Performance-based quality assurance: the regulatory viewpoint

International Nuclear Information System (INIS)

Sajaroff, Pedro M.

2000-01-01

This paper complements and upgrades a previous one recently presented, the aim is a further contribution to a wide dissemination of this new methodology and way of thinking. Modern quality management techniques emphasizes errors prevention instead of finding and correcting them, in line with the new generation of ISO-9000 documents. Performance-based QA is coherent with this 'right-first-time' attitude, resting on the managerial role (establishing and applying policies and instructions allowing to integrate quality objectives to everyday work) and on the responsibility of every single involved person (the attainment of such objectives). The contents of the final draft of the revised IAEA NUSS Code on QA -namely 'Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Facilities', is based on that approach, so it is not perspective. The text only contains ten basic requirements, where the objective is improving nuclear safety through an improvement in the methods applied for attaining quality during design, construction, commissioning, operation and decommissioning of nuclear installations. These requirements are assigned to: 'Management' (QA programme; training and qualification; non-conformance control and corrective actions; document control and records); 'Performance' (work; design; procurement; inspection and testing for acceptance) and 'Assessment' (management self-assessment; independent assessment). The management is responsible for planning, organization, direction, control and support; the line groups are responsible for attaining quality; and the assessment group is responsible for analyzing the management's and the line groups' effectiveness. From the regulatory point of view in the performance context, operating organizations will have to demonstrate the effective fulfillment of QA requirements to the satisfaction of regulatory authorities. This is not a novel mechanism, it is usual within the regulatory performance approach. The Code is

A Process Perspective on Regulation: A Grounded Theory Study into Regulatory Practice in Newly Liberalized Network-Based Markets

NARCIS (Netherlands)

Ubacht, J.

The transition from a former monopolistic towards a more competitive market in
newly liberalized network-based markets raises regulatory issues. National Regulatory Authorities (NRA) face the challenge to deal with these issues in order to guide the transition process. Although this transition

Safety system upgrades to a research reactor: A regulatory perspective

International Nuclear Information System (INIS)

Lamarre, G.B.; Martin, W.G.

2003-01-01

The NRU (National Research Universal) reactor, located at the Chalk River Laboratories of Atomic Energy of Canada Limited (AECL), first achieved criticality November 3, 1957. AECL continues to operate NRU for research to support safety and reliability studies for CANDU reactors and as a major supplier of medical radioisotopes. Following a detailed systematic review and assessment of NRU's design and the condition of its primary systems, AECL formally notified the Canadian Nuclear Safety Commission's (CNSC) predecessor - the Atomic Energy Control Board - in 1992 of its intention to upgrade NRU's safety systems. AECL proposed seven major upgrades to provide improvements in shutdown capability, heat removal, confinement, and reactor monitoring, particularly during and after a seismic event. From a CNSC perspective, these upgrades were necessary to meet modern safety standards. From the start of the upgrades project, the CNSC provided regulatory oversight aimed at ensuring that AECL maintained a structured approach to the upgrades. The elements of the approach include, but are not limited to, the determination of project milestones and target dates; the formalization of the design process and project quality assurance requirements; the requirements for updated documentation, including safety reports, safety notes and commissioning reports; and the approval and authorization process. This paper details, from a regulatory perspective, the structured approach used in approving the design, construction, commissioning and subsequent operation of safety system upgrades for an existing and operating research reactor, including the many challenges faced when attempting to balance the requirements of the upgrades project with AECL's need to keep NRU operating to meet its important research and production objectives. (author)

Adolescents’ and Parents’ Regulatory Focus as Determinants of Future Time Perspective on School and Professional Career

NARCIS (Netherlands)

Andre, L.; van Vianen, A.E.M.; Peetsma, T.T.D.

2017-01-01

Future time perspective (FTP) - individuals' orientation towards future goals and consideration of future consequences - is a successful motivator in education and work. This study is the first that integrates Regulatory focus (RF) theory with FTP theory to explore relationships between adolescents'

Tracing the self-regulatory bases of moral emotions

OpenAIRE

Sheikh, Sana; Janoff-Bulman, Ronnie

2010-01-01

In this article we explore a self-regulatory perspective on the self-evaluative moral emotions, shame and guilt. Broadly conceived, self-regulation distinguishes between two types of motivation: approach/activation and avoidance/inhibition. We use this distinction to conceptually understand the socialization dimensions (parental restrictiveness versus nurturance), associated emotions (anxiety versus empathy), and forms of morality (proscriptive versus prescriptive) that serve as precursors to...

Finding gene regulatory network candidates using the gene expression knowledge base.

Science.gov (United States)

Venkatesan, Aravind; Tripathi, Sushil; Sanz de Galdeano, Alejandro; Blondé, Ward; Lægreid, Astrid; Mironov, Vladimir; Kuiper, Martin

2014-12-10

Network-based approaches for the analysis of large-scale genomics data have become well established. Biological networks provide a knowledge scaffold against which the patterns and dynamics of 'omics' data can be interpreted. The background information required for the construction of such networks is often dispersed across a multitude of knowledge bases in a variety of formats. The seamless integration of this information is one of the main challenges in bioinformatics. The Semantic Web offers powerful technologies for the assembly of integrated knowledge bases that are computationally comprehensible, thereby providing a potentially powerful resource for constructing biological networks and network-based analysis. We have developed the Gene eXpression Knowledge Base (GeXKB), a semantic web technology based resource that contains integrated knowledge about gene expression regulation. To affirm the utility of GeXKB we demonstrate how this resource can be exploited for the identification of candidate regulatory network proteins. We present four use cases that were designed from a biological perspective in order to find candidate members relevant for the gastrin hormone signaling network model. We show how a combination of specific query definitions and additional selection criteria derived from gene expression data and prior knowledge concerning candidate proteins can be used to retrieve a set of proteins that constitute valid candidates for regulatory network extensions. Semantic web technologies provide the means for processing and integrating various heterogeneous information sources. The GeXKB offers biologists such an integrated knowledge resource, allowing them to address complex biological questions pertaining to gene expression. This work illustrates how GeXKB can be used in combination with gene expression results and literature information to identify new potential candidates that may be considered for extending a gene regulatory network.

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 systems-based licensing guidance documentation

International Nuclear Information System (INIS)

Delligatti, M.S.

1991-01-01

The US Nuclear Regulatory Commission (NRC) has developed a series of licensing guidance documents based on the regulatory requirements in Part 60 of Title 10 of the Code of Federal Regulations (10 CFR Part 60). This regulatory systems-based approach to licensing guidance documentation relies on the definition of the high-level waste repository in 10 CFR Part 60. A document which is important for the frame-work it gives to other programmatic licensing guidance is the Draft Regulatory Guide open-quotes Format and Content for the License Application for the High-Level Waste Repositoryclose quotes (FCRG). The FCRG describes a format and content acceptable to NRC for a high-level waste repository license application pursuant to the requirements of 10 CFR Part 60. Other licensing guidance documents will be compatible with the FCRG

Regulatory challenges in the review of data from global clinical trials: the PMDA perspective.

Science.gov (United States)

Asano, K; Tanaka, A; Sato, T; Uyama, Y

2013-08-01

Regulatory agencies face challenges in reviewing data from global clinical trials (GCTs) in the era of globalization of drug development. One major challenge is consideration of ethnic factors in evaluating GCT data so as to extrapolate foreign population data to one's own national population. Here, we present the Pharmaceuticals and Medical Devices Agency (PMDA) perspective in reviewing GCT data in new drug applications (NDAs) and discuss future challenges for new drug approval.

Heart Rate Variability: New Perspectives on Physiological Mechanisms, Assessment of Self-regulatory Capacity, and Health risk.

Science.gov (United States)

McCraty, Rollin; Shaffer, Fred

2015-01-01

Heart rate variability, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operates on different time scales to adapt to environmental and psychological challenges. This article briefly reviews neural regulation of the heart and offers some new perspectives on mechanisms underlying the very low frequency rhythm of heart rate variability. Interpretation of heart rate variability rhythms in the context of health risk and physiological and psychological self-regulatory capacity assessment is discussed. The cardiovascular regulatory centers in the spinal cord and medulla integrate inputs from higher brain centers with afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. We also discuss the intrinsic cardiac nervous system and the heart-brain connection pathways, through which afferent information can influence activity in the subcortical, frontocortical, and motor cortex areas. In addition, the use of real-time HRV feedback to increase self-regulatory capacity is reviewed. We conclude that the heart's rhythms are characterized by both complexity and stability over longer time scales that reflect both physiological and psychological functional status of these internal self-regulatory systems.

Licensing of Generic Medicines: Are There Any Challenges Left? A Pharmaceutical Regulatory Perspective.

Science.gov (United States)

Borg, John Joseph; Tomasi, Paolo; Pani, Luca; Aislaitner, George; Pirozynski, Michal; Leufkens, Hubert; Melchiorri, Daniela

2014-01-01

When an innovative product (innovator) is not covered anymore by intellectual property rights, cheaper equivalent medicinal products (generic products) may be marketed and used in clinical practice. The regulation of generic products is well-established, and is primarily based on standard rules for quality, therapeutic equivalence requirements (the latter in most instances proven through a bioequivalence study), and safety data for the innovator. The extensive experience from bringing generic products to the market over the last decades allows the conclusion that they are well-accepted and provide a useful alternative option for cost-effective pharmacotherapy. While supporting this conclusion, there are a number of issues to be considered during the assessment of a generic product application. Six scenarios are described in total, from an efficacy and a safety perspective, where potential concerns with the current regulatory standards could arise in the approval of generic products. We also propose solutions to these scenarios in order to foster debate on these issues.

The relationship between time perspective and self-regulatory processes, abilities and outcomes: a protocol for a meta-analytical review.

Science.gov (United States)

Baird, Harriet M; Webb, Thomas L; Martin, Jilly; Sirois, Fuschia M

2017-07-05

Both theoretical and empirical evidence suggests that time perspective is likely to influence self-regulatory processes and outcomes. Despite the theoretical and practical significance of such relations, the relationship between time perspective and self-regulatory processes and outcomes across different measures, samples and life domains, including health, has yet to be explored. The proposed review will develop a taxonomy for classifying measures according to the self-regulatory process, ability or outcome that they are likely to reflect. Electronic scientific databases will be searched, along with relevant conference abstract booklets and citation lists. Additionally, a call for unpublished data will be submitted to relevant bodies. To be eligible for inclusion, studies must include a measure of time perspective and a measure of at least one self-regulatory process, ability and/ or outcome. Eligibility will not be restricted by publication date, language, type of sample or setting. The bivariate correlations will be extracted (or calculated) and submitted to a random-effects meta-analysis. The sample-weighted average effect size, heterogeneity, risk of bias and publication bias will be calculated, and the effects of categorical and continuous moderator variables on the effect sizes will be determined. The proposed meta-analysis will synthesise previously conducted research; thus, ethical approval is not required. The findings will be submitted for publication in an international peer-reviewed journal and reported as part of the first author’s PhD thesis. The findings will also be disseminated to the research community and, where appropriate, to other interested parties through presentations at relevant academic and non-academic conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Future time perspective and health behaviors: temporal framing of self-regulatory processes in physical exercise and dietary behaviors.

Science.gov (United States)

Gellert, Paul; Ziegelmann, Jochen P; Lippke, Sonia; Schwarzer, Ralf

2012-04-01

Limitations in perceived lifetime can undermine long-term goal striving. Planning is supposed to translate intentions into health behaviors and to operate as a compensatory strategy to overcome goal striving deficits associated with a limited time perspective. Two longitudinal studies were conducted examining the compensatory role of planning: an online survey on fruit and vegetable consumption (N = 909; 16-78 years; follow-up at 4 months) and a questionnaire study on physical exercise in older adults (N = 289; 60-95 years, over a half-year period). Intentions, planning, and behavior were measured in a behavior-specific, future time perspective in a generic manner. Planning mediated between intentions and both health behaviors. Time perspective operated as a moderator, indicating that in individuals with a more limited time perspective, a stronger effect of planning on health behaviors emerged. Planning as a self-regulatory strategy may compensate for a limited time perspective.

The role of effective communications in Nuclear Regulatory Commission licensing

International Nuclear Information System (INIS)

Counsil, W.G.

1991-01-01

Communications are essential to the licensing and general regulatory program of the Nuclear Regulatory Commission. This paper attempts to identify and address certain aspects of, and approaches to, maintaining effective and efficient communications. It considers, from the perspective of the high-level radioactive waste repository program, both internal communication within the DOE itself and external communication with the Nuclear Regulatory Commission and interested parties. Many of the points presented are based on lessons learned from electric utility experience with nuclear plants

Core damage frequency perspectives based on IPE results

International Nuclear Information System (INIS)

Dingman, S.E.; Camp, A.L.; LaChance, J.L.; Drouin, M.T.

1996-01-01

In November 1988, the US Nuclear Regulatory Commission (NRC) issued Generic Letter 88-20 requesting that all licensees perform an individual Plant Examination (IPE) to identify any plant-specific vulnerability to severe accidents and report the results to the Commission. This paper provides perspectives gained from reviewing 75 Individual Plant Examination (IPE) submittals covering 108 nuclear power plant units. Variability both within and among reactor types is examined to provide perspectives regarding plant-specific design and operational features, and modeling assumptions that play a significant role in the estimates of core damage frequencies in the IPEs

Status of nuclear regulatory research and its future perspectives

International Nuclear Information System (INIS)

Lee, J. I.; Kim, W. S.; Kim, M. W.

1999-01-01

A comprehensive investigation of the regulatory research comprising an examination of the research system, its areas and contents, and the goals and financial resources is undertaken. As a result of this study, the future direction of regulatory research and its implementation strategies are suggested to resolve the current issues emerging from this examination. The major issues identified in the study are; (a) an insufficient investment in nuclear regulatory and safety research, (b) an interfacial discrepancy between similar research areas, and (c) a limitation of utilizing research results. To resolve these issues, several measures are proposed : (1) developing a lead project to establish a comprehensive infrastructure for enhancing research cooperation between nuclear organizations including institutes, industry, and universities, with an aim to improve cooperation between projects and to strengthen overall coordination functions among research projects, (2) introducing a certification system on research outcome to promote the proliferation of both research results themselves and their application with a view to enhancing the research quality, (3) strengthening the cooperative system to promote the international cooperative research, and (4) digitalizing all documents and materials relevant to safety and regulatory research to establish KIMS (knowledge and information based management system). It is expected that the aforementioned measures suggested in this study will enhance the efficiency and effectiveness of both nuclear regulatory and safety research, if they are implemented after deliberating with the government and related nuclear industries in the near future

Nanoparticulate materials and regulatory policy in Europe: An analysis of stakeholder perspectives

International Nuclear Information System (INIS)

Helland, Aasgeir; Kastenholz, Hans; Thidell, Aake; Arnfalk, Peter; Deppert, Knut

2006-01-01

The novel properties of nanoparticulate materials (NPM) and the rapid development of NPM based products have raised many unanswered questions and concerns by different stakeholders over its consequences for the environment and human health. These concerns have led to an increasing discussion in both the US and Europe about possible regulatory policies for NPM. In this article a comparative study of stakeholders' perceptions on regulatory policy issues with NPM in Europe is presented. It was found that industry wants to regulate this area if the scientific evidence demonstrates that NPM are harmful, but also that the regulatory bodies do not find it necessary at this point of time to regulate until scientific evidence demonstrates that NPM are harmful. This research therefore shows that there will most likely not be any regulatory interventions until there is an established and convincing scientific knowledge base demonstrating that NPM can be hazardous. It is furthermore discussed in this article the different roles and responsibilities of the stakeholders in financing the research required to establish the necessary level of fundamental scientific evidence. It was also found that the activity of the regulatory bodies on this issue differ between the European countries

Phylogeny based discovery of regulatory elements

Directory of Open Access Journals (Sweden)

Cohen Barak A

2006-05-01

Full Text Available Abstract Background Algorithms that locate evolutionarily conserved sequences have become powerful tools for finding functional DNA elements, including transcription factor binding sites; however, most methods do not take advantage of an explicit model for the constrained evolution of functional DNA sequences. Results We developed a probabilistic framework that combines an HKY85 model, which assigns probabilities to different base substitutions between species, and weight matrix models of transcription factor binding sites, which describe the probabilities of observing particular nucleotides at specific positions in the binding site. The method incorporates the phylogenies of the species under consideration and takes into account the position specific variation of transcription factor binding sites. Using our framework we assessed the suitability of alignments of genomic sequences from commonly used species as substrates for comparative genomic approaches to regulatory motif finding. We then applied this technique to Saccharomyces cerevisiae and related species by examining all possible six base pair DNA sequences (hexamers and identifying sequences that are conserved in a significant number of promoters. By combining similar conserved hexamers we reconstructed known cis-regulatory motifs and made predictions of previously unidentified motifs. We tested one prediction experimentally, finding it to be a regulatory element involved in the transcriptional response to glucose. Conclusion The experimental validation of a regulatory element prediction missed by other large-scale motif finding studies demonstrates that our approach is a useful addition to the current suite of tools for finding regulatory motifs.

Design reviews from a regulatory perspective

International Nuclear Information System (INIS)

Foster, B.D.

1991-01-01

This paper presents views on the role of the licensing engineer in the design process with specific emphasis on design reviews and the automated information management tools that support design reviews. The licensing engineer is seen as an important member of a design review team. The initial focus of the licensing engineer during design reviews is shown to be on ensuring that applicable regulatory requirements are addressed by the design. The utility of an automated tool, such as a commitments management system, to support regulatory requirements identification is discussed. The next responsibility of the licensing engineer is seen as verifying that regulatory requirements are transformed into measurable performance requirements. Performance requirements are shown to provide the basis for developing detailed design review criteria. Licensing engineer input during design reviews is discussed. This input is shown to be especially critical in cases where review findings may impact application of regulatory requirements. The use of automated tools in supporting design reviews is discussed. An information structure is proposed to support design reviews in a regulated environment. This information structure is shown to be useful to activities beyond design reviews. Incorporation of the proposed information structure into the Licensing Support System is proposed

Upgrading Atucha 1 nuclear power plant. Regulatory perspective

International Nuclear Information System (INIS)

Caruso, G.

1998-01-01

Atucha 1 nuclear power plant has unique design and its commercial operation started in 1974. The upgrading decisions, the basis for an upgrading program and its status of implementation are presented. Regulatory decisions derived from the performance-based approach have the advantage that they enable balancing of the overall plant risk and identifying at different plant levels the areas where improvements are necessary. (author)

A Glance on the Safety Culture in Industrial Gamma Radiography in the Philippines: Regulatory Body Perspective

International Nuclear Information System (INIS)

Borras, A.M.

2016-01-01

The current version of the Code of PNRI Regulations (CPR) Part 11 was published in the Official Gazette on 2010. It is just a year ahead of the publication of the IAEA Specific Safety Guide No. 11. In view of these, radiation safety culture in the practice of industrial gamma radiography was not yet fully introduced in the said national regulations in the country. However, it should not be a reflection that the radiation workers in the country specifically in the said field of practice do not exercise positive safety culture. The Nuclear Regulatory Division (NRD)—regulatory arm, although not yet separated from the Philippine Nuclear Research Institute (PNRI0) as mandated by law — the promotional organization, has a well established and systemic regulatory infrastructure. It is attested by several studies and reports, among others. This study aims to assess the status of the existing safety culture in the conduct of industrial gamma radiography in the country through personnel perception survey of the radiation workers, i.e., managers, radiation safety officers, radiographers and radiographer’s assistants, based on the IAEA five characteristics of safety culture stipulated in the IAEA Safety Guide No. GS-G-3.5, “The Management System for Nuclear Installations”. It is assessed by the NRD of the PNRI. Also, the study determines the existence of safety culture as to the perspective of NRD through observations on the conduct of radiographic operations and walk-through of the facility while using the three-level Schein Model, i.e., “artefacts”, “espoused values” and “basic assumptions” and document reviews, among others

NRC review of passive reactor design certification testing programs: Overview and regulatory perspective

International Nuclear Information System (INIS)

Levin, A.E.

1993-01-01

Reactor vendors are developing new designs for future deployment, including open-quotes passiveclose quotes light water reactors (LWRs), such as General Electric's (G.E.'s) simplified boiling water reactor (SBWR) and Westinghouse's AP600, which depend primarily on inherent processes, such as national convection and gravity feed, for safety injection and emergency core cooling. The U.S. Nuclear Regulatory Commission (NRC) has implemented a new process, certification of standardized reactor designs, for licensing these Plants. Part 52 of Title 10 of the Code of Federal Regulations (10CFR52) contains the requirements that vendors must meet for design certification. One important section, 10CFR52.47, reads open-quotes Certification of a standard design which . . . utilizes simplified, inherent, passive, or other innovative means to accomplish its safety functions will be granted only if: (1) The performance of each safety feature of the design has been demonstrated through either analysis, appropriate test programs, experience, or a combination thereof; (2) Interdependent effects among the safety features have been found acceptable by analysis, appropriate test programs, experience, or a combination thereof; and (3) Sufficient data exist on the safety features of the design to assess the analytical tools used for safety analyses. . . . The vendors have initiated programs to test innovative features of their designs and to develop data bases needed to validate their analytical codes, as required by the design certification rule. Accordingly, the NRC is reviewing and evaluating the vendors programs to ensure that they address adequately key issues concerning safety system performance. This paper provides an overview of the NRC's review process and regulatory perspective

Reduction of regulatory risk: a network economic approach

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2007-01-01

Several definitions of regulatory risk are known from the literature. From the perspective of regulatory reform it is important to differentiate between the impact of a given regulatory scheme on the firm's risk exposure and the risk arising from discretionary behavior of regulatory agencies. Whereas the conse-quences of effective regulation in principle are known and accepted, excessive regulatory discretion may cause a strong need for regulatory reform. Regulatory reform focussing on the re...

Safety culture from a regulatory perspective

International Nuclear Information System (INIS)

Dahlgren, K.

1996-01-01

The Swedish Nuclear Power Inspectorate, SKI, has in its regulatory approach to the area of management and organization focussed on the process of continuous improvement and have in collaboration with Battelle Human Affairs Research Center, Seattle, developed a conceptual model of the important characteristics of a continuous improvement organization and how to assess it. In this work SKI has also recognized the importance of the regulatory goals and strategies adopted by SKI for promoting an improvement process on the part of the utilities, which will be further discussed below. 15 refs

Safety culture from a regulatory perspective

Energy Technology Data Exchange (ETDEWEB)

Dahlgren, K [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

1997-12-31

The Swedish Nuclear Power Inspectorate, SKI, has in its regulatory approach to the area of management and organization focussed on the process of continuous improvement and have in collaboration with Battelle Human Affairs Research Center, Seattle, developed a conceptual model of the important characteristics of a continuous improvement organization and how to assess it. In this work SKI has also recognized the importance of the regulatory goals and strategies adopted by SKI for promoting an improvement process on the part of the utilities, which will be further discussed below. 15 refs.

The Political Economy of Regulatory Change

DEFF Research Database (Denmark)

Buch-Hansen, Hubert

2012-01-01

This article aims to explain the broader evolution of British merger control. To this end it outlines a novel critical political economy perspective on regulation and regulatory change which differs from established political economy approaches, such as the regulatory capitalism/state perspectives...... to the analysis of the evolution of British merger control provides some important new insights, most notably that the content, form, and scope of merger control in Britain have been deeply transformed in accordance with neoliberal ideas since the 1980s and that this process, which was part of a broader...

Systemic Approach to Safety from a Regulatory Perspective

International Nuclear Information System (INIS)

Edland, A.

2016-01-01

In Sweden and especially in the Swedish oversight of nuclear power plants there has been a strong commitment to the interactions between Man-Technology-Organization (MTO) for many years. Safety issues and the importance of working with these issues have often been highlighted in specific oversight actions. Since 30 years there has been a tradition and a development of experience in Sweden taking a systemic MTO approach to safety. Inspection teams have been created with both psychologists and technical expertise in order to cover the whole MTO perspective during oversight inspections at the nuclear power plants. Safety is based on preventive actions where both technology and human behaviour are taken into account. To do this, it is important to have knowledge about the different factors that influence the performance of individuals, groups and organizations. However, it is also important to remember to not only discuss humans, management and organizations in terms of their limitations, errors and shortcomings but also in terms of their strengths in stopping a chain of events, in learning, inventing and improving. Having an integrated view of safety, focussing on the relations between human, technology and organization (MTO) refers to a systemic perspective on how radiation safety are affected by the relationship between: Human’s abilities and limitations; Technical equipment and the surrounding environment; The organization and the opportunities this provides. The Section of Man-Technology-Organization in the Swedish authority consist today of 12 Human factors specialists with behaviour science education. The section is responsible for the oversight at nuclear power plants in many areas; safety management, leadership and organization, safety culture, competence assurance, fitness for duty, suitability, education and staffing, knowledge management, working conditions, MTO perspective/ergonomics of control room work and plant modification, incident analysis and risk

Global Regulatory Differences for Gene- and Cell-Based Therapies

DEFF Research Database (Denmark)

Coppens, Delphi G M; De Bruin, Marie L; Leufkens, Hubert G M

2017-01-01

Gene- and cell-based therapies (GCTs) offer potential new treatment options for unmet medical needs. However, the use of conventional regulatory requirements for medicinal products to approve GCTs may impede patient access and therapeutic innovation. Furthermore, requirements differ between...... jurisdictions, complicating the global regulatory landscape. We provide a comparative overview of regulatory requirements for GCT approval in five jurisdictions and hypothesize on the consequences of the observed global differences on patient access and therapeutic innovation....

Steam Generator tube integrity -- US Nuclear Regulatory Commission perspective

International Nuclear Information System (INIS)

Murphy, E.L.; Sullivan, E.J.

1997-01-01

In the US, the current regulatory framework was developed in the 1970s when general wall thinning was the dominant degradation mechanism; and, as a result of changes in the forms of degradation being observed and improvements in inspection and tube repair technology, the regulatory framework needs to be updated. Operating experience indicates that the current U.S. requirements should be more stringent in some areas, while in other areas they are overly conservative. To date, this situation has been dealt with on a plant-specific basis in the US. However, the NRC staff is now developing a proposed steam generator rule as a generic framework for ensuring that the steam generator tubes are capable of performing their intended safety functions. This paper discusses the current U.S. regulatory framework for assuring steam generator (SG) tube integrity, the need to update this regulatory framework, the objectives of the new proposed rule, the US Nuclear Regulatory Commission (NRC) regulatory guide (RG) that will accompany the rule, how risk considerations affect the development of the new rule, and some outstanding issues relating to the rule that the NRC is still dealing with

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.

Information resources in state regulatory agencies-a California perspective

Energy Technology Data Exchange (ETDEWEB)

DiZio, S.M. [California Environmental Protection Agency, Sacramento (United States)

1990-12-31

Various state regulatory agencies have expressed a need for networking with information gatherers/researchers to produce a concise compilation of primary information so that the basis for regulatory standards can be scientifically referenced. California has instituted several programs to retrieve primary information, generate primary information through research, and generate unique regulatory standards by integrating the primary literature and the products of research. This paper describes these programs.

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...

Some areas of concern in Indian PHWRs from regulatory perspective

Energy Technology Data Exchange (ETDEWEB)

Gupta, V K [Operating Plants Safety Division, Atomic Energy Regulatory Board, Bhabha Atomic Research Centre (BARC), Bombay (India)

1991-04-01

The basic concern from regulatory perspective in the operation of Indian PHWRs is for radiation exposure to the occupational workers and to the members of public during normal operation as well as abnormal conditions. The radiation exposure to the occupational workers is the result of radiation conditions in the plant and the practices followed for operation and maintenance. Both technical and administrative actions are responsible in controlling the radiation exposures. As far as exposure to the members of public is concerned, integrity of heat transport and moderator systems, performance of the ventilation system and integrity of fuel cladding are important elements during normal operation and some of the anticipated operational occurrences. Containment systems play an important role in controlling the impact in public domain during accident conditions. Elaborate emergency preparedness plans ready in advance perfected and optimised through drills and exercises give an assurance that should a mishap occur requiring emergency action in the public domain, adequate and necessary actions to reduce the radiological consequences will be taken. In this context, four areas of interest are: Radiation Exposure of Occupational Workers, Fuel Performance, Containment Systems and Emergency Preparedness in Public Domain. (author)

Some areas of concern in Indian PHWRs from regulatory perspective

International Nuclear Information System (INIS)

Gupta, V.K.

1991-01-01

The basic concern from regulatory perspective in the operation of Indian PHWRs is for radiation exposure to the occupational workers and to the members of public during normal operation as well as abnormal conditions. The radiation exposure to the occupational workers is the result of radiation conditions in the plant and the practices followed for operation and maintenance. Both technical and administrative actions are responsible in controlling the radiation exposures. As far as exposure to the members of public is concerned, integrity of heat transport and moderator systems, performance of the ventilation system and integrity of fuel cladding are important elements during normal operation and some of the anticipated operational occurrences. Containment systems play an important role in controlling the impact in public domain during accident conditions. Elaborate emergency preparedness plans ready in advance perfected and optimised through drills and exercises give an assurance that should a mishap occur requiring emergency action in the public domain, adequate and necessary actions to reduce the radiological consequences will be taken. In this context, four areas of interest are: Radiation Exposure of Occupational Workers, Fuel Performance, Containment Systems and Emergency Preparedness in Public Domain. (author)

Future regulatory research needs on risk-informed and performance-based regulation

International Nuclear Information System (INIS)

Kim, Wong Sik; Kim, Hho Jung

2004-01-01

The USNRC has pursued the incorporation of risk-informed and performance-based regulation (RIPBR) into nuclear safety regulatory system, as an alternative to improve existing nuclear safety regulation of nuclear power plants, which is deterministic and prescriptive. It focuses on the use of risk insight from probabilistic safety assessment (PSA). Recently, it becomes necessary to find a way to improve regulatory efficiency and effectiveness in order to cover the increasing regulatory needs in Korea. Also, the utility has optimized design and operation of the plant using PSA insight and equipment performance information. According to the increase of the necessity for regulatory improvement using risk and performance information, KINS (Korea Institute of Nuclear Safety) is developing, as a part of a mid and long-term project of Nuclear R and D program, how to adopt the RIPBR in Korean nuclear regulatory system. As the interim results, three basic directions and several principles that are necessary to implement RIPBR model were already identified from the previous study. This paper suggests a direction to future regulatory research on RIPBR based on the previous studies including the review of international trend of RIPBR and the evaluation of risk-informed regulatory environment

Manufacturing, regulatory and commercial challenges of biopharmaceuticals production: a Finnish perspective.

Science.gov (United States)

Närhi, Marko; Nordström, Katrina

2005-04-01

Biopharmaceuticals product development is a broad and multidisciplinary field. Science and technology are combined with new manufacturing, regulatory and commercial challenges. However, although there is ample literature on the molecular biology and biochemistry of products, the implementation of processes from test tube to commercial scale has not received similar attention. Consequently, the present study aims to highlight, from practical point of view, some of the key issues involved with manufacturing technologies of biopharmaceuticals at a commercial scale. Regulatory requirements and investments are also addressed based on the practical experiences of start-up and small companies. Finland is used as a case-example of such companies as this is a EU-member state with strong technological growth and rapidly increasing number of biotech companies.

Regulatory Expectations for Safety Culture

Energy Technology Data Exchange (ETDEWEB)

Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-05-15

The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

Regulatory Expectations for Safety Culture

International Nuclear Information System (INIS)

Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

2014-01-01

The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety

Canadian and international approaches to regulatory effectiveness

International Nuclear Information System (INIS)

Lojk, R.

2014-01-01

Regulatory effectiveness is an important attribute of any regulator, particularly nuclear regulators. As the nuclear industry has matured, and as the social landscape has changed, so have views on what constitutes regulatory effectiveness. Canada has evolved its regulatory structure and modernized its legislative framework and technical requirements and guidance over time. In addition, Canada continues to collaborate with international agencies, particularly the NEA and the IAEA, to ensure that there is a common understanding of the indicators and key attributes of regulatory effectiveness. This paper discusses Canadian and international views on the subject, including perspectives from other industries. (author)

Model uncertainty from a regulatory point of view

International Nuclear Information System (INIS)

Abramson, L.R.

1994-01-01

This paper discusses model uncertainty in the larger context of knowledge and random uncertainty. It explores some regulatory implications of model uncertainty and argues that, from a regulator's perspective, a conservative approach must be taken. As a consequence of this perspective, averaging over model results is ruled out

Sequence-based model of gap gene regulatory network.

Science.gov (United States)

Kozlov, Konstantin; Gursky, Vitaly; Kulakovskiy, Ivan; Samsonova, Maria

2014-01-01

The detailed analysis of transcriptional regulation is crucially important for understanding biological processes. The gap gene network in Drosophila attracts large interest among researches studying mechanisms of transcriptional regulation. It implements the most upstream regulatory layer of the segmentation gene network. The knowledge of molecular mechanisms involved in gap gene regulation is far less complete than that of genetics of the system. Mathematical modeling goes beyond insights gained by genetics and molecular approaches. It allows us to reconstruct wild-type gene expression patterns in silico, infer underlying regulatory mechanism and prove its sufficiency. We developed a new model that provides a dynamical description of gap gene regulatory systems, using detailed DNA-based information, as well as spatial transcription factor concentration data at varying time points. We showed that this model correctly reproduces gap gene expression patterns in wild type embryos and is able to predict gap expression patterns in Kr mutants and four reporter constructs. We used four-fold cross validation test and fitting to random dataset to validate the model and proof its sufficiency in data description. The identifiability analysis showed that most model parameters are well identifiable. We reconstructed the gap gene network topology and studied the impact of individual transcription factor binding sites on the model output. We measured this impact by calculating the site regulatory weight as a normalized difference between the residual sum of squares error for the set of all annotated sites and for the set with the site of interest excluded. The reconstructed topology of the gap gene network is in agreement with previous modeling results and data from literature. We showed that 1) the regulatory weights of transcription factor binding sites show very weak correlation with their PWM score; 2) sites with low regulatory weight are important for the model output; 3

Regulatory and institutional challenges of corporate governance in ...

African Journals Online (AJOL)

Regulatory and institutional challenges of corporate governance in post banking consolidation Nigeria. ... PROMOTING ACCESS TO AFRICAN RESEARCH ... From a banking industry perspective, good corporate governance demands

Systemic Risk and Optimal Regulatory Architecture

NARCIS (Netherlands)

Espinosa-Vega, M.A.; Kahn, C.; Matta, R.; Sole, J.

2011-01-01

Until the recent financial crisis, the safety and soundness of financial institutions was assessed from the perspective of the individual institution. The financial crisis highlighted the need to take systemic externalities seriously when rethinking prudential oversight and the regulatory

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.

Analytical perspectives on performance-based management

DEFF Research Database (Denmark)

Wadmann, Sarah; Johansen, Sarah; Lind, Ane

2013-01-01

Performance-based management (PBM) has become a dominant form of governance in health care and there is a need for careful assessment of its function and effects. This article contains a cross-disciplinary literature synthesis of current studies of PBM. Literature was retrieved by database search...... perspectives allows appreciation of otherwise implicit assumptions and potential implications of PBM. Reflections on such differences are important to ensure vigilant appropriation of shifting management tools in health quality governance.......Performance-based management (PBM) has become a dominant form of governance in health care and there is a need for careful assessment of its function and effects. This article contains a cross-disciplinary literature synthesis of current studies of PBM. Literature was retrieved by database searches....... In the functionalist perspective, PBM is perceived as a management tool aimed at improving health care services by means of market-based mechanisms. In the interpretive perspective, the adoption of PBM is understood as consequence of institutional and individual agents striving for public legitimacy. In the post...

Perspectives on reactor safety

Energy Technology Data Exchange (ETDEWEB)

Haskin, F.E. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Chemical and Nuclear Engineering; Camp, A.L. [Sandia National Labs., Albuquerque, NM (United States)

1994-03-01

The US Nuclear Regulatory Commission (NRC) maintains a technical training center at Chattanooga, Tennessee to provide appropriate training to both new and experienced NRC employees. This document describes a one-week course in reactor, safety concepts. The course consists of five modules: (1) historical perspective; (2) accident sequences; (3) accident progression in the reactor vessel; (4) containment characteristics and design bases; and (5) source terms and offsite consequences. The course text is accompanied by slides and videos during the actual presentation of the course.

Perspectives on reactor safety

International Nuclear Information System (INIS)

Haskin, F.E.

1994-03-01

The US Nuclear Regulatory Commission (NRC) maintains a technical training center at Chattanooga, Tennessee to provide appropriate training to both new and experienced NRC employees. This document describes a one-week course in reactor, safety concepts. The course consists of five modules: (1) historical perspective; (2) accident sequences; (3) accident progression in the reactor vessel; (4) containment characteristics and design bases; and (5) source terms and offsite consequences. The course text is accompanied by slides and videos during the actual presentation of the course

Industry perspective on digital upgrades: A utility perspective on digital upgrades

International Nuclear Information System (INIS)

Blauw, R.J.

1994-01-01

Nuclear utilities face the need to upgrade aging and obsolete safety related and other critical equipment. This is the result of operation and maintenance concerns for reliability and maintainability. Digital technology is an option for these upgrades. A number of utilities have attempted exercising the digital option. The regulatory licensing results have been inconsistent and have raised a variety of issues. These issues and the subsequent licensing uncertainties have caused some utilities to temporarily drop digital technology as an upgrade option. Resolution of these issues and the need for regulatory stability is driving the development of industry standards and guidelines. These will provide guidance to support consistent design and implementation of digital upgrades. Successful completion of these documents is necessary for renewed consideration of the use of digital technology. This paper will present a utility perspective on how project management, configuration control, and a rigorous design process can serve to address the present regulatory issues. These issues include commercial grade dedication, reliability, electromagnetic interference, and failure and error management. This perspective is consistent with the standards and guidelines development effort

Perspectives on Regulatory T Cell Therapies

OpenAIRE

Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S.P.; Buer, Jan

2009-01-01

Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (Treg) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, Treg cell therapies and development of drugs that specifically enhance Treg cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human Treg cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 ...

Blockchains and Bitcoin: Regulatory responses to cryptocurrencies

OpenAIRE

Guadamuz, Andres; Marsden, Chris

2015-01-01

This paper examines Bitcoin from a legal and regulatory perspective, answering several important questions.\\ud \\ud We begin by explaining what Bitcoin is, and why it matters. We describe problems with Bitcoin as a method of implementing a cryptocurrency. This introduction to cryptocurrencies allows us eventually to ask the inevitable question: is it legal? What are the regulatory responses to the currency? Can it be regulated?\\ud \\ud We make clear why virtual currencies are of interest, how s...

Genome-scale modeling of yeast: chronology, applications and critical perspectives.

Science.gov (United States)

Lopes, Helder; Rocha, Isabel

2017-08-01

Over the last 15 years, several genome-scale metabolic models (GSMMs) were developed for different yeast species, aiding both the elucidation of new biological processes and the shift toward a bio-based economy, through the design of in silico inspired cell factories. Here, an historical perspective of the GSMMs built over time for several yeast species is presented and the main inheritance patterns among the metabolic reconstructions are highlighted. We additionally provide a critical perspective on the overall genome-scale modeling procedure, underlining incomplete model validation and evaluation approaches and the quest for the integration of regulatory and kinetic information into yeast GSMMs. A summary of experimentally validated model-based metabolic engineering applications of yeast species is further emphasized, while the main challenges and future perspectives for the field are finally addressed. © FEMS 2017.

Hydrogen mitigation systems - a Canadian regulatory perspective

International Nuclear Information System (INIS)

Khosla, J.K.; Rizk, M.

1997-01-01

This is a discussion paper to examine the regulatory requirements that may be necessary for the design, operation and maintenance of the hydrogen mitigation systems. These systems (if deemed necessary to maintain the containment function), may be considered to be a part of the containment systems. Therefore, these requirements are derived mostly from the AECB Regulatory Document R-7, which specifies the requirements for containment systems for CANDU nuclear power plants. Some additional requirements, which are specific to these systems have also been included. These requirements relate to a systematic examination of the hazards of hydrogen, the design basis for the mitigation systems, their functional and design requirements, analytical support to justify their selection, and operating and testing requirements. The requirements for severe accident have not yet been developed. It is, however, anticipated that the design of the hydrogen mitigation system would be such that future requirement can be accommodated. These requirements are intended for application to the new reactors in Canada. For the existing reactors, their application will be subjected to practicability. (author)

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)

Utilizing national and international registries to enhance pre-market medical device regulatory evaluation.

Science.gov (United States)

Yue, Lilly Q; Campbell, Gregory; Lu, Nelson; Xu, Yunling; Zuckerman, Bram

2016-01-01

Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.

The future regulatory environment - a South African perspective

International Nuclear Information System (INIS)

Van der Woude, S.; Leaver, J.; Metcalf, P.E.

2000-01-01

The South African nuclear regulatory authority, the National Nuclear Regulator, regulates nuclear fuel cycle facilities as well as a large variety of mining and minerals processing activities. The future political, social, economical and technological environment, within which these facilities operate, will present numerous challenges to those who will be regulating them. In our presentation the challenges to be fulfilled in discharging the regulatory function are discussed, particularly in the context of a country with a small nuclear programme and a substantial developing component. Amongst the challenges discussed are: As part of the growing internationalization, the need to harmonize standards applied in different countries and the need to balance standards and practice applied in developed countries with resources available in developing countries; The need to consider the impact on the environment and not only on human beings; The impact of rapid advances in information technology on regulation; The maintenance and development of the appropriate expertise in the face of uncertainties regarding the future of the nuclear industry; Public involvement; The demands by society for greater standards of safety but at the same time for more effective and cost-effective regulation; The need for regulators to match customer demands on operators in terms of quality, speed, flexibility and costs; The privatization of nuclear fuel cycle facilities; The increased trend for larger facilities to outsource work to smaller companies; and, The need to balance good practice considerations with quantitatively determined risks in regulatory decision-making. (author)

The future regulatory environment - a South African perspective

Energy Technology Data Exchange (ETDEWEB)

Van der Woude, S.; Leaver, J.; Metcalf, P.E. [National Nuclear Regulator, Centurion (South Africa)

2000-07-01

The South African nuclear regulatory authority, the National Nuclear Regulator, regulates nuclear fuel cycle facilities as well as a large variety of mining and minerals processing activities. The future political, social, economical and technological environment, within which these facilities operate, will present numerous challenges to those who will be regulating them. In our presentation the challenges to be fulfilled in discharging the regulatory function are discussed, particularly in the context of a country with a small nuclear programme and a substantial developing component. Amongst the challenges discussed are: As part of the growing internationalization, the need to harmonize standards applied in different countries and the need to balance standards and practice applied in developed countries with resources available in developing countries; The need to consider the impact on the environment and not only on human beings; The impact of rapid advances in information technology on regulation; The maintenance and development of the appropriate expertise in the face of uncertainties regarding the future of the nuclear industry; Public involvement; The demands by society for greater standards of safety but at the same time for more effective and cost-effective regulation; The need for regulators to match customer demands on operators in terms of quality, speed, flexibility and costs; The privatization of nuclear fuel cycle facilities; The increased trend for larger facilities to outsource work to smaller companies; and, The need to balance good practice considerations with quantitatively determined risks in regulatory decision-making. (author)

Review of SFR Design Safety using Preliminary Regulatory PSA Model

International Nuclear Information System (INIS)

Na, Hyun Ju; Lee, Yong Suk; Shin, Andong; Suh, Nam Duk

2013-01-01

The major objective of this research is to develop a risk model for regulatory verification of the SFR design, and thereby, make sure that the SFR design is adequate from a risk perspective. In this paper, the development result of preliminary regulatory PSA model of SFR is discussed. In this paper, development and quantification result of preliminary regulatory PSA model of SFR is discussed. It was confirmed that the importance PDRC and ADRC dampers is significant as stated in the result of KAERI PSA model. However, the importance can be changed significantly depending on assumption of CCCG and CCF factor of PDRC and ADRC dampers. SFR (sodium-cooled fast reactor) which is Gen-IV nuclear energy system, is designed to accord with the concept of stability, sustainability and proliferation resistance. KALIMER-600, which is under development in Korea, includes passive safety systems (e. g. passive reactor shutdown, passive residual heat removal, and etc.) as well as active safety systems. Risk analysis from a regulatory perspective is needed to support the regulatory body in its safety and licensing review for SFR (KALIMER-600). Safety issues should be identified in the early design phase in order to prevent the unexpected cost increase and delay of the SFR licensing schedule that may be caused otherwise

Application of omics data in regulatory toxicology: report of an international BfR expert workshop.

Science.gov (United States)

Marx-Stoelting, P; Braeuning, A; Buhrke, T; Lampen, A; Niemann, L; Oelgeschlaeger, M; Rieke, S; Schmidt, F; Heise, T; Pfeil, R; Solecki, R

2015-11-01

Advances in omics techniques and molecular toxicology are necessary to provide new perspectives for regulatory toxicology. By the application of modern molecular techniques, more mechanistic information should be gained to support standard toxicity studies and to contribute to a reduction and refinement of animal experiments required for certain regulatory purposes. The relevance and applicability of data obtained by omics methods to regulatory purposes such as grouping of chemicals, mode of action analysis or classification and labelling needs further improvement, defined validation and cautious expert judgment. Based on the results of an international expert workshop organized 2014 by the Federal Institute for Risk Assessment in Berlin, this paper is aimed to provide a critical overview of the regulatory relevance and reliability of omics methods, basic requirements on data quality and validation, as well as regulatory criteria to decide which effects observed by omics methods should be considered adverse or non-adverse. As a way forward, it was concluded that the inclusion of omics data can facilitate a more flexible approach for regulatory risk assessment and may help to reduce or refine animal testing.

RNA regulatory networks in animals and plants: a long noncoding RNA perspective.

Science.gov (United States)

Bai, Youhuang; Dai, Xiaozhuan; Harrison, Andrew P; Chen, Ming

2015-03-01

A recent highlight of genomics research has been the discovery of many families of transcripts which have function but do not code for proteins. An important group is long noncoding RNAs (lncRNAs), which are typically longer than 200 nt, and whose members originate from thousands of loci across genomes. We review progress in understanding the biogenesis and regulatory mechanisms of lncRNAs. We describe diverse computational and high throughput technologies for identifying and studying lncRNAs. We discuss the current knowledge of functional elements embedded in lncRNAs as well as insights into the lncRNA-based regulatory network in animals. We also describe genome-wide studies of large amount of lncRNAs in plants, as well as knowledge of selected plant lncRNAs with a focus on biotic/abiotic stress-responsive lncRNAs. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Personal Perspective on the Initial Federal Health-Based Regulation to Remove Lead from Gasoline

Science.gov (United States)

Bridbord, Kenneth; Hanson, David

2009-01-01

Objective This article describes the personal experience and perspective of the authors, who had primary responsibility for drafting the initial health-based regulation limiting lead content of gasoline during the early 1970s while employed by the U.S. Environmental Protection Agency (EPA). Data source Information used by the U.S. EPA in developing the initial health-based regulation limiting lead content of gasoline in December 1973 and studies documenting the impact of that and subsequent actions. Data extraction Among the lessons learned from this experience is the importance of having input from independent scientists to the regulatory decision-making process. This also demonstrates the critical role of independent peer-reviewed research, such as that supported by the National Institutes of Health, as well as research conducted by scientists from the Centers for Disease Control and Prevention, in delineating the consequences of lead exposure in the population. Data synthesis Removal of lead from gasoline in the United States has been described as one of the great public health achievements of the 20th century, but it almost did not happen. The experience of the authors in developing this regulation may be helpful to others involved in developing health-based regulatory policy in the future. Conclusion The initial U.S. EPA health-based regulation to remove lead from gasoline is clearly an example where science successfully affected public policy. The leadership of the U.S. EPA at that time deserves much credit for establishing an atmosphere in which this was possible. PMID:19672397

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 changes to renewable energy support schemes: An international investment law perspective

OpenAIRE

Paleckaite, Gintare

2014-01-01

Thesist analyzes how regulatory changes related to renewable energy investment support schemes can be perceived under international investment law standards and how possible decisions of international investment law tribunals could impact investment in this sector. This research is based on case studies of two states: Spain and the Czech Republic and claims against them. These cases will assist in analyzing the effects of the amendment/revocation of renewable energy support schemes. Answers t...

Clinical trial regulation in Argentina: overview and analysis of regulatory framework, use of existing tools, and researchers' perspectives to identify potential barriers.

Science.gov (United States)

White, Lauren; Ortiz, Zulma; Cuervo, Luis G; Reveiz, Ludovic

2011-11-01

To review and analyze the regulatory framework of clinical trial registration, use of existing tools (publicly accessible national/international registration databases), and users' perspectives to identify possible barriers to registration compliance by sponsors and researchers in Argentina. Internationally registered trials recruiting patients in Argentina were found through clincialtrials.gov and the International Clinical Trial Registration Platform (ICTRP) and compared with publically available clinical trials registered through the National Administration of Drugs, Foods, and Medical Devices (ANMAT). A questionnaire addressing hypothesized attitudinal, knowledge-related, idiomatic, technical, economic, and regulatory barriers that could discourage or impede registration of clinical trials was developed, and semi-structured, in-depth interviews were conducted with a purposively selected sample of researchers (investigators, sponsors, and monitors) in Argentina. A response rate of 74.3% (n = 29) was achieved, and 27 interviews were ultimately used for analysis. Results suggested that the high proportion of foreign-sponsored or multinational trials (64.8% of all protocols approved by ANMAT from 1994-2006) may contribute to a communication gap between locally based investigators and foreign-based administrative officials. A lack of knowledge about available international registration tools and limited awareness of the importance of registration were also identified as limiting factors for local investigators and sponsors. To increase compliance and promote clinical trial registration in Argentina, national health authorities, sponsors, and local investigators could take the following steps: implement a grassroots educational campaign to improve clinical trial regulation, support local investigator-sponsor-initiated clinical trials, and/or encourage local and regional scientific journal compliance with standards from the International Committee of Medical Journal

Task-based dermal exposure models for regulatory risk assessment

NARCIS (Netherlands)

Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

2006-01-01

The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of

Broadening the cancer and cognition landscape: the role of self-regulatory challenges.

Science.gov (United States)

Arndt, Jamie; Das, Enny; Schagen, Sanne B; Reid-Arndt, Stephanie A; Cameron, Linda D; Ahles, Tim A

2014-01-01

The potentially detrimental effects of cancer and related treatments on cognitive functioning have emerged as one of the key foci of cancer survivorship research, but little is known about how psychological variables other than depression influence these relationships. To illustrate the potential of social psychological perspectives, we examine how a self-regulatory analysis and specific self-regulatory challenges of contending with cancer-related expectancies and stereotypes provide conceptual frameworks for understanding some of the potential causes and consequences of cancer-related cognitive deficits. Literatures on cancer-related cognitive deficits, self-regulatory ego depletion, expectancy stereotypes, and their points of convergence are briefly reviewed. A review and conceptual integration of relevant literatures suggest that coping with cancer can impair self-regulatory capacity. There is an overlap between cognitive deficits associated with self-regulatory challenge and with cancer and its treatment, and restoring self-regulatory resources can attenuate cancer-related cognitive deficits. Examination of specific regulatory challenges of contending with expectancies and stereotypes related to treatment suggests insights that can inform when and among whom cognitive deficits may most likely emerge. Integrating social psychological ideas with a substantial knowledge base can illustrate novel research trajectories that can deepen our understanding of cancer-related cognitive deficits and their impact on psychosocial well-being. Copyright © 2013 John Wiley & Sons, Ltd.

Nuclear Regulatory Commission probabilistic risk assessment implementation program: A status report

International Nuclear Information System (INIS)

Rubin, M.P.; Caruso, M.A.

1996-01-01

The US Nuclear Regulatory Commission (NRC) is undertaking a number of activities intended to increase the consideration of risk significance in its decision processes and the effective use of risk-based technologies in its regulatory activities. Although the NRC is moving toward risk-informed regulation throughout its areas of responsibilities, this paper focuses primarily on those issues associated with reactor regulation. As the NRC completed significant milestones in its development of probabilistic risk assessment (PRA) methodology and gained considerable experience in the limited application of risk assessment to selected regulatory activities, it became evident that a much broader use of risk informed approaches offered advantages to both the NRC and the US commercial nuclear industry. This desire to enhance the use of risk assessment is driven by the clear belief that application of PRA methods will result in direct improvements in nuclear power plant operational safety from the perspective of both the regulator and the plant operator. The NRC believed that an overall policy on the use of PRA methods in nuclear regulatory activities should be established so that the many potential applications of PRA could be implemented in a consistent and predictable manner that would promote regulatory stability and efficiency. This paper describes the key activities that the NRC has undertaken to implement the initial stages of an integrated risk-informed regulatory framework

The Dutch drug policy from a regulatory perspective

NARCIS (Netherlands)

Spapens, A.C.M.; Müller, T.; Van de Bunt, H.G.

2015-01-01

Starting in the 1970s, the Netherlands developed a regulatory regime for narcotic drugs by distinguishing between hashish and marihuana (“soft drugs”) and other drugs (“hard drugs”). The authorities decided to cease prosecuting the possession of consumer quantities of the former type and to allow

Determinants to dose reduction in EMCCR - in regulatory perspective

International Nuclear Information System (INIS)

Mohan, V.; Venkataraman, S.; Venkataraman, R.; Sajeev, B.S.

2006-01-01

Indian PHWRs had experienced three en masse coolant channel replacement campaigns, (EMCCR) first in RAPS-2, next in MAPS-2 and the last in MAPS-1. The campaign is already in full swing at NAPS-1. At MAPS, two EMCCR campaigns were done in a span of four years. The collective dose consumption in the MAPS-1 campaign was only about 25 % that of MAPS-2, a commendable achievement. Based on the experience of RAPS-2 and MAPS-2 campaigns, AERB - through several regulatory means- had given directives for reduction in collective dose in MAPS-1 campaign which was successfully implemented. This paper analyses and quantifies the key factors that contributed to collective dose reduction in MAPS-1 EMCCR. These factors could be put to use in the on going NAPS and forthcoming KAPS campaigns. (author)

Enhancement of Nuclear Safety in Korea: A Regulatory Perspective

International Nuclear Information System (INIS)

Chung, K.Y.

2016-01-01

In the aftermath of Fukushima Daiichi accident in 2011 Korean regulatory body immediately performed special inspections on nuclear power plants (NPPs) and a research reactor in Korea, and issued an enforcement order for the licensees to implement fifty Fukushima action items to address the safety issues identified by the inspections. Subsequently, the licensees have established the implementation plans for resolution of the action items. By the implementation of the action items, the possibility of severe accident due to the extreme hazards has been greatly reduced and the capabilities to mitigate the severe accident, should it occur, have been upgraded. To improve the consistency and predictability of the regulation on severe accidents, Nuclear Safety and Security Commission (NSSC) the regulatory body in Korea, is revising the regulatory framework for severe accidents. The new framework will require the licensee to enhance the capabilities for prevention and mitigation of severe accidents in view of the defence in depth principle, to assess the radiological effects from the severe accidents, and to improve current accident management procedures and guidelines necessary for the prevention and mitigation of severe accidents. This rulemaking also considers the safety principles provided by the IAEA Vienna Declaration in 2015, which require new NPPs to prevent large radioactive releases. (author)

Historical perspectives on evidence-based nursing.

Science.gov (United States)

Beyea, Suzanne C; Slattery, Mary Jo

2013-04-01

The authors of this article offer a review and historical perspective on research utilization and evidence-based practice in nursing. They present the evolution of research utilization to the more contemporary framework of evidence-based nursing practice. The authors address the role of qualitative research in the context of evidence-based practice. Finally, some approaches and resources for learning more about the fundamentals of evidence-based healthcare are provided.

Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

Directory of Open Access Journals (Sweden)

M Venkatesh

2011-01-01

Full Text Available Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20 th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.

Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

Science.gov (United States)

Venkatesh, M.; Bairavi, V. G.; Sasikumar, K. C.

2011-01-01

Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.. PMID:21430959

On regulatory focus and performance in organizational environments

NARCIS (Netherlands)

Beudeker, D.A.

2015-01-01

What motivates people, and when do they perform optimally at work? In this dissertation, a regulatory focus perspective is taken (RFT, Higgins, 1997) to provide answers to these important questions. The results of multiple studies, conducted in complex organizational environments are reported. In

A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

Directory of Open Access Journals (Sweden)

Haitao Guo

2017-01-01

Full Text Available The discovery of cis-regulatory modules (CRMs is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them.

A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

Science.gov (United States)

2017-01-01

The discovery of cis-regulatory modules (CRMs) is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them. PMID:28497059

Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression

Science.gov (United States)

Mars, Ruben A. T.; Nicolas, Pierre; Denham, Emma L.

2016-01-01

SUMMARY Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5′ untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such as Escherichia coli and Salmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacterium Bacillus subtilis. A recent study identified 1,583 putative regulatory RNAs in B. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation in B. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation in B. subtilis mostly involves elements at the 5′ ends of mRNA molecules. These can include 5′ secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs in B. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions in B. subtilis. PMID:27784798

Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression.

Science.gov (United States)

Mars, Ruben A T; Nicolas, Pierre; Denham, Emma L; van Dijl, Jan Maarten

2016-12-01

Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5' untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such as Escherichia coli and Salmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacterium Bacillus subtilis. A recent study identified 1,583 putative regulatory RNAs in B. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation in B. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation in B. subtilis mostly involves elements at the 5' ends of mRNA molecules. These can include 5' secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs in B. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions in B. subtilis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Regulatory RNAs derived from transfer RNA?

Science.gov (United States)

Pederson, Thoru

2010-10-01

Four recent studies suggest that cleavages of transfer RNAs generate products with microRNA-like features, with some evidence of function. If their regulatory functions were to be confirmed, these newly revealed RNAs would add to the expanding repertoire of small noncoding RNAs and would also provide new perspectives on the coevolution of transfer RNA and messenger RNA.

A parallel attractor-finding algorithm based on Boolean satisfiability for genetic regulatory networks.

Directory of Open Access Journals (Sweden)

Wensheng Guo

Full Text Available In biological systems, the dynamic analysis method has gained increasing attention in the past decade. The Boolean network is the most common model of a genetic regulatory network. The interactions of activation and inhibition in the genetic regulatory network are modeled as a set of functions of the Boolean network, while the state transitions in the Boolean network reflect the dynamic property of a genetic regulatory network. A difficult problem for state transition analysis is the finding of attractors. In this paper, we modeled the genetic regulatory network as a Boolean network and proposed a solving algorithm to tackle the attractor finding problem. In the proposed algorithm, we partitioned the Boolean network into several blocks consisting of the strongly connected components according to their gradients, and defined the connection between blocks as decision node. Based on the solutions calculated on the decision nodes and using a satisfiability solving algorithm, we identified the attractors in the state transition graph of each block. The proposed algorithm is benchmarked on a variety of genetic regulatory networks. Compared with existing algorithms, it achieved similar performance on small test cases, and outperformed it on larger and more complex ones, which happens to be the trend of the modern genetic regulatory network. Furthermore, while the existing satisfiability-based algorithms cannot be parallelized due to their inherent algorithm design, the proposed algorithm exhibits a good scalability on parallel computing architectures.

Decommissioning of Australian nuclear facilities - a regulatory perspective

International Nuclear Information System (INIS)

Diamond, T.V.; Mabbott, P.E.; Lawrence, B.R.

2000-01-01

Decommissioning has been a key political, economic and technical issue for the nuclear industry in recent years as older nuclear facilities have been retired. The management of decommissioning is an important part of nuclear safety as the potential exists for occupational exposures that are several times those expected during normal operation. It involves pre-planning and preparatory measures, procedures and instructions, technical and safety assessments, technology for handling large volumes of radioactive material, cost analyses, and a complex decision process. A challenge for the Commonwealth Government regulatory body, the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA), is to allow the Commonwealth entities that operate nuclear facilities ample freedom to address the above, at the same time ensuring that international best practice is invoked to ensure safety. Accordingly, ARPANSA has prepared a regulatory guideline, first drafted by the Nuclear Safety Bureau in March 1997, that documents the process and the criteria that it uses when assessing an application from an operating organisation for a decommissioning licence. Copyright (2000) Australasian Radiation Protection Society Inc

Biosimilars in psoriasis: Clinical practice and regulatory perspectives in Latin America.

Science.gov (United States)

de la Cruz, Claudia; de Carvalho, André V E; Dorantes, Gladys L; Londoño Garcia, Angela M; Gonzalez, Cesar; Maskin, Matías; Podoswa, Nancy; Redfern, Jan S; Valenzuela, Fernando; van der Walt, Joelle; Romiti, Ricardo

2017-01-01

Latin American countries view biosimilar agents as an effective approach to curtail health-care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country-specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health-care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes. © 2016 Japanese Dermatological Association.

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 primer on thermodynamic-based models for deciphering transcriptional regulatory logic.

Science.gov (United States)

Dresch, Jacqueline M; Richards, Megan; Ay, Ahmet

2013-09-01

A rigorous analysis of transcriptional regulation at the DNA level is crucial to the understanding of many biological systems. Mathematical modeling has offered researchers a new approach to understanding this central process. In particular, thermodynamic-based modeling represents the most biophysically informed approach aimed at connecting DNA level regulatory sequences to the expression of specific genes. The goal of this review is to give biologists a thorough description of the steps involved in building, analyzing, and implementing a thermodynamic-based model of transcriptional regulation. The data requirements for this modeling approach are described, the derivation for a specific regulatory region is shown, and the challenges and future directions for the quantitative modeling of gene regulation are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

CoryneRegNet: an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks.

Science.gov (United States)

Baumbach, Jan; Brinkrolf, Karina; Czaja, Lisa F; Rahmann, Sven; Tauch, Andreas

2006-02-14

The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions. CoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria. CoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation.

Organizational behavior of regulatory agencies: a case study of the Bureau of Consumer Services in the Pennsylvania Public Utility Commission

Energy Technology Data Exchange (ETDEWEB)

Silver, J.H.

1981-01-01

Regulatory agencies operate in a complex field of organizations and interest groups. The variety of behaviors that occur in the regulatory field are not satisfactorily explained by current interpretative frameworks. Regulatory agencies are at once criticized and praised. They flourish as organizational entities, yet they exhibit behavior that is often inexplicable. Notions like clientele capture, the politics of regulation, exchange theory, and institutionalized organizations do not singly explain the vagaries of regulatory behavior. A merger of these viewpoints, however, provides a foundation for a comprehensive interpretative framework. A bureau of consumer services within a state public utility commission is viewed as an institutionalized organization. From this perspective, a variety of ritual behaviors, based upon symbolic and tangible interorganizational exchanges are observed and characterized. The outcome of these exchanges is the establishment of the Bureau of Consumer Services as a legitimate regulatory agent with significant impact upon the formulation of regulatory policy in the formal proceedings of the Pennsylvania Public Utility Commission.

Perspectives on reactor safety. Revision 1

International Nuclear Information System (INIS)

Haskin, F.E.; Hodge, S.A.

1997-11-01

The US Nuclear Regulatory Commission (NRC) maintains a technical training center at Chattanooga, Tennessee to provide appropriate training to both new and experienced NRC employees. This document describes a one-week course in reactor safety concepts. The course consists of five modules: (1) the development of safety concepts; (2) severe accident perspectives; (3) accident progression in the reactor vessel; (4) containment characteristics and design bases; and (5) source terms and offsite consequences. The course text is accompanied by slides and videos during the actual presentation of the course

Perspectives on reactor safety. Revision 1

Energy Technology Data Exchange (ETDEWEB)

Haskin, F.E. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Chemical and Nuclear Engineering; Camp, A.L. [Sandia National Labs., Albuquerque, NM (United States); Hodge, S.A. [Oak Ridge National Lab., TN (United States). Engineering Technology Div.

1997-11-01

The US Nuclear Regulatory Commission (NRC) maintains a technical training center at Chattanooga, Tennessee to provide appropriate training to both new and experienced NRC employees. This document describes a one-week course in reactor safety concepts. The course consists of five modules: (1) the development of safety concepts; (2) severe accident perspectives; (3) accident progression in the reactor vessel; (4) containment characteristics and design bases; and (5) source terms and offsite consequences. The course text is accompanied by slides and videos during the actual presentation of the course.

Regulatory Flexibility: An Individual Differences Perspective on Coping and Emotion Regulation.

Science.gov (United States)

Bonanno, George A; Burton, Charles L

2013-11-01

People respond to stressful events in different ways, depending on the event and on the regulatory strategies they choose. Coping and emotion regulation theorists have proposed dynamic models in which these two factors, the person and the situation, interact over time to inform adaptation. In practice, however, researchers have tended to assume that particular regulatory strategies are consistently beneficial or maladaptive. We label this assumption the fallacy of uniform efficacy and contrast it with findings from a number of related literatures that have suggested the emergence of a broader but as yet poorly defined construct that we refer to as regulatory flexibility. In this review, we articulate this broader construct and define both its features and limitations. Specifically, we propose a heuristic individual differences framework and review research on three sequential components of flexibility for which propensities and abilities vary: sensitivity to context, availability of a diverse repertoire of regulatory strategies, and responsiveness to feedback. We consider the methodological limitations of research on each component, review questions that future research on flexibility might address, and consider how the components might relate to each other and to broader conceptualizations about stability and change across persons and situations. © The Author(s) 2013.

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.

Maintenance of ageing CANDU reactors. A regulatory perspective

International Nuclear Information System (INIS)

Dunstan, T.

1996-01-01

The subject of this paper is, 'requirements for maintenance of ageing reactors from the perspective of a regulator', with a focus on the particular theme of; 'continuing safety assurance'. A major role of maintenance is to ensure the continuing reliability and effectiveness of safety related systems and equipment. Continuing safety assurance is an issue the Atomic Energy Control Board has been wrestling with for some time. From my perspective, much remains to be done before the AECB can be confident that Canadian nuclear plants have the necessary programs in place to achieve continuing safety assurance. To introduce the topic, it would be appropriate to say a few words about the AECB's position with respect to the situation at the Pickering NGS. Why did we blow the whistle last August and, what are we doing about it? (author)

CoryneRegNet: An ontology-based data warehouse of corynebacterial transcription factors and regulatory networks

Directory of Open Access Journals (Sweden)

Czaja Lisa F

2006-02-01

Full Text Available Abstract Background The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions. Description CoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria. Conclusion CoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation.

Challenges and Enhancements to the Safety Culture of the Regulatory Body

International Nuclear Information System (INIS)

Niel, Jean-Christophe; Chevet, Pierre Franck; Sheron, Brian; Boyd, Michael; Carlsson, Lennart; Tiippana, Petteri; Burns, Stephen; Jamieson, Terry; Fuketa, Toyoshi; Rzentkowski, Greg; Weiss, Frank Peter; Le Guen, Bernard

2015-06-01

The workshop opened with presentations by both the NEA Director-General and the chair of the three committees directly involved with the safety culture of the regulatory body (SCRB). The opening session set the scene and gave an overview of the SCRB together with presentations and discussions on priorities and challenges. The main session focused on the principles of the SCRB, its implementation and the challenges and enhancements that are being raised and considered. The workshop concluded with a session that looked at findings and conclusions, the way forward and an agreed position on the SCRB. This document brings together the available presentations (slides) given at the workshop: 1 - Introduction: Challenges and Enhancements to the Safety Culture of the Regulatory Body (J-C. Niel); 2 - Thoughts on Safety Culture from a CSNI Perspective (B. Sheron); 3 - Radiological Protection Culture: CRPPH Work (M. Boyd); 4 - Challenges and Enhancements to Safety Culture of the Regulatory Body (L. Carlsson); 5 - Principles for the safety culture of the regulatory body (P. Tiippana); 6 - NRC's Internal Safety Culture: Successes, Challenges, and the Path Forward (S.G. Burns); 7 - Insights on the Canadian Nuclear Safety Commission's Safety Culture Journey (T. Jamieson); 8 - Lessons Learned from the Fukushima Dai-ichi Accident regarding Safety Culture of Regulatory Body (T. Fuketa); 9 - Challenges to Regulatory Bodies' safety culture (P-F. Chevet); 10 - Regulatory Safety Culture: International Perspective (G. Rzentkowski); 11 - Integration of Safety Research into Safety Culture Concepts (F-P. Weiss); 12 - Radiation Protection and Emergency Management Aspects: Culture drawn up by RP professionals (B. Le Guen); 13 - Closing session panel (L. Carlsson)

Engineering nucleases for gene targeting: safety and regulatory considerations.

Science.gov (United States)

Pauwels, Katia; Podevin, Nancy; Breyer, Didier; Carroll, Dana; Herman, Philippe

2014-01-25

Nuclease-based gene targeting (NBGT) represents a significant breakthrough in targeted genome editing since it is applicable from single-celled protozoa to human, including several species of economic importance. Along with the fast progress in NBGT and the increasing availability of customized nucleases, more data are available about off-target effects associated with the use of this approach. We discuss how NBGT may offer a new perspective for genetic modification, we address some aspects crucial for a safety improvement of the corresponding techniques and we also briefly relate the use of NBGT applications and products to the regulatory oversight. Copyright © 2013 Elsevier B.V. All rights reserved.

New perspective and R and D challenges regarding the safe development and use of nuclear energy

International Nuclear Information System (INIS)

Kunihisa, Soda

2008-01-01

The author gave an introduction on the new R and D perspectives and challenges. His presentation underscored that regulatory research is to provide the technical basis for decision making by regulatory bodies and that this basis should be updated to meet the latest development of technology. The main recommendations made at the 2001 Workshop remain valid. The knowledge base and expertise accumulated in the past should be incorporated in an integrated approach to the design, construction, operation and maintenance of next generation reactors. (author)

Waste management strategy for nuclear fusion power systems from a regulatory perspective

Energy Technology Data Exchange (ETDEWEB)

Heckman, R.A.

1977-12-06

A waste management strategy for future nuclear fusion power systems is developed using existing regulatory methodology. The first step is the development of a reference fuel cycle. Next, the waste streams from such a facility are identified. Then a waste management system is defined to safely handle and dispose of these wastes. The future regulator must identify the decisions necessary to establish waste management performance criteria. The data base and methodologies necessary to make these decisions must then be developed. Safe management of nuclear fusion wastes is not only a technological challenge, but encompasses significant social, political, and ethical questions as well.

Waste management strategy for nuclear fusion power systems from a regulatory perspective

International Nuclear Information System (INIS)

Heckman, R.A.

1977-01-01

A waste management strategy for future nuclear fusion power systems is developed using existing regulatory methodology. The first step is the development of a reference fuel cycle. Next, the waste streams from such a facility are identified. Then a waste management system is defined to safely handle and dispose of these wastes. The future regulator must identify the decisions necessary to establish waste management performance criteria. The data base and methodologies necessary to make these decisions must then be developed. Safe management of nuclear fusion wastes is not only a technological challenge, but encompasses significant social, political, and ethical questions as well

Regulatory Perspectives on Risk Management for Lepse De-fuelling Operations

International Nuclear Information System (INIS)

Sneve, Malgorzata; Gordon, Boris

2001-01-01

The Lepse is a ship used for the storage of spent nuclear fuel from nuclear powered ice-breakers in the Murmansk region. Much of the stored spent fuel is damaged. While the status of the vessel may be considered reasonably secure for the present, it is well understood that, at some stage, it will be necessary to remove the spent fuel from the Lepse, so that the long term safe management of the spent fuel can be assured. Plans have been developed for unloading spent fuel from the Lepse. The operations to do this will be non-standard, because of the nature of the storage facilities within the vessel and the poor state of the majority of the spent fuel. For example, specialised equipment will be required for fuel handling, and special arrangements will have to be in place to avoid or mitigate the consequences of possible accidents. Regulatory supervision of these unique operations has also to be specifically provided. Concerning nuclear safety aspects, the Federal Nuclear and Radiation Safety Authority of Russia (Gosatomnadzor) has developed specific regulatory documents, with support from the Scientific and Engineering Centre of Gosatornnadzor and additional support from western agencies. Other regulatory bodies are also involved, concerned with the protection of the environment and other matters

Novel excipients - Regulatory challenges and perspectives - The EU insight.

Science.gov (United States)

Kozarewicz, Piotr; Loftsson, Thorsteinn

2018-05-21

Novel excipients are indispensable in development of modern, advanced drug delivery systems and biotechnology-derived drugs. Although numerous novel excipients are developed for pharmaceutical use, they are not frequently seen in medicinal products due to the strict regulatory requirements and perception that their use makes new product evaluation more complex with risk of delays in the approval process. Regulators regard novel excipients as new substances and whenever new excipient is used in a formulation it must be subjected to full evaluation, similarly to the one required for new active substance. Consequently, the amount of information required in support of the regulatory approval (i.e. marketing authorization) is much more complex and comprehensive than for established excipients. This short review provides an insight into the use of novel excipients in medicinal products approved in the European Union. In addition, barriers and challenges in development of novel excipients are being discussed as well as means to overcome those barriers. Copyright © 2018 Elsevier B.V. All rights reserved.

Transport of radioactive material in Bangladesh: a regulatory perspective

International Nuclear Information System (INIS)

Mollah, A.S.

2004-01-01

Radioactive material is transported in Bangladesh in various types of packages and by different modes of transport. The transport of radioactive materials involves a risk both for the workers and members of the public. The safe transport of radioactive material is ensured in Bangladesh by compliance with Nuclear Safety and Radiation Control (NSRC) Act-93 and NSRC Rules-97. The Bangladesh Atomic Energy Commission (BAEC) is the competent authority for the enforcement of the NSRC act and rules. The competent authority has established regulatory control at each stage to ensure radiation safety to transport workers, members of general public and the environment. An overview is presented of the activities related to the transport of radioactive material in Bangladesh. In particular, the applicable legislation, the scope of authority and the regulatory functions of the competent authority are discussed. The categories of radioactive materials transported and the packaging requirements for the safe transport of these radioactive materials are also described. (author)

Gene regulatory network inference by point-based Gaussian approximation filters incorporating the prior information.

Science.gov (United States)

Jia, Bin; Wang, Xiaodong

2013-12-17

: The extended Kalman filter (EKF) has been applied to inferring gene regulatory networks. However, it is well known that the EKF becomes less accurate when the system exhibits high nonlinearity. In addition, certain prior information about the gene regulatory network exists in practice, and no systematic approach has been developed to incorporate such prior information into the Kalman-type filter for inferring the structure of the gene regulatory network. In this paper, an inference framework based on point-based Gaussian approximation filters that can exploit the prior information is developed to solve the gene regulatory network inference problem. Different point-based Gaussian approximation filters, including the unscented Kalman filter (UKF), the third-degree cubature Kalman filter (CKF3), and the fifth-degree cubature Kalman filter (CKF5) are employed. Several types of network prior information, including the existing network structure information, sparsity assumption, and the range constraint of parameters, are considered, and the corresponding filters incorporating the prior information are developed. Experiments on a synthetic network of eight genes and the yeast protein synthesis network of five genes are carried out to demonstrate the performance of the proposed framework. The results show that the proposed methods provide more accurate inference results than existing methods, such as the EKF and the traditional UKF.

Strengthening Regulatory Competence in Pakistan

International Nuclear Information System (INIS)

Sadiq, M.

2016-01-01

Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

Croatian energy regulatory council - independent Croatian regulatory body

International Nuclear Information System (INIS)

Klepo, M.

2002-01-01

By means of approving five energy laws, the Republic of Croatia established an appropriate legislative framework for energy sector regulation. A series of sub-law acts is presently being elaborated as well as some additional documents in order to bring about transparent and non-discriminatory provisions for the establishment of electric energy, gas, oil/oil derivatives and thermal energy markets, i.e. for the introduction and management of market activities and public services. A considerable share of these activities relates to the definition of transparent regulatory mechanisms that would guarantee the implementation of regulation rules based on the law, and be carried out by the independent regulatory body - Croatian Energy Regulatory Council. The Council's rights and obligations include firm executive functions, which present obligations to every energy entity. A dissatisfied party may set in motion a settlement of dispute, if it maintains that the decisions are not based on the law or reveal a flaw in the procedure. Therefore, it is the Council's priority to always make careful and law-abiding decisions. This paper gives insight into the regulatory framework elements based on the laws including the Council's organisational structure and non-profit entities that will prepare act proposals for the Council and perform other professional activities. (author)

Perspectives on Neoliberalism for Human Service Professionals

DEFF Research Database (Denmark)

Gray, Mel; Dean, Mitchell; Agllias, Kylie

2015-01-01

This article provides an overview of recent perspectives on neoliberalism, which serve as a foundation for the assessment of neoliberalism's influence on human services practice. Conventionally, neoliberalism has been conceived of as an ideology, but more recent perspectives regard neoliberalism...... as an art of government, a thought collective, and an uneven but path-dependent process of regulatory development. We argue that these new perspectives have the potential to contribute to our critical capacity and open avenues for the analysis of contemporary transformations of public policy and its...

Tracking of time-varying genomic regulatory networks with a LASSO-Kalman smoother

OpenAIRE

Khan, Jehandad; Bouaynaya, Nidhal; Fathallah-Shaykh, Hassan M

2014-01-01

It is widely accepted that cellular requirements and environmental conditions dictate the architecture of genetic regulatory networks. Nonetheless, the status quo in regulatory network modeling and analysis assumes an invariant network topology over time. In this paper, we refocus on a dynamic perspective of genetic networks, one that can uncover substantial topological changes in network structure during biological processes such as developmental growth. We propose a novel outlook on the inf...

Department of Energy perspective on high-level waste standards for Yucca Mountain

International Nuclear Information System (INIS)

Brocoum, S.J.; Gil, A.V.; Van Luik, A.E.; Lugo, M.A.

1996-01-01

This paper provides a regulatory perspective from the viewpoint of the potential licensee, the U.S. Department of Energy (DOE), on the National Academy of Sciences (NAS) report on Yucca Mountain standards issued in August 1995, and on how the recommendations in that report should be considered in the development of high-level radioactive waste standards applicable to Yucca Mountain. The paper first provides an overview of the DOE perspective and then discusses several of the issues that are of most importance in the development of the regulatory framework for Yucca Mountain, including both the U.S. Environmental Protection Agency (EPA) standard and the U.S. Nuclear Regulatory Commission (NRC) implementing regulation. These issues include: the regulatory time frame, the risk/dose limit, the definition of the reference biosphere, human intrusion, and natural processes and events

Root cause - A regulatory perspective

International Nuclear Information System (INIS)

Huey, F.R.

1990-01-01

During the past 3 yr, US Nuclear Regulatory Commission (NRC) region V has been pursuing an initiative with region V power reactor licensees to provide improved and more consistent performance in event evaluation. The objectives of the initiative have been to encourage licensees to (a) develop improved skills within the plant organization for events evaluation, with particular emphasis on formal root-cause analysis, and (b) to increase the number of events subjected to root-cause analysis. The NRC's continuing effort now focuses on the need for more consistent quality of event evaluation by licensees. As current licensee programs continue to develop, the NRC will be paying additional attention to how well licensees maintain these programs as an effective and useful tool. Now that licensees have taken the initial steps to establish these programs, licensee management will need to provide continuing attention to ensure that the process does not become overly cumbersome. It is important that the final format for the root-cause programs be easy to use and recognized as being a valuable tool by all licensee personnel involved in the event evaluation process. This will become increasingly important as licensees expand the population of events requiring root-cause analysis and place additional responsibility on the line organization for the implementation of these programs

Radiation and the regulatory landscape of neo2-Darwinism

International Nuclear Information System (INIS)

Rollo, C. David

2006-01-01

Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo 2 -Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology

Radiation and the regulatory landscape of neo2-Darwinism.

Science.gov (United States)

Rollo, C David

2006-05-11

Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo2-Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology.

Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method.

Science.gov (United States)

Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

2017-10-06

Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli , and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs.

The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

Directory of Open Access Journals (Sweden)

Mengge Sun

2016-01-01

Full Text Available MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

GIS-assisted spatial analysis for urban regulatory detailed planning: designer's dimension in the Chinese code system

Science.gov (United States)

Yu, Yang; Zeng, Zheng

2009-10-01

By discussing the causes behind the high amendments ratio in the implementation of urban regulatory detailed plans in China despite its law-ensured status, the study aims to reconcile conflict between the legal authority of regulatory detailed planning and the insufficient scientific support in its decision-making and compilation by introducing into the process spatial analysis based on GIS technology and 3D modeling thus present a more scientific and flexible approach to regulatory detailed planning in China. The study first points out that the current compilation process of urban regulatory detailed plan in China employs mainly an empirical approach which renders it constantly subjected to amendments; the study then discusses the need and current utilization of GIS in the Chinese system and proposes the framework of a GIS-assisted 3D spatial analysis process from the designer's perspective which can be regarded as an alternating processes between the descriptive codes and physical design in the compilation of regulatory detailed planning. With a case study of the processes and results from the application of the framework, the paper concludes that the proposed framework can be an effective instrument which provides more rationality, flexibility and thus more efficiency to the compilation and decision-making process of urban regulatory detailed plan in China.

KIRMES: kernel-based identification of regulatory modules in euchromatic sequences.

Science.gov (United States)

Schultheiss, Sebastian J; Busch, Wolfgang; Lohmann, Jan U; Kohlbacher, Oliver; Rätsch, Gunnar

2009-08-15

Understanding transcriptional regulation is one of the main challenges in computational biology. An important problem is the identification of transcription factor (TF) binding sites in promoter regions of potential TF target genes. It is typically approached by position weight matrix-based motif identification algorithms using Gibbs sampling, or heuristics to extend seed oligos. Such algorithms succeed in identifying single, relatively well-conserved binding sites, but tend to fail when it comes to the identification of combinations of several degenerate binding sites, as those often found in cis-regulatory modules. We propose a new algorithm that combines the benefits of existing motif finding with the ones of support vector machines (SVMs) to find degenerate motifs in order to improve the modeling of regulatory modules. In experiments on microarray data from Arabidopsis thaliana, we were able to show that the newly developed strategy significantly improves the recognition of TF targets. The python source code (open source-licensed under GPL), the data for the experiments and a Galaxy-based web service are available at http://www.fml.mpg.de/raetsch/suppl/kirmes/.

The development of regulatory expectations for computer-based safety systems for the UK nuclear programme

Energy Technology Data Exchange (ETDEWEB)

Hughes, P. J. [HM Nuclear Installations Inspectorate Marine Engineering Submarines Defence Nuclear Safety Regulator Serco Assurance Redgrave Court, Merton Road, Bootle L20 7HS (United Kingdom); Westwood, R.N; Mark, R. T. [FLEET HQ, Leach Building, Whale Island, Portsmouth, PO2 8BY (United Kingdom); Tapping, K. [Serco Assurance,Thomson House, Risley, Warrington, WA3 6GA (United Kingdom)

2006-07-01

The Nuclear Installations Inspectorate (NII) of the UK's Health and Safety Executive (HSE) has completed a review of their Safety Assessment Principles (SAPs) for Nuclear Installations recently. During the period of the SAPs review in 2004-2005 the designers of future UK naval reactor plant were optioneering the control and protection systems that might be implemented. Because there was insufficient regulatory guidance available in the naval sector to support this activity the Defence Nuclear Safety Regulator (DNSR) invited the NII to collaborate with the production of a guidance document that provides clarity of regulatory expectations for the production of safety cases for computer based safety systems. A key part of producing regulatory expectations was identifying the relevant extant standards and sector guidance that reflect good practice. The three principal sources of such good practice were: IAEA Safety Guide NS-G-1.1 (Software for Computer Based Systems Important to Safety in Nuclear Power Plants), European Commission consensus document (Common Position of European Nuclear Regulators for the Licensing of Safety Critical Software for Nuclear Reactors) and IEC nuclear sector standards such as IEC60880. A common understanding has been achieved between the NII and DNSR and regulatory guidance developed which will be used by both NII and DNSR in the assessment of computer-based safety systems and in the further development of more detailed joint technical assessment guidance for both regulatory organisations. (authors)

Generalizing Perspective-based Inspection to handle Object-Oriented Development Artifacts

OpenAIRE

Laitenberger, O.; Atkinson, C.

1998-01-01

The value of software inspection for uncovering defects early in the development lifecycle has been well documented. Of the various types of inspection methods published to date, experiments have shown perspective-based inspection to be one of the most effective, because of its enhanced coverage of the defect space. However, inspections in general, and perspective-based inspections in particular, have so far been applied predominantly in the context of conventional structured development meth...

Regulatory Incentives and Disincentives for Utility Investments in Grid Modernization

Energy Technology Data Exchange (ETDEWEB)

Kihm, Steve [Seventhware, Madison, WI (United States); Beecher, Janice [Michigan State Univ., East Lansing, MI (United States). Inst. of Public Utilities; Lehr, Ronald L.

2017-05-31

Electric power is America's most capital-intensive industry, with more than $100 billion invested each year in energy infrastructure. Investment needs are likely to grow as electric utilities make power systems more reliable and resilient, deploy advanced digital technologies, and facilitate new services to meet some consumers' expectations for greater choice and control. But do current regulatory approaches provide the appropriate incentives for grid modernization investments? This report presents three perspectives: -Financial analyst Steve Kihm begins by explaining that any major investor-owned electric utility that wants to raise capital today can do so at a reasonable cost. The question is whether utility managers want to raise capital for grid modernization. Specifically, they look for investments that create the most value for their existing shareholders. In cases where grid modernization investments are not the best choice in terms of shareholder value, Kihm describes shareholder incentive mechanisms that regulators could consider to encourage such investments when they are in the public interest. -From an institutional perspective, Dr. Janice Beecher finds that the traditional rate-base/rate of return regulatory model provides powerful incentives for utilities to pursue investments, cost control, efficiency and even innovation, and it is well suited to the policy objectives of grid modernization. Prudence of grid modernization investments (fair returns) depends on careful evaluation of the specific asset, and any special incentives (bonus returns) should be used only if they promote economic efficiency consistent with the core goals of economic regulation. According to Beecher, realizing the promises of grid modernization depends on effective implementation of the traditional regulatory model and ratemaking tools to serve the public interest. -Conversely, former commissioner and clean energy consultant Ron Lehr says that rapid electric industry

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.

Nuclear regulatory decision making

International Nuclear Information System (INIS)

Wieland, Patricia; Almeida, Ivan Pedro Salati de

2011-01-01

The scientific considerations upon which the nuclear regulations are based provide objective criteria for decisions on nuclear safety matters. However, the decisions that a regulatory agency takes go far beyond granting or not an operating license based on assessment of compliance. It may involve decisions about hiring experts or research, appeals, responses to other government agencies, international agreements, etc.. In all cases, top management of the regulatory agency should hear and decide the best balance between the benefits of regulatory action and undue risks and other associated impacts that may arise, including issues of credibility and reputation. The establishment of a decision framework based on well established principles and criteria ensures performance stability and consistency, preventing individual subjectivity. This article analyzes the challenges to the decision-making by regulatory agencies to ensure coherence and consistency in decisions, even in situations where there is uncertainty, lack of reliable information and even divergence of opinions among experts. The article explores the basic elements for a framework for regulatory decision-making. (author)

Microresonator-Based Optical Frequency Combs: A Time Domain Perspective

Science.gov (United States)

2016-04-19

AFRL-AFOSR-VA-TR-2016-0165 (BRI) Microresonator-Based Optical Frequency Combs: A Time Domain Perspective Andrew Weiner PURDUE UNIVERSITY 401 SOUTH...Optical Frequency Combs: A Time Domain Perspective 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-12-1-0236 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data

Radiation and the regulatory landscape of neo{sup 2}-Darwinism

Energy Technology Data Exchange (ETDEWEB)

Rollo, C. David [Department of Biology, Life Sciences Building, 1280 Main St. West, Hamilton, Ont., Canada L8S 4K1 (Canada)]. E-mail: rollocd@mcmaster.ca

2006-05-11

Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo{sup 2}-Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology.

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

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)

Future water table rise at Yucca Mountain: A regulatory perspective

International Nuclear Information System (INIS)

Coleman, N.M.

1995-01-01

The U.S. Nuclear Regulatory Commission staff has developed a program of Systematic Regulatory Analysis (SRA). The purpose of this program is to ensure that important technical issues related to compliance with 10 CFR Part 60 will be identified before receipt of a license application. A plan is being developed to review the U.S. Department of Energy's (DOE's) demonstration of compliance in the license application for each part of the regulation. Under the siting criteria of NRC's Part 60, one of the potentially adverse conditions is the possibility that the water table may rise high enough to saturate a repository in the unsaturated zone. DOE must evaluate this and other conditions in a license application for a geologic repository site. DOE's evaluation must show compliance with the requirements of Part 60 with reasonable assurance. This paper describes the NRC staff's preliminary plans to review DOE's demonstration of compliance, including assumptions about a future rise of the water table

R and D perspectives on the advanced nuclear safety regulation system

International Nuclear Information System (INIS)

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

2009-01-01

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

R and D perspectives on the advanced nuclear safety regulation system

Energy Technology Data Exchange (ETDEWEB)

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

2009-04-15

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

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)

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

Regulatory Perspectives on Continuous Pharmaceutical Manufacturing: Moving From Theory to Practice: September 26-27, 2016, International Symposium on the Continuous Manufacturing of Pharmaceuticals.

Science.gov (United States)

Nasr, Moheb M; Krumme, Markus; Matsuda, Yoshihiro; Trout, Bernhardt L; Badman, Clive; Mascia, Salvatore; Cooney, Charles L; Jensen, Keith D; Florence, Alastair; Johnston, Craig; Konstantinov, Konstantin; Lee, Sau L

2017-11-01

Continuous manufacturing plays a key role in enabling the modernization of pharmaceutical manufacturing. The fate of this emerging technology will rely, in large part, on the regulatory implementation of this novel technology. This paper, which is based on the 2nd International Symposium on the Continuous Manufacturing of Pharmaceuticals, describes not only the advances that have taken place since the first International Symposium on Continuous Manufacturing of Pharmaceuticals in 2014, but the regulatory landscape that exists today. Key regulatory concepts including quality risk management, batch definition, control strategy, process monitoring and control, real-time release testing, data processing and management, and process validation/verification are outlined. Support from regulatory agencies, particularly in the form of the harmonization of regulatory expectations, will be crucial to the successful implementation of continuous manufacturing. Collaborative efforts, among academia, industry, and regulatory agencies, are the optimal solution for ensuring a solid future for this promising manufacturing technology. Copyright © 2017 American Pharmacists Association®. All rights reserved.

Self-Regulatory Imagery and Physical Activity in Middle-Aged and Older Adults: A Social-Cognitive Perspective.

Science.gov (United States)

Kosteli, Maria-Christina; Cumming, Jennifer; Williams, Sarah E

2018-01-01

Limited research has investigated exercise imagery use in middle-aged and older adults and its relationship with affective and behavioral correlates. The study examined the association between self-regulatory imagery and physical activity (PA) through key social cognitive variables. Middle-aged and older adults (N = 299; M age = 59.73 years, SD = 7.73, range = 50 to 80) completed self-report measures assessing self-regulatory imagery use, self-efficacy, outcome expectations, perceived barriers, self-regulatory behavior, enjoyment, and PA levels. Path analysis supported a model (χ² [14] = 21.76, p = .08, CFI = .99, TLI = .97, SRMR = .03, RMSEA = .04) whereby self-regulatory imagery positively predicted self-efficacy, outcome expectations, and self-regulatory behaviors. Furthermore, self-regulatory imagery indirectly predicted barriers, outcome expectations, self-regulation, enjoyment, and PA. This research highlights self-regulatory imagery as an effective strategy in modifying exercise-related cognitions and behaviors. Incorporating social cognitive constructs into the design of imagery interventions may increase PA engagement.

Knowledge-Based Economy in Argentina, Costa Rica and Mexico: A Comparative Analysis from the Bio-Economy Perspective

Directory of Open Access Journals (Sweden)

Ana Barbara MUNGARAY-MOCTEZUMA

2015-06-01

Full Text Available The objective of this article is to determine the necessary institutional characteristics of technology and human capital in Argentina, Costa Rica and Mexico in order to evolve towards a knowledge-based economy, addressing the importance of institutions for their development. In particular, the knowledge-based economy is analyzed from the perspective of bioeconomics. Based on the Knowledge Economy Index (KEI which considers 148 indicators, in the following categories: a economic performance and institutional regime; b education and human resources, c innovation, and d information and communication technologies, we selected 13 indicators. We aim to identify the strengths and opportunities for these countries in order to meet the challenges that arise from the paradoxes of technological progress and globalization. In this sense, bioeconomy is approached as part of the economy. This analysis shows, among other things, that Argentina has greater potential to compete in an economy sustained in the creation and dissemination of knowledge, while Costa Rica has an institutional and regulatory environment that is more conducive to the development of business activities, and Mexico faces significant challenges regarding its institutional structure, economic performance and human resources.

Palliative home-based technology from a practitioner's perspective: benefits and disadvantages

Directory of Open Access Journals (Sweden)

Johnston BM

2014-11-01

Full Text Available Bridget M Johnston Sue Ryder Care Centre for the Study of Supportive, Palliative, and End of Life Care, School of Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK Abstract: This critical review paper explores the concept of palliative home-based technology from a practitioner's perspective. The aim of the critical review was to scope information available from published and unpublished research on the current state of palliative home-based technology, practitioner-focused perspectives, patient-focused perspectives, quality of life, and the implications for clinical practice. Published and unpublished studies were included. An example of one UK patient-centered home-based technology is explored as an exemplar. The evidence suggests that despite the challenges, there are numerous examples of good practice in relation to palliative home-based technology. Improvements in technology mean that telehealth has much to offer people being cared for at home with palliative needs. However, some of the evaluative evidence is limited, and further rigor is needed when evaluating future technology-based solutions innovations. Keywords: technology, telehealth, telemedicine, information technology, palliative care, hospice, terminal illness

Biosimilars: a regulatory perspective from America.

Science.gov (United States)

Kay, Jonathan

2011-05-12

Biosimilars are protein products that are sufficiently similar to a biopharmaceutical already approved by a regulatory agency. Several biotechnology companies and generic drug manufacturers in Asia and Europe are developing biosimilars of tumor necrosis factor inhibitors and rituximab. A biosimilar etanercept is already being marketed in Colombia and China. In the US, several natural source products and recombinant proteins have been approved as generic drugs under Section 505(b)(2) of the Food, Drug, and Cosmetic Act. However, because the complexity of large biopharmaceuticals makes it difficult to demonstrate that a biosimilar is structurally identical to an already approved biopharmaceutical, this Act does not apply to biosimilars of large biopharmaceuticals. Section 7002 of the Patient Protection and Affordable Care Act of 2010, which is referred to as the Biologics Price Competition and Innovation Act of 2009, amends Section 351 of the Public Health Service Act to create an abbreviated pathway that permits a biosimilar to be evaluated by comparing it with only a single reference biological product. This paper reviews the processes for approval of biosimilars in the US and the European Union and highlights recent changes in federal regulations governing the approval of biosimilars in the US.

Review of NRC Regulatory processes and functions

International Nuclear Information System (INIS)

1980-01-01

The Advisory Committee on Reactor Safeguards (ACRS) has spent much time over many years observing and examining the NRC licensing process. The Committee is, consequently, in a position to comment on the situation, and it believes this review will be helpful to those examining the regulatory process by discussing how it works, where it is weak, and the opportunities for improvement. The Committee's review may also help put current proposals and discussions in perspective

The Servitization of Manufacturing: A Resource-Based Perspective

DEFF Research Database (Denmark)

Yang, Cheng; Boer, Harry; Johansen, John

2010-01-01

The traditional focus of manufacturing strategy is tremendously impacted by the emergence of servitization as a new empirical phenomenon and the resource-based view (RBV) as a (relatively) new theoretical perspective. In order to understand their influence, this paper firstly tracks the evolution....... Based on the case analyses and inspired by open source software (OSS) and open innovation, a new, open and capability (development) based role of manufacturing is suggested....

Regulatory Risk Reduction for Advanced Reactor Technologies - FY2016 Status and Work Plan Summary

International Nuclear Information System (INIS)

Moe, Wayne Leland

2016-01-01

Millions of public and private sector dollars have been invested over recent decades to realize greater efficiency, reliability, and the inherent and passive safety offered by advanced nuclear reactor technologies. However, a major challenge in experiencing those benefits resides in the existing U.S. regulatory framework. This framework governs all commercial nuclear plant construction, operations, and safety issues and is highly large light water reactor (LWR) technology centric. The framework must be modernized to effectively deal with non-LWR advanced designs if those designs are to become part of the U.S energy supply. The U.S. Department of Energy's (DOE) Advanced Reactor Technologies (ART) Regulatory Risk Reduction (RRR) initiative, managed by the Regulatory Affairs Department at the Idaho National Laboratory (INL), is establishing a capability that can systematically retire extraneous licensing risks associated with regulatory framework incompatibilities. This capability proposes to rely heavily on the perspectives of the affected regulated community (i.e., commercial advanced reactor designers/vendors and prospective owner/operators) yet remain tuned to assuring public safety and acceptability by regulators responsible for license issuance. The extent to which broad industry perspectives are being incorporated into the proposed framework makes this initiative unique and of potential benefit to all future domestic non-LWR applicants

Integrated Financial Supervision: an Institutional Perspective for the Philippines

OpenAIRE

Milo, Melanie S.

2007-01-01

This paper looks at the issue of reforming financial regulatory structures from the New Institutional Economics perspective. In particular, it examines how the broader institutional environment prevailing in developing countries like the Philippines may affect the institutional arrangements for financial regulation, and how these might be taken into consideration when designing or reforming financial regulatory structures. The paper argues that the state of financial conglomerates in the Phil...

ENSI’s regulatory framework strategy

International Nuclear Information System (INIS)

2015-03-01

This short brochure issued by the Swiss Federal Nuclear Safety Inspectorate ENSI defines the organisation’s regulatory framework strategy. Six guiding principles are declared and discussed: Comprehensive harmonisation with relevant international requirements, basing the regulatory framework on existing, tried-and-tested regulations, issuing of its own guidelines only when it is necessary to do so, guidelines to be drawn up transparently and with the involvement of all stakeholders and basing the level of detail of its regulatory framework on hazard potential and risk

State risk discourse and the regulatory preservation of traditional medicine knowledge: The case of acupuncture in Ontario, Canada.

Science.gov (United States)

Ijaz, Nadine; Boon, Heather; Muzzin, Linda; Welsh, Sandy

2016-12-01

Several United Nations bodies have advised countries to actively preserve Traditional Medicine (TM) knowledge and prevent its misappropriation in regulatory structures. To help advance decision-making around this complex regulatory issue, we examine the relationship between risk discourse, epistemology and policy. This study presents a critical, postcolonial analysis of divergent risk discourses elaborated in two contrasting Ontario (Canada) government reports preceding that jurisdiction's regulation of acupuncture, the world's most widely practised TM therapy. The earlier (1996) report, produced when Ontario's regulatory lobby was largely comprised of Chinese medicine practitioners, presents a risk discourse inclusive of biomedical and TM knowledge claims, emphasizing the principle of regulatory 'equity' as well as historical and sociocultural considerations. Reflecting the interests of an increasingly biomedical practitioner lobby, the later (2001) report uses implicit discursive means to exclusively privilege Western scientific perspectives on risk. This report's policy recommendations, we argue, suggest misappropriation of TM knowledge. We advise regulators to consider equitable adaptations to existing policy structures, and to explicitly include TM evidentiary perspectives in their pre-regulatory assessments. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Inferring nonlinear gene regulatory networks from gene expression data based on distance correlation.

Directory of Open Access Journals (Sweden)

Xiaobo Guo

Full Text Available Nonlinear dependence is general in regulation mechanism of gene regulatory networks (GRNs. It is vital to properly measure or test nonlinear dependence from real data for reconstructing GRNs and understanding the complex regulatory mechanisms within the cellular system. A recently developed measurement called the distance correlation (DC has been shown powerful and computationally effective in nonlinear dependence for many situations. In this work, we incorporate the DC into inferring GRNs from the gene expression data without any underling distribution assumptions. We propose three DC-based GRNs inference algorithms: CLR-DC, MRNET-DC and REL-DC, and then compare them with the mutual information (MI-based algorithms by analyzing two simulated data: benchmark GRNs from the DREAM challenge and GRNs generated by SynTReN network generator, and an experimentally determined SOS DNA repair network in Escherichia coli. According to both the receiver operator characteristic (ROC curve and the precision-recall (PR curve, our proposed algorithms significantly outperform the MI-based algorithms in GRNs inference.

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.

NRC review of passive reactor design certification testing programs: Overview, progress, and regulatory perspective

Energy Technology Data Exchange (ETDEWEB)

Levin, A.E.

1995-09-01

New reactor designs, employing passive safety systems, are currently under development by reactor vendors for certification under the U.S. Nuclear Regulatory Commission`s (NRC`s) design certification rule. The vendors have established testing programs to support the certification of the passive designs, to meet regulatory requirements for demonstration of passive safety system performance. The NRC has, therefore, developed a process for the review of the vendors` testing programs and for incorporation of the results of those reviews into the safety evaluations for the passive plants. This paper discusses progress in the test program reviews, and also addresses unique regulatory aspects of those reviews.

Resilient Prosumer Scenario in a Changing Regulatory Environment—The UniRCon Solution

Directory of Open Access Journals (Sweden)

Mihai Sanduleac

2017-11-01

Full Text Available Technological developments are pushing for new solutions based upon massive integration of renewable electricity generation in networks already facing many challenges. This paper presents a novel approach to managing the energy transfer towards prosumers making use of smart management of local energy storage. The proposed design (including storage dimensioning is based on several operating scenarios in which the prosumer might operate as: (i a “load only” entity (from a grid perspective, thus exhibiting investment resiliency against regulatory changes and high energy efficiency; or (ii a prosumer, in case regulatory opportunistic profit might be available. This can be realized within a newly proposed Uni-directional Resilient Consumer (UniRCon architecture. The major aim of the proposed architecture is to achieve optimal self-consumption while avoiding curtailment even in a changing regulatory environment like, for example, the total lack of incentives for generation based on renewable energy sources (RES. One of the major advantages of the proposed architecture consists in the adaptability to changes in the regulatory and market environment. The term resilience is used with multiple meanings: (a the prosumer’s financial resilience against regulatory changes when investment calculations assume no-grid injections; (b the prosumer’s technical resilience, with electrical design based on standalone operation; (c the resilience of clusters of interconnected end-user installations with enabled community-level electricity exchange, independent of the existing main grid supply; (d the contribution to grid resilience, by enabling AC microgrid (MG operation in island mode when large portions of the grid are formed by clusters of UniRCon prosumers (the ease of islanding segmentation of the local grid in case of emergencies. For proof of concept, three use-cases are detailed: (i photovoltaic (PV installations connected behind the meter; (ii PV and

Novel perspectives for the engineering of abiotic stress tolerance in plants.

Science.gov (United States)

Cabello, Julieta V; Lodeyro, Anabella F; Zurbriggen, Matias D

2014-04-01

Adverse environmental conditions pose serious limitations to agricultural production. Classical biotechnological approaches towards increasing abiotic stress tolerance focus on boosting plant endogenous defence mechanisms. However, overexpression of regulatory elements or effectors is usually accompanied by growth handicap and yield penalties due to crosstalk between developmental and stress-response networks. Herein we offer an overview on novel strategies with the potential to overcome these limitations based on the engineering of regulatory systems involved in the fine-tuning of the plant response to environmental hardships, including post-translational modifications, small RNAs, epigenetic control of gene expression and hormonal networks. The development and application of plant synthetic biology tools and approaches will add new functionalities and perspectives to genetic engineering programs for enhancing abiotic stress tolerance. Copyright © 2013 Elsevier Ltd. All rights reserved.

TRUPACT-II, a regulatory perspective

International Nuclear Information System (INIS)

Gregory, P.C.; Spooner, O.R.

1995-01-01

The Transuranic Package Transporter II (TRUPACT-II) is a US Nuclear Regulatory Commission (NRC) certified Type B packaging for the shipment of contact-handled transuranic (CH-TRU) material by the US Department of Energy (DOE). The NRC approved the TRUPACT-II design as meeting the requirements of Title 10, Code of Federal Regulations, Part 71 (10 CFR 71) and issued Certificate of Compliance (CofC) Number 9218 to the DOE. There are currently 15 certified TRUPACT-IIs. Additional TRUPACT-IIs will be required to make more than 15,000 shipments of CH-TRU waste to the Waste Isolation Pilot Plant (WIPP) site near Carlsbad, New Mexico. The TRUPACT-II may also be used for the DOE inter-site and intra-site shipments of CH-TRU waste. The Land Withdrawal Act (Public Law 102-579), enacted by the US Congress, October 30, 1992, and an agreement between the DOE and the State of New Mexico, signed August 4, 1987, both stipulate that only NRC approved packaging may be used for shipments of TRU waste to the WIPP. Early in the TRUPACT-II development phase it was decided that the transportation system (tractor, trailer, and TRUPACT-II) should be highway legal on all routes without the need for oversize and/or overweight permits. In large measure, public acceptance of the DOE's efforts to safely transport CH-TRU waste depends on the public's perception that the TRUPACT-II is in compliance with all applicable regulations, standards, and quality assurance requirements. This paper addresses some of the numerous regulations applicable to Type B packaging, and it describes how the TRUPACT-II complies with these regulations

Dynamic Regulatory Network Reconstruction for Alzheimer’s Disease Based on Matrix Decomposition Techniques

Directory of Open Access Journals (Sweden)

Wei Kong

2014-01-01

Full Text Available Alzheimer’s disease (AD is the most common form of dementia and leads to irreversible neurodegenerative damage of the brain. Finding the dynamic responses of genes, signaling proteins, transcription factor (TF activities, and regulatory networks of the progressively deteriorative progress of AD would represent a significant advance in discovering the pathogenesis of AD. However, the high throughput technologies of measuring TF activities are not yet available on a genome-wide scale. In this study, based on DNA microarray gene expression data and a priori information of TFs, network component analysis (NCA algorithm is applied to determining the TF activities and regulatory influences on TGs of incipient, moderate, and severe AD. Based on that, the dynamical gene regulatory networks of the deteriorative courses of AD were reconstructed. To select significant genes which are differentially expressed in different courses of AD, independent component analysis (ICA, which is better than the traditional clustering methods and can successfully group one gene in different meaningful biological processes, was used. The molecular biological analysis showed that the changes of TF activities and interactions of signaling proteins in mitosis, cell cycle, immune response, and inflammation play an important role in the deterioration of AD.

Establishing neural crest identity: a gene regulatory recipe

Science.gov (United States)

Simões-Costa, Marcos; Bronner, Marianne E.

2015-01-01

The neural crest is a stem/progenitor cell population that contributes to a wide variety of derivatives, including sensory and autonomic ganglia, cartilage and bone of the face and pigment cells of the skin. Unique to vertebrate embryos, it has served as an excellent model system for the study of cell behavior and identity owing to its multipotency, motility and ability to form a broad array of cell types. Neural crest development is thought to be controlled by a suite of transcriptional and epigenetic inputs arranged hierarchically in a gene regulatory network. Here, we examine neural crest development from a gene regulatory perspective and discuss how the underlying genetic circuitry results in the features that define this unique cell population. PMID:25564621

Prediction of transcriptional regulatory elements for plant hormone responses based on microarray data

Directory of Open Access Journals (Sweden)

Yamaguchi-Shinozaki Kazuko

2011-02-01

Full Text Available Abstract Background Phytohormones organize plant development and environmental adaptation through cell-to-cell signal transduction, and their action involves transcriptional activation. Recent international efforts to establish and maintain public databases of Arabidopsis microarray data have enabled the utilization of this data in the analysis of various phytohormone responses, providing genome-wide identification of promoters targeted by phytohormones. Results We utilized such microarray data for prediction of cis-regulatory elements with an octamer-based approach. Our test prediction of a drought-responsive RD29A promoter with the aid of microarray data for response to drought, ABA and overexpression of DREB1A, a key regulator of cold and drought response, provided reasonable results that fit with the experimentally identified regulatory elements. With this succession, we expanded the prediction to various phytohormone responses, including those for abscisic acid, auxin, cytokinin, ethylene, brassinosteroid, jasmonic acid, and salicylic acid, as well as for hydrogen peroxide, drought and DREB1A overexpression. Totally 622 promoters that are activated by phytohormones were subjected to the prediction. In addition, we have assigned putative functions to 53 octamers of the Regulatory Element Group (REG that have been extracted as position-dependent cis-regulatory elements with the aid of their feature of preferential appearance in the promoter region. Conclusions Our prediction of Arabidopsis cis-regulatory elements for phytohormone responses provides guidance for experimental analysis of promoters to reveal the basis of the transcriptional network of phytohormone responses.

Regulatory infrastructure in East and West Asia: Present status and perspectives

International Nuclear Information System (INIS)

Djermouni, B.

2001-01-01

A detailed assessment carried out by the IAEA showed that five Member States in East Asia (Bangladesh, Mongolia, Myanmar, Sri Lanka, Vietnam) and nine Member States in West Asia (Jordan, Kazakhstan, Lebanon, Qatar, Saudi Arabia, Syria, United Arab Emirates, Uzbekistan, Yemen) did not have an adequate radiation and waste safety infrastructure in general and a basic regulatory infrastructure in particular. This indicated the partial or complete lack of control of radiation sources, i.e. location, identification, registration, licensing and inspection. Since 1996, these countries have been participating in the Model Project on Upgrading Radiation and Waste Safety Infrastructure with the primary objective of establishing or upgrading their basic regulatory infrastructure. The results achieved in the establishment/upgrading of this infrastructure and the follow-up and extension to other Member States are presented in this paper. (author)

Regulatory perspective on future climates at Yucca Mountain

International Nuclear Information System (INIS)

Coleman, N.M.; Eisenberg, N.A.; Brooks, D.J.

1996-01-01

Current regulations of the U.S. Nuclear Regulatory Commission (NRC) require that any performance assessment supporting the license application for a high-level waste (HLW) repository must consider the potential for changes in hydrologic conditions caused by reasonably foreseeable climatic conditions. The requirement is important because the earth's climate will almost certainly change significantly during the thousands of years that disposed nuclear wastes will remain hazardous. More importantly, climate controls the range of precipitation, which in turn controls the rates of infiltration, deep percolation, and groundwater flux through a geologic repository located in an unsaturated environment. Therefore, future changes in climate could significantly influence waste isolation in a repository at Yucca Mountain

On the Interplay between Entropy and Robustness of Gene Regulatory Networks

Directory of Open Access Journals (Sweden)

Bor-Sen Chen

2010-05-01

Full Text Available The interplay between entropy and robustness of gene network is a core mechanism of systems biology. The entropy is a measure of randomness or disorder of a physical system due to random parameter fluctuation and environmental noises in gene regulatory networks. The robustness of a gene regulatory network, which can be measured as the ability to tolerate the random parameter fluctuation and to attenuate the effect of environmental noise, will be discussed from the robust H∞ stabilization and filtering perspective. In this review, we will also discuss their balancing roles in evolution and potential applications in systems and synthetic biology.

Establishing Base Elements of Perspective in Order to Reconstruct Architectural Buildings from Photographs

Science.gov (United States)

Dzwierzynska, Jolanta

2017-12-01

The use of perspective images, especially historical photographs for retrieving information about presented architectural environment is a fast developing field recently. The photography image is a perspective image with secure geometrical connection with reality, therefore it is possible to reverse this process. The aim of the herby study is establishing requirements which a photographic perspective representation should meet for a reconstruction purpose, as well as determination of base elements of perspective such as a horizon line and a circle of depth, which is a key issue in any reconstruction. The starting point in the reconstruction process is geometrical analysis of the photograph, especially determination of the kind of perspective projection applied, which is defined by the building location towards a projection plane. Next, proper constructions can be used. The paper addresses the problem of establishing base elements of perspective on the basis of the photograph image in the case when camera calibration is impossible to establish. It presents different geometric construction methods selected dependently on the starting assumptions. Therefore, the methods described in the paper seem to be universal. Moreover, they can be used even in the case of poor quality photographs with poor perspective geometry. Such constructions can be realized with computer aid when the photographs are in digital form as it is presented in the paper. The accuracy of the applied methods depends on the photography image accuracy, as well as drawing accuracy, however, it is sufficient for further reconstruction. Establishing base elements of perspective presented in the paper is especially useful in difficult cases of reconstruction, when one lacks information about reconstructed architectural form and it is necessary to lean on solid geometry.

Regulatory Risk Reduction for Advanced Reactor Technologies – FY2016 Status and Work Plan Summary

Energy Technology Data Exchange (ETDEWEB)

Moe, Wayne Leland [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-08-01

Millions of public and private sector dollars have been invested over recent decades to realize greater efficiency, reliability, and the inherent and passive safety offered by advanced nuclear reactor technologies. However, a major challenge in experiencing those benefits resides in the existing U.S. regulatory framework. This framework governs all commercial nuclear plant construction, operations, and safety issues and is highly large light water reactor (LWR) technology centric. The framework must be modernized to effectively deal with non-LWR advanced designs if those designs are to become part of the U.S energy supply. The U.S. Department of Energy’s (DOE) Advanced Reactor Technologies (ART) Regulatory Risk Reduction (RRR) initiative, managed by the Regulatory Affairs Department at the Idaho National Laboratory (INL), is establishing a capability that can systematically retire extraneous licensing risks associated with regulatory framework incompatibilities. This capability proposes to rely heavily on the perspectives of the affected regulated community (i.e., commercial advanced reactor designers/vendors and prospective owner/operators) yet remain tuned to assuring public safety and acceptability by regulators responsible for license issuance. The extent to which broad industry perspectives are being incorporated into the proposed framework makes this initiative unique and of potential benefit to all future domestic non-LWR applicants

Functional alignment of regulatory networks: a study of temperate phages.

Directory of Open Access Journals (Sweden)

Ala Trusina

2005-12-01

Full Text Available The relationship between the design and functionality of molecular networks is now a key issue in biology. Comparison of regulatory networks performing similar tasks can provide insights into how network architecture is constrained by the functions it directs. Here, we discuss methods of network comparison based on network architecture and signaling logic. Introducing local and global signaling scores for the difference between two networks, we quantify similarities between evolutionarily closely and distantly related bacteriophages. Despite the large evolutionary separation between phage lambda and 186, their networks are found to be similar when difference is measured in terms of global signaling. We finally discuss how network alignment can be used to pinpoint protein similarities viewed from the network perspective.

EU risk governance of 'cloned food': regulatory uncertainty between trade and non-trade

NARCIS (Netherlands)

Weimer, M.; van Asselt, M.B.A.; Versluis, E.; Vos, E.

2013-01-01

This chapter analyzes the difficulties of creating a viable legal framework for ‘cloned food’ in the EU combining a legal perspective with insights from the interdisciplinary research on risk governance. Animal cloning offers an instructive example for the challenges of designing regulatory

Risk-based regulation - an NRC perspective and status

International Nuclear Information System (INIS)

King, T.L.; Murphy, J.A.

1993-01-01

The consideration of risk in regulatory decision making has traditionally been part of the US Nuclear Regulatory Commission's (NRC's) policy and practice. In the early days of regulation, this consideration was more qualitative in nature and was reflected in prescriptive/deterministic regulatory requirements. However, with the development of quantitative risk assessment methods, more detailed and comprehensive (although not complete) risk information on nuclear power plants is available to the designer, operator, and regulator. The availability of such information provides an opportunity to assess the need for change in the current regulatory structure and to develop future regulatory requirements in a less prescriptive, more performance-oriented fashion

The Integrated Model of Sustainability Perspective in Spermatophyta Learning Based on Local Wisdom

Science.gov (United States)

Hartadiyati, E.; Rizqiyah, K.; Wiyanto; Rusilowati, A.; Prasetia, A. P. B.

2017-09-01

In present condition, culture is diminished, the change of social order toward the generation that has no policy and pro-sustainability; As well as the advancement of science and technology are often treated unwisely so as to excite local wisdom. It is therefore necessary to explore intra-curricular local wisdom in schools. This study aims to produce an integration model of sustainability perspectives based on local wisdom on spermatophyta material that is feasible and effective. This research uses define, design and develop stages to an integration model of sustainability perspectives based on local wisdom on spermatophyta material. The resulting product is an integration model of socio-cultural, economic and environmental sustainability perspective and formulated with preventive, preserve and build action on spermatophyta material consisting of identification and classification, metagenesis and the role of spermatophyta for human life. The integration model of sustainability perspective in learning spermatophyta based on local wisdom is considered proven to be effective in raising sustainability’s awareness of high school students.

Continuing Bonds in Bereavement: An Attachment Theory Based Perspective

Science.gov (United States)

Field, Nigel P.; Gao, Beryl; Paderna, Lisa

2005-01-01

An attachment theory based perspective on the continuing bond to the deceased (CB) is proposed. The value of attachment theory in specifying the normative course of CB expression and in identifying adaptive versus maladaptive variants of CB expression based on their deviation from this normative course is outlined. The role of individual…

Anti-regulatory T cells

DEFF Research Database (Denmark)

Andersen, Mads Hald

2017-01-01

responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune...... reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells......Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...

Colloid-facilitated radionuclide transport: a regulatory perspective

Science.gov (United States)

Dam, W. L.; Pickett, D. A.; Codell, R. B.; Nicholson, T. J.

2001-12-01

What hydrogeologic-geochemical-microbial conditions and processes affect migration of radionuclides sorbed onto microparticles or native colloid-sized radionuclide particles? The U.S. Nuclear Regulatory Commission (NRC) is responsible for protecting public health, safety, and the environment at numerous nuclear facilities including a potential high-level nuclear waste disposal site. To fulfill these obligations, NRC needs to understand the mechanisms controlling radionuclide release and transport and their importance to performance. The current focus of NRC staff reviews and technical interactions dealing with colloid-facilitated transport relates to the potential nuclear-waste repository at Yucca Mountain, Nevada. NRC staff performed bounding calculations to quantify radionuclide releases available for ground-water transport to potential receptors from a Yucca Mountain repository. Preliminary analyses suggest insignificant doses of plutonium and americium colloids could be derived from spent nuclear fuel. Using surface complexation models, NRC staff found that colloids can potentially lower actinide retardation factors by up to several orders of magnitude. Performance assessment calculations, in which colloidal transport of plutonium and americium was simulated by assuming no sorption or matrix diffusion, indicated no effect of colloids on human dose within the 10,000 year compliance period due largely to long waste-package lifetimes. NRC staff have identified information gaps and developed technical agreements with the U.S. Department of Energy (DOE) to ensure sufficient information will be presented in any potential future Yucca Mountain license application. DOE has agreed to identify which radionuclides could be transported via colloids, incorporate uncertainties in colloid formation, release and transport parameters, and conceptual models, and address the applicability of field data using synthetic microspheres as colloid analogs. NRC is currently

Development of measures to assess the safety of existing NPPs and the effectiveness of regulations and regulatory actions (including 'prescriptive' and 'performance based' approaches). Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1996-09-01

This report arises from the fourth series of peer discussions on regulatory practices entitled D evelopment of measures to assess the safety of existing nuclear power plants and the effectiveness of regulations and regulatory actions (including 'prescriptive' and 'performance based' approaches) . Senior regulators from 23 Member States participated in four peer group discussions during 1995-1996. This report presents the outcome of these meetings and recommendations of good practices identified by these senior regulators. The purpose of this report is to disseminate the views which the senior regulators presented at the meetings relating to measures used for assessing the safety of existing nuclear power plants and evaluating the effectiveness of regulators and regulatory actions. The intention in doing this is to assist Member States in the enhancement of their regulatory practices by identifying commonly accepted good practices. This report is structured so that it covers the subject matter under the following main headings: 'Prescriptive and Performance Based' Approaches to Regulation; Common Features of Regulatory Approaches; Effectiveness of the Regulator and Regulatory Actions; Recommendations of Good Practice. It is important to note that recommendations of good practice are included if they have been identified by at least one of the groups. It does not follow that all of the groups or individual Member States would necessarily endorse all of the recommendations. However, it is considered that if a single group of senior regulators judge that a particular practice is worthy of recommendation then it should be included for serious consideration. In some cases the same recommendations arise from all of the Groups

GIS Based Measurement and Regulatory Zoning of Urban Ecological Vulnerability

Directory of Open Access Journals (Sweden)

Xiaorui Zhang

2015-07-01

Full Text Available Urban ecological vulnerability is measured on the basis of ecological sensitivity and resilience based on the concept analysis of vulnerability. GIS-based multicriteria decision analysis (GIS-MCDA methods are used, supported by the spatial analysis tools of GIS, to define different levels of vulnerability for areas of the urban ecology. These areas are further classified into different types of regulatory zones. Taking the city of Hefei in China as the empirical research site, this study uses GIS-MCDA, including the index system, index weights and overlay rules, to measure the degree of its ecological vulnerability on the GIS platform. There are eight indices in the system. Raking and analytical hierarchy process (AHP methods are used to calculate index weights according to the characteristics of the index system. The integrated overlay rule, including selection of the maximum value, and weighted linear combination (WLC are applied as the overlay rules. In this way, five types of vulnerability areas have been classified as follows: very low vulnerability, low vulnerability, medium vulnerability, high vulnerability and very high vulnerability. They can be further grouped into three types of regulatory zone of ecological green line, ecological grey line and ecological red line. The study demonstrates that ecological green line areas are the largest (53.61% of the total study area and can be intensively developed; ecological grey line areas (19.59% of the total area can serve as the ecological buffer zone, and ecological red line areas (26.80% cannot be developed and must be protected. The results indicate that ecological green line areas may provide sufficient room for future urban development in Hefei city. Finally, the respective regulatory countermeasures are put forward. This research provides a scientific basis for decision-making around urban ecological protection, construction and sustainable development. It also provides theoretical method

Immobilization of defense high-level waste: an assessment of technological strategies and potential regulatory goals. Volume I

International Nuclear Information System (INIS)

1979-06-01

An investigation was made of the high-level radioactive waste immobilization technology programs in the U.S. and Europe, and of the associated regulatory programs and waste management perspectives in the countries studied. Purpose was to assess the ability of those programs to satisfy DOE waste management needs and U.S. regulatory requirements. This volume includes: introduction, immobilization strategies in the context of waste isolation program needs, high-level waste management as an integrated system, regulatory goals, engineered-barrier characteristics, barrier technology, high-level waste disposal programs, analysis of HLW immobilization technology in the context of policy and regulatory requirements, and waste immobilization program option

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

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.

Inference of hierarchical regulatory network of estrogen-dependent breast cancer through ChIP-based data

Directory of Open Access Journals (Sweden)

Parvin Jeffrey

2010-12-01

Full Text Available Abstract Background Global profiling of in vivo protein-DNA interactions using ChIP-based technologies has evolved rapidly in recent years. Although many genome-wide studies have identified thousands of ERα binding sites and have revealed the associated transcription factor (TF partners, such as AP1, FOXA1 and CEBP, little is known about ERα associated hierarchical transcriptional regulatory networks. Results In this study, we applied computational approaches to analyze three public available ChIP-based datasets: ChIP-seq, ChIP-PET and ChIP-chip, and to investigate the hierarchical regulatory network for ERα and ERα partner TFs regulation in estrogen-dependent breast cancer MCF7 cells. 16 common TFs and two common new TF partners (RORA and PITX2 were found among ChIP-seq, ChIP-chip and ChIP-PET datasets. The regulatory networks were constructed by scanning the ChIP-peak region with TF specific position weight matrix (PWM. A permutation test was performed to test the reliability of each connection of the network. We then used DREM software to perform gene ontology function analysis on the common genes. We found that FOS, PITX2, RORA and FOXA1 were involved in the up-regulated genes. We also conducted the ERα and Pol-II ChIP-seq experiments in tamoxifen resistance MCF7 cells (denoted as MCF7-T in this study and compared the difference between MCF7 and MCF7-T cells. The result showed very little overlap between these two cells in terms of targeted genes (21.2% of common genes and targeted TFs (25% of common TFs. The significant dissimilarity may indicate totally different transcriptional regulatory mechanisms between these two cancer cells. Conclusions Our study uncovers new estrogen-mediated regulatory networks by mining three ChIP-based data in MCF7 cells and ChIP-seq data in MCF7-T cells. We compared the different ChIP-based technologies as well as different breast cancer cells. Our computational analytical approach may guide biologists to

Risk-based regulation: Challenges and opportunities

International Nuclear Information System (INIS)

Bari, R.A.

1995-01-01

Over the last twenty years, man has witnessed a gradual but steady movement toward increased usage of risk-based methods and results in the regulatory process. The ''risk perspective'' as a supportive view to existing (non-risk-based or deterministic) information used in decision making has a firm foothold now in most countries that regulate nuclear power. Furthermore, in the areas outside the nuclear power field, such as health risk assessment, risk-based information is used increasingly to make decisions on potential impacts of chemical, biological, and radiological exposures. Some of the principal concepts and issues that are pertinent to risk-based regulation are reviewed. There is a growing interest in most countries in the use of risk-based methods and results to facilitate decision-making associated with regulatory processes. A summary is presented of the challenges and opportunities related to expanded use of risk-based regulation

Regulatory decision with EPA/NRC/DOE/State Session (Panel)

Energy Technology Data Exchange (ETDEWEB)

O`Donnell, E.

1995-12-31

This panel will cover the Nuclear Regulatory Commission`s (NRC) proposed radiation limits in the Branch Technical Position on Low-Level Radioactive Waste Performance Assessment and the Environmental Protection Agency`s (EPA) draft regulation in Part 193. Representatives from NRC and EPA will discuss the inconsistencies in these two regulations. DOE and state representatives will discuss their perspective on how these regulations will affect low-level radioactive waste performance assessments.

Critical thinking as a self-regulatory process component in teaching and learning.

Science.gov (United States)

Phan, Huy P

2010-05-01

This article presents a theoretically grounded model of critical thinking and self-regulation in the context of teaching and learning. Critical thinking, deriving from an educational psychology perspective is a complex process of reflection that helps individuals become more analytical in their thinking and professional development. My conceptualisation in this discussion paper argues that both theoretical orientations (critical thinking and self-regulation) operate in a dynamic interactive system of teaching and learning. My argument, based on existing research evidence, suggests two important points: (i) critical thinking acts as another cognitive strategy of self-regulation that learners use in their learning, and (ii) critical thinking may be a product of various antecedents such as different self-regulatory strategies.

[Regulatory requirements regarding cell-based medicinal products for human and veterinary use - a comparison].

Science.gov (United States)

Kuhlmann-Gottke, Johanna; Duchow, Karin

2015-11-01

At present, there is no separate regulatory framework for cell-based medicinal products (CBMP) for veterinary use at the European or German level. Current European and national regulations exclusively apply to the corresponding medicinal products for human use. An increasing number of requests for the regulatory classification of CBMP for veterinary use, such as allogeneic stem cell preparations and dendritic cell-based autologous tumour vaccines, and a rise in scientific advice for companies developing these products, illustrate the need for adequate legislation. Currently, advice is given and decisions are made on a case-by-case basis regarding the regulatory classification and authorisation requirements.Since some of the CBMP - in particular in the area of stem-cell products - are developed in parallel for human and veterinary use, there is an urgent need to create specific legal definitions, regulations, and guidelines for these complex innovative products in the veterinary sector as well. Otherwise, there is a risk that that the current legal grey area regarding veterinary medicinal products will impede therapeutic innovations in the long run. A harmonised EU-wide approach is desirable. Currently the European legislation on veterinary medicinal products is under revision. In this context, veterinary therapeutics based on allogeneic cells and tissues will be defined and regulated. Certainly, the legal framework does not have to be as comprehensive as for human CBMP; a leaner solution is conceivable, similar to the special provisions for advanced-therapy medicinal products laid down in the German Medicines Act.

Community-based Ecotourism in Tenganan Dauh Tukad: An Indigenous Conservation Perspective

Directory of Open Access Journals (Sweden)

I Ketut Sardiana

2015-11-01

Full Text Available Abstract Community-based ecotourism involves conservation, business, and community development. It is a subset of nature-based tourism that are owned and managed by the community and used to improve the well-being of its community members. Research conducted in Indigenous Tenganan Dauh Tukad Village, Bali. This paper examines the linkage of community participation in ecotourism with the conservation practices and perspectives. This study revealed that there is a positive linkage between community participation to their practices and perspective of conservation. This includes conservation of biodiversity environment and cultural heritage of the local community.

Regulatory policy and structural change in the natural gas industry: A transaction cost perspective

International Nuclear Information System (INIS)

Sauer, D.G.

1991-01-01

The Federal Energy Regulatory Commission has recently promoted policy initiatives designed to substitute market responsive industry practices for the micro-management regulatory practices previously employed. These new policies are expected to generate a flexible gas pricing policy that more accurately reflects market supply and demand conditions. Historically, much of the regulation of this industry was enacted to ensure that pipeline companies would be able to recover the very large up-front investments in immobile equipment that characterize the production, transportation, storage, and distribution of natural gas. The institutional detail available from historical accounts of the development of the industry are used to describe structural change over time. Regulatory policy, the level of asset specificity, and the extent of secondary environmental uncertainty are all shown to exert significant effects on the level of integration into production, storage and marketing

Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective.

Science.gov (United States)

Solomon, Deepak; Gupta, Nilesh; Mulla, Nihal S; Shukla, Snehal; Guerrero, Yadir A; Gupta, Vivek

2017-11-01

In the past few years, measurement of drug release from pharmaceutical dosage forms has been a focus of extensive research because the release profile obtained in vitro can give an indication of the drug's performance in vivo. Currently, there are no compendial in vitro release methods designed for liposomes owing to a range of experimental challenges, which has created a major hurdle for both development and regulatory acceptance of liposome-based drug products. In this paper, we review the current techniques that are most often used to assess in vitro drug release from liposomal products; these include the membrane diffusion techniques (dialysis, reverse dialysis, fractional dialysis, and microdialysis), the sample-and-separate approach, the in situ method, the continuous flow, and the modified United States Pharmacopeia methods (USP I and USP IV). We discuss the principles behind each of the methods and the criteria that assist in choosing the most appropriate method for studying drug release from a liposomal formulation. Also, we have included information concerning the current regulatory requirements for liposomal drug products in the United States and in Europe. In light of increasing costs of preclinical and clinical trials, applying a reliable in vitro release method could serve as a proxy to expensive in vivo bioavailability studies. Graphical Abstract Appropriate in-vitro drug release test from liposomal products is important to predict the in-vivo performance.

MIRA: An R package for DNA methylation-based inference of regulatory activity.

Science.gov (United States)

Lawson, John T; Tomazou, Eleni M; Bock, Christoph; Sheffield, Nathan C

2018-03-01

DNA methylation contains information about the regulatory state of the cell. MIRA aggregates genome-scale DNA methylation data into a DNA methylation profile for independent region sets with shared biological annotation. Using this profile, MIRA infers and scores the collective regulatory activity for each region set. MIRA facilitates regulatory analysis in situations where classical regulatory assays would be difficult and allows public sources of open chromatin and protein binding regions to be leveraged for novel insight into the regulatory state of DNA methylation datasets. R package available on Bioconductor: http://bioconductor.org/packages/release/bioc/html/MIRA.html. nsheffield@virginia.edu.

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.

Confidential data in a competitive utility environment: A regulatory perspective

Energy Technology Data Exchange (ETDEWEB)

Vine, E.

1996-08-01

Historically, the electric utility industry has been regarded as one of the most open industries in the United States in sharing information but their reputation is being challenged by competitive energy providers, the general public, regulators, and other stakeholders. As the prospect of competition among electricity power providers has increased in recent years, many utilities have been requesting that the data they submit to their utility regulatory commissions remain confidential. Withholding utility information from the public is likely to have serious and significant policy implications with respect to: (1) consumer education, the pursuit of truth, mutual respect among parties, and social cooperation; (2) the creation of a fair market for competitive energy services; (3) the regulatory balance; (4) regional and national assessments of energy-savings opportunities; (5) research and development; and (6) evaluations of utility programs, plans, and policies. In a telephone survey of all public utility commissions (PUCs) that regulate electric and gas utilities in the U.S., we found that almost all PUCs have received requests from utility companies for data to be filed as confidential, and confidential data filings appear to have increased (both in scope and in frequency) in those states where utility restructuring is being actively discussed. The most common types of data submitted as confidential by utilities dealt with specific customer data, market data, avoided costs, and utility costs.

Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

Science.gov (United States)

Bansal, Gulshan; Suthar, Nancy; Kaur, Jasmeen; Jain, Astha

2016-07-01

Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (-80 to 100 °C), humidity (0-100%) and duration (a few hours-36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Cell therapy medicinal product regulatory framework in Europe and its application for MSC based therapy development

Directory of Open Access Journals (Sweden)

Janis eAncans

2012-08-01

Full Text Available Advanced therapy medicinal products (ATMPs, including cell therapy products, form a new class of medicines in the European Union. Since ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT has been established at European Medicines Agency (EMA for centralized classification, certification and evaluation procedures, and other ATMP related tasks. Guidance documents, initiatives and interaction platforms are available to make the new framework more accessible for small and medium-sized enterprises, academia, hospitals and foundations. Good understanding of centralised and national components of the regulatory system is required to plan product development. It is in the best interests of cell therapy developers to utilise provided resources starting with the preclinical stage. Whilst there have not been mesenchymal stem cell (MSC based medicine authorisations in the EU, three MSC products have received marketing approval in other regions since 2011. Information provided on regulatory requirements, procedures and initiatives is aimed to facilitate MSC based medicinal product development and authorisation in the EU.

Unproven stem cell-based interventions & physicians' professional obligations; a qualitative study with medical regulatory authorities in Canada.

Science.gov (United States)

Zarzeczny, Amy; Clark, Marianne

2014-10-14

The pursuit of unproven stem cell-based interventions ("stem cell tourism") is an emerging issue that raises various concerns. Physicians play different roles in this market, many of which engage their legal, ethical and professional obligations. In Canada, physicians are members of a self-regulated profession and their professional regulatory bodies are responsible for regulating the practice of medicine and protecting the public interest. They also provide policy guidance to their members and discipline members for unprofessional conduct. We conducted semi-structured telephone interviews with representatives from six different provincial Colleges of Physicians and Surgeons in Canada to discuss their experiences and perspectives regarding stem cell tourism. Our focus was on exploring how different types of physician involvement in this market would be viewed by physicians' professional regulatory bodies in Canada. When considering physicians' professional obligations, participants drew analogies between stem cell tourism and other areas of medical tourism as well as with some aspects of complementary alternative medicine where existing policies, codes of ethics and regulations provide some guidance. Canadian physicians are required to act in the best interests of their patients, respect patient autonomy, avoid conflicts of interest and pursue evidence-based practice in accordance with accepted standards of care. Physicians who provide unproven treatments falling outside the standard of care, not in the context of an approved research protocol, could be subject to professional discipline. Other types of problematic conduct include referrals involving financial conflict of interest and failure to provide urgent medically necessary care. Areas of ambiguity include physicians' obligations when asked for information and advice about seeking unproven medical treatments, in terms of providing non-urgent follow-up care, and when asked to support efforts to go abroad by

The Canadian Government perspective on cost-effective regulation

International Nuclear Information System (INIS)

Martin, J.K.; Iwankow, C.

1996-01-01

Fiscal constraint, globalization of markets, and accelerated technological change have resulted in a new focus on the cost-effectiveness of government activities and, in turn, on methods of policy evaluation. An exploration of regulatory problems, and the use of regulation as a public policy instrument, reveals a commonalty of experience in all industrialized countries. This paper provides a brief synopsis of the Government of Canada's perspective on cost-effective regulation. To understand cost-effective regulation, this paper examines the principles of regulatory reform which underlie the current strategy of the federal government (collaborative decision-making mechanisms., methods of clear policy evaluation, and well defined lines of accountability). It discusses the nature of, and rationale for, government regulation, the reasons for regulatory reform in the economy, and the principal aims of Canadian regulatory reform and regulatory policy assessment. It does so by specifically addressing the role of cost-benefit analysis in the process of regulatory assessment - a method which involves systematically identifying, and quantifying where possible, the social benefits and costs associated with alternative public policy actions - with a particular focus on regulation which affects the Canadian nuclear industry. (author). 51 refs

The Canadian Government perspective on cost-effective regulation

Energy Technology Data Exchange (ETDEWEB)

Martin, J K; Iwankow, C [Treasury Board of Canada Secretariat, Ottawa, ON (Canada)

1997-12-31

Fiscal constraint, globalization of markets, and accelerated technological change have resulted in a new focus on the cost-effectiveness of government activities and, in turn, on methods of policy evaluation. An exploration of regulatory problems, and the use of regulation as a public policy instrument, reveals a commonalty of experience in all industrialized countries. This paper provides a brief synopsis of the Government of Canada`s perspective on cost-effective regulation. To understand cost-effective regulation, this paper examines the principles of regulatory reform which underlie the current strategy of the federal government (collaborative decision-making mechanisms., methods of clear policy evaluation, and well defined lines of accountability). It discusses the nature of, and rationale for, government regulation, the reasons for regulatory reform in the economy, and the principal aims of Canadian regulatory reform and regulatory policy assessment. It does so by specifically addressing the role of cost-benefit analysis in the process of regulatory assessment - a method which involves systematically identifying, and quantifying where possible, the social benefits and costs associated with alternative public policy actions - with a particular focus on regulation which affects the Canadian nuclear industry. (author). 51 refs.

Using a Design Science Perspective to Understand a Complex Design-Based Research Process

DEFF Research Database (Denmark)

Bækgaard, Lars

2012-01-01

The purpose of the paper is to demonstrate how a design science perspective can be used to describe and understand a set of related design-based research processes. We describe and analyze a case study in a manner that is inspired by design science. The case study involves the design of modeling......-based research processes. And we argue that a design science perspective may be useful for both researchers and practitioners....... tools and the redesign of an information service in a library. We use a set of guidelines from a design science perspective to organize the description and analysis of the case study. By doing this we demonstrate the usefulness of design science as an analytical tool for understanding related design...

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

Stakeholder perspectives on workplace-based performance assessment: towards a better understanding of assessor behaviour.

Science.gov (United States)

de Jonge, Laury P J W M; Timmerman, Angelique A; Govaerts, Marjan J B; Muris, Jean W M; Muijtjens, Arno M M; Kramer, Anneke W M; van der Vleuten, Cees P M

2017-12-01

Workplace-Based Assessment (WBA) plays a pivotal role in present-day competency-based medical curricula. Validity in WBA mainly depends on how stakeholders (e.g. clinical supervisors and learners) use the assessments-rather than on the intrinsic qualities of instruments and methods. Current research on assessment in clinical contexts seems to imply that variable behaviours during performance assessment of both assessors and learners may well reflect their respective beliefs and perspectives towards WBA. We therefore performed a Q methodological study to explore perspectives underlying stakeholders' behaviours in WBA in a postgraduate medical training program. Five different perspectives on performance assessment were extracted: Agency, Mutuality, Objectivity, Adaptivity and Accountability. These perspectives reflect both differences and similarities in stakeholder perceptions and preferences regarding the utility of WBA. In comparing and contrasting the various perspectives, we identified two key areas of disagreement, specifically 'the locus of regulation of learning' (i.e., self-regulated versus externally regulated learning) and 'the extent to which assessment should be standardised' (i.e., tailored versus standardised assessment). Differing perspectives may variously affect stakeholders' acceptance, use-and, consequently, the effectiveness-of assessment programmes. Continuous interaction between all stakeholders is essential to monitor, adapt and improve assessment practices and to stimulate the development of a shared mental model. Better understanding of underlying stakeholder perspectives could be an important step in bridging the gap between psychometric and socio-constructivist approaches in WBA.

Effects of implicit theories of ability and stereotype-inconsistent information on handgrip strength in older adults: A regulatory fit perspective.

Science.gov (United States)

Emile, Mélanie; Chalabaev, Aina; Colson, Serge S; Vaulerin, Jerome; Falzon, Charlene; D'Arripe-Longueville, Fabienne

2017-03-01

This study examined whether stereotype-inconsistent information interacts with implicit theories of ability to affect handgrip strength in older adults. Eighty-two retired older adults (13 men and 69 women) from 61 to 89 years old (M age = 75.8 years; SD = 6.9) performed maximum voluntary contractions (MVC) during a handgrip task in a design manipulating implicit theories of ability and stereotype-inconsistent information related to physical decline with aging. Participants were randomly assigned to one of three groups: incremental condition, entity condition, or control group. The results showed that in the incremental condition the stereotype-inconsistent information improved the peak MVC, the average MVC, the peak rate of force development (RFD), and RFD in the initial 50 ms of the MVC. This study therefore demonstrated that individuals with an incremental mindset who are exposed to stereotype-inconsistent information can boost their physical performance. These findings are discussed from the perspective of regulatory fit (i.e., when task framing is congruent with the individual's goal). © 2016 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.

The Role of Advisory Committees on Regulatory functions: Argentine Experience

International Nuclear Information System (INIS)

Larcher, A. M.; Arias, C.; Kunst, J. J.; Perez, R. M.; Rudelli, M.

2004-01-01

The Argentine Nuclear Regulatory Authority (NRA) has appointed a consultants body that advises its Board of Directors on aspects related to authorization's granting to individuals for the use of radioisotopes and ionizing radiation in medicine, research and industry. Such committee, whose existence goes back to the year 1958, is integrated by prominent professionals knowledgeable about ionizing radiation and radioisotopes applications in the medical, biomedical and industrial fields, representing important professional associations or institutions related to the practices in question. Originally, the committee was conceived as a consultation body to fulfil two important functions: To produce, in a regular way, authorized opinions at experts level to settle down questions relative to the regulation of practices, new at that time in the country, and To submit to a peer review applications for individual authorization for different uses of ionizing radiation previously it's granting by the Regulatory Authority. In this paper the role of the advisory council is analyzed from a historical perspective trying to emphasize an outstanding aspect not sufficiently analyzed linked to the capability that advisory bodies, with representative users' presence, can reach in the interpretation of regulatory standards based on a performance philosophy. Such approach outlines the permanent dilemma about the performance level of the licensee that should satisfy the Regulatory Authority. Once the broad objectives of radiation protection has been defined professional criteria is required for applying them to different practices. Balance between flexibility and avoidance of excessive uncertainty is desirable. In the authors' opinion the inclusion, inside the regulator's structure of consultants bodies giving direct participation to qualified stakeholders, far from harming the necessary independence that should characterize the regulator, on the contrary, allows to have an excellent social

OECD/NEA WGFCS Workshop: Safety Assessment of Fuel Cycle Facilities - Regulatory Approaches and Industry Perspectives

International Nuclear Information System (INIS)

2013-01-01

Nuclear fuel is produced, processed, and stored mainly in industrial-scale facilities. Uranium ores are processed and refined to produce a pure uranium salt stream, Uranium is converted and enriched, nuclear fuel is fabricated (U fuel and U/Pu fuel for the closed cycle option); and spent fuel is stored and reprocessed in some countries (close cycle option). Facilities dedicated to the research and development of new fuel or new processes are also considered as Fuel Cycle Facilities. The safety assessment of nuclear facilities has often been led by the methodology and techniques initially developed for Nuclear Power Plants. As FCFs cover a wide diversity of installations the various approaches of national regulators, and their technical support organizations, for the Safety Assessment of Fuel Cycle Facilities are also diverse, as are the approaches by their industries in providing safety justifications for their facilities. The objective of the Working Group on Fuel Cycle Safety is to advance the understanding for both regulators and operators of relevant aspects of nuclear fuel cycle safety in member countries. A large amount of experience is available in safety assessment of FCFs, which should be shared to develop ideas in this field. To contribute to this task, the Workshop on 'Safety Assessment of Fuel Cycle Facilities - Regulatory Approaches and Industry Perspectives' was held in Toronto, on 27 - 29 September 2011. The workshop was hosted by Canadian Nuclear Safety Commission. The current proceedings provide summary of the results of the workshop with the text of the papers given and presentations made

Understanding the Pathological Basis of Neurological Diseases Through Diagnostic Platforms Based on Innovations in Biomedical Engineering: New Concepts and Theranostics Perspectives

Directory of Open Access Journals (Sweden)

Laura Ganau

2018-02-01

Full Text Available The pace of advancement of genomics and proteomics together with the recent understanding of the molecular basis behind rare diseases could lead in the near future to significant advances in the diagnosing and treating of many pathological conditions. Innovative diagnostic platforms based on biomedical engineering (microdialysis and proteomics, biochip analysis, non-invasive impedance spectroscopy, etc. are introduced at a rapid speed in clinical practice: this article primarily aims to highlight how such platforms will advance our understanding of the pathological basis of neurological diseases. An overview of the clinical challenges and regulatory hurdles facing the introduction of such platforms in clinical practice, as well as their potential impact on patient management, will complement the discussion on foreseeable theranostic perspectives. Indeed, the techniques outlined in this article are revolutionizing how we (1 identify biomarkers that better define the diagnostic criteria of any given disease, (2 develop research models, and (3 exploit the externalities coming from innovative pharmacological protocols (i.e., those based on monoclonal antibodies, nanodrugs, etc. meant to tackle the molecular cascade so far identified.

Nuclear regulatory decision making

International Nuclear Information System (INIS)

2005-01-01

The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear utilities operate their plants at all times in an acceptably safe manner. In meeting this objective, the regulatory body should strive to ensure that its regulatory decisions are technically sound, consistent from case to case, and timely. In addition, the regulator must be aware that its decisions and the circumstances surrounding those decisions can affect how its stakeholders, such as government policy makers, the industry it regulates, and the public, view it as an effective and credible regulator. In order to maintain the confidence of those stakeholders, the regulator should make sure that its decisions are transparent, have a clear basis in law and regulations, and are seen by impartial observers to be fair to all parties. Based on the work of a Nuclear Energy Agency (NEA) expert group, this report discusses some of the basic principles and criteria that a regulatory body should consider in making decisions and describes the elements of an integrated framework for regulatory decision making. (author)

Nuclear waste issues: a perspectives document

International Nuclear Information System (INIS)

Cohen, J.J.; Smith, C.F.; Ciminese, F.J.

1983-02-01

This report contains the results of systematic survey of perspectives on the question of radioactive waste management. Sources of information for this review include the scientific literature, regulatory and government documents, pro-nuclear and anti-nuclear publications, and news media articles. In examining the sources of information, it has become evident that a major distinction can be made between the optimistic or positive viewpoints, and the pessimistic or negative ones. Consequently, these form the principal categories for presentation of the perspectives on the radioactive waste management problem have been further classified as relating to the following issue areas: the physical aspects of radiation, longevity, radiotoxicity, the quantity of radioactive wastes, and perceptual factors

Nuclear waste issues: a perspectives document

Energy Technology Data Exchange (ETDEWEB)

Cohen, J.J.; Smith, C.F.; Ciminese, F.J.

1983-02-01

This report contains the results of systematic survey of perspectives on the question of radioactive waste management. Sources of information for this review include the scientific literature, regulatory and government documents, pro-nuclear and anti-nuclear publications, and news media articles. In examining the sources of information, it has become evident that a major distinction can be made between the optimistic or positive viewpoints, and the pessimistic or negative ones. Consequently, these form the principal categories for presentation of the perspectives on the radioactive waste management problem have been further classified as relating to the following issue areas: the physical aspects of radiation, longevity, radiotoxicity, the quantity of radioactive wastes, and perceptual factors.

A dynamic usage based perspective on L2 writing

NARCIS (Netherlands)

Verspoor, M.H.; Schmid, M.S.; Xu, X.

The goal of this study was to explore the contribution that a dynamic usage based (DUB) perspective can bring to the establishment of objective measures to assess L2 learners' written texts and at the same time to gain insight into the dynamic process of language development. Four hundred and thirty

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

Cell therapy medicinal product regulatory framework in Europe and its application for MSC-based therapy development

Science.gov (United States)

Ancans, Janis

2012-01-01

Advanced therapy medicinal products (ATMPs), including cell therapy products, form a new class of medicines in the European Union. Since the ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT) has been established at the European Medicines Agency (EMA) for centralized classification, certification and evaluation procedures, and other ATMP-related tasks. Guidance documents, initiatives, and interaction platforms are available to make the new framework more accessible for small- and medium-sized enterprises, academia, hospitals, and foundations. Good understanding of the centralized and national components of the regulatory system is required to plan product development. It is in the best interests of the cell therapy developers to utilize the resources provided starting with the pre-clinical stage. Whilst there have been no mesenchymal stem cell (MSC)-based medicine authorizations in the EU, three MSC products have received marketing approval in other regions since 2011. The information provided on the regulatory requirements, procedures, and initiatives is aimed at facilitating MSC-based medicinal product development and authorization in the EU. PMID:22912639

The role of self-regulatory efficacy, moral disengagement and guilt on doping likelihood: A social cognitive theory perspective.

Science.gov (United States)

Ring, Christopher; Kavussanu, Maria

2018-03-01

Given the concern over doping in sport, researchers have begun to explore the role played by self-regulatory processes in the decision whether to use banned performance-enhancing substances. Grounded on Bandura's (1991) theory of moral thought and action, this study examined the role of self-regulatory efficacy, moral disengagement and anticipated guilt on the likelihood to use a banned substance among college athletes. Doping self-regulatory efficacy was associated with doping likelihood both directly (b = -.16, P self-regulatory efficacy influences the likelihood to use banned performance-enhancing substances both directly and indirectly via moral disengagement.

Categorization and selection of regulatory approaches for nuclear power plants

International Nuclear Information System (INIS)

Sugaya, Junko; Harayama, Yuko

2009-01-01

Several new regulatory approaches have been introduced to Japanese nuclear safety regulations, in which a prescriptive and deterministic approach had traditionally predominated. However, the options of regulatory approaches that can possibly be applied to nuclear safety regulations as well as the methodology for selecting the options are not systematically defined. In this study, various regulatory approaches for nuclear power plants are categorized as prescriptive or nonprescriptive, outcome-based or process-based, and deterministic or risk-informed. 18 options of regulatory approaches are conceptually developed and the conditions for selecting the appropriate regulatory approaches are identified. Current issues on nuclear regulations regarding responsibilities, transparency, consensus standards and regulatory inspections are examined from the viewpoints of regulatory approaches to verify usefulness of the categorization and selection concept of regulatory approaches. Finally, some of the challenges at the transitional phase of regulatory approaches are discussed. (author)

Personality and self-regulation: trait and information-processing perspectives.

Science.gov (United States)

Hoyle, Rick H

2006-12-01

This article introduces the special issue of Journal of Personality on personality and self-regulation. The goal of the issue is to illustrate and inspire research that integrates personality and process-oriented accounts of self-regulation. The article begins by discussing the trait perspective on self-regulation--distinguishing between temperament and personality accounts--and the information-processing perspective. Three approaches to integrating these perspectives are then presented. These range from methodological approaches, in which constructs representing the two perspectives are examined in integrated statistical models, to conceptual approaches, in which the two perspectives are unified in a holistic theoretical model of self-regulation. The article concludes with an overview of the special issue contributions, which are organized in four sections: broad, integrative models of personality and self-regulation; models that examine the developmental origins of self-regulation and self-regulatory styles; focused programs of research that concern specific aspects or applications of self-regulation; and strategies for increasing the efficiency and effectiveness of self-regulation.

A regulatory perspective on appropriate seismic loading stress criteria for advanced light water reactor piping systems

International Nuclear Information System (INIS)

Terao, D.

1995-01-01

In the foregoing sections, the author has discussed the NRC staff's perspective on the evolving seismic design criteria for piping systems. He also addressed the need for developing seismic loading stress criteria and provided several recommendations and considerations for ensuring piping functional capability, pressure integrity, and structural integrity. Overall, the general consensus in the NRC staff is that in the past several years, many initiatives have been developed and implemented by the industry and the NRC staff to reduce the excessive conservatisms that might have existed in nuclear piping system design criteria. The regulations, regulatory guides, and Standard Review Plan have been (or are currently in the process of being) revised to reflect these initiatives in an effort to produce requirements and guidelines that will continue to result in a safe and practical design of piping systems. However, further proposals to reduce margins are continually being submitted to the ASME Boiler and Pressure Vessel Code and the NRC for review and approval. Improvements to the piping seismic design criteria are always encouraged, but there is a point at which the benefits might be outweighed by drawbacks. Because of this rapidly evolving situation the need exists for the industry and the NRC staff to develop a course of action to ensure that piping seismic design criteria for future ALWR plants will result in piping system designs that provide adequate safety margins and practical designs at a reasonable cost

Regulatory requirements for clinical trial and marketing authorisation application for cell-based medicinal products.

Science.gov (United States)

Salmikangas, P; Flory, E; Reinhardt, J; Hinz, T; Maciulaitis, R

2010-01-01

The new era of regenerative medicine has led to rapid development of new innovative therapies especially for diseases and tissue/organ defects for which traditional therapies and medicinal products have not provided satisfactory outcome. Although the clinical use and developments of cell-based medicinal products (CBMPs) could be witnessed already for a decade, robust scientific and regulatory provisions for these products have only recently been enacted. The new Regulation for Advanced Therapies (EC) 1394/2007 together with the revised Annex I, Part IV of Directive 2001/83/EC provides the new legal framework for CBMPs. The wide variety of cell-based products and the foreseen limitations (small sample sizes, short shelf life) vs. particular risks (microbiological purity, variability, immunogenicity, tumourigenicity) associated with CBMPs have called for a flexible, case-by-case regulatory approach for these products. Consequently, a risk-based approach has been developed to allow definition of the amount of scientific data needed for a Marketing Authorisation Application (MAA) of each CBMP. The article provides further insight into the initial risk evaluation, as well as to the quality, non-clinical, and clinical requirements of CBMPs. Special somatic cell therapies designed for active immunotherapy are also addressed.

Experience with Regulatory Strategies in Nuclear Power Oversight. Part 1: An International Exploratory Study. Part 2: Workshop Discussions and Conclusions

International Nuclear Information System (INIS)

Melber, Barbara; Durbin, Nancy E.; Tael, Irene

2005-03-01

This report presents the results of a study which explored the use of six different regulatory strategies for oversight of commercial nuclear power facilities: prescriptive, case-based, outcome-based, risk-based, process-based, and self-assessment strategies. Information was collected on experiences with the use of these different regulatory strategies from experts from nuclear regulatory agencies in Canada, Finland, Spain, Sweden, the United Kingdom and the United States. Systematic, structured open-ended interviews with expert regulators with extensive experience were used in order to understand how regulatory strategies are applied in practice. Common patterns were identified regarding: Experts' perspectives on the major benefits and difficulties of using specific regulatory strategies; Experts' experiences with using regulatory strategies for three areas of oversight-design and modifications, quality systems, and training and qualifications; Expert views of the consequences of different regulatory strategies; Issues that emerged in the interviews regarding regulatory strategies. The major benefit of a prescriptive strategy was that it is clear about requirements and expectations. The major difficulties were that it takes responsibility away from the licensee, it requires a high use of regulator resources and is rigid and difficult to change. A case-based strategy had the key benefit of flexibility for adapting regulatory responses to unique situations, but the difficulties of being considered arbitrary, inconsistent, and unfair and requiring heavy resource use. An outcome-based strategy had the main benefit of allowing licensees to decide the best way to operate m order to meet safety goals, but the major difficulty of identifying appropriate ways to measure safety performance. The major benefit of a risk strategy was its use co prioritize safety issues and allocate resources. However, it was considered inappropriate to use as a stand alone strategy and a

Experience with Regulatory Strategies in Nuclear Power Oversight. Part 1: An International Exploratory Study. Part 2: Workshop Discussions and Conclusions

Energy Technology Data Exchange (ETDEWEB)

Melber, Barbara [Melber Consulting, Seattle, WA (United States); Durbin, Nancy E. [Nancy E. Durbin Consulting, Kirkland, WA (United States); Tael, Irene (ed.) [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

2005-03-01

This report presents the results of a study which explored the use of six different regulatory strategies for oversight of commercial nuclear power facilities: prescriptive, case-based, outcome-based, risk-based, process-based, and self-assessment strategies. Information was collected on experiences with the use of these different regulatory strategies from experts from nuclear regulatory agencies in Canada, Finland, Spain, Sweden, the United Kingdom and the United States. Systematic, structured open-ended interviews with expert regulators with extensive experience were used in order to understand how regulatory strategies are applied in practice. Common patterns were identified regarding: Experts' perspectives on the major benefits and difficulties of using specific regulatory strategies; Experts' experiences with using regulatory strategies for three areas of oversight-design and modifications, quality systems, and training and qualifications; Expert views of the consequences of different regulatory strategies; Issues that emerged in the interviews regarding regulatory strategies. The major benefit of a prescriptive strategy was that it is clear about requirements and expectations. The major difficulties were that it takes responsibility away from the licensee, it requires a high use of regulator resources and is rigid and difficult to change. A case-based strategy had the key benefit of flexibility for adapting regulatory responses to unique situations, but the difficulties of being considered arbitrary, inconsistent, and unfair and requiring heavy resource use. An outcome-based strategy had the main benefit of allowing licensees to decide the best way to operate m order to meet safety goals, but the major difficulty of identifying appropriate ways to measure safety performance. The major benefit of a risk strategy was its use co prioritize safety issues and allocate resources. However, it was considered inappropriate to use as a stand alone strategy

Development of the Level 1 PSA Model for PGSFR Regulatory

International Nuclear Information System (INIS)

Na, Hyun Ju; Lee, Yong Suk; Shin, Andong; Suh, Nam Duk

2014-01-01

SFR (sodium-cooled fast reactor) is Gen-IV nuclear energy system, which is designed for stability, sustainability and proliferation resistance. KALIMER-600 and PGSFR (Prototype Gen-IV SFR) are under development in Korea with enhanced passive safety concepts, e.g. passive reactor shutdown, passive residual heat removal, and etc. Risk analysis from a regulatory perspective is necessary for regulatory body to support the safety and licensing review of SFR. Safety issues should be identified in the early design phase in order to prevent the unexpected cost increase and the delay of PGSFR licensing schedule. In this respect, the preliminary PSA Model of KALIMER-600 had been developed for regulatory. In this study, the development of PSA Level 1 Model is presented. The important impact factors in the risk analysis for the PGSFR, such as Core Damage Frequency (CDF), have been identified and the related safety insights have been derived. The PSA level 1 model for PGSFR regulatory is developed and the risk analysis is conducted. Regarding CDF, LOISF frequency, uncertainty parameter for passive system CCF, loss of 125V DC control center bus and damper CCF are identified as the important factors. Sensitivity analyses show that the CDF would be differentiated (lowered) according to their values

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).

Example-based learning: Integrating cognitive and social-cognitive research perspectives

NARCIS (Netherlands)

T.A.J.M. van Gog (Tamara); N. Rummel (Nikol)

2010-01-01

textabstractExample-based learning has been studied from different perspectives. Cognitive research has mainly focused on worked examples, which typically provide students with a written worked-out didactical solution to a problem to study. Social-cognitive research has mostly focused on modeling

Food marketing targeting children: unveiling the ethical perspectives in the discourse on self-regulation.

Science.gov (United States)

Silva, Dillian Adelaine Cesar da; Cunha, Antonio Carlos Rodrigues da; Cunha, Thiago Rocha da; Rosaneli, Caroline Filla

2017-07-01

When it comes to food marketing, children are one of the major targets. Regulatory actions can play a strategic role in health protection. The objective of this research was to characterize the ethical perspective in the discourse against state regulatory actions on food marketing directed at children, aiming to understand the context of the discourse's production and how it creates meaning. The methodology adopted was qualitative, with documentary analysis and use of concepts and procedures from Discourse Analysis. The work of Hans Jonas, specifically his Responsibility Principle, and Garrafa and Port's Intervention Bioethics oriented the analysis. The self-regulation discourse analysis showed an ethical perspective in which relations of consumption predominate over the children´s vulnerability. The rhetorical excess is constant, as well as the use of resources like naturalization, untruthfulness, ideological dissimulation and euphemism. An erasure of social conflicts takes place, and an ahistorical perspective is present. The discourse does not align with Jonas´ Responsibility Principle, nor those of Intervention Bioethics. Lastly, the ethical perspective of the discourse represents a double paradox, because it is a business discourse that hides its competitive roots and metamorphoses into an ethical one.

Groundwater contamination from waste management sites: The interaction between risk-based engineering design and regulatory policy: 1. Methodology

Science.gov (United States)

Massmann, Joel; Freeze, R. Allan

1987-02-01

This paper puts in place a risk-cost-benefit analysis for waste management facilities that explicitly recognizes the adversarial relationship that exists in a regulated market economy between the owner/operator of a waste management facility and the government regulatory agency under whose terms the facility must be licensed. The risk-cost-benefit analysis is set up from the perspective of the owner/operator. It can be used directly by the owner/operator to assess alternative design strategies. It can also be used by the regulatory agency to assess alternative regulatory policy, but only in an indirect manner, by examining the response of an owner/operator to the stimuli of various policies. The objective function is couched in terms of a discounted stream of benefits, costs, and risks over an engineering time horizon. Benefits are in the form of revenues for services provided; costs are those of construction and operation of the facility. Risk is defined as the cost associated with the probability of failure, with failure defined as the occurrence of a groundwater contamination event that violates the licensing requirements established for the facility. Failure requires a breach of the containment structure and contaminant migration through the hydrogeological environment to a compliance surface. The probability of failure can be estimated on the basis of reliability theory for the breach of containment and with a Monte-Carlo finite-element simulation for the advective contaminant transport. In the hydrogeological environment the hydraulic conductivity values are defined stochastically. The probability of failure is reduced by the presence of a monitoring network operated by the owner/operator and located between the source and the regulatory compliance surface. The level of reduction in the probability of failure depends on the probability of detection of the monitoring network, which can be calculated from the stochastic contaminant transport simulations. While

Relationship between regulatory issues and probabilistic risk assessments

International Nuclear Information System (INIS)

Ilberg, D.; Papazoglou, I.

1985-01-01

The objective of this study was to obtain some perspective on the characteristics and the relative number of regulatory issues that are PRA related, i.e., can be effectively addressed by plant specific PRA studies. It was also aimed at developing approaches to resolution of regulatory issues as part of plant specific PRAs. Several ongoing NRC programs include a number of safety-related issues which are applicable to operating plants. A number of these issues include aspects that strongly interact with items addressed in PRA studies. The resolution of several generic issues using PRA studies has already started. A review of over 335 issues included in three NRC programs was conducted: Generic Issue Program (GI); Systematic Evaluation Program (SEP); and TMI Action Plan (TMI). The review identifid 240 items related to PRA, 120 of which were judged to have significant effect on core damage frequency. It is believed that these items can be effectively treated in a PRA study that includes internal and external events

Regulatory RNAs in Bacillus subtilis : a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression

NARCIS (Netherlands)

Mars, Ruben A. T.; Nicolas, Pierre; Denham, Emma L.; van Dijl, Jan Maarten

2016-01-01

Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5= untranslated region. Thus far, most regulatory RNA research has focused on

Development of regulatory policy for SMART-P

Energy Technology Data Exchange (ETDEWEB)

Lee, S. H.; Lee, Y. H.; Moo, Philip; Koh, B. J.; Son, M. K.; Han, G. H.; Kim, D. H. [Korea Association for Nuclear Technology, Daejeon (Korea, Republic of)

2004-06-15

KAERI promoted the construction of a research reactor, SMART-P, the reduced scale of SMART, with intent to demonstrate the safety and performance of SMART. According to this progress, the development of regulatory process for SMART-P became necessary. The establishment of regulatory policy, based on the current regulatory guidelines as well as technical aspect, became essential matters. Considering the on-going small and medium size reactors in near future, the selection of the appropriate measure in the existing regulatory process to SMART-P is very important. Thus the schematic study for the applicable licensing procedure and regulatory requirements suitable for SMART-P is required.

Development of regulatory policy for SMART-P

Energy Technology Data Exchange (ETDEWEB)

Lee, S. H.; Moon, S. H.; Lee, Y. H.; Son, M. K.; Han, K. H.; Kim, D. H. [Korea Association for Nuclear Technology, Taejon (Korea, Republic of)

2003-06-15

KAERI promoted the construction of a research reactor, SMART-P, the reduced scale of SMART, with intent to demonstrate the safety and performance of SMART. According to this progress, the development of regulatory process for SMART-P became necessary. The establishment of regulatory policy, based on the current regulatory guidelines as well as technical aspect, became essential matters. Considering the on-going small and medium size reactors m near future, the selection of the appropriate measure in the existing regulatory process to SMART-P is very important. Thus the schematic study for the applicable licensing procedure and regulatory requirements suitable for SMART-P is required.

Risk literacy for scientists. Invitation to regulatory science

International Nuclear Information System (INIS)

Ono, Kyoko

2012-01-01

This paper discusses a regulatory science, which fills a gap between scientific knowledge and regulatory actions. The author provides examples of the regulatory science employed in chemical risk assessment, such as the linear non-threshold theory. In the regulatory science, scientific data as well as scientific reasoning based on scientific knowledge - or regulatory rules - should play an important role. It is important to recognize that the rules facilitate transparent decision making under conditions of uncertainty and time constraints. Furthermore, the development of traditional or pure science results in the validation of regulatory rules, and subsequently, the regulatory science procedure develops more systematically. The concept of this science should be understood by those engaged in governmental decision making. (author)

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

Development of multipurpose regulatory PSA model

International Nuclear Information System (INIS)

Lee, Chang Ju; Sung, Key Yong; Kim, Hho Jung; Yang, Joon Eon; Ha, Jae Joo

2004-01-01

Generally, risk information for nuclear facilities comes from the results of Probabilistic safety assessment (PSA). PSA is a systematic tool to ensure the safety of nuclear facilities, since it is based on thorough and consistent application of probability models. In particular, the PSA has been widely utilized for risk-informed regulation (RIR), including various licensee-initiated risk-informed applications (RIA). In any regulatory decision, the main goal is to make a sound safety decision based on technically defensible information. Also, due to the increased public requests for giving a safety guarantee, the regulator should provide the visible means of safety. The use of PSA by the regulator can give the answer on this problem. Therefore, in order to study the applicability of risk information for regulatory safety management, it is a demanding task to prepare a well-established regulatory PSA model and tool. In 2002, KINS and KAERI together made a research cooperation to form a working group to develop the regulatory PSA model - so-called MPAS model. The MPAS stands for multipurpose probabilistic analysis of safety. For instance, a role of the MPAS model is to give some risk insights in the preparation of various regulatory programs. Another role of this model is to provide an independent risk information to the regulator during regulatory decision-making, not depending on the licensee's information

Information management applications for the compliance function: a utility perspective

International Nuclear Information System (INIS)

Savoie, R.A.

1986-01-01

Today's complex and changing regulatory environment presents many challenges to those involved in the nuclear power industry. This is particularly true of technical personnel and managers involved in serving the compliance function for nuclear utilities. Adequately supporting the construction, startup, and operations of a nuclear power plant while simultaneously satisfying each regulatory requirement requires the meshing of thousands of individual regulatory tasks with each possible implementation option. The compliance function acts as a screen or filter between the regulatory bodies and the utility nuclear staff. Many varied approaches are taken by utilities in performing this compliance function, both from an organizational and information management perspective. The purpose of this paper is to describe the experiences of Louisiana Power and Light (LP and L) in developing its compliance function and to describe the innovative information management techniques LP and L has developed to serve this function

Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: expert opinions on the state of affairs and the way forward.

Science.gov (United States)

Schiffelers, Marie-Jeanne W A; Blaauboer, Bas J; Bakker, Wieger E; Beken, Sonja; Hendriksen, Coenraad F M; Koëter, Herman B W M; Krul, Cyrille

2014-06-01

Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being accepted for regulatory risk management purposes. This paper describes the barriers and drivers and options to optimize this acceptance process as identified by two expert panels, one on pharmaceuticals and one on chemicals. To untangle the complex acceptance process, the multilevel perspective on technology transitions is applied. This perspective defines influences at the micro-, meso- and macro level which need alignment to induce regulatory acceptance of a 3R model. This paper displays that there are many similar mechanisms within both sectors that prevent 3R models from becoming accepted for regulatory risk assessment and management. Shared barriers include the uncertainty about the value of the new 3R models (micro level), the lack of harmonization of regulatory requirements and acceptance criteria (meso level) and the high levels of risk aversion (macro level). In optimizing the process commitment, communication, cooperation and coordination are identified as critical drivers. Copyright © 2014 Elsevier Inc. All rights reserved.

Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.

Directory of Open Access Journals (Sweden)

Vipin Narang

Full Text Available Human gene regulatory networks (GRN can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs. Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data accompanying this manuscript.

Game-Based Assessments: A Promising Way to Create Idiographic Perspectives

Science.gov (United States)

Walker, A. Adrienne; Engelhard, George, Jr.

2014-01-01

"Game-Based Assessments: A Promising Way to Create Idiographic Perspectives" (Adrienne Walker and George Englehard) comments on: "How Task Features Impact Evidence from Assessments Embedded in Simulations and Games" by Russell G. Almond, Yoon Jeon Kim, Gertrudes Velasquez, and Valerie J. Shute. Here, Walker and Englehard write…

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 model surveillance program based on regulatory experience

International Nuclear Information System (INIS)

Conte, R.J.

1980-01-01

A model surveillance program is presented based on regulatory experience. The program consists of three phases: Program Delineation, Data Acquistion and Data Analysis. Each phase is described in terms of key quality assurance elements and some current philosophies is the United States Licensing Program. Other topics include the application of these ideas to test equipment used in the surveillance progam and audits of the established program. Program Delineation discusses the establishment of administrative controls for organization and the description of responsibilities using the 'Program Coordinator' concept, with assistance from Data Acquisition and Analysis Teams. Ideas regarding frequency of surveillance testing are also presented. The Data Acquisition Phase discusses various methods for acquiring data including operator observations, test procedures, operator logs, and computer output, for trending equipment performance. The Data Analysis Phase discusses the process for drawing conclusions regarding component/equipment service life, proper application, and generic problems through the use of trend analysis and failure rate data. (orig.)

The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

Science.gov (United States)

van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

2015-07-15

Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

Discovering and Exploring State-based Models for Multi-perspective Processes

NARCIS (Netherlands)

van Eck, M.L.; Sidorova, N.; van der Aalst, W.M.P.; La Rosa, M.; Loos, P.; Pastor, O.

2016-01-01

Process mining provides fact-based insights into process behaviour captured in event data. In this work we aim to discover models for processes where different facets, or perspectives, of the process can be identified. Instead of focussing on the events or activities that are executed in the context

Self- and Social Regulation in Learning Contexts: An Integrative Perspective

Science.gov (United States)

Volet, Simone; Vauras, Marja; Salonen, Pekka

2009-01-01

This article outlines the rationale for an integrative perspective of self- and social regulation in learning contexts. The role of regulatory mechanisms in self- and social regulation models is examined, leading to the view that in real time collaborative learning, individuals and social entities should be conceptualized as self-regulating and…

Delay-independent stability of genetic regulatory networks.

Science.gov (United States)

Wu, Fang-Xiang

2011-11-01

Genetic regulatory networks can be described by nonlinear differential equations with time delays. In this paper, we study both locally and globally delay-independent stability of genetic regulatory networks, taking messenger ribonucleic acid alternative splicing into consideration. Based on nonnegative matrix theory, we first develop necessary and sufficient conditions for locally delay-independent stability of genetic regulatory networks with multiple time delays. Compared to the previous results, these conditions are easy to verify. Then we develop sufficient conditions for global delay-independent stability for genetic regulatory networks. Compared to the previous results, this sufficient condition is less conservative. To illustrate theorems developed in this paper, we analyze delay-independent stability of two genetic regulatory networks: a real-life repressilatory network with three genes and three proteins, and a synthetic gene regulatory network with five genes and seven proteins. The simulation results show that the theorems developed in this paper can effectively determine the delay-independent stability of genetic regulatory networks.

Environment, safety, and health regulatory implementation plan

International Nuclear Information System (INIS)

1993-01-01

To identify, document, and maintain the Uranium Mill Tailings Remedial Action (UMTRA) Project's environment, safety, and health (ES ampersand H) regulatory requirements, the US Department of Energy (DOE) UMTRA Project Office tasked the Technical Assistance Contractor (TAC) to develop a regulatory operating envelope for the UMTRA Project. The system selected for managing the UMTRA regulatory operating envelope data bass is based on the Integrated Project Control/Regulatory Compliance System (IPC/RCS) developed by WASTREN, Inc. (WASTREN, 1993). The IPC/RCS is a tool used for identifying regulatory and institutional requirements and indexing them to hardware, personnel, and program systems on a project. The IPC/RCS will be customized for the UMTRA Project surface remedial action and groundwater restoration programs. The purpose of this plan is to establish the process for implementing and maintaining the UMTRA Project's regulatory operating envelope, which involves identifying all applicable regulatory and institutional requirements and determining compliance status. The plan describes how the Project will identify ES ampersand H regulatory requirements, analyze applicability to the UMTRA Project, and evaluate UMTRA Project compliance status

School-Based Health Promotion Intervention: Parent and School Staff Perspectives

Science.gov (United States)

Patino-Fernandez, Anna M.; Hernandez, Jennifer; Villa, Manuela; Delamater, Alan

2013-01-01

Background: The prevalence of childhood obesity is high, particularly among minority youth. The objective of this article was to evaluate parent and school staff perspectives of childhood health and weight qualitatively to guide the development of a school-based obesity prevention program for minority youth. Methods: Hispanic parents (N?=?9) of…

Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

Directory of Open Access Journals (Sweden)

Yoshikazu Nakayama

2015-03-01

Full Text Available Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region.

Structural radioactive waste from 'retubing/refurbishment' of Embalse nuclear power plant. Regulatory perspective

International Nuclear Information System (INIS)

Alvarez, Daniela E.; Lee Gonzales, Horacio M.; Medici, Marcela A.; Piumetti, Elsa H.

2009-01-01

Unlike the building of a new nuclear reactor, the 'retubing / refurbishment' of nuclear reactors that have been in operation for many years, involves the replacement of components in a radioactive environment. This requires a carefully planned radiation protection program to ensure protection of workers, the public and the environment as well as a radioactive waste management program for those radioactive waste generated during the process, which go beyond those generated during the normal operation and maintenance of the plant. Nucleoelectrica Argentina Sociedad Anonima (NA-SA) is scheduled to conduct the Life Extension Process of Embalse Nuclear Power Plant (CNE) which essentially consist of 'retubing / refurbishment' of the installation. The Nuclear Regulatory Authority (ARN) will then have an important activity related to the above process. In particular, this paper will describe some points of interest related to the generation and management of radioactive waste during the 'retubing / refurbishment' of the CNE, from the regulatory point of view. (author)

Perceptions of regulatory approaches

International Nuclear Information System (INIS)

Halin, Magnus; Leinonen, Ruusaliisa

2012-01-01

Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

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

ENSI’s regulatory framework strategy; Regelwerksstrategie des ENSI -- Stratégie réglementaire de l’IFSN -- ENSI’s regulatory framework strategy

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-03-15

This short brochure issued by the Swiss Federal Nuclear Safety Inspectorate ENSI defines the organisation’s regulatory framework strategy. Six guiding principles are declared and discussed: Comprehensive harmonisation with relevant international requirements, basing the regulatory framework on existing, tried-and-tested regulations, issuing of its own guidelines only when it is necessary to do so, guidelines to be drawn up transparently and with the involvement of all stakeholders and basing the level of detail of its regulatory framework on hazard potential and risk.

Prioritization of chemicals in the aquatic environment based on risk assessment: analytical, modeling and regulatory perspective.

Science.gov (United States)

Guillén, D; Ginebreda, A; Farré, M; Darbra, R M; Petrovic, M; Gros, M; Barceló, D

2012-12-01

The extensive and intensive use of chemicals in our developed, highly technological society includes more than 100,000 chemical substances. Significant scientific evidence has lead to the recognition that their improper use and release may result in undesirable and harmful side-effects on both the human and ecosystem health. To cope with them, appropriate risk assessment processes and related prioritization schemes have been developed in order to provide the necessary scientific support for regulatory procedures. In the present paper, two of the elements that constitute the core of risk assessment, namely occurrence and hazard effects, have been discussed. Recent advances in analytical chemistry (sample pre-treatment and instrumental equipment, etc.) have allowed for more comprehensive monitoring of environmental pollution reaching limits of detection up to sub ng L(-1). Alternative to analytical measurements, occurrence models can provide risk managers with a very interesting approach for estimating environmental concentrations from real or hypothetical scenarios. The most representative prioritization schemes used for issuing lists of concerning chemicals have also been examined and put in the context of existing environmental policies for protection strategies and regulations. Finally, new challenges in the field of risk-assessment have been outlined, including those posed by new materials (i.e., nanomaterials), transformation products, multi-chemical exposure, or extension of the risk assessment process to the whole ecosystem. Copyright © 2012 Elsevier B.V. All rights reserved.

Regulatory control of radiation sources in Slovakia

International Nuclear Information System (INIS)

Auxtova, L.

2001-01-01

In Slovakia, there are two regulatory authorities. Regulatory control of the utilization of nuclear energy, based on the Slovak National Council's law No. 130/1998 on the peaceful uses of nuclear energy, is exercised by the Nuclear Regulatory Authority of the Slovak Republic. The second regulatory authority - the Ministry of Health - is empowered by law No. 72/1994 on the protection of human health to license radiation sources and is responsible for radiation protection supervision (there are nearly 3000 establishments with sealed sources, radiation generators and unsealed sources in Slovakia). Pursuant to a new radiation protection regulation based on international standards, radiation sources are to be categorized in six classes according to the associated exposure and contamination hazards. A national strategy for improving the safety of radiation sources over their life-cycle and for the management of disused and orphan sources is being prepared for governmental approval. (author)

Balancing technical and regulatory concerns related to testing and control of performance assessment software

International Nuclear Information System (INIS)

Seitz, R.R.; Matthews, S.D.; Kostelnik, K.M.

1990-01-01

What activities are required to assure that a performance assessment (PA) computer code operates as it is intended? Answers to this question will vary depending on the individual's area of expertise. Different perspectives on testing and control of PA software are discussed based on interpretations of the testing and control process associated with the different involved parties. This discussion leads into the presentation of a general approach to software testing and control that address regulatory requirements. Finally, the need for balance between regulatory and scientific concerns is illustrated through lessons learned in previous implementations of software testing and control programs. Configuration control and software testing are required to provide assurance that a computer code performs as intended. Configuration control provides traceability and reproducibility of results produced with PA software and provides a system to assure that users have access to the current version of the software. Software testing is conducted to assure that the computer code has been written properly, solution techniques have been properly implemented, and the software is capable of representing the behavior of the specific system to be modeled. Comprehensive software testing includes: software analysis, verification testing, benchmark testing, and site-specific calibration/validation testing

Regulatory challenges for the licensing of future nuclear plants: A public interest perspective

International Nuclear Information System (INIS)

Lyman, Edwin S.

2001-01-01

Regulatory challenges concerned with licensing of advanced NPPs must ensure that economic imperatives do not have adverse impacts on safety, risk of radiological sabotage, waste management and disposal, non-proliferation, full opportunity for public participation. This presentation explains the mentioned issues using pebble bed reactor as an example

Experience Transformed into Nuclear Regulatory Improvements in Russia

International Nuclear Information System (INIS)

Sapozhnikov, A.

2016-01-01

The third International Conference on Effective Nuclear Regulatory Systems (Canada, 2013) identified the main action items that should be addressed, implemented and followed up. The key technical and organizational areas important to strengthening reactor and spent fuel safety have been determined as following: • Regulatory lessons learned and actions taken (since the accident at the Fukushima Daiichi NPP); • Waste management and spent fuel safety; • Emergency management; • Emerging programmes; • Human and organizational factors, safety and security culture. Over time many activities based on results of the IAEA Integrated Regulatory Review Service in the Russian Federation, 2019, and post-mission, 2013, have been implemented. At present there is progress for the national action plan on nuclear safety, preparation and conducting of long term spent fuel management, complementary reviews for nuclear facilities other than Nuclear Power Plants, emergency exercises with the regulatory body participation, improving communication, development of national regulations and improvement of regulatory system in the whole. The regulatory body ensures assistance in development of national regulatory infrastructure, safety culture to the countries planning to construct Russian design facilities (NPPs, RRs). The report outlines the results and future actions to improve nuclear regulation based on systematic approach to safety and particularly reflects the specificity of taking measures for the research reactors. (author)

Design Students Perspectives on Assessment Rubric in Studio-Based Learning

Science.gov (United States)

Eshun, Eric F.; Osei-Poku, Patrick

2013-01-01

This study examined students' perspectives on the use of assessment criteria and rubrics in graphic design studio at Kwame Nkrumah University of Science and Technology, Ghana. This assessment strategy was introduced with the desire to improve students' participation and involvement in studio-based learning programme. At the end of the semester, a…

Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective.

Science.gov (United States)

Salmikangas, Paula; Schuessler-Lenz, Martina; Ruiz, Sol; Celis, Patrick; Reischl, Ilona; Menezes-Ferreira, Margarida; Flory, Egbert; Renner, Matthias; Ferry, Nicolas

2015-01-01

With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk-based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs.

Architecture-based regulatory compliance argumentation

DEFF Research Database (Denmark)

Mihaylov, Boyan; Onea, Lucian; Hansen, Klaus Marius

2016-01-01

Standards and regulations are difficult to understand and map to software, which makes compliance with them challenging to argue for software products and development process. This is problematic since lack of compliance may lead to issues with security, safety, and even to economic sanctions....... An increasing number of applications (for example in healthcare) are expected to have to live up to regulatory requirements in the future, which will lead to more software development projects having to deal with such requirements. We present an approach that models regulations such that compliance arguments...... the approach on the migration of the telemedicine platform Net4Care to the cloud, where certain regulations (for example privacy) should be concerned. The approach has the potential to support simpler compliance argumentation with the eventual promise of safer and more secure applications....

A macromarketing perspective on food safety regulation

DEFF Research Database (Denmark)

Bech-Larsen, Tino; Aschemann-Witzel, Jessica

2012-01-01

of the major stakeholders in the Danish food marketing system. Adding to the literature on diffusion of regulatory initiatives, the analysis shows that the Danish ban on trans-fats had—and still has—an important impact on trans-fat regulation in other European and overseas countries. In the final section......This article discusses the implementation and diffusion of mandatory and voluntary food safety regulations from a marketing systems perspective, and specifically applies this framework to an analysis of the antecedents and implications of the Danish 2003 ban on trans-fatty acids (TFAs......). The analysis is based on reviews of published material and on interviews with food marketers, nutrition experts, and policy makers. It is established that the ban was implemented due to scientific proof of health risks associated with the intake of TFAs but also as a result of aligned interests and efforts...

Redesigning the regulatory framework for ambulatory care services in New York.

Science.gov (United States)

Chokshi, Dave A; Rugge, John; Shah, Nirav R

2014-12-01

Policy Points: The landscape of ambulatory care services in the United States is rapidly changing on account of payment reform, primary care transformation, and the rise of convenient care options such as retail clinics. New York State has undertaken a redesign of regulatory policy for ambulatory care rooted in the Triple Aim (better health, higher-quality care, lower costs)-with a particular emphasis on continuity of care for patients. Key tenets of the regulatory approach include defining and tracking the taxonomy of ambulatory care services as well as ensuring that convenient care options do not erode continuity of care for patients. While hospitals remain important centers of gravity in the health system, services are increasingly being delivered through ambulatory care. This shift to ambulatory care is giving rise to new delivery structures, such as retail clinics and urgent care centers, as well as reinventing existing ambulatory care capacity, as seen with the patient-centered medical home model and the movement toward team-based care. To protect the public's interests, oversight of ambulatory care services must keep pace with these rapid changes. With this purpose, in January 2013 the New York Public Health and Health Planning Council undertook a redesign of the regulatory framework for the state's ambulatory care services. This article describes the principles undergirding the framework as well as the regulatory recommendations themselves. We explored and analyzed the regulation of ambulatory care services in New York in accordance with the available gray and peer-reviewed literature and legislative documents. The deliberations of the Public Health and Health Planning Council informed our review. The vision of high-performing ambulatory care should be rooted in the Triple Aim (better health, higher-quality care, lower costs), with a particular emphasis on continuity of care for patients. There is a pressing need to better define the taxonomy of ambulatory

Safety Justification of Software Systems. Software Based Safety Systems. Regulatory Inspection Handbook

International Nuclear Information System (INIS)

Dahll, Gustav; Liwang, Bo; Wainwright, Norman

2006-01-01

The introduction of new software based technology in the safety systems in nuclear power plants also makes it necessary to develop new strategies for regulatory review and assessment of these new systems that is more focused on reviewing the processes at the different phases in design phases during the system life cycle. It is a general requirement that the licensee shall perform different kinds of reviews. From a regulatory point of view it is more cost effective to assess that the design activities at the suppliers and the review activities within the development project are performed with good quality. But the change from more technical reviews over to the development process oriented approach also cause problems. When reviewing development and quality aspects there are no 'hard facts' that can be judged against some specified criteria, the issues are more 'soft' and are more to build up structure of arguments and evidences that the requirements are met. The regulatory review strategy must therefore change to follow the development process over the whole life cycle from concept phase until installation and operation. Even if we know what factors that is of interest we need some guidance on how to interpret and judge the information.For that purpose SKl started research activities in this area at the end of the 1990s. In the first phase, in co-operation with Gustav Dahll at the Halden project, a life cycle model was selected. For the different phases a qualitative influence net was constructed of the type that is used in Bayesian Believe Network together with a discussion on different issues involved. In the second phase of the research work, in co-operation with Norman Wainwright, a former NII inspector, information from a selection of the most important sources as guidelines, IAEA and EC reports etc, was mapped into the influence net structure (the total list on used sources are in the report). The result is presented in the form of questions (Q) and a

Safety Justification of Software Systems. Software Based Safety Systems. Regulatory Inspection Handbook

Energy Technology Data Exchange (ETDEWEB)

Dahll, Gustav (OECD Halden Project, Halden (NO)); Liwaang, Bo (Swedish Nuclear Power Inspectorate, Stockholm (Sweden)); Wainwright, Norman (Wainwright Safety Advice (GB))

2006-07-01

The introduction of new software based technology in the safety systems in nuclear power plants also makes it necessary to develop new strategies for regulatory review and assessment of these new systems that is more focused on reviewing the processes at the different phases in design phases during the system life cycle. It is a general requirement that the licensee shall perform different kinds of reviews. From a regulatory point of view it is more cost effective to assess that the design activities at the suppliers and the review activities within the development project are performed with good quality. But the change from more technical reviews over to the development process oriented approach also cause problems. When reviewing development and quality aspects there are no 'hard facts' that can be judged against some specified criteria, the issues are more 'soft' and are more to build up structure of arguments and evidences that the requirements are met. The regulatory review strategy must therefore change to follow the development process over the whole life cycle from concept phase until installation and operation. Even if we know what factors that is of interest we need some guidance on how to interpret and judge the information.For that purpose SKl started research activities in this area at the end of the 1990s. In the first phase, in co-operation with Gustav Dahll at the Halden project, a life cycle model was selected. For the different phases a qualitative influence net was constructed of the type that is used in Bayesian Believe Network together with a discussion on different issues involved. In the second phase of the research work, in co-operation with Norman Wainwright, a former NII inspector, information from a selection of the most important sources as guidelines, IAEA and EC reports etc, was mapped into the influence net structure (the total list on used sources are in the report). The result is presented in the form of

Regulatory Issues Surrounding Merchant Interconnection

International Nuclear Information System (INIS)

Kuijlaars, Kees-Jan; Zwart, Gijsbert

2003-11-01

We discussed various issues concerning the regulatory perspective on private investment in interconnectors. One might claim that leaving investment in transmission infrastructure to competing market parties is more efficient than relying on regulated investment only (especially in the case of long (DC) lines connecting previously unconnected parts of the grids, so that externalities from e.g. loop flows do not play a significant role). We considered that some aspects of interconnection might reduce these market benefits. In particular, the large fixed costs of interconnection construction may lead to significant under investment (due to both first mover monopoly power and the fact that part of generation cost efficiencies realised by interconnection are not captured by the investor itself, and remain external to the investment decision). Second, merchant ownership restricts future opportunities for adaptation of regulation, as would be required e.g. for introduction of potentially more sophisticated methods of congestion management or market splitting. Some of the disadvantages of merchant investment may be mitigated however by a suitable regulatory framework, and we discussed some views in this direction. The issues we discussed are not intended to give a complete framework, and detailed regulation will certainly involve many more specific requirements. Areas we did not touch upon include e.g. the treatment of deep connection costs, rules for operation and maintenance of the line, and impact on availability of capacity on other interconnections

Regulatory Issues Surrounding Merchant Interconnection

Energy Technology Data Exchange (ETDEWEB)

Kuijlaars, Kees-Jan; Zwart, Gijsbert [Office for Energy Regulation (DTe), The Hague (Netherlands)

2003-11-01

We discussed various issues concerning the regulatory perspective on private investment in interconnectors. One might claim that leaving investment in transmission infrastructure to competing market parties is more efficient than relying on regulated investment only (especially in the case of long (DC) lines connecting previously unconnected parts of the grids, so that externalities from e.g. loop flows do not play a significant role). We considered that some aspects of interconnection might reduce these market benefits. In particular, the large fixed costs of interconnection construction may lead to significant under investment (due to both first mover monopoly power and the fact that part of generation cost efficiencies realised by interconnection are not captured by the investor itself, and remain external to the investment decision). Second, merchant ownership restricts future opportunities for adaptation of regulation, as would be required e.g. for introduction of potentially more sophisticated methods of congestion management or market splitting. Some of the disadvantages of merchant investment may be mitigated however by a suitable regulatory framework, and we discussed some views in this direction. The issues we discussed are not intended to give a complete framework, and detailed regulation will certainly involve many more specific requirements. Areas we did not touch upon include e.g. the treatment of deep connection costs, rules for operation and maintenance of the line, and impact on availability of capacity on other interconnections.

Continuing bonds in bereavement: an attachment theory based perspective.

Science.gov (United States)

Field, Nigel P; Gao, Beryl; Paderna, Lisa

2005-05-01

An attachment theory based perspective on the continuing bond to the deceased (CB) is proposed. The value of attachment theory in specifying the normative course of CB expression and in identifying adaptive versus maladaptive variants of CB expression based on their deviation from this normative course is outlined. The role of individual differences in attachment security on effective versus ineffective use of CB in coping with bereavement also is addressed. Finally, the moderating influence of type of loss (e.g., death of a spouse vs. child), culture, and religion on type of CB expression within an overarching attachment framework is discussed.

Regulatory perspectives on model validation in high-level radioactive waste management programs: A joint NRC/SKI white paper

Energy Technology Data Exchange (ETDEWEB)

Wingefors, S.; Andersson, J.; Norrby, S. [Swedish Nuclear Power lnspectorate, Stockholm (Sweden). Office of Nuclear Waste Safety; Eisenberg, N.A.; Lee, M.P.; Federline, M.V. [U.S. Nuclear Regulatory Commission, Washington, DC (United States). Office of Nuclear Material Safety and Safeguards; Sagar, B.; Wittmeyer, G.W. [Center for Nuclear Waste Regulatory Analyses, San Antonio, TX (United States)

1999-03-01

Validation (or confidence building) should be an important aspect of the regulatory uses of mathematical models in the safety assessments of geologic repositories for the disposal of spent nuclear fuel and other high-level radioactive wastes (HLW). A substantial body of literature exists indicating the manner in which scientific validation of models is usually pursued. Because models for a geologic repository performance assessment cannot be tested over the spatial scales of interest and long time periods for which the models will make estimates of performance, the usual avenue for model validation- that is, comparison of model estimates with actual data at the space-time scales of interest- is precluded. Further complicating the model validation process in HLW programs are the uncertainties inherent in describing the geologic complexities of potential disposal sites, and their interactions with the engineered system, with a limited set of generally imprecise data, making it difficult to discriminate between model discrepancy and inadequacy of input data. A successful strategy for model validation, therefore, should attempt to recognize these difficulties, address their resolution, and document the resolution in a careful manner. The end result of validation efforts should be a documented enhancement of confidence in the model to an extent that the model's results can aid in regulatory decision-making. The level of validation needed should be determined by the intended uses of these models, rather than by the ideal of validation of a scientific theory. This white Paper presents a model validation strategy that can be implemented in a regulatory environment. It was prepared jointly by staff members of the U.S. Nuclear Regulatory Commission and the Swedish Nuclear Power Inspectorate-SKI. This document should not be viewed as, and is not intended to be formal guidance or as a staff position on this matter. Rather, based on a review of the literature and previous

Regulatory perspectives on model validation in high-level radioactive waste management programs: A joint NRC/SKI white paper

International Nuclear Information System (INIS)

Wingefors, S.; Andersson, J.; Norrby, S.

1999-03-01

Validation (or confidence building) should be an important aspect of the regulatory uses of mathematical models in the safety assessments of geologic repositories for the disposal of spent nuclear fuel and other high-level radioactive wastes (HLW). A substantial body of literature exists indicating the manner in which scientific validation of models is usually pursued. Because models for a geologic repository performance assessment cannot be tested over the spatial scales of interest and long time periods for which the models will make estimates of performance, the usual avenue for model validation- that is, comparison of model estimates with actual data at the space-time scales of interest- is precluded. Further complicating the model validation process in HLW programs are the uncertainties inherent in describing the geologic complexities of potential disposal sites, and their interactions with the engineered system, with a limited set of generally imprecise data, making it difficult to discriminate between model discrepancy and inadequacy of input data. A successful strategy for model validation, therefore, should attempt to recognize these difficulties, address their resolution, and document the resolution in a careful manner. The end result of validation efforts should be a documented enhancement of confidence in the model to an extent that the model's results can aid in regulatory decision-making. The level of validation needed should be determined by the intended uses of these models, rather than by the ideal of validation of a scientific theory. This white Paper presents a model validation strategy that can be implemented in a regulatory environment. It was prepared jointly by staff members of the U.S. Nuclear Regulatory Commission and the Swedish Nuclear Power Inspectorate-SKI. This document should not be viewed as, and is not intended to be formal guidance or as a staff position on this matter. Rather, based on a review of the literature and previous

The transcriptional regulatory network of Mycobacterium tuberculosis.

Directory of Open Access Journals (Sweden)

Joaquín Sanz

Full Text Available Under the perspectives of network science and systems biology, the characterization of transcriptional regulatory (TR networks beyond the context of model organisms offers a versatile tool whose potential remains yet mainly unexplored. In this work, we present an updated version of the TR network of Mycobacterium tuberculosis (M.tb, which incorporates newly characterized transcriptional regulations coming from 31 recent, different experimental works available in the literature. As a result of the incorporation of these data, the new network doubles the size of previous data collections, incorporating more than a third of the entire genome of the bacterium. We also present an exhaustive topological analysis of the new assembled network, focusing on the statistical characterization of motifs significances and the comparison with other model organisms. The expanded M.tb transcriptional regulatory network, considering its volume and completeness, constitutes an important resource for diverse tasks such as dynamic modeling of gene expression and signaling processes, computational reliability determination or protein function prediction, being the latter of particular relevance, given that the function of only a small percent of the proteins of M.tb is known.

Task-based dermal exposure models for regulatory risk assessment.

Science.gov (United States)

Warren, Nicholas D; Marquart, Hans; Christopher, Yvette; Laitinen, Juha; VAN Hemmen, Joop J

2006-07-01

The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of new measurements of dermal exposure together with detailed contextual information. This article describes the development of a set of generic task-based models capable of predicting potential dermal exposure to both solids and liquids in a wide range of situations. To facilitate modelling of the wide variety of dermal exposure situations six separate models were made for groupings of exposure scenarios called Dermal Exposure Operation units (DEO units). These task-based groupings cluster exposure scenarios with regard to the expected routes of dermal exposure and the expected influence of exposure determinants. Within these groupings linear mixed effect models were used to estimate the influence of various exposure determinants and to estimate components of variance. The models predict median potential dermal exposure rates for the hands and the rest of the body from the values of relevant exposure determinants. These rates are expressed as mg or microl product per minute. Using these median potential dermal exposure rates and an accompanying geometric standard deviation allows a range of exposure percentiles to be calculated.

Layered signaling regulatory networks analysis of gene expression involved in malignant tumorigenesis of non-resolving ulcerative colitis via integration of cross-study microarray profiles.

Science.gov (United States)

Fan, Shengjun; Pan, Zhenyu; Geng, Qiang; Li, Xin; Wang, Yefan; An, Yu; Xu, Yan; Tie, Lu; Pan, Yan; Li, Xuejun

2013-01-01

Ulcerative colitis (UC) was the most frequently diagnosed inflammatory bowel disease (IBD) and closely linked to colorectal carcinogenesis. By far, the underlying mechanisms associated with the disease are still unclear. With the increasing accumulation of microarray gene expression profiles, it is profitable to gain a systematic perspective based on gene regulatory networks to better elucidate the roles of genes associated with disorders. However, a major challenge for microarray data analysis is the integration of multiple-studies generated by different groups. In this study, firstly, we modeled a signaling regulatory network associated with colorectal cancer (CRC) initiation via integration of cross-study microarray expression data sets using Empirical Bayes (EB) algorithm. Secondly, a manually curated human cancer signaling map was established via comprehensive retrieval of the publicly available repositories. Finally, the co-differently-expressed genes were manually curated to portray the layered signaling regulatory networks. Overall, the remodeled signaling regulatory networks were separated into four major layers including extracellular, membrane, cytoplasm and nucleus, which led to the identification of five core biological processes and four signaling pathways associated with colorectal carcinogenesis. As a result, our biological interpretation highlighted the importance of EGF/EGFR signaling pathway, EPO signaling pathway, T cell signal transduction and members of the BCR signaling pathway, which were responsible for the malignant transition of CRC from the benign UC to the aggressive one. The present study illustrated a standardized normalization approach for cross-study microarray expression data sets. Our model for signaling networks construction was based on the experimentally-supported interaction and microarray co-expression modeling. Pathway-based signaling regulatory networks analysis sketched a directive insight into colorectal carcinogenesis

Methodology for the Systematic Assessment of the Regulatory Competence Needs (SARCoN) for Regulatory Bodies of Nuclear Installations

International Nuclear Information System (INIS)

2015-03-01

A regulatory body’s competence is dependent, among other things, on the competence of its staff. A necessary, but not sufficient, condition for a regulatory body to be competent is that its staff can perform the tasks related to the functions of the regulatory body. In 2001, the IAEA published TECDOC 1254, Training the Staff of the Regulatory Body for Nuclear Facilities: A Competency Framework, which examines the manner in which the recognized regulatory functions of a nuclear regulatory body results in competence needs. Using the internationally recognized systematic approach to training, TECDOC 1254 provides a framework for regulatory bodies for managing training and developing, and maintaining the competence of its staff. It has been successfully used by many regulatory bodies all over the world, including States embarking on a nuclear power programme. The IAEA has also introduced a methodology and an assessment tool — Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) — which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2013, the IAEA published Safety Reports Series No. 79, Managing Regulatory Body Competence, which provides generic guidance based on IAEA safety requirements in the development of a competence management system within a regulatory body’s integrated management system. An appendix in the Safety Report deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an embarking State’s regulatory system. This publication provides guidance for the analysis of required and existing competences to identify those required by the regulatory body to perform its functions and therefore associated needs for acquiring competences. Hence, it is equally applicable to the needs of States embarking on nuclear power

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

[EU law on marketing authorization of medicines. History, current state of development and perspectives].

Science.gov (United States)

Nettesheim, Martin

2008-07-01

The article describes the development of EU policies and regulations on the marketing authorization of medicines. First, it describes the changing perspective of the EU towards the regulation of such authorizations. While its original focus was on the liberalization of national markets, it has today assumed overarching political responsibility for the development and marketing of medicines. Second, the article describes the current, rather fragmented regulatory system. Finally, political perspectives on the integration of markets for medicines are developed.

Construction and Operation of a Deep Geological Spent Fuel Repository in Sweden; Some Regulatory Aspects and Challenges

International Nuclear Information System (INIS)

Hedberg, Bengt

2014-01-01

The implementation of a deep geological spent fuel disposal concept in Sweden poses challenges on both implementer and regulator in many aspects. One such challenge is the application of the regulatory framework in a different situation compared to conventional process type nuclear facilities. A specific challenge in this regard is how to understand and address constraints from post-closure safety related to the construction and operation of the repository. The maybe most challenging aspect, however, is the unusually long time frame, i.e. many generations, for realization of the project. This paper addresses some of these challenges from a regulatory perspective. (authors)

Promoting Prosocial Behavior and Self-Regulatory Skills in Preschool Children through a Mindfulness-Based Kindness Curriculum

Science.gov (United States)

Flook, Lisa; Goldberg, Simon B.; Pinger, Laura; Davidson, Richard J.

2015-01-01

Self-regulatory abilities are robust predictors of important outcomes across the life span, yet they are rarely taught explicitly in school. Using a randomized controlled design, the present study investigated the effects of a 12-week mindfulness-based Kindness Curriculum (KC) delivered in a public school setting on executive function,…

Independent regulatory agencies and rules harmonization for the electricity sector and renewables in the Mediterranean region

International Nuclear Information System (INIS)

Cambini, Carlo; Franzi, Donata

2013-01-01

The paper analyses the existing regulatory framework for the electricity and renewables sectors, and the role of regulatory agencies in Northern Africa and Middle East countries, under the promotion by the European Union. Using data collected through an original survey directed at regulators, ministry departments and energy companies of the southern Mediterranean, the study is aimed at assessing the extent of agencies' independence looking at three main dimensions of independence: regulatory instruments available to regulators and decision making autonomy; regulators' organizational autonomy; and regulators accountability. Results show that those countries having established an independent regulator have a more credible regulatory framework than those countries in which such a body does not exist. In particular, the analysis shows that Turkey, Croatia and Jordan have defined a regulatory framework that limits administrative expropriation and, consequently, creates an environment more suitable for attracting investments in the electricity and renewables sector. On the institutional ground, this is probably related with the harmonization of regulatory standards promoted by the European Union through the neighboring policy, for the Jordan case, and the membership perspective, in the Turkish and Croatian cases. - Highlights: • We analyze the existing regulatory framework in Northern Africa and Middle East countries. • We construct an original dataset through a survey directed to national regulators. • The extent of agencies' independence has been assessed in different dimensions. • These dimensions are decision making autonomy; organizational autonomy; and accountability. • Few countries have defined a regulatory framework limiting administrative expropriation

Time under control: time perspective and desire for control in substance use.

Science.gov (United States)

Fieulaine, Nicolas; Martinez, Frederic

2010-08-01

To investigate the role of time perspective and desire for control in self-reported substance use and to test for a moderating effect of desire for control in the relation between time perspective and substance use. A random sample of 240 persons, aged 15 years and over, selected in various public spaces in an urban region in central France. Time perspective was measured using subscales of the Zimbardo Time Perspective Inventory (ZTPI, Zimbardo & Boyd, 1999), Desire for control was measured using a translated version of the Desire for Control Scale (DCS, Burger & Cooper, 1979), and substance use was self-reported. After controlling for age and gender, significant links were found between time perspective and substance use. Desire for control did not appear to be directly related to substance use. The interaction effect between TP and desire for control appeared to be related to substance use. There was evidence that the relation between TP and substance use is buffered by low desire for control. This study converges with previous studies demonstrating the relation between TP and substance use, but provides evidence of the moderating role played by desire for control. Desire for control thus appears as worthy of interest in the analysis of self-regulatory process, and further research on the links between TP and various aspects of control is required. In order to be more effective, the design of future studies and interventions based on time-related issues should consider how desire for control plays a part in establishing vulnerability profiles. Copyright 2010 Elsevier Ltd. All rights reserved.

Regulatory pathways for vaccines for developing countries.

Science.gov (United States)

Milstien, Julie; Belgharbi, Lahouari

2004-01-01

Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world. PMID:15042235

Strengthening Regulatory Effectiveness in India – Lessons Learnt from Fukushima Accident

International Nuclear Information System (INIS)

Solanki, R.

2016-01-01

Following the Fukushima Daiichi accident in Japan, one of the most important lessons learnt, among other things, was the issue of strengthening the effectiveness of the regulatory bodies. Immediately after the Fukushima accident, National level safety audits were conducted on all operating NPPs in India to review safety of NPPs in India. A national action plan has been prepared to implement the identified short term, midterm and long term measures. The assessment indicates that national response to the Fukushima Accident for safety assessment of NPPs and subsequent actions and initiatives taken for safety enhancement of the NPPs in India are in-line with the objectives of the IAEA Action plan. This paper highlights the actions taken by India in the light of Fukushima Daiichi accident in order to strengthen the regulatory effectiveness through improvements in the existing core processes, challenges faced, Insights gained from the recent initiatives on safety performance indicators and assessment of safety culture, relevant observations of IRRS mission report and Indian perspectives on the further cooperation among the member states for enhancing the regulatory effectiveness for nuclear oversight of regulated organizations. (author)

[Research on problem of exogenous pollution of Chinese medicine resources from perspective of circular economy].

Science.gov (United States)

Yang, Yi; Tian, Kan; Tian, Hong

2016-08-01

Based on the in-depth analysis of the current situation of the exogenous pollution of Chinese medicine resources, this research mainly discusses the intrinsic link and practical significance between the development of circular economy in Chinese medicine resources and the control of the problem of the exogenous pollution from the perspective of circular economy, and proposes some suggestions to develop the recycling economy of Chinese medicine resources from the establishment of legal system, mechanism of development, production norms, industry standards and regulatory system of the recycling of Chinese medicine resources. Copyright© by the Chinese Pharmaceutical Association.

Addressing communications between Regulatory Body and TSO: perceptions and problems

International Nuclear Information System (INIS)

Salati de Almeida, I.P.

2007-01-01

The use of TSO assistance by the Regulatory Bodies is a way of facing the complexity of the technology and issues to be dealt with in the licensing and controlling process in the nuclear area. Although both TSO and Regulatory Body are well prepared and adjusted, the nature and environment of TSO work is rather different from the regulators. Some of the TSO members act as a consultant, giving expert advice to the regulators in a specific subject, some are in charge of inspections and audits, others do the job together with the regulators. The way that a TSO member perceives the work to be done, however, often creates different perspectives for questions related to the licensing and controlling process. These perceptions are usually a source of problems between the two partners, regulators and TSO members. In this paper some of this kind of problems are raised and suggestions of how to deal with them are proposed for discussion. (author)

Event-based cluster synchronization of coupled genetic regulatory networks

Science.gov (United States)

Yue, Dandan; Guan, Zhi-Hong; Li, Tao; Liao, Rui-Quan; Liu, Feng; Lai, Qiang

2017-09-01

In this paper, the cluster synchronization of coupled genetic regulatory networks with a directed topology is studied by using the event-based strategy and pinning control. An event-triggered condition with a threshold consisting of the neighbors' discrete states at their own event time instants and a state-independent exponential decay function is proposed. The intra-cluster states information and extra-cluster states information are involved in the threshold in different ways. By using the Lyapunov function approach and the theories of matrices and inequalities, we establish the cluster synchronization criterion. It is shown that both the avoidance of continuous transmission of information and the exclusion of the Zeno behavior are ensured under the presented triggering condition. Explicit conditions on the parameters in the threshold are obtained for synchronization. The stability criterion of a single GRN is also given under the reduced triggering condition. Numerical examples are provided to validate the theoretical results.

Palliative home-based technology from a practitioner's perspective: benefits and disadvantages

OpenAIRE

Johnston, Bridget

2014-01-01

Bridget M Johnston Sue Ryder Care Centre for the Study of Supportive, Palliative, and End of Life Care, School of Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK Abstract: This critical review paper explores the concept of palliative home-based technology from a practitioner's perspective. The aim of the critical review was to scope information available from published and unpublished research on the current state of palliative home-based tec...

Cloud based spectrum manager for future wireless regulatory environment

CSIR Research Space (South Africa)

Masonta, MT

2015-12-01

Full Text Available The regulatory environment in radio frequency spectrum management lags the advancement of wireless technologies, especially in the area of cognitive radio and dynamic spectrum access. In this paper we argue that the solution towards spectrum Pareto...

Relations between chronic regulatory focus and future time perspective: Results of a cross-lagged structural equation model

NARCIS (Netherlands)

Zacher, H.; Lange, A.H. de

2011-01-01

Future time perspective - the way individuals perceive their remaining time in life - importantly influences socio-emotional goals and motivational outcomes. Recently, researchers have called for studies that investigate relationships between personality and future time perspective. Using a

Relations between chronic regulatory focus and future time perspective : Results of a cross-lagged structural equation model

NARCIS (Netherlands)

Zacher, Hannes; de Lange, Annet H.

Future time perspective - the way individuals perceive their remaining time in life - importantly influences socio-emotional goals and motivational outcomes. Recently, researchers have called for studies that investigate relationships between personality and future time perspective. Using a

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

Directory of Open Access Journals (Sweden)

Dipak Dilip Gadade

2016-12-01

Full Text Available Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development.

Science.gov (United States)

Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

2016-12-01

Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

A New Pose Estimation Algorithm Using a Perspective-Ray-Based Scaled Orthographic Projection with Iteration.

Directory of Open Access Journals (Sweden)

Pengfei Sun

Full Text Available Pose estimation aims at measuring the position and orientation of a calibrated camera using known image features. The pinhole model is the dominant camera model in this field. However, the imaging precision of this model is not accurate enough for an advanced pose estimation algorithm. In this paper, a new camera model, called incident ray tracking model, is introduced. More importantly, an advanced pose estimation algorithm based on the perspective ray in the new camera model, is proposed. The perspective ray, determined by two positioning points, is an abstract mathematical equivalent of the incident ray. In the proposed pose estimation algorithm, called perspective-ray-based scaled orthographic projection with iteration (PRSOI, an approximate ray-based projection is calculated by a linear system and refined by iteration. Experiments on the PRSOI have been conducted, and the results demonstrate that it is of high accuracy in the six degrees of freedom (DOF motion. And it outperforms three other state-of-the-art algorithms in terms of accuracy during the contrast experiment.

Benefits and challenges of international clinical education from a US-based physiotherapist faculty perspective.

Science.gov (United States)

Pechak, Celia; Black, Jill D

2013-12-01

The influence of internationalization on physiotherapist education in at least North American-based programmes has become more apparent. Faculty and students have been involved in various international activities. One category of activities includes international clinical education (ICE), where students earn clinical education credit for their learning activities at international sites. Although this educational strategy appears to be increasingly used in at least the United States and Canada, the related literature is limited in scope. The purpose of this portion of the present study was to investigate the benefits and challenges of ICE for US-based students, US-based physiotherapy programmes and international partners from the perspective of US-based faculty sending students for clinical education internationally. Content analysis was used for this qualitative study. Fifteen US-based faculty members who had experience in sending physiotherapist students for ICE were recruited. The primary researcher conducted semi-structured phone interviews, averaging approximately 60 minutes in length. The primary and secondary researchers completed data analysis using NVivo 8 software (QSR International Inc., Cambridge, MA). Benefits of ICE to the students included exposure to alternate health systems, broadening of student perspectives and clinical competence. Challenges consisted of funding and possible language barrier. Increased visibility, expanded global perspective and faculty collaborations were benefits to the programme. Ensuring a quality learning experience was the greatest programme challenge. Benefits to the international site included education and faculty collaborations/exchanges; challenges were language, student clinical preparation and unfamiliarity with the student evaluation tool. Because the sample was limited to 15 US-based faculty members, the results may not be relevant to all programmes inside or outside of the United States. Additionally, the study

Regulatory perspective on digital instrumentation and control systems for future advanced nuclear power plants

International Nuclear Information System (INIS)

Chiramal, M.

1993-01-01

This paper deals with the question of using digital technology in instrumentation and control systems for modern nuclear power reactors. The general opinion in the industry and among NRC staff is that such technology provides the opportunity for enhanced safety and reliable reactor operations. The major concern is the safe application of this technology so as to avoid common mode or common cause failures in systems. There are great differences between digital and analog system components. SECY-91-292 identifies some general regulatory concerns with regard to digital systems. There is clearly a lack of adequate regulatory direction on the application of digital equipment at this time, but the issue is being addressed by the industry, outside experts, and NRC staff. NRC staff presents a position on the issue of defense-in-depth and diversity with regard to insuring plant safety. Independent manual controls and readouts must be available to allow safe shutdown and monitoring of the plant in the event of safety system failures

Risk perception, safety goals and regulatory decision-making

International Nuclear Information System (INIS)

Hoegberg, Lars

1998-01-01

Deciding on 'how safe is safe enough?' includes value judgements with implications of an ethical and political nature. As regulators are accountable to governments, parliaments and the general public, regulatory decision-making should be characterized by transparency with respect to how such value judgements are reflected in risk assessments and regulatory decisions. Some approaches in this respect are discussed in the paper, based on more than fifteen years of experience in nuclear regulatory decision-making. Issues discussed include: (1) risk profiles and safety goals associated with severe reactor accidents--individual health risks, societal risks and risk of losing investments; (2) risk profile-based licensing of the Swedish SFR final disposal facility for low and intermediate level radioactive waste

Impact of hepatitis C virus polymorphisms on direct-acting antiviral treatment efficacy: Regulatory analyses and perspectives.

Science.gov (United States)

Harrington, Patrick R; Komatsu, Takashi E; Deming, Damon J; Donaldson, Eric F; O'Rear, Julian J; Naeger, Lisa K

2018-06-01

Several highly effective, interferon-free, direct-acting antiviral (DAA)-based regimens are available for the treatment of chronic hepatitis C virus (HCV) infection. Despite impressive efficacy overall, a small proportion of patients in registrational trials experienced treatment failure, which in some cases was associated with the detection of HCV resistance-associated substitutions (RASs) at baseline. In this article, we describe methods and key findings from independent regulatory analyses investigating the impact of baseline nonstructural (NS) 3 Q80K and NS5A RASs on the efficacy of current United States Food and Drug Administration (FDA)-approved regimens for patients with HCV genotype (GT) 1 or GT3 infection. These analyses focused on clinical trials that included patients who were previously naïve to the DAA class(es) in their investigational regimen and characterized the impact of baseline RASs that were enriched in the viral population as natural or transmitted polymorphisms (i.e., not drug-selected RASs). We used a consistent approach to optimize comparability of results across different DAA regimens and patient populations, including the use of a 15% sensitivity cutoff for next-generation sequencing results and standardized lists of NS5A RASs. These analyses confirmed that detection of NS3 Q80K or NS5A baseline RASs was associated with reduced treatment efficacy for multiple DAA regimens, but their impact was often minimized with the use of an intensified treatment regimen, such as a longer treatment duration and/or addition of ribavirin. We discuss the drug resistance-related considerations that contributed to pretreatment resistance testing and treatment recommendations in drug labeling for FDA-approved DAA regimens. Independent regulatory analyses confirmed that baseline HCV RASs can reduce the efficacy of certain DAA-based regimens in selected patient groups. However, highly effective treatment options are available for patients with or without

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...

A global regulatory science agenda for vaccines.

Science.gov (United States)

Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

2013-04-18

The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

International conference on strengthening of nuclear safety in Eastern Europe. Armenian Nuclear Regulatory Authority

International Nuclear Information System (INIS)

Nersesyan, V.

1999-01-01

The status of the Armenian Nuclear Regulatory Authority (ANRA) are described in detail with its main task and responsibilities concerning regulations and surveillance of nuclear and radiation safety. The following issues are presented: nuclear legislation; inspection activities; licensing of significant safety related modifications and modernization of NPPs; incidents at NPPs; personnel training; emergency planning; surveillance of nuclear materials; radioactive waste management; and plan of the ANRA perspective development

Technical, environmental and regulatory aspects of waste management and their reflection in the IAEA programme

International Nuclear Information System (INIS)

Richter, D.K.

1982-01-01

Within the IAEA training course on waste management this paper is intended to overview technological, radiological, encironmental, regulatory and institutional aspects of importance in establishing a waste management policy for nuclear power programmes; the objectives and results of IAEA activities in this field; and some current issues from a national and international perspective with special consideration on the needs of countries embarking on nuclear power. (orig./RW)

Sexual dimorphism of stress response and immune/ inflammatory reaction: the corticotropin releasing hormone perspective

Directory of Open Access Journals (Sweden)

Nicholas V. Vamvakopoulos

1995-01-01

Full Text Available This review higlghts key aspects of corticotropin releasing hormone (CRH biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h CRH gene: (1 a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic glucocorticoid administration in clinical practice and (2 a heuristic diagram to illustrate the proposed modulation of the stress response and immune/ inflammatory reaction by steroid hormones, from the perspective of the CRH system.

Targeting regulatory T cells in cancer.

LENUS (Irish Health Repository)

Byrne, William L

2012-01-31

Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

Risk Analysis as Regulatory Science: Toward The Establishment of Standards.

Science.gov (United States)

Murakami, Michio

2016-09-01

Understanding how to establish standards is essential for risk communication and also provides perspectives for further study. In this paper, the concept of risk analysis as regulatory science for the establishment of standards is demonstrated through examples of standards for evacuation and provisional regulation values in foods and drinking water. Moreover, academic needs for further studies related to standards are extracted. The concepts of the traditional 'Standard I', which has a paternalistic orientation, and 'Standard II', established through stakeholder consensus, are then systemized by introducing the current status of the new standards-related movement that developed after the Fukushima nuclear power plant accident, and the perspectives of the standards are discussed. Preparation of standards on the basis of stakeholder consensus through intensive risk dialogue before a potential nuclear power plant accident is suggested to be a promising approach to ensure a safe society and enhance subjective well-being. © The Author 2016. Published by Oxford University Press.

U.S. Nuclear Regulatory Commission bases for control of solid materials

International Nuclear Information System (INIS)

Meck, R.A.; Cardille, F.P.; Feldman, C.; Gnugnoli, G.N.; Huffert, A.M.; Klementowicz, S.P.

2002-01-01

The U.S. Nuclear Regulatory Commission (NRC) is considering whether to proceed with rulemaking on the control of solid materials with very low levels of associated radioactivity. The current implementation of clearance by NRC licensees is the context for the decision. Inputs to the decision include information gathering efforts of the Commission in the areas of public workshops, dose assessments and inventories, the recommendations of the National Academies' National Research Council (NAs) on regulatory alternatives, and participation in international efforts by the International Atomic Energy Agency (IAEA). (author)

Initial threat assessment. Radiological risks associated with SevRAO facilities falling within the regulatory supervision responsibilities of FMBA[Russian Federation

Energy Technology Data Exchange (ETDEWEB)

Ilin, Leonid; Kochetkov, Oleg; Simakov, Anatoly; Shandala, Natalya; Savkin, Mikhail; Sneve, Malgorzata K.; Boerretzen, Peer; Jaworska, Alicja; Smith, Graham; Barraclough, Ian; Kruse, Phil

2005-07-01

The purpose of this initial threat assessment is to obtain a view, from the regulatory perspective of FMBA, of the most important issues which require supervision and regulatory development, regarding work which has to be carried out at the Andreeva Bay and Grcmikha. The main radiological threats have been identified and actions to reduce the threats have been proposed. Situations where regulations and procedures for workers on-site need to be developed have been identified. This will be a basis for further development of Russian regulation and procedures. (Author)

Safety Management in Non-Nuclear Contexts. Examples from Swedish Railway Regulatory and Company Perspectives

Energy Technology Data Exchange (ETDEWEB)

Salo, Ilkka; Svensson, Ola (Risk Analysis, Social and Decision Research Unit, Dept. of Psychology, Stockholm Univ., Stockholm (Sweden))

2005-06-15

studied organizations respectively. These three chapters give a detailed account of safety management from a system perspective and applications in the organizations studied, and could be read independently of each other. In the fourth chapter the report concludes with summarizing safety management in SRA and SJ by mapping the results on important concepts from the system theoretical framework, and general themes for safety management applicable across contexts are suggested. The qualitative descriptions of the organizations generated a detailed account on how safety is managed in Swedish railway operations. Examples of safety management in practice are given both from the regulatory point of view and from an organizational position close to the actual operations. The Swedish railway operations are strictly regulated and the safety goals are identifiable along the legislative documentation from the government's goals for safe operations expressed in the railway legislation, through SRA's regulations, to SJ's internal regulations. There is a high degree of coherence between SJ's and SRA's formulations of safety management and safe operations in general. Both organizations have their origin in the former national railway company, which may is partly reflected in the high degree of correspondence between the approaches towards safety. Both organizations make use of a system approach to their operations, which are clearly reflected in the highly structured organizations, with core objectives, operational responsibilities, procedures, and information feedback prerequisites sufficiently mapped on the organizational units. The report gives both detailed accounts and summaries of a number of central themes for safety management derived from the system theoretical framework, and also themes relevant for safety management in general. For example: the organizations definitions of safety management, descriptions of the organizational structures, recent

Exploring the miRNA regulatory network using evolutionary correlations.

Directory of Open Access Journals (Sweden)

Benedikt Obermayer

2014-10-01

Full Text Available Post-transcriptional regulation by miRNAs is a widespread and highly conserved phenomenon in metazoans, with several hundreds to thousands of conserved binding sites for each miRNA, and up to two thirds of all genes under miRNA regulation. At the same time, the effect of miRNA regulation on mRNA and protein levels is usually quite modest and associated phenotypes are often weak or subtle. This has given rise to the notion that the highly interconnected miRNA regulatory network exerts its function less through any individual link and more via collective effects that lead to a functional interdependence of network links. We present a Bayesian framework to quantify conservation of miRNA target sites using vertebrate whole-genome alignments. The increased statistical power of our phylogenetic model allows detection of evolutionary correlation in the conservation patterns of site pairs. Such correlations could result from collective functions in the regulatory network. For instance, co-conservation of target site pairs supports a selective benefit of combinatorial regulation by multiple miRNAs. We find that some miRNA families are under pronounced co-targeting constraints, indicating a high connectivity in the regulatory network, while others appear to function in a more isolated way. By analyzing coordinated targeting of different curated gene sets, we observe distinct evolutionary signatures for protein complexes and signaling pathways that could reflect differences in control strategies. Our method is easily scalable to analyze upcoming larger data sets, and readily adaptable to detect high-level selective constraints between other genomic loci. We thus provide a proof-of-principle method to understand regulatory networks from an evolutionary perspective.

Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective

Science.gov (United States)

Martínez-Chavarría, Luary C.; Vadyvaloo, Viveka

2015-01-01

Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens. PMID:26441890

Prediction of Marital Satisfaction based on Coping Skills and Time Perspective

Directory of Open Access Journals (Sweden)

سپیده حق شناس

2018-03-01

Full Text Available The purpose of this study was to predict marital satisfaction based on coping skills and time perspective. The research method was correlation and the statistical population composed of couples living in the 2nddistrict of Tehran. By convenience sampling method, 250 individuals were selected and were asked to complete the ENRICH Marital Satisfaction Scale, the Lazarus & Folkman’s Coping Styles Questionnaire and the Zimbardo’s Time Perspective Inventory. The results showed that 12.5% of variance of marital satisfa-ction can be explained by the time perspective and the use of coping strategies in couples. The findings also indicated that there was a negative association between emotional coping strategies and marital satisfaction; while, there was no significant relationship between problem-oriented strategies and marital satisfaction. In examining the relationship between views of time and marital satisfaction, the results indicated that there was a negative significant relationship between marital satisfaction with past negative view of time, present hedonistic and believing in present fatalistic. According to the results of t-test for gender differences, there was no significant difference between men and women in marital satisfaction, using coping strategies and time views.

Promoting Issues-based STSE Perspectives in Science Teacher Education: Problems of Identity and Ideology

Science.gov (United States)

Pedretti, Erminia G.; Bencze, Larry; Hewitt, Jim; Romkey, Lisa; Jivraj, Ashifa

2008-09-01

Although science, technology, society and environment (STSE) education has gained considerable force in the past few years, it has made fewer strides in practice. We suggest that science teacher identity plays a role in the adoption of STSE perspectives. Simply put, issues-based STSE education challenges traditional images of a science teacher and science instructional ideologies. In this paper, we briefly describe the development of a multimedia documentary depicting issues-based STSE education in a teacher’s class and its subsequent implementation with 64 secondary student-teachers at a large Canadian university. Specifically, we set out to explore: (1) science teacher candidates’ responses to a case of issues-based STSE teaching, and (2) how science teacher identity intersects with the adoption of STSE perspectives. Findings reveal that although teacher candidates expressed confidence and motivation regarding teaching STSE, they also indicated decreased likelihood to teach these perspectives in their early years of teaching. Particular tensions or problems of practice consistently emerged that helped explain this paradox including issues related to: control and autonomy; support and belonging; expertise and negotiating curriculum; politicization and action; and biases and ideological bents. We conclude our paper with a discussion regarding the lessons learned about STSE education, teacher identity and the role of multimedia case methods.

A regulatory perspective on the radiological impact of NORM industries: the case of the Spanish phosphate industry

International Nuclear Information System (INIS)

Garcia-Talavera, M.; Matarranz, J.L.M.; Salas, R.; Ramos, L.

2011-01-01

Radioactive and chemical risks coexist in NORM industries although they are usually addressed separately by regulations. The European Union (EU) has developed extensive legislation concerning both matters, which has been diversely reflected in national policies. We consider the case of the Spanish phosphate industry and analyse to which extent regulatory mandates have reduced the historical and ongoing radiological impact on the environment of phosphate facilities. Although no specific radiological constraints on effluent monitoring and release or on waste disposal have yet been imposed on NORM industries in Spain, other environmental regulations have achieved a substantial reduction on the phosphate industry impact. Nevertheless, a more efficient control could be established by eliminating the current conceptual and practical separation of chemical and radioactive risks in NORM industries. We highlight research needs to accomplish so and propose shorter-term measures that require active cooperation among the regulatory bodies involved. - Research highlights: → The radiological impact of the Spanish phosphate industry has substantially decreased as a side result of environmental regulations on chemical pollution.→ A more efficient control of NORM industries could be established by eliminating the current conceptual and practical separation of chemical and radioactive risks.→ Further research is needed on how interactions between radiation and chemicals might affect regulatory limits and on a systematic way to input stakeholder preferences in MCDA.→ On shorter-term, administrative measures that require active cooperation among the regulatory bodies involved can be taken.

Action Plan on Base Erosion and Profit Shifting: An Indian Perspective.

OpenAIRE

Rao, R. Kavita; Sengupta, D.P.

2014-01-01

The discussion in this paper highlights some evidence to support the notion that there is base erosion in India. On the specific action points listed in the OECD's Action Plan, a perspective from India's stand point has been presented along with a brief discussion on the steps needed to prepare for complying with likely proposed measures.

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

Science.gov (United States)

Krackhardt, Angela M; Anliker, Brigitte; Hildebrandt, Martin; Bachmann, Michael; Eichmüller, Stefan B; Nettelbeck, Dirk M; Renner, Matthias; Uharek, Lutz; Willimsky, Gerald; Schmitt, Michael; Wels, Winfried S; Schüssler-Lenz, Martina

2018-04-01

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

Determining e-learning success factor in higher education based on user perspective using Fuzzy AHP

Directory of Open Access Journals (Sweden)

Anggrainingsih Rini

2018-01-01

Full Text Available Recently almost all universities in the world have implemented E-learning to support their academic system. Previous studies have been conducted to determine CSF using Analytic Hierarchy Process (AHP method. However, AHP method cannot handle the uncertainty and vagueness of the human’s opinion, so then it causes less appropriate decision. Some researcher has proposed to use fuzzy sets theory with AHP to increase the ability of AHP to deal problem regarding the uncertainty/fuzziness. This study aims to determine ranks of priorities of the multiple factors which influence the E-learning success using FAHP method. The respondents consist of ten e-learning’s experts, 305 lecturers, and 4195 students at Sebelas Maret University. The result describes similar success factors ranking between both experienced and non-experienced user (lecturer and student. Then, the result shows that there are five most influencial success factors of e-learning at Sebelas Maret University based on the lectures perspective Financial Policy, Regulatory Policy, Course quality, Relevant Content and Technical Support. On the other hand, according to the student's point of view five most e-learning, critical success factors are Quality of Course, Relevant of Content, Completeness of Content, Attitudes toward Student, and Flexibility in taking Course. Therefore, this finding can be used by E-learning management of Sebelas Maret University to deteremine a strategy to to achieve successful implementation of e-learning at Sebelas Maret University with consider these factors.

Peeling the Onion of Auditory Processing Disorder: A Language/Curricular-Based Perspective

Science.gov (United States)

Wallach, Geraldine P.

2011-01-01

Purpose: This article addresses auditory processing disorder (APD) from a language-based perspective. The author asks speech-language pathologists to evaluate the functionality (or not) of APD as a diagnostic category for children and adolescents with language-learning and academic difficulties. Suggestions are offered from a…

Future perspectives of resin-based dental materials.

Science.gov (United States)

Jandt, Klaus D; Sigusch, Bernd W

2009-08-01

This concise review and outlook paper gives a view of selected potential future developments in the area of resin-based biomaterials with an emphasis on dental composites. A selection of key publications (1 book, 35 scientific original publications and 1 website source) covering the areas nanotechnology, antimicrobial materials, stimuli responsive materials, self-repairing materials and materials for tissue engineering with direct or indirect relations and/or implications to resin-based dental materials is critically reviewed and discussed. Connections between these fields and their potential for resin-based dental materials are highlighted and put in perspective. The need to improve shrinkage properties and wear resistance is obvious for dental composites, and a vast number of attempts have been made to accomplish these aims. Future resin-based materials may be further improved in this respect if, for example nanotechnology is applied. Dental composites may, however, reach a completely new quality by utilizing new trends from materials science, such as introducing nanostructures, antimicrobial properties, stimuli responsive capabilities, the ability to promote tissue regeneration or repair of dental tissues if the composites were able to repair themselves. This paper shows selected potential future developments in the area of resin-based dental materials, gives basic and industrial researchers in dental materials science, and dental practitioners a glance into the potential future of these materials, and should stimulate discussion about needs and future developments in the area.

Safety culture in regulatory expert organization : analysis result of survey for KINS employees

International Nuclear Information System (INIS)

Choi, G. S.; Choi, Y. S.

2003-01-01

Much has been discussed on safety culture of operating organizations, however, little has been done on that of regulatory organization. Current issues and activities related to nuclear safety culture at IAEA, OECD/NEA, etc. were investigated and relevant literatures were reviewed. Elements essential for safety culture of regulatory organization were proposed and survey questionnaire for employees of regulatory expert organization, KINS, was developed based on the elements proposed. The survey result was presented and its implications were discussed. Based on the result, elements of safety culture in regulatory organization were proposed. The result of this survey can be used in developing safety culture model of regulatory organization, measurement method and also promotion of safety culture in regulatory organization

A perspective on risk informed regulation and the maintenance rule

International Nuclear Information System (INIS)

In, Young H.

2006-01-01

Establishing a new regulatory framework for the future can be a complex and difficult task where the current regulatory framework and the past regulatory history must be reconciled. The nuclear regulatory framework will evolve over time, and it is in our best interest to make the right changes, whether the change is incremental or innovative. Basically, the risk-informed regulation (RIR) is an innovative change that must be made incrementally. Therefore, it is important that the changes to the framework are carefully evaluated and studied before the actual implementation. Otherwise, we may see unnecessary patches along the way that can be damaging to the regulatory integrity and the public confidence in the regulation. Even though, the United States has led the risk-informed regulation implementation during last decade, there were some instances where the well intended changes were not well planned and coordinated, resulting in loss of valuable time and resources that led to confusions among involved parties. The risk-informed regulation is an emerging trend worldwide, and Korea is one of the few that are ahead of the pack in embracing this innovative change in the regulation. To better understand and plan for RIR, we need to study both the well-established regulatory framework and the emerging regulatory framework. In addition, the recent trends in other regulatory framework similar to its own should be carefully studied. The reasons for any stagnations or barriers in other regulatory frameworks should be carefully noted and see if we share similar problems so that we can formulate better solutions. Blindly following others regulatory changes is not recommended, since our regulatory environment is unique in itself. We should take their inputs and lessons learned, but adopt them specifically to our industry needs and regulatory environment. This paper will attempt to provide a perspective on the risk-informing process of a nuclear plant by a brief look into two key

Thorium-based nuclear fuel: current status and perspectives

International Nuclear Information System (INIS)

1987-03-01

Until the present time considerable efforts have already been made in the area of fabrication, utilization and reprocessing of Th-based fuels for different types of reactors, namely: by FRG and USA - for HTRs; FRG and Brazil, Italy - for LWRs; India - for HWRs and FBRs. Basic research of thorium fuels and thorium fuel cycles are also being undertaken by Australia, Canada, China, France, FRG, Romania, USSR and other countries. Main emphasis has been given to the utilization of thorium fuels in once-through nuclear fuel cycles, but in some projects closed thorium-uranium or thorium-plutonium fuel cycles are also considered. The purpose of the Technical Committee on the Utilization of Thorium-Based Nuclear Fuel: Current Status and Perspective was to review the world thorium resources, incentives for further exploration, obtained experience in the utilization of Th-based fuels in different types of reactors, basic research, fabrication and reprocessing of Th-based fuels. As a result of the panel discussion the recommendations on future Agency activities and list of major worldwide activities in the area of Th-based fuel were developed. A separate abstract was prepared for each of the 9 papers in this proceedings series

Survey of past base isolation applications in nuclear power plants and challenges to industry/regulatory acceptance

International Nuclear Information System (INIS)

Malushte, S.R.; Whittaker, A.S.

2005-01-01

Seismic base isolation provides many benefits that can facilitate the standardization of future nuclear power plant structures and equipment while reducing the initial/life-cycle cost and construction schedule. This paper presents a survey of past seismic base isolation applications and studies related to nuclear applications and provides a discussion of the challenges that need to be overcome to gain industry and regulatory acceptance for deployment in future US nuclear power plants. Issues related to design, codes/standards/regulations, procurement, and construction, have been identified. (authors)

Does GLP enhance the quality of toxicological evidence for regulatory decisions?

Science.gov (United States)

Borgert, Christopher J.; Becker, Richard A.; Carlton, Betsy D.; Hanson, Mark; Kwiatkowski, Patricia L.; Sue Marty, Mary; McCarty, Lynn S.; Quill, Terry F.; Solomon, Keith; Van Der Kraak, Glen; Witorsch, Raphael J.; Don Yi, Kun

2016-01-01

There is debate over whether the requirements of GLP are appropriate standards for evaluating the quality of toxicological data used to formulate regulations. A group promoting the importance of non-monotonic dose responses for endocrine disruptors contend that scoring systems giving primacy to GLP are biased against non-GLP studies from the literature and are merely record-keeping exercises to prevent fraudulent reporting of data from non-published guideline toxicology studies. They argue that guideline studies often employ insensitive species and outdated methods, and ignore the perspectives of subject-matter experts in endocrine disruption, who should be the sole arbiters of data quality. We believe regulatory agencies should use both non-GLP and GLP studies, that GLP requirements assure fundamental tenets of study integrity not typically addressed by journal peer-review, and that use of standardized test guidelines and GLP promotes consistency, reliability, comparability, and harmonization of various types of studies used by regulatory agencies worldwide. This debate suffers two impediments to progress: a conflation of different phases of study interpretation and levels of data validity, and a misleading characterization of many essential components of GLP and regulatory toxicology. Herein we provide clarifications critical for removing those impediments. PMID:27208076

Implementation of in vitro replacement technologies in regulatory drug testing - An innovation systems perspective

NARCIS (Netherlands)

Kooijman, M.; Van Meer, P.J.K.; Moors, E.H.M.; Hekkert, M.P.; Schellekens, H.

2011-01-01

The replacement of in vivo methods by in vitro methods in regulatory drug testing is rare. The aim of this research is to identify barriers and drivers of the replacement of in vivo methods by in vitro methods in Europe. We studied two cases. The first case is the Draize eye test. Since 2009, the in

The planning, construction, and operation of a radioactive waste storage facility for an Australian state radiation regulatory authority

Energy Technology Data Exchange (ETDEWEB)

Wallace, J.D.; Kleinschmidt, R.; Veevers, P. [Radiation Health, Queensland (Australia)

1995-12-31

Radiation regulatory authorities have a responsibility for the management of radioactive waste. This, more often than not, includes the collection and safe storage of radioactive sources in disused radiation devices and devices seized by the regulatory authority following an accident, abandonment or unauthorised use. The public aversion to all things radioactive, regardless of the safety controls, together with the Not In My Back Yard (NIMBY) syndrome combine to make the establishment of a radioactive materials store a near impossible task, despite the fact that such a facility is a fundamental tool for regulatory authorities to provide for the radiation safety of the public. In Queensland the successful completion and operational use of such a storage facility has taken a total of 8 years of concerted effort by the staff of the regulatory authority, the expenditure of over $2 million (AUS) not including regulatory staff costs and the cost of construction of an earlier separate facility. This paper is a summary of the major developments in the planning, construction and eventual operation of the facility including technical and administrative details, together with the lessons learned from the perspective of the overall project.

Study on the establishment of efficient plan for regulatory activities at NPPs

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Hun; Son, Mun Gyu [Korea Association for Nuclear Technology, Taejon (Korea, Republic of); Kang, Chang Sun; Yun, Jeong Ik; Ko, Hyun Seok; Lee, Young Wook [Seoul National Univ., Seoul (Korea, Republic of)

2001-03-15

In-operation regulatory activities at sites are very important and it should be improved to cope with accidents efficiently and quickly. In case of site survey and safety regulatory inspection regulatory system based on not regulatory headquarter but site regional office should be constructed. In other words, safety assurance and pending problem management considering site situation are needed. In this study, regulatory system at Nuclear Power Plant sites all over the world were reviewed and effective regulatory system of Korea are suggested to maximize the efficiency of license and regulatory manpower and consider the interest of local government and residents.

Glycoconjugate Vaccines: The Regulatory Framework.

Science.gov (United States)

Jones, Christopher

2015-01-01

Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

A flood-based information flow analysis and network minimization method for gene regulatory networks.

Science.gov (United States)

Pavlogiannis, Andreas; Mozhayskiy, Vadim; Tagkopoulos, Ilias

2013-04-24

Biological networks tend to have high interconnectivity, complex topologies and multiple types of interactions. This renders difficult the identification of sub-networks that are involved in condition- specific responses. In addition, we generally lack scalable methods that can reveal the information flow in gene regulatory and biochemical pathways. Doing so will help us to identify key participants and paths under specific environmental and cellular context. This paper introduces the theory of network flooding, which aims to address the problem of network minimization and regulatory information flow in gene regulatory networks. Given a regulatory biological network, a set of source (input) nodes and optionally a set of sink (output) nodes, our task is to find (a) the minimal sub-network that encodes the regulatory program involving all input and output nodes and (b) the information flow from the source to the sink nodes of the network. Here, we describe a novel, scalable, network traversal algorithm and we assess its potential to achieve significant network size reduction in both synthetic and E. coli networks. Scalability and sensitivity analysis show that the proposed method scales well with the size of the network, and is robust to noise and missing data. The method of network flooding proves to be a useful, practical approach towards information flow analysis in gene regulatory networks. Further extension of the proposed theory has the potential to lead in a unifying framework for the simultaneous network minimization and information flow analysis across various "omics" levels.

Session II-H. Regulatory implementation

International Nuclear Information System (INIS)

Farzin, M.H.

1981-01-01

During FY 1981, the program concepts for implementing the NRC and EPA regulations were formed. These concepts consist of: review and critique of proposed rules; interpretation of rules into practical performance objectives; and planning to achieve compliance of total system performance with the rules. Although still flexible because of the lack of final rules, notable advances in implementation of these concepts were achieved in FY 1981. Technically, proposed and draft rules were evaluated and resulting radionuclide release limits were compared for consistency. For issue identification and resolution activity, six LTR's were initiated, and other topics were identified. In activities leading to total system compliance with regulations, planning and implementation efforts were more clearly defined and integrated. Papers reported in this session are: (1) regulatory implementation concepts and program overview; (2) licensing issue resolution; (3) status of NEPA activities in the NNWSI Program; (4) status of NEPA activities in the ONWI Program; (5) NWTS approach to site characterization reporting; and (6) quality assurance perspectives relative to licensing needs

The path from biomarker discovery to regulatory qualification

CERN Document Server

Goodsaid, Federico

2013-01-01

The Path from Biomarker Discovery to Regulatory Qualification is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science. For complimentary access to chapter 13, 'Classic' Biomarkers of Liver Injury, by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site:  http://tinyurl.com/ClassicBiomarkers Contains a collection of experiences of different...

Risk acceptance criteria of the Nuclear Regulatory Authority

International Nuclear Information System (INIS)

Felizia, Eduardo R.

2005-01-01

This report describes some of the regulatory and control functions legally conferred upon the Argentine Nuclear Regulatory Authority concerning radiological risks, as well as a critical analysis of the radiological risk acceptance criteria contained in the Argentine regulatory system. A summary of the application of regulatory standards AR 3.1.3. - 'Radiological criteria related to accidents in nuclear power reactors' and AR 4.1.3. - 'Radiological criteria related to accidents in research reactors' to concrete cases is made, while the favourable and unfavourable aspects of the risk acceptance criteria are discussed. The conclusion is that the Argentine regulatory system contains adequate radiological risk acceptance criteria, that the latter are consistent with the radiological protection principles applicable to man and that, for the moment, there is no need to perform any modifications that would broaden the conceptual framework on which such criteria are based. (author) [es

Training Therapists in Evidence-Based Practice: A Critical Review of Studies From a Systems-Contextual Perspective

OpenAIRE

Beidas, Rinad S.; Kendall, Philip C.

2010-01-01

Evidence-based practice (EBP), a preferred psychological treatment approach, requires training of community providers. The systems-contextual (SC) perspective, a model for dissemination and implementation efforts, underscores the importance of the therapist, client, and organizational variables that influence training and consequent therapist uptake and adoption of EBP. This review critiques the extant research on training in EBP from an SC perspective. Findings suggest that therapist knowled...

The perspective awareness model - Eliciting multiple perspectives to formulate high quality decisions

International Nuclear Information System (INIS)

Boucher, Laurel

2013-01-01

A great deal of attention is given to the importance of communication in environmental remediation and radioactive waste management. However, very little attention is given to eliciting multiple perspectives so as to formulate high quality decisions. Plans that are based on a limited number of perspectives tend to be narrowly focused whereas those that are based on a wide variety of perspectives tend to be comprehensive, higher quality, and more apt to be put into application. In addition, existing methods of dialogue have built-in limitations in that they typically draw from the predominant thinking patterns which focus in some areas but ignore others. This can result in clarity but a lack of comprehensiveness. This paper presents a Perspective Awareness Model which helps groups such as partnering teams, interagency teams, steering committees, and working groups elicit a wide net of perspectives and viewpoints. The paper begins by describing five factors that makes cooperation among such groups challenging. Next, a Perspective Awareness Model that makes it possible to manage these five factors is presented. The two primary components of this model --- the eight 'Thinking Directions' and the 'Shared Documentation' --- are described in detail. Several examples are given to illustrate how the Perspective Awareness Model can be used to elicit multiple perspectives to formulate high quality decisions in the area of environmental remediation and radioactive waste management. (authors)

Managing LLRW from decommissioning of nuclear facilities - a Canadian perspective

Energy Technology Data Exchange (ETDEWEB)

Donders, R E [Atomic Energy of Canada Ltd., Chalk River, ON (Canada). Chalk River Nuclear Labs.; Hardy, D G [Frontenac Consulting Services, Deep River, ON (Canada); De, P L [Low-Level Radioactive Waste Management Office, Gloucester, ON (Canada)

1994-03-01

In Canada, considerable experience has been gained recently in decommissioning nuclear facilities and managing the resulting waste. This experience has raised important issues from both the decommissioning and waste management perspectives. This paper focuses on the waste management aspects of decommissioning. Past experience is reviewed, preliminary estimates of waste volumes and characteristics are provided, and the major technical and regulatory issues are discussed. (author). 5 refs., 1 tab., 2 figs.

Regulatory Oversight of Safety Culture — Korea’s Experience

International Nuclear Information System (INIS)

Jung, S.J.; Choi, Y.S.; Kim, J.T.

2016-01-01

In Korea, a regulatory oversight program of safety culture was launched in 2012 to establish regulatory measures against several events caused by weak safety culture in the nuclear industry. This paper is intended to introduce the preliminary regulatory oversight framework, development and validation of safety culture components, pilot safety culture inspection results and lessons learned. The safety culture model should be based on a sound understanding of the national culture and industry characteristics where the model will be applied. The nuclear safety culture oversight model is being developed and built on the Korean regulatory system to independently assess the nuclear power operating organizations’ safety culture.

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)

Neuroanatomical correlates of time perspective: A voxel-based morphometry study.

Science.gov (United States)

Chen, Zhiyi; Guo, Yiqun; Feng, Tingyong

2018-02-26

Previous studies indicated that time perspective can affect many behaviors, such as decisions, risk taking, substance abuse and health behaviors. However, very little is known about the neural substrates of time perspective (TP). To address this question, we characterized different dimensions of TP (including the Past, Present, and Future TP) using standardized Zimbardo Time Perspective Inventory (ZTPI), and quantified the gray matter volume using voxel-based morphometry (VBM) method across two independent samples. Our whole-brain analysis (sample 1, N=150) revealed Past-Negative TP was positively correlated with the GMV of a cluster in LPFC whereas Past-Positive was negatively correlated with the GMV in OFC, and Future TP was negatively correlated with GMV in mPFC. Moreover, two present scales (Present-Hedonistic and Present-Fatalistic TPs) were positively correlated with the GMV of regions in MTG and precuneus, respectively. We further examined the reliability of these correlations between multidimensional TPs and neuroanatomical structures in another independent sample (sample 2, N=58). Results verified our findings that GMV in LPFC could predict Past-Negative TP while GMV in OFC could predict Past-Positive TP, and the GMV in MTG could predict Present-Hedonistic while the GMV in presuneus could predict Present-Fatalistic, as well as the GMV in mPFC could predict Future TP. Thus, our findings suggest that the existence of selective neural basis underlying TPs, and further provide the stable biomarkers for multidimensional TPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Review of voluntary and regulatory carbon reporting by companies around the world

International Nuclear Information System (INIS)

Borie, Sylvain; Decq, Juliette; Wang, Xin; Alberola, Emilie; Afriat, Marion; Gourdon, Thomas

2016-01-01

What countries have instituted regulations requiring companies to measure their greenhouse gas (GHG) emissions? How could these regulations be strengthened to help meet the '2 deg. C' goal adopted by all member countries at the COP21 summit? In what ways do new French regulations on reporting of significant GHG emissions constitute a major advance in carbon reporting? To complement recent news focusing on reporting of carbon emissions in France, Carbone 4 offers its readers this review to put voluntary and regulatory carbon reporting mechanisms used by companies in a global perspective

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.

Network analysis of transcriptomics expands regulatory landscapes in Synechococcus sp. PCC 7002

Energy Technology Data Exchange (ETDEWEB)

McClure, Ryan S.; Overall, Christopher C.; McDermott, Jason E.; Hill, Eric A.; Markillie, Lye Meng; McCue, Lee Ann; Taylor, Ronald C.; Ludwig, Marcus; Bryant, Donald A.; Beliaev, Alexander S.

2016-08-27

Cyanobacterial regulation of gene expression must contend with a genome organization that lacks apparent functional context, as the majority of cellular processes and metabolic pathways are encoded by genes found at disparate locations across the genome. In addition, the fact that coordinated regulation of cyanobacterial cellular machinery takes place with significantly fewer transcription factors, compared to other Eubacteria, suggests the involvement of post-transcriptional mechanisms and regulatory adaptations which are not fully understood. Global transcript abundance from model cyanobacterium Synechococcus sp. PCC 7002 grown under 42 different conditions was analyzed using context-likelihood of relatedness. The resulting 903-gene network, which was organized into 11 modules, not only allowed classification of cyanobacterial responses to specific environmental variables but provided insight into the transcriptional network topology and led to the expansion of predicted regulons. When used in conjunction with genome sequence, the global transcript abundance allowed identification of putative post-transcriptional changes in expression as well as novel potential targets of both DNA binding proteins and asRNA regulators. The results offer a new perspective into the multi-level regulation that governs cellular adaptations of fast-growing physiologically robust cyanobacterium Synechococcus sp. PCC 7002 to changing environmental variables. It also extends a methodological knowledge-based framework for studying multi-scale regulatory mechanisms that operate in cyanobacteria. Finally, it provides valuable context for integrating systems-level data to enhance evidence-driven genomic annotation, especially in organisms where traditional context analyses cannot be implemented due to lack of operon-based functional organization.

The perspectives of the French biogas market

International Nuclear Information System (INIS)

2012-05-01

After having outlined that France is the fourth European producer of biogas, that regulatory evolutions have been adopted in 2012 to support the market, and that operators are trying to take place on this market, this document proposes the table of content of a market study which addresses the following topics: definition, resources and valorisation modes, legal framework and support measures taken by public authorities, investments, costs and profitability of a biogas project, current status of production and valorisation of biogas in France and market perspectives, presentation of main actors and of their development strategies

Challenges in Strengthening Regulatory Infrastructure in a Non-Nuclear Country

International Nuclear Information System (INIS)

Bosnjak, J.

2016-01-01

The State Regulatory Agency for Radiation and Nuclear Safety (SRARNS) is established as the effectively independent regulatory body for radiation and nuclear safety based on the Law on Radiation and Nuclear Safety in Bosnia and Herzegovina promulgated in November 2007. After its complete reorganization in the last few years, the regulatory system is compatible with relevant IAEA Safety Standards and Guides for safety and security of radioactive sources. The paper gives an overview of the new regulatory framework in Bosnia and Herzegovina, with special focus on challenges faced by Bosnia and Herzegovina, which are actually typical challenges for regulator in small non-nuclear country in strengthening regulatory infrastructure in regulating radiation sources and radioactive waste. (author)

A thermodynamic perspective on food webs: Quantifying entropy production within detrital-based ecosystems

NARCIS (Netherlands)

Meysman, F.J.R.; Bruers, S.

2007-01-01

Because ecosystems fit so nicely the framework of a “dissipative system”, a better integration of thermodynamic and ecological perspectives could benefit the quantitative analysis of ecosystems. One obstacle is that traditional food web models are solely based upon the principles of mass and energy

Regulatory Inspection of Nuclear Power Plants in NEA Member Countries

International Nuclear Information System (INIS)

1978-01-01

Based on the replies to a questionnaire, this report gives a description and comparative evaluation of the regulatory inspection activities in several NEA Member countries. The questionnaire which was circulated to all Member countries requested details on the organisation, system, scope and objectives of nuclear regulatory inspection and the effort required throughout all stages of the life of a nuclear plant including the use of independent bodies or consultants. Additional information was requested on the documentation concerned with regulatory inspections, incident and accident reporting procedures, and the duties, powers and bases for recruitment of regulatory personnel with the object of covering all related aspects. However, because of the differences in national practices and perhaps in the interpretation of the questionnaire, it proved to be extremely difficult to make an evaluation and comparison of inspection activities and effort involved in these Member countries. This report, which includes a section on the nuclear power programme in Member countries, should therefore only be regarded as an initial review but it provides a useful contribution to the exchange of experience and views on regulatory inspection practices

Clinical potential of regulatory T cell therapy in liver diseases: An overview and current perspectives

Directory of Open Access Journals (Sweden)

Hannah Claire Jeffery

2016-09-01

Full Text Available The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes, that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg. The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients.Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment and Good Manufacturing Practice (GMP facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases, chronic rejection and post-transplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases (GVHD and solid organ transplantations. There have not been any new therapies for the autoimmune liver diseases for more than three decades; thus the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior and microenvironment of Treg before applying the cells to the patients.

Steady-State-Preserving Simulation of Genetic Regulatory Systems

Directory of Open Access Journals (Sweden)

Ruqiang Zhang

2017-01-01

Full Text Available A novel family of exponential Runge-Kutta (expRK methods are designed incorporating the stable steady-state structure of genetic regulatory systems. A natural and convenient approach to constructing new expRK methods on the base of traditional RK methods is provided. In the numerical integration of the one-gene, two-gene, and p53-mdm2 regulatory systems, the new expRK methods are shown to be more accurate than their prototype RK methods. Moreover, for nonstiff genetic regulatory systems, the expRK methods are more efficient than some traditional exponential RK integrators in the scientific literature.

Regulation – Do or Die: An Analysis of Factors Critical to New Product Development in a Regulatory Context

Directory of Open Access Journals (Sweden)

Clare O'Dwyer

2017-04-01

Full Text Available This study explores new product development in a strict regulatory and historically secretive environment. Adopting a systems perspective and a mixed methods approach in our research, we examine medical device development in Ireland. Findings indicate that the possession of a regulatory strategy expedites the rate of commercialization, so too does the generation of clear product definitions and marketing claims in the earliest developmental phases. Moreover, results suggest that if the regulated industry strengthens its culture for regulation by prioritizing regulation over speed to market, by encouraging cross-functional team collaborations, and by taking a more proactive approach in post-marketing surveillance activities, it has the potential to improve customer satisfaction and enhance product innovation. This study provides unique empirical data enriched by the homogeneity of its sample. It also contributes guidance to practitioners of new product development within a regulatory context.

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

Consensus-based perspectives of pediatric inpatient eating disorder services.

Science.gov (United States)

O'Brien, Amy; McCormack, Julie; Hoiles, Kimberley J; Watson, Hunna J; Anderson, Rebecca A; Hay, Phillipa; Egan, Sarah J

2018-03-14

There are few evidence-based guidelines for inpatient pediatric eating disorders. The aim was to gain perspectives from those providing and receiving inpatient pediatric eating disorder care on the essential components treatment. A modified Delphi technique was used to develop consensus-based opinions. Participants (N = 74) were recruited for three panels: clinicians (n = 24), carers (n = 31), and patients (n = 19), who endorsed three rounds of statements online. A total of 167 statements were rated, 79 were accepted and reached a consensus level of at least 75% across all panels, and 87 were rejected. All agreed that families should be involved in treatment, and thatpsychological therapy be offered in specialist inpatient units. Areas of disagreement included that patients expressed a desire for autonomy in sessions being available without carers, and that weight gain should be gradual and admissions longer, in contrast to carers and clinicians. Carers endorsed that legal frameworks should be used to retain patients if required, and that inpatients are supervised at all times, in contrast to patients and clinicians. Clinicians endorsed that food access should be restricted outside meal times, in contrast to patients and carers. The findings indicate areas of consensus in admission criteria, and that families should be involved in treatment, family involvement in treatment, while there was disagreement across groups on topics including weight goals and nutrition management. Perspectives from patients, carers, and clinicians may be useful to consider during future revisions of best practice guidelines. © 2018 Wiley Periodicals, Inc.

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...

Stakeholder involvement activities in Slovakia. NRA's Commitment to Transparent Regulatory Process. Stakeholder Involvement in the French Regulatory Process - From Public Information to Public Participation. Stakeholder involvement in nuclear decision making in the Russian Federation

International Nuclear Information System (INIS)

Ziakova, Marta Chairperson; Nuclear Regulatory Authority of the Slovak Republic; Nuclear Regulation Authority - NRA; Ferapontov, Alexey

2017-01-01

Session 2 focused on the regulatory perspectives related to stakeholder involvement in the regulatory decision-making process. Presentations provided the audience with information regarding the international and national legal framework implemented in the Slovak Republic, in France, in Japan and in Russia. Examples of stakeholder involvement, as well as some tools used for this purpose, were presented and discussed. The value of consistency and complementarity between international and national requirements was highlighted. Presentations and discussion confirmed the very close tie between the way the stakeholder involvement process is conducted and the public confidence and perception of reliability the regulatory body may gain, or lose. The four presentations confirmed that stakeholder involvement is a key challenge for maintaining regulatory body credibility, independence and legitimacy. All countries confirmed their commitment to trying to make their stakeholder involvement processes as open, visible, transparent and comprehensive as possible. Involvement represents a long and permanent process which requires investment of time, human resources and money, as well as the ability to reach out, to listen, to share, and to take input into account, while keeping in view the goal of delivering decisions that are as rational and objective as possible. Involving stakeholders is more than informing or communicating. The earlier the stakeholders are involved in the decision-making process, the greater the chance of success. If losing credibility is easy, all regulatory bodies agreed on the long process needed to recover it

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

Regulatory perspective on incomplete control rod insertions

International Nuclear Information System (INIS)

Chatterton, M.

1997-01-01

The incomplete control rod insertions experienced at South Texas Unit 1 and Wolf Creek are of safety concern to the NRC staff because they represent potential precursors to loss of shutdown margin. Even before it was determined if these events were caused by the control rods or by the fuel there was an apparent correlation of the problem with high burnup fuel. It was determined that there was also a correlation between high burnup and high drag forces as well as with rod drop time histories and lack of rod recoil. The NRC staff initial actions were aimed at getting a perspective on the magnitude of the problem as far as the number of plants and the amount of fuel that could be involved, as well as the safety significance in terms of shutdown margin. As tests have been performed and data has been analyzed the focus has shifted more toward understanding the problem and the ways to eliminate it. At this time the staff's understanding of the phenomena is that it was a combination of factors including burnup, power history and temperature. The problem appears to be very sensitive to these factors, the interaction of which is not clearly understood. The model developed by Westinghouse provides a possible explanation but there is not sufficient data to establish confidence levels and sensitivity studies involving the key parameters have not been done. While several fixes to the problem have been discussed, no definitive fixes have been proposed. Without complete understanding of the phenomena, or fixes that clearly eliminate the problem the safety concern remains. The safety significance depends on the amount of shutdown margin lost due to incomplete insertion of the control rods. Were the control rods to stick high in the core, the reactor could not be shutdown by the control rods and other means such as emergency boration would be required

Performance-Based Regulation In A High Distributed Energy Resources Future

Energy Technology Data Exchange (ETDEWEB)

Newton Lowry, Mark [Pacific Economics Group Research LLC, Madison, WI (United States); Woolf, Tim [Synapse Energy Economics, Cambridge, MA (United States); Schwartz, Lisa C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2018-03-07

Performance-based regulation (PBR) of utilities has emerged as an important ratemaking option in the last 25 years. It has been implemented in numerous jurisdictions across the United States and is common in many other advanced industrialized countries. PBR’s appeal lies chiefly in its ability to strengthen utility performance incentives relative to traditional cost-of-service regulation (COSR). Some forms of PBR can streamline regulation and provide utilities with greater operating flexibility. Ideally, the benefits of better performance are shared by the utility and its customers. The shortcomings of traditional COSR in providing electric utilities with incentives that are aligned with certain regulatory goals are becoming increasingly clear. In particular, COSR can provide strong incentives to increase electricity sales and utility rate base. Further, some parties express concern that traditional COSR does not provide utilities with appropriate financial incentives to address evolving industry challenges such as changing customer demands for electricity services, increased levels of distributed energy resources (DERs), and growing pressure to mitigate carbon dioxide emissions. In addition, attention to potential new regulatory models to support the “utility of the future” has renewed interest in PBR. This report describes key elements of PBR and explains some of the advantages and disadvantages of various PBR options. We present pertinent issues from the perspectives of utilities and customers. In practice, these different perspectives are not diametrically opposed. Nonetheless, this framework is useful for illustrating how various aspects of PBR may be viewed by those key groups. Regulators have a unique perspective, in that they must balance consumer, utility, and other interests with the goal of achieving a result that is in the overall public interest.

Finding common ground: perspectives on community-based childhood obesity prevention.

Science.gov (United States)

Porter, Christine M; Pelletier, David L

2012-11-01

To support successful and inclusive community organizing for childhood obesity prevention, this research identified stakeholder perspectives on what communities should do to prevent childhood obesity. It employed factor analysis on statement sorts (Q methodology) conducted by 95 people in an upstate New York community. These participants sorted 36 statements about the issue by how much he or she agreed or disagreed with each. Participants were recruited through strategic snowball sampling to sample a variety of perspectives. The four resulting factors, or perspectives, were interpreted in the context of presort demographic surveys and postsort interviews. This research found one stance that fits the environmental perspective common in public health. The other three factors indicate important variations among perspectives centered on individual responsibility, ranging from libertarian to technocratic views. However, overall, results revealed a substantial degree of agreement among the four perspectives, including on providing access to family activities and on making fruits and vegetables more available and affordable, for example, through subsidies. This article points to common ground for community action on childhood obesity prevention, highlights areas likely to generate considerable contention, and shows whose views are not being accounted for in, at least, this community's childhood obesity prevention project.

Safety Management in Non-Nuclear Contexts. Examples from Swedish Railway Regulatory and Company Perspectives

International Nuclear Information System (INIS)

Salo, Ilkka; Svensson, Ola

2005-06-01

studied organizations respectively. These three chapters give a detailed account of safety management from a system perspective and applications in the organizations studied, and could be read independently of each other. In the fourth chapter the report concludes with summarizing safety management in SRA and SJ by mapping the results on important concepts from the system theoretical framework, and general themes for safety management applicable across contexts are suggested. The qualitative descriptions of the organizations generated a detailed account on how safety is managed in Swedish railway operations. Examples of safety management in practice are given both from the regulatory point of view and from an organizational position close to the actual operations. The Swedish railway operations are strictly regulated and the safety goals are identifiable along the legislative documentation from the government's goals for safe operations expressed in the railway legislation, through SRA's regulations, to SJ's internal regulations. There is a high degree of coherence between SJ's and SRA's formulations of safety management and safe operations in general. Both organizations have their origin in the former national railway company, which may is partly reflected in the high degree of correspondence between the approaches towards safety. Both organizations make use of a system approach to their operations, which are clearly reflected in the highly structured organizations, with core objectives, operational responsibilities, procedures, and information feedback prerequisites sufficiently mapped on the organizational units. The report gives both detailed accounts and summaries of a number of central themes for safety management derived from the system theoretical framework, and also themes relevant for safety management in general. For example: the organizations definitions of safety management, descriptions of the organizational structures, recent processes of organizational

Assessment and inspection tasks of the Spanish regulatory body staff regarding I and C and related systems backfitting in old plants

International Nuclear Information System (INIS)

Cid Campo, R.; Villadoniga, J.I.

1985-01-01

Based on our experience working on backfits of the two oldest plants in Spain, we believe that: (1) Reaching backfitting decisions is one of the most difficult tasks being performed by a regulatory body. (2) Any backfitting decision should be preceded by a thorough review of the safety importance of the situation the backfit is aimed to correct. (3) Backfitting decisions should be reached in an integrated way. A complete review of the plant should be performed to put each backfit in perspective. PRA may be a useful tool to achieve it. (4) Except when there is an immediate need of corrective actions backfitting schedules should be long enough to allow appropriate review by all involved parties

Learner Perspectives of Online Problem-Based Learning and Applications from Cognitive Load Theory

Science.gov (United States)

Chen, Ruth

2016-01-01

Problem-based learning (PBL) courses have historically been situated in physical classrooms involving in-person interactions. As online learning is embraced in higher education, programs that use PBL can integrate online platforms to support curriculum delivery and facilitate student engagement. This report describes student perspectives of the…

Embracing First-Person Perspectives in Soma-Based Design

Directory of Open Access Journals (Sweden)

Kristina Höök

2018-02-01

Full Text Available A set of prominent designers embarked on a research journey to explore aesthetics in movement-based design. Here we unpack one of the design sensitivities unique to our practice: a strong first person perspective—where the movements, somatics and aesthetic sensibilities of the designer, design researcher and user are at the forefront. We present an annotated portfolio of design exemplars and a brief introduction to some of the design methods and theory we use, together substantiating and explaining the first-person perspective. At the same time, we show how this felt dimension, despite its subjective nature, is what provides rigor and structure to our design research. Our aim is to assist researchers in soma-based design and designers wanting to consider the multiple facets when designing for the aesthetics of movement. The applications span a large field of designs, including slow introspective, contemplative interactions, arts, dance, health applications, games, work applications and many others.

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.

Model-based nonlinear control of hydraulic servo systems: Challenges, developments and perspectives

Science.gov (United States)

Yao, Jianyong

2018-06-01

Hydraulic servo system plays a significant role in industries, and usually acts as a core point in control and power transmission. Although linear theory-based control methods have been well established, advanced controller design methods for hydraulic servo system to achieve high performance is still an unending pursuit along with the development of modern industry. Essential nonlinearity is a unique feature and makes model-based nonlinear control more attractive, due to benefit from prior knowledge of the servo valve controlled hydraulic system. In this paper, a discussion for challenges in model-based nonlinear control, latest developments and brief perspectives of hydraulic servo systems are presented: Modelling uncertainty in hydraulic system is a major challenge, which includes parametric uncertainty and time-varying disturbance; some specific requirements also arise ad hoc difficulties such as nonlinear friction during low velocity tracking, severe disturbance, periodic disturbance, etc.; to handle various challenges, nonlinear solutions including parameter adaptation, nonlinear robust control, state and disturbance observation, backstepping design and so on, are proposed and integrated, theoretical analysis and lots of applications reveal their powerful capability to solve pertinent problems; and at the end, some perspectives and associated research topics (measurement noise, constraints, inner valve dynamics, input nonlinearity, etc.) in nonlinear hydraulic servo control are briefly explored and discussed.

Complexity Analysis of Industrial Organizations Based on a Perspective of Systems Engineering Analysts

Directory of Open Access Journals (Sweden)

I. H. Garbie

2011-12-01

Full Text Available Complexity in industrial organizations became more difficult and complex to be solved and it needs more attention from academicians and technicians. For these reasons, complexity in industrial organizations represents a new challenge in the next decades. Until now, analysis of industrial organizations complexity is still remaining a research topic of immense international interest and they require reduction in their complexity. In this paper, analysis of complexity in industrial organizations is shown based on the perspective of systems engineering analyst. In this perspective, analysis of complexity was divided into different levels and these levels were defined as complexity levels. A framework of analyzing these levels was proposed and suggested based on the complexity in industrial organizations. This analysis was divided into four main issues: industrial system vision, industrial system structure, industrial system operating, and industrial system evaluating. This analysis shows that the complexity of industrial organizations is still an ill-structured and a multi-dimensional problem.

Wind energy technical-economic viability under the new regulatory rules of the Brazilian electric sector; Viabilidade tecnico-economica da energia eolica face ao novo marco regulatorio do setor eletrico brasileiro

Energy Technology Data Exchange (ETDEWEB)

Dutra, Ricardo Marques

2001-02-15

The wind energy development in the world shows as one of the most important and promising technologies in the clean energy generation complement. This work presents the wind energy evolution and utilization in the electric power generation, the environmental impacts and perspectives. Considering the great wind potential in Brazil and the new rules of the electric sector, technical feasibility studies were developed based on regions north and northeast wind data as well as economic feasibility studies based on the new regulatory rules for the energy renewable sources. The results show that is possible to generate clean energy within the new context of the electricity sector.(author)

Methodology For Evaluation Of Regulatory Effectiveness In Physical Protection

International Nuclear Information System (INIS)

Izmaylov, Alexander; Valente, John; Griggs, James R.; Rexroth, Paul; Piskarev, Alexander; Babkin, Vladimir; Sokolov, Egor; Melton, Ronald B.; Cunningham, Mitchel E.; Baker, Kathryn A.; Brothers, Alan J.

2005-01-01

Material protection, control, and accounting (MPC and A) regulatory documents play an important role in securing and protecting nuclear material by regulating a variety of activities at different hierarchical levels. The development, implementation, and practical application of these regulatory documents requires a significant investment of financial and material resources. Therefore, it is important to evaluate the effectiveness of the regulatory development process and the extent to which regulations improve the effectiveness of MPC and A at nuclear sites. The joint Russian and U.S. Regulatory Development Project has a goal of evaluating the effectiveness of regulatory documents developed for MPC and A. As part of this joint Project, a methodology for evaluating effectiveness has been developed. This methodology was developed around physical protection objectives. The developed methodology specifies physical protection objectives to be accomplished through the implementation of a regulatory system based on the physical protection goals at the nuclear sites. It includes approaches to assessing regulatory effectiveness, the hierarchical structure of physical protection objectives to be accomplished through implementing regulations, a 'mapping' of the physical protection objectives to the regulatory framework, a list of criteria for evaluating the effectiveness of physical protection regulations and effectiveness indicators, as well as means and methods for gathering information and implementation of this evaluation.

Application of the perspective-based reading technique in the nuclear I and C context. CORSICA work report 2011

Energy Technology Data Exchange (ETDEWEB)

Lahtinen, J.

2012-07-01

Inspections and reviews are one of the most effective ways of detecting errors in software development. The methods are also cost-effective because defects can be spotted early in the development, and thus the cost of repairing the defects is lower. Reading techniques are the procedures that are used in the inspection or review of a software artefact. The most common procedures are simple ad-hoc reading and a checklist- based reading technique. However, more advanced and detailed procedures have been created for various purposes. This report reviews the state-of-the-art software reading techniques used in inspections and reviews, and briefly reviews some of the empirical research in this context. The majority of the empirical research results indicate that, for example, perspective-based reading is more cost-effective and can detect more defects than more basic reading techniques. This report also describes how perspective-based reading can be applied to the inspection of nuclear-domain requirement specifications. For this purpose, seven perspective-based reading scenarios have been created. (orig.)

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.

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.

Regulatory control of radiation sources and radioactive materials: The UK position

International Nuclear Information System (INIS)

Englefield, C.; Holyoak, B.; Ledgerwood, K.; Littlewood, K.

2001-01-01

The paper presents the organizations involved in the regulation of the safety of radiation sources and the security of radioactive materials across the UK. The safety of radiation sources is within the regulatory remit of the Health and Safety Executive, under the Health and safety of Work Act 1974 and associated regulations. Any employer using radiation sources has a statutory duty to comply with this legislation, thereby protecting workers and the public from undue risk. From a radioactive waste management perspective, the storage and use of radioactive materials and the accumulation and disposal of radioactive waste are regulated by the environment agencies of England and Wales, Scotland, and Northern Ireland, under the Radioactive Substances Act 1993. Special regulatory arrangements apply to nuclear sites, such as power stations and fuel cycle plants, and some additional bodies are involved in the regulation of the security of fissile materials. An explanation is given in the paper as to how these organizations to work together to provide a comprehensive and effective regulatory regime. An overview of how these regulators have recently started to work more closely with other enforcement bodies, such as the Police and Customs and Excise is also given, to illustrate the approach that is being applied in the UK to deal with orphan sources and illicit trafficking. (author)

Information processing in the transcriptional regulatory network of yeast: Functional robustness

Directory of Open Access Journals (Sweden)

Dehmer Matthias

2009-03-01

Full Text Available Abstract Background Gene networks are considered to represent various aspects of molecular biological systems meaningfully because they naturally provide a systems perspective of molecular interactions. In this respect, the functional understanding of the transcriptional regulatory network is considered as key to elucidate the functional organization of an organism. Results In this paper we study the functional robustness of the transcriptional regulatory network of S. cerevisiae. We model the information processing in the network as a first order Markov chain and study the influence of single gene perturbations on the global, asymptotic communication among genes. Modification in the communication is measured by an information theoretic measure allowing to predict genes that are 'fragile' with respect to single gene knockouts. Our results demonstrate that the predicted set of fragile genes contains a statistically significant enrichment of so called essential genes that are experimentally found to be necessary to ensure vital yeast. Further, a structural analysis of the transcriptional regulatory network reveals that there are significant differences between fragile genes, hub genes and genes with a high betweenness centrality value. Conclusion Our study does not only demonstrate that a combination of graph theoretical, information theoretical and statistical methods leads to meaningful biological results but also that such methods allow to study information processing in gene networks instead of just their structural properties.

An inquiry into the concept of infancy care based on the perspective of Islam.

Science.gov (United States)

Jafari-Mianaei, Soheila; Alimohammadi, Nasrollah; Banki-Poorfard, Amir-Hossein; Hasanpour, Marzieh

2017-10-01

All schools of thought believe that infancy is crucial to the formation and development of the human character. Nevertheless, a search of literature revealed the lack of a clear definition of the concept of 'infancy care based on an Islamic perspective' in nursing texts. As the lack of a clear definition of a concept conveys the inapplicability of that concept to its relevant field and community, this study was conducted to explore and determine the characteristic features of the concept of infancy care based on the perspective of Islam. Walker and Avant's (Strategies for theory construction in nursing. Prentice Hall, Boston, 2011) literary concept synthesis as the manner of concept development approach was conducted. Islamic documents were surveyed without any time limitation. Findings involved the extraction of six main concepts, including God as the Merciful Nurturer, mother as the symbol of the Creativity and Divinity of God, infant as a person with dignity and potential for excellence, parents as the nurture way paver, basic principles of nurturing, and holistic lifelong health promotion. The theoretical definition of each concept was presented. From the perspective of Islam, infant care is the nurturing of a human who has been conceived with dignity, certain rights, identity, and the capacity for development and excellence. © 2017 John Wiley & Sons Ltd.

A Simulation-Based Approach for Teaching the Systems Perspective of Strategic Performance Management

Science.gov (United States)

Capelo, Carlos; Lopes, Ana; Mata, Ana

2015-01-01

Kaplan and Norton introduced the balanced scorecard (BSC), which is based on a systems perspective of the business strategy and performance measurement. Many organisations around the world use the BSC to define, implement and manage strategy. Nevertheless, there are studies that identify problems and limitations associated with the implementation…

Logical knowledge representation of regulatory relations in biomedical pathways

DEFF Research Database (Denmark)

Zambach, Sine; Hansen, Jens Ulrik

2010-01-01

Knowledge on regulatory relations, in for example regulatory pathways in biology, is used widely in experiment design by biomedical researchers and in systems biology. The knowledge has typically either been represented through simple graphs or through very expressive differential equation...... simulations of smaller parts of a pathway. In this work we suggest a knowledge representation of the most basic relations in regulatory processes regulates, positively regulates and negatively regulates in logics based on a semantic analysis. We discuss the usage of these relations in biology and in articial...... intelligence for hypothesis development in drug discovery....

Students' Perceptions of Teaching in Context-based and Traditional Chemistry Classrooms: Comparing content, learning activities, and interpersonal perspectives

Science.gov (United States)

Overman, Michelle; Vermunt, Jan D.; Meijer, Paulien C.; Bulte, Astrid M. W.; Brekelmans, Mieke

2014-07-01

Context-based curriculum reforms in chemistry education are thought to bring greater diversity to the ways in which chemistry teachers organize their teaching. First and foremost, students are expected to perceive this diversity. However, empirical research on how students perceive their teacher's teaching in context-based chemistry classrooms, and whether this teaching differs from traditional chemistry lessons, is scarce. This study aims to develop our understanding of what teaching looks like, according to students, in context-based chemistry classrooms compared with traditional chemistry classrooms. As such, it might also provide a better understanding of whether teachers implement and attain the intentions of curriculum developers. To study teacher behaviour we used three theoretical perspectives deemed to be important for student learning: a content perspective, a learning activities perspective, and an interpersonal perspective. Data were collected from 480 students in 24 secondary chemistry classes in the Netherlands. Our findings suggest that, according to the students, the changes in teaching in context-based chemistry classrooms imply a lessening of the emphasis on fundamental chemistry and the use of a teacher-centred approach, compared with traditional chemistry classrooms. However, teachers in context-based chemistry classrooms seem not to display more 'context-based' teaching behaviour, such as emphasizing the relation between chemistry, technology, and society and using a student-centred approach. Furthermore, students in context-based chemistry classrooms perceive their teachers as having less interpersonal control and showing less affiliation than teachers in traditional chemistry classrooms. Our findings should be interpreted in the context of former and daily experiences of both teachers and students. As only chemistry is reformed in the schools in which context-based chemistry is implemented, it is challenging for both students and teachers to

Power plant construction contracting in a changing regulatory environment

International Nuclear Information System (INIS)

Person, J.C.

1993-01-01

The 1965 blackout in the Northeast provided the wake-up call that spawned in unprecedented program of power plant construction by electric utilities. This building program began in the late 1960s and continued unabated through the 1970s. Beginning in the late 1970s, state regulators began in era of 'prudence' reviews which disallowed as imprudent significant portions of the costs of certain nuclear units being brought on line at the time. This regulatory experience brought about a fundamental change in the way in which utilities evaluated the need for additional capacity. This paper explores construction contracting trends in light of recent developments in the relationship between the electric utility and the state regulator. It is within this context that the utility decides: (1) whether to build, buy, or save; and (2) if the decision is to build, which project planning and administration considerations will maximize the utility's ability to incorporate project costs into the ratebase. In order to put these issues into their proper perspective, this paper first presents a brief overview of the prudence decisions of the past, and the chilling effect of these decisions generally on new project planning. The paper next focuses on the recent changes to the post-construction prudence review model, including the introduction of pre-approval arrangements and rolling prudence reviews. Following that will be a survey of new construction spending decisions in light of these changes. After an analysis of the bases for the prudence disallowances of the past and the application of the lessons learned from these disallowances to contract planning and administration issues of today, the paper will close with a discussion of the relative advantages and disadvantages of the most commonly used contract delivery methods in today's regulatory environment

Ten perspectives on Nordic energy

Energy Technology Data Exchange (ETDEWEB)

Tennbakk, Berit

2006-10-15

Summary: Perspective no. 1: Costly early learning from the EU ETS - Unforeseen price levels hit industries hard; Perspective no. 2: Market based support schemes - Do they work as intended? Perspective no. 3: New decade in the Nordic energy markets. Perspective no. 4: Reduced CO{sub 2} emissions and more renewables - Are we getting there or not? Perspective no. 5: Interpretation of financial requirements - An impediment to sound investments? Perspective no. 6: Who should invest in infrastructure - Public or private investors? Perspective no. 7: Re regulation is not the answer - Need for coordination calls for a visible hand? Perspective no. 8: Increased infrastructure investments - Due to EU ETS and support schemes for RES. Perspective no. 9: Energy, welfare and industry - Complex links make policy making difficult. Perspective no. 10 'Fuel' for an energy policy discussion - A Nordic energy policy agenda? (AG)

Alignment and prediction of cis-regulatory modules based on a probabilistic model of evolution.

Directory of Open Access Journals (Sweden)

Xin He

2009-03-01

Full Text Available Cross-species comparison has emerged as a powerful paradigm for predicting cis-regulatory modules (CRMs and understanding their evolution. The comparison requires reliable sequence alignment, which remains a challenging task for less conserved noncoding sequences. Furthermore, the existing models of DNA sequence evolution generally do not explicitly treat the special properties of CRM sequences. To address these limitations, we propose a model of CRM evolution that captures different modes of evolution of functional transcription factor binding sites (TFBSs and the background sequences. A particularly novel aspect of our work is a probabilistic model of gains and losses of TFBSs, a process being recognized as an important part of regulatory sequence evolution. We present a computational framework that uses this model to solve the problems of CRM alignment and prediction. Our alignment method is similar to existing methods of statistical alignment but uses the conserved binding sites to improve alignment. Our CRM prediction method deals with the inherent uncertainties of binding site annotations and sequence alignment in a probabilistic framework. In simulated as well as real data, we demonstrate that our program is able to improve both alignment and prediction of CRM sequences over several state-of-the-art methods. Finally, we used alignments produced by our program to study binding site conservation in genome-wide binding data of key transcription factors in the Drosophila blastoderm, with two intriguing results: (i the factor-bound sequences are under strong evolutionary constraints even if their neighboring genes are not expressed in the blastoderm and (ii binding sites in distal bound sequences (relative to transcription start sites tend to be more conserved than those in proximal regions. Our approach is implemented as software, EMMA (Evolutionary Model-based cis-regulatory Module Analysis, ready to be applied in a broad biological context.

Data-driven integration of genome-scale regulatory and metabolic network models

Science.gov (United States)

Imam, Saheed; Schäuble, Sascha; Brooks, Aaron N.; Baliga, Nitin S.; Price, Nathan D.

2015-01-01

Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription, and signaling) have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert—a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or more network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. In this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system. PMID:25999934

Sieve-based relation extraction of gene regulatory networks from biological literature.

Science.gov (United States)

Žitnik, Slavko; Žitnik, Marinka; Zupan, Blaž; Bajec, Marko

2015-01-01

Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice of transforming

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.

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.

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

A cross-cultural analysis of posthumous reproduction: The significance of the gender and margins-of-life perspectives

Directory of Open Access Journals (Sweden)

Yael Hashiloni-Dolev

2017-06-01

Full Text Available The scholarly discussion of posthumous reproduction (PHR focuses on informed consent and the welfare of the future child, for the most part overlooking cultural differences between societies. Based on a cross-cultural comparison of legal and regulatory documents, analysis of pivotal cases and study of scholarly and media discussions in Israel and Germany, this paper analyses the relevant ethical and policy issues, and questions how cultural differences shape the practice of PHR. The findings challenge the common classifications of PHR by highlighting the gender perspective and adding brain-dead pregnant women to the debate. Based on this study’s findings, four neglected cultural factors affecting social attitudes towards PHR are identified: (i the relationship between the pregnant woman and her future child; (ii what constitutes the beginning of life; (iii what constitutes dying; and (iv the social agent(s seeking to have the future child. The paper argues that PHR can be better understood by adding the gender and margins-of-life perspectives, and that future ethical and practical discussions of this issue could benefit from the criteria emerging from this cross-cultural analysis.

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

High-level waste program management: A ratepayers' and regulatory perspective

International Nuclear Information System (INIS)

Anderson, E.G.

1986-01-01

The nation's electric utility regulators have joined the effort to enhance the federal project to dispose of high-level nuclear waste. Because all financial support comes from ratepayers, the National Association of Regulatory Utility Commissioners (NARUC), through the mechanism of a subcommittee, seeks to investigate and monitor the federal program to provide to the Congress and the U.S. Department of Energy (DOE) the NARUC's unique expertise. Its views to enhance program management and improve cost control are its central contribution. While conveying no lack of confidence in the federal management, the NARUC is imparting its relevant experience derived from review of nuclear power plant construction and cost control. Recommendations are made for more cost-effective program direction and views on its management are given. Financial control, public input and cost responsibilities for disposal of defense and commercial wastes are separately identified. Needs for the DOE's heightened insight into and development of the monitored retrievable storage proposal to the Congress are described. Finally, with a warning that there exists a limit to ratepayer funding of this effort, the request is made for Congressional cost-control hearings and for expanded dialogue between the Department of Engery and financially responsible parties

Support in the development of Regulatory Procedures for licensing Lepse Waste Management Operations

International Nuclear Information System (INIS)

2001-05-01

This report describes a project intended to assist Gosatomnadzor of Russia develop a set of documents defining the regulatory requirements for information to be submitted to Gosatomnadzor in support of any application for a licence relating to the removal of spent nuclear fuel from the depot ship Lepse. The project resulted in the development of three regulatory documents covering the documentation required in support of a licence application, the requirements for quality assurance arrangements and the safety analysis report. The working method adopted involved staged development of draft material and review at workshops involving a wide variety of relevant Russian and western organizations. The input and output of the workshops was fully documented to provide an audit trail for the document development and the rationale for what has been included and what is excluded and why. The availability of the regulatory documents in English should significantly assist in the use of the documents by western partners in the actual industrial project. Important experience and information was exchanged among participants in the project. The developing understanding is an important element in providing confidence, from a western perspective, that appropriate regulatory supervision can be applied to industrial projects supported by organizations such as the European Commission and national agencies. The same working methods could be used in the next phase of Lepse regulatory support, i.e., support in development of the procedures for the regulatory review of licence applications, and, subsequently, support in the application of the regulatory inspection process to ensure licence conditions are being complied with. Similarly, these working methods could be used in providing regulatory support for nuclear and radiation safety related to other industrial projects involving radioactive waste management. The participants in this sub-project described in this report were Norwegian

Autonomy and Accountability: Teacher Perspectives on Evidence-Based Practice and Decision-Making for Students with Intellectual and Developmental Disabilities

Science.gov (United States)

Greenway, Rosanne; McCollow, Meaghan; Hudson, Roxanne F.; Peck, Charles; Davis, Carol A.

2013-01-01

The purpose of this study was to examine teacher perspectives about evidence-based practices (EBP) and decision-making for students with intellectual and developmental disabilities. Given the current EBP movement, our study sought to understand practitioner definitions and perspectives on EBP and decision-making. Interview data from nine special…

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...

Recurrent neural network based hybrid model for reconstructing gene regulatory network.

Science.gov (United States)

Raza, Khalid; Alam, Mansaf

2016-10-01

One of the exciting problems in systems biology research is to decipher how genome controls the development of complex biological system. The gene regulatory networks (GRNs) help in the identification of regulatory interactions between genes and offer fruitful information related to functional role of individual gene in a cellular system. Discovering GRNs lead to a wide range of applications, including identification of disease related pathways providing novel tentative drug targets, helps to predict disease response, and also assists in diagnosing various diseases including cancer. Reconstruction of GRNs from available biological data is still an open problem. This paper proposes a recurrent neural network (RNN) based model of GRN, hybridized with generalized extended Kalman filter for weight update in backpropagation through time training algorithm. The RNN is a complex neural network that gives a better settlement between biological closeness and mathematical flexibility to model GRN; and is also able to capture complex, non-linear and dynamic relationships among variables. Gene expression data are inherently noisy and Kalman filter performs well for estimation problem even in noisy data. Hence, we applied non-linear version of Kalman filter, known as generalized extended Kalman filter, for weight update during RNN training. The developed model has been tested on four benchmark networks such as DNA SOS repair network, IRMA network, and two synthetic networks from DREAM Challenge. We performed a comparison of our results with other state-of-the-art techniques which shows superiority of our proposed model. Further, 5% Gaussian noise has been induced in the dataset and result of the proposed model shows negligible effect of noise on results, demonstrating the noise tolerance capability of the model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Implications of a consumer-based perspective for the estimation of GHG emissions. The illustrative case of Luxembourg

International Nuclear Information System (INIS)

Caro, Dario; Rugani, Benedetto; Pulselli, Federico Maria; Benetto, Enrico

2015-01-01

The Kyoto protocol has established an accounting system for national greenhouse gas (GHG) emissions according to a geographic criterion (producer perspective), such as that proposed by the IPCC guidelines for national GHG inventories. However, the representativeness of this approach is still being debated, because the role of final consumers (consumer perspective) is not considered in the emission allocation system. This paper explores the usefulness of a hybrid analysis, including input–output (IO) and process inventory data, as a complementary tool for estimating and allocating national GHG emissions according to both consumer- and producer-based perspectives. We assess the historical GHG impact profile (from 1995 to 2009) of Luxembourg, which is taken as a case study. The country's net consumption over time is estimated to generate about 28,700 Gg CO 2 e/year on average. Compared to the conventional IPCC inventory, the IO-based framework typically shows much higher emission estimations. This relevant discrepancy is mainly due to the different points of view obtained from the hybrid model, in particular with regard to the contribution of imported goods and services. Detailing the GHG inventory by economic activity and considering a wider system boundary make the hybrid IO method advantageous as compared to the IPCC approach, but its effective implementation is still limited by the relatively complex modeling system, as well as the lack of coordination and scarce availability of datasets at the national level. - Highlights: • GHG emissions for Luxembourg are assessed using hybrid input–output (IO) modeling. • Consumer and producer perspectives are compared for the period 1995–2009. • IO-based GHG profiles are remarkably higher than traditional IPCC inventorying. • IO-based GHG accounting presents some advantages but is limited in implementation. • Key-aspects of IPCC and IO-based methods are extensively investigated and compared

Implications of a consumer-based perspective for the estimation of GHG emissions. The illustrative case of Luxembourg

Energy Technology Data Exchange (ETDEWEB)

Caro, Dario, E-mail: caro2@unisi.it [Ecodynamics Group/DEEPS, Department of Environment, Earth and Physical Sciences, University of Siena, Via A. Moro, 2, I-53100 Siena (Italy); Department of Animal Science, University of California, Davis, CA 95616 (United States); Rugani, Benedetto [Public Research Centre Henri Tudor (CRPHT), Resource Centre for Environmental Technologies (CRTE), 6A, avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette (Luxembourg); Pulselli, Federico Maria [Ecodynamics Group/DEEPS, Department of Environment, Earth and Physical Sciences, University of Siena, Via A. Moro, 2, I-53100 Siena (Italy); Benetto, Enrico [Public Research Centre Henri Tudor (CRPHT), Resource Centre for Environmental Technologies (CRTE), 6A, avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette (Luxembourg)

2015-03-01

The Kyoto protocol has established an accounting system for national greenhouse gas (GHG) emissions according to a geographic criterion (producer perspective), such as that proposed by the IPCC guidelines for national GHG inventories. However, the representativeness of this approach is still being debated, because the role of final consumers (consumer perspective) is not considered in the emission allocation system. This paper explores the usefulness of a hybrid analysis, including input–output (IO) and process inventory data, as a complementary tool for estimating and allocating national GHG emissions according to both consumer- and producer-based perspectives. We assess the historical GHG impact profile (from 1995 to 2009) of Luxembourg, which is taken as a case study. The country's net consumption over time is estimated to generate about 28,700 Gg CO{sub 2}e/year on average. Compared to the conventional IPCC inventory, the IO-based framework typically shows much higher emission estimations. This relevant discrepancy is mainly due to the different points of view obtained from the hybrid model, in particular with regard to the contribution of imported goods and services. Detailing the GHG inventory by economic activity and considering a wider system boundary make the hybrid IO method advantageous as compared to the IPCC approach, but its effective implementation is still limited by the relatively complex modeling system, as well as the lack of coordination and scarce availability of datasets at the national level. - Highlights: • GHG emissions for Luxembourg are assessed using hybrid input–output (IO) modeling. • Consumer and producer perspectives are compared for the period 1995–2009. • IO-based GHG profiles are remarkably higher than traditional IPCC inventorying. • IO-based GHG accounting presents some advantages but is limited in implementation. • Key-aspects of IPCC and IO-based methods are extensively investigated and compared.

Regulatory research / Pesquisa regulatória

Directory of Open Access Journals (Sweden)

Altair Souza de Assis

2013-05-01

Full Text Available We present in this paper the concept, importance, and scope of research into the regulatory framework of regulation and legislation, with a particular focus on legislation related to legal metrology. This study also describes a comparative analysis of the various forms of regulation and the associated regulatory research, with the ultimate goal of better defi ning the concept and to validate the need to have research groups within a country’s regulatory bodies. Based on this work, we conclude that regulatory research is a key factor in the success of any regulatory body’s activities. Such research helps to avoid the creation of absurd or impractical regulatory barriers to a country’s technological development, or worse, to permit “orphans,” that is, technologies that are outside regulatory control, as is currently the case. Indeed, for a country to have a robust technological infrastructure, especially if it is still a developing country, strong and competent regulatory control is essential. However, this must be balanced by an atmosphere that fosters continuous and consistent technological innovation, and such development must also be self-sustainable from economic, social, and environmental viewpoints. ------------------------------------------------ Apresenta-se neste trabalho o conceito, a importância e a abrangência da pesquisa regulatória no âmbito da regulação e da regulamentação, com foco particular na regulamentação relacionada à metrologia legal. Faz-se também uma análise comparativa entre as várias formas de regular e regulamentar, e as suas pesquisas regulatórias afi ns, tendo como meta principal situar melhor o conceito e validar a necessidade de se fazer pesquisa nos órgãos e agências regulatórias do país. Com base neste trabalho, concluímos que a pesquisa regulatória é um fator chave para o sucesso de qualquer plano de ação de regulação para os agentes regulatórios do país. Ela ajuda a

Enhancing Student Motivation: A Longitudinal Intervention Study Based on Future Time Perspective Theory

Science.gov (United States)

Schuitema, Jaap; Peetsma, Thea; van der Veen, Ineke

2014-01-01

The authors investigated the effects of an intervention developed to enhance student motivation in the first years of secondary education. The intervention, based on future time perspective (FTP) theory, has been found to be effective in prevocational secondary education (T. T. D. Peetsma & I. Van der Veen, 2008, 2009). The authors extend the…

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...

Structure and drafting of safeguards regulatory documents

International Nuclear Information System (INIS)

Cole, R.J.; Bennett, C.A.; Edelhertz, H.; Wood, M.T.; Brown, R.J.; Roberts, F.P.

1977-09-01

This study develops hypothesis about the relation between the structure and drafting of safeguards regulatory documents and the ability of document users to understand and implement them in a way that reflects the intent and requirements of the NRC. Four decisions are needed to improve communication: (1) Should improvement of safeguards regulatory documents as communication instruments be an explicit NRC program. (2) What specific methods of communication should be the focus of improvement efforts. (3) What actions to improve communications are feasible and desirable. (4) How should the NRC divide its available effort and resources among desirable actions in order to provide the most effective communication through regulatory documents. This volume contains: introduction, conceptual bases, legal requirements, targets, choice of documents, preparation of documents, readability, and further study of recommended changes in structure and drafting

Relational Perspectives on Leading

DEFF Research Database (Denmark)

Relational Perspectives on Leading discusses leadership from a relational and social constructionism perspective as practiced on an everyday basis between people. The book pursues a fast growing, practice-based approach - particularly within the Anglo-Saxon parts of the world - to organization...

Reviewing the regulatory barriers for nanomedicine: global questions and challenges.

Science.gov (United States)

Bowman, Diana M; Gatof, Jake

2015-01-01

Nanomedicine will play an increasing role in prevention and treatment across the entire healthcare spectrum. However, their precise market size, economic value and areas of application remain unclear. This opacity, including the question of what constitutes nanomedicine matters, especially when considered alongside the key regulatory questions and concerns. This article begins by placing these key questions into context in relation to the current scientific state of the art, focusing particular attention on the human health and safety context. In exploring these central questions surrounding the regulation of nanomedicine, this perspective also explores existing and suggested frameworks that aim to deal with emerging technologies more generally. It then outlines priority areas for action and general conclusions specific to nanomedicine.

Management Control Systems and Strategy: A Resource based Perspective. Evidence from Greece

OpenAIRE

Nikolaos Theriou; Dimitrios Maditinos; Georgios N. Theriou

2017-01-01

Purpose: The purpose of this paper is to empirically examine from the resource-based perspective, the relationship between the use of management control systems (MCS) and organisational capabilities in the Greek context. Design/Methodology/Approach: The study follows Henri's (2006) methodology and explores the relationships between the diagnostic and interactive uses of performance measurement systems (PMS) and the five capabilities (e.g. market orientation, organisational learning, entrep...

Identifying noncoding risk variants using disease-relevant gene regulatory networks.

Science.gov (United States)

Gao, Long; Uzun, Yasin; Gao, Peng; He, Bing; Ma, Xiaoke; Wang, Jiahui; Han, Shizhong; Tan, Kai

2018-02-16

Identifying noncoding risk variants remains a challenging task. Because noncoding variants exert their effects in the context of a gene regulatory network (GRN), we hypothesize that explicit use of disease-relevant GRNs can significantly improve the inference accuracy of noncoding risk variants. We describe Annotation of Regulatory Variants using Integrated Networks (ARVIN), a general computational framework for predicting causal noncoding variants. It employs a set of novel regulatory network-based features, combined with sequence-based features to infer noncoding risk variants. Using known causal variants in gene promoters and enhancers in a number of diseases, we show ARVIN outperforms state-of-the-art methods that use sequence-based features alone. Additional experimental validation using reporter assay further demonstrates the accuracy of ARVIN. Application of ARVIN to seven autoimmune diseases provides a holistic view of the gene subnetwork perturbed by the combinatorial action of the entire set of risk noncoding mutations.

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.

Factoring consumers' perspectives into policy decisions for nursing competence.

Science.gov (United States)

Lazarus, Jean B; Lee, N Genell

2006-08-01

Health care delivery competence and accountability have typically been defined from providers' perspectives, rather than those of consumers as purchasers of services. In 1999, in the face of broad public concern about nursing competence the Alabama Board of Nursing developed an accountability model that established consumers at the center of the model and placed accountability for competent nursing practice at all levels of providers including regulatory agencies, health care organizations, educators, and licensees. The Board then authorized two research projects involving first, consumers perceptions on nursing competence and regulation, and second, comparing their perceptions with those of licensees, nurse educators, and organizational leaders (N = 1,127). Comparative data evidenced significant differences between consumers' and other participants' perceptions. This article highlights how policy implications derived from research resulted in regulatory changes for nursing competence. Five years of progress in policy changes made in the interest of public safety are summarized.

Challenges of regulatory rights of half-capacitated persons: A sociological perspective on the French Civil Code reform.

Science.gov (United States)

Eyraud, Benoît

2016-01-01

Democratic societies are based on the principle of equal legal capacity of all citizens to decide and act for themselves in all areas of social life. This "socio-civil capacity", which may involve both material property of an individual, as well as private life in matters ranging from health to personal relationships, is recognized by the law (both codified law and common law). These rights guarantee the autonomy and freedom of individuals in the name of respect for human dignity. Civil capacity of a person is legally diminished because his or her "natural" abilities, capacity, or competence are reduced. Recent social changes have lead to increased uses of legal measures of protection. The reasons for these changes are complex and they are accompanied by legislative reforms that modify the rights of half-capacitated persons. In this article, we examine certain issues of civil capacity rights based on the French example. We start present a perspective of the historical definition and practice of these rights as well as their democratization. Copyright © 2016. Published by Elsevier Ltd.

In silico discovery of transcription regulatory elements in Plasmodium falciparum

Directory of Open Access Journals (Sweden)

Le Roch Karine G

2008-02-01

Full Text Available Abstract Background With the sequence of the Plasmodium falciparum genome and several global mRNA and protein life cycle expression profiling projects now completed, elucidating the underlying networks of transcriptional control important for the progression of the parasite life cycle is highly pertinent to the development of new anti-malarials. To date, relatively little is known regarding the specific mechanisms the parasite employs to regulate gene expression at the mRNA level, with studies of the P. falciparum genome sequence having revealed few cis-regulatory elements and associated transcription factors. Although it is possible the parasite may evoke mechanisms of transcriptional control drastically different from those used by other eukaryotic organisms, the extreme AT-rich nature of P. falciparum intergenic regions (~90% AT presents significant challenges to in silico cis-regulatory element discovery. Results We have developed an algorithm called Gene Enrichment Motif Searching (GEMS that uses a hypergeometric-based scoring function and a position-weight matrix optimization routine to identify with high-confidence regulatory elements in the nucleotide-biased and repeat sequence-rich P. falciparum genome. When applied to promoter regions of genes contained within 21 co-expression gene clusters generated from P. falciparum life cycle microarray data using the semi-supervised clustering algorithm Ontology-based Pattern Identification, GEMS identified 34 putative cis-regulatory elements associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. Among these candidates were novel motifs, as well as many of the elements for which biological experimental evidence already exists in the Plasmodium literature. To provide evidence for the biological relevance of a cell invasion-related element predicted by GEMS, reporter gene and electrophoretic mobility shift assays

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...

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.

Using Patient Avatars to Promote Health Data Sharing Applications: Perspectives and Regulatory Challenges.

Science.gov (United States)

Dahi, Alan; Forgó, Nikolaus; Jensen, Sarah; Stauch, Marc

2016-04-01

The potential of ICT to address problems in modern healthcare is considerable, and an ICT-driven revolution in healthcare appears imminent. Such developments maybe viewed largely in positive terms. Thus they should result in enhanced treatment and care options, empowering patients--including by permitting greater self-management of illness outside hospital, while offering economic benefits and costs savings over traditional healthcare provision. However, the new possibilities also present manifold risks, such as of data breaches, encroachments on subject autonomy, as well as of other harms. This article considers some of the key regulatory challenges against the background of the progress of the current EU Commission-sponsored 'MyHealthAvatar' project.

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...

Current role of the USNRC safety research program in support of the regulatory process

International Nuclear Information System (INIS)

Levine, S.

1979-01-01

The current role of the USNRC's safety research program is shown. Some aspects of this role in the wake of the TMI accident are discused as well as some historical perspective on the development of USNRC's program, its relationship with the NRC mission, an overview of the program activities and some recent research results, and finally the impact of the TMI accident in clarifiying needs for expedited and new research activities, including the need for a greatly enhanced use of probabilistic analysis techniques to improve the coherence of its regulatory process. (author)

Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

Science.gov (United States)

Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

2015-12-01

Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

75 FR 21686 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2010-04-26

... to pay arbitration awards to remain in the securities industry presents regulatory risks and is...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or...

Developing Mindfulness in College Students through Movement-Based Courses: Effects on Self-Regulatory Self-Efficacy, Mood, Stress, and Sleep Quality

Science.gov (United States)

Caldwell, Karen; Harrison, Mandy; Adams, Marianne; Quin, Rebecca H.; Greeson, Jeffrey

2010-01-01

Objective: This study examined whether mindfulness increased through participation in movement-based courses and whether changes in self-regulatory self-efficacy, mood, and perceived stress mediated the relationship between increased mindfulness and better sleep. Participants: 166 college students enrolled in the 2007-2008 academic year in 15 week…

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.

How Perspective-Taking Helps and Hinders Group-Based Guilt as a Function of Group Identification

NARCIS (Netherlands)

Zebel, Sven; Doosje, Bertjan; Spears, Russell

In two studies we hypothesized that outgroup perspective-taking promotes group-based guilt among weakly identified perpetrator group members, but hinders it among higher identifiers. In Study 1, native Dutch participants (N = 153) confronted their group's past mistreatment of outgroups, while

75 FR 5157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Science.gov (United States)

2010-02-01

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Consolidated FINRA Rulebook January 25, 2010. On December 2, 2009, the Financial Industry Regulatory Authority... later in the rulebook consolidation process. It is therefore ordered, pursuant to Section 19(b)(2) of...

77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Science.gov (United States)

2012-08-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal of Proposed Rule Change To Adopt FINRA Rule 2231 (Customer Account Statements) in the Consolidated FINRA Rulebook August 2, 2012. On April 22, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

76 FR 21084 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Science.gov (United States)

2011-04-14

... Securities April 8, 2011. I. Introduction On March 3, 2011, the Financial Industry Regulatory Authority, Inc... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64283; File No. SR-FINRA-2011-012] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer...

Cis-regulatory signatures of orthologous stress-associated bZIP transcription factors from rice, sorghum and Arabidopsis based on phylogenetic footprints

Directory of Open Access Journals (Sweden)

Xu Fuyu

2012-09-01

Full Text Available Abstract Background The potential contribution of upstream sequence variation to the unique features of orthologous genes is just beginning to be unraveled. A core subset of stress-associated bZIP transcription factors from rice (Oryza sativa formed ten clusters of orthologous groups (COG with genes from the monocot sorghum (Sorghum bicolor and dicot Arabidopsis (Arabidopsis thaliana. The total cis-regulatory information content of each stress-associated COG was examined by phylogenetic footprinting to reveal ortholog-specific, lineage-specific and species-specific conservation patterns. Results The most apparent pattern observed was the occurrence of spatially conserved ‘core modules’ among the COGs but not among paralogs. These core modules are comprised of various combinations of two to four putative transcription factor binding site (TFBS classes associated with either developmental or stress-related functions. Outside the core modules are specific stress (ABA, oxidative, abiotic, biotic or organ-associated signals, which may be functioning as ‘regulatory fine-tuners’ and further define lineage-specific and species-specific cis-regulatory signatures. Orthologous monocot and dicot promoters have distinct TFBS classes involved in disease and oxidative-regulated expression, while the orthologous rice and sorghum promoters have distinct combinations of root-specific signals, a pattern that is not particularly conserved in Arabidopsis. Conclusions Patterns of cis-regulatory conservation imply that each ortholog has distinct signatures, further suggesting that they are potentially unique in a regulatory context despite the presumed conservation of broad biological function during speciation. Based on the observed patterns of conservation, we postulate that core modules are likely primary determinants of basal developmental programming, which may be integrated with and further elaborated by additional intrinsic or extrinsic signals in

Using Inequality Measures to Incorporate Environmental Justice into Regulatory Analyses

Science.gov (United States)

Harper, Sam; Ruder, Eric; Roman, Henry A.; Geggel, Amelia; Nweke, Onyemaechi; Payne-Sturges, Devon; Levy, Jonathan I.

2013-01-01

Formally evaluating how specific policy measures influence environmental justice is challenging, especially in the context of regulatory analyses in which quantitative comparisons are the norm. However, there is a large literature on developing and applying quantitative measures of health inequality in other settings, and these measures may be applicable to environmental regulatory analyses. In this paper, we provide information to assist policy decision makers in determining the viability of using measures of health inequality in the context of environmental regulatory analyses. We conclude that quantification of the distribution of inequalities in health outcomes across social groups of concern, considering both within-group and between-group comparisons, would be consistent with both the structure of regulatory analysis and the core definition of environmental justice. Appropriate application of inequality indicators requires thorough characterization of the baseline distribution of exposures and risks, leveraging data generally available within regulatory analyses. Multiple inequality indicators may be applicable to regulatory analyses, and the choice among indicators should be based on explicit value judgments regarding the dimensions of environmental justice of greatest interest. PMID:23999551

Managing Regulatory Body Competence

International Nuclear Information System (INIS)

2013-01-01

In 2001, the IAEA published TECDOC 1254, which examined the way in which the recognized functions of a regulatory body for nuclear facilities results in competence needs. Using the systematic approach to training (SAT), TECDOC 1254 provided a framework for regulatory bodies for managing training and developing and their maintaining their competence. It has been successfully used by many regulators. The IAEA has also introduced a methodology and an assessment tool - Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) - which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2009, the IAEA established a steering committee (supported by a bureau) with the mission to advise the IAEA on how it could best assist Member States to develop suitable competence management systems for their regulatory bodies. The committee recommended the development of a safety report on managing staff competence as an integral part of a regulatory body's management system. This Safety Report was developed in response to this request. It supersedes TECDOC 1254, broadens its application to regulatory bodies for all facilities and activities, and builds upon the experience gained through the application of TECDOC 1254 and SARCoN and the feedback received from Member States. This Safety Report applies to the management of adequate competence as needs change, and as such is equally applicable to the needs of States 'embarking' on a nuclear power programme. It also deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an 'embarking' State's regulatory system

Towards optimal use of available technical resources for regulatory purposes. The Syrian experience

International Nuclear Information System (INIS)

Shweikani, R.; Suman, H.; Othman, I.

2007-01-01

The Atomic Energy commission of Syria (AECS) is nominated by Syrian legislation as the regulatory authority in respect of radiation protection and safety and security of radioactive sources. In addition AECS is providing a wide range of Technical Services (TS) through its various departments. In this paper, the cooperation and coordination between the regulatory authority and the providers of technical services in Syria are described. The adjustment of the regulatory programme as to make maximal use of the available technical resources is presented. It was shown that this relationship does not jeopardize the effective independency of the regulatory authority which is maintained by keeping the regulatory decisions based on pure regulatory considerations. (author)

Individual plant examination program: Perspectives on reactor safety and plant performance. Part 6, appendices A, B, and C

International Nuclear Information System (INIS)

1997-12-01

This report provides perspectives gained by reviewing 75 Individual Plant Examination (IPE) submittals pertaining to 108 nuclear power plant units. IPEs are probabilistic analyses that estimate the core damage frequency (CDF) and containment performance for accidents initiated by internal events (including internal flooding, but excluding internal fire). The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, reviewed the WE submittals with the objective of gaining perspectives in three major areas: (1) improvements made to individual plants as a result of their IPEs and the collective results of the IPE program, (2) plant-specific design and operational features and modeling assumptions that significantly affect the estimates of CDF and containment performance, and (3) strengths and weaknesses of the models and methods used in the IPEs. These perspectives are gained by assessing the core damage and containment performance results, including overall CDF, accident sequences, dominant contributions to component failure and human error, and containment failure modes. In particular, these results are assessed in relation to the design and operational characteristics of the various reactor and containment types, and by comparing the IPEs to probabilistic risk assessment characteristics. Methods, data, boundary conditions, and assumptions used in the IPEs are considered in understanding the differences and similarities observed among the various types of plants

Conformity check of JMTR to new regulatory standards

International Nuclear Information System (INIS)

Watahiki, Shunsuke; Ide, Hiroshi; Hanakawa, Hiroki; Yamaura, Takayuki; Kaminaga, Masanori

2015-01-01

With the lesson learned from the accident of TEPCO Fukushima Daiichi Nuclear Power Station, also based on the international standards, the 'New regulatory standards for nuclear facilities for research! was enforced by the Nuclear Regulatory Authority in December 2013. The main requirements of the new standards are as follows: (1) measures for earthquake, tsunami, and damage from the outside, (2) severity classification, (3) fire protection, (4) flood protection, (5) communication and contacting, (6) measures for the loss of external power supply, (7) monitoring equipment, and (8) expansion prevention of accident that releases a large amounts of radioactive materials. Under the new regulatory standards, it is demanded that the constructions, systems, and equipment with safety functions of the current nuclear facilities should maintain the safety functions in accordance with their importance against the basic ground motions and possible natural phenomena. For the buildings, equipment, and machineries of JMTR nuclear facilities, the severity classification was performed on each of safety function and seismic resistance. Based on the classification results, seismic evaluation and safety analysis were carried out. (A.O.)

O Estado Regulador e o Estado Administrativo: A Expertise Política e o Governo dos Técnicos / The Regulatory State and Administrative State: The Expertise and the Government of Experts

Directory of Open Access Journals (Sweden)

Gilmara Joane Macedo de Medeiros

2016-10-01

Full Text Available Purpose – This essay analyzes the legitimacy of norms produced by the state’s regulatory activity. Underpinnings of the regulatory state and regulatory activity are discussed from the viewpoint of theories that might explain the legitimacy of its normative production, not least the administrative state theory of Dwight Waldo, who defends a government by technicians, valuing expertise. Methodology/approach/design – In the first section, the paper presents concepts of regulation and regulatory state. After that, the paper introduces the underpinnings for legitimate production of norms and the concept of public administration is addressed from the perspectives of the theory proposed by Dwight Waldo. Findings – According to Dwight Waldo, the legitimacy of regulatory decisions taken by a bureaucratic body relies on the technical expertise of its members, admitted through a meritocratic state choice.

Detecting Internal Control Problems Based on COSO and Islamic Perspective: Case on SMEs

Directory of Open Access Journals (Sweden)

Yuniarti Hidayah Suyoso Putra

2014-03-01

Full Text Available Objective – The presence of Small Medium Enterprises (SMEs has been able to be livelihoods sources and absorb more labor, even though it has a relative smaller contribution of additional value compared to the Large-scale Enterprises. The number of economic actors of SMEs spread across area from urban to rural. However, SMEs have faced several serious problems. These problems are caused by the unique characteristics of SMEs itself. First, lack of managerial skills due to limited human resources and lack of monitoring which it is rarely conducted by the manager or the owner. Second, lack of information and technology to carry out operations. Both problems have great impacts in lack of internal controls. Third, SMEs also face problems in developing business scale, limited access to capital to the banks and financial institutions due to the lack of transparency. Therefore, this research aimed to detect to what extent of the problems arising in the application and assessment of internal controls performed by SMEs.Method – The research employs descriptive qualitative research method through direct observation, interview and business documentation owned by the company. Research materials are 29 SMEs consisting of 19 trading SMEs and 10 service SMEs. All SMEs are located in Malang city. Detection of application and assessment of internal controls in this study is based on the COSO framework and the Islamic perspective.Result – Internal control activities indicators apply the five principles of COSO framework which focused on three layers. First layer is self-assessment control area. Second layer is environment control area and the third layer is independent control area. While the Islamic perspective is focused on the internal control of business activities based on the Qur'an and Hadith. The results derive from application and assessment based on COSO framework and Islamic perspectives are complementary in improving the practice of internal

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

Strategic decisions on research for advanced reactors: USNRS perspective

International Nuclear Information System (INIS)

Johnson, M.

2008-01-01

This document provided a perspective on strategic decision on research for advanced reactors. He pointed out that advanced reactors are fundamentally different from LWR and that regulatory tools currently available (e.g. codes and data) will not be applicable to advanced designs. He stated that international co-operation is the only practical way to work together for identifying needed capabilities and tools, including the use of industry facilities. He proposed that, in consideration of its good experience at coordinating research, the CSNI establishes a task group to identify and prioritize research needs. (author)

Nuclear science and technology: perspective prospects for Philippine development

International Nuclear Information System (INIS)

Aleta, C.R.

1996-01-01

The paper provides some historical perspectives on nuclear energy utilization and development in the Philippines. Highlights on applications in agriculture, medicine, industry, environment and regulations are mentioned. Current activities include gamma sterilization, food irradiation, sterile insect technique for pest eradication, medical applications, isotope techniques, radiation protection activities and nuclear power. Prospective contribution of national development through the use of radiation and nuclear techniques include those for water resources assessment, environmental and pollution studies, electricity generation and nuclear desalination. The regulatory aspects in support of the nuclear energy development are also discussed. (author)

Evaluation of research reactor fuel reliability in support of regulatory requirements

International Nuclear Information System (INIS)

Sokolov, Eugene N.

2005-01-01

This standards, codes and practices survey is devoted to the problem of reliability of R and D especially research reactor fuel (RRF) performance-related processes. Regulatory R and D evaluations were based on one standard and just few of them provide correlation to other relative standards whereas synthetic process approach reflects actual status of particular R and D practices. Fuel performance regulatory parameters are based on quality standards. A reliability process-based method similar to PSA/FMEA is proposed to evaluate RRF performance- related parameters in terms of reactor safety. (author)

Evaluation of research reactor fuel reliability in support of regulatory requirements

Energy Technology Data Exchange (ETDEWEB)

Sokolov, Eugene N [Chalk River Laboratories, AECL, Chalk River, ON, K0J 1J0 (Canada)

2005-07-01

This standards, codes and practices survey is devoted to the problem of reliability of R and D especially research reactor fuel (RRF) performance-related processes. Regulatory R and D evaluations were based on one standard and just few of them provide correlation to other relative standards whereas synthetic process approach reflects actual status of particular R and D practices. Fuel performance regulatory parameters are based on quality standards. A reliability process-based method similar to PSA/FMEA is proposed to evaluate RRF performance- related parameters in terms of reactor safety. (author)

Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective.

Science.gov (United States)

Abelin, Atika; Colegate, Tony; Gardner, Stephen; Hehme, Norbert; Palache, Abraham

2011-02-01

As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness. The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade. During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply. Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure. Enhancing

Inference of cancer-specific gene regulatory networks using soft computing rules.

Science.gov (United States)

Wang, Xiaosheng; Gotoh, Osamu

2010-03-24

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

Data-driven integration of genome-scale regulatory and metabolic network models

Directory of Open Access Journals (Sweden)

Saheed eImam

2015-05-01

Full Text Available Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription and signaling have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert – a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or more network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. In this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system.

12 CFR 562.2 - Regulatory reports.

Science.gov (United States)

2010-01-01

... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

Gym-based exoskeleton walking: A preliminary exploration of non-ambulatory end-user perspectives.

Science.gov (United States)

Cahill, Aoife; Ginley, Orna Mc; Bertrand, Courtney; Lennon, Olive

2018-07-01

Robotic walking devices (RWD) have shown many physical benefits in Spinal Cord Injury (SCI) rehabilitation. No study to date has explored end-user perceptions of these devices or gained insight into the use of these devices in a gym-based setting. This preliminary study explores the perspectives of four non-ambulatory individuals with SCI on using an exoskeleton walking device in a gym-based community setting. In-depth, semi-structured interviews were conducted with four SCI individuals living in the community. Interviews were audio-recorded and transcribed verbatim. Inductive thematic analysis established common overarching themes and subthemes. Four primary themes emerged addressing "The Psychological Adjustments Around Using RWDs with Respect to Disability", "Perceived Physical, Social and Psychological Benefits of Using an Exoskeleton", "The Role of External Influences", and "A Wellness Model to Health". A fully integrated gym setting was found to provide a positive and encouraging space to utilise the device. In addition, both the ability to set training goals and the positive attitude of robotic trainers were deemed to be important factors. This preliminary study provides detailed perspectives of four non-ambulatory individuals with SCI on utilising an exoskeleton walking device in a community setting. It suggests that gym-based RWDs impact positively on the users' lives and enhance their perceived wellbeing and sense of community integration. Enabling access to similar, community-based facilities should be prioritised for those with longstanding SCI disability. Copyright © 2018 Elsevier Inc. All rights reserved.

Handbook for value-impact assessments of NRC regulatory actions

International Nuclear Information System (INIS)

Mullen, M.F.; DiPalo, A.J.

1985-01-01

According to current Nuclear Regulatory Commission (NRC) procedures, value-impact (cost-benefit) assessments must be prepared for all rulemaking actions and for a broad range of other regulatory requirements and guidance. Probabilistic risk assessment (PRA) methods furnish an important part of the information base for these assessments. PRA methods are frequently the principal quantitative tool for estimating the benefits (e.g., public risk reduction) of proposed regulatory actions. In December 1983, the NRC published A Handbook for Value-Impact Assessment, NUREG/CR-3568, which provides a set of systematic procedures for performing value-impact assessments. The Handbook contains methods, data, and sources of information that can assist the regulatory analyst in conducting such assessments. The use of probabilistic risk analysis to estimate the benefits of proposed regulatory actions is described. Procedures and methods are also given for evaluating the costs and other consequences associated with regulatory actions. The Handbook has been adopted by the NRC as the recommended guideline for value impact assessments. This paper presents the background, objectives, and scope of the Handbook, describes the value-impact assessment methods (including the use of probabilistic risk assessment to estimate benefits), and discusses a selection of current and planned applications, with examples to illustrate how the methods are used

Ultrathin endoscopes based on multicore fibers and adaptive optics: a status review and perspectives.

Science.gov (United States)

Andresen, Esben Ravn; Sivankutty, Siddharth; Tsvirkun, Viktor; Bouwmans, Géraud; Rigneault, Hervé

2016-12-01

We take stock of the progress that has been made into developing ultrathin endoscopes assisted by wave front shaping. We focus our review on multicore fiber-based lensless endoscopes intended for multiphoton imaging applications. We put the work into perspective by comparing with alternative approaches and by outlining the challenges that lie ahead.

Using hexamers to predict cis-regulatory motifs in Drosophila

Directory of Open Access Journals (Sweden)

Kibler Dennis

2005-10-01

Full Text Available Abstract Background Cis-regulatory modules (CRMs are short stretches of DNA that help regulate gene expression in higher eukaryotes. They have been found up to 1 megabase away from the genes they regulate and can be located upstream, downstream, and even within their target genes. Due to the difficulty of finding CRMs using biological and computational techniques, even well-studied regulatory systems may contain CRMs that have not yet been discovered. Results We present a simple, efficient method (HexDiff based only on hexamer frequencies of known CRMs and non-CRM sequence to predict novel CRMs in regulatory systems. On a data set of 16 gap and pair-rule genes containing 52 known CRMs, predictions made by HexDiff had a higher correlation with the known CRMs than several existing CRM prediction algorithms: Ahab, Cluster Buster, MSCAN, MCAST, and LWF. After combining the results of the different algorithms, 10 putative CRMs were identified and are strong candidates for future study. The hexamers used by HexDiff to distinguish between CRMs and non-CRM sequence were also analyzed and were shown to be enriched in regulatory elements. Conclusion HexDiff provides an efficient and effective means for finding new CRMs based on known CRMs, rather than known binding sites.

75 FR 60157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-09-29

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

Bringing plant-based veterinary vaccines to market: Managing regulatory and commercial hurdles.

Science.gov (United States)

MacDonald, Jacqueline; Doshi, Ketan; Dussault, Marike; Hall, J Christopher; Holbrook, Larry; Jones, Ginny; Kaldis, Angelo; Klima, Cassidy L; Macdonald, Phil; McAllister, Tim; McLean, Michael D; Potter, Andrew; Richman, Alex; Shearer, Heather; Yarosh, Oksana; Yoo, Han Sang; Topp, Edward; Menassa, Rima

2015-12-01

The production of recombinant vaccines in plants may help to reduce the burden of veterinary diseases, which cause major economic losses and in some cases can affect human health. While there is abundant research in this area, a knowledge gap exists between the ability to create and evaluate plant-based products in the laboratory, and the ability to take these products on a path to commercialization. The current report, arising from a workshop sponsored by an Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme, addresses this gap by providing guidance in planning for the commercialization of plant-made vaccines for animal use. It includes relevant information on developing business plans, assessing market opportunities, manufacturing scale-up, financing, protecting and using intellectual property, and regulatory approval with a focus on Canadian regulations. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Process of Fragment-Based Lead Discovery—A Perspective from NMR

Directory of Open Access Journals (Sweden)

Rongsheng Ma

2016-07-01

Full Text Available Fragment-based lead discovery (FBLD has proven fruitful during the past two decades for a variety of targets, even challenging protein–protein interaction (PPI systems. Nuclear magnetic resonance (NMR spectroscopy plays a vital role, from initial fragment-based screening to lead generation, because of its power to probe the intrinsically weak interactions between targets and low-molecular-weight fragments. Here, we review the NMR FBLD process from initial library construction to lead generation. We describe technical aspects regarding fragment library design, ligand- and protein-observed screening, and protein–ligand structure model generation. For weak binders, the initial hit-to-lead evolution can be guided by structural information retrieved from NMR spectroscopy, including chemical shift perturbation, transferred pseudocontact shifts, and paramagnetic relaxation enhancement. This perspective examines structure-guided optimization from weak fragment screening hits to potent leads for challenging PPI targets.

76 FR 20759 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2011-04-13

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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2011-07-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

75 FR 71164 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-11-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

Science.gov (United States)

2012-06-11

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD06-6-000] Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold a joint meeting...

76 FR 60106 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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2011-09-28

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... 14, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

75 FR 41254 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

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2010-07-15

... registered capacity, may work in other investment-related industries, such as financial planning, or may seek...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule..., 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and...

NRC [Nuclear Regulatory Commission] safety research in support of regulation, 1987

International Nuclear Information System (INIS)

1988-05-01

This report, the third in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during 1987. The goal of this office is to ensure that research provides the technical bases for rulemaking and for related decisions in support of NRC licensing and inspection activities. This report describes both the direct contributions to scientific and technical knowledge with regard to nuclear safety and their regulatory applications

Criteria of exemption of regulatory control for radioactive material

International Nuclear Information System (INIS)

Marco A. Medrano Lopez

1991-01-01

Being based on the information contained in the 10 CFR Part 20, of the section 20.301 until the 20.306 where the mechanisms by means of which can prepare the waste of low level are indicated. While the Nuclear Regulatory Commission (NRC) it amended in the year of 1985 the Act of Politics on Low level Wastes, in particular the section 10 of the amendment of the Act, relative to the concept BRC treats those groups of radioactive waste in that their activity contents are so low that they could be exempt of the regulatory control, either liberating them toward the environment or to exempt people or organizations of the regulatory control

Quality management of the nuclear regulatory body. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

2001-09-01

This report is the outcome of the ninth series of peer discussions on regulatory practices entitled Nuclear Regulatory Body Quality Management, held in March and May 2001, and which involved the participation of senior nuclear regulators from 23 IAEA Member States. This report conveys the essence of two peer group discussions and highlights some good practices identified by the participating senior regulators. The objective of the discussions was to share experiences of regulatory bodies in implementing QM systems in their own work so as to ensure that the regulatory control over the licensees is effective and efficient and is commensurate with the mandate assigned by their governments. The shared experiences and good practices presented in the report, however, do not necessarily reflect the views of and good practices endorsed by the governments of the nominating Member States, the organizations to which the regulators belong, or the IAEA. The report sets down the peer group's experience in developing, implementing and evaluating QM within their regulatory bodies and identifies points to bear in mind when introducing such a system. This report is structured so that it covers the subject matter under the main headings of: application of quality management to regulatory work; development and implementation of quality management; assessment and improvement of performance; and good practices

Improving regulatory oversight of maintenance programs

International Nuclear Information System (INIS)

Cook, S.

2008-01-01

Safe nuclear power plant operation requires that risks due to failure or unavailability of Structures, Systems and Components (SSCs) be minimized. Implementation of an effective maintenance program is a key means for achieving this goal. In its regulatory framework, the important relationship between maintenance and safety is acknowledged by the CNSC. A high level maintenance program requirement is included in the Class I Facilities Regulations. In addition, the operating licence contains a condition based on the principle that the design function and performance of SSCs needs to remain consistent with the plant's design and analysis documents. Nuclear power plant licensees have the primary responsibility for safe operation of their facilities and consequently for implementation of a successful maintenance program. The oversight role of the Canadian Nuclear Safety Commission (CNSC) is to ensure that the licensee carries out that responsibility. The challenge for the CNSC is how to do this consistently and efficiently. Three opportunities for improvement to regulatory maintenance oversight are being pursued. These are related to the regulatory framework, compliance verification inspection activities and monitoring of self-reporting. The regulatory framework has been improved by clarifying expectations through the issuance of S-210 'Maintenance Programs for Nuclear Power Plants'. Inspection activities have been improved by introducing new maintenance inspections into the baseline program. Monitoring is being improved by making better use of self-reported and industry produced maintenance related performance indicators. As with any type of program change, the challenge is to ensure the consistent and optimal application of regulatory activities and resources. This paper is a summary of the CNSC's approach to improving its maintenance oversight strategy. (author)

Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems

OpenAIRE

Chen, Yvonne Y.; Jensen, Michael C.; Smolke, Christina D.

2010-01-01

RNA molecules perform diverse regulatory functions in natural biological systems, and numerous synthetic RNA-based control devices that integrate sensing and gene-regulatory functions have been demonstrated, predominantly in bacteria and yeast. Despite potential advantages of RNA-based genetic control strategies in clinical applications, there has been limited success in extending engineered RNA devices to mammalian gene-expression control and no example of their application to functional res...

Future nuclear regulatory challenges

International Nuclear Information System (INIS)

Royen, J.

1998-01-01

In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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2012-02-10

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... thereunder,\\2\\ notice is hereby given that on January 30, 2012, Financial Industry Regulatory Authority, Inc.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

75 FR 59771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

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2010-09-28

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the Proposed Rule.... I. Introduction On July 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k... pertinent distribution-related information from its members in a timely fashion to facilitate its Regulation...

76 FR 50796 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2011-08-16

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Increase the Position Limit for Options on the Standard and Poor's... Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

The French regulatory experience and views on nickel-base alloy PWSCC prevention and treatment

Energy Technology Data Exchange (ETDEWEB)

Turluer, G.; Cattiaux, G.; Monnot, B. [Institut de Radioprotection et de Surete Nucleaire, IRSN, 92 - Fontenay aux Roses (France); Emond, D.; Reuchet, J.; Chartier, Ph. [Direction Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France)

2003-10-01

This paper presents the experience feedback and views of the French Regulatory Authority (ASN) and of the technical support institute (IRSN) on PWSCC prevention since the initiation in 1989 of the 'Inconel Zones Review' requested by ASN to Electricite de France (EDF), the national operator of a fleet of 58 PWRs. This proactive requirement, launched before the discovery, in September 1991, of the only CRDM nozzle leak in France, on Bugey unit 3, was then triggered by the recurrence of many alloy 600 rapid degradations and leaks, world wide, and also in France in the late 1980's, particularly on steam generator tubes and on some pressurizer penetrations. Thus, the ASN requested that EDF, perform a comprehensive (generic) proactive assessment on all the nickel-base alloy components and parts of the main primary circuits, which of course included vessel head penetrations and bottom vessel head penetrations, and some other zones as a first priority. This proactive 'review' did, a minima, include the following tasks and actions: - Update and complete, by an extensive R and D program, the understanding and characterization of the Ni base alloys prone to PWSCC, - Analyze the various materials, metallurgical features, mechanical stresses, and physicochemical conditions of the parts exposed to primary water, in order to predict the occurrence of PWSCC initiation and propagation, - Provide a prioritization of the zones to be inspected, - Implement by improved NDE techniques a practical inspection program on the 58 PWRs, - Prepare and implement any needed mitigation actions as a result of the components conditions assessment. The present paper relates the main features of the French regulatory experience over more than 13 years and recalls the main principles of the assessment, which were applied by ASN. These principles, which are formalized in the current regulation rules revised in 1999, are briefly listed hereunder: - It is based on avoiding and

The French regulatory experience and views on nickel-base alloy PWSCC prevention and treatment

International Nuclear Information System (INIS)

Turluer, G.; Cattiaux, G.; Monnot, B.; Emond, D.; Reuchet, J.; Chartier, Ph.

2003-10-01

This paper presents the experience feedback and views of the French Regulatory Authority (ASN) and of the technical support institute (IRSN) on PWSCC prevention since the initiation in 1989 of the 'Inconel Zones Review' requested by ASN to Electricite de France (EDF), the national operator of a fleet of 58 PWRs. This proactive requirement, launched before the discovery, in September 1991, of the only CRDM nozzle leak in France, on Bugey unit 3, was then triggered by the recurrence of many alloy 600 rapid degradations and leaks, world wide, and also in France in the late 1980's, particularly on steam generator tubes and on some pressurizer penetrations. Thus, the ASN requested that EDF, perform a comprehensive (generic) proactive assessment on all the nickel-base alloy components and parts of the main primary circuits, which of course included vessel head penetrations and bottom vessel head penetrations, and some other zones as a first priority. This proactive 'review' did, a minima, include the following tasks and actions: - Update and complete, by an extensive R and D program, the understanding and characterization of the Ni base alloys prone to PWSCC, - Analyze the various materials, metallurgical features, mechanical stresses, and physicochemical conditions of the parts exposed to primary water, in order to predict the occurrence of PWSCC initiation and propagation, - Provide a prioritization of the zones to be inspected, - Implement by improved NDE techniques a practical inspection program on the 58 PWRs, - Prepare and implement any needed mitigation actions as a result of the components conditions assessment. The present paper relates the main features of the French regulatory experience over more than 13 years and recalls the main principles of the assessment, which were applied by ASN. These principles, which are formalized in the current regulation rules revised in 1999, are briefly listed hereunder: - It is based on avoiding and preventing any leaking on

Inbound medical tourism to Barbados: a qualitative examination of local lawyers' prospective legal and regulatory concerns.

Science.gov (United States)

Crooks, Valorie A; Cohen, I Glenn; Adams, Krystyna; Whitmore, Rebecca; Morgan, Jeffrey

2015-07-28

Enabled by globalizing processes such as trade liberalization, medical tourism is a practice that involves patients' intentional travel to privately obtain medical care in another country. Empirical legal research on this issue is limited and seldom based on the perspectives of destination countries receiving medical tourists. We consulted with diverse lawyers from across Barbados to explore their views on the prospective legal and regulatory implications of the developing medical tourism industry in the country. We held a focus group in February 2014 in Barbados with lawyers from across the country. Nine lawyers with diverse legal backgrounds participated. Focus group moderators summarized the study objective and engaged participants in identifying the local implications of medical tourism and the anticipated legal and regulatory concerns. The focus group was transcribed verbatim and analyzed thematically. Five dominant legal and regulatory themes were identified through analysis: (1) liability; (2) immigration law; (3) physician licensing; (4) corporate ownership; and (5) reputational protection. Two predominant legal and ethical concerns associated with medical tourism in Barbados were raised by participants and are reflected in the literature: the ability of medical tourists to recover medical malpractice for adverse events; and the effects of medical tourism on access to health care in the destination country. However, the participants also identified several topics that have received much less attention in the legal and ethical literature. Overall this analysis reveals that lawyers, at least in Barbados, have an important role to play in the medical tourism sector beyond litigation - particularly in transactional and gatekeeper capacities. It remains to be seen whether these findings are specific to the ecology of Barbados or can be extrapolated to the legal climate of other medical tourism destination countries.

Regulatory control of nuclear power plants

International Nuclear Information System (INIS)

2002-01-01

The purpose of this book is to support IAEA training courses and workshops in the field of regulatory control of nuclear power plants as well as to support the regulatory bodies of Member States in their own training activities. The target group is the professional staff members of nuclear safety regulatory bodies supervising nuclear power plants and having duties and responsibilities in the following regulatory fields: regulatory framework; regulatory organization; regulatory guidance; licensing and licensing documents; assessment of safety; and regulatory inspection and enforcement. Important topics such as regulatory competence and quality of regulatory work as well as emergency preparedness and public communication are also covered. The book also presents the key issues of nuclear safety such as 'defence-in-depth' and safety culture and explains how these should be taken into account in regulatory work, e.g. during safety assessment and regulatory inspection. The book also reflects how nuclear safety has been developed during the years on the basis of operating experience feedback and results of safety research by giving topical examples. The examples cover development of operating procedures and accident management to cope with complicated incidents and severe accidents to stress the importance of regulatory role in nuclear safety research. The main target group is new staff members of regulatory bodies, but the book also offers good examples for more experienced inspectors to be used as comparison and discussion basis in internal workshops organized by the regulatory bodies for refreshing and continuing training. The book was originally compiled on the basis of presentations provided during the two regulatory control training courses in 1997 and 1998. The textbook was reviewed at the beginning of the years 2000 and 2002 by IAEA staff members and consistency with the latest revisions of safety standards have been ensured. The textbook was completed in the

A relative variation-based method to unraveling gene regulatory networks.

Directory of Open Access Journals (Sweden)

Yali Wang

Full Text Available Gene regulatory network (GRN reconstruction is essential in understanding the functioning and pathology of a biological system. Extensive models and algorithms have been developed to unravel a GRN. The DREAM project aims to clarify both advantages and disadvantages of these methods from an application viewpoint. An interesting yet surprising observation is that compared with complicated methods like those based on nonlinear differential equations, etc., methods based on a simple statistics, such as the so-called Z-score, usually perform better. A fundamental problem with the Z-score, however, is that direct and indirect regulations can not be easily distinguished. To overcome this drawback, a relative expression level variation (RELV based GRN inference algorithm is suggested in this paper, which consists of three major steps. Firstly, on the basis of wild type and single gene knockout/knockdown experimental data, the magnitude of RELV of a gene is estimated. Secondly, probability for the existence of a direct regulation from a perturbed gene to a measured gene is estimated, which is further utilized to estimate whether a gene can be regulated by other genes. Finally, the normalized RELVs are modified to make genes with an estimated zero in-degree have smaller RELVs in magnitude than the other genes, which is used afterwards in queuing possibilities of the existence of direct regulations among genes and therefore leads to an estimate on the GRN topology. This method can in principle avoid the so-called cascade errors under certain situations. Computational results with the Size 100 sub-challenges of DREAM3 and DREAM4 show that, compared with the Z-score based method, prediction performances can be substantially improved, especially the AUPR specification. Moreover, it can even outperform the best team of both DREAM3 and DREAM4. Furthermore, the high precision of the obtained most reliable predictions shows that the suggested algorithm may be

A perspective on multi-user interaction design based on an understanding of domestic lighting conflict

NARCIS (Netherlands)

Niemantsverdriet, K.; van Essen, H.A.; Eggen, J.H.

2017-01-01

More and more connected systems are entering the social and shared home environment. Interaction with these systems is often rather individual and based on personal preferences, leading to conflicts in multi-user situations. In this paper, we aim to develop a perspective on how to design for

Causal structure of oscillations in gene regulatory networks: Boolean analysis of ordinary differential equation attractors.

Science.gov (United States)

Sun, Mengyang; Cheng, Xianrui; Socolar, Joshua E S

2013-06-01

A common approach to the modeling of gene regulatory networks is to represent activating or repressing interactions using ordinary differential equations for target gene concentrations that include Hill function dependences on regulator gene concentrations. An alternative formulation represents the same interactions using Boolean logic with time delays associated with each network link. We consider the attractors that emerge from the two types of models in the case of a simple but nontrivial network: a figure-8 network with one positive and one negative feedback loop. We show that the different modeling approaches give rise to the same qualitative set of attractors with the exception of a possible fixed point in the ordinary differential equation model in which concentrations sit at intermediate values. The properties of the attractors are most easily understood from the Boolean perspective, suggesting that time-delay Boolean modeling is a useful tool for understanding the logic of regulatory networks.

Architecture of the 99 bp DNA-six-protein regulatory complex of the lambda att site.

Science.gov (United States)

Sun, Xingmin; Mierke, Dale F; Biswas, Tapan; Lee, Sang Yeol; Landy, Arthur; Radman-Livaja, Marta

2006-11-17

The highly directional and tightly regulated recombination reaction used to site-specifically excise the bacteriophage lambda chromosome out of its E. coli host chromosome requires the binding of six sequence-specific proteins to a 99 bp segment of the phage att site. To gain structural insights into this recombination pathway, we measured 27 FRET distances between eight points on the 99 bp regulatory DNA bound with all six proteins. Triangulation of these distances using a metric matrix distance-geometry algorithm provided coordinates for these eight points. The resulting path for the protein-bound regulatory DNA, which fits well with the genetics, biochemistry, and X-ray crystal structures describing the individual proteins and their interactions with DNA, provides a new structural perspective into the molecular mechanism and regulation of the recombination reaction and illustrates a design by which different families of higher-order complexes can be assembled from different numbers and combinations of the same few proteins.