WorldWideScience

Sample records for regulatory activities travaux

  1. 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

  2. Travaux et publications

    OpenAIRE

    M. Deville

    2010-01-01

    Ouvrages L'Oratoire à Angers aux xviie et xviiie siècles, Paris, 1975, 251 p. Le pouvoir municipal à Angers de 1657 à 1789, 2 vol., Angers, 1984, 293 et 348 p. Articles « La mission du père Honoré de Cannes à Angers en 1684 », Annales de Bretagne et des Pays de l'ouest (en abrégé ABPO dans les articles suivants), 1974, p. 501-516. « L'élection des maires d'Angers au xviiie siècle », Travaux sur le xviiie siècle, Angers, 1978, p 4-18. « Les messagers de l'université d'Angers dans la seconde mo...

  3. 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.

  4. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  5. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    In this last part is reviewed international regulatory activities and bilateral agreements including two parts: concerning European atomic energy community with European commission proposal for a council directive setting up a community framework for nuclear safety, update of the nuclear illustrative programme in the context of the second strategic energy review, european commission recommendation on criteria for the export of radioactive waste and spent fuel to third countries and a communication on nuclear non-proliferation and the second part in relation with international atomic energy agency with a joint convention on the safety of spent fuel management and on safety of radioactive waste management (third review meeting). (N.C.)

  6. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    Different international regulatory activities are presented: recommendation on the protection of the public against exposure to radon in drinking water supplies, amendment to the legislation implementing the regulation on imports of agricultural products originating in third countries following the Chernobyl accident, resolution on the commission green paper towards a European strategy for the security of energy supply, declaration of mandatory nature of the international code for the safe carriage of packaged irradiated nuclear fuel, plutonium and high level radioactive wastes on board ships, adoption of action plan against nuclear terrorism. (N.C.)

  7. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2003-01-01

    Among international regulatory activities we find resolutions adopted by the IAEA general conference (2003), through European Union we find proposals for directives on nuclear safety and radioactive waste management, new regulation on the application of EURATOM safeguards, control of high activity sealed radioactive sources, recommendation on the protection and information of the public with regard to the continued contamination of certain wild food products following the Chernobyl accident, proposals for decisions authorizing the Member states to sign and ratify the Protocol to amend the Paris convention, p)proposals for a directive on environment liability with regard to the prevention and remedying of environmental damage, proposal of a regulation on the law applicable to non-contractual obligation. (N.C.)

  8. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    Concerning International regulatory activities, we find for the european atomic energy community an entry into force of the lisbon treaty (2009), it amends the treaty on European union and replaces the treaty establishing the European Community by the new treaty on the functioning of the European Union; more, an amendment to council regulation on the conditions governing imports of agricultural products originating in third countries following the accident at the Chernobyl nuclear power station (2009). About International atomic energy agency is reported an open-ended meeting of technical and legal experts for sharing of information on states implementation of the code of conduct on the safety and security of radioactive sources and its supplementary guidance on the import and export of radioactive sources (2010). (N.C.)

  9. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2012-01-01

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

  10. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2016-01-01

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

  11. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    The 48. session of the IAEA general conference was held in Vienna from 20 to 24 september 2004 with the participation of delegates from 125 members states and representatives of various international organisations. A number of resolutions were adopted by the conference in the following fields: nuclear safety, radiation, transport and waste safety. The general conference also adopted a resolution on measures to protect against nuclear terrorism. The Director General decided in 2003 to appoint a group of experts to explore and advise on issues related to nuclear liability. This group called the International Expert Group on Nuclear Liability (I.N.L.E.X.) consists of 20 experts members from nuclear power and non nuclear power countries and from shipping and non shipping states. It serves three major functions: to create a forum of expertise to explore and advise on issues related to nuclear liability; to enhance global adherence by nuclear and non nuclear states to an effective nuclear liability regime, inter alia, on the basis of the convention on supplementary compensation for nuclear damage and the annex thereto, the Vienna convention on civil liability for nuclear damage, the Paris convention on third party liability in the field of nuclear energy, the joint protocol relating to the application of the vienna convention and the paris convention and the amendments thereto; and to assist in the development and strengthening of the national nuclear liability legal frameworks in IAEA members states to protect the public and the environment and to enhance nuclear safety. The second part of international regulatory concerns a directive on public access to environmental information made by the European Parliament. (N.C.)

  12. Transparency of nuclear regulatory activities

    International Nuclear Information System (INIS)

    2007-01-01

    One of the main missions of nuclear regulators is to protect the public, and this cannot be completely achieved without public confidence. The more a regulatory process is transparent, the more such confidence will grow. Despite important cultural differences across countries, a number of common features characterise media and public expectations regarding any activity with an associated risk. A common understanding of transparency and main stakeholders' expectations in the field of nuclear safety were identified during this workshop, together with a number of conditions and practices aimed at improving the transparency of nuclear regulatory activities. These conditions and practices are described herein, and will be of particular interest to all those working in the nuclear regulatory field. Their implementation may, however, differ from one country to another depending on national context. (authors)

  13. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

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

  14. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

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

  15. Organisation des travaux ST-CV

    CERN Document Server

    Martel, C; CERN. Geneva. ST Division

    2003-01-01

    Débutée il y a deux ans, la phase de construction des installations de refroidissement du LHC a atteint en 2003 son apogée. De nombreux autres projets sont également gérés par le groupe dans divers secteurs du laboratoire. La spécificité du groupe est de réaliser des installations complexes impliquant des spécificités diverses telles qu’aéraulique, hydraulique, électrique, etc. Pour faire face à ces demandes la section travaux du groupe ST CV a adopté une structure capable de réaliser ces divers projets avec un minimum de personnel. La première partie de ce document décrit l’organisation de la section travaux ST CV. Dans une deuxième partie, les auteurs dressent un état des lieux des chantiers par projet en décrivant plus particulièrement les activités dans les domaines du traitement d’air et de refroidissement par eau.

  16. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    This part gathers the national legislative and regulatory activities. The subjects tackled are as follow: radiological protection (Belgium), transport of radioactive materials (Belgium, France), general legislation (Brazil, Ireland, Republic of Moldova, Serbia, Turkey), third part liability (Japan), radioactive waste management (Korea, Romania, Slovenia, Usa), regime of radioactive materials (Romania), organisation and structure (Switzerland), regime of nuclear installations (Usa), regulations on nuclear trade (Usa). (N.C)

  17. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2015-01-01

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

  18. Organization of nuclear regulatory activities

    International Nuclear Information System (INIS)

    Blidaru, Valentin

    2008-01-01

    The paper presents the structure, missions and organizational aspects of the CNCAN, the National Commission for the control of nuclear activities in Romania. The paper addresses the following main issues: 1.General aspects; 2.Organizational structure of the NRA in Romania; 3.General description of the Division for Nuclear Safety Assessments; 4.Specific activities; 5.Regulatory approaches and practices. Under the title of 'General aspects' the following three basic statements are highlighted: 1.CNCAN is a governmental organization responsible for the development of the regulatory framework, the control of its implementation and the licensing of nuclear facilities; 2.CNCAN is the national authority competent in exercising the regulatory activity, authorization and control in the nuclear field provided by the law No. 111/ 1996 republished in 1998; 3.The Commission exercises its functions independently of the ministries and other authorities of the public control administration being subordinated to the Romanian Government. The organizational structure is as follows: - President, the Managerial Council and the Advisory Council coordinating the four General Divisions that are responsible for: - Nuclear Safety with Division of Nuclear Safety Assessment and Division of Nuclear Objectives Surveillance; - Radiological Safety with Division of Radiological Safety Assessment and Division of Operational Radiation Protection; - Surveillance of Environmental Radioactivity with Division of Assessment and Analysis and Division of National Network; - Development and Resource with the Division of Economy and Division of Human Resources. In addition under direct coordination of the President operate the Division of Radiation Protection, Transport and Radioactive Waste and the Division of International Cooperation and Communication. Specific activities are listed describing among others the issues of: - Safety of nuclear installation; - Evaluation relating to licensing of nuclear

  19. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2011-01-01

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

  20. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following National legislative and regulatory activities: 1 - Argentina: Organisation and structure; 2 - France: Radioactive waste management (Act No. 2016-1015 of 25 July 2016 specifying the procedures for creating a reversible deep geological repository for long-lived medium and high-level radioactive waste), Liability and compensation (Decree No. 2016-333 of 21 March 2016 implementing Article L. 597-28 of the French Environmental Code and relating to third party liability in the field of nuclear energy; Ministerial Order of 19 August 2016 listing the sites benefiting from a reduced amount of liability pursuant to decree No. 2016-333 of 21 March 2016 implementing Article L. 597-28 of the French Environmental Code and relating to third party liability in the field of nuclear energy), Nuclear facilities (Decree No. 2016-846 of 28 June 2016 related to the modification, final shutdown and decommissioning of basic nuclear installations, and to subcontracting); 3 - Germany: Nuclear trade - including non-proliferation (Amendments to the Foreign Trade Act and the Foreign Trade Ordinance (2015)), Radioactive waste management (Act on the Organisational Restructuring in the Field of Radioactive Waste Management (2016); Final report of the Commission to Review the Financing for the Phase-out of Nuclear Energy; Draft Bill of an Act on the Reorganisation of the Responsibility of Nuclear Waste Disposal (2016)); 4 - Lithuania: Nuclear safety and radiological protection (including nuclear emergency planning), Nuclear security (Physical security of sources of ionising radiation), Radioactive waste management, Licensing and regulatory infrastructure (Enforcement measures); 5 - Luxembourg: Radioactive waste management (Agreement between the Grand Duchy of Luxembourg and the Kingdom of Belgium on the Management and Final Disposal of the Radioactive Waste of the Grand Duchy of Luxembourg on the Territory of the Kingdom of Belgium, signed on 4 July 2016); 6

  1. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2015-01-01

    This section treats of the following National legislative and regulatory activities: 1 - Australia: General legislation - Bill to amend the Australian Radiation Protection and Nuclear Safety Act 1998; 2 - France: General legislation - Law No. 2015-992 of 17 August 2015 on the energy transition for green growth; ASN Report on the state of nuclear safety and radiation protection in France in 2014; 3 - Germany: Radioactive waste management - First Ordinance to amend the 2005 Gorleben Development Freeze Ordinance (2015); 4 - Greece: Radioactive waste management - Joint Ministerial Decision establishing the national policy on the management of spent fuel and radioactive waste; 5 - Lithuania: Nuclear safety and radiological protection - Revised requirements for modifications, Plan for enhancement of nuclear safety, New requirements for the commissioning of nuclear power plants, Revised requirements regulating the provision of information on abnormal events; Radioactive waste management - Revised requirements for acceptance criteria for near surface repository; Nuclear security - Revised requirements for physical protection; 6 - Romania: Licensing and regulatory infrastructure - Government Decision No. 600/2014 for approval of National Nuclear Safety and Security; International co-operation - Government Decision No. 525/2014 for approval of the Co-operation Agreement on the radioactive waste management between the French National Radioactive Waste Management Agency (ANDRA) and Nuclear Agency and Radioactive Waste (ANDR) Strategy; Memorandum of Understanding for Co-operation and Exchange of Information in Nuclear Regulatory Matters between the National Commission for Nuclear Activities Control (CNCAN) of Romania and the President of National Atomic Energy Agency (PAA) of Poland; Government Decision No. 540/2015 for approval of the Agreement between the Government of Romania and the Government of the People's Republic of China regarding co-operation in the peaceful

  2. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2001-01-01

    These columns treat of the legislative and regulatory activities of different OECD countries: Australia (environment protection and biodiversity conservation act and regulations, 1999-2000); Bulgaria (basic standards for radiation protection, 2000); France (decree on the standard tax charged on polluting activities due from operators of installations classified for environmental protection purposes, 2000; amendment of the orders on the transport of dangerous goods by road and by rail, 2000); Georgia (law on nuclear and radiation safety, 1998); Germany (amendments to nuclear legislation implementing EURATOM directives, 2000; amendment to the nuclear third party liability provisions of the atomic energy act, 2001; amendment to the foreign trade ordinance, 2000; ordinance on the treatment of foodstuffs with radiation, 2000; general administrative regulations on radioactivity limits in food and feeds); Ireland (European communities regulations on foodstuffs treated with ionizing radiations, 2000); Japan (law for nuclear sitting area development, 2000; Republic of Korea (amendments to the act on compensation for nuclear damage, 2001); Latvia (act on radiation safety and nuclear safety, 2000); Lithuania (resolution approving the decommissioning program for Unit 1, Ignalina NPP, 2001); Luxembourg (grand-ducal regulations on the protection of the public against the risks resulting from ionizing radiation, 2000; grand-ducal regulations relating to foods and food ingredients treated with ionizing radiation, 2000); Mexico (norm regarding selection, qualification and training requirements for staff of a NPP, 2000; norm regarding solid residue as radioactive waste, 2000); Mongolia (law on nuclear weapons free status and its implementing resolution, 2000); Netherlands (amendment to the nuclear energy act, 2000); Norway (act on radiation and use of radiation, 2000); Pakistan (nuclear authority ordinance, 2001); Poland (atomic energy act, 2000); Spain (royal decree on activities

  3. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2013-01-01

    This section reviews the recent National legislative and regulatory activities: Algeria (Establishment of a nuclear security centre); Armenia (Amendment to the Law of the Republic of Armenia on the Safe Utilization of Atomic Energy for Peaceful Purposes); Brazil (creation of a Support Centre for Safety and Radiation Protection - Centro de Apoio a Seguranca Fisica Nuclear e Radiologica - CENASF); Canada (enacting of the Nuclear Terrorism Act,4 which amends the Criminal Code, creating four new Criminal Code offences related to nuclear terrorism; proposal to replace the existing Nuclear Liability Act with the increase of the amount of compensation available to address civil nuclear damage); France (National plan for the management of radioactive materials and waste - PNGMDR; Law No.2013-580 of 4 July 2013 authorising approval of the agreement between France and Monaco on the management of Monegasque radioactive waste in the French territory; Decree No.2013-675 of 25 July 2013 publishing an agreement of co-operation between France and Saudi Arabia for the development of nuclear energy for peaceful purposes); Germany (Act for retrieving radioactive waste from and decommissioning the Asse II Mine); Greece (Decree transposing Council Directive 2011/70/Euratom); Ireland (Adoption of European Communities Regulations on Carriage of Dangerous Goods by Road and Use of Transportable Pressure Equipment); Luxembourg (Transposition of Council Directive 2011/70/Euratom of 19 July 2011 establishing a Community framework for the responsible and safe management of spent fuel and radioactive waste); Poland (New requirements for employees concerning radiological protection; New detailed requirements for nuclear facility siting, design, commissioning and operation, organisational unit commissioning, periodical safety assessment, decommissioning and fund contributions; New regulation on subsidies related to nuclear safety and radiological protection; New requirements on transparency of

  4. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2013-01-01

    - International co-operation: Law ratifying the agreement between the International Atomic Energy Agency and Greece in the area of education and training; - Nuclear safety and radiological protection: Ministerial decision establishing requirements for nuclear safety and regulatory control of research reactors; Moldova - General legislation: New comprehensive law governing nuclear and radiological activities; United States - Issuance of the 'Strategy for the Management and Disposal of Used Nuclear Fuel and High-Level Radioactive Waste'; - Ongoing activities: The Blue Ribbon Commission noted the need for near-term actions that can lay the groundwork for the next generation of nuclear waste policies and programmes included in its recommendations; - Physical protection of by-product material final rulemaking: On 19 March 2013, the NRC published a final rule amending its regulations to establish security requirements for the use and transport of category 1 and category 2 quantities of radioactive material; - Update on the NRC's response to the events at the Fukushima Daiichi nuclear site regarding filtered vents and consideration of economic consequences

  5. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2017-01-01

    This section treats of the following National legislative and regulatory activities: 1 - Algeria, Nuclear safety and radiological protection, Executive Decree No. 17-126 of 27 March 2017; 2 - Belgium, Liability and compensation, Law of 7 December 2016 modifying the law of 22 July 1985 on third party liability in the field of nuclear energy; 3 - Canada, Liability and compensation, Ratification by Canada of the Convention on Supplementary Compensation for Nuclear Damage; 4 - France, Radioactive waste management: Decree No. 2017-231 of 23 February 2017 implementing Article L. 542-1-2 of the French Environmental Code (Code de l'environnement) and setting out the provisions of the National Radioactive Material and Waste Management Plan; and Order of 23 February 2017 implementing Decree No. 2017-231 of 23 February 2017 implementing Article L. 542-1-2 of the French Environmental Code setting out the provisions of the National Radioactive Material and Waste Management Plan; Liability and compensation: Order of 10 November 2016 amending the Appendix to the Order of 19 August 2016, setting the list of reduced liability amount sites pursuant to Decree No. 2016-333 of 21 March 2016 implementing Article L. 597-28 of the Environmental Code and relating to third party liability in the nuclear energy field; International co-operation: Decree No. 2016-1225 of 16 September 2016 making public the Protocol to the Co-operation Agreement between the Government of the French Republic and the Government of the Hashemite Kingdom of Jordan for the Development of the Pacific Uses of Nuclear Energy, signed in Paris on 27 August 2008; 5 - Germany, Transport of radioactive materials: New Versions of Ordinances on the Transport of Dangerous Goods (2017); Radioactive Waste Management: Act on the Reorganisation of the Responsibility of Nuclear Waste Disposal (2017); 6 - Lithuania, Nuclear security: Cyber security; Nuclear installations: Free release criteria of buildings and site of nuclear

  6. The conduct of regulatory activities

    International Nuclear Information System (INIS)

    Wright, H.A.

    1975-01-01

    The main emphasis is placed on the legal responsibility of the utility in UK to build and operate its plant to avoid any nuclear hazard. The regulatory practices have endeavoured to inculcate a proper emphasis towards safety by the people who comprise the management of the utility, and to avoid any erosion of their legal responsibility as the best and possibly only practical means to achieve adequate safety standards. (orig./HP) [de

  7. Regulatory Activities for Licensee's Safety Culture

    International Nuclear Information System (INIS)

    Choi, Young Sung; Choi, Kwang Sik

    2008-01-01

    Weaknesses in safety culture have contributed to a number of incidents/accidents in the nuclear and other high hazard sectors worldwide in the past. These events have fostered an increasing awareness of the need for licensees to develop a strong safety culture to support successful and sustainable nuclear safety performance. Regulatory bodies are taking a growing interest in this issue, and several are actively working to develop and implement approaches to maintaining regulatory oversight of licensee safety culture. However, these approaches are not yet well-established, and it was considered prudent to share experiences and developing methodologies in order to disseminate good practices and avoid potential pitfalls. This paper presents the findings, conclusions and recommendations of international meetings and other countries' activities on safety culture and gives some suggestions for regulators to consider when planning regulatory oversight for licensee's safety culture

  8. SELF-REGULATORY ABILITIES IN PROFESSIONAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    G V Ozhiganova

    2016-12-01

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

  9. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    Belarus: general legislation with amendments to laws on the use of atomic energy (2009) and criminal law on acts concerning the use of radioactive sources and administrative law for non criminal violations of radiation safety requirement (2009). Egypt: general legislation with law on activities in the nuclear and radiation field (2010). France: radioactive waste management with a decree establishing a committee on industrial co-ordination of radioactive waste (2010) and third part liability with a law on the recognition and indemnification of victims of nuclear tests conducted by France (2010). Germany: general legislation with a tenth amendment to the atomic energy act (2010), and act on environmental impact assessment (2009) concerning organisation and structure we find a revised version of statutes of the Radiation Protection Commission (2009), about radiation protection we find an act on the protection against non-ionizing radiation (2009), and for transport of radioactive materials we have an ordinance on the international transport of dangerous goods by road (2009). Ireland: In radiation protection we have an order to amend Regulations on active implantable medical devices (2010). Italy: general legislation we have a decree setting out rules for the sitting, construction and operation of nuclear installations (2010). Romania: general legislation with a law on the reorganisation of public authorities (2009). Slovak Republic: general legislation with an amendment of the atomic act (2009). spain: radioactive waste management with a law regulation limited investment companies quoted on the real estate market (2009). Ukraine: general legislation with an overview of recent amendments to laws in the field of nuclear energy (2009). (N.C.)

  10. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

    These columns summarize the recent changes made in the nuclear legislation and regulation of OECD countries: Argentina: Reorganization of the National Atomic Energy Commission (2001); Canada: Order aiming to increase security at major nuclear installations (2001); France: Establishment of the French Agency for Environmental Health Safety and the Institute for the Protection of Nuclear Safety (2001). Amendment of the Decree on the Holding Company of the Atomic Energy Commission (2001). Decree on the Special Commission for Major Nuclear Installations Classified as Secret (2001).Ordinance on the Implementation of EU Directives in the Field of Protection against Ionising Radiation (2001). Decree on Information of the Public (2001). Decree governing the Safety and Radiation Protection of Nuclear Installations and Activities used for Defence Purposes (2001). Order on Postal Deliveries of Radioactive Materials (2001). Order on the Carriage of Dangerous Goods by Road ('ADR Order') (2001). Order on the Transport of Dangerous Goods by Rail ('RID Order') (2001). Germany: Agreement on the phase-out of nuclear energy (2001). Ordinance implementing Euratom Directives on Radiation Protection (2001). Greece: Radiation Protection Regulations (2001). Italy: Amendment of the Decree implementing the Euratom basic radiation protection standards (2001) Implementation of the European Directive on the Quality of Water Intended for Human Consumption (2001). JAPAN: Revision of the Nuclear Disaster Prevention Guidelines (2000). Republic of Korea: Amendments to the Act on Compensation for Nuclear Damage (2001). Lithuania: Regulations for the Classification of Legal Acts Regulating Nuclear Safety (2001); Hygiene Standard 'Radiation Safety in Nuclear Power Plants' (2001). Guidelines governing the Procedure on Radiological Monitoring and Limitation of Releases of Radionuclides into the Environment from Nuclear Facilities (2001). Law on the Decommissioning Fund for the Ignalina Nuclear Power

  11. Introduction : L'étendue des travaux de Robert Buijtenhuis

    NARCIS (Netherlands)

    Binsbergen, van W.M.J.; Konings, P.J.J.; Binsbergen, van W.M.J.; Hesseling, G.S.C.M.

    2000-01-01

    Cet ouvrage présente onze contributions rédigées par des africanistes qui ont collaboré étroitement avec l'anthropologue politique néerlandais Robert Buijtenhuijs et ont été influencés par ses travaux et sa personnalité. Le livre est un hommage à un auteur qui a été productif dans beaucoup de

  12. Resenha de: Recueil des travaux historiques de Ferdinand Lot

    Directory of Open Access Journals (Sweden)

    Eurípedes Simões de Paula

    1968-03-01

    Full Text Available RECUEIL DES TRAVAUX HISTORIQUES DE FERDINAND LOT. Tome premier. Coleção "Hautes Études Médievales et Modernes". Centre de Recherches d'Histoire et de Philologie de la IVe Section de l'École Pratique des Hautes Études. Prefácio de Ch. Samaran e biografia por I. Vildé-Lot e M. Mahn-Lot. Publicado com o concurso do Centre National de la Recherche Scientifique. Genebra, Librairie Droz e Paris, Librairie Minard. In-89, XVIII -I- 780 pp

  13. Argentina's regulatory body: its communication activities

    International Nuclear Information System (INIS)

    Cesario, Pablo A.; Terigi, Gabriel E.

    2008-01-01

    Full text: The Nuclear Regulatory Authority of Argentina (ARN) is empowered to regulate and control the nuclear activity with regard to radiation and nuclear safety, physical protection and nuclear non-proliferation issues. It must also advise the Executive on issues under its purview. The objective of the Nuclear Regulatory Authority is to establish, develop and enforce a regulatory system applicable to all nuclear activities carried out in Argentina. Two of the goals of this regulatory system are to provide an appropriate standard of protection for individuals against the harmful effects of ionizing radiation, and to maintain a reasonable degree of radiological and nuclear safety in the nuclear activities performed in Argentina. The responsibility of the radiation protection community in performing the tasks to accomplish this goals is twofold. On one hand, it must ensure a high technical quality in performing these functions. It must also provide information on its activities which has to be accurate, comprehensive and understandable. The way a society understands the concept of 'risk' needs to be kept in mind. Risk perception is the subjective judgment that people make about the characteristics and severity of a risk. Cultural theory refers to theories of risk perception that focus on culture, rather than individual psychology as an explanation for differences in risk judgments. It is widely agreed that trust is a key factor in influencing people's perceptions of risk. It is understood there are two main ways trust may impact in risk perceptions: an activity is perceived as more risky if the people or agencies managing it are perceived as untrustworthy; and information presented by trusted sources is given more credibility than information from untrusted sources. One of the primary purposes of ARN's Communication Program is to provide a means whereby those engaged in radiation protection activities may communicate more readily with each other and the public and

  14. Comprendre le risque routier professionnel par l’analyse de l’activité : l’exemple des conducteurs de travaux Understanding occupational road risk by analyzing the activity: The example of project and site supervisors Comprender el riesgo laboral en carreteras a través del análisis de la actividad. El ejemplo de los conductores de trabajos

    Directory of Open Access Journals (Sweden)

    Justine Forrierre

    2010-05-01

    Full Text Available Cet article présente les résultats d’une recherche portant sur le risque routier professionnel rencontré par des travailleurs dont la conduite n’est pas le métier mais qui se déplacent fréquemment : les conducteurs de travaux de chantiers de travaux publics. En adoptant le point de vue de l’activité, nous montrons que la compréhension et la prévention de ce risque nécessitent de connaître et de comprendre l’activité de travail. En effet, l’activité de conduite est une activité de travail et le risque qui lui est lié est un risque au travail. Pour prévenir ce dernier, il est donc nécessaire de dépasser la simple approche comportementale de l’activité de conduite et de prendre en considération l’ensemble des déterminants de l’activité de travail qui font que le conducteur de travaux se déplace et prend des risques sur la route. Nous retiendrons que les aspects organisationnels (prescription, organisation de la production, politique de ressources humaines, matériel (véhicule, outils de communication et interentreprises (relationnel client affectent l’activité de conduite et que la prévention du risque routier nécessite donc une approche globale (aux niveaux individuel et collectif, dans l’entreprise et avec les entreprises extérieures qui touche à ces différents domaines.This paper presents the results of a study on the occupational road risk of workers for whom driving is not their job but who drive frequently: Public Works site supervisors. Using the activity’s theoretical framework, we show that in order to understand and prevent this risk, the work activity needs to be known and understood. In fact, driving is a work activity and the related risk is an occupational risk. To prevent the latter, it is necessary to go beyond the simple behavioural driving activity approach and consider all the determinants of the work activity that cause the work supervisor to drive and take risks on the road

  15. Regulatory effects of fisetin on microglial activation.

    Science.gov (United States)

    Chuang, Jing-Yuan; Chang, Pei-Chun; Shen, Yi-Chun; Lin, Chingju; Tsai, Cheng-Fang; Chen, Jia-Hong; Yeh, Wei-Lan; Wu, Ling-Hsuan; Lin, Hsiao-Yun; Liu, Yu-Shu; Lu, Dah-Yuu

    2014-06-26

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin)-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase)-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

  16. Regulatory Effects of Fisetin on Microglial Activation

    Directory of Open Access Journals (Sweden)

    Jing-Yuan Chuang

    2014-06-01

    Full Text Available Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO production, and inducible nitric oxide synthase (iNOS expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

  17. Activities relating to PSA in the regulatory process

    International Nuclear Information System (INIS)

    Campbell, J.F.; Grint, G.C.

    1994-01-01

    In addition to the IAEA activities concerning the use of PSA in the regulatory process there are two other international initiatives in this area by the European Commission and the OECD's Committee for Nuclear Regulatory Authorities (CRNA). The paper gives a brief outline of these activities as well as introducing an update on the regulatory use of PSA in the UK. 3 refs, 3 tabs

  18. Avancement des travaux électriques LHC point 1

    CERN Document Server

    Delidais, M

    2001-01-01

    Après la première phase d'analyse des principes de la distribution en électricité de la zone 1 du LHC et de l'expérience ATLAS, les études sont à présent orientées vers la définition des implantations des principaux équipements tels que transformateurs, tableaux basse tension, alimentations statiques de sécurité, ainsi que vers la détermination du cheminement des câbles dans les ouvrages de surface et à travers les ouvrages souterrains USA15, UX15 et les galeries de liaison. Les études des services généraux sont également menées pour les bâtiments de surface qui seront mis prochainement à disposition par le génie civil, en particulier la station de refroidissement SF1 ainsi que le bâtiment SUX1 pour lesquels les travaux d'installation devraient débuter sous peu pour être achevés dans le premier trimestre 2001.

  19. Upgrading of regulatory activities in Belarus

    International Nuclear Information System (INIS)

    Rozdyalovskaya, L.F.; Shabanov, V.V.

    1998-01-01

    Upgrading of the National regulatory regime in the Republic of Belarus started in fact in 1992 after the Interregional Nuclear and Radiation Safety Inspectorate had been established in the Gostekhnadzor of Belarus. In this connection, the Gostekhnadzor was transformed into the Gospromatomnadzor - the State Committee for Supervision of Industrial and Nuclear Safety. In 1993, by special decrees issued by the Council of Ministers the Gospromatomnadzor was designated a National Competent Body responsible for nuclear materials. Now the Committee is part of the Ministry for Emergencies. In the Committee, the issues of nuclear and radiation safety are dealt with by 6 departments among which the Department for Nuclear and Radiation Safety Regulation and the Interregional Nuclear and Radiation Safety inspectorate play major role. The created regulatory structure makes it possible to fully perform the control of situation at nuclear- and radiation-hazardous facilities and take adequate measures aimed at strengthening their safety. The priority directions of regulatory work by the Promatomnadzor include development and revision of regulations governing radiation and nuclear safety and upgrading of the training procedure to enhance the radiation safety and technical knowledge of the Promatomnadzor staff. (author)

  20. Regulatory control of maintenance activities in Argentine nuclear power plants

    International Nuclear Information System (INIS)

    Calvo, J.C.; Caruso, G.

    2000-01-01

    The main maintenance objective is to assure that the safety features of structures, components and systems of nuclear power plants are kept as designed. Therefore, there is a direct relationship between safety and maintenance. Owing to the above mentioned, maintenance activities are considered a relevant regulatory issue for the Argentine Nuclear Regulatory Authority (ARN). This paper describes the regulatory control to maintenance activities of Argentine nuclear power plants. It also addresses essential elements for maintenance control, routine inspections, special inspections during planned outages, audits and license conditions and requirements. (author)

  1. Regulatory Activities to the Natural Hazard

    International Nuclear Information System (INIS)

    Choi, Kangryong; Jung, Raeyoung

    2008-01-01

    The safety of the Nuclear Power Plants(NPPs) against the natural hazards has been investigated focused on earthquake and tsunami. Since the mass media and general people have high interests on nuclear safety whenever the natural hazards occur, earthquake and tsunami are not only technical safety concern, but also psychological issues in terms of public acceptance of nuclear energy. The Korean peninsula has been considered as a safe zone compared to neighboring countries against natural hazard, but the historical documents which state severely damaged events due to the strong earthquake make US paying careful attention to assure the safety against natural phenomenon. The potential and characteristics of earthquake and tsunami have been examined, and the status of seismic and tsunami safety of the NPPs in Korea is described. the follow-up action after disastrous huge earthquake and tsunami occurred in neighboring countries is summarized as well. The assessment results show that the NPPs in Korea are well designed, constructed and maintained with certain amount of safety margin against natural hazards, and the utility and the regulatory body are continuously doing an effort to enhance the safety with consideration of lessons learned from big events in other countries

  2. Regulatory Effects of Fisetin on Microglial Activation

    OpenAIRE

    Chuang, Jing-Yuan; Chang, Pei-Chun; Shen, Yi-Chun; Lin, Chingju; Tsai, Cheng-Fang; Chen, Jia-Hong; Yeh, Wei-Lan; Wu, Ling-Hsuan; Lin, Hsiao-Yun; Liu, Yu-Shu; Lu, Dah-Yuu

    2014-01-01

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS...

  3. Case law. Administrative decisions. National legislative and regulatory activities. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2007-01-01

    (Romania), act on administrative and property management of the civilian nuclear energy sector (Russian Federation), amendment of the atomic act (Slovak Republic), regulation on monitoring of radioactivity (Slovenia), regulations on the contents of the annual public report, regulations on the keeping of records, regulations on safety standards and regulatory practices (South Africa), amendment to the act and ordinance on nuclear activities (Sweden), council directive on the supervision and control of shipments of radioactive waste and spent fuel (European Union). (N.C.)

  4. Regulatory oversight of maintenance activities at nuclear power plants

    International Nuclear Information System (INIS)

    Pape, M.

    1997-01-01

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

  5. Cis-regulatory RNA elements that regulate specialized ribosome activity.

    Science.gov (United States)

    Xue, Shifeng; Barna, Maria

    2015-01-01

    Recent evidence has shown that the ribosome itself can play a highly regulatory role in the specialized translation of specific subpools of mRNAs, in particular at the level of ribosomal proteins (RP). However, the mechanism(s) by which this selection takes place has remained poorly understood. In our recent study, we discovered a combination of unique RNA elements in the 5'UTRs of mRNAs that allows for such control by the ribosome. These mRNAs contain a Translation Inhibitory Element (TIE) that inhibits general cap-dependent translation, and an Internal Ribosome Entry Site (IRES) that relies on a specific RP for activation. The unique combination of an inhibitor of general translation and an activator of specialized translation is key to ribosome-mediated control of gene expression. Here we discuss how these RNA regulatory elements provide a new level of control to protein expression and their implications for gene expression, organismal development and evolution.

  6. Comment les travaux de recherche subventionnés par le CRDI ont ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    25 oct. 2010 ... Un engagement à long terme s'impose si l'on veut opérer des changements salutaires et durables dans les pays en développement. Depuis 1970, le CRDI soutient des travaux de recherche qui poursuivent ce but précis. Pour marquer son 40e anniversaire, le Centre s'est penché sur quelques-uns des ...

  7. The medical dictionary for regulatory activities (MedDRA).

    Science.gov (United States)

    Brown, E G; Wood, L; Wood, S

    1999-02-01

    The International Conference on Harmonisation has agreed upon the structure and content of the Medical Dictionary for Regulatory Activities (MedDRA) version 2.0 which should become available in the early part of 1999. This medical terminology is intended for use in the pre- and postmarketing phases of the medicines regulatory process, covering diagnoses, symptoms and signs, adverse drug reactions and therapeutic indications, the names and qualitative results of investigations, surgical and medical procedures, and medical/social history. It can be used for recording adverse events and medical history in clinical trials, in the analysis and tabulations of data from these trials and in the expedited submission of safety data to government regulatory authorities, as well as in constructing standard product information and documentation for applications for marketing authorisation. After licensing of a medicine, it may be used in pharmacovigilance and is expected to be the preferred terminology for international electronic regulatory communication. MedDRA is a hierarchical terminology with 5 levels and is multiaxial: terms may exist in more than 1 vertical axis, providing specificity of terms for data entry and flexibility in data retrieval. Terms in MedDRA were derived from several sources including the WHO's adverse reaction terminology (WHO-ART), Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART), International Classification of Diseases (ICD) 9 and ICD9-CM. It will be maintained, further developed and distributed by a Maintenance Support Services Organisation (MSSO). It is anticipated that using MedDRA will improve the quality of data captured on databases, support effective analysis by providing clinically relevant groupings of terms and facilitate electronic communication of data, although as a new tool, users will need to invest time in gaining expertise in its use.

  8. 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.

  9. Regulatory Activities on Civil Nuclear Safety Equipment in China

    International Nuclear Information System (INIS)

    Gaoshang, Lu; Choi, Kwang Sik

    2011-01-01

    It is stipulated in IAEA Fundamental Safety Principles (SF1) that the fundamental safety objective is to protect people and the environment from harmful effects of ionizing radiation. The fundamental safety objective applies for all facilities and activities and for all stages over the lifetime of a facility or radiation source, including planning, sitting, design, manufacturing, construction, commissioning and operation, as well as decommissioning and closure. So, according to the requirement, the related activities such as design, manufacturing, installation and non-destructive test that conducted on civil nuclear equipment should be well controlled by the vendors, the owner of the nuclear power plants and the regulatory body. To insure the quality of those equipment, Chinese government had taken a series of measures to regulate the related activities on them

  10. 76 FR 18165 - Request for Public Comments Concerning Regulatory Cooperation Activities That Would Help...

    Science.gov (United States)

    2011-04-01

    ... DEPARTMENT OF COMMERCE International Trade Administration Request for Public Comments Concerning Regulatory Cooperation Activities That Would Help Eliminate or Reduce Unnecessary Regulatory Divergences in... ``Help'' tab.) All comments and recommendations submitted in response to this notice will be made...

  11. The Report on Activities of the Nuclear Regulatory Authority of the Slovak Republic. Annual Report 2012

    International Nuclear Information System (INIS)

    2013-04-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2012 is presented. These activities are reported under the headings: Foreword; (1) Legislative activities; (2) Regulatory Activities; (3) Nuclear safety of nuclear power plants; (4) Stress tests on the nuclear power plants; (5) Nuclear Materials in SR; (6) Building Authority; (7) Emergency planning and preparedness; (8) International activities; (9) Public communication; (10) Nuclear Regulatory Authority of the Slovak Republic; (11) Attachments; (12) Abbreviations used.

  12. Knowledge Management Tools in Application to Regulatory Body Activity

    International Nuclear Information System (INIS)

    Volkov, E.

    2016-01-01

    Full text: The paper presents the application of knowledge management tools to regulatory authority activity. Knowledge management tools are considered a means for improving the efficiency of regulator activities. Three case studies are considered: 1. a knowledge management audit procedure in the regulator (tools for knowledge management audit application, results and the audit outcomes); 2. the development of a guide to identify causes of discrepancies and shortcomings revealed during inspections in NPP maintenance (ontologies of factors influencing on a maintenance quality and causes of discrepancies and shortcoming development); 3. the development of a knowledge portal for regulator (regulator needs which could be covered by the portal, definition and basic function of the portal, it’s functioning principles, development goals and tasks, common model, development stages). (author)

  13. Argentine influence on regulatory activities in Latin America

    International Nuclear Information System (INIS)

    Palacios, Elias

    1998-01-01

    An analysis of the nuclear regulatory systems and the nuclear regulations of many Latin American countries shows a substantial influence of the Argentine regulatory structure. This influence is attributed to the early Argentine development of a regulatory and control organization, the teaching of regional training courses and the advice of Argentine experts to Latin-American governments

  14. Implementation of a Quality Management System in regulatory inspection activities

    International Nuclear Information System (INIS)

    Pires do Rio, Monica; Ferreira, Paulo Roberto; Cunha, Paulo G. da; Acar, Maria Elizabeth

    2005-01-01

    The Institute for Radioprotection and Dosimetry - IRD -, of the Brazilian National Nuclear Energy Commission, CNEN, started in 2001, the implementation of a quality management system (SGQ), in the inspection, testing and calibration activities. The SGQ was an institutional guideline and is inserted in a larger system of management of the IRD started in 1999, with the adoption of the National Quality Award criteria - PNQ, within the Project for Excellence in Technological Research of Associacao Brasileira das Instituicoes de Pesquisas Tecnologicas - ABIPTI (Brazilian Association of Technological Research institutions). The proposed quality management system and adopted at the IRD was developed and implemented in accordance with the requirements of NBR ISO/IEC 17025 - General requirements for the competence of testing and calibration laboratories, and ISO/IEC 17020 - General criteria for operation of various types of bodies performing inspections. For regulatory inspection activities, the quality system was implemented on three program inspection services of radiological protection led, respectively, by clinics and hospitals that operate radiotherapy services; industries that use nuclear gauges in their control or productive processes and power reactor operators (CNAAA) - just the environmental part. It was formed a pioneering team of inspectors for standardizing the processes, procedures and starting the implementation of the system in the areas. This work describes the implementation process steps, including difficulties, learning and advantages of the adoption of a quality management system in inspection activities

  15. Regulatory activities in the area of fuel safety and performance

    International Nuclear Information System (INIS)

    Viktorov, A.; Couture, M.

    2005-01-01

    Generic Action Item 94G02 'Impact of Fuel Bundle Condition on Reactor Safety' in many ways determined the present priorities in regulatory activities related to fuel performance. As one of the closure criteria it required that all licensees establish 'an effective formal and systematic process for integrating fuel design, fuel and channel inspection, laboratory examination, research, operating limits and safety analysis'. To date, such a process has been, to a large extent, put in place by all licensees. To assure that such processes remain operational and effective after the GAI closure, CNSC required, through S-99, to report annually on fuel performance and major activities in the fuel safety area. The scope of reported information has been defined to allow CNSC staff evaluation of key events and trends in fuel performance. To compliment reporting by the industry, CNSC staff has conducted targeted inspections of fuel compliance programs at all sites. Combined together, these activities provide the regulator with the confidence that CANDU fuel is robust and operates with safety margins. The scrutiny, to which fuel performance has been subjected lately, has allowed identification of certain programmatic weaknesses and gaps in the knowledge concerning the fuel behaviour under various conditions. It has become apparent that top-level strategies for assessment of fuel performance may have been inadequate and far from systematic; fuel inspection practices and capabilities have varied significantly from site to site; certain issues were identified but remained unaddressed for significant time; priorities in experimental or design support activities were not assigned consistently. The presentation gives examples of areas where, in the opinion of the CNSC staff, further work is required to support fuel design and safety envelopes. The implementation of new CANFLEX fuel designs is currently being considered by the industry and CNSC staff has been engaged in the review

  16. 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.

  17. Future nuclear regulatory challenges. A report by the NEA Committee on Nuclear Regulatory Activities

    International Nuclear Information System (INIS)

    1998-01-01

    Future challenges are considered that may arise from technical, socio-economic and political issues; organizational, management and human aspects; and international issues. The perceived challenges have been grouped into four categories, each covered by a chapter. Technical issues are addressed that many present regulatory challenges in the future: ageing nuclear power plants. External changes to industry are considered next that have an effect on regulators, privatization, cost reduction consequences, commercialization etc. It is followed by the impacts of internal changes: organizational, managerial, human-resources, licensing, staff training etc. Finally, international issues are discussed with potential regulatory impact. (R.P.)

  18. Evolution of nuclear security regulatory activities in Brazil

    International Nuclear Information System (INIS)

    Mello, Luiz A. de; Monteiro Filho, Joselio S.; Belem, Lilia M.J.; Torres, Luiz F.B.

    2009-01-01

    The changing of the world scenario in the last 15 years has increased worldwide the concerns about overall security and, as a consequence, about the nuclear and radioactive material as well as their associated facilities. Considering the new situation, in February 2004, the Brazilian National Nuclear Energy Commission (CNEN), decided to create the Nuclear Security Office. This Office is under the Coordination of Nuclear Safeguards and Security, in the Directorate for Safety, Security and Safeguards (Regulatory Directorate). Before that, security regulation issues were dealt in a decentralized manner, within that Directorate, by different licensing groups in specific areas (power reactors, fuel cycle facilities, radioactive facilities, transport of nuclear material, etc.). This decision was made in order to allow a coordinated approach on the subject, to strengthen the regulation in nuclear/radioactive security, and to provide support to management in the definition of institutional security policies. The CNEN Security Office develops its work based in the CNEN Physical Protection Regulation for Nuclear Operational Units - NE-2.01, 1996, the Convention on the Physical Protection of Nuclear Material and the IAEA Nuclear Security Series . This paper aims at presenting the activities developed and the achievements obtained by this new CNEN office, as well as identifying the issues and directions for future efforts. (author)

  19. Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma

    Directory of Open Access Journals (Sweden)

    Dinesh K. Singh

    2017-01-01

    Full Text Available Efforts to identify and target glioblastoma (GBM drivers have primarily focused on receptor tyrosine kinases (RTKs. Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2 transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2 and zinc-finger E-box binding homeobox 1 (ZEB1, which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo.

  20. 17 CFR 1.59 - Activities of self-regulatory organization employees, governing board members, committee members...

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Activities of self-regulatory... COMMODITY EXCHANGE ACT Miscellaneous § 1.59 Activities of self-regulatory organization employees, governing...) Self-regulatory organization means “self-regulatory organization,” as defined in Commission regulation...

  1. Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics

    KAUST Repository

    Roy, S.; Schmeier, S.; Arner, E.; Alam, Tanvir; Parihar, S. P.; Ozturk, M.; Tamgue, O.; Kawaji, H.; de Hoon, M. J. L.; Itoh, M.; Lassmann, T.; Carninci, P.; Hayashizaki, Y.; Forrest, A. R. R.; Bajic, Vladimir B.; Guler, R.; Consortium, F.; Brombacher, F.; Suzuki, H.

    2015-01-01

    Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics

  2. Role of cooperation activities for capacity building of Romanian Regulatory Authority (CNCAN)

    International Nuclear Information System (INIS)

    Biro, L.; Ciurea-Ercau, C.

    2010-01-01

    With a slow but active nuclear development program of sector since 1980, Romanian regulatory authority had to permanently adapt to the changes in national and international environment in order ensure continuously increase of capacity building and effectiveness, commensurate with the growing nuclear sector. Limited human resources available at the national level put the Romanian Regulatory Authority in the position of building the Technical Support Organization as part of its on organization. International cooperation played an important role in capacity building of Romanian regulatory body and providing necessary assistance in performing regulatory activities or support in development of regulatory framework. Fellowships and technical visits, workshops and training courses provided through IAEA TC at national or regional level, technical assistance provided by European Commission (EC) through PHARE Projects, all provided valuable contribution in assuring training of regulatory staff and development of proper regulatory framework in Romania. Therefore, Romanian Regulatory Authority is putting a strong accent on strengthening and promoting international cooperation through IAEA Technical Cooperation Programme, Molls between regulatory bodies, as one of the key elements in supporting capacity building of regulatory authorities in countries having small or embarking on nuclear power program. Building networks between training centers and research facilities and establishments of regional training centers represent one of the future viable options in preserving knowledge in nuclear field. (author)

  3. 2015 Summary Report on Industrial and Regulatory Engagement Activities

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Kenneth David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    activities and future plans were made to Arizona Public Service, Exelon, Duke Energy, Pacific Gas & Electric, SCANA, Southern Nuclear, South Texas Project, STARS Alliance, Tennessee Valley Authority, and Xcel. Discussions were also held on the pathway goals and activities with major industry support organizations during FY 2102, including the Institute of Nuclear Power Operations (INPO), the Nuclear Information Technology Strategic Leadership (NITSL), the Nuclear Energy Institute (NEI), and the Electric Power Research Institute. The Advanced II&C Pathway work was presented at five major industry conferences and Informal discussions were held with key NRC managers at industry conferences. In addition, discussions were held with NRC senior managers on digital regulatory issues through participation on the NEI Digital I&C Working Group. Meetings were held with major industry suppliers and consultants, to explore opportunities for collaboration and to provide a means of pilot project technology transfer. In the international area, discussions were held with Electricite’ de France (EdF) concerning possible collaboration in the area NPP configuration control using intelligent wireless devices.

  4. 2015 Summary Report on Industrial and Regulatory Engagement Activities

    International Nuclear Information System (INIS)

    Thomas, Kenneth David

    2015-01-01

    activities and future plans were made to Arizona Public Service, Exelon, Duke Energy, Pacific Gas & Electric, SCANA, Southern Nuclear, South Texas Project, STARS Alliance, Tennessee Valley Authority, and Xcel. Discussions were also held on the pathway goals and activities with major industry support organizations during FY 2102, including the Institute of Nuclear Power Operations (INPO), the Nuclear Information Technology Strategic Leadership (NITSL), the Nuclear Energy Institute (NEI), and the Electric Power Research Institute. The Advanced II&C Pathway work was presented at five major industry conferences and Informal discussions were held with key NRC managers at industry conferences. In addition, discussions were held with NRC senior managers on digital regulatory issues through participation on the NEI Digital I&C Working Group. Meetings were held with major industry suppliers and consultants, to explore opportunities for collaboration and to provide a means of pilot project technology transfer. In the international area, discussions were held with Electricite de France (EdF) concerning possible collaboration in the area NPP configuration control using intelligent wireless devices.

  5. Health physics during work on the G. 2 and G. 3 reactor exchanges; La radioprotection des travaux sur les echangeurs des piles G. 2 et G. 3

    Energy Technology Data Exchange (ETDEWEB)

    Rodier, J; Chassany, J; Guillermin, P [Commissariat a l' Energie Atomique, Centre de Production de Plutonium, Marcoule (France). Centre d' Etudes Nucleaires

    1965-07-01

    During this work and its preparation, which took place first at G. 2 and then at G. 3 over a period of 11 months, 15000 measurement results were obtained. Their analysis, together with a consideration of the organisation on the site and of the conclusions drawn from the experiment, shows the various factors which determine the importance of the radio-active dangers. (authors) [French] Au cours de ces travaux et de leur preparation, qui ont eu lieu successivement a G. 3 puis a G. 2, pendant 11 mois, 15 000 resultats de mesures ont ete obtenus. Leur etude, mise en parallele avec l'organisation du chantier et les enseignements tires de l'experience, met en evidence les divers facteurs conditionnant les niveaux de risques radioactifs. (auteurs)

  6. 77 FR 70846 - Regulatory Guide 1.182, “Assessing and Managing Risk Before Maintenance Activities at Nuclear...

    Science.gov (United States)

    2012-11-27

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0285] Regulatory Guide 1.182, ``Assessing and Managing Risk Before Maintenance Activities at Nuclear Power Plants'' AGENCY: Nuclear Regulatory Commission... withdrawing Regulatory Guide (RG)1.182, Revision (Rev.) 0, ``Assessing and Managing Risk Before Maintenance...

  7. Nuclear knowledge management system in the regulatory activity

    International Nuclear Information System (INIS)

    Nosovskij, A.V.; Klevtsov, A.L.; Kravchenko, N.A.

    2010-01-01

    Important issues on collection, storage and spread of knowledge among organisation dealing with the use of nuclear technologies, role of close cooperation between enterprises and organizations in developing knowledge management, general requirements for creating a nuclear knowledge management system are considered. Recommendations and the main mechanisms are identified to create the knowledge management system in technical support organizations of the regulatory authority.

  8. Regulation of Federal radioactive waste activities. Report to Congress on extending the Nuclear Regulatory Commission's licensing or regulatory authority to Federal radioactive waste storage and disposal activities

    International Nuclear Information System (INIS)

    1979-09-01

    The report contains two recommendations for extending the Commission's regulatory authority: (1) NRC licensing authority should be extended to cover all new DOE facilities for disposal of transuranic (TRU) waste and nondefense low-level waste. (2) A pilot program, focused on a few specific DOE waste management activities, should be established to test the feasibility of extending NRC regulatory authority on a consultative basis to DOE waste management activities not now covered by NRC's licensing authority or its extension as recommended in Recommendation 1

  9. Une littérature du foyer : les livres de travaux manuels amateur

    Directory of Open Access Journals (Sweden)

    Claire Le Thomas

    2008-04-01

    Full Text Available Au cours du XIX e siècle naît une littérature entièrement voué au domicile : les manuels de travaux amateur. A travers ces livres se diffusent des usages dédiés à l’embellissement du logis ou à son entretien, c’est-à-dire de nouvelles occupations du temps libre qui accompagnent la transformation des représentations et des usages de l’espace domestique. Le mode d’exposition du discours sur la maison dans ces ouvrages amateur reflète ainsi l’intensité de l’engagement affectif et intellectuel concentré autour du foyer et dévoile la manière dont fut pensée et posée la problématique de l’habitat au cours de la seconde moitié du XIX e siècle.

  10. Status report on NRC's current below regulatory concern activities

    International Nuclear Information System (INIS)

    Dragonette, K.S.

    1988-01-01

    The concept of below regulatory concern (BRC) is not new to the Nuclear Regulatory Commission (NRC) or its predecessor agency, the Atomic Energy Commission. The regulations and licensing decisions have involved limited and de facto decisions on BRC since the beginning. For example, consumer products containing radioactive materials have been approved for distribution to persons exempt from licensing for some time and procedures for survey and release of equipment have traditionally been a part of many licensees' radiation safety programs. However, these actions have generally been ad hoc decisions in response to specific needs and have not been necessarily consistent. The need to deal with this regulatory matter has been receiving attention from both Congress and the NRC Commissioners. NRC response has grown from addressing specific waste streams, to generic rulemaking for wastes, and finally to efforts to develop a broad generic BRC policy. Section 10 of the Low-Level Radioactive Waste Policy Amendments Act of 1985 addressed NRC actions on specific waste streams. In response, NRC issued guidance on rulemaking petitions for specific wastes. NRC also issued an advance notice of proposed rulemaking indicating consideration of Commission initiated regulations to address BRC wastes in a generic manner. The Commissioners have directed staff to develop an umbrella policy for all agency decisions concerning levels of risk or dose that do not require government regulation

  11. Regulatory Audit Activities on Nuclear Design of Reactor Cores

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chae-Yong; Lee, Gil Soo; Lee, Jaejun; Kim, Gwan-Young; Bae, Moo-Hun [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2016-10-15

    Regulatory audit analyses are initiated on the purpose of deep knowledge, solving safety issues, being applied in the review of licensee's results. The current most important safety issue on nuclear design is to verify bias and uncertainty on reactor physics codes to examine the behaviors of high burnup fuel during rod ejection accident (REA) and LOCA, and now regulatory audits are concentrated on solving this issue. KINS develops regulatory audit tools on its own, and accepts ones verified from foreign countries. The independent audit tools are sometimes standardized through participating the international programs. New safety issues on nuclear design, reactor physics tests, advanced reactor core design are steadily raised, which are mainly drawn from the independent examination tools. It is some facing subjects for the regulators to find out the unidentified uncertainties in high burnup fuels and to systematically solve them. The safety margin on nuclear design might be clarified by precisely having independent tools and doing audit calculations by using them. SCALE-PARCS/COREDAX and the coupling with T-H code or fuel performance code would be certainly necessary for achieving these purposes.

  12. Regulatory Audit Activities on Nuclear Design of Reactor Cores

    International Nuclear Information System (INIS)

    Yang, Chae-Yong; Lee, Gil Soo; Lee, Jaejun; Kim, Gwan-Young; Bae, Moo-Hun

    2016-01-01

    Regulatory audit analyses are initiated on the purpose of deep knowledge, solving safety issues, being applied in the review of licensee's results. The current most important safety issue on nuclear design is to verify bias and uncertainty on reactor physics codes to examine the behaviors of high burnup fuel during rod ejection accident (REA) and LOCA, and now regulatory audits are concentrated on solving this issue. KINS develops regulatory audit tools on its own, and accepts ones verified from foreign countries. The independent audit tools are sometimes standardized through participating the international programs. New safety issues on nuclear design, reactor physics tests, advanced reactor core design are steadily raised, which are mainly drawn from the independent examination tools. It is some facing subjects for the regulators to find out the unidentified uncertainties in high burnup fuels and to systematically solve them. The safety margin on nuclear design might be clarified by precisely having independent tools and doing audit calculations by using them. SCALE-PARCS/COREDAX and the coupling with T-H code or fuel performance code would be certainly necessary for achieving these purposes

  13. Program plan for future regulatory activity in nuclear-power-plant maintenance

    International Nuclear Information System (INIS)

    Badalamente, R.V.

    1982-10-01

    The intent of this paper is to describe the results of a study of nuclear power plant (NPP) maintenance conducted by Battelle's Pacific Northwest Laboratories (PNL) for the Nuclear Regulatory Commission (NRC). The purpose of the study for the NRC was to determine problems affecting human performance in NPP maintenance, pinpoint those which adversely affect public health and safety, review strategies for overcoming the problems, and suggest the direction that regulatory activities should take. Results of the study were presented to the NRC (Division of Human Factors Safety) in the form of a recommended program plan for future regulatory activity in NPP maintenance

  14. FDA's Activities Supporting Regulatory Application of "Next Gen" Sequencing Technologies.

    Science.gov (United States)

    Wilson, Carolyn A; Simonyan, Vahan

    2014-01-01

    Applications of next-generation sequencing (NGS) technologies require availability and access to an information technology (IT) infrastructure and bioinformatics tools for large amounts of data storage and analyses. The U.S. Food and Drug Administration (FDA) anticipates that the use of NGS data to support regulatory submissions will continue to increase as the scientific and clinical communities become more familiar with the technologies and identify more ways to apply these advanced methods to support development and evaluation of new biomedical products. FDA laboratories are conducting research on different NGS platforms and developing the IT infrastructure and bioinformatics tools needed to enable regulatory evaluation of the technologies and the data sponsors will submit. A High-performance Integrated Virtual Environment, or HIVE, has been launched, and development and refinement continues as a collaborative effort between the FDA and George Washington University to provide the tools to support these needs. The use of a highly parallelized environment facilitated by use of distributed cloud storage and computation has resulted in a platform that is both rapid and responsive to changing scientific needs. The FDA plans to further develop in-house capacity in this area, while also supporting engagement by the external community, by sponsoring an open, public workshop to discuss NGS technologies and data formats standardization, and to promote the adoption of interoperability protocols in September 2014. Next-generation sequencing (NGS) technologies are enabling breakthroughs in how the biomedical community is developing and evaluating medical products. One example is the potential application of this method to the detection and identification of microbial contaminants in biologic products. In order for the U.S. Food and Drug Administration (FDA) to be able to evaluate the utility of this technology, we need to have the information technology infrastructure and

  15. Role of in-house safety analysis and research activities in regulatory decision making

    International Nuclear Information System (INIS)

    Pradhan, Santosh K.; Nagrale, Dhanesh B.; Gaikwad, Avinash J.

    2015-01-01

    Achievement of an acceptable level of nuclear safety is an essential requirement for the peaceful utilization of nuclear energy. The success of Global Nuclear Safety Regime is built upon a foundation of research. Such research has been sponsored by Governments and industry and has led to improved designs, safer and more reliable plant operation, and improvements in operating plant efficiency. A key element of this research has been the nuclear safety research performed or sponsored by regulatory organizations. In part, it has been the safety research performed or sponsored by regulatory organizations that has contributed to improved safety and has laid the foundation for activities such as risk-informed regulation, plant life extension, improved plant performance (e.g. power uprates) and new plant designs. The regulatory research program is meant to improve the regulatory authority’s knowledge where uncertainty exists, where safety margins are not well-characterized, and where regulatory decisions need to be confirmed in existing or new designs and technologies. The regulatory body get research initiated either in-house or by the licensee or through technical support organizations (TSOs). Research and analysis carried out within the regulatory body is of immense value in this context. This could be in the form of analysis of safety significant events, analysis of severe accidents, review of operating experience, independent checks of critical designs and even review of operator responses under different situations towards arriving at modifications to training programmes and licensing procedures for operating personnel. A latent benefit of regulatory research carried out by the regulators themselves is that it improves their technical competence considerably which in turn leads to high quality safety reviews and improved regulation in general. The aim of the present paper is to provide an overview of role of regulatory research and the in-house regulatory safety

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

    International Nuclear Information System (INIS)

    1994-04-01

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

  17. Current and future applications of PRA in regulatory activities

    Energy Technology Data Exchange (ETDEWEB)

    Speis, T.P.; Murphy, J.A.; Cunningham, M.A. [Nuclear Regulatory Commission, Washington, DC (United States)] [and others

    1995-04-01

    Probabilistic Risk Assessments (PRAs) have proven valuable in providing the regulators, the nuclear plant operators, and the reactor designers insights into plant safety, reliability, design and operation. Both the NRC Commissioners and the staff have grown to appreciate the valuable contributions PRAs can have in the regulatory arena, though I will admit the existence of some tendencies for strict adherence to the deterministic approach within the agency and the public at large. Any call for change, particularly one involving a major adjustment in approach to the regulation of nuclear power, will meet with a certain degree of resistance and retrenchment. Change can appear threatening and can cause some to question whether the safety mission is being fulfilled. This skepticism is completely appropriate and is, in fact, essential to a proper transition towards risk and performance-based approaches. Our task in the Office of Nuclear Regulatory Research is to increase the PRA knowledge base within the agency and develop appropriate guidance and methods needed to support the transitioning process.

  18. Regulatory Endorsement Activities for ASME Nuclear Codes and Standards

    International Nuclear Information System (INIS)

    West, Raymond A.

    2006-01-01

    The ASME Board on Nuclear Codes and Standards (BNCS) has formed a Task Group on Regulatory Endorsement (TG-RE) that is currently in discussions with the United States Nuclear Regulatory Commission (NRC) to look at suggestions and recommendations that can be used to help with the endorsement of new and revised ASME Nuclear Codes and Standards (NC and S). With the coming of new reactors in the USA in the very near future we need to look at both the regulations and all the ASME NC and S to determine where we need to make changes to support these new plants. At the same time it is important that we maintain our operating plants while addressing ageing management needs of our existing reactors. This is going to take new thinking, time, resources, and money. For all this to take place the regulations and requirements that we use must be clear concise and necessary for safety and to that end both the NRC and ASME are working together to make this happen. Because of the influence that the USA has in the world in dealing with these issues, this paper is written to inform the international nuclear engineering community about the issues and what actions are being addressed under this effort. (author)

  19. Les piles à combustible. Bilan des travaux de recherches. Perspectives Fuel Cells. Review of Research. Outlook

    Directory of Open Access Journals (Sweden)

    Breelle Y.

    2006-11-01

    Full Text Available Cet article fait le point, sous forme résumée, des travaux de recherches et de développement menés par l'Institut Français du Pétrole (IFP depuis vingt ans dans le domaine des piles à combustible : sélection des filières directes conduisant au choix de la pile hydrogène-air basse température à électrolyte basique, mise au point des générateurs à hydrogène alimentés en méthanol. On présente les résultats obtenus et les conclusions des enquêtes effectués dans le domaine des groupes électrogènes et des applications spéciales, dans celui de la traction automobile et dans celui de la production massive d'électricité. This article reviews and sums up the research and development done by Institut Français du Pétrole (IFP in the last 20 years in the field of fuel cells, including the selection of direct methods leading to the choice of low-temperature basic-electrolyte hydrogen/air cells and the development of methanol-powered hydrogen generators. The results obtained are desceibed along with the conclusions of surveys made in the field of electric generators and special applications in the fields of automotive traction and massive electricity production.

  20. Role of human neurobehavioural tests in regulatory activity on chemicals

    Science.gov (United States)

    Stephens, R.; Barker, P.

    1998-01-01

    Psychological performance tests have been used since the mid-1960s in occupational and environmental health toxicology. The interpretation of significantly different test scores in neurobehavioural studies is not straightforward in the regulation of chemicals. This paper sets out some issues which emerged from discussions at an international workshop, organised by the United Kingdom Health and Safety Executive (HSE), to discuss differences in interpretation of human neurobehavioural test data in regulatory risk assessments. The difficulties encountered by regulators confronted with neurobehavioural studies seem to be twofold; some studies lack scientific rigor; other studies, although scientifically sound, are problematic because it is not clear what interpretation to place on the results. Issues relating to each of these points are discussed. Next, scenarios within which to consider the outcomes of neurobehavioural studies are presented. Finally, conclusions and recommendations for further work are put forward.   PMID:9624273

  1. Construction of the Database for Tomorrow's Regulatory Activities

    International Nuclear Information System (INIS)

    Lee, Il S.; Kim, Min C.; Kim, Sang J.; Yu, Seon O.; Lee, Kyung W.; Kim, Ji T.; Koo, Bon H.; Lee, Durk H.

    2010-01-01

    KINS has launched a top brand project since early 2007, which called the 'Tracking System for the Implementation of Nuclear Regulation: RTRACER' The one of main contents of RTRACER is promoting nuclear safety by interconnecting the information of the events and that of safety review and regulatory inspection. R-TRACER is composed of three parts. One is the CATS(Corrective Action Tracking System) to carry out the related affairs and to exchange information between organizations concerned efficiently. Another is the SIMS(Safety Issue Management System) to coordinate the safety issues program and to implement the operating experience feedback in a real-time basis. And the other is the DIOS to supply above both systems with core information. This paper is focused on the database structure of the DIOS

  2. The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb

    OpenAIRE

    Cotney, Justin; Leng, Jing; Yin, Jun; Reilly, Steven K.; DeMare, Laura E.; Emera, Deena; Ayoub, Albert E.; Rakic, Pasko; Noonan, James P.

    2013-01-01

    The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find...

  3. Overview of maintenance principles and regulatory supervision of maintenance activities at nuclear power plants in Slovakia

    International Nuclear Information System (INIS)

    Rohar, S.; Cepcek, S.

    1997-01-01

    The maintenance represents one of the most important tools to ensure safe and reliable operation of nuclear power plants. The emphasis of Nuclear Regulatory Authority of the Slovak Republic to the maintenance issue is expressed by requirements in the regulations. The current practice of maintenance management in operated nuclear power plants in Slovak Republic is presented. Main aspects of maintenance, as maintenance programme, organization of maintenance, responsibilities for maintenance are described. Activities of nuclear regulatory authority in maintenance process are presented too. (author)

  4. Peak-valley-peak pattern of histone modifications delineates active regulatory elements and their directionality

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Bagger, Frederik Otzen; Lauridsen, Felicia Kathrine Bratt

    2016-01-01

    Formation of nucleosome free region (NFR) accompanied by specific histone modifications at flanking nucleosomes is an important prerequisite for enhancer and promoter activity. Due to this process, active regulatory elements often exhibit a distinct shape of histone signal in the form of a peak......-valley-peak (PVP) pattern. However, different features of PVP patterns and their robustness in predicting active regulatory elements have never been systematically analyzed. Here, we present PARE, a novel computational method that systematically analyzes the H3K4me1 or H3K4me3 PVP patterns to predict NFRs. We show...... four ENCODE cell lines and four hematopoietic differentiation stages, we identified several enhancers whose regulatory activity is stage specific and correlates positively with the expression of proximal genes in a particular stage. In conclusion, our results demonstrate that PVP patterns delineate...

  5. STATE INSPECTION METHODOLOGY OF ENVIRONMENTAL REGULATORY ACTIVITY FOCUSED ON THE LIFE CYCLE PROCESSESES

    Directory of Open Access Journals (Sweden)

    Yuniey Quiala Armenteros

    2016-10-01

    Full Text Available The Cuban Environmental Regulatory Activity has on the Environmental State Inspection an instrument for control and monitoring of compliance of current legal standards regarding environmental protection and rational use of natural resources. In this research, a design methodology for effective implementation of environmental regulatory activity in Cuba directed to processes is proposed; based on the life cycle assessment and the applicable environmental management standards, including new performance indicators, which form a new tool based on scientific criterions for the Center of Environmental Inspection and Control.

  6. Regulatory crosstalk by protein kinases on CFTR trafficking and activity

    Science.gov (United States)

    Farinha, Carlos Miguel; Swiatecka-Urban, Agnieszka; Brautigan, David; Jordan, Peter

    2016-01-01

    Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e. channel opening and closing) is regulated by protein kinases and phosphatases via phosphorylation and dephosphorylation. Here, we review recent evidence for the role of protein kinases in regulation of CFTR delivery to and retention in the plasma membrane. We review this information in a broader context of regulation of other transporters by protein kinases because the overall functional output of transporters involves the integrated control of both their number at the plasma membrane and their specific activity. While many details of the regulation of intracellular distribution of CFTR and other transporters remain to be elucidated, we hope that this review will motivate research providing new insights into how protein kinases control membrane transport to impact health and disease.

  7. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - New Zealand

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive Substances and Equipment; 4. Nuclear installations; 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities - National Radiation Laboratory - NRL; 2. Advisory bodies - Radiation Protection Advisory Council; 3. Public and semi-public agencies - Research institutes

  8. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.

    Science.gov (United States)

    Fairfax, Benjamin P; Humburg, Peter; Makino, Seiko; Naranbhai, Vivek; Wong, Daniel; Lau, Evelyn; Jostins, Luke; Plant, Katharine; Andrews, Robert; McGee, Chris; Knight, Julian C

    2014-03-07

    To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor-modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.

  9. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Iceland

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances and equipment; 4. Nuclear installations; 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Nuclear security; 9. Transport; 10. Nuclear Third Party Liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Minister of Health and Social Security; Icelandic Radiation Protection Institute)

  10. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Luxembourg

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Framework: 1. General; 2. Mining; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Emergency measures); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability; II. General Institutional Framework: 1. Regulatory and supervisory authorities (Minister of Health; Minister of Labour; Other Ministers competent); 2. Advisory bodies (Higher Health Council)

  11. Guidance and methods for satisfying low specific activity material and surface contaminated object regulatory requirements

    International Nuclear Information System (INIS)

    Pope, R.B.; Shappert, L.B.; Michelhaugh, R.D.; Boyle, R.W.; Easton, E.P.; Coodk, J.R.

    1998-01-01

    The U.S. Department of Transportation (DOT) and the U.S. Nuclear Regulatory Commission (NRC) have prepared a comprehensive set of draft guidance for shippers and inspectors to use when applying the newly imposed regulatory requirements for low specific activity (LSA) material and surface contaminated objects (SCOs). These requirements represent significant departures in some areas from the manner in which these materials and objects were regulated by the earlier versions of the regulations. The proper interpretation and application of the regulatory criteria can require a fairly complex set of decisions be made. To assist those trying these regulatory requirements, a detailed set of logic-flow diagrams representing decisions related to multiple factors were prepared and included in the draft report for comment on Categorizing and Transporting Low Specific Activity Materials and Surface Contaminated Objects, (DOT/NRC, 1997). These logic-flow diagrams, as developed, are specific to the U.S. regulations, but were readily adaptable to the IAEA regulations. The diagrams have been modified accordingly and tied directly to specific paragraphs in IAEA Safety Series No. 6. This paper provides the logic-flow diagrams adapted in the IAEA regulations, and demonstrated how these diagrams can be used to assist consignors and inspectors in assessing compliance of shipments with the LSA material and SCO regulatory requirements. (authors)

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

    Directory of Open Access Journals (Sweden)

    Zinaida P. Arharova

    2013-01-01

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

  13. Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

    Science.gov (United States)

    Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

    2017-07-01

    Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

  14. Probabilistic risk analysis and its role in regulatory activity in a developing country

    International Nuclear Information System (INIS)

    Arredondo-Sanchez, C.

    1985-01-01

    The author discusses the criterion adopted for regulatory activity in a developing country with a nuclear power plant. He describes the problems that have to be overcome as a result of changes in the regulations during construction of the plant. There is discussion of the action taken by the regulatory body when introducing the method of probabilistic risk analysis. The part played by this form of analysis in quantifying the safety objectives proposed in the USA together with its limitations and the problems involved in this methodology are examined. Lastly, the author gives an opinion on the use that probabilistic risk analysis should be put to in developing countries such as Mexico. (author)

  15. Human Epidermal Langerhans Cells Maintain Immune Homeostasis in Skin by Activating Skin Resident Regulatory T Cells

    Science.gov (United States)

    Seneschal, Julien; Clark, Rachael A.; Gehad, Ahmed; Baecher-Allan, Clare M.; Kupper, Thomas S.

    2013-01-01

    Recent discoveries indicate that the skin of a normal individual contains 10-20 billion resident memory T cells ( which include various T helper, T cytotoxic, and T regulatory subsets, that are poised to respond to environmental antigens. Using only autologous human tissues, we report that both in vitro and in vivo, resting epidermal Langerhan cells (LC) selectively and specifically induced the activation and proliferation of skin resident regulatory T cells (Treg), a minor subset of skin resident memory T cells. In the presence of foreign pathogen, however, the same LC activated and induced proliferation of effector memory T (Tem) cells and limited Treg cells activation. These underappreciated properties of LC: namely maintenance of tolerance in normal skin, and activation of protective skin resident memory T cells upon infectious challenge, help clarify the role of LC in skin. PMID:22560445

  16. A balance of activity in brain control and reward systems predicts self-regulatory outcomes

    OpenAIRE

    Lopez, Richard B.; Chen, Pin-Hao A.; Huckins, Jeremy F.; Hofmann, Wilhelm; Kelley, William M.; Heatherton, Todd F.

    2017-01-01

    Abstract Previous neuroimaging work has shown that increased reward-related activity following exposure to food cues is predictive of self-control failure. The balance model suggests that self-regulation failures result from an imbalance in reward and executive control mechanisms. However, an open question is whether the relative balance of activity in brain systems associated with executive control (vs reward) supports self-regulatory outcomes when people encounter tempting cues in daily lif...

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

    Science.gov (United States)

    Sim, B C; Hui, K M

    1994-12-01

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

  18. Regulatory activities and their research and development support in the CSSR

    International Nuclear Information System (INIS)

    Klik, F.; Kriz, Z.

    1977-01-01

    According to the existing laws the Czechoslovak Atomic Energy Commission (CSAEC) is authorized to regulate the Czechoslovak nuclear activities with respect to the nuclear safety, waste management and accountability and control of nuclear materials. Its activity with respect to nuclear safety consists mainly of: preparation of safety code of practices supplemented by safety guides for nuclear facilities, assessment of nuclear safety and issuing of binding opinion on nuclear safety for licensing of nuclear facilities, inspection of nuclear safety during construction and operation of nuclear facilities. The first part of the paper deals with the regulatory implementation. This covers the first stage specified by the construction and operation of research reactors only, the second stage specified by the design, construction, commissioning and operation of the first prototype nuclear power plant and the present stage specified by the construction and commissioning of a number of industrially developed nuclear power reactors. The present stage of regulatory implementation is described in detail. This covers the development of regulatory documentation such as safety code of practices and safety guides and the main safety requirements included in the existing safety code of practices for the siting, design and operation of nuclear power plants equipped with pressure water reactors. Then the general licensing procedures and organization including the structure and contents of safety documentation required for the licensing of siting, construction and operation of nuclear power plants is also described. The paper deals also with the inspection practices applied during construction, commissioning and operation of nuclear power plant in order to verify that the licensing conditions and requirements are fulfilled. The paper gives also some basic information about coordination of CSAEC nuclear safety regulatory activity with the regulatory activities of other governmental bodies

  19. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Slovak Republic

    International Nuclear Information System (INIS)

    2013-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining Regime; 3. Radioactive Substances and Equipment; 4. Nuclear Installations (Licensing and Inspection, including Nuclear Safety; Emergency Response); 5. Trade in Nuclear Materials and Equipment; 6. Radiological Protection; 7. Radioactive Waste Management; 8. Non-proliferation and Physical Protection; 9. Transport; 10. Nuclear Third Party Liability; II. Institutional Framework: 1. Regulatory and Supervisory Authorities (Nuclear Regulatory Authority of the Slovak Republic - UJD; Ministry of Health; Ministry of the Environment; Ministry of the Interior; Ministry of Economy; Ministry of Labour and National Labour Inspectorate); 2. Public and Semi-Public Agencies

  20. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities. Japan

    International Nuclear Information System (INIS)

    2017-01-01

    The NEA has updated, in coordination with the Permanent Delegation of Japan to the OECD, the report on the Regulatory and Institutional Framework for Nuclear Activities in Japan. This country report provides comprehensive information on the regulatory and institutional framework governing nuclear activities in Japan. It provides a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. Content: I - General Regulatory Regime: Introduction; Mining regime; Radioactive substances and equipment; Nuclear installations (Reactor Regulation, Emergency response); Trade in nuclear materials and equipment; Radiological protection; Radioactive waste management; Nuclear safeguards and nuclear security; Transport; Nuclear third party liability. II - Institutional Framework: Regulatory and supervisory authorities (Cabinet Office, Nuclear Regulation Authority (NRA), Ministry of Economy, Trade and Industry (METI), The Agency for Natural Resources and Energy (ANRE), Ministry of Land, Infrastructure, Transport and Tourism (MLIT), Ministry of Education, Culture, Sports, Science and Technology (MEXT)); Advisory bodies (Atomic Energy Commission (AEC), Reactor Safety Examination Committee, Nuclear Fuel Safety Examination Committee, Radiation Council, Other advisory bodies); Public and semi-public agencies (Japan Atomic Energy Agency (JAEA), National Institutes for Quantum and Radiological Science and Technology (QST), Nuclear Damage Compensation and Decommissioning Facilitation Corporation (NDF), Nuclear Waste Management Organisation (NUMO))

  1. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Canada

    International Nuclear Information System (INIS)

    2009-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction (Licensing system; Offences, compliance and enforcement; Regulatory documents; Other relevant legislation); 2. Mining regime; 3. Nuclear substances and radiation devices; 4. Nuclear facilities; 5. Trade in nuclear materials and equipment (Exports, Other imports); 6. Radiation protection; 7. Radioactive waste management; 8. Non-proliferation and nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Governor in council; Minister of natural resources; Other Ministerial authorities; Canadian Nuclear Safety Commission - CNSC); 2. Public and semi-public agencies (National Research Council - NRC; Natural Sciences and Engineering Research Council; Atomic Energy of Canada Ltd. - AECL)

  2. RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation

    Science.gov (United States)

    2013-01-01

    Background The production of enzymes by an industrial strain requires a complex adaption of the bacterial metabolism to the conditions within the fermenter. Regulatory events within the process result in a dynamic change of the transcriptional activity of the genome. This complex network of genes is orchestrated by proteins as well as regulatory RNA elements. Here we present an RNA-Seq based study considering selected phases of an industry-oriented fermentation of Bacillus licheniformis. Results A detailed analysis of 20 strand-specific RNA-Seq datasets revealed a multitude of transcriptionally active genomic regions. 3314 RNA features encoded by such active loci have been identified and sorted into ten functional classes. The identified sequences include the expected RNA features like housekeeping sRNAs, metabolic riboswitches and RNA switches well known from studies on Bacillus subtilis as well as a multitude of completely new candidates for regulatory RNAs. An unexpectedly high number of 855 RNA features are encoded antisense to annotated protein and RNA genes, in addition to 461 independently transcribed small RNAs. These antisense transcripts contain molecules with a remarkable size range variation from 38 to 6348 base pairs in length. The genome of the type strain B. licheniformis DSM13 was completely reannotated using data obtained from RNA-Seq analyses and from public databases. Conclusion The hereby generated data-sets represent a solid amount of knowledge on the dynamic transcriptional activities during the investigated fermentation stages. The identified regulatory elements enable research on the understanding and the optimization of crucial metabolic activities during a productive fermentation of Bacillus licheniformis strains. PMID:24079885

  3. RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation.

    Science.gov (United States)

    Wiegand, Sandra; Dietrich, Sascha; Hertel, Robert; Bongaerts, Johannes; Evers, Stefan; Volland, Sonja; Daniel, Rolf; Liesegang, Heiko

    2013-10-01

    The production of enzymes by an industrial strain requires a complex adaption of the bacterial metabolism to the conditions within the fermenter. Regulatory events within the process result in a dynamic change of the transcriptional activity of the genome. This complex network of genes is orchestrated by proteins as well as regulatory RNA elements. Here we present an RNA-Seq based study considering selected phases of an industry-oriented fermentation of Bacillus licheniformis. A detailed analysis of 20 strand-specific RNA-Seq datasets revealed a multitude of transcriptionally active genomic regions. 3314 RNA features encoded by such active loci have been identified and sorted into ten functional classes. The identified sequences include the expected RNA features like housekeeping sRNAs, metabolic riboswitches and RNA switches well known from studies on Bacillus subtilis as well as a multitude of completely new candidates for regulatory RNAs. An unexpectedly high number of 855 RNA features are encoded antisense to annotated protein and RNA genes, in addition to 461 independently transcribed small RNAs. These antisense transcripts contain molecules with a remarkable size range variation from 38 to 6348 base pairs in length. The genome of the type strain B. licheniformis DSM13 was completely reannotated using data obtained from RNA-Seq analyses and from public databases. The hereby generated data-sets represent a solid amount of knowledge on the dynamic transcriptional activities during the investigated fermentation stages. The identified regulatory elements enable research on the understanding and the optimization of crucial metabolic activities during a productive fermentation of Bacillus licheniformis strains.

  4. Evaluation of the safety culture in the regulatory activity in Camaguey province

    International Nuclear Information System (INIS)

    Naranjo Lopez, A.M.; Barreras Caballero, A.; Damera Martinez, A.

    1999-01-01

    Previous studied accomplished in the country have permitted to evaluate the activity of the regulatory body in nuclear safety matter in part of the national territory. These studies did not encompass the Camaguey province. In the work are shown the results of the study in this part of the territory, accomplished as of the survey elaborated by the National Nuclear Safety Center using guides it ASCOT and other documents of the IAEA

  5. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Poland

    International Nuclear Information System (INIS)

    2015-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment (Licensing; Registration and monitoring of nuclear materials and radioactive sources; High activity sources); 4. Nuclear facilities (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiological protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (The President of the National Atomic Energy Agency - Prezes Panstwowej Agencji Atomistyki (President of the PAA); Minister of Health; Minister of the Environment); 2. Advisory bodies (Council for Nuclear Safety and Radiological Protection); 3. Public and semi-public bodies (Radioactive Waste Management Plant); 4. Research institutes (Central Laboratory for Radiological Protection; National Centre for Nuclear Research; Institute of Nuclear Physics; Institute of Nuclear Chemistry and Technology; Institute of Plasma Physics and Laser Microfusion)

  6. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Finland

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations; (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Ministry of Trade and Industry - KTM; Ministry of Social Affairs and Health; Ministry of the Interior; Ministry of the Environment; Ministry of Foreign Affairs); 2. Advisory bodies (Advisory Committee on Nuclear Energy; Advisory Committee on Nuclear Safety); 3. Public and semi-public agencies (Finnish Radiation and Nuclear Safety Authority - STUK; State Nuclear Waste Management Fund)

  7. Information management systems for integrating the technical data and regulatory requirements of environmental restoration activities

    International Nuclear Information System (INIS)

    Geffen, C.A.; Garrett, B.A.; Walter, M.B.

    1990-03-01

    Current environmental regulations require that comprehensive planning be conducted before remediating a hazardous waste site to characterize the nature and extent of site contamination, calculate the risk to the public, and assess the effectiveness of various remediation technologies. Remediation of Department of Energy (DOE) sites contaminated with hazardous or mixed wastes will require the effective integration of scientific and engineering data with regulatory and institutional requirements. The information management challenge presented by waste site cleanup activities goes beyond merely dealing with the large quantity of data that will be generated. The information must be stored, managed, and presented in a way that provides some consistency in approach across sites, avoids duplication of effort, and facilitates responses to requests for information from the regulators and the public. This paper provides background information on the regulatory requirements for data gathering and analysis for environmental restoration activities, and outlines the data and information management requirements for completing the pre-remediation phases of an environmental restoration project. Information management systems for integrating the regulatory and institutional requirements of the environmental restoration process with the technical data and analysis requirements are also described. 7 refs

  8. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Netherlands

    International Nuclear Information System (INIS)

    2009-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Fissionable materials, ores, radioactive materials and equipment (Fissionable materials and ores; Radioactive materials and equipment); 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection (Protection of workers; Protection of the public; Protection of individuals undergoing medical exposure); 7. Radioactive waste management; 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Minister for Housing, Spatial Planning and the Environment; Minister for Economic Affairs; Minister for Social Affairs and Employment; Minister for Health, Welfare and Sports; Minister for Finance; Minister for Foreign Affairs); 2. Advisory body - Health Council of the Netherlands; 3. Public and semi-public agencies (Nuclear Research and Consultancy Group - NRG; Central Organisation for Radioactive Waste - COVRA)

  9. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Ireland

    International Nuclear Information System (INIS)

    2009-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations; 5. Trade in nuclear materials and equipment; 6. Radiation protection (Radiation protection standards; Emergency response); 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Minister for the Environment, Heritage and Local Government; Minister for Agriculture and Food; Minister for Communications, Marine and Natural Resources; Minister for Finance; Minister for Health and Children; Minister for Defence); 2. Public and semi-public agencies (Radiological Protection Institute of Ireland; Food Safety Authority of Ireland)

  10. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Australia

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I) - General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection (Bilateral safeguards agreements; International Atomic Energy Agency Safeguards Agreement; The South Pacific Nuclear Free Zone Treaty Act; The Comprehensive Nuclear Test-Ban Treaty Act; The Nuclear Non-Proliferation (Safeguards) Act); 9. Transport; 10. Nuclear third party liability; II) - Institutional Framework: 1. Regulatory and supervisory authorities (Minister for Health and Ageing; Minister for Foreign Affairs; Minister for the Environment, Heritage and the Arts; Minister for, Resources, Energy and Tourism); 2. Advisory bodies (Radiation Health and Safety Advisory Council; Advisory Committees); 3. Public and semi-public agencies (Australian Radiation Protection and Nuclear Safety Agency (ARPANSA); Australian Safeguards and Non-Proliferation Office; Australian Nuclear Science and Technology Organisation (ANSTO); Supervising Scientist)

  11. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Turkey

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations; 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Prime Minister; Ministry of Energy and Natural Resources; Ministry of Health; Ministry of the Environment and Forestry); 2. Public and semi-public agencies (Turkish Atomic Energy Authority - TAEK; General Directorate for Mineral Research and Exploration - MTA; ETI Mine Works General Management; Turkish Electric Generation and Transmission Corporation - TEAS; Turkish Electricity Distribution Corporation - TEDAS)

  12. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Spain

    International Nuclear Information System (INIS)

    2010-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response); 5. Trading in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection (Safeguards and non-proliferation; Physical protection); 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Ministry of Industry, Tourism and Trade - MITYC; Ministry of the Interior - MIR; Ministry of Economy and the Exchequer - MEH; Ministry of the Environment and Rural and Marine Affairs - MARM); 2. Public and semi-public agencies (Nuclear Safety Council - CSN; Centre for Energy-related, Environmental and Technological Research - CIEMAT; National Energy Commission - CNE; 3. Public capital companies (Enusa Industrias Avanzadas, s.a. - ENUSA; Empresa Nacional de Residuos Radiactivos, s.a. - ENRESA)

  13. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Japan

    International Nuclear Information System (INIS)

    2011-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Cabinet Office; Minister of Economy, Trade and Industry - METI; Minister of Land, Infrastructure and Transport - MLIT; Minister of Education, Culture, Sports, Science and Technology - MEXT); 2. Advisory bodies (Atomic Energy Commission - AEC; Nuclear Safety Commission - NSC; Radiation Council; Special Committee on Energy Policy; Other advisory bodies); 3. Public and Semi-Public Agencies (Japan Atomic Energy Agency - JAEA)

  14. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Norway

    International Nuclear Information System (INIS)

    2001-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining Regime; 3. Radioactive Substances, Nuclear Fuel and Equipment; 4. Nuclear Installations (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in Nuclear Materials and Equipment (Trade governed by nuclear energy legislation; Trade governed by radiation protection legislation; Trade governed by export/import control legislation); 6. Radiation Protection; 7. Radioactive Waste Management; 8. Non-Proliferation and Physical Protection; 9. Transport; 10. Nuclear Third Party Liability; II. Institutional Framework: 1. Regulatory and Supervisory Authorities: A. Ministerial Level (Ministry of Health and Social Affairs; Ministry of Trade and Industry; Ministry of Foreign Affairs; Other Ministries); B. Subsidiary Level: (The Norwegian Radiation Protection Authority - NRPA; The Norwegian Nuclear Emergency Organisation); 2. Public and Semi-Public Agencies - Institute for Energy Technology - IFE

  15. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Czech Republic

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear items and spent fuel (Ionising radiation sources; Nuclear items; Spent fuel); 4. Nuclear installations (Licensing and inspection, including nuclear safety; Emergency response; Decommissioning); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (State Office for Nuclear Safety - SUJB; Ministry of Industry and Trade; Ministry of the Interior; Ministry of the Environment); 2. Public and semi-public agencies (CEZ, a.s.; National Radiation Protection Institute - NRPI; Radioactive Waste Repository Authority - RAWRA; Diamo; Nuclear Physics Institute - NPI; National Institute for Nuclear, Chemical and Biological Protection; Nuclear Research Institute Rez, a.s. - NRI)

  16. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Mexico

    International Nuclear Information System (INIS)

    2009-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability; 11. Nuclear terrorism; II. Institutional Framework - The federal government: 1. Regulatory and supervisory authorities (Ministry of Energy; Ministry of Health; Ministry of Labour and Social Security; Ministry of the Environment and Natural Resources; Ministry of Communications and Transport); 2. Public and semi-public agencies: (National Nuclear Safety and Safeguards Commission; National Nuclear Research Institute)

  17. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Portugal

    International Nuclear Information System (INIS)

    2011-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Ministry of Health; Minister of Science, Technology and Higher Education; Ministry of Economy and Innovation; Ministry of Environment and Territorial Planning; Other authorities); 2. Advisory bodies (Independent Commission for Radiological Protection and Nuclear Safety - CIPRSN; National Radiation Protection Commission - CNPCR; National Commission for Radiological Emergencies - CNER; Other advisory bodies); 3. Public and semi-public agencies

  18. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Slovenia

    International Nuclear Information System (INIS)

    2013-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in nuclear materials and equipment; 6. Safeguards for nuclear material; 7. Radiation protection; 8. Radioactive waste management; 9. Nuclear security; 10. Transport; 11. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Slovenian Nuclear Safety Administration - SNSA; Slovenian Radiation Protection Administration - SRPA); 2. Advisory bodies; 3. Public and semi-public agencies; 4. Technical support organisations - approved experts

  19. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Hungary

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Atomic Energy Co-ordination Council; Hungarian Atomic Energy Authority - HAEA; Minister for Health; Minister for Local Government and Regional Development and Minister for Justice and Law Enforcement; Minister for Agriculture and Rural Development; Minister for Economy and Transport; Minister of Environment Protection and Water Management; Minister for Defence; Minister for Education; President of the Hungarian Mining and Geological Authority; Governmental Co-ordination Committee); 2. Advisory bodies (Scientific Board); 3. Public and semi-public agencies (Institute for Electric Power Research - VEIKI; Atomic Energy Research Institute - AEKI; Institute of Isotopes; Department of Physical Chemistry of the University of Pannon; Hungarian Power Companies Ltd - MVM Zrt.)

  20. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Denmark

    International Nuclear Information System (INIS)

    2015-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Minister of Health; Minister for the Environment/Minister of Transport and Energy; Minister of Justice; Minister of Defence; National Board of Health; Emergency Management Agency); 2. Advisory bodies (The Danish Ministry of Energy, Supply and Climate and the Danish Energy Agency); 3. Public and semi-public agencies (Risoe National Laboratory)

  1. A study on the influence of the regulatory requirements of a nuclear facility during decommissioning activities

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Seong; Park, Seung Kook; Park, Kook Nam; Hong, Yun Jeong; Park, Jang Jin; Choi, Jong Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    The preliminary decommissioning plan should be written with various chapters such as a radiological characterization, a decommissioning strategy and methods, a design for decommissioning usability, a safety evaluation, decontamination and dismantling activities, radioactive waste management, an environmental effect evaluation, and fire protection. The process requirements of the decommissioning project and the technical requirements and technical criteria should comply with regulatory requirements when dismantling of a nuclear facility. The requirements related to safety in the dismantling of a nuclear facility refer to the IAEA safety serious. The present paper indicates that a decommissioning design and plan, dismantling activities, and a decommissioning project will be influenced by the decommissioning regulatory requirements when dismantling of a nuclear facility. We hereby paved the way to find the effect of the regulatory requirements on the decommissioning of a whole area from the decommissioning strategy to the radioactive waste treatment when dismantling a nuclear facility. The decommissioning requirements have a unique feature in terms of a horizontal relationship as well as a vertical relationship from the regulation requirements to the decommissioning technical requirements. The decommissioning requirements management will be conducted through research that can recognize a multiple relationship in the next stage.

  2. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Greece

    International Nuclear Information System (INIS)

    2015-01-01

    In Greece, there are no nuclear power plants and nuclear energy is not considered as an option in the foreseeable future. There is, however, one nuclear research reactor (in extended shutdown since 2014) and one sub-critical assembly. Radioactive waste originating from medicine, research and industry is classified as low level. Although there is no framework act dealing comprehensively with the different aspects of nuclear energy, there are various laws, decrees and regulations of a more specific nature governing several aspects of nuclear activities. This paper gives information on the general regulatory regime (mining regime, radioactive substances, nuclear fuel and equipment, nuclear installations (licensing and inspection, including nuclear safety, emergency response, trade in nuclear materials and equipment, radiation protection, radioactive waste management, nuclear security, transport, nuclear third party liability) and on the institutional framework with the regulatory and supervisory authorities (Greek Atomic Energy Commission (EEAE))

  3. A balance of activity in brain control and reward systems predicts self-regulatory outcomes.

    Science.gov (United States)

    Lopez, Richard B; Chen, Pin-Hao A; Huckins, Jeremy F; Hofmann, Wilhelm; Kelley, William M; Heatherton, Todd F

    2017-05-01

    Previous neuroimaging work has shown that increased reward-related activity following exposure to food cues is predictive of self-control failure. The balance model suggests that self-regulation failures result from an imbalance in reward and executive control mechanisms. However, an open question is whether the relative balance of activity in brain systems associated with executive control (vs reward) supports self-regulatory outcomes when people encounter tempting cues in daily life. Sixty-nine chronic dieters, a population known for frequent lapses in self-control, completed a food cue-reactivity task during an fMRI scanning session, followed by a weeklong sampling of daily eating behaviors via ecological momentary assessment. We related participants' food cue activity in brain systems associated with executive control and reward to real-world eating patterns. Specifically, a balance score representing the amount of activity in brain regions associated with self-regulatory control, relative to automatic reward-related activity, predicted dieters' control over their eating behavior during the following week. This balance measure may reflect individual self-control capacity and be useful for examining self-regulation success in other domains and populations. © The Author (2017). Published by Oxford University Press.

  4. The mass media role in acceptance activities of Slovak Republic's Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    Seliga, Mojmir

    1998-01-01

    Communication is the vital link between Nuclear Regulatory Authority and the public. If people do not know and understand the facts on which optimal a safety energy choice decisions should be based they cannot make informed decisions on how their own objectives can be met. The following ten commandments of communications are pointed out: be yourself; be comfortable and confident; be honest; be brief; be human; be personal; be positive and consistent; be attentive; be energetic; be committed and sincere. The important aspect is to test whether the nuclear energy in the Slovak Republic is acceptable according to mandatory rules and if its operation is regulated by the state through the independent institution - the Nuclear Regulatory Authority of the Slovak Republic (UJD). The media in Slovakia has on important power. Many organizations are therefore apprehensive when dealing with the press, radio and television. Many people would simply prefer not to get panicked when the dreaded microphones and cameras do appear. UJD considers the whole area of public relations as an essential component of its activity. UJD intends to offer the public true, systematic, qualified, understandable and independent information, regarding the safety of nuclear power plants, as well as regarding the methods and results of UJD work. Generally, public information is considered a significant contribution to the creation of confidence into the regulatory work. The paper presents the UJD communication program and relations with media as well as the preparedness of public information in case of emergency

  5. Waste management regulatory compliance issues related to D ampersand D activities at Oak Ridge National Laboratory (ORNL)

    International Nuclear Information System (INIS)

    Hitch, J.P.; Arnold, S.E.; Burwinkle, T.; Daugherty, D.

    1994-01-01

    The waste management activities at ORNL related to the decontamination and decommissioning (D ampersand D) of radioactively contaminated buildings are divided into four categories: Operational facilities, inactive or surplus facilities, future facilities planning, and D ampersand D activities. This paper only discusses regulatory issues related to inactive or surplus facilities. Additionally, rather than attempting to address all resulting waste streams and related regulations, this paper highlights only a few of the ORNL waste streams that present key regulatory issues

  6. Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites

    Science.gov (United States)

    Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas

    2017-01-01

    The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly. PMID:28949297

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Regulatory inspection activities on nuclear power plant sites during construction in the United Kingdom

    International Nuclear Information System (INIS)

    Jeffery, J.V.

    1977-01-01

    The work of regulatory inspection of the construction of the plant on the site is performed not only by the inspector who has been allocated to inspection duties for that site but also by the specialist staff who are involved with the safety assessment of the plant. The co-ordination of this work is described in the paper and examples are given of inspection activities associated with the enforcement requirements of licence conditions as well as those related to the inspection of the plant itself. (author)

  9. Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

    Directory of Open Access Journals (Sweden)

    Kristina Kirschner

    2015-03-01

    Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

  10. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Sweden

    International Nuclear Information System (INIS)

    2008-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects (The Environmental Code, Environmental impact statement, Permit under the Environmental Code)); 5. Trade in nuclear materials and equipment; 6. Radiological protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability (The Nuclear Liability Act; Chernobyl legislation); II. Institutional Framework: 1. Ministries with responsibilities concerning nuclear activities (Ministry of the Environment; Ministry of Enterprise, Energy and Communications; Ministry of Justice; Ministry of Foreign Affairs); 2. Swedish Radiation Safety Authority

  11. Key regulatory and safety issues emerging NEA activities. Lessons Learned from Fukushima Dai-ichi NPS Accident - Key Regulatory and Safety Issues

    International Nuclear Information System (INIS)

    Nakoski, John

    2013-01-01

    A presentation was provided on the key safety and regulatory issues and an update of activities undertaken by the NEA and its members in response to the accident at the Fukushima Daiichi nuclear power stations (NPS) on 11 March 2011. An overview of the accident sequence and the consequences was provided that identified the safety functions that were lost (electrical power, core cooling, and primary containment) that lead to units 1, 2, and 3 being in severe accident conditions with large off-site releases. Key areas identified for which activities of the NEA and member countries are in progress include accident management; defence-in-depth; crisis communication; initiating events; operating experience; deterministic and probabilistic assessments; regulatory infrastructure; radiological protection and public health; and decontamination and recovery. For each of these areas, a brief description of the on-going and planned NEA activities was provided within the three standing technical committees of the NEA with safety and regulatory mandates (the Committee on Nuclear Regulatory Activities - CNRA, the Committee on the Safety of Nuclear Installations - CSNI, and the Committee on Radiation Protection and Public Health - CRPPH). On-going activities of CNRA include a review of enhancement being made to the regulatory aspects for the oversight of on-site accident management strategies and processes in light of the lessons learned from the accident; providing guidance to regulators on crisis communication; and supporting the peer review of the safety assessments of risk-significant research reactor facilities in light of the accident. Within the scope of the CSNI mandate, activities are being undertaken to better understand accident progression; characteristics of new fuel designs; and a benchmarking study of fast-running software for estimating source term under severe accident conditions to support protective measure recommendations. CSNI also has ongoing work in human

  12. Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics

    KAUST Repository

    Roy, S.

    2015-06-27

    Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff, (M1) and Hivep1, Nfil3, Prdm1, (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.

  13. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Switzerland

    International Nuclear Information System (INIS)

    2010-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment (Nuclear fuels; Radioactive substances and equipment generating ionising radiation); 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection; 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability; 11. Environmental protection; II. Institutional Framework: 1. Regulatory and supervisory authorities (Federal Council; Federal Assembly; Federal Department of the Environment, Transport, Energy and Communications - DETEC; Federal Office of Energy - SFOE; Swiss Federal Nuclear Safety Inspectorate - IFSN; Federal Department of Home Affairs - FDHA; Federal Office of Public Health - FOPH; State Secretariat for Education and Research - SER; Other authorities); 2. Advisory bodies (Swiss Federal Nuclear Safety Commission - KNS; Federal Commission for Radiological Protection and Monitoring of the Radioactivity in the Environment; Federal Emergency Organisation on Radioactivity); 3. Public and semi-public agencies (Paul-Scherrer Institute - PSI; Fund for the decommissioning of nuclear installations and for the waste disposal; National Co-operative for the

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

    International Nuclear Information System (INIS)

    2003-01-01

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

  15. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Belgium

    International Nuclear Information System (INIS)

    2010-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Nuclear facilities (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response; Decommissioning); 4. Trade in nuclear materials and equipment; 5. Radiological protection; 6. Radioactive waste management; 7. Non-proliferation of nuclear weapons and physical protection of nuclear material (International aspects; National control and security measures); 8. Transport; 9. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Federal Agency for Nuclear Control - FANC; Federal Public Service for Home Affairs; Federal Public Service for Economy, SME's, Self-Employed and Energy; Federal Public Service for Employment, Labour and Social Dialogue; Federal Public Service for Defence; Federal Public Service for Foreign Affairs, Foreign Trade and Development Co-operation; Federal Public Planning Service for Science Policy); 2. Advisory bodies (Scientific Council for Ionizing Radiation of the Federal Agency for Nuclear Control; Superior Health Council; Superior Council for Safety, Hygiene and Enhancement of Workplaces; Advisory Committee for the Non-Proliferation of Nuclear Weapons; Commission for Electricity and Gas Regulation - CREG)

  16. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Italy

    International Nuclear Information System (INIS)

    2010-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response); 5. Trade in nuclear materials and equipment (General provisions; Patents); 6. Radiation Protection (Protection of workers; Protection of the public; Protection of the environment); 7. Radioactive Waste Management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear Third Party Liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Interdepartmental Committee for Economic Planning; Nuclear Safety Agency; Prime Minister; Minister for Economic Development; Minister for Labour and Social Security; Minister for Health; Minister for the Environment; Minister for the Interior; Minister for Transport and Navigation; Minister for Foreign Trade (now incorporated in Ministry for Economic Development); Minister for Education; Treasury Minister; Minister for Universities and for Scientific and Technical Research; Minister for Foreign Affairs; State Advocate General); 2. Advisory bodies (Inter-ministerial Council for Consultation and Co-ordination; Coordinating Committee for Radiation Protection of Workers and the Public; Regional and Provincial Commissions for Public Health Protection

  17. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Austria

    International Nuclear Information System (INIS)

    2003-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I) - General Regulatory Regime - General Outline: 1. Introduction; 2. Mining Regime; 3. Radioactive Substances, Nuclear Fuel and Equipment; 4. Nuclear Installations (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in Nuclear Materials and Equipment; 6. Radiation Protection; 7. Radioactive Waste Management; 8. Non-Proliferation and Physical Protection; 9. Transport; 10. Nuclear Third Party Liability; II) - Institutional Framework: 1. Regulatory and Supervisory Authorities: A. Federal Authorities - Bund (The Federal Chancellery; The Federal Minister for Women's Affairs and Consumer Protection; The Federal Minister of the Interior; The Federal Minister for Economic Affairs; The Federal Minister of Finance; The Federal Minister of Labour, Health and Social Affairs; The Federal Minister of Science and Transport; The Federal Minister of Justice; The Federal Minister for the Environment; The Federal Minister for Foreign Affairs) B. Regional Authorities - Laender; C. District Authorities - Bezirksverwaltungsbehorden; 2. Advisory Bodies (Forum for Nuclear Questions, Radiation Protection Commission - SSK); 3. Public and Semi-Public Agencies (The Seibersdorf Austrian Research Centre; The Graz Nuclear Institute; The Nuclear Institute of the Austrian Universities; The Institute of Risk Research, University of Vienna)

  18. Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies

    Directory of Open Access Journals (Sweden)

    Nguyen Diane

    2013-01-01

    Full Text Available Abstract Background The United States (US Food and Drug Administration (FDA is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation to pharmaceutical companies. A regulatory letter represents the FDA’s first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA. This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997–2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Methods Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Results Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total, followed by the Office of Scientific Investigations (131; 5.3%, and the Office of Compliance (105; 4.3%. During the 2nd Clinton Administration (1997–2000 the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001–2008 it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009–2011 it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by

  19. Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies.

    Science.gov (United States)

    Nguyen, Diane; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Montagne, Michael

    2013-01-22

    The United States (US) Food and Drug Administration (FDA) is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA) and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation) to pharmaceutical companies. A regulatory letter represents the FDA's first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA.This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997-2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total), followed by the Office of Scientific Investigations (131; 5.3%), and the Office of Compliance (105; 4.3%). During the 2nd Clinton Administration (1997-2000) the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001-2008) it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009-2011) it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by administration: Clinton (122.3 ± 36.4), Bush (29.5

  20. Regulatory support activities of JNES by thermal-hydraulic and safety analyses

    International Nuclear Information System (INIS)

    Kasahara, Fumio

    2008-01-01

    Current status and some related topics on regulatory support activities of Japan Nuclear Energy Safety Organization (JNES) by thermal-hydraulic and safety analyses are reported. The safety of nuclear facilities is secured primarily by plant owners and operators. However, the regulatory body NISA (Nuclear and Industrial Safety Agency) has conducted a strict regulation to confirm the adequacy of the site condition as well as the basic and detailed design. The JNES has been conducting independent analyses from applicants (audit analyses, etc.) by direction of NISA and supporting its review. In addition to the audit analysis, thermal-hydraulic and safety analyses are used in such areas as analytical evaluation for investigation of causes of accidents and troubles, level 2 PSA for risk informed regulation, etc. Recent activities of audit analyses are for the application of Tsuruga 3 and 4 (APWR), the spent fuel storage facility for the establishment, and the LMFBR Monju for the core change. For the trouble event evaluation, the criticality accident analysis of Sika1 was carried out and the evaluation of effectiveness of accident management (AM) measure for Tomari 3 (PWR) and Monju was performed. The analytical codes for these evaluations are continuously revised by reflecting the state-of-art technical information and validated using the information provided by the data from JAEA, OECD project, etc. (author)

  1. Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

    Science.gov (United States)

    Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

    2017-11-17

    Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

  2. Status on the regulatory aspects in NORM/TENORM activities and waste in Malaysia

    International Nuclear Information System (INIS)

    Hassan, Hasmadi

    2005-01-01

    In Malaysia, waste associated with TENORM are generated mostly in the tin mining and smelting, processing of minerals, and oil and gas industry. As one of a major tin producer in the world and the country current activities in oil production, the amount of waste generated in this kind of activities is quite substantial. Currently the government of Malaysia did not provide any provision in the law specifically for the exclusion of TENORM waste, however, the government did imposed the criteria for exclusion of this waste by adopting the guideline limit established by the IAEA safety series 26, which is very vital for the regulatory body i.e. Atomic Energy Licensing Board (AELB) to overcome the problems in managing some of waste related to TENORM industries. As one example, this guideline has been applied to one of the mineral processing industries in the country on decommissioning and disposing of their waste. Furthermore, due to economic reason and price of tin and its by-product is not viable and profitable so much, making this industry not significant in business and trade industries, several practices have been exempted from the regulatory control under the Atomic Energy Licensing Act, 1984. (author)

  3. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    Energy Technology Data Exchange (ETDEWEB)

    Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

    2013-02-08

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

  4. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    International Nuclear Information System (INIS)

    Takaoka, Yuki; Kawamoto, Seiji; Katayama, Akiko; Nakano, Toshiaki; Yamanaka, Yasushi; Takahashi, Miki; Shimada, Yayoi; Chiang, Kuei-Chen; Ohmori, Naoya; Aki, Tsunehiro; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Chen, Chao-Long; Ono, Kazuhisa

    2013-01-01

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4 + Foxp3 + Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

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

    International Nuclear Information System (INIS)

    2015-01-01

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

  6. TU-AB-204-00: CDRH/FDA Regulatory Processes and Device Science Activities

    International Nuclear Information System (INIS)

    2016-01-01

    The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) and the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC

  7. TU-AB-204-00: CDRH/FDA Regulatory Processes and Device Science Activities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) and the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC

  8. Experience and regulatory activities on advanced instrumentation and control systems applied to nuclear power plants in Korea

    International Nuclear Information System (INIS)

    Kim, B.R.

    1995-01-01

    This paper describes the status for applying microprocessor-based systems to nuclear power plants in Korea and the regulatory activities performed by Korea Institute of Nuclear Safety (KINS). And this presents the development of safety and regulatory technology for advanced I and C systems that has been carried out as a part of the next generation reactor development program in Korea. (author). 3 refs, 4 figs, 1 tab

  9. WAVE regulatory complex activation by cooperating GTPases Arf and Rac1

    DEFF Research Database (Denmark)

    Koronakis, Vassilis; Hume, Peter J; Humphreys, Daniel

    2011-01-01

    The WAVE regulatory complex (WRC) is a critical element in the control of actin polymerization at the eukaryotic cell membrane, but how WRC is activated remains uncertain. While Rho GTPase Rac1 can bind and activate WRC in vitro, this interaction is of low affinity, suggesting other factors may...... be important. By reconstituting WAVE-dependent actin assembly on membrane-coated beads in mammalian cell extracts, we found that Rac1 was not sufficient to engender bead motility, and we uncovered a key requirement for Arf GTPases. In vitro, Rac1 and Arf1 were individually able to bind weakly to recombinant...... be central components in WAVE signalling, acting directly, alongside Rac1....

  10. LWRS II&C Industry and Regulatory Engagement Activities for FY 11

    Energy Technology Data Exchange (ETDEWEB)

    Ken Thomas

    2011-09-01

    To ensure broad industry support and coordination for the Advanced Instrumentation, Information, and Controls (II&C) Systems Technologies research pathway, an engagement process will be continually pursued with nuclear asset owners, vendors, and suppliers, Nuclear Regulatory Commission (NRC), and the major industry support organizations of Electric Power Research Institute (EPRI), Institute of Nuclear Power Operations (INPO), and Nuclear Energy Institute (NEI). Nuclear asset owner engagement is a necessary and enabling activity to obtain data and accurate characterization of long-term operational challenges, assess the suitability of proposed research for addressing long-term needs, and gain access to data and representative infrastructure and expertise needed to ensure success of the proposed research and development (R&D) activities. Engagement with vendors and suppliers will ensure that vendor expectations and needs can be translated into requirements that can be met through technology commercialization.

  11. REFORM OF REGULATORY POLICY IN THE FIELD OF SUPERVISION OF AUDIT ACTIVITY

    Directory of Open Access Journals (Sweden)

    Iryna Kantsir

    2017-12-01

    Full Text Available Reforming the regulatory system and supervision of audit activity in Ukraine is a basic condition for Ukraine’s accession to the European Community, and the introduction of international standards in the field of audit and supervision of audit activity and quality assurance of audit services should be correlated with the standards of European and world audit practice. The dominant factor in the effective functioning of independent control is the choice of a model of supervision of the mechanism for its implementation; effectiveness of the system of monitoring the quality of audit services; effectiveness of legal and regulatory framework of audit activity. The regulation of audit activity is to coordinate direct and indirect actions aimed at the subject of audit activity with the purpose of ensuring the quality of audit services and minimizing the level of audit risk. The purpose of the research is: analysis of the basic models of regulation of audit activity aimed at improving the legal regulation of economic relations in general and subjects of audit activity in particular. Determination of expediency of implementation of public oversight as monitoring of the process of implementation of audit activity in the context of granting the right to conduct audit activities to individuals, implementation of standards of professional ethics and quality control of audit services, permanence of education and imposing sanctions for non-compliance by auditors with the requirements of the current legislation. Method (methodology. In the process of research, general scientific and special methods of scientific knowledge are used: abstract-logical (in the disclosure of theoretical and methodological foundations of public oversight; synthesis and system analysis (substantiation of the essential characteristics of the system of public oversight; system analysis and theoretical generalization (definition of institutional prerequisites for the introduction of

  12. An activating mutation of interferon regulatory factor 4 (IRF4) in adult T cell leukemia.

    Science.gov (United States)

    Cherian, Mathew A; Olson, Sydney; Sundaramoorthi, Hemalatha; Cates, Kitra; Cheng, Xiaogang; Harding, John; Martens, Andrew; Challen, Grant A; Tyagi, Manoj; Ratner, Lee; Rauch, Daniel

    2018-03-14

    The human T cell leukemia virus-1 (HTLV-1) oncoprotein Tax drives cell proliferation and resistance to apoptosis early in the pathogenesis of adult T-cell leukemia (ATL). Subsequently, likely as a result of specific immuno-editing, Tax expression is downregulated and functionally replaced by somatic driver mutations of the host genome. Both amplification and point mutations of interferon regulatory factor 4 (IRF4) have been previously detected in ATL, and the K59R mutation is the most common single-nucleotide variation in IRF4 and is found exclusively in ATL. Here high throughput whole-exome sequencing revealed recurrent activating genetic alterations in the T cell receptor, CD28, and NF-kB pathways. Moreover, we found that IRF4, which is transcriptionally activated downstream of these pathways, is frequently mutated in ATL. IRF4 RNA, protein, and IRF4 transcriptional targets are uniformly elevated in HTLV transformed cells and ATL cell lines, and IRF4 was bound to genomic regulatory DNA of many of these transcriptional targets in HTLV-1 transformed cell lines. We further noted that the K59R IRF4 mutant is expressed at higher levels in the nucleus than is wild-type IRF4, and is transcriptionally more active. Expression of both wild-type and the K59R mutant of IRF4 from a constitutive promoter in retrovirally transduced murine bone marrow cells increased the abundance of T lymphocytes but not myeloid cells or B lymphocytes in mice. IRF4 may represent a therapeutic target in ATL since ATL cells select for a mutant of IRF4 with higher nuclear expression and transcriptional activity, and over-expression of IRF4 induces the expansion of T lymphocytes in vivo. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  13. 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.

  14. GITR ligand-costimulation activates effector and regulatory functions of CD4+ T cells

    International Nuclear Information System (INIS)

    Igarashi, Hanna; Cao, Yujia; Iwai, Hideyuki; Piao, Jinhua; Kamimura, Yosuke; Hashiguchi, Masaaki; Amagasa, Teruo; Azuma, Miyuki

    2008-01-01

    Engagement of glucocorticoid-induced TNFR-related protein (GITR) enables the costimulation of both CD25 - CD4 + effector (Teff) and CD25 + CD4 + regulatory (Treg) cells; however, the effects of GITR-costimulation on Treg function remain controversial. In this study, we examined the effects of GITR ligand (GITRL) binding on the respective functions of CD4 + T cells. GITRL-P815 transfectants efficiently augmented anti-CD3-induced proliferation and cytokine production by Teff cells. Proliferation and IL-10 production in Treg were also enhanced by GITRL transfectants when exogenous IL-2 and stronger CD3 stimulation was provided. Concomitant GITRL-costimulation of Teff and Treg converted the anergic state of Treg into a proliferating state, maintaining and augmenting their function. Thus, GITRL-costimulation augments both effector and regulatory functions of CD4 + T cells. Our results suggest that highly activated and increased ratios of Treg reverse the immune-enhancing effects of GITRL-costimulation in Teff, which may be problematic for therapeutic applications using strong GITR agonists

  15. Localizing potentially active post-transcriptional regulations in the Ewing's sarcoma gene regulatory network

    Directory of Open Access Journals (Sweden)

    Delyon Bernard

    2010-11-01

    Full Text Available Abstract Background A wide range of techniques is now available for analyzing regulatory networks. Nonetheless, most of these techniques fail to interpret large-scale transcriptional data at the post-translational level. Results We address the question of using large-scale transcriptomic observation of a system perturbation to analyze a regulatory network which contained several types of interactions - transcriptional and post-translational. Our method consisted of post-processing the outputs of an open-source tool named BioQuali - an automatic constraint-based analysis mimicking biologist's local reasoning on a large scale. The post-processing relied on differences in the behavior of the transcriptional and post-translational levels in the network. As a case study, we analyzed a network representation of the genes and proteins controlled by an oncogene in the context of Ewing's sarcoma. The analysis allowed us to pinpoint active interactions specific to this cancer. We also identified the parts of the network which were incomplete and should be submitted for further investigation. Conclusions The proposed approach is effective for the qualitative analysis of cancer networks. It allows the integrative use of experimental data of various types in order to identify the specific information that should be considered a priority in the initial - and possibly very large - experimental dataset. Iteratively, new dataset can be introduced into the analysis to improve the network representation and make it more specific.

  16. Activation of counter-regulatory mechanisms in a rat renal acute rejection model

    Directory of Open Access Journals (Sweden)

    Salomon Daniel R

    2008-02-01

    Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

  17. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Germany

    International Nuclear Information System (INIS)

    2011-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment (Definitions; Licensing requirements); 4. Nuclear installations (Licensing regime; Protection of the environment against radiation effects; Emergency response; Surveillance of installations and activities); 5. Trade in nuclear materials and equipment; 6. Radiation protection (General; Principal elements of the Radiation Protection Ordinance; Additional radiation protection norms); 7. Radioactive waste management (Atomic Energy Act 2002; Radiation Protection Ordinance; International obligations); 8. Non-proliferation and physical protection (Non-proliferation regime; Physical protection regime); 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities: Federal authorities (Federal Minister for the Environment, Nature Conservation and Nuclear Safety, Federal Minister for Education and Research, Federal Minister of Finance, Federal Minister of Transport, Building and Urban Affairs, Federal Minister for Economy and Technology, Federal Minister of Defence, Federal Office for Radiation Protection - BfS, Federal Office of Economics and Export Control); Authorities of the Laender; 2. Advisory bodies (Reactor Safety Commission - RSK; Radiation Protection Commission - SSK; Disposal Commission - ESK; Nuclear Technology

  18. Self-Regulatory Strategies as Correlates of Physical Activity Behavior in Persons With Multiple Sclerosis.

    Science.gov (United States)

    Cederberg, Katie L; Balto, Julia M; Motl, Robert W

    2018-05-01

    To examine self-regulation strategies as correlates of physical activity in persons with multiple sclerosis (MS). Cross-sectional, or survey, study. University-based research laboratory. Convenience sample of persons with MS (N=68). Not applicable. Exercise Self-Efficacy Scale (EXSE), 12-item Physical Activity Self-Regulation Scale (PASR-12), and Godin Leisure-Time Exercise Questionnaire (GLTEQ). Correlation analyses indicated that GLTEQ scores were positively and significantly associated with overall self-regulation (r=.43), self-monitoring (r=.45), goal-setting (r=.27), reinforcement (r=.30), time management (r=.41), and relapse prevention (r=.53) PASR-12 scores. Regression analyses indicated that relapse prevention (B=5.01; SE B=1.74; β=.51) and self-monitoring (B=3.65; SE B=1.71; β=.33) were unique predictors of physical activity behavior, and relapse prevention demonstrated a significant association with physical activity behavior that was accounted for by EXSE. Our results indicate that self-regulatory strategies, particularly relapse prevention, may be important correlates of physical activity behavior that can inform the design of future behavioral interventions in MS. Published by Elsevier Inc.

  19. Regulatory Assistance, Stakeholder Outreach, and Coastal and Marine Spatial Planning Activities in Support of Marine and Hydrokinetic Energy Deployment

    Energy Technology Data Exchange (ETDEWEB)

    Geerlofs, Simon H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Copping, Andrea E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Van Cleve, Frances B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Blake, Kara M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hanna, Luke A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2011-09-01

    This fiscal year 2011 progress report summarizes activities carried out under DOE Water Power Task 2.1.7, Permitting and Planning. Activities under Task 2.1.7 address the concerns of a wide range of stakeholders with an interest in the development of the marine and hydrokinetic (MHK) energy industry, including regulatory and resource management agencies, tribes, nongovernmental organizations, and industry.

  20. Physical Activity in the Transition to University: The Role of Past Behavior and Concurrent Self-Regulatory Efficacy

    Science.gov (United States)

    Crozier, Alyson J.; Gierc, Madelaine S. H.; Locke, Sean R.; Brawley, Lawrence R.

    2015-01-01

    Objective: Two studies were conducted to examine the relationship between past physical activity, concurrent self-regulatory efficacy (CSRE), and current physical activity during the transition to university. Participants: Study 1 included 110 first-year undergraduate students recruited during October/November of 2012. Study 2 involved 86…

  1. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells.

    Science.gov (United States)

    Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

    2009-08-11

    The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFbeta, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP- cells. Remarkably, CD25+GARP- T cells expanded in culture contained 3-5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25-GARP- cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) -infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation.

  2. Regulatory inspection activities related to inspection planning, plant maintenance and assessment of safety. Proceedings of an international workshop

    Energy Technology Data Exchange (ETDEWEB)

    Van Binnebeek, J. J. [AIB-Vincotte Nuclear - AVN, Avenue du Roi, 157, B-1060 Brussels (Belgium); Aubrey, Richard; Grandame, Melvyn [Atomic Energy Control Board - AECB, P.O. Box 1046, Station B, 280 Slater Street, Ottawa, Ontario K1P 5S9 (Canada); Aro, Ilari [Finnish Centre for Radiation and Nuclear Safety - STUK, P.O. Box 14, FIN-00881 Helsinki (Finland); Balloffet, Yves [DRIRE Rhone Alpes, 146, rue Pierre Corneille, 69426 Lyon CEDEX 03 (France); Klonk, Hartmut [Bundesamt fuer Strahlenschutz - BfS, Federal Office for Radiation Protection, Postbox 10 01 49, 38201 Salzgitter 1 (Germany); Manzella, Pietro [A.N.P.A., Via V. Brancati, 48, 1-00144 Roma EUR (Italy); Koizumi, Hiroyoshi [Tech. Stan. Dept. - JAPEIC, Shin-Toranomon Bldg., 1-5-11, Akasaka, Minato-ku, Tokyo 107 (Japan); Bouvrie, E.C. des [Ministry of Social Affairs and Employment, Nuclear Safety Dept. KFD, P.O. Box 90804, 2509 LV The Hague (Netherlands); Forsberg, Staffan [Swedish Nuclear Power Inspectorate - SKI, Klarabergsviadukten 90, S-10658 Stockholm (Sweden); Lang, Hans-Guenter [Section Plant Coordination and Inspection, Swiss Federal Nuclear Safety Inspectorate - HSK, CH-5232 Villigen-HSK (Switzerland); Mehew, Robert; Warren, Thomas; Woodhouse, Paul [Health and Safety Executive - NII, St. Peter' s House, Balliol Road, Bootle, Merseyside L20 3LZ (United Kingdom); Gallo, Robert M. [Special Inspection Branch, US Nuclear Regulatory Commission - US NRC, Mail Stop 0-9A1, Washington, DC 20555 (United States); Campbell, Rob [International Atomic Energy Agency - IAEA, P.O. Box 100, A-1400 Vienna (International Atomic Energy Agency (IAEA))

    1997-07-01

    The NEA Committee on Nuclear Regulatory Activities (CNRA) believes that an essential factor in ensuring the safety of nuclear installations is the continuing exchange and analysis of technical information and data. To facilitate this exchange the Committee has established Working Groups and Groups of Experts in specialised topics. CNRA believes that safety inspections are a major element in the regulatory authority's efforts to ensure the safe operation of nuclear facilities. Considering the importance of these issues, the Committee has established a special Working Group on Inspection Practices (WGIP). The purpose of WGIP, is to facilitate the exchange of information and experience related to regulatory safety inspections between CNRA Member countries. This was the 3. international workshop held by the WGIP on regulatory inspection activities. The focus of this workshop was on 3 main topics; Inspection Planning, Plant Maintenance and Assessment of Safety. This document presents the proceedings from the workshop, including: workshop programme, results and conclusions, papers and presentations and the list of participants. The main purpose of the Workshop is to provide a forum of exchange of information on the regulatory inspection activities.

  3. Regulatory inspection activities related to inspection planning, plant maintenance and assessment of safety. Proceedings of an international workshop

    International Nuclear Information System (INIS)

    Van Binnebeek, J.J.; Aubrey, Richard; Grandame, Melvyn; Aro, Ilari; Balloffet, Yves; Klonk, Hartmut; Manzella, Pietro; Koizumi, Hiroyoshi; Bouvrie, E.C. des; Forsberg, Staffan; Lang, Hans-Guenter; Mehew, Robert; Warren, Thomas; Woodhouse, Paul; Gallo, Robert M.; Campbell, Rob; )

    1997-01-01

    The NEA Committee on Nuclear Regulatory Activities (CNRA) believes that an essential factor in ensuring the safety of nuclear installations is the continuing exchange and analysis of technical information and data. To facilitate this exchange the Committee has established Working Groups and Groups of Experts in specialised topics. CNRA believes that safety inspections are a major element in the regulatory authority's efforts to ensure the safe operation of nuclear facilities. Considering the importance of these issues, the Committee has established a special Working Group on Inspection Practices (WGIP). The purpose of WGIP, is to facilitate the exchange of information and experience related to regulatory safety inspections between CNRA Member countries. This was the 3. international workshop held by the WGIP on regulatory inspection activities. The focus of this workshop was on 3 main topics; Inspection Planning, Plant Maintenance and Assessment of Safety. This document presents the proceedings from the workshop, including: workshop programme, results and conclusions, papers and presentations and the list of participants. The main purpose of the Workshop is to provide a forum of exchange of information on the regulatory inspection activities

  4. Proposed Activities to Address Regulatory Gaps and Challenges for Licensing Advanced Reactors Using Seismic Isolation

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, Justin Leigh [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kammerer, Annie M. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Whittaker, Andrew S. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-12-01

    Over the last decade, particularly since implementation of the certified design regulatory approaches outlined in 10 CFR 52, “Licenses, Certifications, and Approvals for Nuclear Power Plants,” interest has been increasing in the use of seismic isolation (SI) technology to support seismic safety in nuclear facilities. In 2009, the United States (U.S.) Nuclear Regulatory Commission (NRC) initiated research activities to develop new guidance targeted at isolated facilities because SI is being considered for nuclear power plants in the U.S. One product of that research, which was developed around a risk-informed regulatory approach, is a draft NRC NUREG series (NUREG/CR) report that investigates and discusses considerations for use of SI in otherwise traditionally founded large light water reactors (LWRs). A coordinated effort led to new provisions for SI of LWRs in the American Society of Civil Engineers standard ASCE/SEI 4-16, “Seismic Analysis of Safety Related Nuclear Structures.” The risk-informed design philosophy that underpinned development of the technical basis for these documents led to a set of proposed performance objectives and acceptance criteria intended to serve as the foundation for future NRC guidance on the use of SI and related technology. Although the guidance provided in the draft SI NUREG/CR report and ASCE/SEI 4 16 provides a sound basis for further development of nuclear power plant designs incorporating SI, these initial documents were focused on surface-founded or near-surface-founded LWRs and were, necessarily, limited in scope. For example, there is limited information in both the draft NUREG/CR report and ASCE/SEI 4-16 related to nonlinear analysis of soil-structure systems for deeply-embedded reactors, the isolation of components, and the use of vertical isolation systems. Also not included in the draft SI NUREG/CR report are special considerations for licensing of isolated facilities using the certified design approach in 10 CFR

  5. Proposed Activities to Address Regulatory Gaps and Challenges for Licensing Advanced Reactors Using Seismic Isolation

    International Nuclear Information System (INIS)

    Coleman, Justin Leigh; Kammerer, Annie M.; Whittaker, Andrew S.

    2016-01-01

    Over the last decade, particularly since implementation of the certified design regulatory approaches outlined in 10 CFR 52, 'Licenses, Certifications, and Approvals for Nuclear Power Plants,' interest has been increasing in the use of seismic isolation (SI) technology to support seismic safety in nuclear facilities. In 2009, the United States (U.S.) Nuclear Regulatory Commission (NRC) initiated research activities to develop new guidance targeted at isolated facilities because SI is being considered for nuclear power plants in the U.S. One product of that research, which was developed around a risk-informed regulatory approach, is a draft NRC NUREG series (NUREG/CR) report that investigates and discusses considerations for use of SI in otherwise traditionally founded large light water reactors (LWRs). A coordinated effort led to new provisions for SI of LWRs in the American Society of Civil Engineers standard ASCE/SEI 4-16, 'Seismic Analysis of Safety Related Nuclear Structures.' The risk-informed design philosophy that underpinned development of the technical basis for these documents led to a set of proposed performance objectives and acceptance criteria intended to serve as the foundation for future NRC guidance on the use of SI and related technology. Although the guidance provided in the draft SI NUREG/CR report and ASCE/SEI 4 16 provides a sound basis for further development of nuclear power plant designs incorporating SI, these initial documents were focused on surface-founded or near-surface-founded LWRs and were, necessarily, limited in scope. For example, there is limited information in both the draft NUREG/CR report and ASCE/SEI 4-16 related to nonlinear analysis of soil-structure systems for deeply-embedded reactors, the isolation of components, and the use of vertical isolation systems. Also not included in the draft SI NUREG/CR report are special considerations for licensing of isolated facilities using the certified design

  6. Office of Nuclear Regulatory Research summary of advanced reactors activities, June 4, 2001

    International Nuclear Information System (INIS)

    2001-01-01

    Pre-application interactions with potential licensee applicants will help NRC prepare for future submittals, through the development of the infrastructure necessary for licensing application reviews. RES has the lead for non-LWR advanced reactor pre-application initiatives and longer-range new technology initiatives. An advanced reactor group has been formed in REAHFB, and is currently performing a pre-application review of Exelon's Pebble Bed Modular Reactor. Recent industry requests for future pre application interaction include General Atomics' Gas Turbine-Modular Helium Reactor (GT-MHR) and Westinghouse International Reactor Innovative and Secure (IRIS) design. RES advanced reactors activities also include participation as an observer in DOE's Generation IV initiative. Pre-Application review objectives include the development of regulatory guidance, licensing approach, and technology-basis expectations for licensing advanced designs, including identifying significant technology, design, safety, licensing and policy issues that would need to be addressed in the licensing process. The presentation described the pre-application process for the Exelon PBMR. NRC first identifies additional information following topical meetings with Exelon, and Exelon formally documents and submits required topical Information. The staff then develops a preliminary assessment and drafts a response which is followed by stakeholder input and comments at a public workshop. Preliminary assessments are discussed with ACRS and ACNW, and Commission papers are written which provide staff positions and recommendations on proposed policy decisions. Some of the significant areas for the PBMR include: Process Issues, Legal and Financial Issues; Regulatory Framework; Fuel Performance and Qualification; Traditional Engineering Design (e.g, Nuclear, Thermal-Fluid, Materials); Fuel Cycle Safety Areas; PRA, SSC Safety Classification; PBMR Prototype Testing

  7. Dual regulatory switch confers tighter control on HtrA2 proteolytic activity.

    Science.gov (United States)

    Singh, Nitu; D'Souza, Areetha; Cholleti, Anuradha; Sastry, G Madhavi; Bose, Kakoli

    2014-05-01

    High-temperature requirement protease A2 (HtrA2), a multitasking serine protease that is involved in critical biological functions and pathogenicity, such as apoptosis and cancer, is a potent therapeutic target. It is established that the C-terminal post-synaptic density protein, Drosophila disc large tumor suppressor, zonula occludens-1 protein (PDZ) domain of HtrA2 plays pivotal role in allosteric modulation, substrate binding and activation, as commonly reported in other members of this family. Interestingly, HtrA2 exhibits an additional level of functional modulation through its unique N-terminus, as is evident from 'inhibitor of apoptosis proteins' binding and cleavage. This phenomenon emphasizes multiple activation mechanisms, which so far remain elusive. Using conformational dynamics, binding kinetics and enzymology studies, we addressed this complex behavior with respect to defining its global mode of regulation and activity. Our findings distinctly demonstrate a novel N-terminal ligand-mediated triggering of an allosteric switch essential for transforming HtrA2 to a proteolytically competent state in a PDZ-independent yet synergistic activation process. Dynamic analyses suggested that it occurs through a series of coordinated structural reorganizations at distal regulatory loops (L3, LD, L1), leading to a population shift towards the relaxed conformer. This precise synergistic coordination among different domains might be physiologically relevant to enable tighter control upon HtrA2 activation for fostering its diverse cellular functions. Understanding this complex rheostatic dual switch mechanism offers an opportunity for targeting various disease conditions with tailored site-specific effector molecules. © 2014 FEBS.

  8. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - France

    International Nuclear Information System (INIS)

    2011-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Framework: 1. General (The French nuclear power programme and its main players; French nuclear law); 2. Mining Regime; 3. Radioactive Substances and Nuclear Equipment (Regulatory diversity; Radioactive sources; Medical activities); 4. Trade in Nuclear Materials and Equipment (Basic nuclear installations - INB; Tax on basic nuclear installations, Additional taxes, Funding nuclear costs; Installations classified for environmental protection purposes (ICPE) using radioactive substances; Nuclear pressure equipment - ESPN; Defence-related nuclear installations and activities - IANID; Emergency plans); 5. Trade in Nuclear Materials and Equipment (General provisions; Patents); 6. Radiation protection (Protection of the public; Protection of workers; Radiation protection inspectors; Labour inspectors; Protection of individuals in a radiological emergency); 7. Radioactive Waste Management (General regulations; Radioactive waste regulations; Discharge of effluents); 8. Non-proliferation and physical protection (Materials not used for the nuclear deterrent; Materials used for the nuclear deterrent); 9. Transport (Licensing and notification regime: Transport of radioactive materials, Transport of nuclear materials, Transport of radioactive substances between member states of the European Union; Methods of transport: Land transport, Sea transport, Air transport, Transport by post); 10

  9. Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

    Directory of Open Access Journals (Sweden)

    Yoichiro Shibata

    2012-06-01

    Full Text Available Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species.

  10. Oncogenic MYC Activates a Feedforward Regulatory Loop Promoting Essential Amino Acid Metabolism and Tumorigenesis.

    Science.gov (United States)

    Yue, Ming; Jiang, Jue; Gao, Peng; Liu, Hudan; Qing, Guoliang

    2017-12-26

    Most tumor cells exhibit obligatory demands for essential amino acids (EAAs), but the regulatory mechanisms whereby tumor cells take up EAAs and EAAs promote malignant transformation remain to be determined. Here, we show that oncogenic MYC, solute carrier family (SLC) 7 member 5 (SLC7A5), and SLC43A1 constitute a feedforward activation loop to promote EAA transport and tumorigenesis. MYC selectively activates Slc7a5 and Slc43a1 transcription through direct binding to specific E box elements within both genes, enabling effective EAA import. Elevated EAAs, in turn, stimulate Myc mRNA translation, in part through attenuation of the GCN2-eIF2α-ATF4 amino acid stress response pathway, leading to MYC-dependent transcriptional amplification. SLC7A5/SLC43A1 depletion inhibits MYC expression, metabolic reprogramming, and tumor cell growth in vitro and in vivo. These findings thus reveal a MYC-SLC7A5/SLC43A1 signaling circuit that underlies EAA metabolism, MYC deregulation, and tumorigenesis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. T Cell Epitope Immunotherapy Induces a CD4+ T Cell Population with Regulatory Activity

    Directory of Open Access Journals (Sweden)

    Verhoef Adrienne

    2005-01-01

    Full Text Available Background Synthetic peptides, representing CD4+ T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils. Methods and Findings In this study we address the mechanism of action of peptide immunotherapy (PIT in cat-allergic, asthmatic patients. Cell-division-tracking dyes, cell-mixing experiments, surface phenotyping, and cytokine measurements were used to investigate immunomodulation in peripheral blood mononuclear cells (PBMCs after therapy. Proliferative responses of PBMCs to allergen extract were significantly reduced after PIT. This was associated with modified cytokine profiles generally characterised by an increase in interleukin-10 and a decrease in interleukin-5 production. CD4+ cells isolated after PIT were able to actively suppress allergen-specific proliferative responses of pretreatment CD4neg PBMCs in co-culture experiments. PIT was associated with a significant increase in surface expression of CD5 on both CD4+ and CD8+ PBMCs. Conclusion This study provides evidence for the induction of a population of CD4+ T cells with suppressor/regulatory activity following PIT. Furthermore, up-regulation of cell surface levels of CD5 may contribute to reduced reactivity to allergen.

  12. Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Marica Grskovic

    2007-08-01

    Full Text Available Understanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cells and identified genes upregulated in pluripotent cells both in vitro and in vivo. These genes are enriched for roles in transcription, chromatin remodeling, cell cycle, and DNA repair. We developed a novel computational algorithm, CompMoby, which combines analyses of sequences both aligned and non-aligned between different genomes with a probabilistic segmentation model to systematically predict short DNA motifs that regulate gene expression. CompMoby was used to identify conserved overrepresented motifs in genes upregulated in pluripotent cells. We show that the motifs are preferentially active in undifferentiated mouse ES and embryonic germ cells in a sequence-specific manner, and that they can act as enhancers in the context of an endogenous promoter. Importantly, the activity of the motifs is conserved in human ES cells. We further show that the transcription factor NF-Y specifically binds to one of the motifs, is differentially expressed during ES cell differentiation, and is required for ES cell proliferation. This study provides novel insights into the transcriptional regulatory networks of pluripotent cells. Our results suggest that this systematic approach can be broadly applied to understanding transcriptional networks in mammalian species.

  13. Insect growth regulatory activity of Vitex trifolia and Vitex agnus-castus essential oils against Spilosoma obliqua.

    Science.gov (United States)

    Tandon, Shishir; Mittal, Ashutosh K; Pant, A K

    2008-06-01

    Essential oils of Vitex trifolia and Vitex agnus-castus were evaluated against Vth instar larvae of Spilosoma obliqua, when applied topically on the dorsal side of mesothoracic region, for insect growth regulatory activity. This treatment caused extended larval period and pupal period, increase in larval mortality and adult deformity and decrease in adult emergence, fecundity of female and egg fertility of test insect.

  14. L'Islam noir à Bahia d'après les travaux de l'école ethnologique brèsilienne

    Directory of Open Access Journals (Sweden)

    Roger Bastide

    1951-03-01

    Full Text Available RICARD (Robert. - L'Islam noir à Bahia d'après les travaux de l'école ethnologique brèsilienne (Primeiro Artigo do Parágrafo Depois da publicação, em frances, do livro de Nina Rodrigues sobre O animismo fetichista dos negros da Bahia e da duas memórias do Piére Etienne, parece que a França pouco tem ouvido falar dos problemas afro-brasileiras.

  15. Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulate Myelination in Zebrafish

    Directory of Open Access Journals (Sweden)

    Yuhei Nishimura

    2016-07-01

    Full Text Available Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS, and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs. Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation

  16. Safety performance indicators used by the Russian Safety Regulatory Authority in its practical activities on nuclear power plant safety regulation

    International Nuclear Information System (INIS)

    Khazanov, A.L.

    2005-01-01

    The Sixth Department of the Nuclear, Industrial and Environmental Regulatory Authority of Russia, Scientific and Engineering Centre for Nuclear and Radiation Safety process, analyse and use the information on nuclear power plants (NPPs) operational experience or NPPs safety improvement. Safety performance indicators (SPIs), derived from processing of information on operational violations and analysis of annual NPP Safety Reports, are used as tools to determination of trends towards changing of characteristics of operational safety, to assess the effectiveness of corrective measures, to monitor and evaluate the current operational safety level of NPPs, to regulate NPP safety. This report includes a list of the basic SPIs, those used by the Russian safety regulatory authority in regulatory activity. Some of them are absent in list of IAEA-TECDOC-1141 ('Operational safety performance indicators for nuclear power plants'). (author)

  17. Decommissioning: Regulatory activities and identification of key organizational and human factors safety issues

    International Nuclear Information System (INIS)

    Durbin, N.E.; Melber, B.D.; Lekberg, A.

    2001-12-01

    In the late 1990's the Swedish government decided to shut down Unit 1 of the Barsebaeck nuclear power plant. This report documents some of the efforts made by the Swedish Nuclear Power Inspectorate (SKI) to address human factors and organizational issues in nuclear safety during decommissioning of a nuclear facility. This report gives a brief review of the background to the decommissioning of Barsebaeck 1 and points out key safety issues that can arise during decommissioning. The main regulatory activities that were undertaken were requirements that the plant provide special safety reports on decommissioning focusing on first, the operation of both units until closure of Unit 1 and second, the operation of Unit 2 when Unit 1 was closed. In addition, SKI identified areas that might be affected by decommissioning and called these areas out for special attention. With regard to these areas of special attention, SKI required that the plant provide monthly reports on changing and emerging issues as well as self-assessments of the areas to be addressed in the special safety reports. Ten key safety issues were identified and evaluated with regard to different stages of decommissioning and with regard to the actions taken by Barsebaeck. Some key conclusions from SKI's experience in regulating a decommissioning nuclear power plant conclude the report

  18. Regulatory cascade and biological activity of Beauveria bassiana oosporein that limits bacterial growth after host death.

    Science.gov (United States)

    Fan, Yanhua; Liu, Xi; Keyhani, Nemat O; Tang, Guirong; Pei, Yan; Zhang, Wenwen; Tong, Sheng

    2017-02-28

    The regulatory network and biological functions of the fungal secondary metabolite oosporein have remained obscure. Beauveria bassiana has evolved the ability to parasitize insects and outcompete microbial challengers for assimilation of host nutrients. A novel zinc finger transcription factor, BbSmr1 ( B. bassiana secondary metabolite regulator 1), was identified in a screen for oosporein overproduction. Deletion of Bbsmr1 resulted in up-regulation of the oosporein biosynthetic gene cluster ( OpS genes) and constitutive oosporein production. Oosporein production was abolished in double mutants of Bbsmr1 and a second transcription factor, OpS3 , within the oosporein gene cluster ( ΔBbsmr1ΔOpS3 ), indicating that BbSmr1 acts as a negative regulator of OpS3 expression. Real-time quantitative PCR and a GFP promoter fusion construct of OpS1 , the oosporein polyketide synthase, indicated that OpS1 is expressed mainly in insect cadavers at 24-48 h after death. Bacterial colony analysis in B. bassiana -infected insect hosts revealed increasing counts until host death, with a dramatic decrease (∼90%) after death that correlated with oosporein production. In vitro studies verified the inhibitory activity of oosporein against bacteria derived from insect cadavers. These results suggest that oosporein acts as an antimicrobial compound to limit microbial competition on B. bassiana -killed hosts, allowing the fungus to maximally use host nutrients to grow and sporulate on infected cadavers.

  19. Regulatory T cell activity in immunosuppresive mice model of pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Li, Jun-Lu; Chen, Ting-Sang; Yuan, Cong-Cong; Zhao, Guo-Qiang; Xu, Min; Li, Xiao-Yan; Cao, Jie; Xing, Li-Hua

    2017-08-01

    Pseudomonas aeruginosa (PA) pneumonia is a refractory, even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process. We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells, i.e., Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10). Seventy-two BALB/c mice were divided into four groups randomly: control (A), PA pneumonia (B), immunosuppression (C) and immunosuppression with PA pneumonia (D). Mice were sacrificed at 4, 8 and 24 h after establishing experimental models. The pathological changes of lung tissue were graded, and the FOXP3 mRNA and serum IL-10 levels were detected. Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C, but significantly pathological changes were found in groups B and D, especially in group D at 8 h (Ppneumonia in immunosuppressive individuals worsens rapidly, which may be associated with Treg cells function disturbance. And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

  20. Systematic approach to training. Experiences from the training activities of regulatory body personnel in STUK

    International Nuclear Information System (INIS)

    Aro, I.

    1998-04-01

    The report describes the experiences obtained of a training programme for nuclear power plant inspectors arranged in the 90's by the Radiation and Nuclear Safety Authority of Finland (STUK). In the implementation of the programme, a systematic method was used to analyse the training needs, to plan, develop and implement the training programme as well as to assess the programme's implementation and results. The method used, 'SAT Ae Systematic Approach to Training', is presented in 'Nuclear Power Plant Personnel Training and its Evaluation, A Guidebook', IAEA Technical Report Series No. 380, which is a publication of the International Atomic Energy Agency. It is recommended that this method be applied in the planning and implementation of nuclear power plant personnel training. The application of the method as a tool for developing the qualifications of nuclear power plant inspectors shows that the method is well suited for use in Finland. Until the 90's, STUK had no systematic approach to training activities. Some training was arranged internally, but training in most respects meant participation in external training events and international seminars. A more systematic approach was adopted in the early 90's. The main goal was to define basic competence profiles for inspectors working in different fields and to provide an internal basic training programme not available externally. The development of the training activities called for a profound renewal of the training function to ensure a systematic approach and high quality. The experiences gained in STUK are useful in co-operation with Eastern and Central European regulatory bodies; they can be utilized when the qualifications of personnel who carry out inspections are developed. This will extensively contribute to the safety of nuclear power plants. (orig.)

  1. Systematic approach to training. Experiences from the training activities of regulatory body personnel in STUK

    Energy Technology Data Exchange (ETDEWEB)

    Aro, I.

    1998-04-01

    The report describes the experiences obtained of a training programme for nuclear power plant inspectors arranged in the 90`s by the Radiation and Nuclear Safety Authority of Finland (STUK). In the implementation of the programme, a systematic method was used to analyse the training needs, to plan, develop and implement the training programme as well as to assess the programme`s implementation and results. The method used, `SAT Ae Systematic Approach to Training`, is presented in `Nuclear Power Plant Personnel Training and its Evaluation, A Guidebook`, IAEA Technical Report Series No. 380, which is a publication of the International Atomic Energy Agency. It is recommended that this method be applied in the planning and implementation of nuclear power plant personnel training. The application of the method as a tool for developing the qualifications of nuclear power plant inspectors shows that the method is well suited for use in Finland. Until the 90`s, STUK had no systematic approach to training activities. Some training was arranged internally, but training in most respects meant participation in external training events and international seminars. A more systematic approach was adopted in the early 90`s. The main goal was to define basic competence profiles for inspectors working in different fields and to provide an internal basic training programme not available externally. The development of the training activities called for a profound renewal of the training function to ensure a systematic approach and high quality. The experiences gained in STUK are useful in co-operation with Eastern and Central European regulatory bodies; they can be utilized when the qualifications of personnel who carry out inspections are developed. This will extensively contribute to the safety of nuclear power plants. (orig.). 2 refs.

  2. Association of Marek's Disease induced immunosuppression with activation of a novel regulatory T cells in chickens.

    Directory of Open Access Journals (Sweden)

    Angila Gurung

    2017-12-01

    Full Text Available Marek's Disease Virus (MDV is an alphaherpesvirus that infects chickens, transforms CD4+ T cells and causes deadly lymphomas. In addition, MDV induces immunosuppression early during infection by inducing cell death of the infected lymphocytes, and potentially due to activation of regulatory T (Treg-cells. Furthermore, immunosuppression also occurs during the transformation phase of the disease; however, it is still unknown how the disease can suppress immune response prior or after lymphoma formation. Here, we demonstrated that chicken TGF-beta+ Treg cells are found in different lymphoid tissues, with the highest levels found in the gut-associated lymphoid tissue (cecal tonsil: CT, fostering an immune-privileged microenvironment exerted by TGF-beta. Surprisingly, significantly higher frequencies of TGF-beta+ Treg cells are found in the spleens of MDV-susceptible chicken lines compared to the resistant line, suggesting an association between TGF-beta+ Treg cells and host susceptibility to lymphoma formation. Experimental infection with a virulent MDV elevated the levels of TGF-beta+ Treg cells in the lungs as early as 4 days post infection, and during the transformation phase of the disease in the spleens. In contrast to TGF-beta+ Treg cells, the levels of CD4+CD25+ T cells remained unchanged during the infection and transformation phase of the disease. Furthermore, our results demonstrate that the induction of TGF-beta+ Treg cells is associated with pathogenesis of the disease, as the vaccine strain of MDV did not induce TGF-beta+ Treg cells. Similar to human haematopoietic malignant cells, MDV-induced lymphoma cells expressed high levels of TGF-beta but very low levels of TGF-beta receptor I and II genes. The results confirm that COX-2/ PGE2 pathway is involved in immunosuppression induced by MDV-lymphoma cells. Taken together, our results revealed a novel TGF-beta+ Treg subset in chickens that is activated during MDV infection and tumour

  3. EU Activities for Training and Tutoring of Nuclear Regulatory Authorities and Technical Support Organisations Outside EU

    International Nuclear Information System (INIS)

    Pauwels, Henri; Daures, Pascal; Stockmann, Ynte

    2014-01-01

    Aim of Training and Tutoring Projects: Transfer of European Union nuclear safety regulatory experience and best practices. The following courses are listed: Courses in Nuclear Safety Regulation, Licensing and Enforcement; Nuclear Safety Assessment and Inspection

  4. The Report on Activities of the Nuclear Regulatory Authority of the Slovak Republic and on Safety of Nuclear Installations in the Slovak Republic in 2011

    International Nuclear Information System (INIS)

    2012-05-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2011 is presented. These activities are reported under the headings: Foreword; (1) Legislative activities; (2) Regulatory Activities; (3) Nuclear safety of nuclear power plants; (4) Nuclear Materials in SR; (5) Nuclear materials and physical protection of nuclear materials; (6) Scope of powers of the office building; (7) Emergency planning and preparedness; (8) International activities; (9) Public communication; (10) Nuclear Regulatory Authority of the Slovak Republic; (11) UJD SR organization chart; The International Nuclear Event Scale (INES); (12) Abbreviations.

  5. Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.

    Directory of Open Access Journals (Sweden)

    Paulo M F Cunha

    2010-07-01

    Full Text Available Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2 or the zinc-finger transcription factor lame duck (lmd lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.

  6. Regulatory activities related with the modification of the frequency of the programmed stoppings of the Argentine nuclear centrals

    International Nuclear Information System (INIS)

    Marino, E.; Calvo, J.; Waldman, R.; Navarro, R.

    2006-01-01

    The mandatory character documentation of the Argentinean nuclear power stations in Embalse and Atucha I, required the realization of a programmed stoppings every twelve months to execute that settled down in the maintenance and surveillance programs for each installation. Nucleoelectrica Argentina S.A., in it character of Responsible Entity of the operation of these power stations, requested to the Argentinean Nuclear Regulatory Authority, in 2003 and 2005 respectively, the authorization to change the period of the repetitive tests and of the preventive maintenance of the systems related with the safety, to extend them from twelve to eighteen months. The mentioned applications were founded in economic aspects and in inclining to a decrease in the doses of the workers that perform in the activities that are carried out in the programmed stops. The adopted position by the Nuclear Regulatory Authority to decide on these applications was based on the result of diverse evaluations that included the use of the Probabilistic Analysis of Safety specific of each power station, the operative experience resultant of the execution of the preventive maintenance program, and of the results of the repetitive tests and of the inspections in service. The regulatory decisions were different in each case. Indeed, the Embalse nuclear power station was authorized by the Regulatory Authority to modify from twelve to eighteen months the period among the realization of the repetitive tests and of the preventive maintenance, conditioned to the execution of some specific regulatory requirements. On the other hand, the Atucha I nuclear power station was not authorized to modify this period. In this presentation that is detailed the acted by the Nuclear Regulatory Authority in both cases, the used analysis tools, and the foundation of the adopted decisions. (Author)

  7. The multifaceted activity of the VirF regulatory protein in the Shigella lifestyle

    Directory of Open Access Journals (Sweden)

    Maria Letizia Di Martino

    2016-09-01

    Full Text Available Shigella is a highly adapted human pathogen, mainly found in the developing world and causing a severe enteric syndrome. The highly sophisticated infectious strategy of Shigella banks on the capacity to invade the intestinal epithelial barrier and cause its inflammatory destruction. The cellular pathogenesis and clinical presentation of shigellosis are the sum of the complex action of a large number of bacterial virulence factors mainly located on a large virulence plasmid (pINV. The expression of pINV genes is controlled by multiple environmental stimuli through a regulatory cascade involving proteins and sRNAs encoded by both the pINV and the chromosome. The primary regulator of the virulence phenotype is VirF, a DNA-binding protein belonging to the AraC family of transcriptional regulators. The virF gene, located on the pINV, is expressed only within the host, mainly in response to the temperature transition occurring when the bacterium transits from the outer environment to the intestinal milieu. VirF then acts as anti-H-NS protein and directly activates the icsA and virB genes, triggering the full expression of the invasion program of Shigella. In this review we will focus on the structure of VirF, on its sophisticated regulation, and on its role as major player in the path leading from the non invasive to the invasive phenotype of Shigella. We will address also the involvement of VirF in mechanisms aimed at withstanding adverse conditions inside the host, indicating that this protein is emerging as a global regulator whose action is not limited to virulence systems. Finally, we will discuss recent observations conferring VirF the potential of a novel antibacterial target for shigellosis.

  8. The diabetes type 1 locus Idd6 modulates activity of CD4+CD25+ regulatory T-cells.

    Science.gov (United States)

    Rogner, Ute Christine; Lepault, Françoise; Gagnerault, Marie-Claude; Vallois, David; Morin, Joëlle; Avner, Philip; Boitard, Christian

    2006-01-01

    The genetic locus Idd6 confers susceptibility to the spontaneous development of type 1 diabetes in the NOD mouse. Our studies on disease resistance of the congenic mouse strain NOD.C3H 6.VIII showed that Idd6 influences T-cell activities in the peripheral immune system and suggest that a major mechanism by which the Idd6 locus modifies diabetes development is via modulation of regulatory T-cell activities. Our transfer experiments using total splenocytes and purified T-cells demonstrated that the locus specifically controls the efficiency of disease protection mediated by the regulatory CD4(+)CD25(+) T-cell subset. Our data also implicate the Idd6 locus in controlling the balance between infiltrating lymphocytes and antigen-presenting cells within the pancreatic islet.

  9. Regulatory behavior and frontal activity: Considering the role of revised-BIS in relative right frontal asymmetry.

    Science.gov (United States)

    Gable, Philip A; Neal, Lauren B; Threadgill, A Hunter

    2018-01-01

    Essential to human behavior are three core personality systems: approach, avoidance, and a regulatory system governing the two motivational systems. Decades of research has linked approach motivation with greater relative left frontal-cortical asymmetry. Other research has linked avoidance motivation with greater relative right frontal-cortical asymmetry. However, past work linking withdrawal motivation with greater relative right frontal asymmetry has been mixed. The current article reviews evidence suggesting that activation of the regulatory system (revised Behavioral Inhibition System [r-BIS]) may be more strongly related to greater relative right frontal asymmetry than withdrawal motivation. Specifically, research suggests that greater activation of the r-BIS is associated with greater relative right frontal activity, and reduced r-BIS activation is associated with reduced right frontal activity (greater relative left frontal activity). We review evidence examining trait and state frontal activity using EEG, source localization, lesion studies, neuronal stimulation, and fMRI supporting the idea that r-BIS may be the core personality system related to greater relative right frontal activity. In addition, the current review seeks to disentangle avoidance motivation and r-BIS as substrates of relative right frontal asymmetry. © 2017 Society for Psychophysiological Research.

  10. 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)

  11. Regulatory barriers for activating flexibility in the Nordic-Baltic electricity market

    DEFF Research Database (Denmark)

    Bergaentzlé, Claire; Skytte, Klaus; Soysal, Emilie Rosenlund

    2017-01-01

    to flexibility. We find that the most restrictive barriers against flexibility are emitted by public authorities as part of broader policy strategies. Overall, we find that current regulatory and market framework conditions do not hinder flexibility. However, despite that, flexibility remains limited due......, load adjustment or to a greater coupling to other energy sectors. In this paper, we identify the framework conditions that influence the provision of VRE-friendly flexibility in the Nordic and Baltic electricity sector, i.e., the market and regulatory settings that act as drivers or barriers...... to a lack of coherent instruments intended to both the demand and supply-side to effectively act flexibly....

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

    DEFF Research Database (Denmark)

    Fang, Xin; Sastry, Anand; Mih, Nathan

    2017-01-01

    Transcriptional regulatory networks (TRNs) have been studied intensely for >25 y. Yet, even for the Escherichia coli TRN-probably the best characterized TRN-several questions remain. Here, we address three questions: (i) How complete is our knowledge of the E. coli TRN; (ii) how well can we predi...

  13. Direct activation of a notochord cis-regulatory module by Brachyury and FoxA in the ascidian Ciona intestinalis.

    Science.gov (United States)

    Passamaneck, Yale J; Katikala, Lavanya; Perrone, Lorena; Dunn, Matthew P; Oda-Ishii, Izumi; Di Gregorio, Anna

    2009-11-01

    The notochord is a defining feature of the chordate body plan. Experiments in ascidian, frog and mouse embryos have shown that co-expression of Brachyury and FoxA class transcription factors is required for notochord development. However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both. We have identified an easily testable model for such investigations in a 155-bp notochord-specific CRM from the ascidian Ciona intestinalis. This CRM contains functional binding sites for both Ciona Brachyury (Ci-Bra) and FoxA (Ci-FoxA-a). By combining point mutation analysis and misexpression experiments, we demonstrate that binding of both transcription factors to this CRM is necessary and sufficient to activate transcription. To gain insights into the cis-regulatory criteria controlling its activity, we investigated the organization of the transcription factor binding sites within the 155-bp CRM. The 155-bp sequence contains two Ci-Bra binding sites with identical core sequences but opposite orientations, only one of which is required for enhancer activity. Changes in both orientation and spacing of these sites substantially affect the activity of the CRM, as clusters of identical sites found in the Ciona genome with different arrangements are unable to activate transcription in notochord cells. This work presents the first evidence of a synergistic interaction between Brachyury and FoxA in the activation of an individual notochord CRM, and highlights the importance of transcription factor binding site arrangement for its function.

  14. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Republic of Korea

    International Nuclear Information System (INIS)

    2009-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General regulatory regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Protection of the environment against radiation effects; Emergency response); 5. Trade in nuclear materials and equipment; 6. Radiation protection) (Protection of workers; Protection of the public); 7. Radioactive waste management; 8. Non-proliferation and physical protection; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Minister of Education, Science and Technology, including the Nuclear Energy Bureau; Minister of Knowledge Economy); 2. Advisory bodies (Atomic Energy Commission; Atomic Energy Safety Commission); 3. Public and semi-public agencies (Korean Atomic Energy Research Institute - KAERI; Korean Institute for Nuclear Safety - KINS; Korean Electric Power Company - KEPCO; Korean Hydro and Nuclear Power - KHNP)

  15. Development of guidance on applications of regulatory requirements for low specific activity materials and surface contaminated objects

    International Nuclear Information System (INIS)

    Pope, R.B.; Easton, E.P.; Shankman, S.F.

    1997-01-01

    In 1985, the International Atomic Energy Agency issued revised regulations for the safe transport of radioactive material. Significant among the changes were major revisions to requirements for Low Specific Activity (LSA) material and Surface Contaminated Objects (SCOs). In preparation for the adoption of these requirements into regulations in the United States, it became apparent that guidance on how to apply these requirements, clarifying technical uncertainties and ensuring proper implementation, would be needed both by the regulators and those regulated. Thus, the US Department of Transportation and the US Nuclear Regulatory Commission, with the assistance of staff from Oak Ridge National Laboratory, are preparing regulatory guidance for LSA material and SCO transport. The guidance will present examples of acceptable methods for demonstrating compliance with the revised rules. Ideas being investigated for inclusion in the pending guidance are discussed in this paper. Under current plans, the guidance will be issued for public comment prior to final issuance of the guidance in 1997

  16. Development of guidance on applications of regulatory requirements for low specific activity materials and surface contaminated objects

    International Nuclear Information System (INIS)

    Pope, R.B.; Easton, E.P.; Shankman, S.F.; Boyle, R.W.

    1997-01-01

    In 1985, the International Atomic Energy Agency issued revised regulations for the safe transport of radioactive material. Significant among the changes were major revisions to requirements for Low Specific Activity (LSA) material and Surface Contaminated Objects (SCOs). In preparation for the adoption of these requirements into regulations in the United States, it became apparent that guidance on how to apply these requirements, clarifying technical uncertainties and ensuring proper implementation, would be needed both by the regulators and those regulated. Thus, the US Department of Transportation and the U.S. Nuclear Regulatory Commission, with the assistance of staff from Oak Ridge National Laboratory, are preparing regulatory guidance for LSA material and SCO transport. The guidance will present examples of acceptable methods for demonstrating compliance with the revised rules. Ideas being investigated for inclusion in the pending guidance are discussed in this paper. Under current plans, the guidance will be issued for public comment prior to final issue of the guidance in 1997. (Author)

  17. Guide d’indexation des travaux de fin d’étude en médecine générale

    OpenAIRE

    Jamoulle, Marc

    2017-01-01

    Le Centre de Coordination Francophone pour la Formation en Médecine Générale (CCFFMG) (www.ccffmg.be) a été chargé d’organiser la mise en ligne publique des Travaux de Fin d’Étude (TFE). Le TFE est réalisé à la fin du master de spécialité des départements de médecine générale de l’Université Libre de Bruxelles (ULB), l’Université Catholique de Louvain (UCL) et Université de Liège (ULg). Un site dédié (www.mgtfe.be) propose un guide de rédaction en ligne. Ce site offre aussi la description et ...

  18. Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation.

    Science.gov (United States)

    Ringelstein-Harlev, Shimrit; Avivi, Irit; Fanadka, Mona; Horowitz, Netanel A; Katz, Tami

    2018-02-15

    Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia. Co-culture assays were used to examine the ability of CLL cells to suppress autologous T-cell immune responses. IL-10 potency of CLL cells was assessed following stimulation with activators of the toll-like receptor 9 (TLR9) or CD40 and was correlated with the inhibitory activity of the cells. TLR9-activated CLL cells were found to increase the frequency of CD4 + CD25 hi FOXp3 + regulatory T-cells (Tregs) and to inhibit autologous CD4 + T-cell proliferation. This signaling cascade proved to control IL-10 generation in CLL cells, which in turn promoted the inhibition of T-cell proliferation by CLL cells. However, CD40 activation of CLL cells, while exhibiting a similar ability to augment Treg frequency, did not either affect IL-10 generation or T-cell proliferation. In conclusion, CLL cells demonstrate a unique clonal quality of adopting Breg properties which promote modulation of T-cell characteristics. TLR9 appears to be a potent activator of regulatory abilities in CLL cells, possibly contributing to preferential immune escape of TLR9-responsive cells.

  19. Regulation of Federal radioactive waste activities. Summary of report to Congress on extending the Nuclear Regulatory Commission's licensing or regulatory authority to Federal radioactive waste storage and disposal activities

    International Nuclear Information System (INIS)

    Smith, R.D.

    1979-09-01

    The NRC Authorization Bill for FY 1979 directed NRC to conduct a study of extending the Commission's licensing or regulatory authority to include categories of existing and future Federal radioactive waste storage and disposal activities not presently subject to such authority. The report includes a complete listing and inventory of all radioactive waste storage and disposal activities now being conducted or planned by Federal agencies. The NRC study has attempted to present a general comparison of the relative hazards associated with defense-generated and commercial wastes. Options for extending Commission authority were developed and analyzed. The implications of NEPA were analyzed in the context of these options. The national security implications of extending NRC's regulatory authority over DOE programs are examined and evaluated. Costs and benefits are identified and assessed. The Commission's recommendations, based on the study, are to extend licensing authority over new DOE disposal activities involving transuranic wastes and non-defense low-level waste and to initiate a pilot program to test the feasibility of NRC playing a consultative role in the evaluation of existing DOE activities

  20. Regulatory and law framework of agricultural methanization and composting activities. User's guide

    International Nuclear Information System (INIS)

    2008-08-01

    After a presentation of the general context of organic waste management (its techniques, materials, legal and regulatory sources, i.e. European and French laws), this guide indicates the main regulatory and law aspects to those wishing to implement a project of methanization or composting of organic by-products in the agricultural sector. Several aspects are therefore discussed and presented in practical sheets. They concern the health and environment regulation, but not the professional risk prevention (explosion, fire, and so on). These aspects are the project setting up, input materials (animal by-products, organic materials coming from agricultural production or from out of it), waste collection and transport, process steps, organic product valorization, biogas valorization, solid and liquid release management

  1. 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)

  2. Characterization of a putative cis-regulatory element that controls transcriptional activity of the pig uroplakin II gene promoter

    International Nuclear Information System (INIS)

    Kwon, Deug-Nam; Park, Mi-Ryung; Park, Jong-Yi; Cho, Ssang-Goo; Park, Chankyu; Oh, Jae-Wook; Song, Hyuk; Kim, Jae-Hwan; Kim, Jin-Hoi

    2011-01-01

    Highlights: → The sequences of -604 to -84 bp of the pUPII promoter contained the region of a putative negative cis-regulatory element. → The core promoter was located in the 5F-1. → Transcription factor HNF4 can directly bind in the pUPII core promoter region, which plays a critical role in controlling promoter activity. → These features of the pUPII promoter are fundamental to development of a target-specific vector. -- Abstract: Uroplakin II (UPII) is a one of the integral membrane proteins synthesized as a major differentiation product of mammalian urothelium. UPII gene expression is bladder specific and differentiation dependent, but little is known about its transcription response elements and molecular mechanism. To identify the cis-regulatory elements in the pig UPII (pUPII) gene promoter region, we constructed pUPII 5' upstream region deletion mutants and demonstrated that each of the deletion mutants participates in controlling the expression of the pUPII gene in human bladder carcinoma RT4 cells. We also identified a new core promoter region and putative negative cis-regulatory element within a minimal promoter region. In addition, we showed that hepatocyte nuclear factor 4 (HNF4) can directly bind in the pUPII core promoter (5F-1) region, which plays a critical role in controlling promoter activity. Transient cotransfection experiments showed that HNF4 positively regulates pUPII gene promoter activity. Thus, the binding element and its binding protein, HNF4 transcription factor, may be involved in the mechanism that specifically regulates pUPII gene transcription.

  3. Research and regulatory review

    International Nuclear Information System (INIS)

    Macleod, J.S.; Fryer, D.R.H.

    1979-01-01

    To enable the regulatory review to be effectively undertaken by the regulatory body, there is a need for it to have ready access to information generated by research activities. Certain advantages have been seen to be gained by the regulatory body itself directly allocating and controlling some portion of these activities. The princial reasons for reaching this conclusion are summarised and a brief description of the Inspectorates directly sponsored programme outlined. (author)

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

    International Nuclear Information System (INIS)

    Woodhouse, P.A.

    1995-01-01

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

  5. Effect of Simulated Microgravity on the Activity of Regulatory Enzymes of Glycolysis and Gluconeogenesis in Mice Liver

    Science.gov (United States)

    Ramirez, Joaquin; Periyakaruppan, Adaikkappan; Sarkar, Shubhashish; Ramesh, Govindarajan T.; Sharma, S. Chidananda

    2014-02-01

    Gravity supports all the life activities present on earth. Microgravity environments have effect on the biological functions and physiological status of an individual. The present study was undertaken to investigate the effect of simulated microgravity on important regulatory enzymes of carbohydrate metabolism in liver using HLS mice model. Following hind limb unloading of mice for 11 days the animal's average body weights were found to be not different, while the liver weights were decreased and found to be significantly different ( p gluconeogenesis in liver and reciprocally regulated.

  6. The Report on Activities of the Nuclear Regulatory Authority of the Slovak Republic and on Safety of Nuclear Installations in the Slovak Republic in 2010

    International Nuclear Information System (INIS)

    2010-05-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2010 is presented. These activities are reported under the headings: Address of the Chairperson; (1) Legislative activities; (2) Issuance of authorizations, assessment, supervisory activities and enforcement; (3) Nuclear safety of nuclear power plants; (4) Nuclear materials and physical protection of nuclear materials; (5) Powers of the office building; (6) Emergency planning and preparedness; (7) International activities; (8) Public communication; (9) Nuclear Regulatory Authority of the Slovak Republic; (10) Appendix: UJD SR organization chart; The International Nuclear Event Scale (INES); Abbreviations.

  7. Report on activities of Nuclear Regulatory Authority of the Slovak Republic and safety of nuclear installations in the Slovak Republic in 2008. Annual report

    International Nuclear Information System (INIS)

    Zemanova, D.; Pirozekova, M.

    2009-04-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2008 is presented. These activities are reported under the headings: (1) Foreword; (2) Legislation; (3) Issuance of authorizations, assessment, supervisory activities and enforcement; (4) Nuclear safety of nuclear installations in the Slovak Republic; (5) Safety of other nuclear installations; (6) Management of radioactive waste; (7) Nuclear materials and physical protection of nuclear materials; (8) Activity of Building Office; (9) Emergency planning and preparedness; (10) International activities; (11) Public communication; (11) Nuclear Regulatory Authority of the Slovak Republic; (12) UJD SR organization chart; (13) Abbreviations

  8. Quality Management System Improves Effectiveness and Quality of Activities of Radiation Protection Regulatory Body in Lithuania

    International Nuclear Information System (INIS)

    Mastauskas, A.

    2016-01-01

    Processes of creation of quality management system (QMS) in regulatory body in radiation protection field – Radiation Protection Centre (RPC) and the benefit of this system to ensure the quality of the performance of functions are described. RPC QMS compliant with ISO 9001:2008 standard and in line with the requirements of the IAEA GSR- 3 document. It allowed achieving a new quality of works carried out by RPC. Because creation and introduction of the QMS is a continuous process, the QMS of RPC is continually renewed and new procedures are developed.

  9. A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

    Science.gov (United States)

    Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

    2015-08-01

    Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. TLR5 signaling enhances the proliferation of human allogeneic CD40-activated B cell induced CD4hiCD25+ regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Ping-Lung Chan

    Full Text Available Although diverse functions of different toll-like receptors (TLR on human natural regulatory T cells have been demonstrated recently, the role of TLR-related signals on human induced regulatory T cells remain elusive. Previously our group developed an ex vivo high-efficient system in generating human alloantigen-specific CD4(hiCD25(+ regulatory T cells from naïve CD4(+CD25(- T cells using allogeneic CD40-activated B cells as stimulators. In this study, we investigated the role of TLR5-related signals on the generation and function of these novel CD4(hiCD25(+ regulatory T cells. It was found that induced CD4(hiCD25(+ regulatory T cells expressed an up-regulated level of TLR5 compared to their precursors. The blockade of TLR5 using anti-TLR5 antibodies during the co-culture decreased CD4(hiCD25(+ regulatory T cells proliferation by induction of S phase arrest. The S phase arrest was associated with reduced ERK1/2 phosphorylation. However, TLR5 blockade did not decrease the CTLA-4, GITR and FOXP3 expressions, and the suppressive function of CD4(hiCD25(+ regulatory T cells. In conclusion, we discovered a novel function of TLR5-related signaling in enhancing the proliferation of CD4(hiCD25(+ regulatory T cells by promoting S phase progress but not involved in the suppressive function of human CD40-activated B cell-induced CD4(hiCD25(+ regulatory T cells, suggesting a novel role of TLR5-related signals in the generation of induced regulatory T cells.

  11. Development of a stable uranium recovery regulatory framework for uranium recovery activities in the United States

    International Nuclear Information System (INIS)

    Layton, M.C.; Abrams, C.E.

    2000-01-01

    The U.S. Nuclear Regulatory Commission (NRC) has historically regulated operations at all uranium and thorium recovery facilities under the authority of the Atomic Energy Act of 1954, as amended. Uranium recovery facilities are those plants, or portions of facilities that process uranium- or thorium-bearing material primarily for its source material content. The uranium recovery industry expressed some concerns over several aspects of the NRC's practices, as described in the NRC's guidance documents. In April 1998, the National Mining Association submitted a report to the Commission, that identified specific concerns with NRC's current position and guidance regarding concurrent jurisdiction at uranium mills; dual regulatory authority at in situ leach facilities; the use of mill tailings impoundments for disposal of radioactive material other than 11e.(2) byproduct material; and the ability to process alternate feed material at uranium mills. The NRC staff addressed most of these concerns in two SECY (staff recommendations) papers that were concurrently provided to the Commission, along with a SECY paper on a draft rulemaking plan relating to these and other issues. The issues addressed in these papers included a new rulemaking, disposal of materials other than 11 e.(2) byproduct material, processing of materials other than natural ores, and improved efficiency for regulating in situ leach uranium facilities. The Commission issued final policy decisions on these issues and directions for NRC staff to implement those decisions in July 2000. (author)

  12. Survey of state regulatory activities on least cost planning for gas utilities

    International Nuclear Information System (INIS)

    Goldman, C.A.; Hopkins, M.E.

    1991-04-01

    Integrated resource planning involves the creation of a process in which supply-side and demand-side options are integrated to create a resource mix that reliably satisfies customers' short-term and long-term energy service needs at the lowest cost. Incorporating the concept of meeting customer energy service needs entails a recognition that customers' costs must be considered along with the utility's costs in the economic analysis of energy options. As applied to gas utilities, an integrated resource plan seeks to balance cost and reliability, and should not be interpreted simply as the search for lowest commodity costs. All state commissions were surveyed to assess the current status of gas planning and demand-side management and to identify significant regulatory issues faced by commissions during the next several years. The survey was to determine the extent to which they have undertaken least-cost planning for gas utilities. The survey included the following topics: (1) status of state PUC least-cost planning regulations and practices for gas utilities; (2) type and scope ofnatural gas DSM programs in effect, includeing fuel substitution; (3) economic tests and analysis methods used to evaluate DSM programs; (4) relationship between prudence reviews of gas utility purchasing practices and integrated resource planning; and (5) key regulatory issues facing gas utilities during the next five years. 34 refs., 6 figs., 10 tabs

  13. Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations.

    Science.gov (United States)

    Qing, Xiao-Yu; Steenackers, Hans; Venken, Tom; De Maeyer, Marc; Voet, Arnout

    2017-11-01

    The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation-mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function. Disruption or stabilization of protein-protein interactions at the dimerization interface may inhibit or enhance the expression of PhoP-dependent genes. In this study, we performed molecular dynamics simulations on the active and inactive dimers and monomers of the PhoP regulatory domains, followed by pocket-detecting screenings and a quantitative hot-spot analysis in order to assess the druggability of the protein. Consistent with prior hypothesis, the calculation of the binding free energy shows that phosphorylation enhances dimerization of PhoP. Furthermore, we have identified two different putative binding sites at the dimerization active site (the α4-β5-α5 face) with energetic "hot-spot" areas, which could be used to search for modulators of protein-protein interactions. This study delivers insight into the dynamics and druggability of the dimerization interface of the PhoP regulatory domain, and may serve as a basis for the rational identification of new antimicrobial drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. How Has CDER Prepared for the Nano Revolution? A Review of Risk Assessment, Regulatory Research, and Guidance Activities.

    Science.gov (United States)

    Tyner, Katherine M; Zheng, Nan; Choi, Stephanie; Xu, Xiaoming; Zou, Peng; Jiang, Wenlei; Guo, Changning; Cruz, Celia N

    2017-07-01

    The Nanotechnology Risk Assessment Working Group in the Center for Drug Evaluation and Research (CDER) within the United States Food and Drug Administration (FDA) was established to assess the potential impact of nanotechnology on drug products. One of the working group's major initiatives has been to conduct a comprehensive risk management exercise regarding the potential impact of nanomaterial pharmaceutical ingredients and excipients on drug product quality, safety, and efficacy. This exercise concluded that current review practices and regulatory guidance are capable of detecting and managing the potential risks to quality, safety, and efficacy when a drug product incorporates a nanomaterial. However, three risk management areas were identified for continued focus during the review of drug products containing nanomaterials: (1) the understanding of how to perform the characterization of nanomaterial properties and the analytical methods used for this characterization, (2) the adequacy of in vitro tests to evaluate drug product performance for drug products containing nanomaterials, and (3) the understanding of properties arising from nanomaterials that may result in different toxicity and biodistribution profiles for drug products containing nanomaterials. CDER continues to actively track the incorporation of nanomaterials in drug products and the methodologies used to characterize them, in order to continuously improve the readiness of our science- and risk-based review approaches. In parallel to the risk management exercise, CDER has also been supporting regulatory research in the area of nanotechnology, specifically focused on characterization, safety, and equivalence (between reference and new product) considerations. This article provides a comprehensive summary of regulatory and research efforts supported by CDER in the area of drug products containing nanomaterials and other activities supporting the development of this emerging technology.

  15. Development of joint regulatory guidance on the management of higher activity radioactive wastes on nuclear licensed sites - 16095

    International Nuclear Information System (INIS)

    Bacon, Mick; Ilett, Doug; Whittall, Andy

    2009-01-01

    In 2006 the UK Government's response (1) to recommendations by its Committee on Radioactive Waste Management (CoRWM) established, in England and Wales, that geological disposal, supported by safe and secure interim storage, is the preferred route for the long-term management of higher-activity radioactive waste (i.e. that which is not suitable for near-surface disposal). It also gave the responsibility for delivering the programme for a deep geological repository to the Nuclear Decommissioning Authority (NDA). The Scottish Government has a policy of long term, near site, near surface safe and secure interim storage. To support the open and transparent approach promised by Government, the Health and Safety Executive (HSE), the Environment Agency and the Scottish Environment Protection Agency (SEPA) are developing joint guidance on the management of higher-activity radioactive waste to explain regulatory objectives in securing safe and secure interim storage and the associated management of radioactive wastes. The guidance comes in two parts: - Guidance on the regulatory process; - Technical guidance modules. The guidance promotes a cradle to grave approach to radioactive waste management and by aligning the regulatory interests of environmental and safety regulators it delivers one of the Government's 'Better Regulation' objectives. This paper describes the process by which the joint guidance was produced with particular emphasis on stakeholder engagement. It describes the key features of the guidance, including the concept of the radioactive waste management case (RWMC). Finally the problems encountered with dissemination and implementation are discussed together with measures taken by the regulators to improve these aspects. (1) : UK Government and the devolved administrations, 'Response to the Report and Recommendations from the Committee on Radioactive Waste Management (CoRWM)', (PB 12303) October 2006. www

  16. 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...

  17. CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis Disease Activity.

    Science.gov (United States)

    Khattab, Sahar S; El-Saied, Amany M; Mohammed, Rehab A; Mohamed, Eman E

    2016-06-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed immune regulation, inducing a progressive cartilage and bone destruction. Despite enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results are reported concerning T-regs in peripheral blood (PB) of RA patients. To determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T-regs) with RA disease activity. Forty females with RA, classified according to the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low disease activity; and 20 age and sex matched healthy controls, were enrolled to study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild-moderate or low disease activity (P <0.001). The frequencies of the T- regs showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+ CD127low T-regs is significantly lower in highly active RA patients compared to patients with lower activity or controls. Copyright© by the Egyptian Association of Immunologists.

  18. Activation of the aryl hydrocarbon receptor reduces the number of precursor and effector T cells, but preserves thymic CD4(+)CD25(+)Foxp3(+) regulatory T cells

    NARCIS (Netherlands)

    Schulz, V.J.; Smit, J.J.; Bol-Schoenmakers, M.; van Duursen, M.B.M.; van den Berg, M.; Pieters, R.H.H.

    2012-01-01

    Aryl hydrocarbon receptor (AhR) activation suppresses immune responses, including allergic sensitization, by increasing the percentage of regulatory (Treg) cells. Furthermore, AhR activation is known to affect thymic precursor T cells. However, the effect of AhR activation on intrathymic

  19. Perceived success/failure and attributions associated with self-regulatory efficacy to meet physical activity recommendations for women with arthritis.

    Science.gov (United States)

    Spink, Kevin S; Brawley, Lawrence R; Gyurcsik, Nancy C

    2016-10-01

    The relationship between attributional dimensions women assign to the cause of their perceived success or failure at meeting the recommended physical activity dose and self-regulatory efficacy for future physical activity was examined among women with arthritis. Women (N = 117) aged 18-84 years, with self-reported medically-diagnosed arthritis, completed on-line questions in the fall of 2013 assessing endurance physical activity, perceived outcome for meeting the recommended levels of endurance activity, attributions for one's success or failure in meeting the recommendations, and self-regulatory efficacy to schedule/plan endurance activity over the next month. The main theoretically-driven finding revealed that the interaction of the stability dimension with perceived success/failure was significantly related to self-regulatory efficacy for scheduling and planning future physical activity (β = 0.35, p = .002). Outcomes attributed to more versus less stable factors accentuated differences in self-regulatory efficacy beliefs following perceived success and failure at being active. It appears that attributional dimensions were associated with self-regulatory efficacy in women with arthritis. This suggests that rather than objectively observed past mastery experience, women's subjective perceptions and explanations of their past experiences were related to efficacy beliefs, especially following a failure experience.

  20. U.S. Nuclear Regulatory Commission Role and Activities Related to U.S. Department of Energy Incidental Waste Determinations

    International Nuclear Information System (INIS)

    Bradford, A.H.; Esh, D.W.; Ridge, A.C.

    2006-01-01

    Section 3116 of the Ronald W. Reagan National Defense Authorization Act for Fiscal Year 2005 (NDAA) requires the U.S. Department of Energy (DOE) to consult with the U.S. Nuclear Regulatory Commission (NRC) for certain non-high level waste (HLW) determinations. Under the NDAA, NRC performs consultative technical reviews of DOE's waste determinations and monitors DOE's disposal actions for such waste, but the NRC does not have regulatory authority over DOE's waste disposal activities. The NDAA provides the criteria that must be met to determine that waste is not HLW. The criteria require that the waste does not need to be disposed of in a geologic repository, that highly radioactive radionuclides be removed to the maximum extent practical, and that the performance objectives of 10 CFR 61, Subpart C, be met. The performance objectives contain criteria for protection of the public, protection of inadvertent intruders, protection of workers, and stability of the disposal site after closure. This paper describes NRC's approach to implementing its responsibilities under the NDAA, as well as similar activities being performed for sites not covered by the NDAA. (authors)

  1. Industry perceptions of the impact of the U.S. Nuclear Regulatory Commission on nuclear power plant activities. Draft report

    Energy Technology Data Exchange (ETDEWEB)

    Davis, A Bert; Pederson, Cynthia D

    1990-03-01

    Teams of senior managers from the U.S. Nuclear Regulatory Commission (NRC) surveyed licensee staff members representing 13 nuclear power utilities from across the country to obtain their candid views of the effectiveness and impact of NRC regulatory activities. Licensee comments addressed the full scope of NRC activities and the impact of agency actions on licensee resources, staff performance, planning and scheduling, and organizational effectiveness. The principal themes of the survey respondents' comments are that (1) licensees acquiesce to NRC requests to avoid poor ratings on NRC Systematic Assessment of Licensee Performance (SALP) reports and the consequent financial and public perception problems that result, even if the requests require the expenditure of significant resources on matters of marginal safety significance, and (2) NRC so dominates licensee resources through its existing and changing formal and informal requirements that licensees believe that their plants, though not unsafe, would have better reliability, and may even achieve a higher degree of safety, if licensees were freer to manage their own resources. This draft report does not attempt to defend any NRC position; endorse or refute licensee perceptions; or explain any action taken by NRC in fulfilling its responsibilities to protect the health and safety of the public. Senior RC managers have made a preliminary evaluation of the information in this report and have made recommendations to address licensee concerns in some areas. The final evaluation and recommendations will be published at a later date as the final NUREG. (author)

  2. Report on activities of Nuclear Regulatory Authority of the Slovak Republic and safety of nuclear installations in the Slovak Republic in 2007. Annual report

    International Nuclear Information System (INIS)

    2007-04-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2007 is presented. These activities are reported under the headings: (1) Foreword; (2) Legislation; (3) Issuance of authorizations, assessment, supervisory activities and enforcement; (4) Nuclear safety of nuclear installations in the Slovak Republic; (5) Safety of other nuclear installations; (6) Management of radioactive waste; (7) Nuclear materials; (8) Emergency planning and preparedness; (9) International activities; (10) Public communication; (11) Nuclear Regulatory Authority of the Slovak Republic; (12) Abbreviations

  3. Report on activities of Nuclear Regulatory Authority of the Slovak Republic and safety of nuclear installations in the Slovak Republic in 2009. Annual report

    International Nuclear Information System (INIS)

    2010-04-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2009 is presented. These activities are reported under the headings: (1) Foreword; (2) Legislation; (3) Issuance of authorizations, assessment, supervisory activities and enforcement; (4) Nuclear safety of nuclear installations in the Slovak Republic; (5) Safety of other nuclear installations; (6) Management of radioactive waste; (7) Nuclear materials and physical protection of nuclear materials; (8) Emergency planning and preparedness; (9) International activities; (10) Public communication; (11) Nuclear Regulatory Authority of the Slovak Republic; (12) UJD SR organization chart; (13) Abbreviations.

  4. Drinking Water Research Division's research activities in support of EPA's regulatory agenda

    International Nuclear Information System (INIS)

    Clark, R.M.; Feige, W.A.

    1991-01-01

    The Safe Drinking Water Act and its Amendments will have a dramatic impact on the way in which one views the treatment and distribution of water in the U.S. The paper discusses the regulatory agenda, including proposed and promulgated regulations for volatile and synthetic organic contaminants, pesticides, lead, copper, inorganic contaminants, and radionuclides. In addition, the Surface Water Treatment and Coliform Rules are discussed in some detail. Tables are presented that list the Maximum Contaminant Levels (MCLs) and Maximum Contaminant Level Goals (MCLGs), as well as Best Available Technology (BAT) for reducing many of these contaminants to acceptable levels. Finally, a discussion of expected disinfection requirements and the regulation of disinfection by-products (DBP) is made. Treatment techniques for controlling DBPs are briefly described

  5. Construction of the Database for Tomorrow's Regulatory Activities

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Il S.; Kim, Min C.; Kim, Sang J.; Yu, Seon O.; Lee, Kyung W.; Kim, Ji T.; Koo, Bon H.; Lee, Durk H. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2010-10-15

    KINS has launched a top brand project since early 2007, which called the 'Tracking System for the Implementation of Nuclear Regulation: RTRACER' The one of main contents of RTRACER is promoting nuclear safety by interconnecting the information of the events and that of safety review and regulatory inspection. R-TRACER is composed of three parts. One is the CATS(Corrective Action Tracking System) to carry out the related affairs and to exchange information between organizations concerned efficiently. Another is the SIMS(Safety Issue Management System) to coordinate the safety issues program and to implement the operating experience feedback in a real-time basis. And the other is the DIOS to supply above both systems with core information. This paper is focused on the database structure of the DIOS

  6. Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

    Science.gov (United States)

    Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

    2017-11-22

    Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

  7. On the evolution of the regulatory guidance for seismic qualification of electric and active mechanical equipment for nuclear power plants

    International Nuclear Information System (INIS)

    Ng, Ching Hang; Chen, Pei-Ying

    2009-01-01

    All electric and active mechanical equipment important to safety for nuclear power plants must be seismically qualified by testing, analysis, or combined analysis and testing. The general requirements for seismic qualification of electric and active mechanical equipment in nuclear power plants are delineated in Appendix S, 'Earthquake Engineering Criteria for Nuclear Power Plants,' to Title 10, Part 50, 'Domestic Licensing of Production and Utilization Facilities,' of the Code of Federal Regulations (10 CFR Part 50), item 52.47(20) of 10 CFR 52.47, 'Contents of Applications; Technical Information,' and Appendix A, 'Seismic and Geologic Siting Criteria for Nuclear Power Plants,' to 10 CFR Part 100, 'Reactor Site Criteria.' The United States Nuclear Regulatory Commission (NRC) issued Revision 2 of Regulatory Guide (RG) 1.100, 'Seismic Qualification of Electric and Mechanical for Nuclear Power Plants' in 1988, which endorsed, with restrictions, exceptions, and clarifications, Institute of Electrical and Electronics Engineers (IEEE) Standard 344-1987 'IEEE Recommended Practice for Seismic Qualification of Class 1E Equipment for Nuclear Power Generating Stations,' for use in seismic qualification of both electric and mechanical equipment. In 2008, the staff at the NRC drafted Revision 3 of RG 1.100 to endorse, with restrictions, exceptions, and clarifications, the IEEE Std 344-2004 and the American Society of Mechanical Engineers (ASME) QME-1-2007 'Qualification of Active Mechanical Equipment Used in Nuclear Power Plants.' IEEE Std 344-2004 was an update of Std 344-1987 and ASME QME-1-2007 was an update of QME-1-2002. The major changes in IEEE Std 344-2004 and ASME QME-1-2007 include the update and expansion of criteria and procedures describing the use of experience data as a method for seismic qualification of Class 1E electric equipment (including I and C components) as well as active mechanical equipment. In this paper, the staff will compare the draft Revision 3 to

  8. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes.

    Science.gov (United States)

    Xu, Lei; Zhou, Xinying; Wang, Wenshi; Wang, Yijin; Yin, Yuebang; Laan, Luc J W van der; Sprengers, Dave; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2016-10-01

    IFN regulatory factor 1 (IRF1) is one of the most important IFN-stimulated genes (ISGs) in cellular antiviral immunity. Although hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide, how ISGs counteract HEV infection is largely unknown. This study was conducted to investigate the effect of IRF1 on HEV replication. Multiple cell lines were used in 2 models that harbor HEV. In different HEV cell culture systems, IRF1 effectively inhibited HEV replication. IRF1 did not trigger IFN production, and chromatin immunoprecipitation sequencing data analysis revealed that IRF1 bound to the promoter region of signal transducers and activators of transcription 1 (STAT1). Functional assay confirmed that IRF1 could drive the transcription of STAT1, resulting in elevation of total and phosphorylated STAT1 proteins and further activating the transcription of a panel of downstream antiviral ISGs. By pharmacological inhibitors and RNAi-mediated gene-silencing approaches, we revealed that antiviral function of IRF1 is dependent on the JAK-STAT cascade. Furthermore, induction of ISGs and the anti-HEV effect of IRF1 overlapped that of IFNα, but was potentiated by ribavirin. We demonstrated that IRF1 effectively inhibits HEV replication through the activation of the JAK-STAT pathway, and the subsequent transcription of antiviral ISGs, but independent of IFN production.-Xu, L., Zhou, X., Wang, W., Wang, Y., Yin, Y., van der Laan, L. J. W., Sprengers, D., Metselaar, H. J., Peppelenbosch, M. P., Pan, Q. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes. © FASEB.

  9. Regulatory proteins (inhibitors or activators) affect estimates of Msub(r) of enzymes and receptors by radiation inactivation

    International Nuclear Information System (INIS)

    Potier, M.; Giroux, S.

    1985-01-01

    The radiation-inactivation method allows the determination of the Msub(r) of enzymes and receptors by monitoring the decay of biological activity as a function of absorbed dose. The presence of regulatory or effector proteins (inhibitors or activators) associated with an enzyme or receptor, or released in the preparation after tissue homogenization, may affect the decay of biological activity. How the activity is affected, however, will depend on the type of inhibition (competitive or non-competitive), the inhibitor or activator concentration, the dissociation constant of the enzyme-effector system, and the effector Msub(r) relative to that of the enzyme. Since little is known on how effector proteins influence radiation inactivation of enzymes and receptors, we have considered a theoretical model in an effort to provide a framework for the interpretation of experimentally obtained data. Our model predicts that competitive and non-competitive inhibitors of enzymes could be distinguished by analysing irradiated samples with various substrate concentrations. Inhibitors will decrease whereas activators will increase the apparent target size of enzymes or receptors. (author)

  10. LAG-3 Represents a Marker of CD4+ T Cells with Regulatory Activity in Patients with Bone Fracture.

    Science.gov (United States)

    Wang, Jun; Ti, Yunfan; Wang, Yicun; Guo, Guodong; Jiang, Hui; Chang, Menghan; Qian, Hongbo; Zhao, Jianning; Sun, Guojing

    2018-04-19

    The lymphocyte activation gene 3 (LAG-3) is a CD4 homolog with binding affinity to MHC class II molecules. It is thought that LAG-3 exerts a bimodal function, such that co-ligation of LAG-3 and CD3 could deliver an inhibitory signal in conventional T cells, whereas, on regulatory T cells, LAG-3 expression could promote their inhibitory function. In this study, we investigated the role of LAG-3 expression on CD4 + T cells in patients with long bone fracture. We found that LAG-3 + cells represented approximately 13% of peripheral blood CD4 + T cells on average. Compared to LAG-3 - CD4 + T cells, LAG-3 + CD4 + T cells presented significantly higher Foxp3 and CTLA-4 expression. Directly ex vivo or with TCR stimulation, LAG-3 + CD4 + T cells expressed significantly higher levels of IL-10 and TGF-β than LAG-3 - CD4 + T cells. Interestingly, blocking the LAG-3-MHC class II interaction actually increased the IL-10 expression by LAG-3 + CD4 + T cells. The frequency of LAG-3 + CD4 + T cell was positively correlated with restoration of healthy bone function in long bone fracture patients. These results together suggested that LAG-3 is a marker of CD4 + T cells with regulatory function; at the same time, LAG-3 might have limited the full suppressive potential of Treg cells.

  11. Regulatory oversight of maintenance activities at nuclear power plants in France

    International Nuclear Information System (INIS)

    Bouton, J.P.; Lallement, J.

    1997-01-01

    In France the nuclear safety authority sets out the main safety objectives but the operator remains the first responsible for the NPP safety. During the operation, operators have to demonstrate that the safety level remains the same as defined in the design studies. Maintenance contributes to meet this objective. The French regulation insists on the quality of the safety related components maintenance, especially in the 1984 order. All gap between results and requirements have to be analyzed by operator who provide feedback measures to avoid similar failure to occur. This gap have to be mentioned to regulators. The use of probabilistic safety analysis (PSA) and reliability centered maintenance (RCM) methods is not well developed in France to optimize maintenance. For the French regulatory, the major difficulties in the use of PSA are: The impossibility to detect unanticipated failure mode; the validity of the input data; the validity of model use, based on ''engineering judgement''. For the specific case of passive components inspection, such as the vessel of the primary circuit, the French regulator has already indicated to the operator that the optimization of maintenance by use of PSA cannot be used, for the following reasons: The safety analysis does not take into account the failure of the vessel; unanticipated failure modes have already damaged part of the primary circuit; the use of defense in depth concept requires a systematic detection of any defect on the vessel. (author)

  12. Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer.

    Science.gov (United States)

    Santagata, Sara; Napolitano, Maria; D'Alterio, Crescenzo; Desicato, Sonia; Maro, Salvatore Di; Marinelli, Luciana; Fragale, Alessandra; Buoncervello, Maria; Persico, Francesco; Gabriele, Lucia; Novellino, Ettore; Longo, Nicola; Pignata, Sandro; Perdonà, Sisto; Scala, Stefania

    2017-09-29

    With the intent to identify biomarkers in renal cell carcinoma (RCC) the functional status of T-regulatory cells (Tregs) was investigated in primary RCC. Tregs were isolated from tumoral-(TT), peritumoral tissue-(PT) and peripheral blood-(PB) of 42 primary RCC patients and function evaluated through effector T cells (Teff) proliferation, cytokines release and demethylation of Treg Specific Region (TSDR). The highest value of Tregs was detected in TT with the uppermost amount of effector-Tregs-(CD4 + CD25 hi FOXP3 hi CD45RA - ). PB-RCC Tregs efficiently suppress Teff proliferation compared to healthy donor (HD)-Tregs and, at the intrapatient evaluation, TT-derived Tregs were the most suppressive. Higher demethylation TSDR was detected in TT- and PB-RCC Tregs vs HD-Tregs ( P <0,001). CXCR4 is highly expressed on Tregs, thus we wished to modulate Tregs function through CXCR4 inhibition. CXCR4 antagonism, elicited by a new peptidic antagonist, Peptide-R29, efficiently reversed Tregs suppression of Teff proliferation. Thus Tregs functional evaluation precisely reflects Tregs status and may be a reliable biomarker of tumoral immune response. In addition, treatment with CXCR4 antagonist, impairing Tregs function, could improve the anticancer immune response, in combination with conventional therapy and/or immunotherapy such as checkpoints inhibitors.

  13. Regulatory aspects and activities in the field of radioactive waste management in Bulgaria

    International Nuclear Information System (INIS)

    Kastchiev, G.

    2001-01-01

    Bulgaria uses nuclear power for electricity generation and for a variety of nuclear applications in industry, research and medicine. Six WWER type Nuclear Power Plants (NPPs) went into operation at Kozloduy between 1974 and 1991. Until 1988 spent fuel was transported back to the former Soviet Union, but since then has been stored on site. Operational low level waste is stored on site, but since 1993 a volume reduction strategy using supercompaction has been employed, which has reduced stored waste volumes by a factor of four. Institutional radioactive wastes are disposed at the Novi Han near surface repository, located 35 km from Sofia. It was commissioned in 1964 and is now about half full. Siting studies have begun for a new near surface repository that would accept both institutional and NPP waste. A legislative and regulatory framework, as well as organizational and institutional arrangements, are in place. A national strategy that includes provisions for compiling a national inventory of spent fuel and radioactive waste and provisions for funding spent fuel and radioactive waste management, has been developed. The paper elaborates on the current situation regarding radioactive waste management in Bulgaria. (author)

  14. How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity.

    Science.gov (United States)

    Grass, G Daniel; Toole, Bryan P

    2015-11-24

    Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumour initiation to establishment of distant metastases. Complex signalling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical with several other protein factors, including basigin (Bsg), all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound [membrane-type MMPs (MT-MMPs)] in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity. © 2016 Authors.

  15. Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action

    International Nuclear Information System (INIS)

    Zhang, Haimou; Qin, Gangjian; Liang, Gang; Li, Jinan; Chiu, Isaac; Barrington, Robert A.; Liu, Dongxu

    2007-01-01

    Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-κB activation and nuclear translocation in an IκBα-dependent manner. The inhibitory effects were associated with reduction of inhibitor IκB kinase activity and stabilization of the NF-κB inhibitor IκB. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations

  16. How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity

    Science.gov (United States)

    Grass, G. Daniel; Toole, Bryan P.

    2015-01-01

    Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumour initiation to establishment of distant metastases. Complex signalling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical with several other protein factors, including basigin (Bsg), all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound [membrane-type MMPs (MT-MMPs)] in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity. PMID:26604323

  17. Differential Delivery of Genomic Double-Stranded RNA Causes Reovirus Strain-Specific Differences in Interferon Regulatory Factor 3 Activation.

    Science.gov (United States)

    Stuart, Johnasha D; Holm, Geoffrey H; Boehme, Karl W

    2018-05-01

    Serotype 3 (T3) reoviruses induce substantially more type 1 interferon (IFN-I) secretion than serotype 1 (T1) strains. However, the mechanisms underlying differences in IFN-I production between T1 and T3 reoviruses remain undefined. Here, we found that differences in IFN-I production between T1 and T3 reoviruses correlate with activation of interferon regulatory factor 3 (IRF3), a key transcription factor for the production of IFN-I. T3 strain rsT3D activated IRF3 more rapidly and to a greater extent than the T1 strain rsT1L, in simian virus 40 (SV40) immortalized endothelial cells (SVECs). Differences in IRF3 activation between rsT1L and rsT3D were observed in the first hours of infection and were independent of de novo viral RNA and protein synthesis. NF-κB activation mirrored IRF3 activation, with rsT3D inducing more NF-κB activity than rsT1L. We also found that IRF3 and NF-κB are activated in a mitochondrial antiviral-signaling protein (MAVS)-dependent manner. rsT1L does not suppress IRF3 activation, as IRF3 phosphorylation could be induced in rsT1L-infected cells. Transfected rsT1L and rsT3D RNA induced IRF3 phosphorylation, indicating that genomic RNA from both strains has the capacity to activate IRF3. Finally, bypassing the normal route of reovirus entry by transfecting in vitro -generated viral cores revealed that rsT1L and rsT3D core particles induced equivalent IRF3 activation. Taken together, our findings indicate that entry-related events that occur after outer capsid disassembly, but prior to deposition of viral cores into the cytoplasm, influence the efficiency of IFN-I responses to reovirus. This work provides further insight into mechanisms by which nonenveloped viruses activate innate immune responses. IMPORTANCE Detection of viral nucleic acids by the host cell triggers type 1 interferon (IFN-I) responses, which are critical for containing and clearing viral infections. Viral RNA is sensed in the cytoplasm by cellular receptors that initiate

  18. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.

    Directory of Open Access Journals (Sweden)

    Caitlin O'Mahony

    Full Text Available Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kappaB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kappaB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappaB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis-fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kappaB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappaB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.

  19. Association of serotonin transporter promoter regulatory region polymorphism and cerebral activity to visual presentation of food.

    Science.gov (United States)

    Kaurijoki, Salla; Kuikka, Jyrki T; Niskanen, Eini; Carlson, Synnöve; Pietiläinen, Kirsi H; Pesonen, Ullamari; Kaprio, Jaakko M; Rissanen, Aila; Tiihonen, Jari; Karhunen, Leila

    2008-07-01

    Recent functional magnetic resonance imaging (fMRI) studies have revealed links between genetic polymorphisms and cognitive and behavioural processes. Serotonin is a classical neurotransmitter of central nervous system, and it is connected to the control of appetite and satiety. In this study, the relationship between the functional variation in the serotonin transporter gene and the activity in the left posterior cingulate cortex (PCC), a brain area activated by visual food stimuli was explored. Thirty subjects underwent serial fMRI studies and provided DNA for genetic analyses. Subjects homozygous for the long allele exhibited greater left PCC activity in the comparison food > non-food compared with individuals heterozygous or homozygous for the short allele. The association between genotype and activation was linear, the subjects with two copies of the long allele variant having the strongest activation. These results demonstrate the possible genetically driven variation in the response of the left PCC to visual presentation of food in humans.

  20. Quantitative structure-activity relationships for predicting potential ecological hazard of organic chemicals for use in regulatory risk assessments.

    Science.gov (United States)

    Comber, Mike H I; Walker, John D; Watts, Chris; Hermens, Joop

    2003-08-01

    The use of quantitative structure-activity relationships (QSARs) for deriving the predicted no-effect concentration of discrete organic chemicals for the purposes of conducting a regulatory risk assessment in Europe and the United States is described. In the United States, under the Toxic Substances Control Act (TSCA), the TSCA Interagency Testing Committee and the U.S. Environmental Protection Agency (U.S. EPA) use SARs to estimate the hazards of existing and new chemicals. Within the Existing Substances Regulation in Europe, QSARs may be used for data evaluation, test strategy indications, and the identification and filling of data gaps. To illustrate where and when QSARs may be useful and when their use is more problematic, an example, methyl tertiary-butyl ether (MTBE), is given and the predicted and experimental data are compared. Improvements needed for new QSARs and tools for developing and using QSARs are discussed.

  1. Use of Advanced Tsunami Hazard Assessment Techniques and Tsunami Source Characterizations in U.S. and International Nuclear Regulatory Activities

    Science.gov (United States)

    Kammerer, A. M.; Godoy, A. R.

    2009-12-01

    In response to the 2004 Indian Ocean Tsunami, as well as the anticipation of the submission of license applications for new nuclear facilities, the United States Nuclear Regulatory Commission (US NRC) initiated a long-term research program to improve understanding of tsunami hazard levels for nuclear power plants and other coastal facilities in the United States. To undertake this effort, the US NRC organized a collaborative research program jointly undertaken with researchers at the United States Geological Survey (USGS) and the National Oceanic and Atmospheric Administration (NOAA) for the purpose of assessing tsunami hazard on the Atlantic and Gulf Coasts of the United States. This study identified and modeled both seismic and landslide tsunamigenic sources in the near- and far-field. The results from this work are now being used directly as the basis for the review of tsunami hazard at potential nuclear plant sites. This application once again shows the importance that the earth sciences can play in addressing issues of importance to society. Because the Indian Ocean Tsunami was a global event, a number of cooperative international activities have also been initiated within the nuclear community. The results of US efforts are being incorporated into updated regulatory guidance for both the U.S. Nuclear Regulatory Commission and the United Nation’s International Atomic Energy Agency (IAEA). Coordinated efforts are underway to integrate state-of-the art tsunami warning tools developed by NOAA into NRC and IAEA activities. The goal of the warning systems project is to develop automated protocols that allow scientists at these agencies to have up-to-the minute user-specific information in hand shortly after a potential tsunami has been identified by the US Tsunami Warning System. Lastly, USGS and NOAA scientists are assisting the NRC and IAEA in a special Extra-Budgetary Program (IAEA EBP) on tsunami being coordinated by the IAEA’s International Seismic Safety

  2. Leishmania major Infection Activates NF-κB and Interferon Regulatory Factors 1 and 8 in Human Dendritic Cells▿

    Science.gov (United States)

    Jayakumar, Asha; Donovan, Michael J.; Tripathi, Vinita; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann

    2008-01-01

    The salient feature of dendritic cells (DC) is the initiation of appropriate adaptive immune responses by discriminating between pathogens. Using a prototypic model of intracellular infection, we previously showed that Leishmania major parasites prime human DC for efficient interleukin-12 (IL-12) secretion. L. major infection is associated with self-limiting cutaneous disease and powerful immunity. In stark contrast, the causative agent of visceral leishmaniasis, Leishmania donovani, does not prime human DC for IL-12 production. Here, we report that DC priming by L. major infection results in the early activation of NF-κB transcription factors and the up-regulation and nuclear translocation of interferon regulatory factor 1 (IRF-1) and IRF-8. The inhibition of NF-κB activation by the pretreatment of DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 expression. We further demonstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their consensus binding sites on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signaling cascade or induces an autocrine pathway that activates IRF-1 and IRF-8, ultimately resulting in IL-12 transcription. PMID:18316378

  3. Age- and Activity-Related Differences in the Abundance of Myosin Essential and Regulatory Light Chains in Human Muscle

    Directory of Open Access Journals (Sweden)

    James N. Cobley

    2016-04-01

    Full Text Available Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM. We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping.

  4. A mechano-regulatory bone-healing model incorporating cell-phenotype specific activity

    NARCIS (Netherlands)

    Isaksson, H.E.; Donkelaar, van C.C.; Huiskes, R.; Ito, K.

    2008-01-01

    Phenomenological computational models of tissue regeneration and bone healing have been only partially successful in predicting experimental observations. This may be a result of simplistic modeling of cellular activity. Furthermore, phenomenological models are limited when considering the effects

  5. Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions

    DEFF Research Database (Denmark)

    Rennie, Sarah; Dalby, Maria; van Duin, Lucas

    2018-01-01

    Transcriptional regulation is tightly coupled with chromosomal positioning and three-dimensional chromatin architecture. However, it is unclear what proportion of transcriptional activity is reflecting such organisation, how much can be informed by RNA expression alone and how this impacts disease...... proportion of total levels and is highly informative of topological associating domain activities and organisation, revealing boundaries and chromatin compartments. Furthermore, expression data alone accurately predict individual enhancer-promoter interactions, drawing features from expression strength...... between transcription and chromatin architecture....

  6. Survey by senior NRC management to obtain veiwpoints on the safety impact of regulatory activities from representative utilities operating and constructing nuclear power plants

    International Nuclear Information System (INIS)

    1981-08-01

    A survey of licensee staff members representing the several organizational elements in different licensee corporate and plant staffs was conducted by senior NRC management to obtain licensee views on the potential safety consequences and impact of NRC regulatory activities. The comments received addressed the full scope of NRC activities and the negative impact of agency actions on licensee resources, staff performance, planning and scheduling, and organizational effectiveness. The findings of the survey is that the pace and nature of regulatory actions have created a potential safety problem which deserves further evaluation by the agency

  7. Inspection activities of the Mexican regulatory body during the construction stage of the first unit of Laguna Verde Nuclear Power Plant

    International Nuclear Information System (INIS)

    Salgado Gonzalez, Julio Ricardo

    1996-01-01

    The paper addresses the regulatory framework established for the design, construction and operation of the NPP. The regulatory bases of the inspection program are mentioned.A summary of the inspection and reviewing activities carried out by the former Nuclear Safety Management Construction area during the construction stage, taking the year 1977 as the beginning of regular inspection activities for this construction stage, and up to the year 1987, when this one is considered as practically completed, and a stage of pre-operational tests has been started. Finally, the main inspection areas are described, and a summary is given of the classification of deficiencies detected during the inspections

  8. Identification of cis-regulatory sequences that activate transcription in the suspensor of plant embryos.

    Science.gov (United States)

    Kawashima, Tomokazu; Wang, Xingjun; Henry, Kelli F; Bi, Yuping; Weterings, Koen; Goldberg, Robert B

    2009-03-03

    Little is known about the molecular mechanisms by which the embryo proper and suspensor of plant embryos activate specific gene sets shortly after fertilization. We analyzed the upstream region of the scarlet runner bean (Phaseolus coccineus) G564 gene to understand how genes are activated specifically within the suspensor during early embryo development. Previously, we showed that the G564 upstream region has a block of tandem repeats, which contain a conserved 10-bp motif (GAAAAG(C)/(T)GAA), and that deletion of these repeats results in a loss of suspensor transcription. Here, we use gain-of-function (GOF) experiments with transgenic globular-stage tobacco embryos to show that only 1 of the 5 tandem repeats is required to drive suspensor-specific transcription. Fine-scale deletion and scanning mutagenesis experiments with 1 tandem repeat uncovered a 54-bp region that contains all of the sequences required to activate transcription in the suspensor, including the 10-bp motif (GAAAAGCGAA) and a similar 10-bp-like motif (GAAAAACGAA). Site-directed mutagenesis and GOF experiments indicated that both the 10-bp and 10-bp-like motifs are necessary, but not sufficient to activate transcription in the suspensor, and that a sequence (TTGGT) between the 10-bp and the 10-bp-like motifs is also necessary for suspensor transcription. Together, these data identify sequences that are required to activate transcription in the suspensor of a plant embryo after fertilization.

  9. Moonlighting kinases with guanylate cyclase activity can tune regulatory signal networks

    KAUST Repository

    Irving, Helen R.; Kwezi, Lusisizwe; Wheeler, Janet I.; Gehring, Christoph A

    2012-01-01

    Guanylate cyclase (GC) catalyzes the formation of cGMP and it is only recently that such enzymes have been characterized in plants. One family of plant GCs contains the GC catalytic center encapsulated within the intracellular kinase domain of leucine rich repeat receptor like kinases such as the phytosulfokine and brassinosteroid receptors. In vitro studies show that both the kinase and GC domain have catalytic activity indicating that these kinase-GCs are examples of moonlighting proteins with dual catalytic function. The natural ligands for both receptors increase intracellular cGMP levels in isolated mesophyll protoplast assays suggesting that the GC activity is functionally relevant. cGMP production may have an autoregulatory role on receptor kinase activity and/or contribute to downstream cell expansion responses. We postulate that the receptors are members of a novel class of receptor kinases that contain functional moonlighting GC domains essential for complex signaling roles.

  10. Moonlighting kinases with guanylate cyclase activity can tune regulatory signal networks

    KAUST Repository

    Irving, Helen R.

    2012-02-01

    Guanylate cyclase (GC) catalyzes the formation of cGMP and it is only recently that such enzymes have been characterized in plants. One family of plant GCs contains the GC catalytic center encapsulated within the intracellular kinase domain of leucine rich repeat receptor like kinases such as the phytosulfokine and brassinosteroid receptors. In vitro studies show that both the kinase and GC domain have catalytic activity indicating that these kinase-GCs are examples of moonlighting proteins with dual catalytic function. The natural ligands for both receptors increase intracellular cGMP levels in isolated mesophyll protoplast assays suggesting that the GC activity is functionally relevant. cGMP production may have an autoregulatory role on receptor kinase activity and/or contribute to downstream cell expansion responses. We postulate that the receptors are members of a novel class of receptor kinases that contain functional moonlighting GC domains essential for complex signaling roles.

  11. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Hu, Mintao [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Zhang, Peng [Nanjing Medical University, Nanjing, Jiangsu (China); Cao, Hong [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Wang, Yongzhen [The Second Hospital of Nanjing, Nanjing, Jiangsu (China); Wang, Zheng; Su, Tingting [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China)

    2013-05-10

    Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

  12. Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.).

    Science.gov (United States)

    Yin, Tao; Wu, Hanying; Zhang, Shanglong; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming; Liu, Jingmei

    2009-01-01

    A 1.8 kb 5'-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from -986 to -959 and from -472 to -424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative beta-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were approximately 10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves.

  13. Antidiabetic activity of Ganoderma lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice.

    Science.gov (United States)

    Xiao, Chun; Wu, Qingping; Zhang, Jumei; Xie, Yizhen; Cai, Wen; Tan, Jianbin

    2017-01-20

    Ganoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action. Four polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice. Fasting serum glucose (FSG), fasting serum insulin (FSI) and epididymal fat/BW ratio were measured at the end of the experiment. In liver, the mRNA levels of hepatic glucose regulatory enzymes were determined by quantitative polymerase chain reaction (qPCR) and the protein levels of phospho-AMP-activated protein kinase (p-AMPK)/AMPK were determined by western blotting test. In epididymal fat tissue, the mRNA and protein levels GLUT4, resistin, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC1) were determined by qPCR and immuno-histochemistry. The structure of polysaccharide F31 was obtained from GPC, FTIR NMR and GC-MS spectroscopy, RESULTS: F31 significantly decreased FSG (P<0.05), FSI and epididymal fat/BW ratio (P<0.01). In liver, F31 decreased the mRNA levels of hepatic glucose regulatory enzymes, and up-regulated the ratio of phospho-AMP-activated protein kinase (p-AMPK)/AMPK. In epididymal fat tissue, F31 increased the mRNA levels of GLUT4 but decreased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1) and resistin. Immuno-histochemistry results revealed F31 increased the protein levels of GLUT4 and decreased resistin. Data suggested that the main bioactives in GLPs was F31, which was determined to be a β-heteropolysaccharide with the weight-average molecular weight of 15.9kDa. The possible action mechanism of F31 may be associated with down-regulation of the hepatic glucose regulated enzyme mRNA levels via AMPK activation, improvement of insulin resistance and decrease of epididymal fat/BW ratio. These

  14. Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels

    Science.gov (United States)

    Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

    2015-01-01

    Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

  15. Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels.

    Directory of Open Access Journals (Sweden)

    Qijing Chen

    Full Text Available Large conductance Ca2+-activated potassium channels (BK are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α and BK (α+β1 currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1. Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms.

  16. Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

    Science.gov (United States)

    Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming; Eliceiri, Kevin W; Ahlquist, Paul; Sherer, Nathan M

    2017-02-01

    Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. © 2017 Pocock et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  17. A novel method for predicting activity of cis-regulatory modules, based on a diverse training set.

    Science.gov (United States)

    Yang, Wei; Sinha, Saurabh

    2017-01-01

    With the rapid emergence of technologies for locating cis-regulatory modules (CRMs) genome-wide, the next pressing challenge is to assign precise functions to each CRM, i.e. to determine the spatiotemporal domains or cell-types where it drives expression. A popular approach to this task is to model the typical k-mer composition of a set of CRMs known to drive a common expression pattern, and assign that pattern to other CRMs exhibiting a similar k-mer composition. This approach does not rely on prior knowledge of transcription factors relevant to the CRM or their binding motifs, and is thus more widely applicable than motif-based methods for predicting CRM activity, but is also prone to false positive predictions. We present a novel strategy to improve the above-mentioned approach: to predict if a CRM drives a specific gene expression pattern, assess not only how similar the CRM is to other CRMs with similar activity but also to CRMs with distinct activities. We use a state-of-the-art statistical method to quantify a CRM's sequence similarity to many different training sets of CRMs, and employ a classification algorithm to integrate these similarity scores into a single prediction of the CRM's activity. This strategy is shown to significantly improve CRM activity prediction over current approaches. Our implementation of the new method, called IMMBoost, is freely available as source code, at https://github.com/weiyangedward/IMMBoost CONTACT: sinhas@illinois.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Microfilament regulatory protein MENA increases activity of RhoA and promotes metastasis of hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Ling; Yang, Xiao-Mei; Li, Jun; Zhang, Yan-Li; Qin, Wenxin; Zhang, Zhi-Gang

    2014-09-10

    Mammalian enabled (MENA), usually known as a direct regulator of microfilament polymerization and bundling, promotes metastasis in various cancers. Here we focus on the role of MENA in hepatocellular carcinoma (HCC) metastasis and the relevant mechanism from the view of RhoA activity regulation. By HCC tissue microarray analysis, we found that MENA expression was positively associated with satellite lesions (PMENA staining in HCC tissues had significantly higher rates of early recurrence in the intermediate MENA expression group. Knockdown of MENA significantly suppressed HCC cell migration and invasion in vitro, as well as their intrahepatic and distant metastasis in vivo. Knockdown of MENA also decreased filopodia and stress fibers in SMMC-7721 cells. Furthermore, a decrease of RhoA activity was detected by a pull-down assay in SMMC-7721-shMENA cells. The ROCK inhibitor, Y-27632, suppressed migration of both MENA knockdown SMMC-7721 cells and control cells, but diminished their difference. Thus, our findings suggest that MENA promotes HCC cell motility by activating RhoA. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Le traitement de la variation linguistique dans les travaux universitaires sur les langues pratiquées en Algérie : Cas de quelques positions de recherche

    Directory of Open Access Journals (Sweden)

    Chachou Ibtissem

    2016-01-01

    Full Text Available Notre contribution porte sur les dynamiques de recherche sur la question de la variation (ou leur absence par rapport aux langues pratiquées en Algérie. Ces langues sont l’arabe algérien, le français, les langues berbères et l’arabe institutionnel, et ce dans les domaines formels et informels. Notre corpus renferme un échantillon représentatif des écrits portant sur des pratiques plurilingues et/ ou les théorisant, lesquelles pratiques sont saisies et analysées des points de vue sociolinguistique et sociodidactique. Ces écrits/résultats sont l’oeuvre de chercheurs algériens dont les travaux sont repris par les jeunes chercheurs notamment et qui leur servent souvent de références et d’appuis théoriques. Nous tenterons à travers cette contribution, autant que faire se peut, de dégager ces positionnements théoriques, d’en interroger les soubassements d’ordre épistémique et d’identifier clairement les orientations, les priorités et les attentes pour la recherche en didactique et en sociolinguistique. Il s’agira notamment de mesurer leur apport pour la recherche dans le domaine des sciences du langage, leur pertinence ainsi que leur utilité, mais d’observer également ce qui peut handicaper la réflexion sur des questions aussi sensibles tant elles sont innervées par des considérations idéologiques dont le linguiste n’échappe pas toujours.

  20. Regulatory supervision of industrial waste containing very low activities of man-made radionuclides at SevRAO facility

    International Nuclear Information System (INIS)

    Sneve, Malgorzata K.; Kochetkov, Oleg; Monastyrskaya, Svetlana; Barchukov, Valerie; Romanov, Vladimir

    2008-01-01

    Full text: Large amounts of waste and materials with very low activity level are generated during operation and especially during decommissioning of nuclear facilities. Selection of the optimum economic and ecologically safe management option of such material is complicated by its specific features: very low level radiation exposure to individuals but rather large initial amounts of waste. On the one hand, it is a poor use of limited resources to em place such low activity waste into expensive facilities for radioactive waste storage and disposal if the radiological impact would be very small even for a much less expensive option; on the other hand, there is some apprehension regarding safety both about its disposal to landfills for conventional (non-radioactive) waste disposal, and about its limited or unlimited re-use or re-cycling. To regulate such waste management, a special waste category is introduced - very low level waste (VLLW). This category includes waste containing radionuclides with specific activity levels, which are higher than clearance levels, but do not need high containment and isolation. This paper discusses experience of regulatory development for VLLW control during remediation of radiation hazardous facilities in northwest Russia. The work has promoted identification of some challenges, whose solution has affected the waste management strategy at the sites. One of the main problems resolved was the selection of criteria according to which waste is allocated to the VLLW category. These is turn were partly determined by the radiological criteria chosen for protection of the public during this waste disposal. Elaboration of safe VLLW management strategy depends upon a source of waste generation and of its radiological composition. The VLLW management strategy at an operating enterprise, e.g. a nuclear power plant is rather different from the strategy implemented at the plant under decommissioning, or at storage facilities for the legacy waste

  1. Planning of the regulatory inspection activity during manufacturing, construction and operation of the Italian nuclear plants

    International Nuclear Information System (INIS)

    Messore, G.A.

    1977-01-01

    After a brief review of the provisions in force in Italy on the inspection of nuclear installations the paper deals with the main criteria which determine the general and annual inspection programmes for every nuclear installation and the procedures for recording the results of inspections. It also describes the classification of nuclear installations into different categories according to the degree of hazard presented by their respective activities and consequently, the selection of the minimum number of inspections to be conducted every year for each of these categories. (NEA) [fr

  2. A Survey of 6,300 Genomic Fragments for cis-Regulatory Activity in the Imaginal Discs of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Aurélie Jory

    2012-10-01

    Full Text Available Over 6,000 fragments from the genome of Drosophila melanogaster were analyzed for their ability to drive expression of GAL4 reporter genes in the third-instar larval imaginal discs. About 1,200 reporter genes drove expression in the eye, antenna, leg, wing, haltere, or genital imaginal discs. The patterns ranged from large regions to individual cells. About 75% of the active fragments drove expression in multiple discs; 20% were expressed in ventral, but not dorsal, discs (legs, genital, and antenna, whereas ∼23% were expressed in dorsal but not ventral discs (wing, haltere, and eye. Several patterns, for example, within the leg chordotonal organ, appeared a surprisingly large number of times. Unbiased searches for DNA sequence motifs suggest candidate transcription factors that may regulate enhancers with shared activities. Together, these expression patterns provide a valuable resource to the community and offer a broad overview of how transcriptional regulatory information is distributed in the Drosophila genome.

  3. p75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3.

    Science.gov (United States)

    Pham, Dan Duc; Do, Hai Thi; Bruelle, Céline; Kukkonen, Jyrki P; Eriksson, Ove; Mogollón, Isabel; Korhonen, Laura T; Arumäe, Urmas; Lindholm, Dan

    2016-05-13

    Nerve growth factor (NGF) influences the survival and differentiation of a specific population of neurons during development, but its role in non-neuronal cells has been less studied. We observed here that NGF and its pro-form, pro-NGF, are elevated in fatty livers from leptin-deficient mice compared with controls, concomitant with an increase in low density lipoprotein receptors (LDLRs). Stimulation of mouse primary hepatocytes with NGF or pro-NGF increased LDLR expression through the p75 neurotrophin receptor (p75NTR). Studies using Huh7 human hepatocyte cells showed that the neurotrophins activate the sterol regulatory element-binding protein-2 (SREBP2) that regulates genes involved in lipid metabolism. The mechanisms for this were related to stimulation of p38 mitogen-activated protein kinase (p38 MAPK) and activation of caspase-3 and SREBP2 cleavage following NGF and pro-NGF stimulations. Cell fractionation experiments showed that caspase-3 activity was increased particularly in the membrane fraction that harbors SREBP2 and caspase-2. Experiments showed further that caspase-2 interacts with pro-caspase-3 and that p38 MAPK reduced this interaction and caused caspase-3 activation. Because of the increased caspase-3 activity, the cells did not undergo cell death following p75NTR stimulation, possibly due to concomitant activation of nuclear factor-κB (NF-κB) pathway by the neurotrophins. These results identify a novel signaling pathway triggered by ligand-activated p75NTR that via p38 MAPK and caspase-3 mediate the activation of SREBP2. This pathway may regulate LDLRs and lipid uptake particularly after injury or during tissue inflammation accompanied by an increased production of growth factors, including NGF and pro-NGF. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Nuclear legislation: analytical study. Regulatory and institutional framework for nuclear activities

    International Nuclear Information System (INIS)

    2001-01-01

    Australia' s basic legislation in the nuclear field consists in five Acts passed by the Federal Parliament. These Acts are as follow: the South Pacific nuclear free zone treaty Act; the nuclear non-proliferation act; the Australian nuclear science and technology organisation act; the Australian nuclear science and technology organisation amendment act; the radiation protection and nuclear safety act. The two first Acts were prompted by the need for domestic legislation to implement Australia 's international obligations. The third arose from a long-standing recognition that the Atomic energy Act was inappropriate as the legislative basis for the activities of Australia 's national nuclear organisation. For its part the fourth Act introduced some necessary changes into the Australian nuclear science and technology organisation Act. Finally, the fifth act establishes a regime to regulate the operation of nuclear installations and the management of radiation sources, where the activities are undertaken by Commonwealth entities. Each of these Acts is discussed in more details in this work. (N.C.)

  5. Novel Concept of CD4-Mediated Activation of Regulatory T Cells for the Treatment of Graft-Versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Janine Schlöder

    2017-11-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host disease (GvHD after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia. Several novel cell-based immunomodulatory strategies for treatment or prevention of GvHD have been developed. Herein, thymus-derived regulatory T cells (tTreg, essential for the maintenance of peripheral immunologic tolerance, are in the focus of investigation. However, due to the limited number of tTreg in the peripheral blood, a complex, time- and cost-intensive in vitro expansion protocol is necessary for the production of an efficient cellular therapeutic. We demonstrated that activation of tTreg using the CD4-binding human immunodeficiency virus-1 protein gp120 leads to a substantially increased suppressor activity of tTreg without the need for additional expansion. Gp120-activated tTreg prevent GvHD development in a preclinical humanized mouse model. In addition, gp120 is not only effective in prevention but also in therapy of GvHD by suppressing all clinical symptoms and improving survival of treated mice. These data indicate that tTreg activation by gp120 is a feasible and potent strategy for significant functional improvement of tTreg as cellular therapeutic for GvHD treatment without the need of complicated, time-intensive, and expensive in vitro expansion of isolated tTreg.

  6. Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

    Science.gov (United States)

    Molins, B; Mesquida, M; Lee, R W J; Llorenç, V; Pelegrín, L; Adán, A

    2015-03-01

    The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells. © 2014 British Society for Immunology.

  7. Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity.

    Science.gov (United States)

    Tong, Jiefei; Elowe, Sabine; Nash, Piers; Pawson, Tony

    2003-02-21

    Signaling by the Eph family of receptor tyrosine kinases (RTKs) is complex, because they can interact with a variety of intracellular targets, and can potentially induce distinct responses in different cell types. In NG108 neuronal cells, activated EphB2 recruits p120RasGAP, in a fashion that is associated with down-regulation of the Ras-Erk mitogen-activated kinase (MAPK) pathway and neurite retraction. To pursue the role of the Ras-MAPK pathway in EphB2-mediated growth cone collapse, and to explore the biochemical and biological functions of Eph receptors, we sought to re-engineer the signaling properties of EphB2 by manipulating its regulatory motifs and SH2 binding sites. An EphB2 mutant that retained juxtamembrane (JM) RasGAP binding sites but incorporated a Grb2 binding motif at an alternate RasGAP binding site within the kinase domain had little effect on basal Erk MAPK activation. In contrast, elimination of all RasGAP binding sites, accompanied by the addition of a Grb2 binding site within the kinase domain, led to an increase in phospho-Erk levels in NG108 cells following ephrin-B1 stimulation. Functional assays indicated a correlation between neurite retraction and the ability of the EphB2 mutants to down-regulate Ras-Erk MAPK signaling. These data suggest that EphB2 can be designed to repress, stabilize, or activate the Ras-Erk MAPK pathway by the manipulation of RasGAP and Grb2 SH2 domain binding sites and support the notion that Erk MAPK regulation plays a significant role in axon guidance. The behavior of EphB2 variants with mutations in the JM region and kinase domains suggests an intricate pattern of regulation and target recognition by Eph receptors.

  8. Regulatory management of NORM wastes from petroleum exploration activities in the Northern Territory

    International Nuclear Information System (INIS)

    Cassels, B.; Waite, A.

    2001-01-01

    During September 1996, history was made with what the authors believe to be the first Australian sub-seafloor disposal of NORM scale resulting from petroleum exploration activities. Approximately 800 kg of scale with a maximum 226 RaT 228 Ra activity concentration of 600 kBq.kg -1 was disposed off via downhole well injection to and concrete capping of a dry exploration well. This scale material was removed from pipework which had measured external surface dose rates in excess of 30 μSv.hr -1 . Subsequent disposals have occurred in accordance with strictly applied radiation protection requirements and in accordance with the legislative framework applicable to such activities in the offshore waters regulated by the Northern Territory in conjunction with the Commonwealth Government, which are briefly described. A summary of NORM disposals that have taken place to date in the Northern Territory is also provided. NORM scale accretes in pipework due to changes in the conditions of formation water associated with oil deposits. Radium isotopes and their decay products exist in the formation water of oil reservoirs, particularly in the Middle and Lower Jurassic formations which together account for 70% of the production operations around the world that experience the formation of radioactive scale. During the first major scale removal exercise it was found that scale build up in the pipes ranged between 11 mm and 42 mm reducing the internal diameter from a nominal 203 mm to 120 mm. The average production rate prior to descaling operations was around 1,700 m 3 of crude per day, rising to around 2,500 m 3 per day post-descaling. The effect of scale removal on productivity is the principle driving force for its removal. The Northern Territory Department of Mines and Energy and Territory Health Services reviewed all aspects of proposals and reached agreement with the client on all aspects prior to issuing approvals under the Petroleum (Submerged Lands) Act and the Radiation

  9. Enhanced Suppressive Activity of Regulatory T Cells in the Microenvironment of Malignant Pleural Effusions

    Directory of Open Access Journals (Sweden)

    Joanna Budna

    2018-01-01

    Full Text Available Cancer metastatic spread to serous cavity causes malignant pleural effusions (MPEs, indicating dismal prognosis. Tumor microenvironment can implement suppressive activity on host immune responses. Thus, we investigated the prevalence of Tregs and the relationship between them and TGF-β and IL-10 concentrations and measured expression of FOXP3, CTLA-4, CD28, and GITR genes, as well as protein expression of selected genes in benign effusions and MPEs. The percentage of Tregs was determined by means of multicolor flow cytometry system. TGF-β and IL-10 concentrations were measured using human TGF-β1 and IL-10 ELISA kit. Relative mRNA expression of studied genes was analyzed by real-time PCR. The frequency of Tregs was significantly higher in MPEs compared to benign effusions; however, the level of TGF-β and IL-10 in analyzed groups was comparable, and no correlation between concentrations of TGF-β and IL-10 and percentage of Tregs was observed. Relative mRNA expression of all the genes was higher in CD4+CD25+ compared to CD4+CD25− cells. In CD4+CD25+ cells from MPEs, relative mRNA expression of FOXP3, CTLA-4, and CD28 genes was significantly higher than in benign effusions; however, the level of CD4+CD25+CTLA-4+ cells in analyzed groups showed no significant differences. We found numerous genes correlations in an entire CD4+CD25+ cell subset and CD4+CD25+ cells from MPEs. Enhanced suppressive activity of Tregs is observed in the microenvironment of MPEs. Understanding of relations between cellular and cytokine immunosuppressive factors in tumor microenvironment may determine success of anticancer response.

  10. A central regulatory system largely controls transcriptional activation and repression responses to phosphate starvation in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Regla Bustos

    2010-09-01

    Full Text Available Plants respond to different stresses by inducing or repressing transcription of partially overlapping sets of genes. In Arabidopsis, the PHR1 transcription factor (TF has an important role in the control of phosphate (Pi starvation stress responses. Using transcriptomic analysis of Pi starvation in phr1, and phr1 phr1-like (phl1 mutants and in wild type plants, we show that PHR1 in conjunction with PHL1 controls most transcriptional activation and repression responses to phosphate starvation, regardless of the Pi starvation specificity of these responses. Induced genes are enriched in PHR1 binding sequences (P1BS in their promoters, whereas repressed genes do not show such enrichment, suggesting that PHR1(-like control of transcriptional repression responses is indirect. In agreement with this, transcriptomic analysis of a transgenic plant expressing PHR1 fused to the hormone ligand domain of the glucocorticoid receptor showed that PHR1 direct targets (i.e., displaying altered expression after GR:PHR1 activation by dexamethasone in the presence of cycloheximide corresponded largely to Pi starvation-induced genes that are highly enriched in P1BS. A minimal promoter containing a multimerised P1BS recapitulates Pi starvation-specific responsiveness. Likewise, mutation of P1BS in the promoter of two Pi starvation-responsive genes impaired their responsiveness to Pi starvation, but not to other stress types. Phylogenetic footprinting confirmed the importance of P1BS and PHR1 in Pi starvation responsiveness and indicated that P1BS acts in concert with other cis motifs. All together, our data show that PHR1 and PHL1 are partially redundant TF acting as central integrators of Pi starvation responses, both specific and generic. In addition, they indicate that transcriptional repression responses are an integral part of adaptive responses to stress.

  11. GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3+ regulatory T cells

    OpenAIRE

    Tran, Dat Q.; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M.

    2009-01-01

    TGF-β family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-β is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFβ-binding protein (LTBP) to produce a large latent form. Latent TGF-β is also found on the surface of activated FOXP3+ regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule ...

  12. Safety-Related Contractor Activities at Nuclear Power Plants. New Challenges for Regulatory Oversight

    Energy Technology Data Exchange (ETDEWEB)

    Chockie, Alan [Chockie Group International, Inc., Seattle, WA (United States)

    2005-09-15

    The use of contractors has been an integral and important part of the design, construction, operation, and maintenance of nuclear power plants. To ensure the safe and efficient completion of contracted tasks, each nuclear plant licensee has developed and refined formal contract management processes to meet their specific needs and plant requirements. Although these contract management processes have proven to be effective tools for the procurement of support and components tailored to the needs of nuclear power plants, contractor-related incidents and accidents have revealed some serious weaknesses with the implementation of these processes. Identifying and addressing implementation problems are becoming more complicated due to organizational and personnel changes affecting the nuclear power industry. The ability of regulators and licensees to effectively monitor and manage the safety-related performance of contractors will likely be affected by forthcoming organization and personnel changes due to: the aging of the workforce; the decline of the nuclear industry; and the deregulation of nuclear power. The objective of this report is to provide a review of current and potential future challenges facing safety-related contractor activities at nuclear power plants. The purpose is to assist SKI in establishing a strategy for the proactive oversight of contractor safety-related activities at Swedish nuclear power plants and facilities. The nature and role of contractors at nuclear plants is briefly reviewed in the first section of the report. The second section describes the essential elements of the contract management process. Although organizations have had decades of experience with the a contract management process, there remain a number of common implantation weaknesses that have lead to serious contractor-related incidents and accidents. These implementation weaknesses are summarized in the third section. The fourth section of the report highlights the

  13. Safety-Related Contractor Activities at Nuclear Power Plants. New Challenges for Regulatory Oversight

    International Nuclear Information System (INIS)

    Chockie, Alan

    2005-09-01

    The use of contractors has been an integral and important part of the design, construction, operation, and maintenance of nuclear power plants. To ensure the safe and efficient completion of contracted tasks, each nuclear plant licensee has developed and refined formal contract management processes to meet their specific needs and plant requirements. Although these contract management processes have proven to be effective tools for the procurement of support and components tailored to the needs of nuclear power plants, contractor-related incidents and accidents have revealed some serious weaknesses with the implementation of these processes. Identifying and addressing implementation problems are becoming more complicated due to organizational and personnel changes affecting the nuclear power industry. The ability of regulators and licensees to effectively monitor and manage the safety-related performance of contractors will likely be affected by forthcoming organization and personnel changes due to: the aging of the workforce; the decline of the nuclear industry; and the deregulation of nuclear power. The objective of this report is to provide a review of current and potential future challenges facing safety-related contractor activities at nuclear power plants. The purpose is to assist SKI in establishing a strategy for the proactive oversight of contractor safety-related activities at Swedish nuclear power plants and facilities. The nature and role of contractors at nuclear plants is briefly reviewed in the first section of the report. The second section describes the essential elements of the contract management process. Although organizations have had decades of experience with the a contract management process, there remain a number of common implantation weaknesses that have lead to serious contractor-related incidents and accidents. These implementation weaknesses are summarized in the third section. The fourth section of the report highlights the

  14. CP110 exhibits novel regulatory activities during centriole assembly in Drosophila

    Science.gov (United States)

    Franz, Anna; Roque, Hélio; Saurya, Saroj; Dobbelaere, Jeroen

    2013-01-01

    CP110 is a conserved centriole protein implicated in the regulation of cell division, centriole duplication, and centriole length and in the suppression of ciliogenesis. Surprisingly, we report that mutant flies lacking CP110 (CP110Δ) were viable and fertile and had no obvious defects in cell division, centriole duplication, or cilia formation. We show that CP110 has at least three functions in flies. First, it subtly influences centriole length by counteracting the centriole-elongating activity of several centriole duplication proteins. Specifically, we report that centrioles are ∼10% longer than normal in CP110Δ mutants and ∼20% shorter when CP110 is overexpressed. Second, CP110 ensures that the centriolar microtubules do not extend beyond the distal end of the centriole, as some centriolar microtubules can be more than 50 times longer than the centriole in the absence of CP110. Finally, and unexpectedly, CP110 suppresses centriole overduplication induced by the overexpression of centriole duplication proteins. These studies identify novel and surprising functions for CP110 in vivo in flies. PMID:24297749

  15. Below Regulatory Concern Owners Group: An evaluation of dry active waste sorting: Final report

    International Nuclear Information System (INIS)

    Casey, S.M.

    1989-02-01

    The objective of this research was to determine the accuracy of manual inspection of Dry Active Waste (DAW). Three studies were conducted at two nuclear power plants in which unmodified DAW waste streams of roughly 10,000 items each were inspected by technicians using pancake probes. Sorting performance was measured unobtrusively by intercepting the ''outflow'' from inspection stations. Verification of sorting accuracy was performed with a prototype, semi-automated sorting table employing a matrix of fixed plastic scintillation detectors. More than 30,000 items of trash were examined, classified, counted, and verified, and the composition of the ''inflow'' to the inspection stations was determined by reconstructing the ''outflow'' components, as determined during verification procedures. The results showed that between 1 and 19% of all items in each of the three DAW waste streams were contaminated at levels ≥100 ccpm. Sixty-two percent of the ''contaminated'' items in Study I, 87% of the contaminated items in Study II, and 97% of the contaminated items in Study III were detected. One-half to one percent of all items classified as <100 ccpm by technicians were actually ≥100 ccpm. False positive rates were very high in all three studies. The production rates and accuracy obtained on the semi-automated plastic scintillation sorting table used during the verification stages of this project greatly exceeded the rates for manual sorting. 9 figs., 13 tabs

  16. Requirement Management between Regulatory Framework and Dismantling Activities for Decommissioning of a Nuclear Facility

    International Nuclear Information System (INIS)

    Park, H.S.; Jin, H.G.; Hong, Y.J.; Choi, J.W.; Park, S.

    2016-01-01

    Full text: The decommissioning and environmental remediation (D&ER) projects require stepwise long-term research and development (R&D) such as a shutdown, transition, decontamination and decommissioning (D&D) activities, radioactive waste management, and site restoration. During each step of the D&ER projects, a significant amount of information and knowledge such as experimental data, databases, design drawings, technical reports, guidelines, operation manuals, and modeling and simulation reports are produced. Knowledge based on experiences by staff members participating in each step of the D&ER project are also very important. Such knowledge based on experiences may disappear with the retirement of staff members if there are no effective and systematic approaches for its acquisition and storage. Therefore, to perform the D&ER project successfully, it is necessary to preserve written theses and experiences systematically. The integrated knowledge management system (KMS) for the D&ER projects have never been developed. Therefore, the establishment of an integrated KMS is necessary for the effective performance of D&ER projects. This study introduces a decommissioning procedure requirement management system as a part of the KMS related to the D&ER projects. (author

  17. Impairment of interferon regulatory factor-3 activation by hepatitis C virus core protein basic amino acid region 1.

    Science.gov (United States)

    Inoue, Kazuaki; Tsukiyama-Kohara, Kyoko; Matsuda, Chiho; Yoneyama, Mitsutoshi; Fujita, Takashi; Kuge, Shusuke; Yoshiba, Makoto; Kohara, Michinori

    2012-11-30

    Interferon regulatory factor-3 (IRF-3), a key transcriptional factor in the type I interferon system, is frequently impaired by hepatitis C virus (HCV), in order to establish persistent infection. However, the exact mechanism by which the virus establishes persistent infection has not been fully understood yet. The present study aimed to investigate the effects of various HCV proteins on IRF-3 activation, and elucidate the underlying mechanisms. To achieve this, full-length HCV and HCV subgenomic constructs corresponding to structural and each of the nonstructural proteins were transiently transfected into HepG2 cells. IFN-β induction, plaque formation, and IRF-3 dimerization were elicited by Newcastle disease virus (NDV) infection. The expressions of IRF-3 homodimer and its monomer, Ser386-phosphorylated IRF-3, and HCV core protein were detected by immunofluorescence and western blotting. IFN-β mRNA expression was quantified by real-time PCR (RT-PCR), and IRF-3 activity was measured by the levels of IRF-3 dimerization and phosphorylation, induced by NDV infection or polyriboinosinic:polyribocytidylic acid [poly(I:C)]. Switching of the expression of the complete HCV genome as well as the core proteins, E1, E2, and NS2, suppressed IFN-β mRNA levels and IRF-3 dimerization, induced by NDV infection. Our study revealed a crucial region of the HCV core protein, basic amino acid region 1 (BR1), to inhibit IRF-3 dimerization as well as its phosphorylation induced by NDV infection and poly (I:C), thus interfering with IRF-3 activation. Therefore, our study suggests that rescue of the IRF-3 pathway impairment may be an effective treatment for HCV infection. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.

    Directory of Open Access Journals (Sweden)

    Ayelet Kaminitz

    Full Text Available BACKGROUND: Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff and regulatory T cells (Treg to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice. PRINCIPAL FINDINGS: Both effector (CD25(-, FoxP3(- and suppressor (CD25(+, FoxP3(+ CD4(+ T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP trangeneess. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL in both strains. The effector and suppressor CD4(+ subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4(+CD25(- T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice. CONCLUSION: These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis.

  19. Suppression of Natural Killer Cell Activity by Regulatory NKT10 Cells Aggravates Alcoholic Hepatosteatosis

    Directory of Open Access Journals (Sweden)

    Kele Cui

    2017-10-01

    Full Text Available We and others have found that the functions of hepatic natural killer (NK cells are inhibited but invariant NKT (iNKT cells become activated after alcohol drinking, leaving a possibility that there exists interplay between NK cells and iNKT cells during alcoholic liver disease. Here, in a chronic plus single-binge ethanol consumption mouse model, we observed that NK cells and interferon-γ (IFN-γ protected against ethanol-induced liver steatosis, as both wild-type (WT mice treated with anti-asialo GM1 antibody and IFN-γ-deficient GKO mice developed more severe alcoholic fatty livers. As expected, IFN-γ could directly downregulate lipogenesis in primary hepatocytes in vitro. On the contrary, iNKT cell-deficient Jα18−/− or interleukin-10 (IL-10−/− mice showed fewer alcoholic steatosis, along with the recovered number and IFN-γ release of hepatic NK cells, and exogenous IL-10 injection was sufficient to compensate for iNKT cell deficiency. Furthermore, NK cell depletion in Jα18−/− or IL-10−/− mice caused more severe hepatosteatosis, implying NK cells are the direct effector cells to inhibit liver steatosis. Importantly, adoptive transfer of iNKT cells purified from normal but not IL-10−/− mice resulted in suppression of the number and functions of NK cells and aggravated alcoholic liver injury in Jα18−/− mice, indicating that IL-10-producing iNKT (NKT10 cells are the regulators on NK cells. Conclusion: Ethanol exposure-triggered NKT10 cells antagonize the protective roles of NK cells in alcoholic hepatosteatosis.

  20. Role of regulatory subunits and protein kinase inhibitor (PKI) in determining nuclear localization and activity of the catalytic subunit of protein kinase A.

    Science.gov (United States)

    Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S

    1999-03-05

    Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.

  1. Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts.

    Science.gov (United States)

    Lisse, Thomas S; Chun, Rene F; Rieger, Sandra; Adams, John S; Hewison, Martin

    2013-06-01

    When bound to the vitamin D receptor (VDR), the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of osteoblast transcription. Less clear is the impact of 1,25D on posttranscriptional events in osteoblasts, such as the generation and action of microRNAs (miRNAs). Microarray analysis using replicate (n = 3) primary cultures of human osteoblasts (HOBs) identified human miRNAs that were differentially regulated by >1.5-fold following treatment with 1,25D (10 nM, 6 hours), which included miRNAs 637 and 1228. Quantitative reverse transcription PCR analyses showed that the host gene for miR-1228, low-density lipoprotein receptor-related protein 1 (LRP1), was coinduced with miR-1228 in a dose-dependent fashion following treatment with 1,25D (0.1-10 nM, 6 hours). By contrast, the endogenous host gene for miR-637, death-associated protein kinase 3 (DAPK3), was transcriptionally repressed by following treatment with 1,25D. Analysis of two potential targets for miR-637 and miR-1228 in HOB, type IV collagen (COL4A1) and bone morphogenic protein 2 kinase (BMP2K), respectively, showed that 1,25D-mediates suppression of these targets via distinct mechanisms. In the case of miR-637, suppression of COL4A1 appears to occur via decreased levels of COL4A1 mRNA. By contrast, suppression of BMP2K by miR-1228 appears to occur by inhibition of protein translation. In mature HOBs, small interfering RNA (siRNA) inactivation of miR-1228 alone was sufficient to abrogate 1,25D-mediated downregulation of BMP2K protein expression. This was associated with suppression of prodifferentiation responses to 1,25D in HOB, as represented by parallel decrease in osteocalcin and alkaline phosphatase expression. These data show for the first time that the effects of 1,25D on human bone cells are not restricted to classical VDR-mediated transcriptional responses but also involve miRNA-directed posttranscriptional mechanisms. Copyright © 2013 American Society for Bone and

  2. Generation of dTALEs and Libraries of Synthetic TALE-Activated Promoters for Engineering of Gene Regulatory Networks in Plants.

    Science.gov (United States)

    Schreiber, Tom; Tissier, Alain

    2017-01-01

    Transcription factors with programmable DNA-binding specificity constitute valuable tools for the design of orthogonal gene regulatory networks for synthetic biology. Transcription activator-like effectors (TALEs), as natural transcription regulators, were used to design, build, and test libraries of synthetic TALE-activated promoters (STAPs) that show a broad range of expression levels in plants. In this chapter, we present protocols for the construction of artificial TALEs and corresponding STAPs.

  3. Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

    Science.gov (United States)

    Heit, Antje; Gebhardt, Friedemann; Lahl, Katharina; Neuenhahn, Michael; Schmitz, Frank; Anderl, Florian; Wagner, Hermann; Sparwasser, Tim; Busch, Dirk H; Kastenmüller, Kathrin

    2008-06-01

    Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

  4. Direct activation of EXPANSIN14 by LBD18 in the gene regulatory network of lateral root formation in Arabidopsis.

    Science.gov (United States)

    Kim, Jungmook; Lee, Han Woo

    2013-02-01

    Root system architecture is important for plants to adapt to a changing environment. The major determinant of the root system is lateral roots originating from the primary root. The developmental process of lateral root formation can be divided into priming, initiation, primordium development and the emergence of lateral roots, and is well characterized in Arabidopsis. The hormone auxin plays a critical role in lateral root development, and several auxin response modules involving AUXIN RESPONSE FACTORS (ARFs), transcriptional regulators of auxin-regulated genes and Aux/IAA, negative regulators of ARFs, regulate lateral root formation. The LATERAL ORGAN BOUNDARIES DOMAIN/ASYMMETRIC LEAVES2-LIKE (LBD/ASL) gene family encodes a unique class of transcription factors harbouring a conserved plant-specific lateral organ boundary domain and plays a role in lateral organ development of plants including lateral root formation. In our previous study, we showed that LBD18 stimulates lateral root formation in combination with LBD16 downstream of ARF7 and ARF19 during the auxin response. We have recently demonstrated that LBD18 activates expression of EXP14, a gene encoding the cell-wall loosening factor, by directly binding to the EXP14 promoter to promote lateral root emergence. Here we present the molecular function of LBD18 and its gene regulatory network during lateral root formation.

  5. An empirical model of Onecut binding activity at the sea urchin SM50 C-element gene regulatory region.

    Science.gov (United States)

    Otim, Ochan

    2017-01-01

    Studying the formation of endoskeleton in many species is complex and difficult. The sea urchin embryo offers an unparalleled platform for understanding this process because of the ease with which its skeletogenic mesenchyme cells can be manipulated. In this study, preliminary evidence from biochemical studies towards understanding the role of the Onecut transcription factor during sea urchin skeletogenic mesenchyme cell specification is presented. Based on the evidence, an empirical model is proposed showing how Onecut, together with associated co-factors, may be using the C-element of the SM50 gene regulatory region in advance of the sea urchin Strongylocentrotus purpuratus spicule development. In the model, Onecut recognizes and binds the DNA sequence CATCGATCTC in the C-element without temporal restriction. Onecut then utilizes different sets of co-factors to switch from its unknown function early in development (four cell stage to the mesenchyme blastula stage), to its known role in the oral-aboral boundary thereafter. At the writing of this report, definitive evidence as to whether the "early" factors are expressed in all cells except the micromere lineages, or whether the "late" factors are expressed in micromere descendants or ectodermal precursors only are lacking. The former would suggest a possible Onecut repression function for the early co-factors outside the micromere lineages; the latter scenario would suggest a Onecut activation function for the late co-factors in the presumptive ciliary band.

  6. Japanese encephalitis virus non-coding RNA inhibits activation of interferon by blocking nuclear translocation of interferon regulatory factor 3.

    Science.gov (United States)

    Chang, Ruey-Yi; Hsu, Ta-Wen; Chen, Yen-Lin; Liu, Shu-Fan; Tsai, Yi-Jer; Lin, Yun-Tong; Chen, Yi-Shiuan; Fan, Yi-Hsin

    2013-09-27

    Noncoding RNA (ncRNA) plays a critical role in modulating a broad range of diseases. All arthropod-borne flaviviruses produce short fragment ncRNA (sfRNA) collinear with highly conserved regions of the 3'-untranslated region (UTR) in the viral genome. We show that the molar ratio of sfRNA to genomic RNA in Japanese encephalitis virus (JEV) persistently infected cells is greater than that in acutely infected cells, indicating an sfRNA role in establishing persistent infection. Transfecting excess quantities of sfRNA into JEV-infected cells reduced interferon-β (IFN-β) promoter activity by 57% and IFN-β mRNA levels by 52%, compared to mock-transfected cells. Transfection of sfRNA into JEV-infected cells also reduced phosphorylation of interferon regulatory factor-3 (IRF-3), the IFN-β upstream regulator, and blocked roughly 30% of IRF-3 nuclear localization. Furthermore, JEV-infected sfRNA transfected cells produced 23% less IFN-β-stimulated apoptosis than mock-transfected groups did. Taken together, these results suggest that sfRNA plays a role against host-cell antiviral responses, prevents cells from undergoing apoptosis, and thus contributes to viral persistence. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Report on Activities of the Nuclear Regulatory Authority of the Slovak Republic and on Safety of Nuclear Installations in the Slovak Republic in 2005. Annual report 2005

    International Nuclear Information System (INIS)

    Zemanova, D.; Seliga, M.; Sladek, V.

    2006-04-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic in 2005 is presented. These activities are reported under the headings: Foreword; (1) Vision, Mission and Principles of Activities; (2) Legislation; (3) Issuance of Authorisations, Safety Assessment and Enforcement; (4) Nuclear Safety of Nuclear Installations in the Slovak Republic; (4.1) Nuclear installations in operation in the Slovak Republic; (4.2) Nuclear Installations under construction in the Slovak Republic; (4.3) Decommissioning of nuclear installations in the Slovak Republic; (5) Spent Fuel and Radioactive Waste Management and Safety of other Nuclear Installations in the Slovak Republic; (5.1) Generation and minimisation of radioactive waste; (5.2) Management of radioactive waste; (5.3) Pre-disposal management of radioactive waste; (5.4) Disposal of radioactive waste; (5.5) Shipment of radioactive waste; (5.6) Safety of other nuclear installations in the Slovak Republic; (6) Personnel Qualification and Training; (7) Nuclear Materials and Physical Protection of Nuclear installations; (8) Emergency Preparedness; (9) International Co-operation; (10) Public Communication; (11) UJD SR; (11.1) UJD SR organizational chart; (11.2) UJD SR organizational chart; (11.3) Human resources and training; (11.4) Internal system of quality assurance; (11.5) Development of UJD SR regulatory activities; Appendix: Abbreviations; Development of UJD SR regulatory activities

  8. Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells.

    Directory of Open Access Journals (Sweden)

    Michel Lecendreux

    Full Text Available Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1 has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml. This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA- associated to an activated phenotype (increase in CD69 and CD25 expression in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression, and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing, in NT1.

  9. Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells.

    Science.gov (United States)

    Lecendreux, Michel; Churlaud, Guillaume; Pitoiset, Fabien; Regnault, Armelle; Tran, Tu Anh; Liblau, Roland; Klatzmann, David; Rosenzwajg, Michelle

    2017-01-01

    Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.

  10. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    1999-01-01

    The 43 rd Session of the IAEA General Conference was held in Vienna from 27 September to 1 October 1999 with delegations from 11 member states and representatives of various international organisations in attendance. Resolutions were adopted inter alia in the following areas: nuclear radiation and waste safety; strengthening IAEA technical co-operation; strengthening the IAEA's safeguards system; safeguards in the democratic people's republic of Korea; non proliferation safeguards in the middle east; illicit trafficking in nuclear materials and nuclear inspections in Iraq. The second part deals with the regulation laying down detailed rules for the application of the 1990 regulation on imports of agricultural products originating in third countries following the Chernobyl accident and recommendation on a classification system for solid radioactive waste. (A.L.B.)

  11. The adeno-associated virus major regulatory protein Rep78-c-Jun-DNA motif complex modulates AP-1 activity

    International Nuclear Information System (INIS)

    Prasad, C. Krishna; Meyers, Craig; Zhan Dejin; You Hong; Chiriva-Internati, Maurizio; Mehta, Jawahar L.; Liu Yong; Hermonat, Paul L.

    2003-01-01

    Multiple epidemiologic studies show that adeno-associated virus (AAV) is negatively associated with cervical cancer (CX CA), a cancer which is positively associated with human papillomavirus (HPV) infection. Mechanisms for this correlation may be by Rep78's (AAV's major regulatory protein) ability to bind the HPV-16 p97 promoter DNA and inhibit transcription, to bind and interfere with the functions of the E7 oncoprotein of HPV-16, and to bind a variety of HPV-important cellular transcription factors such as Sp1 and TBP. c-Jun is another important cellular factor intimately linked to the HPV life cycle, as well as keratinocyte differentiation and skin development. Skin is the natural host tissue for both HPV and AAV. In this article it is demonstrated that Rep78 directly interacts with c-Jun, both in vitro and in vivo, as analyzed by Western blot, yeast two-hybrid cDNA, and electrophoretic mobility shift-supershift assay (EMSA supershift). Addition of anti-Rep78 antibodies inhibited the EMSA supershift. Investigating the biological implications of this interaction, Rep78 inhibited the c-Jun-dependent c-jun promoter in transient and stable chloramphenicol acetyl-transferase (CAT) assays. Rep78 also inhibited c-Jun-augmented c-jun promoter as well as the HPV-16 p97 promoter activity (also c-Jun regulated) in in vitro transcription assays in T47D nuclear extracts. Finally, the Rep78-c-Jun interaction mapped to the amino-half of Rep78. The ability of Rep78 to interact with c-Jun and down-regulate AP-1-dependent transcription suggests one more mechanism by which AAV may modulate the HPV life cycle and the carcinogenesis process

  12. The Use of the Medical Dictionary for Regulatory Activities in the Identification of Mitochondrial Dysfunction in HIV-Infected Children.

    Science.gov (United States)

    Chernoff, Miriam; Ford-Chatterton, Heather; Crain, Marilyn J

    2012-10-01

    To demonstrate the utility of a medical terminology-based method for identifying cases of possible mitochondrial dysfunction (MD) in a large cohort of youths with perinatal HIV infection and to describe the scoring algorithms. Medical Dictionary for Regulatory Activities (MedDRA) ® version 6 terminology was used to query clinical criteria for mitochondrial dysfunction by two published classifications, the Enquête Périnatale Française (EPF) and the Mitochondrial Disease Classification (MDC). Data from 2,931 participants with perinatal HIV infection on PACTG 219/219C were analyzed. Data were qualified for severity and persistence, after which clinical reviews of MedDRA-coded and other study data were performed. Of 14,000 data records captured by the EPF MedDRA query, there were 3,331 singular events. Of 18,000 captured by the MDC query, there were 3,841 events. Ten clinicians blindly reviewed non MedDRA-coded supporting data for 15 separate clinical conditions. We used the Statistical Analysis System (SAS) language to code scoring algorithms. 768 participants (26%) met the EPF case definition of possible MD; 694 (24%) met the MDC case definition, and 480 (16%) met both definitions. Subjective application of codes could have affected our results. MedDRA terminology does not include indicators of severity or persistence. Version 6.0 of MedDRA did not include Standard MedDRA Queries, which would have reduced the time needed to map MedDRA terms to EPF and MDC criteria. Together with a computer-coded scoring algorithm, MedDRA terminology enabled identification of potential MD based on clinical data from almost 3000 children with substantially less effort than a case by case review. The article is accessible to readers with a background in statistical hypothesis testing. An exposure to public health issues is useful but not strictly necessary.

  13. 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

  14. Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas' disease.

    Directory of Open Access Journals (Sweden)

    Paulo Marcos Matta Guedes

    Full Text Available BACKGROUND: Myocardium damage during Chagas' disease results from the immunological imbalance between pro- and production of anti-inflammatory cytokines and has been explained based on the Th1-Th2 dichotomy and regulatory T cell activity. Recently, we demonstrated that IL-17 produced during experimental T. cruzi infection regulates Th1 cells differentiation and parasite induced myocarditis. Here, we investigated the role of IL-17 and regulatory T cell during human Chagas' disease. METHODOLOGY/PRINCIPAL FINDINGS: First, we observed CD4(+IL-17(+ T cells in culture of peripheral blood mononuclear cells (PBMC from Chagas' disease patients and we evaluated Th1, Th2, Th17 cytokine profile production in the PBMC cells from Chagas' disease patients (cardiomyopathy-free, and with mild, moderate or severe cardiomyopathy cultured with T. cruzi antigen. Cultures of PBMC from patients with moderate and severe cardiomyopathy produced high levels of TNF-α, IFN-γ and low levels of IL-10, when compared to mild cardiomyopathy or cardiomyopathy-free patients. Flow cytometry analysis showed higher CD4(+IL-17(+ cells in PBMC cultured from patients without or with mild cardiomyopathy, in comparison to patients with moderate or severe cardiomyopathy. We then analyzed the presence and function of regulatory T cells in all patients. All groups of Chagas' disease patients presented the same frequency of CD4(+CD25(+ regulatory T cells. However, CD4(+CD25(+ T cells from patients with mild cardiomyopathy or cardiomyopathy-free showed higher suppressive activity than those with moderate and severe cardiomyopathy. IFN-γ levels during chronic Chagas' disease are inversely correlated to the LVEF (P = 0.007, r = -0.614, while regulatory T cell activity is directly correlated with LVEF (P = 0.022, r = 0.500. CONCLUSION/SIGNIFICANCE: These results indicate that reduced production of the cytokines IL-10 and IL-17 in association with high levels of IFN-γ and TNF

  15. CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity.

    Science.gov (United States)

    Akane, Kazuyuki; Kojima, Seiji; Mak, Tak W; Shiku, Hiroshi; Suzuki, Haruhiko

    2016-03-01

    The Fas/FasL (CD95/CD178) system is required for immune regulation; however, it is unclear in which cells, when, and where Fas/FasL molecules act in the immune system. We found that CD8(+)CD122(+) cells, which are mostly composed of memory T cells in comparison with naïve cells in the CD8(+)CD122(-) population, were previously shown to include cells with regulatory activity and could be separated into CD49d(low) cells and CD49d(high) cells. We established in vitro and in vivo experimental systems to evaluate the regulatory activity of CD122(+) cells. Regulatory activity was observed in CD8(+)CD122(+)CD49d(low) but not in CD8(+)CD122(+)CD49d(high) cells, indicating that the regulatory cells in the CD8(+)CD122(+) population could be narrowed down to CD49d(low) cells. CD8(+)CD122(-) cells taken from lymphoproliferation (lpr) mice were resistant to regulation by normal CD122(+) Tregs. CD122(+) Tregs taken from generalized lymphoproliferative disease (gld) mice did not regulate wild-type CD8(+)CD122(-) cells, indicating that the regulation by CD122(+) Tregs is Fas/FasL-dependent. CD122(+) Tregs taken from IL-10-deficient mice could regulate CD8(+)CD122(-) cells as equally as wild-type CD122(+) Tregs both in vitro and in vivo. MHC class I-missing T cells were not regulated by CD122(+) Tregs in vitro. CD122(+) Tregs also regulated CD4(+) cells in a Fas/FasL-dependent manner in vitro. These results suggest an essential role of Fas/FasL as a terminal effector of the CD122(+) Tregs that kill activated T cells to maintain immune homeostasis.

  16. Activation of Salmonella Typhi-specific regulatory T cells in typhoid disease in a wild-type S. Typhi challenge model.

    OpenAIRE

    Monica A McArthur; Stephanie Fresnay; Laurence S Magder; Thomas C Darton; Claire Jones; Claire S Waddington; Christoph J Blohmke; Gordon Dougan; Brian Angus; Myron M Levine; Andrew J Pollard; Marcelo B Sztein

    2015-01-01

    Salmonella Typhi (S. Typhi), the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. Currently available vaccines are moderately efficacious, and identification of immunological responses associated with protection or disease will facilitate the development of improved vaccines. We investigated S. Typhi-specific modulation of activation and homing potential of circulating regulatory T cells (Treg) by flow and mass cytometry using specimens obtained from a h...

  17. Methods and pitfalls in searching drug safety databases utilising the Medical Dictionary for Regulatory Activities (MedDRA).

    Science.gov (United States)

    Brown, Elliot G

    2003-01-01

    The Medical Dictionary for Regulatory Activities (MedDRA) is a unified standard terminology for recording and reporting adverse drug event data. Its introduction is widely seen as a significant improvement on the previous situation, where a multitude of terminologies of widely varying scope and quality were in use. However, there are some complexities that may cause difficulties, and these will form the focus for this paper. Two methods of searching MedDRA-coded databases are described: searching based on term selection from all of MedDRA and searching based on terms in the safety database. There are several potential traps for the unwary in safety searches. There may be multiple locations of relevant terms within a system organ class (SOC) and lack of recognition of appropriate group terms; the user may think that group terms are more inclusive than is the case. MedDRA may distribute terms relevant to one medical condition across several primary SOCs. If the database supports the MedDRA model, it is possible to perform multiaxial searching: while this may help find terms that might have been missed, it is still necessary to consider the entire contents of the SOCs to find all relevant terms and there are many instances of incomplete secondary linkages. It is important to adjust for multiaxiality if data are presented using primary and secondary locations. Other sources for errors in searching are non-intuitive placement and the selection of terms as preferred terms (PTs) that may not be widely recognised. Some MedDRA rules could also result in errors in data retrieval if the individual is unaware of these: in particular, the lack of multiaxial linkages for the Investigations SOC, Social circumstances SOC and Surgical and medical procedures SOC and the requirement that a PT may only be present under one High Level Term (HLT) and one High Level Group Term (HLGT) within any single SOC. Special Search Categories (collections of PTs assembled from various SOCs by

  18. 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

  19. Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4+ T-Cell Responses-Brief Report

    NARCIS (Netherlands)

    Meiler, Svenja; Smeets, Esther; Winkels, Holger; Shami, Annelie; Pascutti, Maria Fernanda; Nolte, Martijn A.; Beckers, Linda; Weber, Christian; Gerdes, Norbert; Lutgens, Esther

    2016-01-01

    Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is expressed on CD4(+) effector memory T cells and regulatory T cells; however, its role on these functionally opposing cell types in atherosclerosis is not fully understood. Low-density lipoprotein

  20. THE RELATIONSHIP OF FoxP3+ T REGULATORY CELLS TO DISEASE ACTIVITY AND ANTIBODY LEVELS IN EARLY RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    A. S. Avdeeva

    2017-01-01

    Full Text Available Objective: to analyze the relationship of the count of FoxP3+ T regulatory cells (Tregs to the clinical and laboratory parameters of disease activity and the levels of antibodies in a group of patients with early rheumatoid arthritis (RA.Subjects and methods. The investigation enrolled 45 patients with early RA (2010 ACR/EULAR criteria who had not previously received treatment with methotrexate, including 39 women; median age was 52.0 [32.5; 57.5] years; disease duration, 5 [4; 6] months, DAS28 5.01 [4.18; 5.8]; 71.1% of the patients were rheumatoid factor (RF positive and 88.9% were anti-cyclic citrullinated peptide positive. The relative and absolute counts of Treg (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127-; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; FoxP3+CD274+ were measured by immunofluorescence staining and multicolor flow cytometry. A control group consisted of 20 healthy donors who were matched for sex and age with the examined patients.Results and discussion. DАS28 was high, moderate, and low in 22 (48.9%, 20 (44.4%, and 3 (6.7% patients, respectively. As compared with the healthy donors, the patients with early RA were observed to have lower values in the percentage of FoxP3+CD25+ cells, in the percentage and absolute count of FoxP3+ICOS+ cells, in the percentage and absolute count of FoxP3+CD154+ and FoxP3+ CD274+ T cells; p<0.05 in all cases. Negative correlation was recorded between the percentage of FoxP3+CD25+ and C-reactive protein (CRP (r=-0.4; that of CD152+intracellular and DAS28 (r=-0.35, ESR (r=-0.46, CRP (r=-0.54; that of FoxP3+CD127 and CRP (r=-0.42; that of CD25+CD127 and DAS28 (r=-0.38, SDAI (r=-0.41, CDAI (r=-0.36, ESR (r=-0.39, CRP (r=-0.47; p<0.05 in all cases.The patients who were seronegative for RF were found to have higher values in the percentage of CD25+CD127, in the percentage and absolute count of Foxp3+CD154+ and Foxp3+CD274+ T lymphocytes.Conclusion. The given data may indicate that the

  1. Development of regulatory guidance on safety reviews of nuclear power plants in Germany. A survey on accomplished and current PSA activities

    International Nuclear Information System (INIS)

    Berg, H.-P.; Froehmel, T.; Goertz, R.; Rehs, B.

    2005-01-01

    The paper describes the key points of the accomplished and current regulatory activities in order to revise PSA guide and the corresponding technical documents in Germany. The regulatory German PSA guide covers the fundamental requirements concerning the performance of PSAs in the frame of comprehensive safety reviews. The technical details regarding the performance of PSA are set out in two technical documents (PSA Methods and PSA Data) that have been developed by a working group of PSA experts (FAK PSA). Based on the experiences from the first series of PSRs, international experiences and the fact that PSR is mandatory since April 2002 revisions of all guides are underway. The first guide to be updated is the PSA guide together with the corresponding technical documents. The working programme and the revision process of FAK PSA was finished at the end of 2004 and the technical documents have recently been republished. (author)

  2. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  3. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

    Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...... by the International Transitional Administrations (ITAs) in Kosovo and Iraq as well as global supply chains and their impact on the garment industry in Bangladesh....

  4. Current concepts on integrative safety assessment of active substances of botanical, mineral or chemical origin in homeopathic medicinal products within the European regulatory framework.

    Science.gov (United States)

    Buchholzer, Marie-Luise; Werner, Christine; Knoess, Werner

    2014-03-01

    For active substances of botanical, mineral or chemical origin processed in homeopathic medicinal products for human use, the adequate safety principles as with other human medicinal products are applied in line with the European regulatory framework. In homeopathy, nonclinical safety assessment is facing a particular challenge because of a multitude and diversity of source materials used and due to rarely available toxicological data. Thus, current concepts applied by the national regulatory authority in Germany (BfArM) on integrative safety assessment of raw materials used in homeopathic medicinal products involve several evaluation approaches like the use of the Lowest Human Recommended Dose (LHRD), toxicological limit values, Threshold of Toxicological Concern (TTC), data from food regulation or the consideration of unavoidable environmental or dietary background exposure. This publication is intended to further develop and clarify the practical use of these assessment routes by exemplary application on selected homeopathic preparations. In conclusion, the different approaches are considered a very useful scientific and simultaneously pragmatic procedure in differentiated risk assessment of homeopathic medicinal products. Overall, this paper aims to increase the visibility of the safety issues in homeopathy and to stimulate scientific discussion of worldwide existing regulatory concepts on homeopathic medicinal products. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data

    Science.gov (United States)

    Schrader, Alexandra; Meyer, Katharina; Walther, Neele; Stolz, Ailine; Feist, Maren; Hand, Elisabeth; von Bonin, Frederike; Evers, Maurits; Kohler, Christian; Shirneshan, Katayoon; Vockerodt, Martina; Klapper, Wolfram; Szczepanowski, Monika; Murray, Paul G.; Bastians, Holger; Trümper, Lorenz; Spang, Rainer; Kube, Dieter

    2016-01-01

    To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through αIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR.1, includes numerous cell cycle regulators. A reduced expression of BCR.1 genes after BCR activation was observed in different cell lines and also in CD10+ germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term αIgM treatment. Furthermore, an inverse correlation of BCR.1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR.1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery. PMID:27166259

  6. CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells.

    Science.gov (United States)

    Solstad, Therese; Bains, Simer Jit; Landskron, Johannes; Aandahl, Einar Martin; Thiede, Bernd; Taskén, Kjetil; Torgersen, Knut Martin

    2011-11-10

    Human CD4(+)FoxP3(+) T cells are functionally and phenotypically heterogeneous providing plasticity to immune activation and regulation. To better understand the functional dynamics within this subset, we first used a combined strategy of subcellular fractionation and proteomics to describe differences at the protein level between highly purified human CD4(+)CD25(+) and CD4(+)CD25(-) T-cell populations. This identified a set of membrane proteins highly expressed on the cell surface of human regulatory T cells (Tregs), including CD71, CD95, CD147, and CD148. CD147 (Basigin or Emmprin) divided CD4(+)CD25(+) cells into distinct subsets. Furthermore, CD147, CD25, FoxP3, and in particular CTLA-4 expression correlated. Phenotypical and functional analyses suggested that CD147 marks the switch between resting (CD45RA(+)) and activated (CD45RO(+)) subsets within the FoxP3(+) T-cell population. Sorting of regulatory T cells into CD147(-) and CD147(+) populations demonstrated that CD147 identifies an activated and highly suppressive CD45RO(+) Treg subset. When analyzing CD4(+) T cells for their cytokine producing potential, CD147 levels grouped the FoxP3(+) subset into 3 categories with different ability to produce IL-2, TNF-α, IFN-γ, and IL-17. Together, this suggests that CD147 is a direct marker for activated Tregs within the CD4(+)FoxP3(+) subset and may provide means to manipulate cells important for immune homeostasis.

  7. Regulatory Control of Radiation Sources. Safety Guide

    International Nuclear Information System (INIS)

    2009-01-01

    This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

  8. Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells.

    Science.gov (United States)

    Haushalter, Kristofer J; Casteel, Darren E; Raffeiner, Andrea; Stefan, Eduard; Patel, Hemal H; Taylor, Susan S

    2018-03-23

    cAMP-dependent protein kinase (PKAc) is a pivotal signaling protein in eukaryotic cells. PKAc has two well-characterized regulatory subunit proteins, RI and RII (each having α and β isoforms), which keep the PKAc catalytic subunit in a catalytically inactive state until activation by cAMP. Previous reports showed that the RIα regulatory subunit is phosphorylated by cGMP-dependent protein kinase (PKG) in vitro , whereupon phosphorylated RIα no longer inhibits PKAc at normal (1:1) stoichiometric ratios. However, the significance of this phosphorylation as a mechanism for activating type I PKA holoenzymes has not been fully explored, especially in cellular systems. In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells. Analysis of a phosphomimetic substitution in RIα (S101E) showed that modification of this site increases PKAc activity in vitro and in cells, even without cAMP stimulation. Numerous techniques were used to show that although Ser 101 variants of RIα can bind PKAc, the modified linker region of the S101E mutant has a significantly reduced affinity for the PKAc active site. These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. We have thus proposed a model to explain how PKG phosphorylation of RIα creates a "sensitized intermediate" state that is in effect primed to trigger PKAc activity.

  9. GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3+ regulatory T cells

    Science.gov (United States)

    Tran, Dat Q.; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M.

    2009-01-01

    TGF-β family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-β is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFβ-binding protein (LTBP) to produce a large latent form. Latent TGF-β is also found on the surface of activated FOXP3+ regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-β to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-β and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-β expression on activated Tregs and recombinant latent TGF-β1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-β on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism. PMID:19651619

  10. GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells.

    Science.gov (United States)

    Tran, Dat Q; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M

    2009-08-11

    TGF-beta family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-beta is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFbeta-binding protein (LTBP) to produce a large latent form. Latent TGF-beta is also found on the surface of activated FOXP3(+) regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-beta to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-beta and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-beta expression on activated Tregs and recombinant latent TGF-beta1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-beta on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism.

  11. The regulatory process of the Visual and Technological Education teachers' activity: analysis of the impact of the 2012 Curricular Restructure in Portugal

    Directory of Open Access Journals (Sweden)

    Cláudia Pereira

    2017-12-01

    Full Text Available This paper aims at exploring a case study of a group of teachers of the 2 nd Cycle of Basic Education, for pupils aged 10 and 11 according to the Portuguese Education System, who belong to the disciplinary group of Visual and Technological Education. The analysis is twofold: it focuses on the one hand on understanding the changes in the work activity and the constraints that resulted from changes in education implemented at national level; and on the other hand on the identification of regulatory strategies developed by the teachers. Based on the fieldwork (individual interviews, activity analysis, documentary analysis there is evidence of variations and constraints, as a result from the changes, both in the teachers' activity (e.g. increase in the workload and in their health (e.g. tiredness, anxiety, disappointment. In order to face the constraints they were experiencing, the teachers developed individual, but also group regulatory strategies, demonstrating the protective and supportive effect the group had in the continuity of the work and in the preservation of these teachers' health.

  12. The DNA binding and activation domains of Gal4p are sufficient for conveying its regulatory signals.

    OpenAIRE

    Ding, W V; Johnston, S A

    1997-01-01

    The transcriptional activation function of the Saccharomyces cerevisiae activator Gal4p is known to rely on a DNA binding activity at its amino terminus and an activation domain at its carboxy terminus. Although both domains are required for activation, truncated forms of Gal4p containing only these domains activate poorly in vivo. Also, mutations in an internal conserved region of Gal4p inactivate the protein, suggesting that this internal region has some function critical to the activity of...

  13. Developing regulatory approaches

    International Nuclear Information System (INIS)

    Axelsson, Lars

    2012-01-01

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

  14. Safety of nuclear installations in the Slovak Republic and activities of the Nuclear Regulatory Authority of the Slovak Republic in 2007

    International Nuclear Information System (INIS)

    Zemanova, D.

    2008-01-01

    Prepared pursuant to the provisions of the Atomic Act, the report provides information on the safety of nuclear installation in the Slovak Republic and activities of the Nuclear Regulatory Authority of the Slovak Republic ( UJD SR). UJD SR executes its activities in the area of legislation, issuance of authorizations and permissions for the siting, construction, operation and decommissioning of nuclear installations, in the area of reviews, assessments and control of nuclear safety of nuclear installations and emergency planning, in the area of records and accountability of nuclear materials, independent public information and in the area of international co-operation focused on peaceful uses of nuclear power. Based on the results of inspection activities and evaluation of safety indicators, UJD SR assessed the operation of nuclear installations in the Slovak Republic as safe and reliable. No significant event that could have a negative impact on the personnel, population or environment occurred in 2007. (orig.)

  15. Report on Activities of the Nuclear Regulatory Authority of the Slovak Republic and on Safety of Nuclear Installations in the Slovak Republic in 2006. Annual Report 2006

    International Nuclear Information System (INIS)

    Zemanova, D.; Pirozekova, M.

    2007-04-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic in 2006 is presented. These activities are reported under the headings: Foreword; (1) Vision, Mission and Principles of Activities; (2) Legislation; (3) Issuance of Authorisations, Safety Assessment and Enforcement; (3.1) Issuance of Authorizations/Permissions; (3.2) Assessment and Inspections Activities; (3.3) Safety Assessment and Enforcement; (4) Nuclear Safety of Nuclear Installations in the Slovak Republic; (4.1) Nuclear installations in operation in the Slovak Republic; (4.2) Nuclear Installations under construction in the Slovak Republic; (4.3) Decommissioning of nuclear installations in the Slovak Republic; (5) Safety of Other Nuclear Installations; (5.1) Other Nuclear Installations in Operation; (5.2) Other Nuclear Installations under Construction; (5.3) Other Nuclear Installations under Decommissioning; (6) Management of Radioactive Waste; (6.1) Generation and minimisation of radioactive waste; (6.2) Management of radioactive waste; (6.3) Pre-disposal management of radioactive waste; (6.4) Disposal of radioactive waste; (6.5) Shipment of radioactive waste; (7) Nuclear Materials; (7.1) Accounting for and Control of Nuclear Materials; (7.2) Shipment of Nuclear Materials; (7.3) Illicit Trafficking of Nuclear Materials and Other Radioactive Material; (8) Emergency Planning and Preparedness; (9) International Activities; (9.1) European Affairs; (9.2) Membership in International Organisations; (9.3) Fulfilment of Obligations under International Contractual Instruments; (9.4) Bilateral Co-operation; (10) Public Communication; (11) UJD SR; (11.1) Economy Data; (11.2) Human resources and training; (11.3) Internal Management Quality System; (11.4) Development of UJD SR Regulatory Activities; (12) Abbreviations

  16. 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

  17. Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy

    Directory of Open Access Journals (Sweden)

    Caminade Anne-Marie

    2009-09-01

    Full Text Available Abstract Background Adoptive cell therapy with allogenic NK cells constitutes a promising approach for the treatment of certain malignancies. Such strategies are currently limited by the requirement of an efficient protocol for NK cell expansion. We have developed a method using synthetic nanosized phosphonate-capped dendrimers allowing such expansion. We are showing here that this is due to a specific inhibitory activity towards CD4+ T cell which could lead to further medical applications of this dendrimer. Methods Mononuclear cells from human peripheral blood were used to investigate the immunomodulatory effects of nanosized phosphonate-capped dendrimers on interleukin-2 driven CD4+T cell expansion. Proliferation status was investigated using flow cytometry analysis of CFSE dilution and PI incorporation experiments. Magnetic bead cell sorting was used to address activity towards individual or mixed cell sub-populations. We performed equilibrium binding assay to assess the interaction of fluorescent dendrimers with pure CD4+ T cells. Results Phosphonate-capped dendrimers are inhibiting the activation, and therefore the proliferation; of CD4+ T cells in IL-2 stimulated PBMCs, without affecting their viability. This allows a rapid enrichment of NK cells and further expansion. We found that dendrimer acts directly on T cells, as their regulatory property is maintained when stimulating purified CD4+ T cells with anti-CD3/CD28 microbeads. Performing equilibrium binding assays using a fluorescent analogue, we show that the phosphonate capped-dendrimers are specifically interacting with purified CD4+ T cells. Ultimately, we found that our protocol prevents the IL-2 related expansion of regulatory T cells that would be deleterious for the activity of infused NK cells. Conclusion High yield expansion of NK cells from human PBMCs by phosphonate-capped dendrimers and IL-2 occurs through the specific inhibition of the CD4+ lymphocyte compartment. Given the

  18. Modulation of redox regulatory molecules and electron transport chain activity in muscle of air breathing fish Heteropneustes fossilis under air exposure stress.

    Science.gov (United States)

    Paital, Biswaranjan

    2014-01-01

    Responses of redox regulatory system to long-term survival (>18 h) of the catfish Heteropneustes fossilis in air are not yet understood. Lipid and protein oxidation level, oxidant (H2O2) generation, antioxidative status (levels of superoxide dismutase, catalase, glutathione peroxidase and reductase, ascorbic acid and non-protein sulfhydryl) and activities of respiratory complexes (I, II, III and IV) in mitochondria were investigated in muscle of H. fossilis under air exposure condition (0, 3, 6, 12 and 18 h at 25 °C). The increased levels of both H2O2 and tissue oxidation were observed due to the decreased activities of antioxidant enzymes in muscle under water deprivation condition. However, ascorbic acid and non-protein thiol groups were the highest at 18 h air exposure time. A linear increase in complex II activity with air exposure time and an increase up to 12 h followed by a decrease in activity of complex I at 18 h were observed. Negative correlation was observed for complex III and V activity with exposure time. Critical time to modulate the above parameters was found to be 3 h air exposure. Dehydration induced oxidative stress due to modulation of electron transport chain and redox metabolizing enzymes in muscle of H. fossilis was clearly observed. Possible contribution of redox regulatory system in muscle tissue of the fish for long-term survival in air is elucidated. Results of the present study may be useful to understand the redox metabolism in muscle of fishes those are exposed to air in general and air breathing fishes in particular.

  19. Quality assurance within regulatory bodies

    International Nuclear Information System (INIS)

    1999-06-01

    The IAEA directed extensive efforts during the years 1991 to 1995 to the integral revision of all NUSS quality assurance publications, which were approved and issued as Safety Series No.50-C/SG-Q, Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Installations (1996). When these quality assurance publications were developed, their prime focus was on requirements against which work performed by the licensees could be measured and assessed by the regulatory bodies. In this way, they only helped to facilitate the functions of regulators. No requirements or recommendations were provided on how the regulators should ensure the effective implementation of their own activities. The present publication is a first attempt to collect, integrate and offer available experience to directly support performance of regulatory activities. It presents a comprehensive compilation on the application of quality assurance principles and methods by regulatory bodies to their activities. The aim is consistent good performance of regulatory activities through a systematic approach

  20. Aromatic inhibitors derived from ammonia-pretreated lignocellulose hinder bacterial ethanologenesis by activating regulatory circuits controlling inhibitor efflux and detoxification

    Directory of Open Access Journals (Sweden)

    David H. Keating

    2014-08-01

    Full Text Available Efficient microbial conversion of lignocellulosic hydrolysates to biofuels is a key barrier to the economically viable deployment of lignocellulosic biofuels. A chief contributor to this barrier is the impact on microbial processes and energy metabolism of lignocellulose-derived inhibitors, including phenolic carboxylates, phenolic amides (for ammonia-pretreated biomass, phenolic aldehydes, and furfurals. To understand the bacterial pathways induced by inhibitors present in ammonia-pretreated biomass hydrolysates, which are less well studied than acid-pretreated biomass hydrolysates, we developed and exploited synthetic mimics of ammonia-pretreated corn stover hydrolysate (ACSH. To determine regulatory responses to the inhibitors normally present in ACSH, we measured transcript and protein levels in an Escherichia coli ethanologen using RNA-seq and quantitative proteomics during fermentation to ethanol of synthetic hydrolysates containing or lacking the inhibitors. Our study identified four major regulators mediating these responses, the MarA/SoxS/Rob network, AaeR, FrmR, and YqhC. Induction of these regulons was correlated with a reduced rate of ethanol production, buildup of pyruvate, depletion of ATP and NAD(PH, and an inhibition of xylose conversion. The aromatic aldehyde inhibitor 5-hydroxymethylfurfural appeared to be reduced to its alcohol form by the ethanologen during fermentation, whereas phenolic acid and amide inhibitors were not metabolized. Together, our findings establish that the major regulatory responses to lignocellulose-derived inhibitors are mediated by transcriptional rather than translational regulators, suggest that energy consumed for inhibitor efflux and detoxification may limit biofuel production, and identify a network of regulators for future synthetic biology efforts.

  1. Direct regulatory immune activity of lactic acid bacteria on Der p 1-pulsed dendritic cells from allergic patients.

    Science.gov (United States)

    Pochard, Pierre; Hammad, Hamida; Ratajczak, Céline; Charbonnier-Hatzfeld, Anne-Sophie; Just, Nicolas; Tonnel, André-Bernard; Pestel, Joël

    2005-07-01

    Lactic acid bacteria (LAB) are suggested to play a regulatory role in the development of allergic reactions. However, their potential effects on dendritic cells (DCs) directing the immune polarization remain unclear. The immunologic effect of Lactobacillus plantarum NCIMB 8826 (LAB1) on monocyte-derived dendritic cells (MD-DCs) from patients allergic to house dust mite was evaluated. MD-DCs were stimulated for 24 hours with the related allergen Der p 1 in the presence or absence of LAB1. Cell-surface markers were assessed by means of FACS analysis, and the key polarizing cytokines IL-12 and IL-10 were quantified. The subsequent regulatory effect of pulsed MD-DCs on naive or memory T cells was evaluated by determining the T-cell cytokine profile. LAB1 induced the maturation of MD-DCs, even if pulsed with Der p 1. Interestingly, after incubation with LAB1 and Der p 1, MD-DCs produced higher amounts of IL-12 than Der p 1-pulsed DCs. Indeed, the T H 2 cytokine (IL-4 and IL-5) production observed when naive or memory autologous T cells were cocultured with Der p 1-pulsed MD-DCs was highly reduced in the presence of LAB1. Finally, in contrast to naive or memory T cells exposed once to Der p 1-pulsed DCs, T cells stimulated by MD-DCs pulsed with Der p 1 and LAB1 failed to produce T H 2 cytokines in response to a new stimulation with Der p 1-pulsed DCs. Thus in the presence of LAB1, MD-DCs from allergic patients tend to reorientate the T-cell response toward a beneficial T H 1 profile.

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

    International Nuclear Information System (INIS)

    Anon.

    2012-01-01

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

  3. The Hepatitis C Virus-induced NLRP3 Inflammasome Activates the Sterol Regulatory Element-binding Protein (SREBP) and Regulates Lipid Metabolism.

    Science.gov (United States)

    McRae, Steven; Iqbal, Jawed; Sarkar-Dutta, Mehuli; Lane, Samantha; Nagaraj, Abhiram; Ali, Naushad; Waris, Gulam

    2016-02-12

    Hepatitis C virus (HCV) relies on host lipids and lipid droplets for replication and morphogenesis. The accumulation of lipid droplets in infected hepatocytes manifests as hepatosteatosis, a common pathology observed in chronic hepatitis C patients. One way by which HCV promotes the accumulation of intracellular lipids is through enhancing de novo lipogenesis by activating the sterol regulatory element-binding proteins (SREBPs). In general, activation of SREBPs occurs during cholesterol depletion. Interestingly, during HCV infection, the activation of SREBPs occurs under normal cholesterol levels, but the underlying mechanisms are still elusive. Our previous study has demonstrated the activation of the inflammasome complex in HCV-infected human hepatoma cells. In this study, we elucidate the potential link between chronic hepatitis C-associated inflammation and alteration of lipid homeostasis in infected cells. Our results reveal that the HCV-activated NLRP3 inflammasome is required for the up-regulation of lipogenic genes such as 3-hydroxy-3-methylglutaryl-coenzyme A synthase, fatty acid synthase, and stearoyl-CoA desaturase. Using pharmacological inhibitors and siRNA against the inflammasome components (NLRP3, apoptosis-associated speck-like protein containing a CARD, and caspase-1), we further show that the activation of the NLRP3 inflammasome plays a critical role in lipid droplet formation. NLRP3 inflammasome activation in HCV-infected cells enables caspase-1-mediated degradation of insulin-induced gene proteins. This subsequently leads to the transport of the SREBP cleavage-activating protein·SREBP complex from the endoplasmic reticulum to the Golgi, followed by proteolytic activation of SREBPs by S1P and S2P in the Golgi. Typically, inflammasome activation leads to viral clearance. Paradoxically, here we demonstrate how HCV exploits the NLRP3 inflammasome to activate SREBPs and host lipid metabolism, leading to liver disease pathogenesis associated with

  4. Activities of the Nuclear Regulatory Authority of the Slovak Republic and safety of nuclear facilities in the Slovak Republic in 1994

    International Nuclear Information System (INIS)

    1995-01-01

    The report summarizes activities of the Nuclear Regulatory Authority of the Slovak Republic (NRA SR) in 1994 and briefly presents results of the national expert supervision over nuclear safety facilities in the SR in 1994. In 1994, the NRA SR have performed a national supervision of following organizations: SE, a.s. - Jaslovske Bohunice Nuclear Power Plant (V-1 Nuclear Power Plant (V-1 NPP), V-2 Nuclear Power Plant (V-2 NPP), A-1 Nuclear Power Plant (A-1 NPP)); Mochovce Nuclear Power Plant; Radioactive waste repository, Mochovce); Organizations providing a specialized training of NPP personnel; Organizations providing specific deliveries and activities for the nuclear power industry; Organizations having an owner of nuclear materials; Organizations providing activities related to import of radioactive sources; Organizations using radioactive sources. Organization structure of the NRA SR is explained. In the presented Chapter 1 - Safety of nuclear power plants in the Slovak Republic - safety aspects of the Slovak NPPs are reported. The next activities are reported: nuclear materials and safeguards; radioactive waste; emergency planning and NRA SR's control and crisis centre; international activities to improve the national surveillance quality; other activities

  5. 78 FR 54502 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-09-04

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of a Proposed Rule... Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or ``Commission... or manipulative motivation for the trading activity at issue.\\4\\ Specifically, proposed Supplementary...

  6. Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.

    Science.gov (United States)

    Niles, Brad J; Clegg, Michael S; Hanna, Lynn A; Chou, Susan S; Momma, Tony Y; Hong, Heeok; Keen, Carl L

    2008-02-22

    One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

  7. Main Activities to Improve the Control of Radioactive Sources and Maintain an Effective Regulatory Nuclear Systems in Brazil

    International Nuclear Information System (INIS)

    Marechal, M.H.

    2016-01-01

    Since 2006, the Directorate of Nuclear Safety and Security, DRS, of National Nuclear Energy Commission, CNEN, has gone through many improvements. In 2006 CNEN signed the commitment to the recommendations of the Code of Conduct on The Safety and Security of Radioactive Sources and the Guidance on The Import and Export of Radioactive Sources. The DRS is responsible for the licensing and control of nuclear facilities, fuel cycle, waste management and the control of radioactive sources and authorizations of medical and industrial installations. In 2009 the department responsible for the control of radioactive sources and authorizations of medical and industrial installations implemented an “Electronic Management System” in which this System integrates the transport department and waste management department. The Electronic Management System is linked to the register of radioactive sources and facilities and there is an access on line to the Customs, making the control of import and export of radioactive sources robust, efficient and fast. During the period from 2006 until 2015 the most relevant regulations related to the control of radioactive sources and authorizations of medical and industrial installations were reviewed and some were elaborated and issued. These documents were in line with the Categorization of Radioactive Sources and the International Basic Safety Standards, issued in the IAEA Safety Standard Series as General Safety Requirements Part 3 (GSR Part 3). The paper describes all the steps that were adopted in order to implement these systems and the improvements on our Nuclear Regulatory Systems. (author)

  8. FOXP3 renders activated human regulatory T cells resistant to restimulation-induced cell death by suppressing SAP expression.

    Science.gov (United States)

    Katz, Gil; Voss, Kelsey; Yan, Toria F; Kim, Yong Chan; Kortum, Robert L; Scott, David W; Snow, Andrew L

    2018-05-01

    Restimulation-induced cell death (RICD) is an apoptotic program that regulates effector T cell expansion, triggered by repeated stimulation through the T cell receptor (TCR) in the presence of interleukin-2 (IL-2). Although CD4 + regulatory T cells (Tregs) consume IL-2 and experience frequent TCR stimulation, they are highly resistant to RICD. Resistance in Tregs is dependent on the forkhead box P3 (FOXP3) transcription factor, although the mechanism remains unclear. T cells from patients with X-linked lymphoproliferative disease (XLP-1), that lack the adaptor molecule SLAM-associated protein (SAP), are also resistant to RICD. Here we demonstrate that normal Tregs express very low levels of SAP compared to conventional T cells. FOXP3 reduces SAP expression by directly binding to and repressing the SH2D1A (SAP) promoter. Indeed, ectopic SAP expression restores RICD sensitivity in human FOXP3 + Tregs. Our findings illuminate the mechanism behind FOXP3-mediated RICD resistance in Tregs, providing new insight into their long-term persistence. Published by Elsevier Inc.

  9. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion.

    Science.gov (United States)

    Coffelt, Seth B; Chen, Yung-Yi; Muthana, Munitta; Welford, Abigail F; Tal, Andrea O; Scholz, Alexander; Plate, Karl H; Reiss, Yvonne; Murdoch, Craig; De Palma, Michele; Lewis, Claire E

    2011-04-01

    Angiopoietin 2 (ANGPT2) is a proangiogenic cytokine whose expression is often upregulated by endothelial cells in tumors. Expression of its receptor, TIE2, defines a highly proangiogenic subpopulation of myeloid cells in circulation and tumors called TIE2-expressing monocytes/macrophages (TEMs). Genetic depletion of TEMs markedly reduces tumor angiogenesis in various tumor models, emphasizing their essential role in driving tumor progression. Previously, we demonstrated that ANGPT2 augments the expression of various proangiogenic genes, the potent immunosuppressive cytokine, IL-10, and a chemokine for regulatory T cells (Tregs), CCL17 by TEMs in vitro. We now show that TEMs also express higher levels of IL-10 than TIE2(-) macrophages in tumors and that ANGPT2-stimulated release of IL-10 by TEMs suppresses T cell proliferation, increases the ratio of CD4(+) T cells to CD8(+) T cells, and promotes the expansion of CD4(+)CD25(high)FOXP3(+) Tregs. Furthermore, syngeneic murine tumors expressing high levels of ANGPT2 contained not only high numbers of TEMs but also increased numbers of Tregs, whereas genetic depletion of tumor TEMs resulted in a marked reduction in the frequency of Tregs in tumors. Taken together, our data suggest that ANGPT2-stimulated TEMs represent a novel, potent immunosuppressive force in tumors.

  10. Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity.

    Science.gov (United States)

    Slobodin, Gleb; Ahmad, Mohammad Sheikh; Rosner, Itzhak; Peri, Regina; Rozenbaum, Michael; Kessel, Aharon; Toubi, Elias; Odeh, Majed

    2010-01-01

    The role and function of T regulatory (Treg) cells have not been fully investigated in patients with systemic sclerosis (SSc). Ten patients with SSc donated 20ml of peripheral blood. Activity (Valentini) and severity (Medsger) scores for SSc were calculated for all patients. Healthy volunteers (controls) were matched to each patient by gender and age. CD4(+) cells were separated using the MACS system. The numbers of Treg cells were estimated by flow cytometry after staining for CD4, CD25, and FoxP3 and calculated as patient-to-control ratio separately for each experiment. Correlations with activity and severity indices of the disease were performed. Twenty-four-hour production of TGF-beta and IL-10 by activated CD4(+) cells was measured by ELISA in culture supernatants. The numbers of Treg cells, expressed as patient-to-control ratio, correlated significantly with both activity and severity indices (r=0.71, p=0.034 and r=0.67, p=0.044, respectively). ELISA-measured production of TGF-beta and IL-10 by CD4(+) cells was similar in patients and controls. Increased numbers of Treg cells are present in patients with SSc, correlating with activity and severity of the disease. This expansion of Treg cells was not accompanied, however, by heightened TGF-beta or IL-10 production. Further studies to elaborate the causes and functional significance of Treg cell expansion in SSc are needed. 2010 Elsevier Inc. All rights reserved.

  11. Initial high-resolution microscopic mapping of active and inactive regulatory sequences proves non-random 3D arrangements in chromatin domain clusters.

    Science.gov (United States)

    Cremer, Marion; Schmid, Volker J; Kraus, Felix; Markaki, Yolanda; Hellmann, Ines; Maiser, Andreas; Leonhardt, Heinrich; John, Sam; Stamatoyannopoulos, John; Cremer, Thomas

    2017-08-07

    The association of active transcription regulatory elements (TREs) with DNAse I hypersensitivity (DHS[+]) and an 'open' local chromatin configuration has long been known. However, the 3D topography of TREs within the nuclear landscape of individual cells in relation to their active or inactive status has remained elusive. Here, we explored the 3D nuclear topography of active and inactive TREs in the context of a recently proposed model for a functionally defined nuclear architecture, where an active and an inactive nuclear compartment (ANC-INC) form two spatially co-aligned and functionally interacting networks. Using 3D structured illumination microscopy, we performed 3D FISH with differently labeled DNA probe sets targeting either sites with DHS[+], apparently active TREs, or DHS[-] sites harboring inactive TREs. Using an in-house image analysis tool, DNA targets were quantitatively mapped on chromatin compaction shaped 3D nuclear landscapes. Our analyses present evidence for a radial 3D organization of chromatin domain clusters (CDCs) with layers of increasing chromatin compaction from the periphery to the CDC core. Segments harboring active TREs are significantly enriched at the decondensed periphery of CDCs with loops penetrating into interchromatin compartment channels, constituting the ANC. In contrast, segments lacking active TREs (DHS[-]) are enriched toward the compacted interior of CDCs (INC). Our results add further evidence in support of the ANC-INC network model. The different 3D topographies of DHS[+] and DHS[-] sites suggest positional changes of TREs between the ANC and INC depending on their functional state, which might provide additional protection against an inappropriate activation. Our finding of a structural organization of CDCs based on radially arranged layers of different chromatin compaction levels indicates a complex higher-order chromatin organization beyond a dichotomic classification of chromatin into an 'open,' active and 'closed

  12. Src Family Kinases Regulate Interferon Regulatory Factor 1 K63 Ubiquitination following Activation by TLR7/8 Vaccine Adjuvant in Human Monocytes and B Cells

    Directory of Open Access Journals (Sweden)

    Lorenza Tulli

    2018-03-01

    Full Text Available Toll-like receptors (TLRs play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF family, which in turn results in triggering of several cellular functions associated with these receptors. A role for Src family kinases (SFKs in this signaling pathway has also been established. Our work and that of others have shown that this type of kinases is activated following engagement of several TLRs, and that this event is essential for the initiation of specific downstream cellular response. In particular, we have previously demonstrated that activation of SFKs is required for balanced production of pro-inflammatory cytokines by monocyte-derived dendritic cells after stimulation with R848, an agonist of human TLRs 7/8. We also showed that TLR7/8 triggering leads to an increase in interferon regulatory factor 1 (IRF-1 protein levels and that this effect is abolished by inhibition of SFKs, suggesting a critical role of these kinases in IRF-1 regulation. In this study, we first confirmed the key role of SFKs in TLR7/8 signaling for cytokine production and accumulation of IRF-1 protein in monocytes and in B lymphocytes, two other type of antigen-presenting cells. Then, we demonstrate that TLR7 triggering leads to an increase of K63-linked ubiquitination of IRF-1, which is prevented by SFKs inhibition, suggesting a key role of these kinases in posttranslational regulation of IRF-1 in the immune cells. In order to understand the mechanism that links SFKs activation to IRF-1 K63-linked ubiquitination, we examined SFKs and IRF-1 possible interactors and proved that activation of SFKs is necessary for their

  13. Regulatory Assistance, Stakeholder Outreach, and Coastal and Marine Spatial Planning Activities In Support Marine and Hydrokinetic Energy Deployment: Task 2.1.7 Permitting and Planning Fiscal Year 2012 Year-End Report

    Energy Technology Data Exchange (ETDEWEB)

    Geerlofs, Simon H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hanna, Luke A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Judd, Chaeli R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Blake, Kara M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2012-09-01

    This fiscal year 2012 year-end report summarizes activities carried out under DOE Water Power task 2.1.7, Permitting and Planning. Activities under Task 2.1.7 address the concerns of a wide range of stakeholders with an interest in the development of the MHK industry, including regulatory and resource management agencies, tribes, NGOs, and industry.

  14. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  15. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  16. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  17. Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Zhonghua; Qiao, Ling; Zhou, Yan [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada); Babiuk, Lorne A. [University of Alberta, Edmonton, Alberta (Canada); Liu, Qiang, E-mail: qiang.liu@usask.ca [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada)

    2010-11-19

    Research highlights: {yields} A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone. {yields} HCV-3a NS5A increases mature SREBP-1c protein level. {yields} HCV-3a NS5A activates SREBP-1c transcription. {yields} Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation. {yields} Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A. -- Abstract: Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that the nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.

  18. Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1

    International Nuclear Information System (INIS)

    Xiang, Zhonghua; Qiao, Ling; Zhou, Yan; Babiuk, Lorne A.; Liu, Qiang

    2010-01-01

    Research highlights: → A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone. → HCV-3a NS5A increases mature SREBP-1c protein level. → HCV-3a NS5A activates SREBP-1c transcription. → Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation. → Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A. -- Abstract: Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that the nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.

  19. The role of regulatory T cells during the attenuation of graft-versus-leukemia activity following donor leukocyte infusion in mice.

    Science.gov (United States)

    Choi, Mi-Sun; Lim, Ji-Young; Cho, Byung-Sik; Kim, Yoo-Jin; Chung, Nack-Gyun; Jeong, Dae Chul; Youn, Hyewon; Lee, Chulbom; Choi, Eun Young; Min, Chang-Ki

    2011-12-01

    We investigated how the graft-versus-leukemia (GVL) effect is attenuated in the tumor microenvironment using a murine model of non-myeloablative allo-HSCT (NM-HSCT) plus delayed donor leukocyte infusion (DLI) in a haploidentical B6→F1 strain combination. In-line with aggravated leukemia growth, the proportions of effector T cells expressing IFN-γ (Teffs) in spleen were reduced and attenuated GVL activity was found to be accompanied by a rebound in CD4(+)Foxp3(+) regulatory T cells (Tregs) in tumor-draining lymph nodes and tumor tissues. DLI-derived Tregs and Teffs may be potential indicators of presence of leukemic progression after DLI in this GVL model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Identification of a negative regulatory region for the exchange activity and characterization of T332I mutant of Rho guanine nucleotide exchange factor 10 (ARHGEF10).

    Science.gov (United States)

    Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu

    2011-08-26

    The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1-332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant.

  1. Identification of a Negative Regulatory Region for the Exchange Activity and Characterization of T332I Mutant of Rho Guanine Nucleotide Exchange Factor 10 (ARHGEF10)*

    Science.gov (United States)

    Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu

    2011-01-01

    The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1–332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant. PMID:21719701

  2. 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

  3. How short RNAs impact the human ribonuclease Dicer activity: putative regulatory feedback-loops and other RNA-mediated mechanisms controlling microRNA processing.

    Science.gov (United States)

    Koralewska, Natalia; Hoffmann, Weronika; Pokornowska, Maria; Milewski, Marek; Lipinska, Andrea; Bienkowska-Szewczyk, Krystyna; Figlerowicz, Marek; Kurzynska-Kokorniak, Anna

    2016-01-01

    Ribonuclease Dicer plays a pivotal role in RNA interference pathways by processing long double-stranded RNAs and single-stranded hairpin RNA precursors into small interfering RNAs (siRNAs) and microRNAs (miRNAs), respectively. While details of Dicer regulation by a variety of proteins are being elucidated, less is known about non-protein factors, e.g. RNA molecules, that may influence this enzyme's activity. Therefore, we decided to investigate the question of whether the RNA molecules can function not only as Dicer substrates but also as its regulators. Our previous in vitro studies indicated that the activity of human Dicer can be influenced by short RNA molecules that either bind to Dicer or interact with its substrates, or both. Those studies were carried out with commercial Dicer preparations. Nevertheless, such preparations are usually not homogeneous enough to carry out more detailed RNA-binding studies. Therefore, we have established our own system for the production of human Dicer in insect cells. In this manuscript, we characterize the RNA-binding and RNA-cleavage properties of the obtained preparation. We demonstrate that Dicer can efficiently bind single-stranded RNAs that are longer than ~20-nucleotides. Consequently, we revisit possible scenarios of Dicer regulation by single-stranded RNA species ranging from ~10- to ~60-nucleotides, in the context of their binding to this enzyme. Finally, we show that siRNA/miRNA-sized RNAs may affect miRNA production either by binding to Dicer or by participating in regulatory feedback-loops. Altogether, our studies suggest a broad regulatory role of short RNAs in Dicer functioning.

  4. A flexible regulatory framework

    International Nuclear Information System (INIS)

    Silvennoinen, T.

    2000-01-01

    Regulatory reform of the Finnish electricity market meant opening up potentially competitive parts of the electricity sector to competition and eliminating all unnecessary forms of regulation covering generation, wholesale supply, retail supply, and foreign trade in electricity. New types of control and regulatory mechanisms and institutions were set up for those parts of the electricity industry that were excluded from competition, such as network operations. Network activities now have to be licensed, whereas no licence is needed for generation or supply. A new sector-specific regulatory authority was established in 1995 to coincide with the implementation of the Electricity Market Act, known as the Electricity Market Authority. This is responsible for regulating network activities and retail supply to captive customers. The core function of the authority, which employs some 14 people, is to promote the smooth operation of the Finnish electricity market and to oversee the implementation of the Electricity Market Act and its provisions. Its most important duties are linked to overseeing the process by which network companies price their electricity. As price regulation no longer exists, all the companies in the electricity sector set their tariffs independently, even network companies. The job of controlling the pricing of network services is handed by the Electricity Market Authority, following the principles of competition control. Pricing control takes place ex post - after a pricing system has been adopted by a company and concentrates on individual cases and companies. There is no ex ante system of setting or approving prices and tariffs by the regulator. The tariffs and pricing of network services can be evaluated, however, by both the Electricity Market Authority and the Finnish Competition Authority, which have overlapping powers as regards the pricing of network activities. The Finnish regulatory framework can be described as a system of light

  5. [Regulatory B cells activated by CpG-ODN combined with anti-CD40 monoclonal antibody inhibit CD4(+)T cell proliferation].

    Science.gov (United States)

    Wang, Keng; Tao, Lei; Su, Jianbing; Zhang, Yueyang; Zou, Binhua; Wang, Yiyuan; Li, Xiaojuan

    2016-09-01

    Objective To observe the immunosuppressive function of regulatory B cells (Bregs) in vitro after activated by CpG oligodeoxynucleotide (CpG-ODN) and anti-CD40 mAb. Methods Mice splenic CD5(+)CD1d(high)B cells and CD5(-)CD1d(low)B cells were sorted by flow cytometry. These B cells were first stimulated with CpG-ODN combined with anti-CD40 mAb for 24 hours, and then co-cultured with purified CD4(+)T cells. The interleukin 10 (IL-10) expression in the activated Bregs and other B cell subset, as well as the proliferation and interferon γ (IFN-γ) expression in the CD4(+) T cells activated by anti-CD3 mAb plus anti-CD28 mAb were determined by flow cytometry. Results CD5(+)CD1d(high) B cells activated by CpG-ODN plus anti-CD40 mAb blocked the up-regulated CD4(+)T proliferation and significantly reduced the IFN-γ level. At the same time, activated CD5(-)CD1d(low)B cells showed no inhibitory effect on CD4(+)T cells. Further study revealed that IL-10 expression in the CD5(+)CD1d(high) B cells were much higher than that in the CD5(-)CD1d(low)B cells after stimulated with CpG-ODN combined with anti-CD40 mAb for 24 hours. Conclusion CD5(+)CD1d(high) B cells activated by CpG-ODN combined with anti-CD40 mAb have immune inhibitory effects on CD4(+)T cell activation in vitro , which possibly due to IL-10 secretion.

  6. 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

  7. Introduction of the U.S. Nuclear Regulatory Commission's Activities to Reflect Lessons Learned from Fukushima Nuclear Accident

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jongtae; Hong, Seong-Wan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Gun Hong [Kyungwon E-C Co., Seongnam (Korea, Republic of)

    2014-10-15

    The Charter requires the staff to highlight potential policy issues for the Commission and provide the Commission every 6 months an update on the review work conducted under the Charter. The recent status of NRC's activities and related program to reflect the lesson-learned from the Fukushima Daiichi nuclear power plant's severe accident are introduced in this paper. A wide variety of the U.S. NRC's activities to reflect lessons learned from the Fukushima nuclear accidents was investigated. From the investigation, it was found that most of NRC's activities, based on the Fukushima Near-Term Task Force (NTTF) recommendations, are being implemented in a comprehensive and systematic manner. The NRC staff initially prioritized the NTTF recommendations based on its judgment of the potential and relative safety enhancement which could be realized by each. As a result of the staff's prioritization and assessment process, the NTTF recommendations were prioritized into three tiers (i.e., Tier 1, 2 and 3). Tier 1 recommendations are which the staff determined should be started without unnecessary delay and for which sufficient resource flexibility, including availability of critical skill sets, exists. Tier 2 recommendations are which could not be initiated in the near term due to factors that include the need for further technical assessment and alignment, dependence on Tier 1 issues, or availability of critical skill sets. Tier 3 recommendations are that require further staff study to support a regulatory action, have an associated shorter term action that needs to be completed to inform the longer-term action, are dependent on the availability of critical skill sets, or are dependent on the resolution of NTTF Recommendation 1. Through the implementation of each tier activities, existing layers of defense in depth are expected to be gradually bolstered, and such a regulatory approach is much similar in the other countries. It was also found that

  8. Introduction of the U.S. Nuclear Regulatory Commission's Activities to Reflect Lessons Learned from Fukushima Nuclear Accident

    International Nuclear Information System (INIS)

    Kim, Jongtae; Hong, Seong-Wan; Kim, Gun Hong

    2014-01-01

    The Charter requires the staff to highlight potential policy issues for the Commission and provide the Commission every 6 months an update on the review work conducted under the Charter. The recent status of NRC's activities and related program to reflect the lesson-learned from the Fukushima Daiichi nuclear power plant's severe accident are introduced in this paper. A wide variety of the U.S. NRC's activities to reflect lessons learned from the Fukushima nuclear accidents was investigated. From the investigation, it was found that most of NRC's activities, based on the Fukushima Near-Term Task Force (NTTF) recommendations, are being implemented in a comprehensive and systematic manner. The NRC staff initially prioritized the NTTF recommendations based on its judgment of the potential and relative safety enhancement which could be realized by each. As a result of the staff's prioritization and assessment process, the NTTF recommendations were prioritized into three tiers (i.e., Tier 1, 2 and 3). Tier 1 recommendations are which the staff determined should be started without unnecessary delay and for which sufficient resource flexibility, including availability of critical skill sets, exists. Tier 2 recommendations are which could not be initiated in the near term due to factors that include the need for further technical assessment and alignment, dependence on Tier 1 issues, or availability of critical skill sets. Tier 3 recommendations are that require further staff study to support a regulatory action, have an associated shorter term action that needs to be completed to inform the longer-term action, are dependent on the availability of critical skill sets, or are dependent on the resolution of NTTF Recommendation 1. Through the implementation of each tier activities, existing layers of defense in depth are expected to be gradually bolstered, and such a regulatory approach is much similar in the other countries. It was also found that

  9. Nuclear regulatory developments in Canada

    International Nuclear Information System (INIS)

    Binder, M.

    2012-01-01

    This paper from CNSC discusses nuclear regulatory developments in Canada. It starts with the Fukushima accident and the effect on the nuclear sector. It summarises what CNSC has done, what it has learned and their plans going forward. It has made recommendations to IAEA for international enhancements to regulatory procedures. It outline the activities of Canada's nuclear power plants, Canada's uranium projects, deep geological repository and waste management as well as nuclear research in Canada.

  10. Regulatory facility guide for Ohio

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, S.S.; Bock, R.E.; Francis, M.W.; Gove, R.M.; Johnson, P.E.; Kovac, F.M.; Mynatt, J.O. [Oak Ridge National Lab., TN (United States); Rymer, A.C. [Transportation Consulting Services, Knoxville, TN (United States)

    1994-02-28

    The Regulatory Facility Guide (RFG) has been developed for the DOE and contractor facilities located in the state of Ohio. It provides detailed compilations of international, federal, and state transportation-related regulations applicable to shipments originating at destined to Ohio facilities. This RFG was developed as an additional resource tool for use both by traffic managers who must ensure that transportation operations are in full compliance with all applicable regulatory requirements and by oversight personnel who must verify compliance activities.

  11. Optimizing Combinations of Flavonoids Deriving from Astragali Radix in Activating the Regulatory Element of Erythropoietin by a Feedback System Control Scheme

    Directory of Open Access Journals (Sweden)

    Hui Yu

    2013-01-01

    Full Text Available Identifying potent drug combination from a herbal mixture is usually quite challenging, due to a large number of possible trials. Using an engineering approach of the feedback system control (FSC scheme, we identified the potential best combinations of four flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-β-D-glucoside deriving from Astragali Radix (AR; Huangqi, which provided the best biological action at minimal doses. Out of more than one thousand possible combinations, only tens of trials were required to optimize the flavonoid combinations that stimulated a maximal transcriptional activity of hypoxia response element (HRE, a critical regulator for erythropoietin (EPO transcription, in cultured human embryonic kidney fibroblast (HEK293T. By using FSC scheme, 90% of the work and time can be saved, and the optimized flavonoid combinations increased the HRE mediated transcriptional activity by ~3-fold as compared with individual flavonoid, while the amount of flavonoids was reduced by ~10-fold. Our study suggests that the optimized combination of flavonoids may have strong effect in activating the regulatory element of erythropoietin at very low dosage, which may be used as new source of natural hematopoietic agent. The present work also indicates that the FSC scheme is able to serve as an efficient and model-free approach to optimize the drug combination of different ingredients within a herbal decoction.

  12. Annual Report 2008. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2009-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across four parts and seven annexes the activities developed by the organism during 2008. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the occupational surveillance; the environmental monitoring; improved organizational and budgetary developments. Also, this publication have annexes with the following content: regulatory documents; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

  13. Annual Report 2007. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2008-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across tree parts and seven annexes the activities developed by the organism during 2007. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the occupational surveillance; the environmental monitoring; improved organizational. Also, this publication have annexes with the following content: regulatory documents; inspections to medical, industrial and training installations; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

  14. Annual Report 2009. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2010-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across four parts and seven annexes the activities developed by the organism during 2009. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the environmental monitoring; the occupational surveillance; the training and the public information; improved organizational and budgetary developments. Also, this publication have annexes with the following content: regulatory documents; inspections to medical, industrial and training installations; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

  15. Regulatory Interactions of Csr Components: the RNA Binding Protein CsrA Activates csrB Transcription in Escherichia coli

    OpenAIRE

    Gudapaty, Seshagirirao; Suzuki, Kazushi; Wang, Xin; Babitzke, Paul; Romeo, Tony

    2002-01-01

    The global regulator CsrA (carbon storage regulator) of Escherichia coli is a small RNA binding protein that represses various metabolic pathways and processes that are induced in the stationary phase of growth, while it activates certain exponential phase functions. Both repression and activation by CsrA involve posttranscriptional mechanisms, in which CsrA binding to mRNA leads to decreased or increased transcript stability, respectively. CsrA also binds to a small untranslated RNA, CsrB, f...

  16. In vitro metabolism and bioavailability tests for endocrine active substances: What is needed next for regulatory purposes?

    Science.gov (United States)

    Legistation and prospective legislative proposals internationally (may) require that chemicals be tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive in vitro are considered to be endocrine active substances (EAS) and may be puta...

  17. CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation

    NARCIS (Netherlands)

    Manjarrez-Orduno, N.; Marasco, E.; Chung, S.A.; Katz, M.S.; Kiridly, J.F.; Simpfendorfer, K.R.; Freudenberg, J.; Ballard, D.H.; Nashi, E.; Hopkins, T.J.; Cunninghame Graham, D.S.; Lee, A.T.; Coenen, M.J.H.; Franke, B.; Swinkels, D.W.; Graham, R.R.; Kimberly, R.P.; Gaffney, P.M.; Vyse, T.J.; Behrens, T.W.; Criswell, L.A.; Diamond, B.; Gregersen, P.K.

    2012-01-01

    The c-Src tyrosine kinase, Csk, physically interacts with the intracellular phosphatase Lyp (encoded by PTPN22) and can modify the activation state of downstream Src kinases, such as Lyn, in lymphocytes. We identified an association of CSK with systemic lupus erythematosus (SLE) and refined its

  18. Bases de données NoSQL et Big Data concevoir des bases de données pour le Big Data : cours et travaux pratiques niveau B

    CERN Document Server

    Lacomme, Philippe; Phan, Raksmey

    2014-01-01

    Les bases de données NoSQL, ou non relationnelles, procèdent d'une logique différente du modèle SQL pour stocker de très grands volumes de données de natures variées. Elles s'affranchissent des contraintes classiques et fournissent une architecture nouvelle, souple et performante. Le Big Data rassemble des technologies répondant aux 4 V : Volume important, Variété d'informations, Vélocité du traitement, Variabilité des sources. L'ouvrage s'emploie à rendre ces techniques accessibles. Il propose une présentation synthétique des systèmes de bases de données NoSQL dans une approche transversale sur plusieurs plateformes : NetBeans et Eclipse. Le propos est constamment illustré par de nombreux exemples implémentés sous forme de travaux pratiques utilisant : Oracle, MongoDB, Cassandra, Neo4j, Redi et Hbase. Des vidéos et des compléments gratuits sont disponibles sur le site web du livre : http://www.isima.fr/~lacomme/NoSQL/."

  19. Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients.

    Science.gov (United States)

    Carrion, F; Nova, E; Ruiz, C; Diaz, F; Inostroza, C; Rojo, D; Mönckeberg, G; Figueroa, F E

    2010-03-01

    Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

  20. Rac1-Rab11-FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T-cell activation.

    Science.gov (United States)

    Bouchet, Jérôme; Del Río-Iñiguez, Iratxe; Lasserre, Rémi; Agüera-Gonzalez, Sonia; Cuche, Céline; Danckaert, Anne; McCaffrey, Mary W; Di Bartolo, Vincenzo; Alcover, Andrés

    2016-06-01

    The immunological synapse generation and function is the result of a T-cell polarization process that depends on the orchestrated action of the actin and microtubule cytoskeleton and of intracellular vesicle traffic. However, how these events are coordinated is ill defined. Since Rab and Rho families of GTPases control intracellular vesicle traffic and cytoskeleton reorganization, respectively, we investigated their possible interplay. We show here that a significant fraction of Rac1 is associated with Rab11-positive recycling endosomes. Moreover, the Rab11 effector FIP3 controls Rac1 intracellular localization and Rac1 targeting to the immunological synapse. FIP3 regulates, in a Rac1-dependent manner, key morphological events, like T-cell spreading and synapse symmetry. Finally, Rab11-/FIP3-mediated regulation is necessary for T-cell activation leading to cytokine production. Therefore, Rac1 endosomal traffic is key to regulate T-cell activation. © 2016 The Authors.

  1. Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schonlein purpura and systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Beale, M.G.; Nash, G.S.; Bertovich, M.J.; MacDermott, R.P.

    1982-01-01

    The immunoglobulin synthesizing activities of peripheral mononuclear cells (MNC) from five patients with Henoch-Schonlein purpura (HSP) and eight patients with active systemic lupus erythematosus (SLE) were compared. Cumulative amounts of IgM, IgG, and IgA synthesized and secreted by unstimulated and PWM-stimulated patient cells over a 12-day period were determied in a solid-phase radioimmunoassay. In unstimulated control cultures mean rates of IgM, IgG, and IgA synthesis were less than 250 ng/ml. The synthetic activities of patient MNC were markedly increased. In HSP cultures IgA was the major immunoglobulin class produced (2810 x/divide 1.33 ng/ml) followed by IgG (1754 x/divide 1.32 ng/ml) and IgM (404 x/divide 1.16 ng/ml). In SLE cultures IgA and IgG syntheses were equally elevated (4427 x/divide 1.20 and 4438 x/divide 1.49 ng/ml, respectively) whereas IgM synthesis averaged 967 x/divide 1.66 ng/ml. PWM stimulation of pateient MNC caused a sharp decline in the synthesis of all three immunoglobulin classes. After T cell depletion B cell-enriched fractions from HSP and SLE patients maintained high levels of IgA and IgG synthesis that were inhibited by PWM and by normal allogeneic but not autologous T cells. In PWM-stimulted co-cultures, patient T cells nonspecifically suppressed the synthetic activities of autologous and control B cells. in contrast patient B cells achieved normal levels of immunoglobulin synthesis when cultured with control T cells plus PWM. In longitudinal studies patient B and T cell disturbances persisted despite clinical improvement

  2. Nuclear legislation. Analytical study. Regulatory and Institutional framework for nuclear activities in OECD Member countries. Volume I

    International Nuclear Information System (INIS)

    1983-01-01

    This study is part of a series of analytical studies of the major aspects of nuclear legislation in OECD Member countries and is published in two volumes. This Volume I of the study is a revision and an expansion of a 1969 study concerning the organisation and general regime governing nuclear activities. The national studies were prepared, to the extent possible, following a standard plan for all countries to facilitate information retrieval and comparison. (NEA) [fr

  3. Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.

    Directory of Open Access Journals (Sweden)

    Barbara Ensoli

    2010-11-01

    Full Text Available Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4(+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002. Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002, served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4(+ and CD8(+ cellular activation (CD38 and HLA-DR together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4(+ T cells and B cells with reduction of CD8(+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4(+ and CD8(+ T cells were accompanied by increases of CD4(+ and CD8(+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite

  4. 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

  5. Nuclear legislation analytical study. Regulatory and institutional framework for nuclear activities in OECD member countries. Volume II

    International Nuclear Information System (INIS)

    1984-01-01

    This study is part of a series of analytical studies of the major aspects of nuclear legislation in OECD Member countries and is published in two volumes. This volume II of the study is a revision and an expansion of a 1969 study concerning the organisation and general regime governing nuclear activities. The national studies were prepared, to the extent possible, following a standard plan for all countries to facilitate information retrieval and comparison. This volume also contains tables of international conventions of relevance to the nuclear field. (NEA) [fr

  6. [Advances in research on regulatory effects of chemical ingredients of traditional Chinese medicine on UDP-glucuronosyltransferase 1A1 expression and activity].

    Science.gov (United States)

    Xin, Hong; Xu, Wei

    2017-02-01

    Uridine 5'-diphosphate-glucuronosyltransferase1A1(UGT1A1) is a major phase Ⅱ metabolism enzyme, responsible for glucuronidation and elimination of drugs and endogenous compounds, playing a vital role in sustaining endogenous metabolism balance. Therefore, changes in UGT1A1 expression/functional can not only cause adverse clinical drug/herbs-drug interactions, but also lead to metabolic disorder of endogenous substances, causing high blood bilirubin, bilirubin encephalopathy and liver injury, as well as other side effects. To date, many studies have found that a variety of clinical medicines and medicinal ingredients can regulate UGT1A1 activity. This article would summarize the advances in research on drug metabolism and toxicology in domestic and foreign literature, and investigate the regulatory effects of different types of traditional Chinese medicine(TCM) ingredients(such as flavonoids, coumarins, alkaloids) on UGT1A1 expression and activity, including inhibitory effect of TCM chemical ingredients on UGT1A1 and effect of TCM chemical ingredients on UGT1A1. It is hoped that this review could provide depth understanding and certain reference for the interaction between chemical ingredients of TCM and UGT1A1, which is of great significance to guide the rational clinical use in future. Copyright© by the Chinese Pharmaceutical Association.

  7. Mutation of the regulatory phosphorylation site of tobacco nitrate reductase results in constitutive activation of the enzyme in vivo and nitrite accumulation.

    Science.gov (United States)

    Lillo, Cathrine; Lea, Unni S; Leydecker, Marie-Thérèse; Meyer, Christian

    2003-09-01

    In wild-type Nicotiana plumbaginifolia and other higher plants, nitrate reductase (NR) is rapidly inactivated/activated in response to dark/light transitions. Inactivation of NR is believed to be caused by phosphorylation at a special conserved regulatory Ser residue, Ser 521, and interactions with divalent cations and inhibitory 14-3-3 proteins. A transgenic N. plumbaginifolia line (S(521)) was constructed where the Ser 521 had been changed by site-directed mutagenesis into Asp. This mutation resulted in complete abolishment of inactivation in response to light/dark transitions or other treatments known to inactivate NR. During prolonged darkness, NR in wild-type plants is in the inactivated form, whereas NR in the S(521) line is always in the active form. Differences in degradation rate between NR from S(521) and lines with non-mutated NR were not found. Kinetic constants like Km values for NADH and NO3(-) were not changed, but a slightly different pH profile was observed for mutated NR as opposed to non-mutated NR. Under optimal growth conditions, the phenotype of the S(521) plants was not different from the wild type (WT). However, when plants were irrigated with high nitrate concentration, 150 mM, the transgenic plants accumulated nitrite in darkness, and young leaves showed chlorosis.

  8. The changing regulatory environment

    International Nuclear Information System (INIS)

    Caron, G.

    1999-01-01

    The role and value of regulation in the energy sector was discussed, demonstrating how, despite common perception, regulation is an essential part of Canada's strategy to find and develop new opportunities. The future vision of regulation for industry participants was presented with particular focus on issues related to streamlining the regulatory process. As far as pipelines are concerned, regulatory actions are necessary to facilitate capacity increases and to ensure the line's integrity, safety and environmental record. Furthermore, regulation provides economic solutions where market forces cannot provide them, as for example where business has elements of monopoly. It arbitrates interests of landowners, business, consumers, and environmental groups. It looks for ways to ensure conditions under which competition can flourish. It acts as the guardian of citizens' rights in a democratic society by providing citizens with an opportunity to be heard on the building or expansion of pipelines and associated facilities. As citizens become more and more concerned about their property and the land that surrounds them, citizen involvement in decision making about how industry activity affects their quality of life will become correspondingly more important. Regulatory agencies are committed to facilitate this engagement by flexible hearing procedures and by making use of evolving communication and information technology

  9. Aspergillus fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate Cell Wall Homeostasis through Modulation of Chitin Synthase Activity

    Directory of Open Access Journals (Sweden)

    Arsa Thammahong

    2017-04-01

    Full Text Available Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslA and tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity. Loss of tslA reduces trehalose content in both conidia and mycelia, impairs cell wall integrity, and significantly alters cell wall structure. To gain mechanistic insights into the role that TslA plays in cell wall homeostasis, immunoprecipitation assays coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS were used to reveal a direct interaction between TslA and CsmA, a type V chitin synthase enzyme. TslA regulates not only chitin synthase activity but also CsmA sub-cellular localization. Loss of TslA impacts the immunopathogenesis of murine invasive pulmonary aspergillosis through altering cytokine production and immune cell recruitment. In conclusion, our data provide a novel model whereby proteins in the trehalose pathway play a direct role in fungal cell wall homeostasis and consequently impact fungus-host interactions.

  10. Bicarbonate-mediated transcriptional activation of divergent operons by the virulence regulatory protein, RegA, from Citrobacter rodentium.

    Science.gov (United States)

    Yang, Ji; Hart, Emily; Tauschek, Marija; Price, G Dean; Hartland, Elizabeth L; Strugnell, Richard A; Robins-Browne, Roy M

    2008-04-01

    Regulation of virulence gene expression plays a central role in the pathogenesis of enteric bacteria as they encounter diverse environmental conditions in the gastrointestinal tract of their hosts. In this study, we investigated environmental regulation of two putative virulence determinants adcA and kfc by RegA, an AraC/XylS-like regulator, from Citrobacter rodentium, and identified bicarbonate as the environmental signal which induced transcription of adcA and kfc through RegA. Primer extension experiments showed that adcA and kfc were divergently transcribed from sigma(70) promoters. In vivo and in vitro experiments demonstrated that bicarbonate facilitated and stabilized the binding of RegA to an operator located between the two promoters. The interaction of RegA with its DNA target resulted in the formation of a nucleosome-like structure, which evidently displaced the histone-like proteins, H-NS and StpA, from the adcA and kfc promoter regions, leading to transcriptional derepression. In addition, our results indicated that RegA also behaved as a Class I activator by directly stimulating transcription initiation by RNA polymerase. This is the first report to describe the molecular mechanism by which an environmental chemical stimulates transcription of virulence-associated genes of an enteric pathogen through an AraC/XlyS-like activator.

  11. Legal and regulatory aspects of optimization comprehensive support service and combat activity of the Security service of Ukraine and the National guard of Ukraine emergency social situation

    Directory of Open Access Journals (Sweden)

    В. В. Мацюк

    2015-05-01

    Full Text Available Problem setting. The status of comprehensive support of military units in the world’s leading powers is considered to be one of the key factors which defines the success of the social emergency settling operations. The experience of service and military application of the National Guard of Ukraine in the anti-terrorist operation zone on the South-East of Ukraine shows that emergency response tasks are generally carried out in cooperation with other Ukrainian security sector authorities, mostly with the Security Service of Ukraine. However, the forces joint managing authority chiefs usually do not cover the matter of such activities’ comprehensive support, which forces the commanders of the military units to rely on themselves in this question. Recent research and publications analysis. The analysis of research of status and development prospects of the comprehensive support of the Armed Forces of Ukraine, other security authorities, armies of the world’s leading powers, peculiarities of creation and functioning of such systems, application of their means and powers, scientific thought on the problems of service and military application of the National Guard units has shown the problematic tasks of the joint unit comprehensive support system optimization. Therefore, the question of regulatory and legal support of this process is of current importance. Paper objective. The objective of this paper is to define regulatory and legal aspects of comprehensive support optimization of the Security Service of Ukraine and the National Guard of Ukraine service and combat activities during social emergencies. Paper main body. According to the current legislation, comprehensive support comprises of the following types of support: operative (also called military, moral and psychological, materiel (logistical. All other types of support are parts of these three basic ones. Their examination is necessary due to the fact, that there is confusion in the

  12. Activation of an immune-regulatory macrophage response and inhibition of lung inflammation in a mouse model of COPD using heat-shock protein alpha B-crystallin-loaded PLGA microparticles

    NARCIS (Netherlands)

    van Noort, J.M.; Bsibsi, M.; Nacken, P.J.; Gerritsen, W.H.; Amor, S.; Holtman, I.R.; Boddeke, E.; van Ark, I.; Leusink-Muis, T.; Folkerts, G.; Hennink, W.E.; Amidi, M.

    2013-01-01

    As an extracellular protein, the small heat-shock protein alpha B-crystallin (HSPB5) has anti-inflammatory effects in several mouse models of inflammation. Here, we show that these effects are associated with the ability of HSPB5 to activate an immune-regulatory response in macrophages via

  13. Activation of an immune-regulatory macrophage response and inhibition of lung inflammation in a mouse model of COPD using heat-shock protein alpha B-crystallin-loaded PLGA microparticles

    NARCIS (Netherlands)

    van Noort, Johannes M.; Bsibsi, Malika; Nacken, Peter J.; Gerritsen, Wouter H.; Amor, Sandra; Holtman, Inge R.; Boddeke, Erik; van Ark, Ingrid; Leusink-Muis, Thea; Folkerts, Gert; Hennink, Wim E.; Amidi, Maryam

    As an extracellular protein, the small heat-shock protein alpha B-crystallin (HSPB5) has anti-inflammatory effects in several mouse models of inflammation. Here, we show that these effects are associated with the ability of HSPB5 to activate an immune-regulatory response in macrophages via

  14. Comparing motivational, self-regulatory and habitual processes in a computer-tailored physical activity intervention in hospital employees - protocol for the PATHS randomised controlled trial.

    Science.gov (United States)

    Kwasnicka, Dominika; Vandelanotte, Corneel; Rebar, Amanda; Gardner, Benjamin; Short, Camille; Duncan, Mitch; Crook, Dawn; Hagger, Martin S

    2017-05-26

    Most people do not engage in sufficient physical activity to confer health benefits and to reduce risk of chronic disease. Healthcare professionals frequently provide guidance on physical activity, but often do not meet guideline levels of physical activity themselves. The main objective of this study is to develop and test the efficacy of a tailored intervention to increase healthcare professionals' physical activity participation and quality of life, and to reduce work-related stress and absenteeism. This is the first study to compare the additive effects of three forms of a tailored intervention using different techniques from behavioural theory, which differ according to their focus on motivational, self-regulatory and/or habitual processes. Healthcare professionals (N = 192) will be recruited from four hospitals in Perth, Western Australia, via email lists, leaflets, and posters to participate in the four group randomised controlled trial. Participants will be randomised to one of four conditions: (1) education only (non-tailored information only), (2) education plus intervention components to enhance motivation, (3) education plus components to enhance motivation and self-regulation, and (4) education plus components to enhance motivation, self-regulation and habit formation. All intervention groups will receive a computer-tailored intervention administered via a web-based platform and will receive supporting text-messages containing tailored information, prompts and feedback relevant to each condition. All outcomes will be assessed at baseline, and at 3-month follow-up. The primary outcome assessed in this study is physical activity measured using activity monitors. Secondary outcomes include: quality of life, stress, anxiety, sleep, and absenteeism. Website engagement, retention, preferences and intervention fidelity will also be evaluated as well as potential mediators and moderators of intervention effect. This is the first study to examine a tailored

  15. Comparing motivational, self-regulatory and habitual processes in a computer-tailored physical activity intervention in hospital employees - protocol for the PATHS randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Dominika Kwasnicka

    2017-05-01

    Full Text Available Abstract Background Most people do not engage in sufficient physical activity to confer health benefits and to reduce risk of chronic disease. Healthcare professionals frequently provide guidance on physical activity, but often do not meet guideline levels of physical activity themselves. The main objective of this study is to develop and test the efficacy of a tailored intervention to increase healthcare professionals’ physical activity participation and quality of life, and to reduce work-related stress and absenteeism. This is the first study to compare the additive effects of three forms of a tailored intervention using different techniques from behavioural theory, which differ according to their focus on motivational, self-regulatory and/or habitual processes. Methods/Design Healthcare professionals (N = 192 will be recruited from four hospitals in Perth, Western Australia, via email lists, leaflets, and posters to participate in the four group randomised controlled trial. Participants will be randomised to one of four conditions: (1 education only (non-tailored information only, (2 education plus intervention components to enhance motivation, (3 education plus components to enhance motivation and self-regulation, and (4 education plus components to enhance motivation, self-regulation and habit formation. All intervention groups will receive a computer-tailored intervention administered via a web-based platform and will receive supporting text-messages containing tailored information, prompts and feedback relevant to each condition. All outcomes will be assessed at baseline, and at 3-month follow-up. The primary outcome assessed in this study is physical activity measured using activity monitors. Secondary outcomes include: quality of life, stress, anxiety, sleep, and absenteeism. Website engagement, retention, preferences and intervention fidelity will also be evaluated as well as potential mediators and moderators of intervention

  16. Distal loop flexibility of a regulatory domain modulates dynamics and activity of C-terminal SRC kinase (csk.

    Directory of Open Access Journals (Sweden)

    Sulyman Barkho

    Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Csk and SFKs share a modular design with the kinase domain downstream of the N-terminal SH2 and SH3 domains that regulate catalytic function and membrane localization. While the function of interfacial segments in these multidomain kinases are well-investigated, little is known about how surface sites and long-range, allosteric coupling control protein dynamics and catalytic function. The SH2 domain of Csk is an essential component for the down-regulation of all SFKs. A unique feature of the SH2 domain of Csk is the tight turn in place of the canonical CD loop in a surface site far removed from kinase domain interactions. In this study, we used a combination of experimental and computational methods to probe the importance of this difference by constructing a Csk variant with a longer SH2 CD loop to mimic the flexibility found in homologous kinase SH2 domains. Our results indicate that while the fold and function of the isolated domain and the full-length kinase are not affected by loop elongation, native protein dynamics that are essential for efficient catalysis are perturbed. We also identify key motifs and routes through which the distal SH2 site might influence catalysis at the active site. This study underscores the sensitivity of intramolecular signaling and catalysis to native protein dynamics that arise from modest changes in allosteric regions while providing a potential strategy to alter intrinsic activity and signaling modulation.

  17. A minimal murine Msx-1 gene promoter. Organization of its cis-regulatory motifs and their role in transcriptional activation in cells in culture and in transgenic mice.

    Science.gov (United States)

    Takahashi, T; Guron, C; Shetty, S; Matsui, H; Raghow, R

    1997-09-05

    To dissect the cis-regulatory elements of the murine Msx-1 promoter, which lacks a conventional TATA element, a putative Msx-1 promoter DNA fragment (from -1282 to +106 base pairs (bp)) or its congeners containing site-specific alterations were fused to luciferase reporter and introduced into NIH3T3 and C2C12 cells, and the expression of luciferase was assessed in transient expression assays. The functional consequences of the sequential 5' deletions of the promotor revealed that multiple positive and negative regulatory elements participate in regulating transcription of the Msx-1 gene. Surprisingly, however, the optimal expression of Msx-1 promoter in either NIH3T3 or C2C12 cells required only 165 bp of the upstream sequence to warrant detailed examination of its structure. Therefore, the functional consequences of site-specific deletions and point mutations of the cis-acting elements of the minimal Msx-1 promoter were systematically examined. Concomitantly, potential transcriptional factor(s) interacting with the cis-acting elements of the minimal promoter were also studied by gel electrophoretic mobility shift assays and DNase I footprinting. Combined analyses of the minimal promoter by DNase I footprinting, electrophoretic mobility shift assays, and super shift assays with specific antibodies revealed that 5'-flanking regions from -161 to -154 and from -26 to -13 of the Msx-1 promoter contains an authentic E box (proximal E box), capable of binding a protein immunologically related to the upstream stimulating factor 1 (USF-1) and a GC-rich sequence motif which can bind to Sp1 (proximal Sp1), respectively. Additionally, we observed that the promoter activation was seriously hampered if the proximal E box was removed or mutated, and the promoter activity was eliminated completely if the proximal Sp1 site was similarly altered. Absolute dependence of the Msx-1 minimal promoter on Sp1 could be demonstrated by transient expression assays in the Sp1-deficient

  18. Common and distinct DNA-binding and regulatory activities of the BEN-solo transcription factor family.

    Science.gov (United States)

    Dai, Qi; Ren, Aiming; Westholm, Jakub O; Duan, Hong; Patel, Dinshaw J; Lai, Eric C

    2015-01-01

    Recently, the BEN (BANP, E5R, and NAC1) domain was recognized as a new class of conserved DNA-binding domain. The fly genome encodes three proteins that bear only a single BEN domain ("BEN-solo" factors); namely, Insensitive (Insv), Bsg25A (Elba1), and CG9883 (Elba2). Insv homodimers preferentially bind CCAATTGG palindromes throughout the genome to mediate transcriptional repression, whereas Bsg25A and Elba2 heterotrimerize with their obligate adaptor, Elba3 (i.e., the ELBA complex), to recognize a CCAATAAG motif in the Fab-7 insulator. While these data suggest distinct DNA-binding properties of BEN-solo proteins, we performed reporter assays that indicate that both Bsg25A and Elba2 can individually recognize Insv consensus sites efficiently. We confirmed this by solving the structure of Bsg25A complexed to the Insv site, which showed that key aspects of the BEN:DNA recognition strategy are similar between these proteins. We next show that both Insv and ELBA proteins are competent to mediate transcriptional repression via Insv consensus sequences but that the ELBA complex appears to be selective for the ELBA site. Reciprocally, genome-wide analysis reveals that Insv exhibits significant cobinding to class I insulator elements, indicating that it may also contribute to insulator function. Indeed, we observed abundant Insv binding within the Hox complexes with substantial overlaps with class I insulators, many of which bear Insv consensus sites. Moreover, Insv coimmunoprecipitates with the class I insulator factor CP190. Finally, we observed that Insv harbors exclusive activity among fly BEN-solo factors with respect to regulation of Notch-mediated cell fate choices in the peripheral nervous system. This in vivo activity is recapitulated by BEND6, a mammalian BEN-solo factor that conserves the Notch corepressor function of Insv but not its capacity to bind Insv consensus sites. Altogether, our data define an array of common and distinct biochemical and functional

  19. Impact of the Staphylococcus epidermidis LytSR two-component regulatory system on murein hydrolase activity, pyruvate utilization and global transcriptional profile

    Directory of Open Access Journals (Sweden)

    Yu Fangyou

    2010-11-01

    Full Text Available Abstract Background Staphylococcus epidermidis has emerged as one of the most important nosocomial pathogens, mainly because of its ability to colonize implanted biomaterials by forming a biofilm. Extensive studies are focused on the molecular mechanisms involved in biofilm formation. The LytSR two-component regulatory system regulates autolysis and biofilm formation in Staphylococcus aureus. However, the role of LytSR played in S. epidermidis remained unknown. Results In the present study, we demonstrated that lytSR knock-out in S. epidermidis did not alter susceptibility to Triton X-100 induced autolysis. Quantitative murein hydrolase assay indicated that disruption of lytSR in S. epidermidis resulted in decreased activities of extracellular murein hydrolases, although zymogram showed no apparent differences in murein hydrolase patterns between S. epidermidis strain 1457 and its lytSR mutant. Compared to the wild-type counterpart, 1457ΔlytSR produced slightly more biofilm, with significantly decreased dead cells inside. Microarray analysis showed that lytSR mutation affected the transcription of 164 genes (123 genes were upregulated and 41 genes were downregulated. Specifically, genes encoding proteins responsible for protein synthesis, energy metabolism were downregulated, while genes involved in amino acid and nucleotide biosynthesis, amino acid transporters were upregulated. Impaired ability to utilize pyruvate and reduced activity of arginine deiminase was observed in 1457ΔlytSR, which is consistent with the microarray data. Conclusions The preliminary results suggest that in S. epidermidis LytSR two-component system regulates extracellular murein hydrolase activity, bacterial cell death and pyruvate utilization. Based on the microarray data, it appears that lytSR inactivation induces a stringent response. In addition, LytSR may indirectly enhance biofilm formation by altering the metabolic status of the bacteria.

  20. A regulatory hydrophobic area in the flexible joint region of plasminogen activator inhibitor-1, defined with fluorescent activity-neutralizing ligands. Ligand-induced serpin polymerization

    DEFF Research Database (Denmark)

    Egelund, R; Einholm, A P; Pedersen, K E

    2001-01-01

    by all tested nonfluorescent neutralizers, indicating that all neutralizers bind to a common hydrophobic area preferentially accessible in active PAI-1. Activity neutralization proceeded through two consecutive steps as follows: first step is conversion to forms displaying substrate behavior toward u......PA, and second step is to forms inert to uPA. With some neutralizers, the second step was associated with PAI-1 polymerization. Vitronectin reduced the susceptibility to the neutralizers. Changes in sensitivity to activity neutralization by point mutations were compatible with the various neutralizers having...

  1. Chimeric exchange of coronavirus nsp5 proteases (3CLpro) identifies common and divergent regulatory determinants of protease activity.

    Science.gov (United States)

    Stobart, Christopher C; Sexton, Nicole R; Munjal, Havisha; Lu, Xiaotao; Molland, Katrina L; Tomar, Sakshi; Mesecar, Andrew D; Denison, Mark R

    2013-12-01

    Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of severe human respiratory disease. A conserved step of CoV replication is the translation and processing of replicase polyproteins containing 16 nonstructural protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a conserved 3-domain structure and catalytic residues. However, the intra- and intermolecular determinants of nsp5 activity and their conservation across divergent CoVs are unknown, in part due to challenges in cultivating many human and zoonotic CoVs. To test for conservation of nsp5 structure-function determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV) genomes encoding nsp5 proteases of human and bat alphacoronaviruses and betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral recovery with efficient replication albeit with impaired fitness in direct competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear differences in viability and temperature-sensitive phenotypes compared with MHV nsp5. These data indicate tight genetic linkage and coevolution between nsp5 protease and the genomic background and identify differences in intramolecular networks regulating nsp5 function. Our results also provide evidence that chimeric viruses within coronavirus genogroups can be used to test nsp5 determinants of function and inhibition in common isogenic backgrounds and cell types.

  2. A Scalable Weight-Free Learning Algorithm for Regulatory Control of Cell Activity in Spiking Neuronal Networks.

    Science.gov (United States)

    Zhang, Xu; Foderaro, Greg; Henriquez, Craig; Ferrari, Silvia

    2018-03-01

    Recent developments in neural stimulation and recording technologies are providing scientists with the ability of recording and controlling the activity of individual neurons in vitro or in vivo, with very high spatial and temporal resolution. Tools such as optogenetics, for example, are having a significant impact in the neuroscience field by delivering optical firing control with the precision and spatiotemporal resolution required for investigating information processing and plasticity in biological brains. While a number of training algorithms have been developed to date for spiking neural network (SNN) models of biological neuronal circuits, exiting methods rely on learning rules that adjust the synaptic strengths (or weights) directly, in order to obtain the desired network-level (or functional-level) performance. As such, they are not applicable to modifying plasticity in biological neuronal circuits, in which synaptic strengths only change as a result of pre- and post-synaptic neuron firings or biological mechanisms beyond our control. This paper presents a weight-free training algorithm that relies solely on adjusting the spatiotemporal delivery of neuron firings in order to optimize the network performance. The proposed weight-free algorithm does not require any knowledge of the SNN model or its plasticity mechanisms. As a result, this training approach is potentially realizable in vitro or in vivo via neural stimulation and recording technologies, such as optogenetics and multielectrode arrays, and could be utilized to control plasticity at multiple scales of biological neuronal circuits. The approach is demonstrated by training SNNs with hundreds of units to control a virtual insect navigating in an unknown environment.

  3. The use of a medical dictionary for regulatory activities terminology (MedDRA) in prescription-event monitoring in Japan (J-PEM).

    Science.gov (United States)

    Yokotsuka, M; Aoyama, M; Kubota, K

    2000-07-01

    The Medical Dictionary for Regulatory Activities Terminology (MedDRA) version 2.1 (V2.1) was released in March 1999 accompanied by the MedDRA/J V2.1J specifically for Japanese users. In prescription-event monitoring in Japan (J-PEM), we have employed the MedDRA/J for data entry, signal generation and event listing. In J-PEM, the lowest level terms (LLTs) in the MedDRA/J are used in data entry because the richness of LLTs is judged to be advantageous. A signal is generated normally at the preferred term (PT) level, but it has been found that various reporters describe the same event using descriptions that are potentially encoded by LLTs under different PTs. In addition, some PTs are considered too specific to generate the proper signal. In the system used in J-PEM, when an LLT is selected as a candidate to encode an event, another LLT under a different PT, if any, is displayed on the computer screen so that it may be coded instead of, or in addition to, the candidate LLT. The five-level structure of the MedDRA is used when listing events but some modification is required to generate a functional event list.

  4. Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

    Science.gov (United States)

    Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

    2013-02-01

    The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

  5. Viral RNA-Unprimed Rig-I Restrains Stat3 Activation in the Modulation of Regulatory T Cell/Th17 Cell Balance.

    Science.gov (United States)

    Yang, Hui; Guo, He-Zhou; Li, Xian-Yang; Lin, Jian; Zhang, Wu; Zhao, Jun-Mei; Zhang, Hong-Xin; Chen, Sai-Juan; Chen, Zhu; Zhu, Jiang

    2017-07-01

    Innate immunity activation by viral RNA-primed retinoid acid inducible gene-I (Rig-I) in CD4 + T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA-unliganded Rig-I (apo-Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of Rig-I -/- CD4 + T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance. Mechanistically, apo-Rig-I physically associates with Stat3, thereby inhibiting Jak1's association with Stat3 while facilitating Shp2's association to inhibit p-Stat3 levels. Interestingly, inhibition of Stat3 ameliorates the Treg/Th17 imbalance and the colitis observed in Rig-I -/- mice. Collectively, these results uncover an independent functional contribution of the apo-Rig-I/Stat3 interaction in the maintenance of Treg/Th17 cell balance. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. Review of Development Status of Nuclear Superheat; Expose sur l'etat actuel des travaux concernant la surchauffe nucleaire; Obzor razrabotki voprosa o yadernykh peregrevatelyakh; Estudio de los progresos realizados en niateria de sobrecalentamiento nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Imhoff, D. H.; Pennington, R. T. [General Electric Company, San Jose, CA (United States)

    1963-10-15

    The General Electric Company has been actively engaged in development work on nuclear superheat from light-water-moderated reactors since 1959, at which time the Company-financed Superheat Advance Demonstration Experiment (SADE) produced the first nuclear superheated steam in the United States. The current status of nuclear superheat is divided into two major categories. The first is a description of the three major superheat fuel irradiation facilities used by the General Electric Company, and the second is a description of the two major development programme activities with an up-to-date review of the significant superheat development results. 1. Major development facilities: (a) A brief description is given of the Superheat Advance Demonstration Experiment (SADE) utilized in the Vallecitos Boiling Water Reactor (VBWR), with tables of operating conditions, fuel elements irradiated during the period between May 1959, and June 1962, and a discussion of significant experimental results. (b) A brief description is given of the Expanded Superheat Advance Demonstration Experiment (E-SADE) in operation in the Vallecitos Boiling Water Reactor, with tables of operating conditions, fuel elements irradiated in the E-SADE facility and a discussion of the significant development results. (c) A brief description is given of the Empire States Atomic Development Associates-Vallecitos Experimental Superheat Reactor (ESADA-VESR), list of expected operated conditions including design conditions of the initial superheat core loading, and a report on the current status of construction. 2. Major superheat development programme activities: (a) A brief description is given of the United States Atomic Energy Commission (USAEC) sponsored Nuclear Superheat Project which has been in progress at the San Jose site of the General Electric Company since July 1959 A brief description of the individual tasks is given with tables giving significant development results in the areas of superheat

  7. Active site-targeted covalent irreversible inhibitors of USP7 impair the functions of Foxp3+ T-regulatory cells by promoting ubiquitination of Tip60.

    Directory of Open Access Journals (Sweden)

    Feng Wang

    Full Text Available Accumulation of Foxp3+ T-regulatory (Treg cells in the tumor microenvironment is associated with tumor immune evasion and poor patient outcome in the case of many solid tumors. Current therapeutic strategies for blocking Treg functions are not Treg-specific, and display only modest and transient efficacy. Recent studies revealed that ubiquitin-specific protease 7 (USP7 is essential for Treg functions by stabilizing expression of Tip60 and Foxp3, which together are central to the development and maintenance of the Treg cell lineage. Pharmacological inhibition of USP7 is therefore a promising strategy for suppressing Treg functions and promoting anti-tumor immunity. Previously, we reported the P5091 series of small molecule USP7 inhibitors and demonstrated their direct anti-tumor activity in vivo using xenograft models. However, the precise mechanism of action of these compounds was not well defined. In this study, we report the development and characterization of P217564, a second-generation USP7 inhibitor with improved potency and selectivity. P217564 selectively targets the catalytic cleft of USP7 and modifies its active site cysteine (C223 by forming a covalent adduct. Irreversible inhibition of USP7 results in durable downstream biological responses in cells, including down-regulation of Tip60 and consequent impairment of Treg suppressive function. In addition, we demonstrate that both USP7 and various USP7 substrates are subjected to Lys48-mediated ubiquitin modification, consistent with increased proteasomal degradation of these proteins because of USP7 inhibition.

  8. Nuclear Envelope Phosphatase 1-Regulatory Subunit 1 (Formerly TMEM188) Is the Metazoan Spo7p Ortholog and Functions in the Lipin Activation Pathway*

    Science.gov (United States)

    Han, Sungwon; Bahmanyar, Shirin; Zhang, Peixiang; Grishin, Nick; Oegema, Karen; Crooke, Roseann; Graham, Mark; Reue, Karen; Dixon, Jack E.; Goodman, Joel M.

    2012-01-01

    Lipin-1 catalyzes the formation of diacylglycerol from phosphatidic acid. Lipin-1 mutations cause lipodystrophy in mice and acute myopathy in humans. It is heavily phosphorylated, and the yeast ortholog Pah1p becomes membrane-associated and active upon dephosphorylation by the Nem1p-Spo7p membrane complex. A mammalian ortholog of Nem1p is the C-terminal domain nuclear envelope phosphatase 1 (CTDNEP1, formerly “dullard”), but its Spo7p-like partner is unknown, and the need for its existence is debated. Here, we identify the metazoan ortholog of Spo7p, TMEM188, renamed nuclear envelope phosphatase 1-regulatory subunit 1 (NEP1-R1). CTDNEP1 and NEP1-R1 together complement a nem1Δspo7Δ strain to block endoplasmic reticulum proliferation and restore triacylglycerol levels and lipid droplet number. The two human orthologs are in a complex in cells, and the amount of CTDNEP1 is increased in the presence of NEP1-R1. In the Caenorhabditis elegans embryo, expression of nematode CTDNEP1 and NEP1-R1, as well as lipin-1, is required for normal nuclear membrane breakdown after zygote formation. The expression pattern of NEP1-R1 and CTDNEP1 in human and mouse tissues closely mirrors that of lipin-1. CTDNEP1 can dephosphorylate lipins-1a, -1b, and -2 in human cells only in the presence of NEP1-R1. The nuclear fraction of lipin-1b is increased when CTDNEP1 and NEP1-R1 are co-expressed. Therefore, NEP1-R1 is functionally conserved from yeast to humans and functions in the lipin activation pathway. PMID:22134922

  9. Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

    Science.gov (United States)

    Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

    2017-01-01

    The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by

  10. Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT genomic binding patterns discerns cell-specific cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Kang Keunsoo

    2013-01-01

    Full Text Available Abstract Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM, which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors.

  11. 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

  12. 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

  13. Menin and RNF20 recruitment is associated with dynamic histone modifications that regulate signal transducer and activator of transcription 1 (STAT1-activated transcription of the interferon regulatory factor 1 gene (IRF1

    Directory of Open Access Journals (Sweden)

    Buro Lauren J

    2010-09-01

    Full Text Available Abstract Background Signal transducer and activator of transcription (STAT activation of gene expression is both rapid and transient, and when properly executed it affects growth, differentiation, homeostasis and the immune response, but when dysregulated it contributes to human disease. Transcriptional activation is regulated by alterations to the chromatin template. However, the role of histone modification at gene loci that are activated for transcription in response to STAT signaling is poorly defined. Results Using chromatin immunoprecipitation, we profiled several histone modifications during STAT1 activation of the interferon regulatory factor 1 gene (IRF1. Methylated lysine histone proteins H3K4me2, H3K4me3, H3K79me3, H3K36me3 and monoubiquitinated histone ubH2B are dynamic and correlate with interferon (IFNγ induction of STAT1 activity. Chemical inhibition of H3K4 methylation downregulates IRF1 transcription and decreases RNA polymerase II (Pol II occupancy at the IRF1 promoter. MEN1, a component of a complex proteins associated with Set1 (COMPASS-like complex and the hBRE1 component, RNF20, are localized to IRF1 in the uninduced state and are further recruited when IRF1 is activated. RNAi-mediated depletion of RNF20 lowers both ubH2B and H3K4me3, but surprisingly, upregulates IFNγ induced IRF1 transcription. The dynamics of phosphorylation in the C-terminal domain (CTD of Pol II are disrupted during gene activation as well. Conclusions H2B monoubiquitination promotes H3K4 methylation, but the E3 ubiquitin ligase, RNF20, is repressive of inducible transcription at the IRF1 gene locus, suggesting that ubH2B can, directly or indirectly, affect Pol II CTD phosphorylation cycling to exert control on ongoing transcription.

  14. The inhibition of the mitochondrial F1FO-ATPase activity when activated by Ca2+ opens new regulatory roles for NAD.

    Science.gov (United States)

    Nesci, Salvatore; Trombetti, Fabiana; Ventrella, Vittoria; Pirini, Maurizio; Pagliarani, Alessandra

    2018-01-26

    The mitochondrial F1FO-ATPase is uncompetitively inhibited by NAD+ only when the natural cofactor Mg2+ is replaced by Ca2+, a mode putatively involved in cell death. The Ca2+-dependent F1FO-ATPase is also inhibited when NAD+ concentration in mitochondria is raised by acetoacetate. The enzyme inhibition by NAD+ cannot be ascribed to any de-ac(et)ylation or ADP-ribosylation by sirtuines, as it is not reversed by nicotinamide. Moreover, the addition of acetyl-CoA or palmitate, which would favor the enzyme ac(et)ylation, does not affect the F1FO-ATPase activity. Consistently, NAD+ may play a new role, not associated with redox and non-redox enzymatic reactions, in the Ca2+-dependent regulation of the F1FO-ATPase activity.

  15. Enabling legislation and regulatory determinations for a nuclear power programme

    International Nuclear Information System (INIS)

    Ha Vinh Phuong

    1977-01-01

    General remarks on objectives and scope of enabling legislation, on the regulatory body and on the IAEA activities and assistance in regulatory matters e.g. the IAEA Safety Guides which are in preparation. (HP) [de

  16. Functional and topological characteristics of mammalian regulatory domains

    Science.gov (United States)

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

    2014-01-01

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

  17. Regulatory activities related with the modification of the frequency of the programmed stoppings of the Argentine nuclear centrals; Actividades regulatorias relacionadas con la modficacion de la frecuencia de las paradas programadas de las centrales nucleares argentinas

    Energy Technology Data Exchange (ETDEWEB)

    Marino, E.; Calvo, J.; Waldman, R.; Navarro, R

    2006-07-01

    The mandatory character documentation of the Argentinean nuclear power stations in Embalse and Atucha I, required the realization of a programmed stoppings every twelve months to execute that settled down in the maintenance and surveillance programs for each installation. Nucleoelectrica Argentina S.A., in it character of Responsible Entity of the operation of these power stations, requested to the Argentinean Nuclear Regulatory Authority, in 2003 and 2005 respectively, the authorization to change the period of the repetitive tests and of the preventive maintenance of the systems related with the safety, to extend them from twelve to eighteen months. The mentioned applications were founded in economic aspects and in inclining to a decrease in the doses of the workers that perform in the activities that are carried out in the programmed stops. The adopted position by the Nuclear Regulatory Authority to decide on these applications was based on the result of diverse evaluations that included the use of the Probabilistic Analysis of Safety specific of each power station, the operative experience resultant of the execution of the preventive maintenance program, and of the results of the repetitive tests and of the inspections in service. The regulatory decisions were different in each case. Indeed, the Embalse nuclear power station was authorized by the Regulatory Authority to modify from twelve to eighteen months the period among the realization of the repetitive tests and of the preventive maintenance, conditioned to the execution of some specific regulatory requirements. On the other hand, the Atucha I nuclear power station was not authorized to modify this period. In this presentation that is detailed the acted by the Nuclear Regulatory Authority in both cases, the used analysis tools, and the foundation of the adopted decisions. (Author)

  18. Regulatory activities in reactor safety

    International Nuclear Information System (INIS)

    Salvatore, J.E.L.

    1987-01-01

    The safety phylosophy in designs and operation of nuclear power plants and, the steps for evaluating the safety and quality assurance, in the licensing procedure are described. The CNEN organization structure and the licensing procedure for nuclear power plants in Brazil are presented. (M.C.K.) [pt

  19. National Legislative and Regulatory Activities

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    This section gathers several amendments, rules and acts published in 2010 and sorted by country: 1 - Bulgaria: Amendment to the Act on the Safe Use of Nuclear Energy (2010); 2 - France: Law on the new organisation of the electricity market (2010); 3 - Germany: Amendment to the Atomic Energy Act extending the operating lifetime of nuclear power plants (2010); Amendment to the Reliability Assessment Ordinance (2010); Amendment to the Ordinance on Persons Responsible for Nuclear Safety and on Reportable Events (2010); Amendment to the Environmental Impact Assessment Act (2010); 4 - Greece: Decree transposing European Council Directive 2006/117/EURATOM (2010); 5 - India: Civil Nuclear Liability Act (2010); 6 - Romania: Amendment to Article 35 of Law 111/1996 regarding new tasks of CNCAN (2010); Order approving norms regarding the radiological monitoring or recyclable metal materials (2010); 7 - Serbia: Establishment of the Agency for Radiation Protection and Nuclear Safety (2009); 8 - Slovenia: Rules on operational safety of radiation and nuclear facilities (2009); Rules on radiation and nuclear safety factors (2009); Act on Liability for Nuclear Damage (2010); 9 - Sweden: Abolishment of the Act on phasing out of nuclear energy (2010); Act on Liability and Compensation for Nuclear Damage (2010); 10 - United States: Final rule on the independent storage of spent nuclear fuel (2010); Status of the high-level waste repository programme (2010); Comprehensive Iran Sanctions, Accountability and Divestment Act (2010); Final rule on the export and import of nuclear equipment and material (2010)

  20. Regulatory Control of Radiation Sources. Safety Guide (Arabic Edition)

    International Nuclear Information System (INIS)

    2012-01-01

    This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

  1. Les travaux d'utilité collective

    OpenAIRE

    Marchal, Emmanuelle

    1988-01-01

    Une étude réalisée par le CEE en 1986 avait permis d'analyser les conditions dans lesquelles différents organismes publics utilisaient les stagiaires TUC. Des spécificités importantes concernant le mode de sélection, ainsi que l'organisation des stages, conduisaient à identifier plusieurs politiques des organismes : occupation des jeunes stagiaires dans des petites communes pour atténuer le chômage, stages de formation professionnelle supposant une sélection rigoureuse, ou encore situation...

  2. 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)

  3. Nuclear Regulatory Authority of the Slovak Republic. Annual Report 2016

    International Nuclear Information System (INIS)

    2017-01-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2016 is presented. These activities are reported under the headings: Foreword by the Chairperson; (1) Legislative activities; (2) Regulatory Activities; (3) Nuclear safety of nuclear installations; (4) Nuclear Materials; (5) Competence of the building authority; (6) Emergency planning and preparedness; (7) International activities; (8) Public relations; (9) Nuclear Regulatory Authority of the Slovak Republic; (10) Annexes; (11) Abbreviations.

  4. Nuclear Regulatory Authority of the Slovak Republic. Annual Report 2013

    International Nuclear Information System (INIS)

    2014-04-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2013 is presented. These activities are reported under the headings: Foreword by the Chairperson; (1) Legislative activities; (2) Regulatory Activities; (3) Nuclear safety of nuclear power plants; (4) Nuclear Materials in SR; (5) Building Authority; (6) Emergency planning and preparedness; (7) International activities; (8) Public communication; (9) Nuclear Regulatory Authority of the Slovak Republic; (10) Annexes; (11) (12) Abbreviations.

  5. Nuclear Regulatory Authority of the Slovak Republic. Annual Report 2015

    International Nuclear Information System (INIS)

    2016-01-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2015 is presented. These activities are reported under the headings: Foreword by the Chairperson; (1) Legislative activities; (2) Regulatory Activities; (3) Safety of nuclear installations; (4) Nuclear Materials; (5) Competence of the building authority; (6) Emergency planning and preparedness; (7) International activities; (8) Public relations; (9) Nuclear Regulatory Authority of the Slovak Republic; (10) Annexes; (11) Abbreviations.

  6. Professional and Regulatory Search

    Science.gov (United States)

    Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

  7. Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

    Science.gov (United States)

    Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

    2014-06-01

    The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

  8. The regulatory dynamic

    International Nuclear Information System (INIS)

    Dybwad, C.

    2001-01-01

    An outline of the activities and efforts expanded by the National Energy Board to adjust to the changing natural gas market was provided in this presentation. The author began by defining the role of the National Energy Board in energy markets. It must ensure the adoption of rules and procedures that result in a more competitive and efficient market. Light-handed regulatory techniques are the norm, and the National Energy Board is now committed to facilitating the availability and flow of information so that all parties know where opportunities exist, the terms offered to buy or sell goods and services, their quality and costs. It will specialize in providing new participants with information on the workings of the market, who the players are, the regulatory processes in place, and how, when and where the market can be accessed. The manner in which the Board deals with information was reviewed, providing examples along the way to clarify some points. Some of the documents produced by the National Energy Board are being reviewed with the intent of making them easier to read and understand. Audio streaming over the Internet is another avenue being pursued to ensure individuals can listen in real time to hearings without having to be present in the room. The National Energy Board is also exploring alternative dispute resolution techniques. Consultation with energy market participants represents another facet of these efforts to be more accessible and responsive

  9. Regulatory authority information system RAIS

    International Nuclear Information System (INIS)

    Ortiz, P.; Mrabit, K.; Miaw, S.

    2000-01-01

    In this lecture the principles of the regulatory authority information system (RAIS) are presented. RAIS is a tool currently being developed by the IAEA for the Regulatory Authorities. It is a part of a set of supporting actions designed to assist member states in achieving the objectives of the Model project on radiation and waste safety infrastructure. RAIS is a tool that provides the management of the Regulatory Authority with the key information needed for the planning and implementation of activities and to ensure confidence that resources are optimally used. The RAIS contains five modules: Inventory of installations and radiation sources; Authorization process; Inspection and follow-up actions; Information on personal dosimetry; Assessment of effectiveness by means of performance indicators

  10. 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.

  11. 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

  12. Regulatory control, legislation and framework

    International Nuclear Information System (INIS)

    Parthasarathy, K.S.

    1998-01-01

    The legislation and regulations, a regulatory authority to authorise and inspect the regulated activities and to enforce the legislation and regulations, sufficient financial and man-power resources are the essential parts of a national infrastructure to implement the Basic Safety Standards. The legal framework consists of legislation (Act passed by Parliament) and the regulations (framed by the government and endorsed by the Parliament). This paper is primarily deals with the the legal framework set up in India for atomic energy activities

  13. SU-F-19A-07: Is a Day30 Scan Necessary to Evaluate Activity-Based Regulatory Compliance in Permanent Interstitial Brachytherapy for Prostate Cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Kapur, P; Ford, J; Moghanaki, D; Datsang, R; Chang, M; Rosu, M [Virginia Commonwealth University, Richmond, Virginia (United States); Veterans Affairs Medical Center, Richmond, VA (United States); Hagan, M; Palta, J [Virginia Commonwealth University, Richmond, Virginia (United States); Veterans Affairs Medical Center, Richmond, VA (United States); National Radiation Oncology Program, Richmond, VA (United States)

    2014-06-15

    Purpose: To evaluate the Medical Event (ME) criteria for I-125 prostate implants based on the assessment of post implant dosimetry on “Day0”/“Day30” imaging. The new ME criteria do not mandate a timeframe for this assessment. The compliance criteria are: more than 80% of the activity from the written directive for treatment site (TS) must be implanted inside TS, and doses to 1cc of either uninvolved rectum (D1-UR) or uninvolved bladder (D1-UB), or 2cc of other non-specified tissue (D2-UT) must be less than 150% of the planned dose. Methods: “Day0”/“Day30” post-implant analyses for 25 patients were evaluated. Treatment plans had a peripheral loading pattern with 2 core needles placed at least 10 mm away from urethra, with several seeds planned outside of the prostate for adequate target coverage. TS were a uniform 5 mm expansion of the prostate, except posteriorly (no expansion). Results: “Day0”/“Day30”analyses found no MEs. The relative changes for D1-UR, D1-UB, and D2-UT were (ranges): [−37.0, 38.2]%, [−96.5, 74.7]%, and [−41.2, 37.7]%. Furthermore, changes did not correlate with prostate volume changes of −18.7% [σ:16.0%, range:−60.5%, +6.4%]. These unfavorable changes did not lead to ME at “Day30” because these values were generally well below 150% at “Day0”. However, D2-UT dose values exceeded those for D1-UR and D1-UB at both “Day0”/“Day30”. Conclusion: The total activity was relatively insensitive to changes in target volume from “Day0” to ”Day30”. The dose metrics of interest, albeit susceptible to large, often unfavorable changes, remained less than the 150% threshold. Data from this study suggest that “Day0” can be used for the regulatory compliance evaluation. However, further evaluation at “Day30” is advisable if D2-UT is 110% or above (based on the largest D2-UT increase of 37.7% observed in this patient population). Future rigorous statistical analysis of a larger cohort will afford a

  14. Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD-1, TIGIT, and TIM-3 in Lymphocytes From Patients With Systemic Sclerosis.

    Science.gov (United States)

    Fleury, Michelle; Belkina, Anna C; Proctor, Elizabeth A; Zammitti, Christopher; Simms, Robert W; Lauffenburger, Douglas A; Snyder-Cappione, Jennifer E; Lafyatis, Robert; Dooms, Hans

    2018-04-01

    Immune dysfunction is an important component of the disease process underlying systemic sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. This study was undertaken to measure the expression and function of the coinhibitory receptors (co-IRs) programmed cell death 1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in lymphocyte subsets from the peripheral blood of patients with SSc. Co-IR expression levels on subsets of immune cells were analyzed using a 16-color flow cytometry panel. The functional role of co-IRs was determined by measuring cytokine production after in vitro stimulation of SSc and healthy control peripheral blood mononuclear cells (PBMCs) in the presence of co-IR-blocking antibodies. Supernatants from cultures of stimulated PBMCs were added to SSc fibroblasts, and their impact on fibroblast gene expression was measured. Mathematical modeling was used to reveal differences between co-IR functions in SSc patients and healthy controls. Levels of the co-IRs PD-1 and TIGIT were increased, and each was coexpressed, in distinct T cell subsets from SSc patients compared to healthy controls. Levels of TIM-3 were increased in SSc natural killer cells. PD-1, TIGIT, and TIM-3 antibody blockade revealed patient-specific roles of each of these co-IRs in modulating activation-induced T cell cytokine production. In contrast to healthy subjects, blockade of TIGIT and TIM-3, but not PD-1, failed to reverse inhibited cytokine production in SSc patients, indicating that enhanced T cell exhaustion is present in SSc. Finally, cytokines secreted in anti-TIM-3-treated PBMC cultures distinctly changed the gene expression profile in SSc fibroblasts. The altered expression and regulatory capacity of co-IRs in SSc lymphocytes may contribute to disease pathophysiology by modulating the cytokine-mediated cross-talk of

  15. Annual Report 2010. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2010-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across six chapters and seven annexes the activities developed by the organism during 2010. The main topic are: institutional issues; regulatory guides and standards; argentinean nuclear regulatory system; quality assurance of the ARN; the institutional communications; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the safeguards and the physical protection; the environmental control; the institutional relations; the training and the public information. Also, this publication have annexes with the following content: the regulatory framework; regulatory documents; inspections to medical, industrial and training installations; measurement and evaluation of the drinking water of Ezeiza; international expert's report on the application of the international standards of radiological protection of the public in the zone of the Ezeiza Atomic Center; ethical code

  16. Annual Report 2011. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2011-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across six chapters and seven annexes the activities developed by the organism during 2011. The main topic are: institutional issues; regulatory guides and standards; argentinean nuclear regulatory system; quality assurance of the ARN; the institutional communications; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the safeguards and the physical protection; the environmental control; the institutional relations; the training and the public information. Also, this publication have annexes with the following content: the regulatory framework; regulatory documents; inspections to medical, industrial and training installations; measurement and evaluation of the drinking water of Ezeiza; international expert's report on the application of the international standards of radiological protection of the public in the zone of the Ezeiza Atomic Center; ethical code

  17. 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

  18. Regulatory actions post - Fukushima

    International Nuclear Information System (INIS)

    Ciurea Ercau, C.

    2013-01-01

    The paper presents the results of the safety reviews performed in Romania after the Fukushima accident and the resulting actions for improving the safety. The actions taken by the National Commission for Nuclear Activities Control (CNCAN) to improve the regulatory framework include the development of new regulations and the enhancement of inspection practices, taking account of the lessons learned from the Fukushima accident. A regulation on the response to transients, accidents and emergency situations at nuclear power plants has been developed, which includes requirements on transient and accident scenarios that have to be covered by the Emergency Operating Procedures (EOPs), accident scenarios to be covered by the Severe Accident Management Guidelines (SAMGs), emergency situations to be covered by the on-site emergency response plan and emergency response procedures. (authors)

  19. Oxymatrine attenuates hepatic steatosis in non-alcoholic fatty liver disease rats fed with high fructose diet through inhibition of sterol regulatory element binding transcription factor 1 (Srebf1) and activation of peroxisome proliferator activated receptor alpha (Pparα).

    Science.gov (United States)

    Shi, Li-juan; Shi, Lei; Song, Guang-yao; Zhang, He-fang; Hu, Zhi-juan; Wang, Chao; Zhang, Dong-hui

    2013-08-15

    The aim of this study was to examine the therapeutic effect of oxymatrine, a monomer isolated from the medicinal plant Sophora flavescens Ait, on the hepatic lipid metabolism in non-alcoholic fatty liver (NAFLD) rats and to explore the potential mechanism. Rats were fed with high fructose diet for 8 weeks to establish the NAFLD model, then were given oxymatrine treatment (40, 80, and 160 mg/kg, respectively) for another 8 weeks. Body weight gain, liver index, serum and liver lipids, and histopathological evaluation were measured. Enzymatic activity and gene expression of the key enzymes involved in the lipogenesis and fatty acid oxidation were assayed. The results showed that oxymatrine treatment reduced body weight gain, liver weight, liver index, dyslipidemia, and liver triglyceride level in a dose dependant manner. Importantly, the histopathological examination of liver confirmed that oxymatrine could decrease the liver lipid accumulation. The treatment also decreased the fatty acid synthase (FAS) enzymatic activity and increased the carnitine palmitoyltransferase 1A (CPT1A) enzymatic activity. Besides, oxymatrine treatment decreased the mRNA expression of sterol regulatory element binding transcription factor 1(Srebf1), fatty acid synthase (Fasn), and acetyl CoA carboxylase (Acc), and increased the mRNA expression of peroxisome proliferator activated receptor alpha (Pparα), carnitine palmitoyltransferase 1A (Cpt1a), and acyl CoA oxidase (Acox1) in high fructose diet induced NAFLD rats. These results suggested that the therapeutic effect of oxymatrine on the hepatic steatosis in high fructose diet induced fatty liver rats is partly due to down-regulating Srebf1 and up-regulating Pparα mediated metabolic pathways simultaneously. © 2013 Elsevier B.V. All rights reserved.

  20. Regulatory Activities of the President of the Office of Electronic Communications versus competitiveness and fi nancial situation of the enterprises on the example of TP Group

    Directory of Open Access Journals (Sweden)

    Ewa M. Kwiatkowska

    2014-09-01

    Full Text Available Purpose: The aim of this paper is to present the regulatory obligations imposed by the President of the Office of Electronic Communications (hereafter: President of UKE on telecom enterprises with significant market power in the retail and wholesale telecommunications markets. Methodology: The decisions addressed to TP Group entities were analyzed as well as the fi nancial statements presenting the economic volume achieved for the period 2006–2013. Findings: In the analyzed period for entities of the TP Group were applied a range of regulatory obligations, that should result in disabling the use of their monopoly position and transfer their position between telecommunications markets. Regulatory obligations imposed by the President of UKE on TP Group entities did not affect to a significant extent the situation of the group. Fluctuations of analyzed financial f gures seem to be primarily the result of internal management decisions rather than a comprehensive range of sector-specific regulation in telecommunications. These researches indicate the need for a deeper analysis of the perception of the effects of regulatory actions by stakeholders in the telecommunications sector.

  1. Alterations in the regulatory volume decrease (RVD) and swelling-activated Cl- current associated with neuroendocrine differentiation of prostate cancer epithelial cells.

    NARCIS (Netherlands)

    Lemonnier, L.; Lazarenko, R.; Shuba, Y.; Thebault, S.C.; Roudbaraki, M.; Lepage, G.; Prevarskaya, N.; Skryma, R.

    2005-01-01

    Neuroendocrine (NE) differentiation of prostate epithelial/basal cells is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. Here we report for the first time on alterations in regulatory volume decrease (RVD) and its key determinant,

  2. An Exploration of the Legal and Regulatory Environment of Privacy and Security through Active Research, Guided Study, Blog Creation, and Discussion

    Science.gov (United States)

    Peslak, Alan R.

    2010-01-01

    One of the most important topics for today's information technology professional is the study of legal and regulatory issues as they relate to privacy and security of personal and business data and identification. This manuscript describes the topics and approach taken by the instructors that focuses on independent research of source documents and…

  3. IL-15 Renders Conventional Lymphocytes Resistant to Suppressive Functions of Regulatory T Cells through Activation of the Phosphatidylinositol 3-Kinase Pathway

    NARCIS (Netherlands)

    Ahmed, Melika Ben; Hmida, Nadia Belhadj; Moes, Nicolette; Buyse, Sophie; Abdeladhim, Maha; Louzir, Hechmi; Cerf-Bensussan, Nadine

    2009-01-01

    IL-15 drives chronic inflammation in several human diseases. We have recently shown that IL-15 inhibits the immunosuppressive effects of TGF-beta through blockage of the Smad3-signaling pathway. Data pointing to reciprocal interactions between TGF-beta and CD4(+) regulatory T cells led us to

  4. Regulatory framework for the management of radioactive wastes in Argentina

    International Nuclear Information System (INIS)

    D'Amato, E.; Siraky, G.; Petraitis, E.; Novo, R.

    2000-01-01

    The legal and regulatory framework within which the radioactive waste management is carried out in Argentina are exposed. The activities of the Nuclear Regulatory Authority (ARN) in relation to facility inspections, safety assessments and collaboration with international agencies in the matter are also presented. Further, the regulatory criteria applied to waste management are reported. (author)

  5. CD4+ T helper cells and regulatory T cells in active lupus nephritis: an imbalance towards a predominant Th1 response?

    Science.gov (United States)

    Mesquita, D; Kirsztajn, G Mastroianni; Franco, M F; Reis, L A; Perazzio, S F; Mesquita, F V; Ferreira, V da Silva; Andrade, L E Coelho; de Souza, A W Silva

    2018-01-01

    The objective of this study was to evaluate the frequency of CD4 + T cell subsets in peripheral blood mononuclear cells (PBMC), urine and renal tissue from patients with lupus nephritis (LN). PBMC and urinary cells were collected from 17 patients with active LN, 20 disease controls (DC) with primary glomerulonephritis and 10 healthy controls (HC) and were analysed by flow cytometry with markers for T helper type 1 (Th1), Th2, Th17 and regulatory T cells (T reg ) cells. T cell subsets were assessed by immunohistochemistry from LN biopsy specimens from 12 LN patients. T cell subtypes in PBMC were re-evaluated at 6 months of therapy. CD4 + T cells were decreased in PBMC in LN compared with DC and HC (P = 0·0001). No differences were observed in urinary CD4 + T cell subsets between LN and DC. The frequency of urinary Th17 cells was higher in patients with non-proliferative than in proliferative LN (P = 0·041). CD3 + and T-box 21 ( Tbet+) cells were found in glomeruli and interstitium of LN patients, while forkhead box protein 3 (FoxP3), retinoid-related orphan receptor gamma (ROR-γ) and GATA binding protein 3 (GATA-3) were present only in glomeruli. Th1 cells in PBMC were correlated negatively with urinary Th1 cells (Rho = -0·531; P = 0·028) and with T bet in renal interstitium (Rho = -0·782; P = 0·004). At 6 months, LN patients showed an increase in Th17 cells in PBMC. In conclusion, the inverse association between Th1 cells from PBMC and urinary/renal tissue indicate a role for Th1 in LN pathophysiology. Urinary Th17 cells were associated with less severe LN, and Th17 increased in PBMC during therapy. Urinary CD4 + T cells were not different between LN and DC. © 2017 British Society for Immunology.

  6. The R2R3-MYB–Like Regulatory Factor EOBI, Acting Downstream of EOBII, Regulates Scent Production by Activating ODO1 and Structural Scent-Related Genes in Petunia[C][W

    Science.gov (United States)

    Spitzer-Rimon, Ben; Farhi, Moran; Albo, Boaz; Cna’ani, Alon; Ben Zvi, Michal Moyal; Masci, Tania; Edelbaum, Orit; Yu, Yixun; Shklarman, Elena; Ovadis, Marianna; Vainstein, Alexander

    2012-01-01

    Flower scent is a highly dynamic trait, under developmental, spatial, and diurnal regulation. The mechanism governing scent production is only beginning to be unraveled. In petunia (Petunia hybrida), EMISSION OF BENZENOIDS II (EOBII) controls transcription of both the shikimate pathway-regulating MYB factor ODORANT1 (ODO1) and phenylpropanoid scent-related structural genes. A promoter-activation screen identified an R2R3-MYB–like regulatory factor of phenylpropanoid volatile biosynthesis acting downstream of EOBII, designated EOBI. EOBI silencing led to downregulation of ODO1 and numerous structural scent-related genes from both the shikimate and phenylpropanoid pathways. The ability of EOBI to directly activate ODO1, as revealed by electrophoretic mobility shift assay and yeast one-hybrid analysis, place EOBI upstream of ODO1 in regulating substrate availability for volatile biosynthesis. Interestingly, ODO1-silenced transgenic petunia flowers accumulated higher EOBI transcript levels than controls, suggesting a complex feedback loop between these regulatory factors. The accumulation pattern of EOBI transcript relative to EOBII and ODO1, and the effect of up/downregulation of EOBII on transcript levels of EOBI and ODO1, further support these factors' hierarchical relationships. The dependence of scent production on EOBI expression and its direct interaction with both regulatory and structural genes provide evidence for EOBI’s wide-ranging involvement in the production of floral volatiles. PMID:23275577

  7. The R2R3-MYB-like regulatory factor EOBI, acting downstream of EOBII, regulates scent production by activating ODO1 and structural scent-related genes in petunia.

    Science.gov (United States)

    Spitzer-Rimon, Ben; Farhi, Moran; Albo, Boaz; Cna'ani, Alon; Ben Zvi, Michal Moyal; Masci, Tania; Edelbaum, Orit; Yu, Yixun; Shklarman, Elena; Ovadis, Marianna; Vainstein, Alexander

    2012-12-01

    Flower scent is a highly dynamic trait, under developmental, spatial, and diurnal regulation. The mechanism governing scent production is only beginning to be unraveled. In petunia (Petunia hybrida), EMISSION OF BENZENOIDS II (EOBII) controls transcription of both the shikimate pathway-regulating MYB factor ODORANT1 (ODO1) and phenylpropanoid scent-related structural genes. A promoter-activation screen identified an R2R3-MYB-like regulatory factor of phenylpropanoid volatile biosynthesis acting downstream of EOBII, designated EOBI. EOBI silencing led to downregulation of ODO1 and numerous structural scent-related genes from both the shikimate and phenylpropanoid pathways. The ability of EOBI to directly activate ODO1, as revealed by electrophoretic mobility shift assay and yeast one-hybrid analysis, place EOBI upstream of ODO1 in regulating substrate availability for volatile biosynthesis. Interestingly, ODO1-silenced transgenic petunia flowers accumulated higher EOBI transcript levels than controls, suggesting a complex feedback loop between these regulatory factors. The accumulation pattern of EOBI transcript relative to EOBII and ODO1, and the effect of up/downregulation of EOBII on transcript levels of EOBI and ODO1, further support these factors' hierarchical relationships. The dependence of scent production on EOBI expression and its direct interaction with both regulatory and structural genes provide evidence for EOBI's wide-ranging involvement in the production of floral volatiles.

  8. Regulatory network controlling extracellular proteins in Erwinia carotovora subsp. carotovora: FlhDC, the master regulator of flagellar genes, activates rsmB regulatory RNA production by affecting gacA and hexA (lrhA) expression.

    Science.gov (United States)

    Cui, Yaya; Chatterjee, Asita; Yang, Hailian; Chatterjee, Arun K

    2008-07-01

    Erwinia carotovora subsp. carotovora produces an array of extracellular proteins (i.e., exoproteins), including plant cell wall-degrading enzymes and Harpin, an effector responsible for eliciting hypersensitive reaction. Exoprotein genes are coregulated by the quorum-sensing signal, N-acyl homoserine lactone, plant signals, an assortment of transcriptional factors/regulators (GacS/A, ExpR1, ExpR2, KdgR, RpoS, HexA, and RsmC) and posttranscriptional regulators (RsmA, rsmB RNA). rsmB RNA production is positively regulated by GacS/A, a two-component system, and negatively regulated by HexA (PecT in Erwinia chrysanthemi; LrhA [LysR homolog A] in Escherichia coli) and RsmC, a putative transcriptional adaptor. While free RsmA, an RNA-binding protein, promotes decay of mRNAs of exoprotein genes, binding of RsmA with rsmB RNA neutralizes the RsmA effect. In the course of studies of GacA regulation, we discovered that a locus bearing strong homology to the flhDC operon of E. coli also controls extracellular enzyme production. A transposon insertion FlhDC(-) mutant produces very low levels of pectate lyase, polygalacturonase, cellulase, protease, and E. carotovora subsp. carotovora Harpin (Harpin(Ecc)) and is severely attenuated in its plant virulence. The production of these exoproteins is restored in the mutant carrying an FlhDC(+) plasmid. Sequence analysis and transcript assays disclosed that the flhD operon of E. carotovora subsp. carotovora, like those of other enterobacteria, consists of flhD and flhC. Complementation analysis revealed that the regulatory effect requires functions of both flhD and flhC products. The data presented here show that FlhDC positively regulates gacA, rsmC, and fliA and negatively regulates hexA (lrhA). Evidence shows that FlhDC controls extracellular protein production through cumulative effects on hexA and gacA. Reduced levels of GacA and elevated levels of HexA in the FlhDC(-) mutant are responsible for the inhibition of rsmB RNA

  9. Regulatory Network Controlling Extracellular Proteins in Erwinia carotovora subsp. carotovora: FlhDC, the Master Regulator of Flagellar Genes, Activates rsmB Regulatory RNA Production by Affecting gacA and hexA (lrhA) Expression▿

    Science.gov (United States)

    Cui, Yaya; Chatterjee, Asita; Yang, Hailian; Chatterjee, Arun K.

    2008-01-01

    Erwinia carotovora subsp. carotovora produces an array of extracellular proteins (i.e., exoproteins), including plant cell wall-degrading enzymes and Harpin, an effector responsible for eliciting hypersensitive reaction. Exoprotein genes are coregulated by the quorum-sensing signal, N-acyl homoserine lactone, plant signals, an assortment of transcriptional factors/regulators (GacS/A, ExpR1, ExpR2, KdgR, RpoS, HexA, and RsmC) and posttranscriptional regulators (RsmA, rsmB RNA). rsmB RNA production is positively regulated by GacS/A, a two-component system, and negatively regulated by HexA (PecT in Erwinia chrysanthemi; LrhA [LysR homolog A] in Escherichia coli) and RsmC, a putative transcriptional adaptor. While free RsmA, an RNA-binding protein, promotes decay of mRNAs of exoprotein genes, binding of RsmA with rsmB RNA neutralizes the RsmA effect. In the course of studies of GacA regulation, we discovered that a locus bearing strong homology to the flhDC operon of E. coli also controls extracellular enzyme production. A transposon insertion FlhDC− mutant produces very low levels of pectate lyase, polygalacturonase, cellulase, protease, and E. carotovora subsp. carotovora Harpin (HarpinEcc) and is severely attenuated in its plant virulence. The production of these exoproteins is restored in the mutant carrying an FlhDC+ plasmid. Sequence analysis and transcript assays disclosed that the flhD operon of E. carotovora subsp. carotovora, like those of other enterobacteria, consists of flhD and flhC. Complementation analysis revealed that the regulatory effect requires functions of both flhD and flhC products. The data presented here show that FlhDC positively regulates gacA, rsmC, and fliA and negatively regulates hexA (lrhA). Evidence shows that FlhDC controls extracellular protein production through cumulative effects on hexA and gacA. Reduced levels of GacA and elevated levels of HexA in the FlhDC− mutant are responsible for the inhibition of rsmB RNA production

  10. Annual Report 2013. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2010-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across seven parts and eight annexes the activities developed by the organism during 2013. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the environmental monitoring; the occupational surveillance; the training and the public information; improved organizational and budgetary developments. Also, this publication has annexes with the following content: regulatory documents; inspections to medical; presentations of publications from ARN staff; measurement and evaluation of the drinking water of Ezeiza; international expert report on the implementation of international standards on radiation protection in the Ezeiza Atomic Center; Code of Ethics of the Nuclear Regulatory Authority.

  11. The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjögren's Syndrome.

    Science.gov (United States)

    Fonseca, Valter R; Romão, Vasco C; Agua-Doce, Ana; Santos, Mara; López-Presa, Dolores; Ferreira, Ana Cristina; Fonseca, João Eurico; Graca, Luis

    2018-05-01

    To investigate whether the balance of blood follicular helper T (Tfh) cells and T follicular regulatory (Tfr) cells can provide information about ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome (SS). We prospectively recruited 56 patients clinically suspected of having SS. Sixteen of these patients subsequently fulfilled the American-European Consensus Group criteria for SS and were compared to 16 patients with non-SS sicca syndrome. Paired blood and minor salivary gland (MSG) biopsy samples were analyzed to study Tfr cells and subsets of Tfh cells in both compartments. Patients with primary SS had normal Tfh cell counts in peripheral blood; however, activated programmed death 1-positive (PD-1+) inducible costimulator-positive (ICOS+) Tfh cells in peripheral blood were strongly associated with disease activity assessed by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSGs, being strongly associated with B cell, CD4+ T cell, and PD-1+ICOS+ T cell infiltration in MSGs, and was especially increased in patients with focal sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (odds ratio [OR] 12.96, P = 0.028) and the presence of focal sialadenitis (OR 10, P = 0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker. The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity. © 2018, American College of Rheumatology.

  12. 78 FR 68893 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2013-11-15

    ... that the size of the BBO equals the minimum quote size. Number of market makers actively quoting...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Extend the Tier Size Pilot of FINRA Rule 6433 (Minimum Quotation Size...

  13. Regulatory Commission of Alaska

    Science.gov (United States)

    Map Help Regulatory Commission of Alaska Login Forgot Password Arrow Image Forgot password? View Cart login Procedures for Requesting Login For Consumers General Information Telephone Electric Natural Gas

  14. Compliance. Regulatory policy P-211

    International Nuclear Information System (INIS)

    2001-05-01

    This regulatory policy describes the basic principles and directives for establishing and conducting the Canadian Nuclear Safety Commission (CNSC) Compliance Program. The program is aimed at securing compliance by regulated persons with regulatory requirements made under the Nuclear Safety and Control Act ('the Act'). The policy applies to persons who are regulated by the CNSC through the Act, regulations and licences, as well as by decisions and orders made under the Act. The policy applies to officers and employees of the CNSC, and its authorized representatives or agents, who are involved in developing and carrying out compliance activities. Compliance, in the context of this policy, means conformity by regulated persons with the legally binding requirements of the Act, and the CNSC regulations, licences, decisions, and orders made under the Act. Compliance activities are CNSC measures of promotion, verification and enforcement aimed at securing compliance by regulated person with the applicable legally binding requirements. (author)

  15. Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85α regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain.

    Science.gov (United States)

    Hofmann, Bianca T; Jücker, Manfred

    2012-10-01

    The phosphoinositide 3-kinase (PI3K) is frequently activated in human cancer cells due to gain of function mutations in the catalytic (p110) and the regulatory (p85) subunits. The regulatory subunit consists of an SH3 domain and two SH2 domains. An oncogenic form of p85α named p65 lacking the c-terminal SH2 domain (cSH2) has been cloned from an irradiation-induced murine thymic lymphoma and transgenic mice expressing p65 in T lymphocytes develop a lymphoproliferative disorder. We have recently detected a c-terminal truncated form of p85α named p76α in a human lymphoma cell line lacking most of the cSH2 domain due to a frame shift mutation. Here, we report that the deletion of the cSH2 domain enhances the activating effects of the n-terminal SH2 domain (nSH2) mutants K379E and R340E on the PI3K/Akt pathway and micro tumor formation in a focus assay. Further analysis revealed that this transforming effect is mediated by activation of the catalytic PI3K isoform p110α and downstream signaling through mTOR. Our data further support a mechanistic model in which mutations of the cSH2 domain of p85α can abrogate its negative regulatory function on PI3K activity via the nSH2 domain of p85α. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. 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

  17. L’effet de la personnalité sur la performance des étudiants universitaires en sciences de l’administration à l’examen écrit, au test à choix multiple et aux travaux pratiques

    Directory of Open Access Journals (Sweden)

    Sawsen Lakhal

    2017-03-01

    Full Text Available Plusieurs programmes universitaires en sciences de l’administration au Canada ont implanté des réformes majeures, suite aux demandes des organismes d’agrément tels que l’Association to Advance Collegiate Schools of Business (AACSB. Conséquemment, de plus en plus de méthodes d’évaluation des apprentissages sont utilisées. Toutefois, l’introduction de ces méthodes dans les programmes d’études pourrait engendrer des biais aux résultats de l’évaluation des apprentissages. L’étude des facteurs pouvant avoir un effet sur la performance des étudiants aux différentes méthodes d’évaluation devient pertinente dans ce contexte. Ainsi, l’objectif de cette étude consiste à vérifier si la personnalité telle que définie par le modèle des cinq facteurs influence la performance à l’examen écrit, au test à choix multiples et aux travaux pratiques. Deux variables contrôle, le genre et l’âge, sont inclus dans les analyses. Un échantillon de 378 étudiants inscrits à un cours de premier cycle universitaire en sciences de l’administration a répondu à un questionnaire en ligne. Les résultats des analyses des régressions linéaires multiples indiquent que ce ne sont pas toujours les mêmes facteurs de la personnalité qui sont sollicités d’une méthode d’évaluation à l’autre, indiquant l’existence potentielle de biais à l’évaluation des apprentissages. Ces résultats sont discutés au regard de la littérature plus large dans le domaine et touchant à d’autres programmes d’études universitaires. In Canada, a number of university programs in business administration have imbedded major reforms, following requests from accreditation bodies such as the Association to Advance Collegiate Schools of Business (AACSB. Consequently, more and more learning assessment methods are used. However, the introduction of these methods in curricula could lead to bias to the results of learning assessment. In

  18. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-10-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  19. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  20. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-01-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  1. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1991-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  2. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-08-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  3. Trust in regulatory regimes

    NARCIS (Netherlands)

    Six, Frédérique; Verhoest, Koen

    2017-01-01

    Within political and administrative sciences generally, trust as a concept is contested, especially in the field of regulatory governance. This groundbreaking book is the first to systematically explore the role and dynamics of trust within regulatory regimes. Conceptualizing, mapping and analyzing

  4. Nuclear Regulatory legislation

    International Nuclear Information System (INIS)

    1984-06-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 97th Congress, 2nd Session, has been prepared by the Office of the Executive Legal Director, U.S. Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document

  5. Improving nuclear regulatory effectiveness

    International Nuclear Information System (INIS)

    2001-01-01

    Ensuring that nuclear installations are operated and maintained in such a way that their impact on public health and safety is as low as reasonably practicable has been and will continue to be the cornerstone of nuclear regulation. In the past, nuclear incidents provided the main impetus for regulatory change. Today, economic factors, deregulation, technological advancements, government oversight and the general requirements for openness and accountability are leading regulatory bodies to review their effectiveness. In addition, seeking to enhance the present level of nuclear safety by continuously improving the effectiveness of regulatory bodies is seen as one of the ways to strengthen public confidence in the regulatory systems. This report covers the basic concepts underlying nuclear regulatory effectiveness, advances being made and future requirements. The intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  6. Regulatory Office for Network Industries

    International Nuclear Information System (INIS)

    2005-01-01

    The main goal of the economic regulation of network industries is to ensure a balance between the interests of consumers and investors and to encourage providing high-quality goods and services. The task of the regulatory authority is to protect the interests of consumers against monopolistic behaviour of regulated enterprises. At the same time, the regulatory office has to protect the interests of investors by giving them an opportunity to achieve an adequate return on their investments. And last, but not least, the regulatory office has to provide regulated enterprises with appropriate incentives to make them function in an efficient and effective manner and to guarantee the security of delivery of energies and related services. All this creates an efficient regulatory framework that is capable of attracting the required amount and type of investments. This also means providing third party access to the grids, the opening of energy markets, the un-bundling of accounts according to production, distribution, transmission and other activities and the establishment of a transparent and stable legislative environment for regulated companies, investors and consumers. Otherwise, in the long run consumers may suffer from a serious deterioration of service quality, although in the short run they are protected against increased prices. Under the Act No. 276/2001 Coll. on Regulation of Network Industries and on amendment of some acts the Office for Regulation of Network Industries has been commissioned to implement the main objectives of regulation of network industries. By network industries the Act No. 276/2001 Coll. on Regulation means the following areas: (a) Production, purchase, transit and distribution of electricity; (b) Production, purchase, transit and distribution of gas; (c) Production, purchase and distribution of heat; (d) Water management activities relating to the operation of the public water supply system or the public sewerage system; (e) Water management

  7. Diagnosis of the Brazilian Nuclear Regulatory body

    International Nuclear Information System (INIS)

    Santos Gomes, Rogerio dos; Magalhaes Ennes Ennes, Edson Carlos

    2008-01-01

    This work has the objective to present the diagnosis of the existing structure in the Brazilian Government to ensure the radioprotection and nuclear safety in the country, being compared the current situation with the conclusions presented in another studies, carried through in last 30 years, with special attention in the existence of the necessary available to support and independence of the national regulatory body for the development of the regulatory inspections activities in the radioprotection and nuclear safety. (author)

  8. A unified architecture of transcriptional regulatory elements

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  9. Mathematical model of the glucose-insulin regulatory system: From the bursting electrical activity in pancreatic β-cells to the glucose dynamics in the whole body

    Science.gov (United States)

    Han, Kyungreem; Kang, Hyuk; Choi, M. Y.; Kim, Jinwoong; Lee, Myung-Shik

    2012-10-01

    A theoretical approach to the glucose-insulin regulatory system is presented. By means of integrated mathematical modeling and extensive numerical simulations, we probe the cell-level dynamics of the membrane potential, intracellular Ca2+ concentration, and insulin secretion in pancreatic β-cells, together with the whole-body level glucose-insulin dynamics in the liver, brain, muscle, and adipose tissues. In particular, the three oscillatory modes of insulin secretion are reproduced successfully. Such comprehensive mathematical modeling may provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination.

  10. Guidelines for IAEA International Regulatory Review Teams (IRRTs)

    International Nuclear Information System (INIS)

    1993-04-01

    This document is intended to be used by International regulatory review teams in reviewing the activities of a regulatory body as applicable to the regulation of nuclear power plants. The mission will, however, take note of any other activities of the regulatory body when drawing up the review report. The document does not specifically deal with the functions of a regulatory body responsible for other types of nuclear facilities or related nuclear activities, but it is intended that the concepts presented in the document could be applied where appropriate. Refs

  11. Mathematical model of the glucose–insulin regulatory system: From the bursting electrical activity in pancreatic β-cells to the glucose dynamics in the whole body

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kyungreem [College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Kang, Hyuk [National Institute for Mathematical Sciences, Daejeon 305-340 (Korea, Republic of); Choi, M.Y., E-mail: mychoi@snu.ac.kr [Department of Physics and Astronomy and Center for Theoretical Physics, Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, Jinwoong, E-mail: jwkim@snu.ac.kr [College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Lee, Myung-Shik [Department of Medicine, Samsung Medical Center, and School of Medicine, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of)

    2012-10-01

    A theoretical approach to the glucose–insulin regulatory system is presented. By means of integrated mathematical modeling and extensive numerical simulations, we probe the cell-level dynamics of the membrane potential, intracellular Ca{sup 2+} concentration, and insulin secretion in pancreatic β-cells, together with the whole-body level glucose–insulin dynamics in the liver, brain, muscle, and adipose tissues. In particular, the three oscillatory modes of insulin secretion are reproduced successfully. Such comprehensive mathematical modeling may provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination. -- Highlights: ► We present a mathematical model for the glucose–insulin regulatory system. ► This model combines the microscopic insulin secretion mechanism in a pancreatic β-cell and macroscopic glucose dynamics at the whole-body level. ► This work is expected to provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination.

  12. Mathematical model of the glucose–insulin regulatory system: From the bursting electrical activity in pancreatic β-cells to the glucose dynamics in the whole body

    International Nuclear Information System (INIS)

    Han, Kyungreem; Kang, Hyuk; Choi, M.Y.; Kim, Jinwoong; Lee, Myung-Shik

    2012-01-01

    A theoretical approach to the glucose–insulin regulatory system is presented. By means of integrated mathematical modeling and extensive numerical simulations, we probe the cell-level dynamics of the membrane potential, intracellular Ca 2+ concentration, and insulin secretion in pancreatic β-cells, together with the whole-body level glucose–insulin dynamics in the liver, brain, muscle, and adipose tissues. In particular, the three oscillatory modes of insulin secretion are reproduced successfully. Such comprehensive mathematical modeling may provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination. -- Highlights: ► We present a mathematical model for the glucose–insulin regulatory system. ► This model combines the microscopic insulin secretion mechanism in a pancreatic β-cell and macroscopic glucose dynamics at the whole-body level. ► This work is expected to provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination.

  13. Regulatory risk coherence

    International Nuclear Information System (INIS)

    Remick, F.J.

    1992-01-01

    As one of the most progressive users of risk assessment in decision making, the US Nuclear Regulatory Commission (NRC) is in a position to play an important role in influencing the development of standard government wide policies for the application of risk assessment in decision making. The NRC, with the support of the nuclear industry, should use the opportunity provided by its experience with risk assessment to actively encourage the adoption of standard national and international health-based safety goals and at the same time accelerate its own efforts to implement the safety goals it has already developed for itself. There are signs of increased recognition of the need for consistency and coherence in the application of risk assessment in government decision making. The NRC and the nuclear industry have recently taken a great step toward establishing a consistant and coherent risk assessment-based culture in the US nuclear industry. As a result of Generic Letter 88-20, which asks each commercial nuclear power plant licensee to perform an individual plant examination by September 1992, for the first time a risk assessment characterizing initiating events in each plant will exist

  14. 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.

  15. Molecular dissection of the C-terminal regulatory domain of the plant plasma membrane H+-ATPase AHA2: Mapping of residues that when altered give rise to an activated enzyme

    DEFF Research Database (Denmark)

    Axelsen, K.B.; Venema, K.; Jah, T.

    1999-01-01

    in an extension of the C-terminus unique to plant H+-ATPases, Alteration of residues in both regions led to increased binding of yeast 14-3-3 protein to the plasma membrane of transformed cells. Taken together, our data suggest that modification of residues in two regions of the C-terminal regulatory domain......The plasma membrane H+-ATPase is a proton pump belonging to the P-type ATPase superfamily and is important for nutrient acquisition in plants, The H+-ATPase is controlled by an autoinhibitory C-terminal regulatory domain and is activated by 14-3-3 proteins which bind to this part of the enzyme......+-ATPase. The enzymes were characterized by their ability to promote growth in acidic conditions and to promote H+ extrusion from intact cells, both of which are measures of plasma membrane H+-ATPase activity, and were also characterized with respect to kinetic properties such as affinity for H+ and ATP. Residues...

  16. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-10-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  17. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-04-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  18. Through the regulatory hoop

    International Nuclear Information System (INIS)

    Kirner, N.P.

    1985-01-01

    There are many regulatory hoops through which waste generators, brokers, and disposal site operators must jump to dispose of waste safely. As the proposed exclusionary date of January 1, 1986, approaches, these regulatory hoops have the distinct possibility of multiplying or at least changing shape. The state of Washington, in its role as an Agreement State with the US Nuclear Regulatory Commission, licenses and inspects the commercial operator of the Northwest Compact's low-level radioactive waste disposal site on the Hanford Reservation. Washington has received as much as 53%, or 1.4 million cubic feet per year, of the nation's total volume of waste disposed. To control such a large volume of waste, a regulatory program involving six agencies has developed over the years in Washington

  19. National legislative and regulatory activities: Armenia, Australia, Austria, Belgium, Brazil, France, Germany, Hungary, India, Ireland, Lithuania, Moldova, Poland, Portugal, Romania, Slovenia, Sweden, Ukraine, United States

    International Nuclear Information System (INIS)

    Anon.

    2012-01-01

    Armenia: Nuclear safety and radiation protection (New procedure for investigation of nuclear power plant operational events, New requirements for the accounting of radiation sources). Australia: Radioactive waste management (New law regarding the development of a radioactive waste management facility). Austria: Nuclear safety and radiation protection (Substantive changes to nuclear safety and radiation protection requirements). Belgium: Nuclear security (New requirements for the protection of critical infrastructures); Nuclear safety (Changes to safety measures for nuclear facilities); Nuclear safety and radiation protection (New requirements regarding the detection of orphan sources, New requirements regarding medical uses of radiation, A new framework for monitoring radon exposure). Brazil: Nuclear security (Establishment of new nuclear security organisation). France: Liability and compensation (Increase in the amount of operator liability in case of nuclear incident); General legislation (New comprehensive requirements for basic nuclear installations, New report by the Court of Auditors (Cour des Comptes) on the costs of nuclear energy). Germany: Nuclear safety and radiation protection (Amendments to the Radiation Protection Ordinance and to the X-Rays Ordinance); Transport of radioactive material (New consolidated versions of Ordinances on the Transport of Dangerous Goods); International trade (Changes to the list of foreign trade laws and regulations, Changes to the basic legal instruments governing foreign trade). Hungary: Nuclear safety and radiation protection (Changes to nuclear safety requirements); General legislation (Modification of Act CXVI of 1996 on Atomic Energy). India: Liability and compensation (Final versions of recent liability and compensation legislation available online). Ireland: Transport of radioactive material (New regulations relating to the transport of dangerous goods by road). Lithuania: Licensing and regulatory infrastructure

  20. Regulatory framework for nuclear power plant operation

    International Nuclear Information System (INIS)

    Perez Alcaniz, T.; Esteban Barriendos, M.

    1995-01-01

    As the framework of standards and requirements covering each phase of nuclear power plant project and operation developed, plant owners defined their licensing commitments (codes, rules and design requirements) during the project and construction phase before start-up and incorporated regulatory requirements imposed by the regulatory Body during the licensing process prior to operation. This produces a regulatory framework for operating a plant. It includes the Licensing Basis, which is the starting point for analyzing and incorporating new requirements, and for re-evaluation of existing ones. This presentation focuses on the problems of applying this regulatory framework to new operating activities, in particular to new projects, analyzing new requirements, and reconsidering existing ones. Clearly establishing a plant's licensing basis allows all organizations involved in plant operation to apply the requirements in a more rational way. (Author)

  1. 77 FR 58022 - Montana Regulatory Program

    Science.gov (United States)

    2012-09-19

    ... precludes in situ gasification projects from including carbon capture and sequestration (CCS) under the... Conservation as the regulatory authority for CCS activities within the State. SB498 generally established that..., the Board would regulate any proposed CCS activities appropriately. CCS operations have potential...

  2. Regulatory Myeloid Cells in Transplantation

    Science.gov (United States)

    Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

    2013-01-01

    Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

  3. The Regulatory and Kinase Domains but Not the Interdomain Linker Determine Human Double-stranded RNA-activated Kinase (PKR) Sensitivity to Inhibition by Viral Non-coding RNAs.

    Science.gov (United States)

    Sunita, S; Schwartz, Samantha L; Conn, Graeme L

    2015-11-20

    Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an important component of the innate immune system that presents a crucial first line of defense against viral infection. PKR has a modular architecture comprising a regulatory N-terminal dsRNA binding domain and a C-terminal kinase domain interposed by an unstructured ∼80-residue interdomain linker (IDL). Guided by sequence alignment, we created IDL deletions in human PKR (hPKR) and regulatory/kinase domain swap human-rat chimeric PKRs to assess the contributions of each domain and the IDL to regulation of the kinase activity by RNA. Using circular dichroism spectroscopy, limited proteolysis, kinase assays, and isothermal titration calorimetry, we show that each PKR protein is properly folded with similar domain boundaries and that each exhibits comparable polyinosinic-cytidylic (poly(rI:rC)) dsRNA activation profiles and binding affinities for adenoviral virus-associated RNA I (VA RNAI) and HIV-1 trans-activation response (TAR) RNA. From these results we conclude that the IDL of PKR is not required for RNA binding or mediating changes in protein conformation or domain interactions necessary for PKR regulation by RNA. In contrast, inhibition of rat PKR by VA RNAI and TAR RNA was found to be weaker than for hPKR by 7- and >300-fold, respectively, and each human-rat chimeric domain-swapped protein showed intermediate levels of inhibition. These findings indicate that PKR sequence or structural elements in the kinase domain, present in hPKR but absent in rat PKR, are exploited by viral non-coding RNAs to accomplish efficient inhibition of PKR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. First update to the US Nuclear Regulatory Commission's regulatory strategy for the high-level waste repository program

    International Nuclear Information System (INIS)

    Johnson, R.L.; Linehan, J.J.

    1991-01-01

    The US Nuclear Regulatory Commission (NRC) staff has updated its initial regulatory strategy for the High-Level Waste Repository Licensing Program. The update describes changes to the initial strategy and summarizes progress and future activities. This paper summarizes the first update of the regulatory strategy. In general the overall strategy of identifying and reducing uncertainties is unchanged. Identifying regulatory and institutional uncertainties is essentially complete, and therefore, the current and future emphasis is on reducing those regulatory and institutional uncertainties identified to date. The NRC staff has improved the methods of reducing regulatory uncertainties by (1) enhancing the technical basis preparation process for potential rulemakings and guidance and (2) designing a new guidance document, called a staff position, for clarifying regulatory uncertainties. For guiding the US DOE's reduction of technical uncertainties, the NRC staff will give more emphasis to prelicense application reviews and less emphasis on preparing staff technical positions

  5. Regulatory aspects of NPP safety

    International Nuclear Information System (INIS)

    Stuller, J.; Brandejs, P.; Miasnikov, A.; Svab, M.

    1999-01-01

    In beginning, a history of legislative process regulating industrial utilisation of nuclear energy is given, including detailed list of decrees issued by the first regulatory body supervising Czech nuclear installations - Czechoslovak Atomic Energy Commission (CSKAE). Current status of nuclear regulations and radiation protection, especially in connection with Atomic Act (Act No 18/1997 Coll.), is described. The Atomic Act transfers into the Czech legal system a number of obligations following from the Vienna Convention on Civil Liability for Nuclear Damage and Joint Protocol relating to the Application of the Vienna and Paris Convention, to which the Czech Republic had acceded. Actual duties and competence of current nuclear regulatory body - State Office for Nuclear Safety (SUJB) - are given in detail. Execution of the State supervision of peaceful utilisation of nuclear energy and ionising radiation is laid out in several articles of the Act, which comprises: control activities of the SUJB, remedial measures, penalties. Material and human resources are sufficient for fulfilment of the basic functions for which SUJB is authorised by the law. For 1998, the SUJB allotted staff of 149, approximately 2/3 of that number are nuclear safety and radiation protection inspectors. The SUJB budget for 1998 is approximately 180 million Czech crowns (roughly 6 million US dollars). Inspection activity of SUJB is carried out in three different ways: routine inspections, planned specialised inspections, inspections as a response to a certain situation (ad-hoc inspections). Approach to the licensing of major plant upgrades and backfittings are mainly illustrated on the Temelin NPP licensing. Regulatory position and practices concerning review activities are presented. (author)

  6. 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

  7. Potent Nematicidal Activity and New Hybrid Metabolite Production by Disruption of a Cytochrome P450 Gene Involved in the Biosynthesis of Morphological Regulatory Arthrosporols in Nematode-Trapping Fungus Arthrobotrys oligospora.

    Science.gov (United States)

    Song, Tian-Yang; Xu, Zi-Fei; Chen, Yong-Hong; Ding, Qiu-Yan; Sun, Yu-Rong; Miao, Yang; Zhang, Ke-Qin; Niu, Xue-Mei

    2017-05-24

    Types of polyketide synthase-terpenoid synthase (PKS-TPS) hybrid metabolites, including arthrosporols with significant morphological regulatory activity, have been elucidated from nematode-trapping fungus Arthrobotrys oligospora. A previous study suggested that the gene cluster AOL_s00215 in A. oligospora was involved in the production of arthrosporols. Here, we report that disruption of one cytochrome P450 monooxygenase gene AOL_s00215g280 in the cluster resulted in significant phenotypic difference and much aerial hyphae. A further bioassay indicated that the mutant showed a dramatic decrease in the conidial formation but developed numerous traps and killed 85% nematodes within 6 h in contact with prey, in sharp contrast to the wild-type strain with no obvious response. Chemical investigation revealed huge accumulation of three new PKS-TPS epoxycyclohexone derivatives with different oxygenated patterns around the epoxycyclohexone moiety and the absence of arthrosporols in the cultural broth of the mutant ΔAOL_s00215g280. These findings suggested that a study on the biosynthetic pathway for morphological regulatory metabolites in nematode-trapping fungus would provide an efficient way to develop new fungal biocontrol agents.

  8. Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet-induced obesity and glucose intolerance in mice that lack PKA regulatory subunit type IIα.

    Science.gov (United States)

    London, Edra; Nesterova, Maria; Sinaii, Ninet; Szarek, Eva; Chanturiya, Tatyana; Mastroyannis, Spyridon A; Gavrilova, Oksana; Stratakis, Constantine A

    2014-09-01

    The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cβ resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease.

  9. 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)

  10. 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)

  11. Systematic identification of regulatory variants associated with cancer risk.

    Science.gov (United States)

    Liu, Song; Liu, Yuwen; Zhang, Qin; Wu, Jiayu; Liang, Junbo; Yu, Shan; Wei, Gong-Hong; White, Kevin P; Wang, Xiaoyue

    2017-10-23

    Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities. From 10,673 SNPs linked with 996 cancer risk-associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the fragments that positively regulate gene expression, and 758 SNPs in the fragments with negative regulatory activities. Among them, 70 variants are regulatory variants for which the two alleles confer different regulatory activities. We analyze in depth two regulatory variants-breast cancer risk SNP rs11055880 and leukemia risk-associated SNP rs12142375-and demonstrate their endogenous regulatory activities on expression of ATF7IP and PDE4B genes, respectively, using a CRISPR-Cas9 approach. By identifying regulatory variants associated with cancer susceptibility and studying their molecular functions, we hope to help the interpretation of GWAS results and provide improved information for cancer risk assessment.

  12. Feline glycoprotein A repetitions predominant anchors transforming growth factor beta on the surface of activated CD4(+)CD25(+) regulatory T cells and mediates AIDS lentivirus-induced T cell immunodeficiency.

    Science.gov (United States)

    Miller, Michelle M; Fogle, Jonathan E; Ross, Peter; Tompkins, Mary B

    2013-04-01

    Using the feline immunodeficiency virus (FIV) model for AIDS-lentivirus infection, our laboratory has previously demonstrated that T regulatory (Treg) cell-mediated immune T and B cell dysfunction contributes to lentivirus persistence and chronic disease through membrane bound transforming growth factor beta (mTGFb). Studying Treg cells in the context of infection has been problematic as no inducible marker for activated Treg cells had been identified. However, recent reports in human Treg studies have described a novel protein, glycoprotein A repetitions predominant (GARP), as a unique marker of activated human Treg cells that anchors mTGFb. Herein we extend these studies to the feline Treg system, identifying feline GARP and demonstrating that human and feline GARP proteins are homologous in structure, expression pattern, and ability to form a complex with TGFb. We further demonstrate that GARP and TGFb form a complex on the surface of activated Treg cells and that these GARP(+)TGFb(+) Treg cells are highly efficient suppressor cells. Analysis of expression of this Treg activation marker in the FIV-AIDS model reveals an up-regulation of GARP expressing Treg cells during chronic FIV infection. We demonstrate that the GARP(+) Treg cells from FIV-infected cats suppress T helper cells in vivo and that blocking GARP or TGFb eliminates this suppression. These data suggest that GARP is expressed in complex with TGFb on the surface of activated Treg cells and plays an important role in TGFb(+) Treg-mediated T cell immune suppression during lentivirus infection.

  13. Safety research programs sponsored by Office of Nuclear Regulatory Research

    International Nuclear Information System (INIS)

    Weiss, A.J.; Azarm, A.; Baum, J.W.

    1989-07-01

    This progress report describes current activities and technical progress in the programs at Brookhaven National Laboratory sponsored by the Division of Regulatory Applications, Division of Engineering, Division of Safety Issue Resolution, and Division of Systems Research of the US Nuclear Regulatory Commission, Office of Nuclear Regulatory Research following the reorganization in July 1988. The previous reports have covered the period October 1, 1976 through September 30, 1988

  14. Mission Risk Reduction Regulatory Change Management

    Science.gov (United States)

    Scroggins, Sharon

    2007-01-01

    NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

  15. Mutant Forms of the Azotobacter vinelandii Transcriptional Activator NifA Resistant to Inhibition by the NifL Regulatory Protein

    OpenAIRE

    Reyes-Ramirez, Francisca; Little, Richard; Dixon, Ray

    2002-01-01

    The Azotobacter vinelandii σ54-dependent transcriptional activator protein NifA is regulated by the NifL protein in response to redox, carbon, and nitrogen status. Under conditions inappropriate for nitrogen fixation, NifL inhibits transcription activation by NifA through the formation of the NifL-NifA protein complex. NifL inhibits the ATPase activity of the central AAA+ domain of NifA required to drive open complex formation by σ54-RNA polymerase and may also inhibit the activator-polymeras...

  16. Nuclear Regulatory Legislation

    International Nuclear Information System (INIS)

    1989-08-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 100th Congress, 2nd Session, has been prepared by the Office of the General Counsel,