Theory to investigate the interaction between self-efficacy and outcomeexpectations on individuals’ intentions to adopt health behaviors. The participants, 959 individuals (Survey 1) and 2400 individuals (Survey 2), reported self-efficacy be......In this paper we apply the principle of RegulatoryFocus Theory to investigate the interaction between self-efficacy and outcomeexpectations on individuals’ intentions to adopt health behaviors. The participants, 959 individuals (Survey 1) and 2400 individuals (Survey 2), reported self...

Drug interactions evaluation: An integrated part of risk assessment of therapeutics

International Nuclear Information System (INIS)

Zhang, Lei; Reynolds, Kellie S.; Zhao, Ping; Huang, Shiew-Mei

2010-01-01

Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance ( (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf)) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industry and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a 'Drug Development and Drug Interactions' website to provide up-to-date information regarding evaluation of drug interactions ( (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm)). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process.

Challenges in orphan drug development and regulatory policy in China.

Science.gov (United States)

Cheng, Alice; Xie, Zhi

2017-01-18

While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

Aggregation of topological motifs in the Escherichia coli transcriptional regulatory network

Directory of Open Access Journals (Sweden)

Barabási Albert-László

2004-01-01

Full Text Available Abstract Background Transcriptional regulation of cellular functions is carried out through a complex network of interactions among transcription factors and the promoter regions of genes and operons regulated by them.To better understand the system-level function of such networks simplification of their architecture was previously achieved by identifying the motifs present in the network, which are small, overrepresented, topologically distinct regulatory interaction patterns (subgraphs. However, the interaction of such motifs with each other, and their form of integration into the full network has not been previously examined. Results By studying the transcriptional regulatory network of the bacterium, Escherichia coli, we demonstrate that the two previously identified motif types in the network (i.e., feed-forward loops and bi-fan motifs do not exist in isolation, but rather aggregate into homologous motif clusters that largely overlap with known biological functions. Moreover, these clusters further coalesce into a supercluster, thus establishing distinct topological hierarchies that show global statistical properties similar to the whole network. Targeted removal of motif links disintegrates the network into small, isolated clusters, while random disruptions of equal number of links do not cause such an effect. Conclusion Individual motifs aggregate into homologous motif clusters and a supercluster forming the backbone of the E. coli transcriptional regulatory network and play a central role in defining its global topological organization.

Regulatory approach to risk informed decision making in India

International Nuclear Information System (INIS)

Chande, S.K.; Koley, J.

2001-01-01

Atomic Energy Regulatory Board (AERB), the authority for licensing and monitoring safety in Indian Nuclear Power Plants (NPPs), makes use of insights gained from PSA together with the results of the other deterministic analyses in taking decisions regarding the acceptability of the safety of the NPPs. PSA provides an estimation of risks; it also gives information on a balanced design by revealing interaction between engineered features and weak areas in a design. For regulatory use, PSA needs to be carried out using standardized methodology and state of the art technology. PSA helps regulators in taking faster and consistent decisions. Keeping in mind the limitations associated with PSA study, AERB has decided to adopt risk-informed decision making in regulatory licensing process. This paper describes the AERB policy regarding PSA and gives an overview of the experience in this area. (author)

Transcriptional Regulatory Network Analysis of MYB Transcription Factor Family Genes in Rice

Directory of Open Access Journals (Sweden)

Shuchi eSmita

2015-12-01

Full Text Available MYB transcription factor (TF is one of the largest TF families and regulates defense responses to various stresses, hormone signaling as well as many metabolic and developmental processes in plants. Understanding these regulatory hierarchies of gene expression networks in response to developmental and environmental cues is a major challenge due to the complex interactions between the genetic elements. Correlation analyses are useful to unravel co-regulated gene pairs governing biological process as well as identification of new candidate hub genes in response to these complex processes. High throughput expression profiling data are highly useful for construction of co-expression networks. In the present study, we utilized transcriptome data for comprehensive regulatory network studies of MYB TFs by top down and guide gene approaches. More than 50% of OsMYBs were strongly correlated under fifty experimental conditions with 51 hub genes via top down approach. Further, clusters were identified using Markov Clustering (MCL. To maximize the clustering performance, parameter evaluation of the MCL inflation score (I was performed in terms of enriched GO categories by measuring F-score. Comparison of co-expressed cluster and clads analyzed from phylogenetic analysis signifies their evolutionarily conserved co-regulatory role. We utilized compendium of known interaction and biological role with Gene Ontology enrichment analysis to hypothesize function of coexpressed OsMYBs. In the other part, the transcriptional regulatory network analysis by guide gene approach revealed 40 putative targets of 26 OsMYB TF hubs with high correlation value utilizing 815 microarray data. The putative targets with MYB-binding cis-elements enrichment in their promoter region, functional co-occurrence as well as nuclear localization supports our finding. Specially, enrichment of MYB binding regions involved in drought-inducibility implying their regulatory role in drought

Mining Gene Regulatory Networks by Neural Modeling of Expression Time-Series.

Science.gov (United States)

Rubiolo, Mariano; Milone, Diego H; Stegmayer, Georgina

2015-01-01

Discovering gene regulatory networks from data is one of the most studied topics in recent years. Neural networks can be successfully used to infer an underlying gene network by modeling expression profiles as times series. This work proposes a novel method based on a pool of neural networks for obtaining a gene regulatory network from a gene expression dataset. They are used for modeling each possible interaction between pairs of genes in the dataset, and a set of mining rules is applied to accurately detect the subjacent relations among genes. The results obtained on artificial and real datasets confirm the method effectiveness for discovering regulatory networks from a proper modeling of the temporal dynamics of gene expression profiles.

Reforming Brazil's offshore oil and gas safety regulatory framework: Lessons from Norway, the United Kingdom and the United States

International Nuclear Information System (INIS)

Mendes, Pietro A.S.; Hall, Jeremy; Matos, Stelvia; Silvestre, Bruno

2014-01-01

We propose reforming the Brazilian regulatory safety framework (BRSF) for offshore oil and gas production and drilling operations. Brazil has emerged as a leading offshore producer with extensive proven reserves yet to be exploited. However, the BRSF has not been updated since 2007, and there are now major concerns about the industry's safety, particularly after the BP Deepwater Horizon accident, along with the technical challenges due to extreme conditions under which Brazil's resources are located. Drawing on experiences from three leading offshore oil and gas producers (Norway, the UK, and the US), we recommend the adoption of three best practices: the UK's ‘safety case’ approach (where operators are expected to provide convincing and valid arguments that a system is sufficiently safe for a given application in a specific environment), Norway's ‘barrier management’ (evidence that there are at least two tested and independent barriers to avoid accidents) and greater investment in safety research and development, as suggested by the US's National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling. We discuss implications for policy reform and how best practices can be applied within the Brazilian context. - Highlights: • Description of the Brazilian regulatory safety framework (BRSF). • Comparison between BRSF and regulatory frameworks of leading offshore oil and gas jurisdictions (Norway, UK and US). • Recommendations for BRSF to include the safety case, barrier management and increased investment in safety technology

Nuclear power reactor licensing and regulation in the United States

International Nuclear Information System (INIS)

Shapar, H.K.

1979-01-01

The report is devoted to four subjects: an explanation of the origins, statutory basis and development of the present regulatory system in the United States; a description of the various actions which must be taken by a license applicant and by the Nuclear Regulatory Commission before a nuclear power plant can be constructed and placed on-line, an account of the current regulatory practices followed by the US NRC in licensing nuclear power reactors; an identification of some of the 'lessons learned' from the Three Mile Island accident and some proposed regulatory and legislative solutions. (NEA) [fr

Steam generator tube integrity requirements and operating experience in the United States

International Nuclear Information System (INIS)

Karwoski, K.J.

2009-01-01

Steam generator tube integrity is important to the safe operation of pressurized-water reactors. For ensuring tube integrity, the U.S. Nuclear Regulatory Commission uses a regulatory framework that is largely performance based. This performance-based framework is supplemented with some prescriptive requirements. The framework recognizes that there are three combinations of tube materials and heat treatments currently used in the United States and that the operating experience depends, in part, on the type of material used. This paper summarizes the regulatory framework for ensuring steam generator tube integrity, it highlights the current status of steam generators, and it highlights some of the steam generator issues and challenges that exist in the United States. (author)

A Point Source of a Different Color: Identifying a Gap in United States Regulatory Policy for “Green” CSO Treatment Using Constructed Wetlands

Directory of Open Access Journals (Sweden)

Zeno F. Levy

2014-04-01

Full Text Available Up to 850 billion gallons of untreated combined sewer overflow (CSO is discharged into waters of the United States each year. Recent changes in CSO management policy support green infrastructure (GI technologies as “front of the pipe” approaches to discharge mitigation by detention/reduction of urban stormwater runoff. Constructed wetlands for CSO treatment have been considered among suites of GI solutions. However, these wetlands differ fundamentally from other GI technologies in that they are “end of the pipe” treatment systems that discharge from a point source, and are therefore regulated in the U.S. under the National Pollution Discharge Elimination System (NPDES. We use a comparative regulatory analysis to examine the U.S. policy framework for CSO treatment wetlands. We find in all cases that permitting authorities have used best professional judgment to determine effluent limits and compliance monitoring requirements, referencing technology and water quality-based standards originally developed for traditional “grey” treatment systems. A qualitative comparison with Europe shows less stringent regulatory requirements, perhaps due to institutionalized design parameters. We recommend that permitting authorities develop technical guidance documents for evaluation of “green” CSO treatment systems that account for their unique operational concerns and benefits with respect to sustainable development.

Conserved cis-regulatory regions in a large genomic landscape control SHH and BMP-regulated Gremlin1 expression in mouse limb buds

Directory of Open Access Journals (Sweden)

Zuniga Aimée

2012-08-01

Full Text Available Abstract Background Mouse limb bud is a prime model to study the regulatory interactions that control vertebrate organogenesis. Major aspects of limb bud development are controlled by feedback loops that define a self-regulatory signalling system. The SHH/GREM1/AER-FGF feedback loop forms the core of this signalling system that operates between the posterior mesenchymal organiser and the ectodermal signalling centre. The BMP antagonist Gremlin1 (GREM1 is a critical node in this system, whose dynamic expression is controlled by BMP, SHH, and FGF signalling and key to normal progression of limb bud development. Previous analysis identified a distant cis-regulatory landscape within the neighbouring Formin1 (Fmn1 locus that is required for Grem1 expression, reminiscent of the genomic landscapes controlling HoxD and Shh expression in limb buds. Results Three highly conserved regions (HMCO1-3 were identified within the previously defined critical genomic region and tested for their ability to regulate Grem1 expression in mouse limb buds. Using a combination of BAC and conventional transgenic approaches, a 9 kb region located ~70 kb downstream of the Grem1 transcription unit was identified. This region, termed Grem1 Regulatory Sequence 1 (GRS1, is able to recapitulate major aspects of Grem1 expression, as it drives expression of a LacZ reporter into the posterior and, to a lesser extent, in the distal-anterior mesenchyme. Crossing the GRS1 transgene into embryos with alterations in the SHH and BMP pathways established that GRS1 depends on SHH and is modulated by BMP signalling, i.e. integrates inputs from these pathways. Chromatin immunoprecipitation revealed interaction of endogenous GLI3 proteins with the core cis-regulatory elements in the GRS1 region. As GLI3 is a mediator of SHH signal transduction, these results indicated that SHH directly controls Grem1 expression through the GRS1 region. Finally, all cis-regulatory regions within the Grem1

Regulatory Challenges for Cartilage Repair Technologies.

Science.gov (United States)

McGowan, Kevin B; Stiegman, Glenn

2013-01-01

In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

78 FR 47011 - Software Unit Testing for Digital Computer Software Used in Safety Systems of Nuclear Power Plants

Science.gov (United States)

2013-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Software Unit Testing for Digital Computer Software... revised regulatory guide (RG), revision 1 of RG 1.171, ``Software Unit Testing for Digital Computer Software Used in Safety Systems of Nuclear Power Plants.'' This RG endorses American National Standards...

77 FR 50722 - Software Unit Testing for Digital Computer Software Used in Safety Systems of Nuclear Power Plants

Science.gov (United States)

2012-08-22

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Software Unit Testing for Digital Computer Software...) is issuing for public comment draft regulatory guide (DG), DG-1208, ``Software Unit Testing for Digital Computer Software used in Safety Systems of Nuclear Power Plants.'' The DG-1208 is proposed...

Spent fuel pool cooling system upgrade for Kori Unit 1

International Nuclear Information System (INIS)

Sun Park, Jong; In Shin, Kyung

2014-01-01

Following Fukushima nuclear power plant accident, the needs for reliable performance of its own safety functions of Spent Fuel Pool Cooling System (SFPCS) has risen significantly to maintain the plant in a safe condition. Regulatory Guide 1.13 of United States Nuclear Regulatory Commission (USNRC) requires the SFPCS shall be designed safety related as Quality Group C and Seismic Category 1. However, the existing Spent Fuel Pool (SFP) of KORI Unit 1 was not designed as a safety system. In order to comply with the above licensing requirement for the extended operational life of KORI Unit 1, it has been decided to add a safety related Seismic Category 1 Makeup System to KORI Unit 1 and the existing SFPCS to be modified in dedicated channels with safety related equipment to enhance system's reliability as a means of providing diversity. This paper focuses on describing the relevant design requirements, applications, and supplemental facilities to the SFPCS of KORI Unit 1. (authors)

Development of an international BRC [Below Regulatory Concern] limit

International Nuclear Information System (INIS)

Kennedy, W.E. Jr.

1987-07-01

The International Atomic Energy Agency (IAEA) has recently investigated the exemption from regulatory control of radiation sources containing limited quantities of radioactive materials. Early efforts were entitled de minimis and were aimed at establishing a philosophical basis and radiation dose limits. The main objectives of more recent work on exemption are to illustrate a method for developing practical radiological criteria, to establish generic criteria, and to determine the practicability of the preliminary exemption principles. The method used to develop the criteria relies on models to evaluate the potential radiation exposure pathways and scenarios for individuals and population groups potentially present following the unrestricted release of materials. This paper describes the assessment methods, presents the generic results expressed in terms of the limiting concentrations of selected radionuclides in municipal waste, and provides a comparison with recent regulatory efforts in the United States for considering selected wastes being Below Regulatory Concern (BRC). 17 refs., 4 tabs

Politically Induced Regulatory Risk and Independent Regulatory Agencies

OpenAIRE

Strausz, Roland

2015-01-01

Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

Impact of Interactive Online Units on Learning Science among Students with Learning Disabilities and English Learners

Science.gov (United States)

Terrazas-Arellanes, Fatima E.; Gallard M., Alejandro J.; Strycker, Lisa A.; Walden, Emily D.

2018-01-01

The purpose of this study was to document the design, classroom implementation, and effectiveness of interactive online units to enhance science learning over 3 years among students with learning disabilities, English learners, and general education students. Results of a randomised controlled trial with 2,303 middle school students and 71…

Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I.

Science.gov (United States)

Suzuki, Toru; Muto, Shinsuke; Miyamoto, Saku; Aizawa, Kenichi; Horikoshi, Masami; Nagai, Ryozo

2003-08-01

Transcription involves molecular interactions between general and regulatory transcription factors with further regulation by protein-protein interactions (e.g. transcriptional cofactors). Here we describe functional interaction between DNA-binding transcription factor and histone chaperone. Affinity purification of factors interacting with the DNA-binding domain of the transcription factor Sp1 showed Sp1 to interact with the histone chaperone TAF-I, both alpha and beta isoforms. This interaction was specific as Sp1 did not interact with another histone chaperone CIA nor did other tested DNA-binding regulatory factors (MyoD, NFkappaB, p53) interact with TAF-I. Interaction of Sp1 and TAF-I occurs both in vitro and in vivo. Interaction with TAF-I results in inhibition of DNA-binding, and also likely as a result of such, inhibition of promoter activation by Sp1. Collectively, we describe interaction between DNA-binding transcription factor and histone chaperone which results in negative regulation of the former. This novel regulatory interaction advances our understanding of the mechanisms of eukaryotic transcription through DNA-binding regulatory transcription factors by protein-protein interactions, and also shows the DNA-binding domain to mediate important regulatory interactions.

Economic analysis requirements in support of orbital debris regulatory policy

Science.gov (United States)

Greenberg, Joel S.

1996-10-01

As the number of Earth orbiting objects increases so does the potential for generating orbital debris with the consequent increase in the likelihood of impacting and damaging operating satellites. Various debris remediation approaches are being considered that encompass both in-orbit and return-to-Earth schema and have varying degrees of operations, cost, international competitiveness, and safety implications. Because of the diversity of issues, concerns and long-term impacts, there is a clear need for the setting of government policies that will lead to an orderly abatement of the potential orbital debris hazards. These policies may require the establishment of a supportive regulatory regime. The Department of Transportation is likely to have regulatory responsibilities relating to orbital debris stemming from its charge to protect the public health and safety, safety of property, and national security interests and foreign policy interests of the United States. This paper describes DOT's potential regulatory role relating to orbital debris remediation, the myriad of issues concerning the need for establishing government policies relating to orbital debris remediation and their regulatory implications, the proposed technological solutions and their economic and safety implications. Particular emphasis is placed upon addressing cost-effectiveness and economic analyses as they relate to economic impact analysis in support of regulatory impact analysis.

Regulatory control for safe usage of radiation sources in India

International Nuclear Information System (INIS)

Ghosh, P.K.; Sonawane, A.U.

1998-01-01

The widespread applications of radioactive materials and radiation generating equipment in the field of industry, medicine agriculture and research in India necessitated the establishment of an efficient regulatory framework and consequently the Atomic Energy Regulatory Board (AERB) was constituted to exercise regulatory control over the safe usage of the radioactive materials and the radiation generating equipment. The Atomic Energy Act, 1962 and the Radiation Protection Rules, 1971 promulgated under the Act forms the basis of radiation safety in India and Chairman, AERB is the Competent Authority to enforce the regulatory provisions of the Radiation Protection Rules, 1971, for safe use of radiation source in the country. AERB has published a number of documents such as Radiation Surveillance Procedures, Standards, Codes, Guides and Manuals for safe use and handling of radioactive materials and radiation generating equipment. Apart from nuclear fuel cycle documents, these publications pertain to industrial radiography, medical application of radiation, transport of radioactive material, industrial gamma irradiators, X-ray units etc. AERB safety related publications are based on international standards e.g. BSS, IAEA, ICRP, ISO etc. This paper outlines the methodology of regulatory control exercised by AERB for safe use of the radioactive materials and the radiation generating equipment in the country. (author)

Eating on impulse: Implicit attitudes, self-regulatory resources, and trait self-control as determinants of food consumption.

Science.gov (United States)

Wang, Yan; Wang, Lei; Cui, Xianghua; Fang, Yuan; Chen, Qianqiu; Wang, Ya; Qiang, Yao

2015-12-01

Self-regulatory resources and trait self-control have been found to moderate the impulse-behavior relationship. The current study investigated whether the interaction of self-regulatory resources and trait self-control moderates the association between implicit attitudes and food consumption. One hundred twenty female participants were randomly assigned to either a depletion condition in which their self-regulatory resources were reduced or a no-depletion condition. Participants' implicit attitudes for chocolate were measured with the Single Category Implicit Association Test and self-report measures of trait self-control were collected. The dependent variable was chocolate consumption in an ostensible taste and rate task. Implicit attitudes predicted chocolate consumption in depleted participants but not in non-depleted participants. However, this predictive power of implicit attitudes on eating in depleted condition disappeared in participants with high trait self-control. Thus, trait self-control and self-regulatory resources interact to moderate the prediction of implicit attitude on eating behavior. Results suggest that high trait self-control buffers the effect of self-regulatory depletion on impulsive eating. Copyright © 2015 Elsevier Ltd. All rights reserved.

A canonical correlation analysis-based dynamic bayesian network prior to infer gene regulatory networks from multiple types of biological data.

Science.gov (United States)

Baur, Brittany; Bozdag, Serdar

2015-04-01

One of the challenging and important computational problems in systems biology is to infer gene regulatory networks (GRNs) of biological systems. Several methods that exploit gene expression data have been developed to tackle this problem. In this study, we propose the use of copy number and DNA methylation data to infer GRNs. We developed an algorithm that scores regulatory interactions between genes based on canonical correlation analysis. In this algorithm, copy number or DNA methylation variables are treated as potential regulator variables, and expression variables are treated as potential target variables. We first validated that the canonical correlation analysis method is able to infer true interactions in high accuracy. We showed that the use of DNA methylation or copy number datasets leads to improved inference over steady-state expression. Our results also showed that epigenetic and structural information could be used to infer directionality of regulatory interactions. Additional improvements in GRN inference can be gleaned from incorporating the result in an informative prior in a dynamic Bayesian algorithm. This is the first study that incorporates copy number and DNA methylation into an informative prior in dynamic Bayesian framework. By closely examining top-scoring interactions with different sources of epigenetic or structural information, we also identified potential novel regulatory interactions.

Impact of interactive online units on learning science among students with learning disabilities and English learners

Science.gov (United States)

Terrazas-Arellanes, Fatima E.; Gallard M., Alejandro J.; Strycker, Lisa A.; Walden, Emily D.

2018-03-01

The purpose of this study was to document the design, classroom implementation, and effectiveness of interactive online units to enhance science learning over 3 years among students with learning disabilities, English learners, and general education students. Results of a randomised controlled trial with 2,303 middle school students and 71 teachers across 13 schools in two states indicated that online units effectively deepened science knowledge across all three student groups. Comparing all treatment and control students on pretest-to-posttest improvement on standards-based content-specific assessments, there were statistically significant mean differences (17% improvement treatment vs. 6% control; p English learner status, indicating that these two groups performed similarly to their peers; students with learning disabilities had significantly lower assessment scores overall. Teachers and students were moderately satisfied with the units.

76 FR 39812 - Scotts Miracle-Gro Co.; Regulatory Status of Kentucky Bluegrass Genetically Engineered for...

Science.gov (United States)

2011-07-07

... engineered for herbicide tolerance without the use of plant pest components, does not meet the definition of... Environmental Analysis Branch, Biotechnology Regulatory Services, APHIS, 4700 River Road, Unit 147, Riverdale... introduction of a plant pest or noxious weed into the United States or dissemination of a plant pest or noxious...

Interactive baby feeding bottle

NARCIS (Netherlands)

2013-01-01

An interactive baby bottle with an electronic unit is disclosed. The electronic unit comprises a sensor unit configured to sense the heart beat of a person bottle feeding a baby and an actuator unit configured to transmit the sensed heart beat to the baby. The disclosed interactive baby bottle can

RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins Involved in a Posttranscriptional Iron Regulatory Mechanism

Science.gov (United States)

Figueroa-Angulo, Elisa E.; Calla-Choque, Jaeson S.; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

2015-01-01

Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

Staff perceptions of challenging parent-staff interactions and beneficial strategies in the Neonatal Intensive Care Unit.

Science.gov (United States)

Friedman, Joshua; Friedman, Susan Hatters; Collin, Marc; Martin, Richard J

2018-01-01

To characterise neonatal intensive care unit (NICU) staff perceptions regarding factors which may lead to more challenging staff-parent interactions, and beneficial strategies for working with families with whom such interactions occur. A survey of 168 physician and nursing staff at two NICUs in American teaching hospitals inquired about their perceptions of challenging parent-staff interactions and situations in which such interactions were likely to occur. From a medical perspective, staff perceptions of challenging interactions were noted when infants had recent decompensation, high medical complexity, malformations or long duration of stay in the NICU. From a psychological/social perspective, a high likelihood of challenging interactions was noted with parents who were suspicious, interfere with equipment, or parents who hover in the NICU, express paranoid or delusional thoughts, repeat questions, perceive the staff as inaccessible, are managing addictions, or who require child protective services involvement. Frequent family meetings, grieving opportunities, education of parents, social work referrals, clearly defined rules, partnering in daily care and support groups were perceived as the most beneficial strategies for improving difficult interactions. This study delineates what staff perceive as challenging interactions and provides support for an educational and interventional role that incorporates mental health professionals. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Interactive visualization of gene regulatory networks with associated gene expression time series data

NARCIS (Netherlands)

Westenberg, M.A.; Hijum, van S.A.F.T.; Lulko, A.T.; Kuipers, O.P.; Roerdink, J.B.T.M.; Linsen, L.; Hagen, H.; Hamann, B.

2008-01-01

We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,

Regulatory strategies for high-level radioactive waste management in nine countries: Final report

International Nuclear Information System (INIS)

1987-12-01

This report provides information on the regulatory strategies being developed or implemented in nine countries for the management and disposal of spent nuclear fuel and high-level radioactive waste. The study was performed by International Energy Associates Limited on behalf of Pacific Northwest Laboratories and the US Department of Energy. IEAL obtained information for this report from the regulatory authorities in each country, who also later reviewed drafts of the respective country sections of the report. The nine countries surveyed were Belgium, Canada, the Federal Republic of Germany, France, Japan, Sweden, Switzerland, the United Kingdom and the United States. These countries were selected for study because they are among the largest producers of nuclear energy in the world today and have aggressive programs for spent fuel management and waste disposal

International Expert Team Concludes IAEA Peer Review of Slovakia's Regulatory Framework for Nuclear Safety

International Nuclear Information System (INIS)

2012-01-01

that consideration of these would enhance the overall performance of the regulatory system: Coordination and allocation of responsibilities among State Authorities in the area of safety and improvement of planning and coordination of their activities; The development of a national policy and strategy document for nuclear safety; and A unified national radiation monitoring system to ensure its results could be used by competent authorities in normal situations as well as during emergencies. In a preliminary report, the IAEA has conveyed the team's main conclusions to UJD SR. A final report will be submitted to the Government of Slovakia in about three months. UJD SR has informed the team that the final report will be publicly available. The IAEA encourages nations to invite a follow-up IRRS mission about two years after the mission has been completed. Background. The IRRS mission to Slovakia was conducted from 28 May to 7 June 2012, mainly in Bratislava. The IRRS team carried out a review of nuclear legal and regulatory framework for nuclear safety. Special attention was given to the review of the regulatory implications for Slovakia of the TEPCO Fukushima Daiichi accident. The review addressed all facilities regulated by UJD SR including nine nuclear power units, as well as spent fuel and waste management facilities. The IRRS mission did not include a comprehensive review of the national regulatory infrastructure for radiation safety of Slovakia, which is planned to be covered in the IRRS follow-up mission. Team experts came from twelve different countries: Belgium, Brazil, Czech Republic, Finland, France, Hungary, Romania, Slovenia, South Korea, Sweden, Ukraine and United Kingdom. The IRRS team consisted also of 6 IAEA staff members. Quick Facts. Slovakia has nine nuclear power reactors at two sites (Bohunice, Mochovce): 3 units are in decommissioning, four units are in operation and two units under construction. Slovakia has no other fuel cycle facilities or research

A tale of three labels: translating the JUPITER trial data into regulatory claims.

Science.gov (United States)

Ridker, Paul M

2011-08-01

Whether a pivotal randomized trial will be interpreted in a similar and consistent manner by different regulatory agencies is uncertain as policy perspectives may play a role in data interpretation and the translation of trial results into clinical practice. Using a contemporary example, to compare and contrast regulatory claims in the United States, Europe, and Canada that derive from a pivotal clinical trial. The recently completed JUPITER trial of rosuvastatin as compared to placebo conducted among 17,802 men and women with LDL-C JUPITER trial provides an opportunity to compare and contrast how regulatory agencies in the United States, Canada, and Europe chose to interpret an identical database. Labeling indications based on earlier statin trials of primary and secondary prevention were also reviewed. JUPITER demonstrated a 44% reduction (p JUPITER trial population by stipulating that those eligible for treatment should be older men and women with hsCRP >2 mg/L, plus one additional risk factor for heart disease. The Canadian label is silent on age and hsCRP (the major trial inclusion criterion), stipulating instead that treatment can be considered for those with 'at least two conventional risk factors for cardiovascular disease,' a group more inclusive than that studied. In contrast, the European Medicines Agency label limits treatment only to 'high risk individuals' ignoring hsCRP and using instead a post hoc definition of 'high risk' that comprised a subgroup of less than 10% of the study population who contributed but 67 events to the study total and did not show statistical significance when compared to placebo. None of the regulatory labels included the trial primary endpoint; instead, each focused on separate and different components of the primary endpoint. Similar discrepancies were found between European and North American regulatory agencies with regard to earlier pivotal trials of statins for primary prevention, but not for secondary prevention. The

Regulatory oversight of maintenance activities at nuclear power plants

International Nuclear Information System (INIS)

Pape, M.

1997-01-01

Regulation of nuclear safety in the UK is based on monitoring of compliance with licence conditions. This paper discusses legislation aspects, license conditions, license requirements for maintenance and maintenance activities in the UK. It also addresses the regulator utility interaction, the regulatory inspection of maintenance and the trends in maintenance. (author)

Application of Regulatory Focus Theory to Search Advertising

Science.gov (United States)

Mowle, Elyse N.; Georgia, Emily J.; Doss, Brian D.; Updegraff, John A.

2015-01-01

Purpose The purpose of this paper is to test the utility of regulatory focus theory principles in a real-world setting; specifically, Internet hosted text advertisements. Effect of compatibility of the ad text with the regulatory focus of the consumer was examined. Design/methodology/approach Advertisements were created using Google AdWords. Data were collected for the number of views and clicks each ad received. Effect of regulatory fit was measured using logistic regression. Findings Logistic regression analyses demonstrated that there was a strong main effect for keyword, such that users were almost six times as likely to click on a promotion advertisement as a prevention advertisement, as well as a main effect for compatibility, such that users were twice as likely to click on an advertisement with content that was consistent with their keyword. Finally, there was a strong interaction of these two variables, such that the effect of consistent advertisements was stronger for promotion searches than for prevention searches. Research limitations/implications The effect of ad compatibility had medium to large effect sizes, suggesting that individuals’ state may have more influence on advertising response than do individuals’ traits (e.g. personality traits). Measurement of regulatory fit was limited by the constraints of Google AdWords. Practical implications The results of this study provide a possible framework for ad creation for Internet advertisers. Originality/value This paper is the first study to demonstrate the utility of regulatory focus theory in online advertising. PMID:26430293

Spatial interactions database development for effective probabilistic risk assessment

International Nuclear Information System (INIS)

Liming, J. K.; Dunn, R. F.

2008-01-01

In preparation for a subsequent probabilistic risk assessment (PRA) fire risk analysis update, the STP Nuclear Operating Company (STPNOC) is updating its spatial interactions database (SID). This work is being performed to support updating the spatial interactions analysis (SIA) initially performed for the original South Texas Project Electric Generating Station (STPEGS) probabilistic safely assessment (PSA) and updated in the STPEGS Level 2 PSA and IPE Report. S/A is a large-scope screening analysis performed for nuclear power plant PRA that serves as a prerequisite basis for more detailed location-dependent, hazard-spec analyses in the PRA, such as fire risk analysis, flooding risk analysis, etc. SIA is required to support the 'completeness' argument for the PRA scope. The objectives of the current SID development effort are to update the spatial interactions analysis data, to the greatest degree practical, to be consistent with the following: the as-built plant as of December 31, 2007 the in-effect STPNOC STPEGS Units 1 and 2 PRA the current technology and intent of NUREG/CR-6850 guidance for lire risk analysis database support the requirements for PRA SIA, including fire and flooding risk analysis, established by NRC Regulatory Guide 1.200 and the ASME PRA Standard (ASME RA-S-2002 updated through ASME RA-Sc-2007,) This paper presents the approach and methodology for state-of-the-art SID development and applications, including an overview of the SIA process for nuclear power plant PRA. The paper shows how current relational database technology and existing, conventional station information sources can be employed to collect, process, and analyze spatial interactions data for the plant in an effective and efficient manner to meet the often challenging requirements of industry guidelines and standards such as NUREG/CR-6850, NRC Regulatory Guide 1.200, and ASME RA-S-2002 (updated through ASME RA-Sc 2007). This paper includes tables and figures illustrating how SIA

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

OpenAIRE

Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the exis...

Below regulatory concern - or simply exempt?

International Nuclear Information System (INIS)

Brodsky, A.

1991-01-01

The US Nuclear Regulatory Commission published a policy statement last summer on ''below regulatory concern'' (BRC), which exempted small quantities of radioactive material from regulatory control and would allow the deregulated disposal of some low level waste. The policy drew opposition from several groups. NRC is not planning to revise its BRC policy statement, but wants to develop a concensus on how to implement the policy. Although the Commission's publication of a long needed policy framework for guiding exemption decisions should be welcomed by those of us who have been concerned with making such decisions, there is an urgent need for further consensus building. The policy statement offers only broad guidelines, some of which could be confusing and seem contradictory. The policy statement by itself could further erode public confidence in the NRC's commitment to specific limits of risk, and the ability of its staff to independently evaluate the risks. Another reason why it is appropriate and urgent to embark upon consensus building involving all parties and the public, is that the risks of low level radioactive waste disposal as practiced and proposed in the United States have long been exaggerated in biased reports that receive most media attention. A consensus process needs to be established so that the public can have confidence that its concerns have been properly addressed. (author)

Trans-acting translational regulatory RNA binding proteins.

Science.gov (United States)

Harvey, Robert F; Smith, Tom S; Mulroney, Thomas; Queiroz, Rayner M L; Pizzinga, Mariavittoria; Dezi, Veronica; Villenueva, Eneko; Ramakrishna, Manasa; Lilley, Kathryn S; Willis, Anne E

2018-05-01

The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary to provide mRNA-specific translation, and these interact with 5' and 3' untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans-acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans-acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans-acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Translation Regulation Translation > Translation Mechanisms. © 2018 Medical Research Council and University of Cambridge. WIREs RNA published by Wiley Periodicals, Inc.

78 FR 18947 - Fisheries of the Northeastern United States; Tilefish Fishery Management Plan; Regulatory...

Science.gov (United States)

2013-03-28

... during the current fishing year for failure to pay the cost recovery fee, rather than not renewing the... an IFQ cost recovery fee as described in paragraph (h)(4) of this section; or any other failure to... Plan; Regulatory Amendment, Corrections, and Clarifications AGENCY: National Marine Fisheries Service...

Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

International Nuclear Information System (INIS)

Illizastigui, P.F.

2016-01-01

The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

An integer optimization algorithm for robust identification of non-linear gene regulatory networks

Directory of Open Access Journals (Sweden)

Chemmangattuvalappil Nishanth

2012-09-01

Full Text Available Abstract Background Reverse engineering gene networks and identifying regulatory interactions are integral to understanding cellular decision making processes. Advancement in high throughput experimental techniques has initiated innovative data driven analysis of gene regulatory networks. However, inherent noise associated with biological systems requires numerous experimental replicates for reliable conclusions. Furthermore, evidence of robust algorithms directly exploiting basic biological traits are few. Such algorithms are expected to be efficient in their performance and robust in their prediction. Results We have developed a network identification algorithm to accurately infer both the topology and strength of regulatory interactions from time series gene expression data in the presence of significant experimental noise and non-linear behavior. In this novel formulism, we have addressed data variability in biological systems by integrating network identification with the bootstrap resampling technique, hence predicting robust interactions from limited experimental replicates subjected to noise. Furthermore, we have incorporated non-linearity in gene dynamics using the S-system formulation. The basic network identification formulation exploits the trait of sparsity of biological interactions. Towards that, the identification algorithm is formulated as an integer-programming problem by introducing binary variables for each network component. The objective function is targeted to minimize the network connections subjected to the constraint of maximal agreement between the experimental and predicted gene dynamics. The developed algorithm is validated using both in silico and experimental data-sets. These studies show that the algorithm can accurately predict the topology and connection strength of the in silico networks, as quantified by high precision and recall, and small discrepancy between the actual and predicted kinetic parameters

The role of the US regulatory process in public acceptance of nuclear power

International Nuclear Information System (INIS)

Rowden, M.A.

1977-01-01

This paper focuses, on NRC's regulatory responsibilities in relation to public acceptance of nuclear power. Since public attitudes in the United States may influence reaction to nuclear power in other nations, it is fair to say that the credibility of our regulatory program has international significance. Stated simply, unless the public is convinced that the regulatory process is effective in assuring safety, safeguarding nuclear facilities and materials, and protecting the environment, the use of nuclear power could be curtailed or even brought to a halt. Not only must the regulatory process be effective, it must at the same time be recognized by the public as being effective. Opinion polls in the United States have shown consistently that a majority of Americans believe it is important to develop nuclear power to help meet our future energy needs. The direction of public concern has shifted from year to year. Most recently, public apprehension has been expressed about the potential hazards of long-term storage of the high-level wastes from spent fuel reprocessing, and about the risks that nuclear materials and facilities may be subject to theft or diversion or sabotage. Uppermost in the public mind is the question whether the regulatory process can cope with these potential threats to public health and safety. The licensing process of the NRC is conducted in full public view. Issues of a generic nature are aired in rulemaking hearings, while each proposal to construct and operate a nuclear power plant or a facility such as fuel reprocessing plant is the subject of public hearings, which are held near the site of the proposed plant. During the last two years, we have noted that some persons who object to nuclear power plants have indicated that they believe that decisions to permit construction of such plants should be made at the State government level, rather than by a Federal agency. As a result, there now are movements to enact State laws and to set up State

[Integrative parent-infant psychotherapy for early regulatory and relationship disorders].

Science.gov (United States)

Papousek, Mechthild; de Chuquisengo, Ruth Wollwerth

2006-01-01

The author introduces both the concept and practice of Integrative Parent-Infant Psychotherapy (IPI-P), a treatment specifically designed for the most frequent developmental problems and psychological needs of infants and their parents. Based on growing knowledge from interdisciplinary infancy research, both basic and clinical, IPI-P has been developed and practised in the "Munich Interdisciplinary Research and Intervention Program" for early regulatory and relationship disorders since the early nineties. Preverbal parent-infant communication represents both the port of entry into the system and the main focus of diagnostics, developmental counselling, interaction guidance, or psychodynamic psychotherapy of distorted communication and distressed/disordered relationships. The method of videomicroanalysis during video-feedback with the parent has proven particularly efficient--while observing, reliving and working through brief episodes of recorded parent-infant interaction. The author illustrates the diagnostic and therapeutic procedures with excerpts from psychotherapy of a toddler with an age-specific regulatory disorder in the context of severely distressed primary relationships.

The evolving regulation of uranium recovery operations in the United States: Inovative approaches are necessary for cost effective regulatory oversight

International Nuclear Information System (INIS)

Thompson, A.J.; Lehrenbaum, W.U.; Lashway, D.C.

2000-01-01

The US domestic uranium industry is at a crossroads. Historic low prices for uranium, combined with stringent and often irrational regulatory requirements, pose a very real threat to the industry's continued viability. The Nuclear Regulatory Commission has taken a number of innovative steps to reform and rationalize its regulatory program. However, if the domestic uranium recovery industry is to remain viable, additional steps toward innovation and reform are needed, and effective implementation of reforms adopted by the Commission is essential. (author)

International Nuclear Safety Experts Conclude IAEA Peer Review of Korea's Regulatory System

International Nuclear Information System (INIS)

2011-01-01

organizational change management are needed; Regulations and guides should be developed for decommissioning and management of spent fuel. Regulations should be changed to require a quality assurance plan for the licensing of research and test reactors; and Enhancements to the licensing process are needed to clarify and strengthen the safety information in license amendments and assessment reports. Background The IRRS mission to the Republic of Korea was conducted from 10 to 22 July, mainly in Daejeon. The team also visited several nuclear installations, including a nuclear power plant, a research reactor and the country's emergency response centres. The IRRS team reviewed the following regulatory areas: the government's responsibilities and functions in the nuclear safety regime; the responsibilities and functions of the regulatory body and its management system; the activities of the regulatory body including authorizations; review and assessment; inspection and enforcement processes; and the development of regulations and guides. Team experts came from 14 different countries: Canada, China, the Czech Republic, Finland, France, Hungary, Mexico, Slovakia, Slovenia, Sweden, Switzerland, the United Kingdom, United Arab Emirates and the United States. About IRRS Missions IRRS missions are designed to strengthen and enhance the effectiveness of the national nuclear regulatory infrastructure of States, whilst recognizing the ultimate responsibility of each State to ensure safety in this area. This is done through consideration of both regulatory, technical and policy issues, with comparisons against IAEA safety standards and, where appropriate, good practices elsewhere. (IAEA)

Regulatory challenges facing the global nuclear energy partnership

International Nuclear Information System (INIS)

Lyman, Edwin S.

2007-01-01

In January 2006 the Department of Energy (DOE) announced the creation of the Global Nuclear Energy Partnership (GNEP), an ambitious plan to reshape the nuclear energy production sector both in the United States and worldwide. If fully realized in the United States, GNEP would entail the construction of a large number of sodium-cooled fast reactors utilizing actinide-based fuels, multiple commercial-scale reprocessing plants for both light-water and fast reactors, and fast reactor fuel fabrication plants. It appears likely that the first commercial-scale GNEP facilities, as well as a future full-scale GNEP complex, would fall under the licensing jurisdiction of the Nuclear Regulatory Commission (NRC). This will be a challenging endeavor for the NRC, primarily because the proposed GNEP facilities will in large part be based on novel and untested designs and processes that have not been developed on a commercial scale. In order to effectively regulate the GNEP complex, the NRC will have to quickly address the many technical and policy questions that will arise in any GNEP licensing scheme. This paper identifies some difficult issues that will be encountered in GNEP licensing by examining the potential implications of NRC's current policies and regulatory requirements, and analyzing the impacts of some emerging post-9/11 security issues. (author)

Regulatory acceptance of the proposed well abandonment program for the present landfill, Operable Unit 7, Rocky Flats Environmental Technology Site, Golden, Colorado

International Nuclear Information System (INIS)

Wood, M.R.

1995-01-01

The regulatory agencies approved a well abandonment program for the Present Landfill, Operable Unit (OU) 7 at the Rocky Flats Environmental Technology Site, only three months after preparation. The proposed well abandonment program consists of abandoning 26 of the 54 existing monitoring wells in OU 7 that are currently sampled quarterly as Resource Conservation and Recovery Act (RCRA) compliance wells or sitewide groundwater protection wells. Well abandonment was proposed on the basis that the purpose of each well has been fulfilled, the wells fall under the footprint of the landfill cap, the presence of the wells would compromise the integrity of the cap because holes would have to be cut in the synthetic liner, and unequal compaction of the fill material around the wells would potentially cause differential settlement of the cap. The proposal provided the technical justification to abandon the wells in place. The timely approval of the proposal by the regulatory agencies will allow the abandonment of the wells during fiscal year 1995 under the sitewide Well Abandonment and Replacement Program (WARP). Cost savings resulting from a decrease in the number of wells to be sampled under the groundwater monitoring program are estimated at $416,000 per year. This paper presents a summary of the well abandonment program, discusses the timely approvals required for implementation, and present the potential cost savings that can be achieved through implementation of the program

On the Concept of Cis-regulatory Information: From Sequence Motifs to Logic Functions

Science.gov (United States)

Tarpine, Ryan; Istrail, Sorin

The regulatory genome is about the “system level organization of the core genomic regulatory apparatus, and how this is the locus of causality underlying the twin phenomena of animal development and animal evolution” (E.H. Davidson. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution, Academic Press, 2006). Information processing in the regulatory genome is done through regulatory states, defined as sets of transcription factors (sequence-specific DNA binding proteins which determine gene expression) that are expressed and active at the same time. The core information processing machinery consists of modular DNA sequence elements, called cis-modules, that interact with transcription factors. The cis-modules “read” the information contained in the regulatory state of the cell through transcription factor binding, “process” it, and directly or indirectly communicate with the basal transcription apparatus to determine gene expression. This endowment of each gene with the information-receiving capacity through their cis-regulatory modules is essential for the response to every possible regulatory state to which it might be exposed during all phases of the life cycle and in all cell types. We present here a set of challenges addressed by our CYRENE research project aimed at studying the cis-regulatory code of the regulatory genome. The CYRENE Project is devoted to (1) the construction of a database, the cis-Lexicon, containing comprehensive information across species about experimentally validated cis-regulatory modules; and (2) the software development of a next-generation genome browser, the cis-Browser, specialized for the regulatory genome. The presentation is anchored on three main computational challenges: the Gene Naming Problem, the Consensus Sequence Bottleneck Problem, and the Logic Function Inference Problem.

Review of regulatory requirements relevant to calibration of monitoring instruments in research reactors

Energy Technology Data Exchange (ETDEWEB)

Gomaa, Hassan; Khedr, Ahmed; El-Din Talha, Kamal [Egyptian Nuclear and Radiological Regulatory Authority, Cairo (Egypt). Nuclear Safety Engineering Dept.

2015-05-15

The objective of this work is to demonstrate the regulatory requirements pertaining to calibration of monitoring instruments in research reactors. The regulatory statements concerning this subject in IAEA safety standards and the implementation of such regulations in twelve countries with different levels of nuclear programs are surveyed: Australia, Bulgaria, Canada, Egypt, Finland, Germany, Hungary, Slovenia, South Korea, Spain, United Kingdom of England and United States of America. In addition, the requirements of ISO/IEC17025 and NUPIC (Nuclear Utilities Procurement Issues Committee) are compared. Seven technical and administrate aspects are suggested as the comparison criteria and the explicit expression of the statements, the level of document (i.e.: act, requirement or guide) are the considered resources. The main differences and similarities between the different approaches are identified in order to provide an input for future development of the national regulations.

"I can be happy even when I lose the game": the influence of chronic regulatory focus and primed self-construal on exergamers' mood.

Science.gov (United States)

Jin, Seung-A Annie

2010-08-01

This research explored the effects of priming interdependent self-construals (collective self ) versus independent self-construals (private self ) on exergame players' mood in response to negative performance feedback. An experiment was conducted to test the interaction effects of self-construal priming as a situational factor and game players' chronic regulatory focus as an individual difference factor. To this end, the author leveraged a video-game console (Wii) and an exergame (Dance Dance Revolution) in a controlled, randomized 2 x 2 (experimental priming: interdependent self-construal vs. independent self-construal x game players' chronic promotion regulatory focus: low vs. high) between-subjects factorial design experiment (N = 58). The results of a two-way analysis of variance demonstrated the proposed interaction effect between primed self-construal and game players' chronic regulatory focus on the game players' mood in response to negative performance. The theoretical mechanism underlying the two-way interaction is explicated by regulatory focus and the primed self-construals is explicated by regulatory focus theory and two-basket theory. Practical implications for game developers and theoretical contributions to video-game research are discussed.

Green electricity policies in the United States: case study

International Nuclear Information System (INIS)

Menz, Fredric C.

2005-01-01

While there has been interest in promoting the use of renewable energy in electricity production for a number of years in the United States, the market share of non-hydro renewable energy sources in electricity production has remained at about 2 percent over the past decade. The paper reviews the principal energy resources used for electricity production, considers the changing regulatory environment for the electricity industry, and describes government policies that have been used to promote green electricity in the United States, with an emphasis on measures adopted by state governments. Factors influencing the development of green power markets are also discussed, including underlying economic issues, public policy measures, the regulatory environment, external costs, and subsidies. Without significant increases in fossil fuel prices, much more stringent environmental regulations, or significant changes in electricity customer preferences, green electricity markets are likely to develop slowly in the United States

Behavioral Economic Laboratory Research in Tobacco Regulatory Science.

Science.gov (United States)

Tidey, Jennifer W; Cassidy, Rachel N; Miller, Mollie E; Smith, Tracy T

2016-10-01

Research that can provide a scientific foundation for the United States Food and Drug Administration (FDA) tobacco policy decisions is needed to inform tobacco regulatory policy. One factor that affects the impact of a tobacco product on public health is its intensity of use, which is determined, in part, by its abuse liability or reinforcing efficacy. Behavioral economic tasks have considerable utility for assessing the reinforcing efficacy of current and emerging tobacco products. This paper provides a narrative review of several behavioral economic laboratory tasks and identifies important applications to tobacco regulatory science. Behavioral economic laboratory assessments, including operant self-administration, choice tasks and purchase tasks, can be used generate behavioral economic data on the effect of price and other constraints on tobacco product consumption. These tasks could provide an expedited simulation of the effects of various tobacco control policies across populations of interest to the FDA. Tobacco regulatory research questions that can be addressed with behavioral economic tasks include assessments of the impact of product characteristics on product demand, assessments of the abuse liability of novel and potential modified risk tobacco products (MRTPs), and assessments of the impact of conventional and novel products in vulnerable populations.

Differential susceptibility in education: interaction between genes, regulatory skills, and computer games

OpenAIRE

Kegel, Cornelia Aria Theodore

2011-01-01

Early interventions address concerns that an unacceptably large number of children are already, by four years of age, lacking in competencies fundamental to success in learning to read. Using a randomized controlled trial, the studies presented in this thesis examined program features and children’s behavioral and genetic characteristics (e.g., regulatory skills and DRD4) that might be of influence on learning effects of an exemplary computer intervention program Living Letters. Our conclusio...

Ten years of unitization in Brazil; Dez anos de unitizacoes no Brazil

Energy Technology Data Exchange (ETDEWEB)

Bonolo, Daniel Dellamora; Almeida, Mateus Passeri de [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil)

2012-07-01

The unitization concept, as used by the oil industry, was established in Brazil through Art 27 of the Law 9.478/97, also known as the Petroleum Law, and the first process was initiated in 2002. Within these 10 years, four processes were started and finalized, approved by ANP. These processes were developed in a maturing regulatory environment, which was improved in 2010. This article deals with the peculiarities of these processes, putting in context the regulatory framework and doubts at the time. We also verse about the regulatory scene after 2010, pointing out the main enhancements made. It is concluded that, although essential, an elaborated regulation is not the only important factor for the success of a unitization agreement, but also the agreement between parties, which has been encouraged by ANP.(author)

Regulatory networks, legal federalism, and multi-level regulatory systems

OpenAIRE

Kerber, Wolfgang; Wendel, Julia

2016-01-01

Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

Regulatory variation: an emerging vantage point for cancer biology.

Science.gov (United States)

Li, Luolan; Lorzadeh, Alireza; Hirst, Martin

2014-01-01

Transcriptional regulation involves complex and interdependent interactions of noncoding and coding regions of the genome with proteins that interact and modify them. Genetic variation/mutation in coding and noncoding regions of the genome can drive aberrant transcription and disease. In spite of accounting for nearly 98% of the genome comparatively little is known about the contribution of noncoding DNA elements to disease. Genome-wide association studies of complex human diseases including cancer have revealed enrichment for variants in the noncoding genome. A striking finding of recent cancer genome re-sequencing efforts has been the previously underappreciated frequency of mutations in epigenetic modifiers across a wide range of cancer types. Taken together these results point to the importance of dysregulation in transcriptional regulatory control in genesis of cancer. Powered by recent technological advancements in functional genomic profiling, exploration of normal and transformed regulatory networks will provide novel insight into the initiation and progression of cancer and open new windows to future prognostic and diagnostic tools. © 2013 Wiley Periodicals, Inc.

Framing of information on the use of public finances, regulatory fit of recipients and tax compliance

Science.gov (United States)

Holler, Marianne; Hoelzl, Erik; Kirchler, Erich; Leder, Susanne; Mannetti, Lucia

2010-01-01

Information campaigns to increase tax compliance could be framed in different ways. They can either highlight the potential gains when tax compliance is high, or the potential losses when compliance is low. According to regulatory focus theory, such framing should be most effective when it is congruent with the promotion or prevention focus of its recipients. Two studies confirmed the hypothesized interaction effects between recipients' regulatory focus and framing of information campaigns, with tax compliance being highest under conditions of regulatory fit. To address taxpayers effectively, information campaigns by tax authorities should consider the positive and negative framing of information, and the moderating effect of recipients' regulatory focus. PMID:20495689

Framing of information on the use of public finances, regulatory fit of recipients and tax compliance.

Science.gov (United States)

Holler, Marianne; Hoelzl, Erik; Kirchler, Erich; Leder, Susanne; Mannetti, Lucia

2008-08-01

Information campaigns to increase tax compliance could be framed in different ways. They can either highlight the potential gains when tax compliance is high, or the potential losses when compliance is low. According to regulatory focus theory, such framing should be most effective when it is congruent with the promotion or prevention focus of its recipients. Two studies confirmed the hypothesized interaction effects between recipients' regulatory focus and framing of information campaigns, with tax compliance being highest under conditions of regulatory fit. To address taxpayers effectively, information campaigns by tax authorities should consider the positive and negative framing of information, and the moderating effect of recipients' regulatory focus.

International Expert Team Concludes IAEA Peer Review of Finland's Regulatory Framework for Nuclear and Radiation Safety

International Nuclear Information System (INIS)

2012-01-01

Full text: International safety experts today concluded a two-week International Atomic Energy Agency (IAEA) mission to review the regulatory framework for nuclear and radiation safety in Finland. In its preliminary report, the Integrated Regulatory Review Service (IRRS) mission team found that the Radiation and Nuclear Safety Authority of Finland (STUK) is a competent and highly credible regulator that is open and transparent and derives great strength from the technical competence of its staff. ''Finland's comprehensive regulatory framework allows STUK to operate in practice as an independent regulatory body,'' said team leader Philippe Jamet, a commissioner of the French regulatory body ASN. The mission was conducted at the request of the Government of Finland from 15-26 October. The team interviewed members of STUK and officials from various ministries, as well as key players in the Finnish safety framework. Such IRRS missions are peer reviews based on IAEA Safety Standards, not inspections or audits. The team was made up of 18 members from Bulgaria, Canada, the Czech Republic, France, Germany, Iceland, Ireland, Romania, the Russian Federation, South Africa, Slovakia, Slovenia, Spain, Sweden, the United Arab Emirates, the United Kingdom and the United States, as well as six IAEA staff members. 'The IRRS mission and preparation for it was a unique occasion that involved the whole organization, provided motivation for improvement of the safety framework in Finland and assists STUK review its mission', said Tero Varjoranta, Director General of STUK. The IRRS team identified a number of good practices and achievements, including: - STUK's excellence in its safety assessment of nuclear power plants and waste repositories, in particular its demonstration that long-term political commitment is a necessity to sustain the creation of a waste repository as well as its regulatory oversight of medical applications of radiation sources; and - STUK's excellent record in

78 FR 65007 - Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 3

Science.gov (United States)

2013-10-30

... NUCLEAR REGULATORY COMMISSION [Docket No. 052-00026; NRC-2008-0252] Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 3 AGENCY: Nuclear Regulatory Commission. ACTION: Determination of inspections, tests, analyses, and acceptance criteria completion...

Regulatory Oversight for New Projects - Challenges and Improvement in Regulation

International Nuclear Information System (INIS)

Lall, F.

2016-01-01

From inception, there has been rise in number of Nuclear Power Plants (NPP) even though very few accidents / events led to intermittent setbacks. However these accidents / events have posed challenges towards enhancement of safety and scope of regulation in all phases of NPP such as siting, design, construction, commissioning and decommissioning. It is essential to ensure compliance to these enhanced safety requirements during all phases of NPP. New and evolutionary reactors are under threshold for regulatory consideration world over. The variety of technologies and genres by themselves pose challenges to regulatory bodies. These challenges are to be addressed through systematic enhancement of the regulation including updating of regulatory documents. The paper touches upon some key elements to be considered towards such enhancement of regulation during all stages of NPP. These being; ensuring quality assurance, regulatory oversight especially over supply chain and contractors, counterfeit material specifically in case of international dealings, emergency handling in case of multi-unit site, feedback and associated enhancements from international events, construction experience database and feedback for safety enhancement, qualification and acceptance of first of a kind systems, regulatory enforcement specifically in case of imported reactors and maintaining interface between safety and security. Regulation in present context has become dynamic and Regulatory bodies need to continue enhancement of its current regulation taking into account the technological developments, feedback from construction, operation and accidents in the current fleet of plants. The paper touches upon some of these elements and highlights the challenges and improvements in regulation. (author)

Drug-device combination products: regulatory landscape and market growth.

Science.gov (United States)

Bayarri, L

2015-08-01

Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Regulatory focus and generalized trust: the impact of prevention-focused self-regulation on trusting others.

Science.gov (United States)

Keller, Johannes; Mayo, Ruth; Greifeneder, Rainer; Pfattheicher, Stefan

2015-01-01

The current research suggests that taking self-regulatory mechanisms into account provides insights regarding individuals' responses to threats in social interactions. In general, based on the notion that a prevention-focused orientation of self-regulation is associated with a need for security and a vigilant tendency to avoid losses and other types of negative events we advocate that a prevention-focused orientation, both as a disposition as well as a situationally induced state, lowers generalized trust, thus hindering cooperation within social interactions that entail threats. Specifically, we found that the more individuals' habitual self-regulatory orientation is dominated by a prevention focus, the less likely they are to score high on a self-report measure of generalized trust (Study 1), and to express trust in a trust game paradigm as manifested in lower sums of transferred money (Studies 2 and 3). Similar findings were found when prevention focus was situationally manipulated (Study 4). Finally, one possible factor underlying the impact of prevention-focused self-regulation on generalized trust was demonstrated as individuals with a special sensitivity to negative information were significantly affected by a subtle prevention focus manipulation (versus control condition) in that they reacted with reduced trust in the trust game (Study 5). In sum, the current findings document the crucial relevance of self-regulatory orientations as conceptualized in regulatory focus theory regarding generalized trust and responses to threats within a social interaction. The theoretical and applied implications of the findings are discussed.

Regulatory Focus and Generalized Trust: The Impact of Prevention-focused Self-regulation on Trusting Others

Directory of Open Access Journals (Sweden)

Johannes eKeller

2015-03-01

Full Text Available The current research suggests that taking self-regulatory mechanisms into account provides insights regarding individuals’ responses to threats in social interactions. In general, based on the notion that a prevention-focused orientation of self-regulation is associated with a need for security and a vigilant tendency to avoid losses and other types of negative events we advocate that a prevention-focused orientation, both as a disposition as well as a situationally induced state, lowers generalized trust, thus hindering cooperation within social interactions that entail threats. Specifically, we found that the more individuals’ habitual self-regulatory orientation is dominated by a prevention focus, the less likely they are to score high on a self-report measure of generalized trust (Study 1, and to express trust in a trust game paradigm as manifested in lower sums of transferred money (Studies 2 and 3. Similar findings were found when prevention focus was situationally manipulated (Study 4. Finally, one possible factor underlying the impact of prevention-focused self-regulation on generalized trust was demonstrated as individuals with a special sensitivity to negative information were significantly affected by a subtle prevention focus manipulation (vs. control condition in that they reacted with reduced trust in the trust game (Study 5. In sum, the current findings document the crucial relevance of self-regulatory orientations as conceptualized in regulatory focus theory regarding generalized trust and responses to threats within a social interaction. The theoretical and applied implications of the findings are discussed.

Conflicts and misapplications of ANSI N509, N510, U.S. NRC Regulatory Guide 1.52 and 1.140

International Nuclear Information System (INIS)

Kovach, J.L.

1987-01-01

The nuclear industry in the early 1970's attempted to standardize air cleaning system design and testing by the development of ANSI N509, Nuclear Power Air Cleaning Units and Components and ANSI N510, Testing of Nuclear Air Cleaning Systems. Parallel to those and leaning somewhat on the same information, the USNRC has prepared first, Regulatory Guide 1.52, Design, Testing, and Maintenance Criteria for Atmosphere Clean Up of System Air Filtration and Adsorption Units of Light Water Cooled Nuclear Reactor plants, and regulatory guide 1.140, Design, Testing, and Maintenance Criteria for Normal Ventilation Exhaust System Air Filtration and Adsorption Units of Light Water Cooled Nuclear Power Plants. These documents were a good starting point and should have been the basis for the evolution of sound engineering practices. Instead of that path, the subsequent revisions were narrow in scope, uncoordinated, rarely based on experience and became nearly unworkable. Starting with the scope statement (or equivalent for the regulatory guides) the problems began to occur. Ten recommendations are made for eliminating the troublesome aspects of the regulations

QuIN: A Web Server for Querying and Visualizing Chromatin Interaction Networks.

Directory of Open Access Journals (Sweden)

Asa Thibodeau

2016-06-01

Full Text Available Recent studies of the human genome have indicated that regulatory elements (e.g. promoters and enhancers at distal genomic locations can interact with each other via chromatin folding and affect gene expression levels. Genomic technologies for mapping interactions between DNA regions, e.g., ChIA-PET and HiC, can generate genome-wide maps of interactions between regulatory elements. These interaction datasets are important resources to infer distal gene targets of non-coding regulatory elements and to facilitate prioritization of critical loci for important cellular functions. With the increasing diversity and complexity of genomic information and public ontologies, making sense of these datasets demands integrative and easy-to-use software tools. Moreover, network representation of chromatin interaction maps enables effective data visualization, integration, and mining. Currently, there is no software that can take full advantage of network theory approaches for the analysis of chromatin interaction datasets. To fill this gap, we developed a web-based application, QuIN, which enables: 1 building and visualizing chromatin interaction networks, 2 annotating networks with user-provided private and publicly available functional genomics and interaction datasets, 3 querying network components based on gene name or chromosome location, and 4 utilizing network based measures to identify and prioritize critical regulatory targets and their direct and indirect interactions.QuIN's web server is available at http://quin.jax.org QuIN is developed in Java and JavaScript, utilizing an Apache Tomcat web server and MySQL database and the source code is available under the GPLV3 license available on GitHub: https://github.com/UcarLab/QuIN/.

QuIN: A Web Server for Querying and Visualizing Chromatin Interaction Networks.

Science.gov (United States)

Thibodeau, Asa; Márquez, Eladio J; Luo, Oscar; Ruan, Yijun; Menghi, Francesca; Shin, Dong-Guk; Stitzel, Michael L; Vera-Licona, Paola; Ucar, Duygu

2016-06-01

Recent studies of the human genome have indicated that regulatory elements (e.g. promoters and enhancers) at distal genomic locations can interact with each other via chromatin folding and affect gene expression levels. Genomic technologies for mapping interactions between DNA regions, e.g., ChIA-PET and HiC, can generate genome-wide maps of interactions between regulatory elements. These interaction datasets are important resources to infer distal gene targets of non-coding regulatory elements and to facilitate prioritization of critical loci for important cellular functions. With the increasing diversity and complexity of genomic information and public ontologies, making sense of these datasets demands integrative and easy-to-use software tools. Moreover, network representation of chromatin interaction maps enables effective data visualization, integration, and mining. Currently, there is no software that can take full advantage of network theory approaches for the analysis of chromatin interaction datasets. To fill this gap, we developed a web-based application, QuIN, which enables: 1) building and visualizing chromatin interaction networks, 2) annotating networks with user-provided private and publicly available functional genomics and interaction datasets, 3) querying network components based on gene name or chromosome location, and 4) utilizing network based measures to identify and prioritize critical regulatory targets and their direct and indirect interactions. QuIN's web server is available at http://quin.jax.org QuIN is developed in Java and JavaScript, utilizing an Apache Tomcat web server and MySQL database and the source code is available under the GPLV3 license available on GitHub: https://github.com/UcarLab/QuIN/.

Safety culture as a matter of regulatory control and regulatory effectiveness

International Nuclear Information System (INIS)

Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

2002-01-01

More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

78 FR 53483 - Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 3

Science.gov (United States)

2013-08-29

... NUCLEAR REGULATORY COMMISSION [Docket No. 052-00025; NRC-2008-0252] Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 3 AGENCY: Nuclear Regulatory Commission. ACTION: Determination of inspections, tests, analyses, and acceptance criteria (ITAAC) completion...

78 FR 53484 - Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 4

Science.gov (United States)

2013-08-29

... NUCLEAR REGULATORY COMMISSION [Docket No. 052-00026; NRC-2008-0252] Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 4 AGENCY: Nuclear Regulatory Commission. ACTION: Determination of inspections, tests, analyses, and acceptance criteria (ITAAC) completion...

Fukushima Daiichi Unit 1 Ex-Vessel Prediction: Core Concrete Interaction

International Nuclear Information System (INIS)

Robb, Kevin R; Farmer, Mitchell; Francis, Matthew W

2015-01-01

Lower head failure and corium concrete interaction were predicted to occur at Fukushima Daiichi Unit 1 (1F1) by several different system-level code analyses, including MELCOR v2.1 and MAAP5. Although these codes capture a wide range of accident phenomena, they do not contain detailed models for ex-vessel core melt behavior. However, specialized codes exist for analysis of ex-vessel melt spreading (e.g., MELTSPREAD) and long-term debris coolability (e.g., CORQUENCH). On this basis, an analysis was carried out to further evaluate ex-vessel behavior for 1F1 using MELTSPREAD and CORQUENCH. Best-estimate melt pour conditions predicted by MELCOR v2.1 and MAAP5 were used as input. MELTSPREAD was then used to predict the spatially dependent melt conditions and extent of spreading during relocation from the vessel. The results of the MELTSPREAD analysis are reported in a companion paper. This information was used as input for the long-term debris coolability analysis with CORQUENCH.

A HLA class I cis-regulatory element whose activity can be modulated by hormones.

Science.gov (United States)

Sim, B C; Hui, K M

1994-12-01

To elucidate the basis of the down-regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA-binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis-regulatory element (NRE) has been identified using band-shift assays employing DNA sequences derived from the 5'-flanking region of HLA class I genes. This 9-bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expression of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti-sense orientation. More interestingly, NRE can suppress dexamethasone-mediated gene activation in the context of the reported glucocorticoid-responsive element (GRE) in MCF-7 cells but has no influence on the estrogen-mediated transcriptional activation of MCF-7 cells in the context of the reported estrogen-responsive element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down-regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans-activators are novel and suggest a versatile form of transcriptional control.

Upgrading nuclear regulatory infrastructure in Armenia

International Nuclear Information System (INIS)

Martirosyan, A.; Amirjanyan, A.; Kacenelenbogen, S.

2010-01-01

Armenia is contemplating an upgrade to its national power generation capacity to meet replacement and future energy needs. Unit 2 of ANPP is scheduled for shutdown after replacement power generation capacities are in place. A recent alternative energy study indicates viability of the nuclear option to replace this capacity. Some technology-specific proposals are being considered by the Ministry of Energy of Armenia. It is likely that the reactor technology decision will be made in the not too distant future. The existing reactor continues to be operated in the regulatory framework developed in the Soviet Union and adopted in Armenia. Given the interest in the new reactor, Armenia launched a project to review the existing system of regulation and to bring it into harmony with modern practice in preparation for the new reactor project development. The new regulatory framework will be needed as a basis for any potential tendering process. The US NRC and ANRA have agreed to perform a review and update nuclear legislation and the system of regulation in this area. The first step in this process was to develop an action plan for such program. The action plan describes the overall strategy of ANRA to modify existing or develop new processes and requirements, identifies the major Laws that need to be reviewed given practical legal considerations to construct and operate the reactor and Armenia's international obligations under various conventions. This work included review of existing models of regulation in different countries with 'small' nuclear program, including IAEA recommendations as well as existing legislation in Armenia in this area and development of a strategy for the regulatory model development. In addition, the plan to develop requirements for ANRA staffing and training needs to meet its regulatory obligations under the new reactor development process was developed

78 FR 38411 - Vogtle Electric Generating Plant, Unit 4; Inspections, Tests, Analyses, and Acceptance Criteria

Science.gov (United States)

2013-06-26

... Plant, Unit 4; Inspections, Tests, Analyses, and Acceptance Criteria AGENCY: Nuclear Regulatory Commission. ACTION: Determination of inspections, tests, analyses, and acceptance criteria completion. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) staff has determined that the inspections, tests...

Electricity generation: regulatory mechanisms to incentive renewable alternative energy sources in Brazil

International Nuclear Information System (INIS)

Cavaliero, Carla Kazue Nakao; Silva, E.P. da

2005-01-01

The dissemination of renewable alternative energy sources for electricity generation has always being done through regulatory mechanisms, created and managed by the government of each country. Since these sources are more costly to generate, they have received incentives in response to worldwide environmental concerns, above all with regard to the reduction of CO 2 emissions. In Brazil, the electricity generation from renewable alternative sources is experiencing a new phase of growth. Until a short time ago, environmental appeal was the strongest incentive to these sources in Brazil but it was insufficient to attain its objective. With the electricity crisis and the rationing imposed in 2001, another important factor gained awareness: the need to diversify energy sources. Within this context, this work has the objective of analyzing the regulatory mechanisms recently developed to stimulate electricity generation from renewable alternative energy sources in Brazil by following the experience of other countries such as the United States, United Kingdom and Germany

The African Health Profession Regulatory Collaborative for Nurses and Midwives

Directory of Open Access Journals (Sweden)

McCarthy Carey F

2012-08-01

Full Text Available Abstract Background More than thirty-five sub-Saharan African countries have severe health workforce shortages. Many also struggle with a mismatch between the knowledge and competencies of health professionals and the needs of the populations they serve. Addressing these workforce challenges requires collaboration among health and education stakeholders and reform of health worker regulations. Health professional regulatory bodies, such as nursing and midwifery councils, have the mandate to reform regulations yet often do not have the resources or expertise to do so. In 2011, the United States of America Centers for Disease Control and Prevention began a four-year initiative to increase the collaboration among national stakeholders and help strengthen the capacity of health professional regulatory bodies to reform national regulatory frameworks. The initiative is called the African Health Regulatory Collaborative for Nurses and Midwives. This article describes the African Health Regulatory Collaborative for Nurses and Midwives and discusses its importance in implementing and sustaining national, regional, and global workforce initiatives. Discussion The African Health Profession Regulatory Collaborative for Nurses and Midwives convenes leaders responsible for regulation from 14 countries in East, Central and Southern Africa. It provides a high profile, south-to-south collaboration to assist countries in implementing joint approaches to problems affecting the health workforce. Implemented in partnership with Emory University, the Commonwealth Secretariat, and the East, Central and Southern African College of Nursing, this initiative also supports four to five countries per year in implementing locally-designed regulation improvement projects. Over time, the African Health Regulatory Collaborative for Nurses and Midwives will help to increase the regulatory capacity of health professional organizations and ultimately improve regulation and

[Effects of functional interactions between nonhomologous insulators Wari and Su(Hw)].

Science.gov (United States)

Erokhin, M M; Georgiev, P G; Chetverina, D A

2010-01-01

Insulators are regulatory DNA elements restricting gene activation by enhancers. Interactions between insulators can lead to both insulation and activation of promoters by enhancers. In this work, we analyzed the effects of interaction of two Drosophila insulators, Wari and Su(Hw). The functional interaction between these insulators was found to enhance the activity of the Su(Hw) insulator only, but not of the Wari insulator. This suggests that the formation of a chromatin loop between interacting insulators is not a key factor for enhancement of insulation, which is in disagreement with the main idea of structural models. In addition, the effect of interaction between Wari and Su(Hw) depends on a distance between them and on the position in the system relative to other regulatory elements.

WWER nuclear waste management regulatory experience in Finland

International Nuclear Information System (INIS)

Varjoranta, Tero

2000-01-01

About 30% of all electricity produced in Finland is generated by nuclear power. Four reactors, with a total capacity of 2 656 MW e (net), are currently in operation. At Loviisa, there are two 488 MW e WWER units (recently upgraded 440-units) and at Olkiluoto two 840 MW e BWR units. At the Loviisa plant conditioning, storage and final disposal of low-and intermediate-level wastes from reactor operation will take place at the NPP sites. Intermediate level ion exchange resins and evaporation concentrates are currently stored in tanks. However, a license application for constructing a solidification plant based on cementation is currently under STUKs regulatory review. The construction of the final repository for I/LLW at the Loviisa site was started in 1993 and the Government granted the operating license in 1998. The nuclear legislation requires disposal of spent fuel into the Finnish bedrock. (Authors)

DnaA protein DNA-binding domain binds to Hda protein to promote inter-AAA+ domain interaction involved in regulatory inactivation of DnaA.

Science.gov (United States)

Keyamura, Kenji; Katayama, Tsutomu

2011-08-19

Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis.

DnaA Protein DNA-binding Domain Binds to Hda Protein to Promote Inter-AAA+ Domain Interaction Involved in Regulatory Inactivation of DnaA*

Science.gov (United States)

Keyamura, Kenji; Katayama, Tsutomu

2011-01-01

Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis. PMID:21708944

Creating and validating cis-regulatory maps of tissue-specific gene expression regulation

Science.gov (United States)

O'Connor, Timothy R.; Bailey, Timothy L.

2014-01-01

Predicting which genomic regions control the transcription of a given gene is a challenge. We present a novel computational approach for creating and validating maps that associate genomic regions (cis-regulatory modules–CRMs) with genes. The method infers regulatory relationships that explain gene expression observed in a test tissue using widely available genomic data for ‘other’ tissues. To predict the regulatory targets of a CRM, we use cross-tissue correlation between histone modifications present at the CRM and expression at genes within 1 Mbp of it. To validate cis-regulatory maps, we show that they yield more accurate models of gene expression than carefully constructed control maps. These gene expression models predict observed gene expression from transcription factor binding in the CRMs linked to that gene. We show that our maps are able to identify long-range regulatory interactions and improve substantially over maps linking genes and CRMs based on either the control maps or a ‘nearest neighbor’ heuristic. Our results also show that it is essential to include CRMs predicted in multiple tissues during map-building, that H3K27ac is the most informative histone modification, and that CAGE is the most informative measure of gene expression for creating cis-regulatory maps. PMID:25200088

76 FR 21932 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Science.gov (United States)

2011-04-19

... statement therein, as follows: I. Introduction On February 4, 2011, the Financial Industry Regulatory...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting Approval of a... Financial Industry Regulatory Authority, Inc. (``FINRA'') to amend Rule 13806 of the Code of Arbitration...

IAEA Mission Concludes Peer Review of Viet Nam's Radiation and Nuclear Regulatory Framework

International Nuclear Information System (INIS)

2014-01-01

Senior international nuclear safety and radiation protection experts today concluded a 10-day International Atomic Energy Agency (IAEA) mission to review how Viet Nam's regulatory framework for nuclear and radiation safety has incorporated recommendations and suggestions from an earlier review, conducted in 2009. The Integrated Regulatory Review Service (IRRS) follow-up mission, requested by the Viet Nam Agency for Radiation and Nuclear Safety (VARANS), also reviewed the development of the regulatory safety infrastructure to support Viet Nam's nuclear power programme. The eight-member team comprised senior regulatory experts from Canada, France, Pakistan, Slovenia, United Arab Emirates and the United States of America, as well as three IAEA staff members. The IRRS team said in its preliminary assessment that Viet Nam had made progress since 2009, but that some key recommendations still needed to be addressed. Particular strengths identified by the team included: The commitment of VARANS staff to develop legislation and regulations in the field of nuclear and radiation safety; VARANS' efforts to implement practices that are in line with IAEA Safety Standards and internationally recognized good practices; A willingness to receive feedback regarding the efforts to establish and implement a regulation programme; and Progress made in developing the regulatory framework to support the introduction of nuclear power. The team identified the following areas as high-priority steps to further strengthen radiation and nuclear safety in Viet Nam: The effective independence of the regulatory decision-making process needs to be urgently addressed; Additional resources are needed to regulate existing radiation facilities and activities, as well as the country's research reactor; Efforts to increase the capacity of VARANS to regulate the developing nuclear power programme should continue; The draft Master Plan for the Development of Nuclear Power Infrastructure should be finalized

Regulatory inspection of nuclear facilities and enforcement by the regulatory body. Safety guide

International Nuclear Information System (INIS)

2002-01-01

The purpose of this Safety Guide is to provide recommendations for regulatory bodies on the inspection of nuclear facilities, regulatory enforcement and related matters. The objective is to provide the regulatory body with a high level of confidence that operators have the processes in place to ensure compliance and that they do comply with legal requirements, including meeting the safety objectives and requirements of the regulatory body. However, in the event of non-compliance, the regulatory body should take appropriate enforcement action. This Safety Guide covers regulatory inspection and enforcement in relation to nuclear facilities such as: enrichment and fuel manufacturing plants; nuclear power plants; other reactors such as research reactors and critical assemblies; spent fuel reprocessing plants; and facilities for radioactive waste management, such as treatment, storage and disposal facilities. This Safety Guide also covers issues relating to the decommissioning of nuclear facilities, the closure of waste disposal facilities and site rehabilitation. Section 2 sets out the objectives of regulatory inspection and enforcement. Section 3 covers the management of regulatory inspections. Section 4 covers the performance of regulatory inspections, including internal guidance, planning and preparation, methods of inspection and reports of inspections. Section 5 deals with regulatory enforcement actions. Section 6 covers the assessment of regulatory inspections and enforcement activities. The Appendix provides further details on inspection areas for nuclear facilities

Approach of Czech regulatory body to LBB

Energy Technology Data Exchange (ETDEWEB)

Tendera, P.

1997-04-01

At present there are two NPPs equipped with PWR units in Czech Republic. The Dukovany, NPP is about ten years in operation (four units 440 MW - WWBFL model 213) and Tomelin NPP is under construction (two units 1000 MW - WWER model 320). Both NPPs were built to Soviet design and according to Soviet regulations and standards but most of equipment for primary circuits was supplied by home manufacturers. The objective of the Czech LBB program is to prove the LBB status of the primary piping systems of there NPPs and the LBB concept is a part of strategy to meet western style safety standards. The reason for the Czech LBB project is a lack of some standard safety Facilities too. For both Dukovany and Tomelin NPPs a full LBB analysis should be carried out. The application of LBB to the piping system should be also a cost effective means to avoid installations of pipe whip restraints and jet shields. The Czech regulatory body issued non-mandatory requirement, {open_quotes}Leak Before Break{close_quotes} which is in compliance with national legal documents and which is based on the US NRC Regulatory Procedures and US standards (ASMF CODE, ANSI). The requirement has been published in the document {open_quotes}Safety of Nuclear Facilities{close_quotes} No 1/1991 as {open_quotes}Requirements on the Content and Format of Safety Reports and their Supplements{close_quote} and consist of two parts (1) procedure for obtaining proof of evidence {open_quotes}Leak Before Break{close_quotes} (2) leak detection systems for the pressurized reactor primary circuit. At present some changes concerning both parts of the above document will be introduced. The reasons for this modifications will be presented.

Approach for Czech regulatory body to LBB

Energy Technology Data Exchange (ETDEWEB)

Tendera, P. [State Office for Nuclear Safety (SONS), Prague (Czech Republic)

1997-04-01

At present there are two NPPs equipped with PWR units in Czech Republic. The Dukovany NPP is about ten years in operation (four units 440 MW - WWER model 213) and Temelin NPP is under construction (two units 1000 MW-WWER model 320). Both NPPs were built to Soviet design and according to Soviet regulations and standards but most of equipment for primary circuits was supplied by home manufactures. The objective for the Czech LBB programme is to prove the LBB status of the primary piping systems of these NPPs and the LBB concept is a part of strategy to meet western style safety standards. The reason for the Czech LBB project is a lack of some standard safety facilities, too. For both Dukovany and Temolin NPPs a full LBB analysis should be carried out. The application of LBB to the piping system should be also a cost effective means to avoid installations of pipe whip restraints and jet shields. The Czech regulatory body issued non-mandatory requirement {open_quotes}Leak Before Break{close_quotes} which is in compliance with national legal documents and which is based on the US NRC Regulatory Procedures and US standards (ASME, CODE, ANSI). The requirement has been published in the document {open_quotes}Safety of Nuclear Facilities{close_quotes} No. 1/1991 as {open_quotes}Requirements on the Content and Format of Safety Reports and their Supplements{close_quotes} and consists of two parts (1) procedure for obtaining proof of evidence {open_quotes}Leak Before Break{close_quotes} (2) leak detection systems for the pressurized reactor primary circuit. At present some changes concerning both parts of the above document will be introduced. The reasons for this modifications will be presented.

An assessment of the contribution of NRC [Nuclear Regulatory Commission] regulatory growth to nuclear plant cost growth using engineering scope changes

International Nuclear Information System (INIS)

Cohen, S.

1987-03-01

The purpose of this study is to determine the contribution of NRC regulations to the growth in nuclear power plant capital costs using the case study method. The two plants selected for the case studies are Florida Power and Light Company's (FP and L) St. Lucie Unit 1 (SL1) and St. Lucie Unit 2 (SL2). SL1 was constructed in the early 1970s and was granted an operating license in 1976. SL2 was constructed in the late 1970s and early 1980s, and was granted an operating license in 1983. The information bases were the amendments to the contracts between FP and L and its architect-engineer/constructor, i.e., the ''scope changes''. These were examined and analyzed for causation, i.e., NRC-initiated or utility-initiated, and all of the costs associated with scope changes of each type were aggregated to determine the contribution of each. Although the scope changes accounted for only a small fraction of the total cost growth for either plant, they were still used to determine the relative contribution of regulatory growth to cost growth. Unexpectedly, a significantly higher percentage of out-of-scope work (approximately 84%) was attributable to NRC regulatory requirements for SL1 than SL2 (approximately 47%). These results were unexpected because SL2 was constructed during a period in which regulation was considered to be particularly unstable. However, a more detailed analysis of causation indicates that a shift occurred from an ad-hoc mode of regulation in the early 1970s to a more prescriptive process in the late 1970s. Thus the number of formal NRC requirements may not be a valid measure of regulatory stability

Dual Nature of Translational Control by Regulatory BC RNAs ▿

Science.gov (United States)

Eom, Taesun; Berardi, Valerio; Zhong, Jun; Risuleo, Gianfranco; Tiedge, Henri

2011-01-01

In higher eukaryotes, increasing evidence suggests, gene expression is to a large degree controlled by RNA. Regulatory RNAs have been implicated in the management of neuronal function and plasticity in mammalian brains. However, much of the molecular-mechanistic framework that enables neuronal regulatory RNAs to control gene expression remains poorly understood. Here, we establish molecular mechanisms that underlie the regulatory capacity of neuronal BC RNAs in the translational control of gene expression. We report that regulatory BC RNAs employ a two-pronged approach in translational control. One of two distinct repression mechanisms is mediated by C-loop motifs in BC RNA 3′ stem-loop domains. These C-loops bind to eIF4B and prevent the factor's interaction with 18S rRNA of the small ribosomal subunit. In the second mechanism, the central A-rich domains of BC RNAs target eIF4A, specifically inhibiting its RNA helicase activity. Thus, BC RNAs repress translation initiation in a bimodal mechanistic approach. As BC RNA functionality has evolved independently in rodent and primate lineages, our data suggest that BC RNA translational control was necessitated and implemented during mammalian phylogenetic development of complex neural systems. PMID:21930783

1992 Nuclear Regulatory Commission Annual Report

International Nuclear Information System (INIS)

1993-01-01

This is the 18th annual report of the US Nuclear Regulatory Commission (NRC), covering events and activities occurring in fiscal year 1992 (the year ending September 30, 1992), with some treatment of events from the last quarter of calendar year 1992. The NRC was created by enactment in the Congress of the Energy Reorganization Act of 1974. It is an independent agency of the Federal Government. The five NRC Commissioners are nominated by the President and confirmed by the United States Senate. The Chairman of the Commission is appointed by the President from among the Commissioners confirmed

GREAT: a web portal for Genome Regulatory Architecture Tools.

Science.gov (United States)

Bouyioukos, Costas; Bucchini, François; Elati, Mohamed; Képès, François

2016-07-08

GREAT (Genome REgulatory Architecture Tools) is a novel web portal for tools designed to generate user-friendly and biologically useful analysis of genome architecture and regulation. The online tools of GREAT are freely accessible and compatible with essentially any operating system which runs a modern browser. GREAT is based on the analysis of genome layout -defined as the respective positioning of co-functional genes- and its relation with chromosome architecture and gene expression. GREAT tools allow users to systematically detect regular patterns along co-functional genomic features in an automatic way consisting of three individual steps and respective interactive visualizations. In addition to the complete analysis of regularities, GREAT tools enable the use of periodicity and position information for improving the prediction of transcription factor binding sites using a multi-view machine learning approach. The outcome of this integrative approach features a multivariate analysis of the interplay between the location of a gene and its regulatory sequence. GREAT results are plotted in web interactive graphs and are available for download either as individual plots, self-contained interactive pages or as machine readable tables for downstream analysis. The GREAT portal can be reached at the following URL https://absynth.issb.genopole.fr/GREAT and each individual GREAT tool is available for downloading. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

A map of directional genetic interactions in a metazoan cell.

Science.gov (United States)

Fischer, Bernd; Sandmann, Thomas; Horn, Thomas; Billmann, Maximilian; Chaudhary, Varun; Huber, Wolfgang; Boutros, Michael

2015-03-06

Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene-gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations.

Informed consent for anaesthesiological and intensive care unit ...

African Journals Online (AJOL)

2013-03-04

Mar 4, 2013 ... care unit research: a South African perspective. De Roubaix JAM, MBChB, .... (g) the development of new applications of health technology. The last two items .... Consent in emergency and ICU care: SA regulatory guidelines.

The interplay between regulatory focus and temporal distance in the health context

NARCIS (Netherlands)

Berezowska, Aleksandra; Fischer, Arnout R.H.; Trijp, van Hans C.M.

2018-01-01

Objectives: This study identifies how the interaction between temporal distance, regulatory focus, and framing of health outcomes affects individuals' intention to adopt a personalized nutrition service. Design: A 2 (temporal distance: immediate health outcomes vs. delayed health outcomes) × 2

Summary of the financial and ratepayer impacts of nuclear power plant regulatory reform

International Nuclear Information System (INIS)

Turpin, A.Y.

1985-05-01

This report estimates the financial impact on utilities and ratepayers of nuclear power plant regulatory reforms. Three situations are investigated: (1) no reform, (2) combined early-site-permit and preapproval-of-design reforms, and (3) total reform. Also, two types of capacity additions are evaluated using two utility companies as case studies: (1) nuclear plus generic capacity, and (2) all-nuclear capacity. Results indicate that both the shorter construction lead-time afforded by nuclear regulatory reform and the timing of new capacity additions are extremely important in enabling a utility to remain in a healthy financial position while adding capacity to meet future demand and at the same time reducing the price of electricity to the ratepayers. The lower added capital costs and fuel cost savings obtained from reformed nuclear units allow a utility dependent on oil and gas steam generation to experience price decreases as these new units begin commercial operation. The study also points out that in simulations excluding the shorter lead-time generic capacity, price increases were greater and financial performance was worse for both utilities. These facts indicate the importance of shortening the construction lead-time through nuclear regulatory reform so that nuclear power will be more competitive with coal. 19 refs., 4 figs., 3 tabs

RPA Interacts with HIRA and Regulates H3.3 Deposition at Gene Regulatory Elements in Mammalian Cells.

Science.gov (United States)

Zhang, Honglian; Gan, Haiyun; Wang, Zhiquan; Lee, Jeong-Heon; Zhou, Hui; Ordog, Tamas; Wold, Marc S; Ljungman, Mats; Zhang, Zhiguo

2017-01-19

The histone chaperone HIRA is involved in depositing histone variant H3.3 into distinct genic regions, including promoters, enhancers, and gene bodies. However, how HIRA deposits H3.3 to these regions remains elusive. Through a short hairpin RNA (shRNA) screening, we identified single-stranded DNA binding protein replication protein A (RPA) as a regulator of the deposition of newly synthesized H3.3 into chromatin. We show that RPA physically interacts with HIRA to form RPA-HIRA-H3.3 complexes, and it co-localizes with HIRA and H3.3 at gene promoters and enhancers. Depletion of RPA1, the largest subunit of the RPA complex, dramatically reduces both HIRA association with chromatin and the deposition of newly synthesized H3.3 at promoters and enhancers and leads to altered transcription at gene promoters. These results support a model whereby RPA, best known for its role in DNA replication and repair, recruits HIRA to promoters and enhancers and regulates deposition of newly synthesized H3.3 to these regulatory elements for gene regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Protein-protein interactions in the regulation of WRKY transcription factors.

Science.gov (United States)

Chi, Yingjun; Yang, Yan; Zhou, Yuan; Zhou, Jie; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

2013-03-01

It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all analyzed WRKY proteins recognize the TTGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcription factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biological processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.

Barack Obama’s infrastructure policies for the United States

NARCIS (Netherlands)

Auger, J.F.

2008-01-01

The new president of the United States, Barack Obama, has set his policies on infrastructures. To carry them out, he will resort mostly to economics incentives and, to a lesser extent, regulatory constraints.

Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - United States

International Nuclear Information System (INIS)

2015-01-01

This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment (Special nuclear material; Source material; By-product material; Agreement state programmes); 4. Nuclear installations (Initial licensing; Operation and inspection, including nuclear safety; Operating licence renewal; Decommissioning; Emergency response); 5. Radiological protection (Protection of workers; Protection of the public); 6. Radioactive waste management (High-level waste; Low-level waste; Disposal at sea; Uranium mill tailings; Formerly Utilized Sites Remedial Action Program - FUSRAP); 7. Non-proliferation and exports (Exports of source material, special nuclear material, production or utilisation facilities and sensitive nuclear technology; Exports of components; Exports of by-product material; Exports and imports of radiation sources; Conduct resulting in the termination of exports or economic assistance; Subsequent arrangements; Technology exports; Information and restricted data); 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Nuclear Regulatory Commission - NRC; Department of Energy - DOE; Department of Labor - DOL; Department of Transportation - DOT; Environmental Protection Agency - EPA); 2. Public and semi-public agencies: A. Cabinet-level departments (Department of

Learning gene regulatory networks from only positive and unlabeled data

Directory of Open Access Journals (Sweden)

Elkan Charles

2010-05-01

Full Text Available Abstract Background Recently, supervised learning methods have been exploited to reconstruct gene regulatory networks from gene expression data. The reconstruction of a network is modeled as a binary classification problem for each pair of genes. A statistical classifier is trained to recognize the relationships between the activation profiles of gene pairs. This approach has been proven to outperform previous unsupervised methods. However, the supervised approach raises open questions. In particular, although known regulatory connections can safely be assumed to be positive training examples, obtaining negative examples is not straightforward, because definite knowledge is typically not available that a given pair of genes do not interact. Results A recent advance in research on data mining is a method capable of learning a classifier from only positive and unlabeled examples, that does not need labeled negative examples. Applied to the reconstruction of gene regulatory networks, we show that this method significantly outperforms the current state of the art of machine learning methods. We assess the new method using both simulated and experimental data, and obtain major performance improvement. Conclusions Compared to unsupervised methods for gene network inference, supervised methods are potentially more accurate, but for training they need a complete set of known regulatory connections. A supervised method that can be trained using only positive and unlabeled data, as presented in this paper, is especially beneficial for the task of inferring gene regulatory networks, because only an incomplete set of known regulatory connections is available in public databases such as RegulonDB, TRRD, KEGG, Transfac, and IPA.

Major nuclear safety and regulatory issues in Korea

International Nuclear Information System (INIS)

Chang, Soon Heung

2004-01-01

Recently the value of nuclear energy is being re-considered due to the increase of oil price, the lack of energy supply, and the competition with renewable energy source. In Unites States, Europe, and East Asia, the prospects for continuous nuclear energy development or the policy for retaining nuclear energy have been announced. According to the nuclear energy promotion plan in Korea, there are 19 operating nuclear plants currently and more 7 plants will be constructed in the future. Until now, qualitative as well as quantitative growth is remarkable. Korean nuclear power plants achieved world-best level of capacity factor. However, because of the various nuclear industrial activities, we have a lot of regulatory issues for operating plants, building new plants, and other nuclear related facilities such as research reactors or radioactive waste storage facility. In this article, important regulatory issues which are emerging in Korea will be reviewed and the approaches to solve the issues including public acceptance will be presented. Especially, I will go into detail of two special case studies: The one is the thermal sleeve separation incident in Younggwang nuclear units 5 and 6 whose outage lasts about 80 days and 90 days respectively, which is not common in worldwide nuclear history. The other is about consensus meeting of Korea nuclear energy policy which was managed by a non-governmental organization. (author)

Biodiversity maintenance in food webs with regulatory environmental feedbacks.

Science.gov (United States)

Bagdassarian, Carey K; Dunham, Amy E; Brown, Christopher G; Rauscher, Daniel

2007-04-21

Although the food web is one of the most fundamental and oldest concepts in ecology, elucidating the strategies and structures by which natural communities of species persist remains a challenge to empirical and theoretical ecologists. We show that simple regulatory feedbacks between autotrophs and their environment when embedded within complex and realistic food-web models enhance biodiversity. The food webs are generated through the niche-model algorithm and coupled with predator-prey dynamics, with and without environmental feedbacks at the autotroph level. With high probability and especially at lower, more realistic connectance levels, regulatory environmental feedbacks result in fewer species extinctions, that is, in increased species persistence. These same feedback couplings, however, also sensitize food webs to environmental stresses leading to abrupt collapses in biodiversity with increased forcing. Feedback interactions between species and their material environments anchor food-web persistence, adding another dimension to biodiversity conservation. We suggest that the regulatory features of two natural systems, deep-sea tubeworms with their microbial consortia and a soil ecosystem manifesting adaptive homeostatic changes, can be embedded within niche-model food-web dynamics.

Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin Gene-Related Peptide.

Science.gov (United States)

Szklany, Kirsten; Ruiter, Evelyn; Mian, Firoz; Kunze, Wolfgang; Bienenstock, John; Forsythe, Paul; Karimi, Khalil

2016-01-01

The nervous and immune systems communicate bidirectionally, utilizing diverse molecular signals including cytokines and neurotransmitters to provide an integrated response to changes in the body's internal and external environment. Although, neuro-immune interactions are becoming better understood under inflammatory circumstances and it has been evidenced that interaction between neurons and T cells results in the conversion of encephalitogenic T cells to T regulatory cells, relatively little is known about the communication between neurons and naïve T cells. Here, we demonstrate that following co-culture of naïve CD4+ T cells with superior cervical ganglion neurons, the percentage of Foxp3 expressing CD4+CD25+ cells significantly increased. This was mediated in part by immune-regulatory cytokines TGF-β and IL-10, as well as the neuropeptide calcitonin gene-related peptide while vasoactive intestinal peptide was shown to play no role in generation of T regulatory cells. Additionally, T cells co-cultured with neurons showed a decrease in the levels of pro-inflammatory cytokine IFN-γ released upon in vitro stimulation. These findings suggest that the generation of Tregs may be promoted by naïve CD4+ T cell: neuron interaction through the release of neuropeptide CGRP.

CoryneRegNet 4.0 – A reference database for corynebacterial gene regulatory networks

Directory of Open Access Journals (Sweden)

Baumbach Jan

2007-11-01

Full Text Available Abstract Background Detailed information on DNA-binding transcription factors (the key players in the regulation of gene expression and on transcriptional regulatory interactions of microorganisms deduced from literature-derived knowledge, computer predictions and global DNA microarray hybridization experiments, has opened the way for the genome-wide analysis of transcriptional regulatory networks. The large-scale reconstruction of these networks allows the in silico analysis of cell behavior in response to changing environmental conditions. We previously published CoryneRegNet, an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks. Initially, it was designed to provide methods for the analysis and visualization of the gene regulatory network of Corynebacterium glutamicum. Results Now we introduce CoryneRegNet release 4.0, which integrates data on the gene regulatory networks of 4 corynebacteria, 2 mycobacteria and the model organism Escherichia coli K12. As the previous versions, CoryneRegNet provides a web-based user interface to access the database content, to allow various queries, and to support the reconstruction, analysis and visualization of regulatory networks at different hierarchical levels. In this article, we present the further improved database content of CoryneRegNet along with novel analysis features. The network visualization feature GraphVis now allows the inter-species comparisons of reconstructed gene regulatory networks and the projection of gene expression levels onto that networks. Therefore, we added stimulon data directly into the database, but also provide Web Service access to the DNA microarray analysis platform EMMA. Additionally, CoryneRegNet now provides a SOAP based Web Service server, which can easily be consumed by other bioinformatics software systems. Stimulons (imported from the database, or uploaded by the user can be analyzed in the context of known

Arrangement between the US Nuclear Regulatory Commission (USNRC) and the Belgian Government for Exchange of Technical Information in Regulatory Matters and in Cooperation in Safety Research and in Standards Development

International Nuclear Information System (INIS)

1978-01-01

This Arrangement was concluded on 6 June 1978 between the United States Nuclear Regulatory Commission and the Belgian Government for exchange of technical information in regulatory matters and in co-operation in safety research and in standards development. Both Parties agree to exchange, as available, technical information related to the regulation of safety and the environmental impact of designated nuclear energy facilities and to safety research of designated types of nuclear facilities. As regards co-operation in safety research, the execution of joint programmes and projects under which activities are divided between the two Parties will be agreed on a case by case basis. The Parties further agree to co-operate in the development of regulatory standards applicable to the designated nuclear facilities. The Arrangement is valid for 5 years and may be extended. (NEA) [fr

77 FR 50533 - Dominion Nuclear Connecticut, Inc.; Millstone Power Station, Unit 3

Science.gov (United States)

2012-08-21

....; Millstone Power Station, Unit 3 AGENCY: Nuclear Regulatory Commission. ACTION: Environmental assessment and... search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems... Optimized ZIRLO\\TM\\ fuel rod cladding in future core reload applications for Millstone Power Station, Unit 3...

Regulatory guidance document

International Nuclear Information System (INIS)

1994-05-01

The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

Safety R and D Needs in Multi-Unit PSA from a Regulatory Viewpoint

Energy Technology Data Exchange (ETDEWEB)

Heo, Gyunyoung; Yoon, Ji Woong [Kyung Hee University, Yongin (Korea, Republic of); Kim, Man Cheol [Chung-Ang University, Seoul (Korea, Republic of)

2016-10-15

The Nuclear Safety and Security Commission (NSSC) NSSC’s recent approval of the construction permits and operation licenses of Shin Kori units 3 to 6 has brought attention to the multi-unit probabilistic safety assessment (PSA). The disaster in Fukushima revealed the risks associated with the use of spent fuel pools (SFPs), and the linear (or non-linear) consequences of radiation leaks from multi-units in particular, has raised concerns. The number of nuclear power plants (NPPs) in operation will increase to ten at the Kori and Shin Kori sites when the construction of Units 5 and 6 is complete - the highest concentration of power reactors in one region in world history. Nuclear disasters do not happen frequently, but when one does happen, its cascading effects can inflict massive human and environmental loss. Proper safety measures are needed as more nuclear installations are put in place. Nuclear regulators are forced to promptly produce a sufficient degree of realistic and objective risk assessment results to meet the rapidly-increasing demand for multi-unit PSA, while striving to achieve matching levels of technological development. The issues with the technological aspects of PSA would still be inherent even after a few years of research, and ensuring the safety of multi-units would still prove challenging. Experts are however relieved that the general public is now much more familiar with the concept of PSA than in the past, which indicates a rise in the degree of public understanding of technology. More studies should be done on multi-unit regulation and safety so as to steer the government in the proper direction for enacting policies aimed to ensure the health of local residents. In conclusion, the technical problems associated with multi-unit PSA that were not mentioned in this paper are essentially similar to their single-unit counterparts, therefore, reinforcing the base infrastructure of PSAs in general will work towards resolving such technical

77 FR 35079 - License Renewal Application for Seabrook Station, Unit 1 ; NextEra Energy Seabrook, LLC

Science.gov (United States)

2012-06-12

... NUCLEAR REGULATORY COMMISSION [Docket No. 50-443; NRC-2010-0206] License Renewal Application for Seabrook Station, Unit 1 ; NextEra Energy Seabrook, LLC AGENCY: Nuclear Regulatory Commission. ACTION: License renewal application; intent to prepare supplement to draft [[Page 35080

[Impact of regulatory measures in the trends of community consumption of antibiotics in Chile].

Science.gov (United States)

Bavestrello, Luis; Cabello, Angela; Casanova, Dunny

2002-11-01

The indiscriminate use of antibiotics increases the appearance of bacterial resistance and forces the use of more expensive alternatives. The Chilean Ministry of Health is regulating the consumption of antibiotics since September 1999. These regulatory measures restricted the sale of antibiotics only when these were prescribed by an MD or an DS. To study the impact of these regulatory measures on antibiotics sales in pharmacies. A retrospective analysis of antibiotics sales in pharmacies from 1996 to 2000. The information was obtained from the International Marketing System (IMS Health), an auditing system of pharmacy sales. The consumption unit used was the Defined Daily Dose per 1000 inhabitants/day (DDD). There was an important reduction in DDD, after the introduction of regulatory measures, for amoxicillin, ampicillin, erythromycin, trimethoprim/sulpha, chroramphenicol, cloxacillin and phenoxymethylpenicillin. There was also a important fall in sales, expressed in dollars. The regulatory measures of the Ministry of Health, had an immediate and great impact on antibiotics sales in Chile.

NatalieQ: A web server for protein-protein interaction network querying

NARCIS (Netherlands)

El-Kebir, M.; Brandt, B.W.; Heringa, J.; Klau, G.W.

2014-01-01

Background Molecular interactions need to be taken into account to adequately model the complex behavior of biological systems. These interactions are captured by various types of biological networks, such as metabolic, gene-regulatory, signal transduction and protein-protein interaction networks.

A summary of radiological waste disposal practices in the United States and the United Kingdom - 16379

International Nuclear Information System (INIS)

Maranville, Victoria M.; McGrath, Richard

2009-01-01

A systematic review of near-surface repositories for radioactive waste in the United States (US) was conducted. The main focus of the review consisted of a literature search of available documents and other published sources on low level radioactive waste (LLRW) disposal practices, remediation of LLRW sites in the US, and public participation for remediation efforts of near-surface radiological waste disposal sites in the US. This review was undertaken to provide background information in support of work by the United Kingdom's (UK) Low Level Waste Repository (LLWR) and to aid in optimizing the future management of this site. The review contained a summary of the US and UK radiological waste classification requirements including a discussion of the waste types, disposal requirements, and the differences between US and UK disposal practices. A regulatory overview and evolution of regulatory requirements in the US is presented. The UK regulatory environment is also discussed and contrasted to the US process. The public participation, as part of the US regulatory process, is provided and the mechanism for stakeholder identification and involvement is detailed. To demonstrate how remediation of radiologically impacted sites is implemented in the US, existing US case studies, in which remediation activities were carried out, were reviewed. The following information was compiled: type of wastes disposed of to US shallow ground facilities [with comparison with UK classifications], facility designs (with special emphasis on those directly comparable to the subsurface conditions in the UK), and deficiencies identified in operation or in demonstrating safe post closure; and processes and difficulties in remedial actions encountered at the selected sites. Stakeholder involvement is discussed within the case studies. Publicly available information related to radiological waste management and disposal practices were reviewed. Two sites are presented in this publication for

The Regulatory Function of Eosinophils.

Science.gov (United States)

Wen, Ting; Rothenberg, Marc E

2016-10-01

Eosinophils are a minority circulating granulocyte classically viewed as being involved in host defense against parasites and promoting allergic reactions. However, a series of new regulatory functions for these cells have been identified in the past decade. During homeostasis, eosinophils develop in the bone marrow and migrate from the blood into target tissues following an eotaxin gradient, with interleukin-5 being a key cytokine for eosinophil proliferation, survival, and priming. In multiple target tissues, eosinophils actively regulate a variety of immune functions through their vast arsenal of granule products and cytokines, as well as direct cellular interaction with cells in proximity. The immunologic regulation of eosinophils extends from innate immunity to adaptive immunity and also involves non-immune cells. Herein, we summarize recent findings regarding novel roles of murine and human eosinophils, focusing on interactions with other hematopoietic cells. We also review new experimental tools available and remaining questions to uncover a greater understanding of this enigmatic cell.

78 FR 79709 - Duke Energy Florida, Inc., Crystal River Unit 3 Nuclear Generating Plant Post-Shutdown...

Science.gov (United States)

2013-12-31

... NUCLEAR REGULATORY COMMISSION [Docket No. 50-302; NRC-2013-0283] Duke Energy Florida, Inc., Crystal River Unit 3 Nuclear Generating Plant Post-Shutdown Decommissioning Activities Report AGENCY: Nuclear Regulatory Commission (NRC). ACTION: Notice of receipt; availability; public meeting; and request...

Nanoscale multireference quantum chemistry: full configuration interaction on graphical processing units.

Science.gov (United States)

Fales, B Scott; Levine, Benjamin G

2015-10-13

Methods based on a full configuration interaction (FCI) expansion in an active space of orbitals are widely used for modeling chemical phenomena such as bond breaking, multiply excited states, and conical intersections in small-to-medium-sized molecules, but these phenomena occur in systems of all sizes. To scale such calculations up to the nanoscale, we have developed an implementation of FCI in which electron repulsion integral transformation and several of the more expensive steps in σ vector formation are performed on graphical processing unit (GPU) hardware. When applied to a 1.7 × 1.4 × 1.4 nm silicon nanoparticle (Si72H64) described with the polarized, all-electron 6-31G** basis set, our implementation can solve for the ground state of the 16-active-electron/16-active-orbital CASCI Hamiltonian (more than 100,000,000 configurations) in 39 min on a single NVidia K40 GPU.

75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

Science.gov (United States)

2010-03-10

... the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2, 2010. The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold...

Unsolved problems in applying U.S. regulatory guides to control system equipment

International Nuclear Information System (INIS)

Stade, R.E.

1978-01-01

Two current problems encountered when designing control systems to the United States Regulatory Guide requirements are discussed. They are: 1) Level of surge voltages that should be specified when procuring solid state control and instrumentation systems and equipment. 2) The approach to be used qualifying equipment that must meet the aging requirements. (author)

The importance of the practical training, the retraining and the accreditation of the personnel with regulatory functions

International Nuclear Information System (INIS)

Menossi, Carlos A.

2004-01-01

Medicine, industry, hydrology, research, development and academic scenarios are, nowadays the focus for a wide application of radioisotope techniques of permanently increasing use. This situation should move the governments towards the improvement of their infrastructures and the updating of the nuclear regulatory authorities knowledge. The regulation and control of radioactive sources and its associated practices, to guarantee its safe use and minimize the derived risks from those practices, constitute the main tasks of nuclear regulatory institutions. On the other hand, it is known that personnel with regulatory functions has further interaction with people responsible of facilities and practices (users). In fact, most of these people only have contact with the regulatory authority through the inspector visits, the documents, notes or requirements received. For such a reason, nuclear regulatory authority management success or failure depends fundamentally on the successes or errors occurring in the course of these interactions. Due to it, it should be kept in mind that a successful management of a Nuclear Regulatory Authority implies: a) The users accomplish the effective standards and satisfy the authority requirements, and b) An attitude of respect is induced in the users by the appropriate regulatory function. That is to say because the 'inspectors' possess the necessary technical knowledge. In that sense, with the experience of many years, improvements have been introduced in the radiological protection Post Graduate Course program. This course sponsored by the IAEA has been given in Argentina for 24 years. Such improvements have been made to allow participants that will perform regulatory functions to have enough sessions of practical training, demonstrations, laboratory exercises, case studies and technical visits. This formation course will be supplemented by an accreditation and training on the job. The scope and dimension of the improvements are

PPI-IRO: A two-stage method for protein-protein interaction extraction based on interaction relation ontology

KAUST Repository

Li, Chuanxi; Chen, Peng; Wang, Rujing; Wang, Xiujie; Su, Yaru; Li, Jinyan

2014-01-01

Mining Protein-Protein Interactions (PPIs) from the fast-growing biomedical literature resources has been proven as an effective approach for the identifi cation of biological regulatory networks. This paper presents a novel method based on the idea

Audit Calculations of LBLOCA for Ulchin Unit 1 and 2 Power Up rate

Energy Technology Data Exchange (ETDEWEB)

Kang, Donggu; Huh, Byunggil; Yoo, Seunghunl; Yang, Chaeyong; Seul, Kwangwon [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2013-05-15

The KINS-Realistic Evaluation Model (KINS-REM) was developed for the independent audit calculation in 1991, and the code accuracy and statistical method have been improved. To support the licensing review and to confirm the validity of licensee's calculation, regulatory auditing calculations have been also conducted. Currently, the modification of Ulchin 1 and 2 operating license for 4.5% power up rate is under review. In this study, the regulatory audit calculation for LBLOCA of Ulchin Unit 1 and 2 with 4.5% power up rate was performed by applying KINS-REM. In this study, the regulatory audit calculation for LBLOCA of Ulchin Unit 1 and 2 with 4.5% power up rate was performed by applying KINS-REM. It is confirmed that the analysis results of LBLOCA for Ulchin 1 and 2 power up rate meets the PCT acceptance criteria.

THE ROLE OF SELF-REGULATORY AUDITING ASSOCIATIONS IN ARRANGEMENT OF AUDIT ACTIVITIES QUALITY CONTROL

Directory of Open Access Journals (Sweden)

Zinaida P. Arharova

2013-01-01

Full Text Available The role of self-regulatory organizations in audit activities quality control is revealed in this article. Creation of a united audit association is the basis of certain regulating and auditing functions transfer from the government to the public sector.

Glucokinase regulatory protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome.

Directory of Open Access Journals (Sweden)

Pablo Perez-Martinez

Full Text Available Glucokinase Regulatory Protein (GCKR plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS risk.To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP and n-3 PUFA in MetS subjects.Homeostasis model assessment of insulin resistance (HOMA-IR, HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019, C-peptide (P = 0.004, HOMA-IR (P = 0.008 and CRP (P = 0.032 as compared with subjects carrying the minor T-allele (Leu446. In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.ClinicalTrials.gov NCT00429195.

Regulatory interactions of stress and reward on rat forebrain opioidergic and GABAergic circuitry.

Science.gov (United States)

Christiansen, A M; Herman, J P; Ulrich-Lai, Y M

2011-03-01

Palatable food intake reduces stress responses, suggesting that individuals may consume such ?comfort? food as self-medication for stress relief. The mechanism by which palatable foods provide stress relief is not known, but likely lies at the intersection of forebrain reward and stress regulatory circuits. Forebrain opioidergic and gamma-aminobutyric acid ergic signaling is critical for both reward and stress regulation, suggesting that these systems are prime candidates for mediating stress relief by palatable foods. Thus, the present study (1) determines how palatable ?comfort? food alters stress-induced changes in the mRNA expression of inhibitory neurotransmitters in reward and stress neurocircuitry and (2) identifies candidate brain regions that may underlie comfort food-mediated stress reduction. We used a model of palatable ?snacking? in combination with a model of chronic variable stress followed by in situ hybridization to determine forebrain levels of pro-opioid and glutamic acid decarboxylase (GAD) mRNA. The data identify regions within the extended amygdala, striatum, and hypothalamus as potential regions for mediating hypothalamic-pituitary-adrenal axis buffering following palatable snacking. Specifically, palatable snacking alone decreased pro-enkephalin-A (ENK) mRNA expression in the anterior bed nucleus of the stria terminalis (BST) and the nucleus accumbens, and decreased GAD65 mRNA in the posterior BST. Chronic stress alone increased ENK mRNA in the hypothalamus, nucleus accumbens, amygdala, and hippocampus; increased dynorphin mRNA in the nucleus accumbens; increased GAD65 mRNA in the anterior hypothalamus and BST; and decreased GAD65 mRNA in the dorsal hypothalamus. Importantly, palatable food intake prevented stress-induced gene expression changes in subregions of the hypothalamus, BST, and nucleus accumbens. Overall, these data suggest that complex interactions exist between brain reward and stress pathways and that palatable snacking can

The impact of environmental regulations on United States crude oil supplies

International Nuclear Information System (INIS)

Godec, M.L.; Biglarbigi, K.

1991-01-01

A number of legislative and regulatory initiatives being considered to protect the environment could affect the economics of oil and gas exploration and production (E and P) in the Unites States. This paper summarizes the results of a comprehensive assessment of the potential cumulative energy and economic impacts of environmental regulatory initiatives on United States crude oil supplies. The results of the analysis clearly will determine the level of impact, but the results show that significant impacts are felt over a wide range of regulations, over a wide range of crude oil prices, and at two levels of development for extraction technologies. The regulations evaluated all have an impact on all resource categories analyzed in the study

Regulatory Approach To and Lessons Learned with Licensing of Service Life Extension at PAKS NPP

International Nuclear Information System (INIS)

Petofi, G.

2012-01-01

Paks Nuclear Power Plant of Hungary decided to extend the original design lifetime of the plant by 20 years, which expires on December 31, 2012 concerning unit 1. The Hungarian Atomic Energy Authority established the legal environments in order to license the extension using an approach similar to that followed in the United States. The regulation specifies the pre-conditions for the extension, defines the scoping and screening process for the passive and long lived systems, structures and components to be involved in the licensing and the respective methods of treatment and also determines how the active components shall be dealt with during the extended lifetime. The regulatory procedure is a two-step process including the oversight of the preparatory programme of the operator for the extension that started 4 years before the expiry of the lifetime and the licensing process itself, which is currently under way for unit 1 after the submittal of the licensee's application at the end of 2011. The first experiences with the regulatory assessment of the application are available yet and presented in this paper. (author)

75 FR 63878 - Self-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate...

Science.gov (United States)

2010-10-18

...-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of...(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory...

In silico analysis, mapping of regulatory elements and corresponding dna-protein interaction in polyphenol oxidase gene promoter from different rice varieties

International Nuclear Information System (INIS)

Mahmood, T.; Rehman, M.; Aziz, E.

2015-01-01

Polyphenol oxidase (PPO) is an important enzyme that has positive impact regarding plant resistance against different biotic and abiotic stresses. In the present study PPO promoter from six different rice varieties was amplified and then analyzed for cis- and trans-acting elements. The study revealed a total of 79 different cis-acting regulatory elements including 11 elements restricted to only one or other variety. Among six varieties Pakhal-Basmati had highest number (5) of these elements, whereas C-622 and Rachna-Basmati have no such sequences. Rachna-Basmati, IR-36-Basmati and Kashmir- Basmati had 1, 2 and 3 unique elements, respectively. Different elementsrelated to pathogen, salt and water stresses were found, which may be helpful in controlling PPO activity according to changing environment. Moreover, HADDOCK was used to understand molecular mechanism of PPO regulation and it was found that DNA-protein interactions are stabilized by many potential hydrogen bonds. Adenine and arginine were the most reactive residues in DNA and proteins respectively.Structural comparison of different protein-DNA complexes show that even a highly conserved transcriptional factor can adopt different conformations when they contact a different DNA binding sequence, however their stable interactions depend on the number of hydrogen bonds formed and distance. (author)

76 FR 71510 - Meeting of the Assembly of the Administrative Conference of the United States

Science.gov (United States)

2011-11-18

... administrative agencies, the President, Congress, and the Judicial Conference of the United States regarding the... participation and efficiency in the rulemaking process, reduce unnecessary litigation in the regulatory process, improve the use of science in the regulatory process, and improve the effectiveness of laws applicable to...

Regulatory site of inorganic pyrophosphatase. Interaction with substrate analogs

International Nuclear Information System (INIS)

Baikov, A.A.; Pavlov, A.R.; Avaeva, S.M.

1986-01-01

The effect of four PP 1 analogs with the structure PXP (X = N, C), phosphate, and the complex Cr(H 2 O) 4 PP 1 on the activity of inorganic pyrophosphatase from baker's yeast was studied over a wide range of substrate (Mg-PP 1 ) concentrations (lower limit 0.5 μM). The enzyme activity decreased in the presence of imidodiphosphate, hydroxymethane diphosphonate [PC(OH)P], and P 1 , and a double reciprocal plot of the rate of hydrolysis of Mg-PP 1 versus its concentration became linear. Small amounts of methane diphosphonate (PCP), ethane-1-hydroxy-1,1-diphosphonate (0.1-1μM), and Cr(H 2 O) 4 PP 1 (10 μM) activated the enzyme almost 2-fold by a competitive mechanism. The activation was due to an increase in the affinity of the protein for the activating Mg 2+ ion. Ultrafiltration showed that the pyrophosphatase molecule has 2.1 and 3.1 binding sites for PCP and PC(OHP)P, respectively. These results confirm the hypothesis that the enzyme contains a regulatory site whose occupation by PP 1 , P 1 , and substrate analogs increases the affinity of the protein for the activating metal

Authority defied: need for cognitive closure influences regulatory control when resisting authority.

Science.gov (United States)

Damen, Tom G E; van Leeuwen, Matthijs L; Dijksterhuis, Ap; van Baaren, Rick B

2014-08-01

The present studies examined whether differences in need for cognitive closure (NCC) were related to differences in regulatory control when confronted with authority. In two studies, levels of regulatory control were measured when participants resisted (Study 1; N = 46) or prepared to resist the influence attempt of an authority figure (Study 2; N = 50). Results showed that resisting the influence attempt from a high-authority figure was more depleting for participants higher in NCC compared to individuals lower in NCC. However, when they were given instructions and time to prepare the act of resistance, individuals high in NCC actually showed an increase in regulatory control. Authority is usually viewed as a general principle of influence; however, the present studies suggest that there are individual differences that influence how people may experience interactions with authorities. © 2013 Wiley Periodicals, Inc.

Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

Science.gov (United States)

Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

2015-12-01

Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

Physical and Visual Accessibilities in Intensive Care Units: A Comparative Study of Open-Plan and Racetrack Units.

Science.gov (United States)

Rashid, Mahbub; Khan, Nayma; Jones, Belinda

2016-01-01

This study compared physical and visual accessibilities and their associations with staff perception and interaction behaviors in 2 intensive care units (ICUs) with open-plan and racetrack layouts. For the study, physical and visual accessibilities were measured using the spatial analysis techniques of Space Syntax. Data on staff perception were collected from 81 clinicians using a questionnaire survey. The locations of 2233 interactions, and the location and length of another 339 interactions in these units were collected using systematic field observation techniques. According to the study, physical and visual accessibilities were different in the 2 ICUs, and clinicians' primary workspaces were physically and visually more accessible in the open-plan ICU. Physical and visual accessibilities affected how well clinicians' knew their peers and where their peers were located in these units. Physical and visual accessibilities also affected clinicians' perception of interaction and communication and of teamwork and collaboration in these units. Additionally, physical and visual accessibilities showed significant positive associations with interaction behaviors in these units, with the open-plan ICU showing stronger associations. However, physical accessibilities were less important than visual accessibilities in relation to interaction behaviors in these ICUs. The implications of these findings for ICU design are discussed.

77 FR 29701 - Impact of Construction (Under a Combined License) of New Nuclear Power Plant Units on Operating...

Science.gov (United States)

2012-05-18

... New Nuclear Power Plant Units on Operating Units at Multi-Unit Sites AGENCY: Nuclear Regulatory... construct and operate new nuclear power plants (NPPs) on multi-unit sites to provide an evaluation of the... License) of New Nuclear Power Plants on Operating Units at Multi-Unit Sites (Package). ML112630039 Federal...

Uncovering transcriptional interactions via an adaptive fuzzy logic approach

Directory of Open Access Journals (Sweden)

Chen Chung-Ming

2009-12-01

Full Text Available Abstract Background To date, only a limited number of transcriptional regulatory interactions have been uncovered. In a pilot study integrating sequence data with microarray data, a position weight matrix (PWM performed poorly in inferring transcriptional interactions (TIs, which represent physical interactions between transcription factors (TF and upstream sequences of target genes. Inferring a TI means that the promoter sequence of a target is inferred to match the consensus sequence motifs of a potential TF, and their interaction type such as AT or RT is also predicted. Thus, a robust PWM (rPWM was developed to search for consensus sequence motifs. In addition to rPWM, one feature extracted from ChIP-chip data was incorporated to identify potential TIs under specific conditions. An interaction type classifier was assembled to predict activation/repression of potential TIs using microarray data. This approach, combining an adaptive (learning fuzzy inference system and an interaction type classifier to predict transcriptional regulatory networks, was named AdaFuzzy. Results AdaFuzzy was applied to predict TIs using real genomics data from Saccharomyces cerevisiae. Following one of the latest advances in predicting TIs, constrained probabilistic sparse matrix factorization (cPSMF, and using 19 transcription factors (TFs, we compared AdaFuzzy to four well-known approaches using over-representation analysis and gene set enrichment analysis. AdaFuzzy outperformed these four algorithms. Furthermore, AdaFuzzy was shown to perform comparably to 'ChIP-experimental method' in inferring TIs identified by two sets of large scale ChIP-chip data, respectively. AdaFuzzy was also able to classify all predicted TIs into one or more of the four promoter architectures. The results coincided with known promoter architectures in yeast and provided insights into transcriptional regulatory mechanisms. Conclusion AdaFuzzy successfully integrates multiple types of

Regulatory analysis for resolution of USI A-17

International Nuclear Information System (INIS)

Thatcher, D.F.

1989-08-01

This report presents a summary of the regulatory analysis conducted by the NRC staff to evaluate the value and impact of potential alternatives for the resolution of Unresolved Safety Issue (USI) A-17, ''Systems Interactions in Nuclear Power Plants.'' The NRC staff's proposed resolution offered in this report is based on this analysis. The staff's technical finding regarding interactions can be found in NUREG-1174. Adverse systems interactions (ASIs) involve subtle and often very complicated plant-specific dependencies between components and systems, possible compounded by inducing erroneous human intervention. The staff has identified actions to be taken by licensees and the NRC to resolve USI A-17; the staff has also made the judgment that these actions, together with other ongoing activities, would reduce the risk from adverse systems interactions. As discussed further in this report, the staff judgment that the actions are sufficient is not based on the assertion that all systems interactions have been identified, but rather that the A-17 actions, plus other activities by the licensees and staff, will identify precursors to potentially risk-significant interactions so that the action can be taken if deemed necessary

IAEA Mission Concludes Peer Review of Pakistan's Nuclear Regulatory Framework

International Nuclear Information System (INIS)

2014-01-01

An international team of senior nuclear safety experts today concluded a nine-day International Atomic Energy Agency (IAEA) mission to review the regulatory framework for the safety of operating nuclear power plants in the United States of America (USA). The Integrated Regulatory Review Service (IRRS) mission was a follow-up to the IRRS mission to the US Nuclear Regulatory Commission (NRC) that was conducted in 2010, with the key additional aim of reviewing whether the response of the US regulatory regime to the implications of the accident at TEPCO's Fukushima Daiichi Plant had been timely and effective. The mission team concluded that the recommendations and suggestions made by the 2010 IRRS mission have been taken into account systematically under the NRC's subsequent action plan, with significant progress in many areas and many improvements carried out. One of two recommendations and 19 out of 20 suggestions made by the 2010 IRRS mission have been effectively addressed and can therefore be considered closed. The outstanding recommendation relates to the NRC's review of its Management System, which is in the process of being finalised. The IRRS team also found that the NRC acted promptly and effectively after the Fukushima accident in the interests of public health and safety, and that the report of its Near-Term Task Force represents a sound and ample basis for taking into account the lessons learned from the accident

The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

Science.gov (United States)

Vaidya, A; Brown, J M; Williams, J S

2015-09-01

There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.

Regulatory activities; Actividades regulatorias

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

Loregic: A Method to Characterize the Cooperative Logic of Regulatory Factors

Science.gov (United States)

Wang, Daifeng; Yan, Koon-Kiu; Sisu, Cristina; Cheng, Chao; Rozowsky, Joel; Meyerson, William; Gerstein, Mark B.

2015-01-01

The topology of the gene-regulatory network has been extensively analyzed. Now, given the large amount of available functional genomic data, it is possible to go beyond this and systematically study regulatory circuits in terms of logic elements. To this end, we present Loregic, a computational method integrating gene expression and regulatory network data, to characterize the cooperativity of regulatory factors. Loregic uses all 16 possible two-input-one-output logic gates (e.g. AND or XOR) to describe triplets of two factors regulating a common target. We attempt to find the gate that best matches each triplet’s observed gene expression pattern across many conditions. We make Loregic available as a general-purpose tool (github.com/gersteinlab/loregic). We validate it with known yeast transcription-factor knockout experiments. Next, using human ENCODE ChIP-Seq and TCGA RNA-Seq data, we are able to demonstrate how Loregic characterizes complex circuits involving both proximally and distally regulating transcription factors (TFs) and also miRNAs. Furthermore, we show that MYC, a well-known oncogenic driving TF, can be modeled as acting independently from other TFs (e.g., using OR gates) but antagonistically with repressing miRNAs. Finally, we inter-relate Loregic’s gate logic with other aspects of regulation, such as indirect binding via protein-protein interactions, feed-forward loop motifs and global regulatory hierarchy. PMID:25884877

Requirements for US regulatory approval of the International Thermonuclear Experimental Reactor (ITER)

International Nuclear Information System (INIS)

Petti, D.A.; Haire, J.C.

1993-12-01

The International Thermonuclear Experimental Reactor (ITER) is the first fusion machine that will have sufficient decay heat and activation product inventory to pose potential nuclear safety concerns. As a result, nuclear safety and environmental issues will be much more important in the approval process for the design, siting, construction, and operation of ITER in the United States than previous fusion devices, such as the Tokamak Fusion Test Reactor. The purpose of this report is (a) to provide an overview of the regulatory approval process for a Department of Energy (DOE) nuclear facility; (b) to present the dose limits used by DOE to protect workers, the public, and the environment from the risks of exposure to radiation and hazardous materials; (c) to discuss some key nuclear safety-related issues that must be addressed early in the Engineering Design Activities (EDA) to obtain regulatory approval; and (d) to provide general guidelines to the ITER Joint Central Team (JCT) concerning the development of a regulatory framework for the ITER project

Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE

DEFF Research Database (Denmark)

Liu, Yawei; Teige, Ingrid; Birnir, Bryndis

2006-01-01

Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflamma......Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS......) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1-TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between...... neurons and T cells results in the conversion of encephalitogenic T cells to CD25+ TGF-beta1+ CTLA-4+ FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4...

National legislative and regulatory activities: Armenia, Australia, Austria, Belgium, Brazil, France, Germany, Hungary, India, Ireland, Lithuania, Moldova, Poland, Portugal, Romania, Slovenia, Sweden, Ukraine, United States

International Nuclear Information System (INIS)

Anon.

2012-01-01

(Changes to site evaluation reports); Nuclear safety and radiation protection (Amendments to various laws relating to nuclear safety, Revised requirements relating to modifications of nuclear installations, New safety reporting requirements, New requirements relating to releases of radionuclides, New conditions for removal of items from regulatory control, New radiation protection requirements, New inspection procedure requirements, New procedure for compliance enforcement); Nuclear security (Establishment of a design basis threat review process). Moldova: General legislation (Co-operation with the International Atomic Energy Agency). Poland: General legislation (Amendments to the Atomic Law Act); Liability and compensation (New requirements for civil liability insurance); Organisation and structure (New advisory council established); Nuclear safety and radiation protection (New requirements for employees working at nuclear power plants). Portugal: General legislation (Integration of the Nuclear Technological Institute into the Technical University of Lisbon); Nuclear safety and radiation protection (Creation of the Regulatory Commission for the Safety of Nuclear Facilities). Romania: Environmental protection (Changes to fuel production regulations). Slovenia: Nuclear safety and radiation protection (New rules governing worker qualification); Sweden: Nuclear safety and radiation protection (New regulation on clearance from regulation). Ukraine: General legislation (New requirements relating to the purchase of fuel elements); Nuclear safety and radiation protection (New plans for a comprehensive safety upgrade, New community outreach requirements, New transparency and information availability requirements); Nuclear security (Changes to the state-level physical protection regime); Radioactive waste management (New centralised repository planned) United States: Radioactive waste management (Status of the high-level waste repository programme, Issuance of the Final Report of

Reconstruction and analysis of transcription factor-miRNA co-regulatory feed-forward loops in human cancers using filter-wrapper feature selection.

Directory of Open Access Journals (Sweden)

Chen Peng

Full Text Available BACKGROUND: As one of the most common types of co-regulatory motifs, feed-forward loops (FFLs control many cell functions and play an important role in human cancers. Therefore, it is crucial to reconstruct and analyze cancer-related FFLs that are controlled by transcription factor (TF and microRNA (miRNA simultaneously, in order to find out how miRNAs and TFs cooperate with each other in cancer cells and how they contribute to carcinogenesis. Current FFL studies rely on predicted regulation information and therefore suffer the false positive issue in prediction results. More critically, FFLs generated by existing approaches cannot represent the dynamic and conditional regulation relationship under different experimental conditions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we proposed a novel filter-wrapper feature selection method to accurately identify co-regulatory mechanism by incorporating prior information from predicted regulatory interactions with parallel miRNA/mRNA expression datasets. By applying this method, we reconstructed 208 and 110 TF-miRNA co-regulatory FFLs from human pan-cancer and prostate datasets, respectively. Further analysis of these cancer-related FFLs showed that the top-ranking TF STAT3 and miRNA hsa-let-7e are key regulators implicated in human cancers, which have regulated targets significantly enriched in cellular process regulations and signaling pathways that are involved in carcinogenesis. CONCLUSIONS/SIGNIFICANCE: In this study, we introduced an efficient computational approach to reconstruct co-regulatory FFLs by accurately identifying gene co-regulatory interactions. The strength of the proposed feature selection method lies in the fact it can precisely filter out false positives in predicted regulatory interactions by quantitatively modeling the complex co-regulation of target genes mediated by TFs and miRNAs simultaneously. Moreover, the proposed feature selection method can be generally applied to

78 FR 22347 - GPU Nuclear Inc., Three Mile Island Nuclear Power Station, Unit 2, Exemption From Certain...

Science.gov (United States)

2013-04-15

... NUCLEAR REGULATORY COMMISSION [Docket No. 50-320; NRC-2013-0065] GPU Nuclear Inc., Three Mile Island Nuclear Power Station, Unit 2, Exemption From Certain Security Requirements AGENCY: Nuclear... and State Materials and Environmental Management Programs, U.S. Nuclear Regulatory Commission...

Integration of steady-state and temporal gene expression data for the inference of gene regulatory networks.

Science.gov (United States)

Wang, Yi Kan; Hurley, Daniel G; Schnell, Santiago; Print, Cristin G; Crampin, Edmund J

2013-01-01

We develop a new regression algorithm, cMIKANA, for inference of gene regulatory networks from combinations of steady-state and time-series gene expression data. Using simulated gene expression datasets to assess the accuracy of reconstructing gene regulatory networks, we show that steady-state and time-series data sets can successfully be combined to identify gene regulatory interactions using the new algorithm. Inferring gene networks from combined data sets was found to be advantageous when using noisy measurements collected with either lower sampling rates or a limited number of experimental replicates. We illustrate our method by applying it to a microarray gene expression dataset from human umbilical vein endothelial cells (HUVECs) which combines time series data from treatment with growth factor TNF and steady state data from siRNA knockdown treatments. Our results suggest that the combination of steady-state and time-series datasets may provide better prediction of RNA-to-RNA interactions, and may also reveal biological features that cannot be identified from dynamic or steady state information alone. Finally, we consider the experimental design of genomics experiments for gene regulatory network inference and show that network inference can be improved by incorporating steady-state measurements with time-series data.

The core to regulatory reform

International Nuclear Information System (INIS)

Partridge, J.W. Jr.

1993-01-01

Federal Energy Regulatory Commission (FERC) Orders 436, 500, and 636, the Clean Air Act Amendments of 1990, Public Utility Holding Company Act reform, and the 1992 Energy Policy Act all can have significant effects on an LDC's operations. Such changes in an LDC's environments must be balanced by changes within the utility, its marketplace, and its state regulatory environment. The question is where to start. For Columbia Gas Distribution Cos., based in Columbus, OH, the new operating foundation begins with each employee. Internal strength is critical in designing initiatives that meet the needs of the marketplace and are well-received by regulators. Employees must understand not only the regulatory environment in which the LDC operates, but also how their work contributes to a positive regulatory relationship. To achieve this, Columbia initiated the COntinuing Regulatory Education program, or CORE, in 1991. CORE is a regulatory-focused, information-initiative program coordinated by Columbia's Regulatory Policy, Planning, and Government Affairs Department. The CORE programs can take many forms, such as emerging issue discussions, dialogues with regulators and key parties, updates on regulatory fillings, regulatory policy meetings, and formal training classes. The speakers and discussion facilitators can range from human resource department trainers to senior officers, from regulatory department staff members to external experts, or from state commissioners to executives from other LDCs. The goals of CORE initiatives are to: Support a professional level of regulatory expertise through employee participation in well-developed regulatory programs presented by credible experts. Encourage a constructive state regulatory environment founded on communication and cooperation. CORE achieves these goals via five program levels: introductory basics, advanced learning, professional expertise, crossfunctional dialogues, and external idea exchanges

Genome-wide profiling of the PIWI-interacting RNA-mRNA regulatory networks in epithelial ovarian cancers.

Science.gov (United States)

Singh, Garima; Roy, Jyoti; Rout, Pratiti; Mallick, Bibekanand

2018-01-01

PIWI-interacting (piRNAs), ~23-36 nucleotide-long small non-coding RNAs (sncRNAs), earlier believed to be germline-specific, have now been identified in somatic cells, including cancer cells. These sncRNAs impact critical biological processes by fine-tuning gene expression at post-transcriptional and epigenetic levels. The expression of piRNAs in ovarian cancer, the most lethal gynecologic cancer is largely uncharted. In this study, we investigated the expression of PIWILs by qRT-PCR and western blotting and then identified piRNA transcriptomes in tissues of normal ovary and two most prevalent epithelial ovarian cancer subtypes, serous and endometrioid by small RNA sequencing. We detected 219, 256 and 234 piRNAs in normal ovary, endometrioid and serous ovarian cancer samples respectively. We observed piRNAs are encoded from various genomic regions, among which introns harbor the majority of them. Surprisingly, piRNAs originated from different genomic contexts showed the varied level of conservations across vertebrates. The functional analysis of predicted targets of differentially expressed piRNAs revealed these could modulate key processes and pathways involved in ovarian oncogenesis. Our study provides the first comprehensive piRNA landscape in these samples and a useful resource for further functional studies to decipher new mechanistic views of piRNA-mediated gene regulatory networks affecting ovarian oncogenesis. The RNA-seq data is submitted to GEO database (GSE83794).

The evolving regulation of uranium recovery operations in the United States of America: Innovative approaches are necessary for cost effective regulatory oversight

International Nuclear Information System (INIS)

Thompson, A.J.; Lehrenbaum, W.U.; Lashway, D.C.

2002-01-01

The US domestic uranium industry is at a crossroads. Historic low prices for uranium, combined with stringent and often irrational regulatory requirements, pose a very real threat to the industry's continued viability. The Nuclear Regulatory Commission has taken a number of innovative steps to reform and rationalize its regulatory programme. However, if the domestic uranium recovery industry is to remain viable, additional steps toward innovation and reform are needed, and effective implementation of reforms adopted by the Commission is essential. (author)

76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Science.gov (United States)

2011-10-26

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). For convenience...

75 FR 17456 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Science.gov (United States)

2010-04-06

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... terms. For more information about the rulebook consolidation process, see Information Notice, March 12...

Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers

International Nuclear Information System (INIS)

1997-11-01

The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference

Theoretical approaches to the steady-state statistical physics of interacting dissipative units

Science.gov (United States)

Bertin, Eric

2017-02-01

The aim of this review is to provide a concise overview of some of the generic approaches that have been developed to deal with the statistical description of large systems of interacting dissipative ‘units’. The latter notion includes, e.g. inelastic grains, active or self-propelled particles, bubbles in a foam, low-dimensional dynamical systems like driven oscillators, or even spatially extended modes like Fourier modes of the velocity field in a fluid. We first review methods based on the statistical properties of a single unit, starting with elementary mean-field approximations, either static or dynamic, that describe a unit embedded in a ‘self-consistent’ environment. We then discuss how this basic mean-field approach can be extended to account for spatial dependences, in the form of space-dependent mean-field Fokker-Planck equations, for example. We also briefly review the use of kinetic theory in the framework of the Boltzmann equation, which is an appropriate description for dilute systems. We then turn to descriptions in terms of the full N-body distribution, starting from exact solutions of one-dimensional models, using a matrix-product ansatz method when correlations are present. Since exactly solvable models are scarce, we also present some approximation methods which can be used to determine the N-body distribution in a large system of dissipative units. These methods include the Edwards approach for dense granular matter and the approximate treatment of multiparticle Langevin equations with colored noise, which models systems of self-propelled particles. Throughout this review, emphasis is put on methodological aspects of the statistical modeling and on formal similarities between different physical problems, rather than on the specific behavior of a given system.

US decommissioning strategy in today's regulatory, technical, political, and economic environments

International Nuclear Information System (INIS)

Colvin, J.F.

1995-01-01

The United States commercial nuclear power industry is nearly forty years old. Soon after the turn of the century, the United States expects to see a significant rise in the number of plants requiring decommissioning. This, coupled with recent economic pressures which are impacting the U.S. electrical generation industry and have resulted in the premature shutdown of some nuclear power plants, heighten the need for clear regulations and standards addressing facility closure and decommissioning. Since the issue of decommissioning involves public health and safety, technical, environmental and financial aspects, this complex regulatory environment poses a major challenge to the industry in this area. There are three fundamental issues facing utilities as they develop strategies for the eventual decommissioning of their nuclear power plants. These issues are the regulatory approach to decommissioning, the question of the availability of adequate funding, including the uncertainty resulting from the uncertainty of waste disposal options, and the need to meet environmental standards for the protection of health and safety. Futhermore, these issues, in particular the economic-related issues, are magnified in the event of prematurely shut down nuclear power plant. (Author)

Regulatory frameworks for hydropower in Europe. Comparing the examples of Germany, France and the United Kingdom; Regulatorische Rahmenbedingungen fuer die Wasserkraftnutzung in Europa am Beispiel der Laender Deutschland, Frankreich und Grossbritannien

Energy Technology Data Exchange (ETDEWEB)

Krull, Devid; Schneider, Claus Till; Detering, Michael [innogy SE, Essen (Germany). Sparte Erneuerbare Energien; Logie, Andrew [innogy SE, Perth (United Kingdom). Hydro Development; Seyler, Juergen [Energies France S.A.S., Paris (France)

2016-11-01

The regulatory framework for hydro power in the European countries Germany, United Kingdom and France is compared. All have as a common target on the one hand an increase of the share of renewable energy production and to this means a support regime for hydro power among other renewable technologies. The respective support mechanisms in the three countries are summarised. As part of the implementation of the European Water Framework Directive the countries formulate stricter environmental requirements for water bodies leading to reduced electricity generation and necessary investments in technical adaptations.

78 FR 62784 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Science.gov (United States)

2013-10-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer... 5210 (Publication of Transactions and Quotations) October 4, 2013. I. Introduction On August 15, 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

Radioactive residues at nuclear sites in the United States of America

International Nuclear Information System (INIS)

Fiore, J.; Rampertaap, A.; Greeves, J.; MacKinney, J.; Raguso, M.; Selstrom, J.

2000-01-01

The United States of America has a large number of sites where radioactive materials have been mined, processed, produced, or used. Upon completion of activities at these sites, some will be cleaned up completely and released for unrestricted future use. However, at other sites, contamination will remain on the site following cleanup, requiring long term institutional controls. Depending on the purpose or the activity conducted at a specific site, these locations are generally under the jurisdiction of a federal agency: the United States Department of Energy, the United States Nuclear Regulatory Commission, the United States Environmental Protection Agency, or the United States Department of Defense. However, under certain conditions, the Nuclear Regulatory Commission relinquishes regulatory authority to individual states to regulate the commercial uses of radioactive materials (except for nuclear reactors), so some locations with radioactive materials are under the jurisdiction of individual states. Other sites with naturally occurring radioactive contamination may also be controlled by individual states. One or two sites under the jurisdiction of each agency are discussed where radioactive materials either existed in the past or exist today, and the source of contamination, the anticipated end state, and the process by which the responsible agency did or will conduct cleanup and site closure are described. Several issues are reviewed that must be addressed in order to design and implement remediations that will ensure long term protection for the environment and future inhabitants. The role of citizens in environmental cleanups is examined, and how institutional controls may be applied to ensure long term protection of remediations that leave some contaminants in place. (author)

Occupational noise exposure and regulatory adherence in music venues in the United Kingdom

Directory of Open Access Journals (Sweden)

Christopher Barlow

2012-01-01

Full Text Available Noise in most working environments is an unwanted by-product of the process. In most countries, noise exposure for workers has been controlled by legislation for many years. In the music industry the "noise" is actually the "desired" product, and for a long time the UK entertainment industry was exempt from these regulations. From April 2008, however, it became regulated under the Noise at Work Regulations 2005, meaning that employers from orchestras to nightclubs are legally required to adhere to the same requirements (based on ISO 9612:2009 for controlling noise exposure for their staff that have been applied to other industries for many years. A key question is to what degree, 2 years after implementation, these employers are complying with their legal responsibilities to protect the staff from noise? This study assessed four public music venues where live and/or recorded music is regularly played. Thirty staff members in different roles in the venues were monitored using noise dosimetry to determine noise exposure. Questionnaires were used to determine work patterns, attitudes to noise and hearing loss, and levels of training about noise risk. Results showed that the majority of staff (70% in all venues exceeded the daily noise exposure limit value in their working shift. Use of hearing protection was rare (<30% and not enforced by most venues. The understanding of the hazard posed by noise was low, and implementation of the noise regulations was haphazard, with staff regularly exceeding regulatory limits. The implication is that the industry is failing to meet regulatory requirements.

IAEA Mission Concludes Peer Review of UK's Nuclear Regulatory Framework

International Nuclear Information System (INIS)

2013-01-01

Full text: Senior international nuclear safety and radiation protection experts today concluded a ten-day International Atomic Energy Agency (IAEA) mission to review the regulatory framework for nuclear and radiation safety in the United Kingdom (UK). The Integrated Regulatory Review Service (IRRS) mission team said in its preliminary findings that the UK had made considerable progress since reviews in 2006 and 2009. It also identified good practices in the country's nuclear regulatory system. In addition to following up previous missions, a key objective was to review the effectiveness of the role of the Office of Nuclear Regulation (ONR), the UK's nuclear regulator, in ensuring the safety of radioactive waste management and decommissioning, occupational radiation protection, and public and environmental exposures, including emergency planning and response. The mission also considered the response of the UK's regulatory regime to the implications of the Fukushima Daichi accident had been timely and effective. Recommendations and suggestions were made to the ONR and the Government aimed at strengthening the effectiveness of the country's regulatory framework and functions in line with IAEA Safety Standards, the control of radioactive discharges and environmental monitoring. 'The staff of ONR is clearly dedicated to their mission to secure the protection of people and society from the hazards of the nuclear industry. I am confident that ONR will use the results of this mission to further enhance their regulatory programs', said Bill Borchardt, mission leader and former Executive Director of the United States Nuclear Regulatory Commission (NRC). 'The staff were open and cooperative in their discussions; they provided the fullest practicable assistance, and accepted advice from the Team for continuous improvement in their regulatory work'. ONR's Chief Executive, John Jenkins, said that the full report of the IRRS mission will enhance regulatory effectiveness in the UK

Nuclear safety philosophy in the United Kingdom