WorldWideScience

Sample records for active regulatory processes

  1. Regulatory activities

    International Nuclear Information System (INIS)

    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. 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.

  3. Organization of nuclear regulatory activities

    International Nuclear Information System (INIS)

    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

  4. Modelling Nonstationary Gene Regulatory Processes

    Directory of Open Access Journals (Sweden)

    Marco Grzegorcyzk

    2010-01-01

    Full Text Available An important objective in systems biology is to infer gene regulatory networks from postgenomic data, and dynamic Bayesian networks have been widely applied as a popular tool to this end. The standard approach for nondiscretised data is restricted to a linear model and a homogeneous Markov chain. Recently, various generalisations based on changepoint processes and free allocation mixture models have been proposed. The former aim to relax the homogeneity assumption, whereas the latter are more flexible and, in principle, more adequate for modelling nonlinear processes. In our paper, we compare both paradigms and discuss theoretical shortcomings of the latter approach. We show that a model based on the changepoint process yields systematically better results than the free allocation model when inferring nonstationary gene regulatory processes from simulated gene expression time series. We further cross-compare the performance of both models on three biological systems: macrophages challenged with viral infection, circadian regulation in Arabidopsis thaliana, and morphogenesis in Drosophila melanogaster.

  5. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Different national legislative and regulatory activities in the field of nuclear energy are exposed here; from the radiation protection and the safe use of nuclear energy, to the question of radioactive waste management, the nuclear area is seen through the national decrees, amendments orders and acts for eighteen countries. (N.C.)

  6. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    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

  7. The integration of optimization in the regulatory process

    International Nuclear Information System (INIS)

    The purpose of this paper is to describe how optimization fits in a complex regulatory regime aimed at protection of the public health and safety. The comments and observations about optimization in the regulatory process are based mainly on the authors' experience in a single agency, the US Nuclear Regulatory Commission (NRC). The NRC regulates a broad spectrum of nuclear activities ranging from nuclear power reactors and the nuclear fuel cycle to the use of radioisotopes in industry, research and medicine

  8. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    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

  9. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    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

  10. Regulatory control of food irradiation processes

    International Nuclear Information System (INIS)

    Ionizing radiation has a long history of successful use in treating a variety of nonfood products, but its application to foods is a new challenge. In order to meet this challenge, regulatory requirements and standards for the irradiation treatment of foods are needed. Many countries have already established rules and protocols for the use of ionizing radiation on a variety of food products and the food industry has recognized the need for standards for the irradiation treatment of foods, in many cases more stringent than those applied for other processes. While standardization and control of the irradiation process are imperative for its proper application to food, they are not the parameters that will govern the successful implementation and acceptance of food irradiation. The technology will be successful only if the public accepts it as a safe and useful process. Recent surveys show that dissemination of accurate and complete facts about irradiation is a key to public education about the technology. The United States Department of Agriculture (USDA) agrees that public information is important and, while it feels that industry must play the primary role, it is participating in several public information activities. Many U.S. government agencies are involved in food irradiation, protecting the public from hazards associated with ionizing radiation technology, monitoring the safety and wholesomeness of the food supply, and developing and transferring the technology to the private sector. There are only a few approved uses of food irradiation in the U.S. at the present time and very little food is being processed using the technology. The regulatory agencies are requiring proper labeling and packaging, and effective quality control systems as prerequisites for the use of irradiation. Methods for detecting if a food has been irradiated are also under development, although they should not be a prerequisite for the application of the technology to foods. (author)

  11. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    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

  12. Argentina's regulatory body: its communication activities

    International Nuclear Information System (INIS)

    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

  13. Regulatory fit messages and physical activity motivation.

    Science.gov (United States)

    Pfeffer, Ines

    2013-04-01

    Targeted communication about health behaviors seems to be more effective than mass communication in which undifferentiated audiences receive identical messages. Regulatory focus is psychological variable that can be used to build two target groups: promotion-focused or prevention-focused people. It is hypothesized that targeting messages to an individual's regulatory focus creates regulatory fit and is more successful to promote a physically active lifestyle than nonfit messages. Two different print messages promoting a physically active lifestyle derived from regulatory focus theory (promotion message vs. prevention message) were randomly assigned to N = 98 participants after measuring their regulatory focus. It was examined whether regulatory fit between the regulatory focus and the assigned print message would lead to more positive evaluations in the dependent variables inclination toward the message (preference for the message), intention to perform the behavior, prospective and retrospective feelings associated with the behavior (positive and negative), and perceived value of the behavior directly after reading the message. Hierarchical linear regression analyses revealed that regulatory fit led to stronger intentions in the prevention-message condition and more prospective positive and retrospective positive feelings associated with the behavior in the promotion-message condition in contrast to the nonfit conditions. Prospective positive feelings associated with the behavior mediated the effect of regulatory fit on intention. The results partly provided support for the regulatory fit concept. Matching print messages to the regulatory focus of individuals seems to be a useful approach to enhance physical activity motivation. Future studies should include an objective measure of physical activity behavior.

  14. Shaping Formal Networks throug the Regulatory Process

    NARCIS (Netherlands)

    Hall, Thad E.; O'Toole, Laurence J.

    2004-01-01

    Recent research has shown that, at the federal level, new or amended programs typically create networks consisting of multiactor structures spanning governments, sectors, and/or agencies. This study examines the implementation structures created through the regulatory process. We find that in a majo

  15. Review of NRC Regulatory processes and functions

    International Nuclear Information System (INIS)

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

  16. Attribute Exploration of Gene Regulatory Processes

    CERN Document Server

    Wollbold, Johannes

    2012-01-01

    This thesis aims at the logical analysis of discrete processes, in particular of such generated by gene regulatory networks. States, transitions and operators from temporal logics are expressed in the language of Formal Concept Analysis. By the attribute exploration algorithm, an expert or a computer program is enabled to validate a minimal and complete set of implications, e.g. by comparison of predictions derived from literature with observed data. Here, these rules represent temporal dependencies within gene regulatory networks including coexpression of genes, reachability of states, invariants or possible causal relationships. This new approach is embedded into the theory of universal coalgebras, particularly automata, Kripke structures and Labelled Transition Systems. A comparison with the temporal expressivity of Description Logics is made. The main theoretical results concern the integration of background knowledge into the successive exploration of the defined data structures (formal contexts). Applyi...

  17. A review of NRC regulatory processes and functions

    International Nuclear Information System (INIS)

    A reexamination by the ACRS of the Regulatory Process has been made. Objectives were to provide in a single source, ACRS' understanding of the Regulatory Process and to point out perceived weaknesses and to make appropriate recommendations for change

  18. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    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.)

  19. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    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

  20. Bioattractors: dynamical systems theory and the evolution of regulatory processes.

    Science.gov (United States)

    Jaeger, Johannes; Monk, Nick

    2014-06-01

    In this paper, we illustrate how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems. Our argument is that the genotype-phenotype map can be characterized by the phase portrait of the underlying regulatory process. The features of this portrait--such as attractors with associated basins and their bifurcations--define the regulatory and evolutionary potential of a system. We show how the geometric analysis of phase space connects Waddington's epigenetic landscape to recent computational approaches for the study of robustness and evolvability in network evolution. We discuss how the geometry of phase space determines the probability of possible phenotypic transitions. Finally, we demonstrate how the active, self-organizing role of the environment in phenotypic evolution can be understood in terms of dynamical systems concepts. This approach yields mechanistic explanations that go beyond insights based on the simulation of evolving regulatory networks alone. Its predictions can now be tested by studying specific, experimentally tractable regulatory systems using the tools of modern systems biology. A systematic exploration of such systems will enable us to understand better the nature and origin of the phenotypic variability, which provides the substrate for evolution by natural selection.

  1. Safety indicators in the nuclear regulatory process in South Africa

    International Nuclear Information System (INIS)

    In support of the approach adopted by the nuclear regulatory authority (National Nuclear Regulator - NNR) in South Africa, which combines risk, deterministic and process based thinking, the use of safety indicators is considered an important means of providing objective evidence of the success or failure of safety related activities or processes, as well as direct evidence of the status of safety factors relating to the plant, licensed site, the workforce, the public and the environment. The use of safety indicators helps to focus attention on weak areas and to provide information in a format which can be trended and which is readily reportable and comprehensible to the licensee management, public and different levels of the various regulatory and government organisations. The primary objectives of the system of safety goals and indicators is as follows: - To provide an objective measure of compliance of the licensed site with the safety case for the site, in terms of factors relating to plant health, workforce, public and environment, and trending thereof. - To provide an objective measure of the status of supporting safety related activities and safety factors. - To help focus resources on areas of concern in all licensing and safety assurance activities (inspection, assessment, pro-active work, guidelines etc), in a graded manner taking into account the status of relevant safety factors. - To facilitate reporting of the safety status of licensed facilities to different levels of the licensee and regulatory organisations. This paper describes the recent developments of safety goals and indicators as applied in the reactor licensing process in South Africa. The monitoring of a nuclear facility in terms of nuclear safety assurance involves a large volume of information from diverse sources and of different levels of significance. An indicator system linked to a compliance assurance programme and reporting and assessment system as described in this paper provides an

  2. The U.S. Nuclear Regulatory Commission's decommissioning process

    International Nuclear Information System (INIS)

    The term 'Decommission' is defined in the U.S.. Nuclear Regulatory Commission's (USNRC's) regulations at 10 CFR 20.1003 as to remove a facility or site safely from service and reduce residual radioactivity to a level that permits 1) release of the property for unrestricted use and termination of the license; or, 2) release of the property under restricted conditions and the termination of the license. USNRC's decommissioning program encompasses the decommissioning of all NRC licensed facilities, ranging from routine license terminations for sealed source users, to the oversight of complex sites and those on the Site Decommissioning Management Plan (SDMP), as well as power and non-power reactors. This paper describes the USNRC's decommissioning process for materials and reactor facilities and presents an overview of USNRC's decommissioning program activities. (author)

  3. ICT Support for Regulatory Compliance of Business Processes

    OpenAIRE

    Governatori, Guido

    2014-01-01

    In this paper we propose an ITC (Information and Communication Technology) approach to support regulatory compliance for business processes, and we report on the development and evaluation of a business process compliance checker called Regorous, based on the compliance-by-design methodology proposed by Governatori and Sadiq

  4. Process improvement for regulatory analyses of custom-blend fertilizers.

    Science.gov (United States)

    Wegner, Keith A

    2014-01-01

    Chemical testing of custom-blend fertilizers is essential to ensure that the products meet the formulation requirements. For purposes of proper crop nutrition and consumer protection, regulatory oversight promotes compliance and particular attention to blending and formulation specifications. Analyses of custom-blend fertilizer products must be performed and reported within a very narrow window in order to be effective. The Colorado Department of Agriculture's Biochemistry Laboratory is an ISO 17025 accredited facility and conducts analyses of custom-blend fertilizer products primarily during the spring planting season. Using the Lean Six Sigma (LSS) process, the Biochemistry Laboratory has reduced turnaround times from as much as 45 days to as little as 3 days. The LSS methodology focuses on waste reduction through identifying: non-value-added steps, unneeded process reviews, optimization of screening and confirmatory analyses, equipment utilization, nonessential reporting requirements, and inefficient personnel deployment. Eliminating these non-value-added activities helped the laboratory significantly shorten turnaround time and reduce costs. Key improvement elements discovered during the LSS process included: focused sample tracking, equipment redundancy, strategic supply stocking, batch size optimization, critical sample paths, elimination of nonessential QC reviews, and more efficient personnel deployment.

  5. Process improvement for regulatory analyses of custom-blend fertilizers.

    Science.gov (United States)

    Wegner, Keith A

    2014-01-01

    Chemical testing of custom-blend fertilizers is essential to ensure that the products meet the formulation requirements. For purposes of proper crop nutrition and consumer protection, regulatory oversight promotes compliance and particular attention to blending and formulation specifications. Analyses of custom-blend fertilizer products must be performed and reported within a very narrow window in order to be effective. The Colorado Department of Agriculture's Biochemistry Laboratory is an ISO 17025 accredited facility and conducts analyses of custom-blend fertilizer products primarily during the spring planting season. Using the Lean Six Sigma (LSS) process, the Biochemistry Laboratory has reduced turnaround times from as much as 45 days to as little as 3 days. The LSS methodology focuses on waste reduction through identifying: non-value-added steps, unneeded process reviews, optimization of screening and confirmatory analyses, equipment utilization, nonessential reporting requirements, and inefficient personnel deployment. Eliminating these non-value-added activities helped the laboratory significantly shorten turnaround time and reduce costs. Key improvement elements discovered during the LSS process included: focused sample tracking, equipment redundancy, strategic supply stocking, batch size optimization, critical sample paths, elimination of nonessential QC reviews, and more efficient personnel deployment. PMID:25051621

  6. Appetitive and regulatory processes in young adolescent drinkers

    NARCIS (Netherlands)

    M.E. van Hemel-Ruiter; P.J. de Jong; R.W. Wiers

    2011-01-01

    Dual-process models of addiction propose that alcohol (mis)use develops because of an imbalance between a fast automatic appetitive system, in which stimuli are valued in terms of their emotional and motivational significance and a slower controlled regulatory system, which acts on deliberate consid

  7. Prospective Activities outlined for Regulatory Approval in Ghana Overview

    Energy Technology Data Exchange (ETDEWEB)

    Abrefah, R.G.; Odoi, H.C.; Mo, S.C.; Morman, J.A.; Liaw, J.

    2015-01-01

    The Ghana Research Reactor-1 (GHARR-1) is one of Chinese’s Miniature Neutron Source Reactor (MNSR) which was purchased under a tripartite agreement between Ghana, China and the IAEA. The reactor was installed in 1994 and has since been in operation without any incident. It has been used chiefly for Neutron Activation Analysis (NAA) and Training of students in the field of Nuclear Engineering. The GHARR-1 has been earmarked for the Conversion of Core from HEU to LEU which is in accordance with the GTRI program and other related and/or associated programs. Over the past few years the National Nuclear Research Institute (NNRI), the Operating Organization of the Research Reactor for the Ghana Atomic Energy Commission (GAEC), has undertaken various tasks in order to implement the replacement of the reactor core. After completion, of the neutronic calculations, results showed that that an LEU fuel of 12.5% enrichment was desirable. However, recent developments have shown that an LEU fuel with 13% enrichment will be fabricated by the manufacturers, which is captured in a fuel specification document sent to NNRI by the CIAE. It is therefore imperative that all neutronic and thermal hydraulic calculation be done again to help acquire regulatory approval. Furthermore, the radiation exposure to personnel involved in the conversion must be estimated to help convince our regulators. This paper outlines the processes and activities that will enable us meet regulatory requirements.

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

    International Nuclear Information System (INIS)

    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

  9. Managing the high level waste nuclear regulatory commission licensing process

    International Nuclear Information System (INIS)

    This paper reports that the process for obtaining Nuclear Regulatory Commission permits for the high level waste storage facility is basically the same process commercial nuclear power plants followed to obtain construction permits and operating licenses for their facilities. Therefore, the experience from licensing commercial reactors can be applied to the high level waste facility. Proper management of the licensing process will be the key to the successful project. The management of the licensing process was categorized into four areas as follows: responsibility, organization, communication and documentation. Drawing on experience from nuclear power plant licensing and basic management principles, the management requirement for successfully accomplishing the project goals are discussed

  10. Multivariate Hawkes process models of the occurrence of regulatory elements

    DEFF Research Database (Denmark)

    Carstensen, L; Sandelin, A; Winther, Ole;

    2010-01-01

    BACKGROUND: A central question in molecular biology is how transcriptional regulatory elements (TREs) act in combination. Recent high-throughput data provide us with the location of multiple regulatory regions for multiple regulators, and thus with the possibility of analyzing the multivariate...... distribution of the occurrences of these TREs along the genome. RESULTS: We present a model of TRE occurrences known as the Hawkes process. We illustrate the use of this model by analyzing two different publically available data sets. We are able to model, in detail, how the occurrence of one TRE is affected....... For each of the two data sets we provide two results: first, a qualitative description of the dependencies among the occurrences of the TREs, and second, quantitative results on the favored or avoided distances between the different TREs. CONCLUSIONS: The Hawkes process is a novel way of modeling the joint...

  11. 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...

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

    International Nuclear Information System (INIS)

    (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.)

  13. System engineering in the Nuclear Regulatory Commission licensing process: Program architecture process and structure

    International Nuclear Information System (INIS)

    In October 1987, the U.S. Nuclear Regulatory Commission (NRC) established the Center for Nuclear Waste Regulatory Analyses at Southwest Research Institute in San Antonio, Texas. The overall mission of the center is to provide a sustained level of high-quality research and technical assistance in support of NRC regulatory responsibilities under the Nuclear Waste Policy Act (NWPA). A key part of that mission is to assist the NRC in the development of the program architecture - the systems approach to regulatory analysis for the NRC high-level waste repository licensing process - and the development and implementation of the computer-based Program Architecture Support System (PASS). This paper describes the concept of program architecture, summarizes the process and basic structure of the PASS relational data base, and describes the applications of the system

  14. Safety and regulatory aspects of radiation processing facilities in India

    International Nuclear Information System (INIS)

    The number of gamma and electron radiation processing facilities (RPFs) is increasing all over the world. This is mainly due to their multifarious applications in the field of medicine, industry, agriculture and research. The most wide spread use of these facilities are for sterilisation of medical and pharmaceutical products, preservation of food stuffs, polymer synthesis and modifications, eradication of insect infestation and in the management of public health and environment. In India, at present, a total of nineteen gamma radiation-processing facilities (GRAPFs) are under operation for various purposes, four are under construction and several facilities have obtained site clearance for installation of GRAPF. There are five radiation processing accelerator (RPA) facilities operating in the country for other than food irradiation purposes. The ISOMED, the first commercial gamma radiation processing plant for sterilisation of medical products was commissioned at the Bhabha Atomic Research Centre (BARC), Mumbai in 1974 by the Department of Atomic Energy (DAE), Government of India. The regulatory controls have been briefly outlined in this article

  15. Establishment of the nuclear regulatory framework for the process of decommissioning of nuclear installations in Mexico

    International Nuclear Information System (INIS)

    Today has not managed any process of decommissioning of nuclear installations in the country; however because of the importance of the subject and the actions to be taken to long term, the Comision Nacional de Seguridad Nuclear y Salvaguardias (CNSNS) in Mexico, accordance with its objectives is developing a National Nuclear Regulatory Framework and defined requirements to ensure the implementation of appropriate safety standards when such activities are performed. In this regard, the national nuclear regulatory framework for nuclear installations and the particular case of nuclear power reactors is presented, as well as a proposed licensing process for the nuclear power plant of Laguna Verde based on international regulations and origin country regulations of the existing reactors in nuclear facilities in accordance with the license conditions of operation to allow to define and incorporate such regulation. (Author)

  16. Oscillatory Activities in Regulatory Biological Networks and Hopf Bifurcation

    Institute of Scientific and Technical Information of China (English)

    YAN Shi-Wei; WANG Qi; XIE Bai-Song; ZHANG Feng-Shou

    2007-01-01

    Exploiting the nonlinear dynamics in the negative feedback loop, we propose a statistical signal-response model to describe the different oscillatory behaviour in a biological network motif. By choosing the delay as a bifurcation parameter, we discuss the existence of Hopf bifurcation and the stability of the periodic solutions of model equations with the centre manifold theorem and the normal form theory. It is shown that a periodic solution is born in a Hopf bifurcation beyond a critical time delay, and thus the bifurcation phenomenon may be important to elucidate the mechanism of oscillatory activities in regulatory biological networks.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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.

  19. Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells

    Science.gov (United States)

    Marcel, Nimi; Sarin, Apurva

    2016-01-01

    Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1-/- Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation. DOI: http://dx.doi.org/10.7554/eLife.14023.001 PMID:27267497

  20. 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.

  1. CO2 – intrinsic product, essential substrate and regulatory trigger of microbial and mammalian production processes

    Directory of Open Access Journals (Sweden)

    Bastian eBlombach

    2015-08-01

    Full Text Available Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. As a consequence CO2/HCO3- dissociation equilibria arise in fermenters by the growing culture. Anaplerotic reactions make use of the abundant CO2/HCO3- levels for refueling citric acid cycle demands and for enabling oxaloacetate derived products. At the same time CO2 is released manifold in metabolic reactions via decarboxylation activity. The levels of extracellular CO2/HCO3- depend on cellular activities and physical constraints such like hydrostatic pressures, aeration and the efficiency of mixing in large-scale bioreactors. Besides, local CO2/HCO3- levels might also act as metabolic inhibitors or transcriptional effectors triggering regulatory events inside the cells. This review gives an overview about fundamental physicochemical properties of CO2/HCO3- in microbial and mammalian cultures effecting cellular physiology, production processes, metabolic activity and transcriptional regulation.

  2. Application of best available science to the regulatory process

    International Nuclear Information System (INIS)

    The current grant is a continuation of a previous grant awarded to the Institute for Regulatory Science. In July, 1989, the functions of the Institute were transferred to the University of Maryland and the studies started at the Institute were continued at the University. The current grant started February 1, 1990. Therefore, much of the discussion in this progress report relies upon the grant funded at the Institute for Regulatory Science. This progress report covers the period from February 1, 1990 to January 31, 1991. The objective of the project is to assure that societal decisions are based on the best available science (BAS). A great deal of progress was made to establish relevant organizations for the development of consensus on relevant scientific information. During the next year, emphasis will be placed on Resource Conservation and Recovery Act (RCRA), particularly as related to its reauthorization and mixed waste

  3. Practical-Moral Knowledge: The Social Organization of Regulatory Processes in Academic Contexts

    Science.gov (United States)

    Stone, Lynda D.; Kerrick, Madeleine R.; Stoeckl, Rita F.

    2013-01-01

    In this article, we developed a theoretical frame to analyze how practical-moral knowledge structures the regulatory processes of learning to control and direct behavior during literacy lessons in two elementary classrooms. We describe how regulatory behaviors were congruent with the local social and moral order, constituents of practical-moral…

  4. Neuroimaging of developmental psychopathologies: the importance of self-regulatory and neuroplastic processes in adolescence.

    Science.gov (United States)

    Spessot, Alexandra L; Plessen, Kerstin J; Peterson, Bradley S

    2004-06-01

    Normal brain maturational and developmental processes, together with plastic reorganization of the brain in response to experiential demands, contribute to the acquisition of improved capacities for self-regulation and impulse control during adolescence. The frontal lobe is a main focus for these developmental and plastic processes during the transition from adolescence into adulthood. Tourette syndrome (TS), defined as the chronic presence of motor and vocal tics, has been increasingly conceptualized as a disorder of impaired self-regulatory control. This disordered control is thought to give rise to semicompulsory urges to perform the movements that constitute simple tics, complex tics, or compulsions. Neuroimaging studies suggest that the expression of the genetic diathesis to TS is influenced by genetic and nongenetic factors affecting activity-dependent reorganization of neuroregulatory systems, thereby influencing the phenotype, illness severity, and adult outcome of tic disorders. Similar developmental processes during adolescence likely determine the phenotype and natural history of a broad range of other complex neuropsychiatric disorders of childhood onset, and they likely contribute to the acquisition of improved self-regulatory capacities that characterize normal adolescent development.

  5. Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation.

    Science.gov (United States)

    Simandi, Zoltan; Horvath, Attila; Nagy, Peter; Nagy, Laszlo

    2016-01-01

    Embryonic development is a multistep process involving activation and repression of many genes. Enhancer elements in the genome are known to contribute to tissue and cell-type specific regulation of gene expression during the cellular differentiation. Thus, their identification and further investigation is important in order to understand how cell fate is determined. Integration of gene expression data (e.g., microarray or RNA-seq) and results of chromatin immunoprecipitation (ChIP)-based genome-wide studies (ChIP-seq) allows large-scale identification of these regulatory regions. However, functional validation of cell-type specific enhancers requires further in vitro and in vivo experimental procedures. Here we describe how active enhancers can be identified and validated experimentally. This protocol provides a step-by-step workflow that includes: 1) identification of regulatory regions by ChIP-seq data analysis, 2) cloning and experimental validation of putative regulatory potential of the identified genomic sequences in a reporter assay, and 3) determination of enhancer activity in vivo by measuring enhancer RNA transcript level. The presented protocol is detailed enough to help anyone to set up this workflow in the lab. Importantly, the protocol can be easily adapted to and used in any cellular model system. PMID:27403939

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

    International Nuclear Information System (INIS)

    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.)

  7. Neuroimaging of developmental psychopathologies: the importance of self-regulatory and neuroplastic processes in adolescence

    DEFF Research Database (Denmark)

    Spessot, Alexandra L; Plessen, Kerstin J; Peterson, Bradley S

    2004-01-01

    for these developmental and plastic processes during the transition from adolescence into adulthood. Tourette syndrome (TS), defined as the chronic presence of motor and vocal tics, has been increasingly conceptualized as a disorder of impaired self-regulatory control. This disordered control is thought to give rise...... to semicompulsory urges to perform the movements that constitute simple tics, complex tics, or compulsions. Neuroimaging studies suggest that the expression of the genetic diathesis to TS is influenced by genetic and nongenetic factors affecting activity-dependent reorganization of neuroregulatory systems, thereby...... influencing the phenotype, illness severity, and adult outcome of tic disorders. Similar developmental processes during adolescence likely determine the phenotype and natural history of a broad range of other complex neuropsychiatric disorders of childhood onset, and they likely contribute to the acquisition...

  8. Health physics self-assessment and the nuclear regulatory oversight process at a nuclear power plant

    International Nuclear Information System (INIS)

    The U.S. Nuclear Regulatory Commission has developed improvements in their Nuclear Power Plant inspection, assessment and enforcement practices. The objective of these changes was to link regulatory action with power plant performance through a risk- informed process which is intended to enhance objectivity. One of the Strategic Performance Areas of focus by the U.S. NRC is radiation safety. Two cornerstones, Occupational Radiation Safety and Public Radiation Safety, make up this area. These cornerstones are being evaluated through U.S. NRC Performance Indicators (PI) and baseline site inspections. Key to the U.S. NRC's oversight program is the ability of the licensee to implement a self-assessment program which pro-actively identifies potential problems and develops improvements to enhance management's effectiveness. The Health Physics Self-Assessment Program at San Onofre Nuclear Generating Station (SONGS) identifies radiation protection-related weakness or negative trends. The intended end result is improved performance through rapid problem identification, timely evaluation, corrective action and follow-up effectiveness reviews. A review of the radiation protection oversight process and the SONGS Health Physics Self-Assessment Program will be presented. Lessons learned and management tools, which evaluate workforce and Health Physics (HP) staff performance to improve radiological practices, are discussed. (author)

  9. Gene-Regulatory Activity of α-Tocopherol

    Directory of Open Access Journals (Sweden)

    John K. Lodge

    2010-03-01

    Full Text Available Vitamin E is an essential vitamin and a lipid soluble antioxidant, at least, under in vitro conditions. The antioxidant properties of vitamin E are exerted through its phenolic hydroxyl group, which donates hydrogen to peroxyl radicals, resulting in the formation of stable lipid species. Beside an antioxidant role, important cell signalling properties of vitamin E have been described. By using gene chip technology we have identified α-tocopherol sensitive molecular targets in vivo including christmas factor (involved in the blood coagulation and 5α-steroid reductase type 1 (catalyzes the conversion of testosterone to 5α-dihydrotestosterone being upregulated and γ-glutamyl-cysteinyl synthetase (the rate limiting enzyme in GSH synthesis being downregulated due to a-tocopherol deficiency. α-Tocopherol regulates signal transduction cascades not only at the mRNA but also at the miRNA level since miRNA 122a (involved in lipid metabolism and miRNA 125b (involved in inflammation are downregulated by α-tocopherol. Genetic polymorphisms may determine the biological and gene-regulatory activity of a-tocopherol. In this context we have recently shown that genes encoding for proteins involved in peripheral α-tocopherol transport and degradation are significantly affected by the apoE genotype.

  10. Evolution of nuclear security regulatory activities in Brazil

    International Nuclear Information System (INIS)

    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)

  11. Evolution of nuclear security regulatory activities in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Luiz A. de; Monteiro Filho, Joselio S.; Belem, Lilia M.J.; Torres, Luiz F.B. [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Diretoria de Radioprotecao e Segurania Nuclear. Coordenacao de Salvaguardas e Protecao Fisica], e-mail: gpf@cnen.gov.br

    2009-07-01

    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)

  12. Paramutation: a process for acquiring trans-generational regulatory states.

    Science.gov (United States)

    Erhard, Karl F; Hollick, Jay B

    2011-04-01

    Basic tenets of Mendelian inheritance are violated by paramutations in which trans-homolog interactions lead to heritable changes in gene regulation and phenotype. First described in plants, similar behaviors have now been noted in diverse eukaryotes. Genetic and molecular studies of paramutations occurring in maize indicate that components of a small interfering RNA (siRNA) biogenesis pathway are required for the maintenance of meiotically heritable regulatory states. Although these findings lead to a hypothesis that siRNAs themselves mediate paramutation interactions, an assessment of existing data supports the opinion that siRNAs alone are insufficient. Recent evidence implies that transcription of paramutation-associated repeats and siRNA-facilitated chromatin changes at affected loci are involved in directing and maintaining the heritable changes in gene regulation that typify paramutations. PMID:21420347

  13. 45 CFR 73a.735-502 - Employees in regulatory activities.

    Science.gov (United States)

    2010-10-01

    ... regulatory activities. (a) An employee in regulatory activities (“control activity” employee) may hold... conditions are met: (i) Retention of the financial interest does not give rise to an actual conflict of... control of the employee that resulted in the interest becoming prohibited; (iii) No direct...

  14. Modelling the conditional regulatory activity of methylated and bivalent promoters

    OpenAIRE

    Budden, David M.; Hurley, Daniel G.; Edmund J Crampin

    2015-01-01

    Background Predictive modelling of gene expression is a powerful framework for the in silico exploration of transcriptional regulatory interactions through the integration of high-throughput -omics data. A major limitation of previous approaches is their inability to handle conditional interactions that emerge when genes are subject to different regulatory mechanisms. Although chromatin immunoprecipitation-based histone modification data are often used as proxies for chromatin accessibility, ...

  15. 2015 Summary Report on Industrial and Regulatory Engagement Activities

    International Nuclear Information System (INIS)

    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.

  16. 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.

  17. Nuclear Regulatory Commission's antitrust review process: an analysis of the impacts

    International Nuclear Information System (INIS)

    The Nuclear Regulatory Commission's (NRC) antitrust process is reviewed and its impacts to small systems and applicant systems are studied. This process takes the form of a description of the NRC's antitrust review process as implemented, a generic categorization of potential impacts and individual case-by-case studies of four different utilities

  18. Conduct of regulatory review and assessment during the licensing process for nuclear power plants

    International Nuclear Information System (INIS)

    This Safety Guide was prepared as part of the Agency's programme, referred to as the NUSS programme, for establishing Codes of Practice and Safety Guides relating to nuclear power plants. It supplements the Code of Practice on Governmental Organization for the Regulation of Nuclear Power Plants (IAEA Safety Series No. 50-C-G) and is concerned with the review and assessment by the regulatory body of all information submitted in support of licence applications, in the various phases of the licensing process. The purpose of the Guide is to provide information, recommendations and guidance for the conduct of these activities. The scope of the review and assessment will encompass the safety aspects of siting, construction, commissioning, operation and decommissioning of each nuclear power plant

  19. The role of independent scientific and engineering analyses in the regulatory process

    International Nuclear Information System (INIS)

    Since it was established in 1987 by the U.S. Nuclear Regulatory Commission (NRC), the Center for Nuclear Waste Regulatory Analyses (CNWRA) has assisted NRC in fulfilling its responsibilities under the Nuclear Waste Policy Act related to a potential repository at Yucca Mountain, Nevada, and interim storage facilities for spent nuclear fuel and high-level radioactive waste. CNWRA attributes have assured its success in assisting NRC. These attributes include clearly defined roles and responsibilities, which encompass independent scientific and engineering analyses. Examples illustrate how these analyses have enhanced the regulatory process. (author)

  20. Synthesis of TP3 Fragment via One Pot Strategy and Its Immune Regulatory Activity

    Institute of Scientific and Technical Information of China (English)

    WANG Li-feng; CHEN Jie; SHAN Hui-jie; LI Wei

    2005-01-01

    We have modified the previously described one-pot peptide synthesis method. The modified method has been successfully applied to the synthesis of TP3. Furthermore, the immune regulatory activity of TP3 has been characterized. The results show that the modified one-pot method can be used to synthesize the biological active peptide with the advantages of low cost and high productivity. Moreover, TP3 has a higher immune regulatory activity than TP5.

  1. Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination.

    Science.gov (United States)

    Austenaa, Liv M I; Barozzi, Iros; Simonatto, Marta; Masella, Silvia; Della Chiara, Giulia; Ghisletti, Serena; Curina, Alessia; de Wit, Elzo; Bouwman, Britta A M; de Pretis, Stefano; Piccolo, Viviana; Termanini, Alberto; Prosperini, Elena; Pelizzola, Mattia; de Laat, Wouter; Natoli, Gioacchino

    2015-11-01

    Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adaptor protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1 H3K4 methyltransferases and the nuclear protein phosphatase 1 (PP1) complexes to the initiating Pol II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1, or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes and active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs. PMID:26593720

  2. Animal experimentation in Malta : regulatory processes and future perspectives

    OpenAIRE

    Scerri, Charles

    2009-01-01

    Prior to Malta’s accession to the European Union (EU) in May 2004, new legislative processes regulating the use of animals for scientific research purposes were adopted in line with the provisions found under the European Union Council Directive 86/609/EEC. The scope of these regulations is to protect animals used or intended to be used in scientific experimental procedures which may cause pain, suffering, distress or lasting harm, using evaluation procedures that promote refinement, reductio...

  3. 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.

  4. 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)

    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

  5. Regulatory network of inflammation downstream of proteinase-activated receptors

    Directory of Open Access Journals (Sweden)

    Hurst Robert E

    2007-03-01

    Full Text Available Abstract Background Protease-activated receptors (PAR are present in the urinary bladder, and their expression is altered in response to inflammation. PARs are a unique class of G protein-coupled that carry their own ligands, which remain cryptic until unmasked by proteolytic cleavage. Although the canonical signal transduction pathway downstream of PAR activation and coupling with various G proteins is known and leads to the rapid transcription of genes involved in inflammation, the effect of PAR activation on the downstream transcriptome is unknown. We have shown that intravesical administration of PAR-activating peptides leads to an inflammatory reaction characterized by edema and granulocyte infiltration. Moreover, the inflammatory response to intravesical instillation of known pro-inflammatory stimuli such as E. coli lipopolysaccharide (LPS, substance P (SP, and antigen was strongly attenuated by PAR1- and to a lesser extent by PAR2-deficiency. Results Here, cDNA array experiments determined inflammatory genes whose expression is dependent on PAR1 activation. For this purpose, we compared the alteration in gene expression in wild type and PAR1-/- mice induced by classical pro-inflammatory stimuli (LPS, SP, and antigen. 75 transcripts were considered to be dependent on PAR-1 activation and further annotated in silico by Ingenuity Pathways Analysis (IPA and gene ontology (GO. Selected transcripts were target validated by quantitative PCR (Q-PCR. Among PAR1-dependent transcripts, the following have been implicated in the inflammatory process: b2m, ccl7, cd200, cd63, cdbpd, cfl1, dusp1, fkbp1a, fth1, hspb1, marcksl1, mmp2, myo5a, nfkbia, pax1, plaur, ppia, ptpn1, ptprcap, s100a10, sim2, and tnfaip2. However, a balanced response to signals of injury requires a transient cellular activation of a panel of genes together with inhibitory systems that temper the overwhelming inflammation. In this context, the activation of genes such as dusp1 and

  6. Organization and practices on regulatory review in the licensing process of nuclear power plants in Spain

    International Nuclear Information System (INIS)

    The actual organisation, practices and experience of the JEN Nuclear Safety Department on the regulatory review in the licensing process of nuclear power plants in Spain, are presented. Topics to be covered are: The structure, organisation, staff and principal functional areas of the NSD, the academic qualifications and work experience of the NSD personnel, recruiting and training, the conduct of the regulatory review during the licensing process and working procedures, the manpower and coverage of the different technical areas, the principal problems and conclusions. (author)

  7. 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.

  8. One hub-one process: a tool based view on regulatory network topology

    Directory of Open Access Journals (Sweden)

    Sneppen Kim

    2008-03-01

    Full Text Available Abstract Background The relationship between the regulatory design and the functionality of molecular networks is a key issue in biology. Modules and motifs have been associated to various cellular processes, thereby providing anecdotal evidence for performance based localization on molecular networks. Results To quantify structure-function relationship we investigate similarities of proteins which are close in the regulatory network of the yeast Saccharomyces Cerevisiae. We find that the topology of the regulatory network only show weak remnants of its history of network reorganizations, but strong features of co-regulated proteins associated to similar tasks. These functional correlations decreases strongly when one consider proteins separated by more than two steps in the regulatory network. The network topology primarily reflects the processes that is orchestrated by each individual hub, whereas there is nearly no remnants of the history of protein duplications. Conclusion Our results suggests that local topological features of regulatory networks, including broad degree distributions, emerge as an implicit result of matching a number of needed processes to a finite toolbox of proteins.

  9. 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.

  10. Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression

    OpenAIRE

    Fairfax, B. P.; Humburg, P.; Makino, S.; Naranbhai, V; Wong, D.; Lau, E; Jostins, L; Plant, K.; Andrews, R; McGee, C.; Knight, J.C.

    2014-01-01

    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-eQTL...

  11. Emergent self-regulatory activity among young children during scientific inquiry: An analysis of six kindergarten children

    Science.gov (United States)

    Lomangino, Adrienne Gelpi

    2000-10-01

    This qualitative investigation extends the study of self-regulation to examine young children's developing self-regulated learning competencies. The framework for this research draws upon social cognitive, developmental, and sociocultural perspectives on self-regulation and research on children's scientific thinking. Taking a multiple case study approach, this study examines six kindergarten children's emerging self-regulatory competencies during inquiry-based science instruction. Data were collected during two inquiry-based science programs of study, one pertaining to light and shadow and a second pertaining to motion on inclined planes. Data sources included: videotaped records of the instruction, transcriptions of the videotapes, interviews with the children and teacher, student work, and field notes. Taking an inductive approach to analysis, patterns in the children's activity were identified through a recursive process of defining and refining categories that characterized the children's verbal and behavioral activity. Each case study examines a child's behavior within each phase of the inquiry for evidence of emerging self-regulatory competence. Analysis revealed nascent forms of goal-setting and planning, monitoring, resource management, seeking social assistance, and evaluating. Monitoring activity occurred more frequently than planning or evaluating. For several children, animating materials served to promote motivation. Children's efforts to support peers' activity and monitor the meaning of ongoing discourse contrast with common assumptions about children's attention to others' thinking. Variations in self-regulatory activity were found across phases of instruction. The children exhibited interpersonal self-regulatory efforts, in which monitoring and control of the self was entwined with the activity of others. Joint participation also played a critical role in supporting the metacognitive demands of self-regulation and prompting metacognitive awareness

  12. The regulatory perspective: Role of regulatory review of the safety case for preparing and performing the Swiss site selection process

    International Nuclear Information System (INIS)

    Swiss legislation requires for all types of radioactive waste the safe and permanent disposal in deep geological repositories within Switzerland by stipulating a step-by-step procedure for site selection and licensing of the disposal facilities. Each step requires safety considerations or safety analyses which are reviewed by the Swiss Federal Nuclear Safety Inspectorate (ENSI, former HSK). The principle steps of radioactive waste disposal include: i) Demonstration of disposal feasibility for all types of radioactive waste in Switzerland. ii) Site selection process in three stages to narrow down the number of suitable sites to one for realisation ('Sectoral Plan for Geological Repositories'). iii) Construction, operation and closure of the repositories according to Swiss legislation in five steps [licence for geological investigations, general licence (decision-in-principle), construction licence, operation licence, closure order. Step i) was completed in 2006 when the Swiss Federal Council (Swiss federal government) approved the demonstration of disposal feasibility for high-level and long-lived intermediate level waste submitted by the implementer in 2002. The site selection process started in 2008 [Step ii)] according to a site selection concept (BFE, 2008) which was approved by the Federal Council after broad consultation. The process is organised and co-ordinated by the Swiss Federal Office of Energy (SFOE, in German BFE) and is carried out in accordance with the land use planning legislation. Safety is of highest priority in the site selection process, but socioeconomic aspects are also taken into account. The site selection procedure is based on a stepwise approach. In the first of three stages, six potential siting areas for L/ILW and three potential siting areas for HLW were proposed by the implementer (Nagra) for each repository type, based on safety criteria defined by the regulatory authority ENSI. ENSI has reviewed the documentation and has agreed with

  13. Patients' perspectives on the role of their complaints in the regulatory process

    NARCIS (Netherlands)

    R. Bouwman (Renée); M. Bomhoff (Manja); P.B.M. Robben (Paul); R.D. Friele (Roland)

    2016-01-01

    textabstractBackground: Governments in several countries are facing problems concerning the accountability of regulators in health care. Questions have been raised about how patients' complaints should be valued in the regulatory process. However, it is not known what patients who made complaints ex

  14. Modelling non-stationary dynamic gene regulatory processes with the BGM model

    NARCIS (Netherlands)

    Grzegorczyk, Marco; Husmeier, Dirk; Rahnenfuehrer, Joerg

    2011-01-01

    Recently, a Bayesian network model for inferring non-stationary regulatory processes from gene expression time series has been proposed. The Bayesian Gaussian Mixture (BGM) Bayesian network model divides the data into disjunct compartments (data subsets) by a free allocation model, and infers networ

  15. Self-Regulatory Processes Mediate the Intention-Behavior Relation for Adherence and Exercise Behaviors

    NARCIS (Netherlands)

    Bruin, de M.; Sheeran, P.; Kok, G.; Hiemstra, A.; Prins, J.M.; Hospers, H.J.; Breukelen, G.J.P.

    2012-01-01

    Objectives: Understanding the gap between people's intentions and actual health behavior is an important issue in health psychology. Our aim in this study was to investigate whether self-regulatory processes (monitoring goal progress and responding to discrepancies) mediate the intention-behavior re

  16. Self-regulatory processes mediate the intention-behavior relation for adherence and exercise behaviors

    NARCIS (Netherlands)

    M. de Bruin; P. Sheeran; G. Kok; A. Hiemstra; J.M. Prins; H.J. Hospers; G.J.P. van Breukelen

    2012-01-01

    Objectives: Understanding the gap between people's intentions and actual health behavior is an important issue in health psychology. Our aim in this study was to investigate whether self-regulatory processes (monitoring goal progress and responding to discrepancies) mediate the intention-behavior re

  17. 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.; Copping, Andrea E.; Van Cleve, Frances B.; Blake, Kara M.; Hanna, Luke A.

    2011-09-30

    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. Objectives for Task 2.1.7 are the following: • to work with stakeholders to streamline the MHK regulatory permitting process • to work with stakeholders to gather information on needs and priorities for environmental assessment of MHK development • to communicate research findings and directions to the MHK industry and stakeholders • to engage in spatial planning processes in order to further the development of the MHK industry. These objectives are met through three subtasks, each of which is described in this report: • 2.1.7.1—Regulatory Assistance • 2.1.7.2—Stakeholder Outreach • 2.1.7.3—Coastal and Marine Spatial Planning. As MHK industry partners work with the regulatory community and stakeholders to plan, site, permit, and license MHK technologies, they have an interest in a predictable, efficient, and transparent process. Stakeholders and regulators have an interest in processes that result in sustainable use of ocean space with minimal effects to existing ocean users. Both stakeholders and regulators have an interest in avoiding legal challenges by meeting the intent of federal, state, and local laws that govern siting and operation of MHK technologies. The intention of work under Task 2.1.7 is to understand and work to address these varied interests, reduce conflict, identify efficiencies, and ultimately reduce the regulatory costs, time, and potential environmental impacts associated with developing, siting, permitting, and deploying MHK systems.

  18. Using giant scarlet runner bean embryos to uncover regulatory networks controlling suspensor gene activity

    Directory of Open Access Journals (Sweden)

    Kelli F. Henry

    2015-02-01

    Full Text Available One of the major unsolved issues in plant development is understanding the regulatory networks that control the differential gene activity that is required for the specification and development of the two major embryonic regions, the embryo proper and suspensor. Historically, the giant embryo of scarlet runner bean (SRB, Phaseolus coccineus, has been used as a model system to investigate the physiological events that occur early in embryogenesis – focusing on the question of what role the suspensor region plays. A major feature distinguishing SRB embryos from those of other plants is a highly enlarged suspensor containing at least 200 cells that synthesize growth regulators required for subsequent embryonic development. Recent studies have exploited the giant size of the SRB embryo to micro-dissect the embryo proper and suspensor regions in order to use genomics-based approaches to identify regulatory genes that may be involved in controlling suspensor and embryo proper differentiation, as well as the cellular processes that may be unique to each embryonic region. Here we review the current genomics resources that make SRB embryos a compelling model system for studying the early events required to program embryo development.

  19. The Chromatin-Modifying Enzyme Ezh2 Is Critical for the Maintenance of Regulatory T Cell Identity after Activation

    OpenAIRE

    DuPage, Michel; Chopra, Gaurav; Quiros, Jason; Rosenthal, Wendy L.; Morar, Malika M.; Holohan, Dan; Zhang, Ruan; Turka, Laurence; Marson, Alexander; Bluestone, Jeffrey A.

    2015-01-01

    Regulatory T cells (Treg cells) are required for immune homeostasis. Chromatin remodeling is essential for establishing diverse cellular identities, but how the epigenetic program in Treg cells is maintained throughout the dynamic activation process remains unclear. Here we have shown that CD28 co-stimulation, an extracellular cue intrinsically required for Treg cell maintenance, induced the chromatin-modifying enzyme, Ezh2. Treg-specific ablation of Ezh2 resulted in spontaneous autoimmunity ...

  20. Magnetohydrodynamic process in solar activity

    Directory of Open Access Journals (Sweden)

    Jingxiu Wang

    2014-01-01

    Full Text Available Magnetohydrodynamics is one of the major disciplines in solar physics. Vigorous magnetohydrodynamic process is taking place in the solar convection zone and atmosphere. It controls the generating and structuring of the solar magnetic fields, causes the accumulation of magnetic non-potential energy in the solar atmosphere and triggers the explosive magnetic energy release, manifested as violent solar flares and coronal mass ejections. Nowadays detailed observations in solar astrophysics from space and on the ground urge a great need for the studies of magnetohydrodynamics and plasma physics to achieve better understanding of the mechanism or mechanisms of solar activity. On the other hand, the spectacular solar activity always serves as a great laboratory of magnetohydrodynamics. In this article, we reviewed a few key unresolved problems in solar activity studies and discussed the relevant issues in solar magnetohydrodynamics.

  1. Career management: an active process.

    Science.gov (United States)

    Mackowiak, J; Eckel, F M

    1985-03-01

    The self-assessment, goal-setting, and career-planning techniques of career management are discussed, and the organization's role in career management is discussed. Career management is a planned process, initiated and carried out by an individual with the assistance of others. Because work and nonwork activities are so interrelated, career and life management planning can maximize a pharmacist's personal success. The career- and life-management process begins with the development of a personal definition of success. A self-assessment must be made of one's values, needs, interests, and activities. The next step of the process involves setting goals and establishing a plan or strategy to achieve them. Establishing a career path requires researching alternate career goals. Career competencies are identified that can increase an employee's chances of success. The employer shares the responsibility for career development through coaching, job structuring, and keeping the employee aware of constraints. Through the integration of the roles of the individual and the organization in the career-management process, employees can optimize their contribution to an organization. Pharmacists can successfully manage their careers by applying the techniques of self-assessment, goal setting, and career planning. PMID:3985018

  2. Transcriptional Regulatory Circuits Controlling Brown Fat Development and Activation

    OpenAIRE

    Seale, Patrick

    2015-01-01

    Brown and beige adipose tissue is specialized for heat production and can be activated to reduce obesity and metabolic dysfunction in animals. Recent studies also have indicated that human brown fat activity levels correlate with leanness. This has revitalized interest in brown fat biology and has driven the discovery of many new regulators of brown fat development and function. This review summarizes recent advances in our understanding of the transcriptional mechanisms that control brown an...

  3. Systematic Approach to Computational Design of Gene Regulatory Networks with Information Processing Capabilities.

    Science.gov (United States)

    Moskon, Miha; Mraz, Miha

    2014-01-01

    We present several measures that can be used in de novo computational design of biological systems with information processing capabilities. Their main purpose is to objectively evaluate the behavior and identify the biological information processing structures with the best dynamical properties. They can be used to define constraints that allow one to simplify the design of more complex biological systems. These measures can be applied to existent computational design approaches in synthetic biology, i.e., rational and automatic design approaches. We demonstrate their use on a) the computational models of several basic information processing structures implemented with gene regulatory networks and b) on a modular design of a synchronous toggle switch.

  4. Evaluation of regulatory processes affecting nuclear power plant early site approval and standardization

    International Nuclear Information System (INIS)

    This report presents the results of a survey and evaluation of existing federal, state and local regulatory considerations affecting siting approval of power plants in the United States. Those factors that may impede early site approval of nuclear power plants are identified, and findings related to the removal of these impediments and the general improvement of the approval process are presented. A brief evaluation of standardization of nuclear plant design is also presented

  5. 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.

  6. [ASSESSMENT OF EXTREME FACTORS OF SHIFT WORK IN ARCTIC CONDITIONS BY WORKERS WITH DIFFERENT REGULATORY PROCESSES].

    Science.gov (United States)

    Korneeva, Ya A; Simonova, N N

    2016-01-01

    A man working on a shift basis in the Arctic, every day is under the influence of various extreme factors which are inevitable for oil and gas indudtry. To adapt to shift work employees use various resources of the individual. The purpose of research is the determination of personal resources of shift workers to overcome the adverse factors of the environment in the Arctic. The study involved 191 builder of main gas pipelines, working in shifts in the Tyumen region (the length of the shift 52 days of arrival) at the age of 23 to 59 (mean age 34.9 ± 8.1) years. Methods: psychological testing, questioning, observation, descriptive statistics, discriminant step by step analysis. There was revealed the correlation between the subjective assessment of the majority of adverse climatic factors in the regulatory process "assessment of results"; production factors--regulatory processes such as flexibility, autonomy, simulation, and the general level of self-regulation; social factors are more associated with the severity of such regulatory processes, flexibility and evaluation of results. PMID:27430072

  7. The regulatory cascade that activates the Hrp regulon in Erwinia herbicola pv. gypsophilae.

    Science.gov (United States)

    Nizan-Koren, R; Manulis, S; Mor, H; Iraki, N M; Barash, I

    2003-03-01

    The pathogenicity of Erwinia herbicola pv. gypsophilae (Ehg) is dependent on a plasmid (pPATH(Ehg)) that harbors the hrp gene cluster and additional virulence genes. The hrp regulatory cascade of Ehg comprises an hrpXY operon encoding a two-component system; hrpS encoding a transcriptional factor of the NtrC family and hrpL encoding an alternative sigma factor. Results obtained suggest the following signal transduction model for activating the Hrp regulon: phosphorylated HrpY activates hrpS, HrpS activates hrpL, and HrpL activates genes containing "hrp box" promoter. This model was supported by studies on the effects of mutations in the regulatory genes on pathogenicity and complementation analysis. Nonpolar mutations in hrpX did not affect virulence or transcription of downstream genes. Site-directed mutagenesis of the conserved aspartate 57 in HrpY suggested that its phosphorylation is crucial for activating the hrp regulatory cascade. Studies on the effects of mutations in the hrp regulatory genes on transcriptional activity of downstream genes or of their isolated promoters in planta showed dependency of hrpS expression on active HrpY, of hrpL expression on active HrpS, and of hrpN or hrpJ expression on active HrpL. These results were also partially supported by overexpression of regulatory genes under in vitro conditions. The hrpXY is constitutively expressed with high basal levels under repressive conditions, in contrast to hrpS and hrpL, which exhibit low basal expression levels and are environmentally regulated. PMID:12650456

  8. A novel processing system of sterol regulatory element-binding protein-1c regulated by polyunsaturated fatty acid.

    Science.gov (United States)

    Nakakuki, Masanori; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Mizuguchi, Kiyoshi; Shimano, Hitoshi

    2014-05-01

    The proteolytic cascade is the key step in transactivation of sterol regulatory element-binding proteins (SREBPs), a transcriptional factor of lipid synthesis. Proteolysis of SREBP-2 is strictly regulated by sterols, but that of SREBP-1c was not strongly sterol-regulated, but inhibited by polyunsaturated fatty acids (PUFAs). In this study, the proteolytic processing of SREBP-1 and -2 was examined by transfection studies of cDNA-encoding mutants in which all the known cleavage sites were disrupted. In cultured cells, sterol-regulated SREBP-2 processing was completely eliminated by mutation of cleavage sites. In contrast, the corresponding SREBP-1c mutants as well as wild type exhibited large amounts of cleaved products in the nuclear extracts from culture cells and murine liver in vivo. The nuclear form of the mutant SREBP-1c was induced by delipidated condition and suppressed by eicosapentaenoic acid, an n-3 PUFA, but not by sterols. This novel processing mechanism was affected by neither SREBP cleavage-activating protein (SCAP) nor insulin-induced gene (Insig)-1, unlike SREBP-2, but abolished by a serine protease inhibitor. Through analysis of deletion mutant, a site-2 protease recognition sequence (DRSR) was identified to be involved in this novel processing. These findings suggest that SREBP-1c cleavage could be subjected to a novel PUFA-regulated cleavage system in addition to the sterol-regulatory SCAP/Insig system.

  9. CO2 - Intrinsic Product, Essential Substrate, and Regulatory Trigger of Microbial and Mammalian Production Processes.

    Science.gov (United States)

    Blombach, Bastian; Takors, Ralf

    2015-01-01

    Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. As a consequence, [Formula: see text] dissociation equilibria arise in fermenters by the growing culture. Anaplerotic reactions make use of the abundant [Formula: see text] levels for refueling citric acid cycle demands and for enabling oxaloacetate-derived products. At the same time, CO2 is released manifold in metabolic reactions via decarboxylation activity. The levels of extracellular [Formula: see text] depend on cellular activities and physical constraints such as hydrostatic pressures, aeration, and the efficiency of mixing in large-scale bioreactors. Besides, local [Formula: see text] levels might also act as metabolic inhibitors or transcriptional effectors triggering regulatory events inside the cells. This review gives an overview about fundamental physicochemical properties of [Formula: see text] in microbial and mammalian cultures effecting cellular physiology, production processes, metabolic activity, and transcriptional regulation. PMID:26284242

  10. Distribution of the trehalase activation response and the regulatory trehalase gene among yeast species.

    Science.gov (United States)

    Soto, T; Fernández, J; Cansado, J; Vicente, J; Gacto, M

    1997-12-01

    In Saccharomyces cerevisiae and other yeasts the activity of regulatory trehalases increases in response to the addition of glucose and to thermal changes in the extracellular medium. We have performed an screening on the extent of this response among different representative yeast species and the results show that this ability is displayed only by a few members of the Saccharomycetaceae family. However, all yeasts examined contain a gene related to that coding for regulatory trehalase in S. cerevisiae. This finding reveals that the operational distinction between regulatory and nonregulatory trehalase in yeasts is not a property of the enzyme by itself but relays on the expression of accompanying mechanisms able to modulate trehalase activity.

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

    International Nuclear Information System (INIS)

    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

  12. 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

    2014-03-01

    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. PMID:24604202

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

    Science.gov (United States)

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

    1998-01-01

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

  14. Neuroimaging of developmental psychopathologies: the importance of self-regulatory and neuroplastic processes in adolescence

    DEFF Research Database (Denmark)

    Spessot, Alexandra L; Plessen, Kerstin J; Peterson, Bradley S

    2004-01-01

    influencing the phenotype, illness severity, and adult outcome of tic disorders. Similar developmental processes during adolescence likely determine the phenotype and natural history of a broad range of other complex neuropsychiatric disorders of childhood onset, and they likely contribute to the acquisition...... for these developmental and plastic processes during the transition from adolescence into adulthood. Tourette syndrome (TS), defined as the chronic presence of motor and vocal tics, has been increasingly conceptualized as a disorder of impaired self-regulatory control. This disordered control is thought to give rise...

  15. Radiation processing activities at OGFL

    International Nuclear Information System (INIS)

    CONCAST group of Industries has set up the first Radiation Processing Plant in Eastern India as 'VIKIRAN' named as Organic Green Foods Ltd., situated at Dankuni (Durgapur Highway Express) 25 km away from central Kolkata on August 21, 2004. Shri Sanjay Sureka, Managing Director of Organic Green Foods Ltd., Kolkata belongs to the famous CONCAST Group of Industries operates the largest plant of West Bengal engaged in manufacturing of Steel Industry. The facility was aimed at improving the quality of healthcare products and devices as well as Laboratory, Spice, Herbal and Ayurvedic Products of large volumes on an industrial scale. The operation of VIKIRAN for the last ten years, has unambiguously proved that both the above objectives have been fully met and now radiation sterilization has emerged as an efficient and effective industrial process. The irradiator is a panoramic wet storage class-IV type. This Facility is designed for 1000 KCi activity of source and is suitable in medium and high dose range application. VIKIRAN offers radiation sterilization service to more than 100 manufacturers

  16. Use of PSA in the regulatory process. Report of the specialist's meeting. Working material

    International Nuclear Information System (INIS)

    The objective of this meeting was to focus on the role of the regulator in relation to PSA, to give a picture of the present status, and near term plans, of the requirements placed on licensees and of the uses, formal and informal, made of PSA in regulatory decision making. One such use, in which there is currently much interest, is known as Risk-Based Regulation. This term has various connotations but essentially refers to a more flexible and efficient application of Technical Specifications in the interests of gains in both economy and safety. The position in many countries is one of change in the use of PSA by regulators, and hence any report can only give a snapshot in time. It has to be noted that a number of countries, with important nuclear power programmes, were not represented at the meeting, and so the overall picture is not as comprehensive as might have been hoped. The field of the discussion in the meeting was divided into three areas, progressed in three working groups, namely: Regulatory requirements related to PSA, Regulatory uses of PSA, and Risk-Based Regulation. The outcomes are covered in the next three sections. The fifth section of this report gives the overall conclusions of the meeting and the final section makes some recommendations for future IAEA activities in these areas. Refs, figs, tabs

  17. The role of learning environment on high school chemistry students' motivation and self-regulatory processes

    Science.gov (United States)

    Judd, Jeffrey S.

    Changes to the global workforce and technological advancements require graduating high school students to be more autonomous, self-directed, and critical in their thinking. To reflect societal changes, current educational reform has focused on developing more problem-based, collaborative, and student-centered classrooms to promote effective self-regulatory learning strategies, with the goal of helping students adapt to future learning situations and become life-long learners. This study identifies key features that may characterize these "powerful learning environments", which I term "high self-regulating learning environments" for ease of discussion, and examine the environment's role on students' motivation and self-regulatory processes. Using direct observation, surveys, and formal and informal interviews, I identified perceptions, motivations, and self-regulatory strategies of 67 students in my high school chemistry classes as they completed academic tasks in both high and low self-regulating learning environments. With social cognitive theory as a theoretical framework, I then examined how students' beliefs and processes changed after they moved from low to a high self-regulating learning environment. Analyses revealed that key features such as task meaning, utility, complexity, and control appeared to play a role in promoting positive changes in students' motivation and self-regulation. As embedded cases, I also included four students identified as high self-regulating, and four students identified as low self-regulating to examine whether the key features of high and low self-regulating learning environments played a similar role in both groups. Analysis of findings indicates that key features did play a significant role in promoting positive changes in both groups, with high self-regulating students' motivation and self-regulatory strategies generally remaining higher than the low self-regulating students; this was the case in both environments. Findings

  18. Actual operation and regulatory activities on steam generator replacement in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Saeki, Hitoshi [Kyushu Electric Power Co., Inc., Fukyoka (Japan)

    1997-02-01

    This paper summarizes the operating reactors in Japan, and the status of the steam generators in these plants. It reviews plans for replacement of existing steam generators, and then goes into more detail on the planning and regulatory steps which must be addressed in the process of accomplishing this maintenance. The paper also reviews the typical steps involved in the process of removal and replacement of steam generators.

  19. Regulatory issues associated with exclusion, exemption, and clearance related to the mining and minerals processing industries

    International Nuclear Information System (INIS)

    The concepts of exclusion, exemption and clearance have been established in international recommendations and, standards for radiation protection and the management of radioactive waste in recent years. The consistent application of these concepts has given rise to various problems in different spheres of use. This is particularly the case in the mining and minerals processing industries dealing with materials exhibiting elevated concentrations of naturally occurring radionuclides. This paper takes the South African mining industry as an example and highlights some of the issues that have arisen in applying these concepts within a regulatory control regime. (author)

  20. Protein phosphatase 2A regulatory subunit B56α limits phosphatase activity in the heart.

    Science.gov (United States)

    Little, Sean C; Curran, Jerry; Makara, Michael A; Kline, Crystal F; Ho, Hsiang-Ting; Xu, Zhaobin; Wu, Xiangqiong; Polina, Iuliia; Musa, Hassan; Meadows, Allison M; Carnes, Cynthia A; Biesiadecki, Brandon J; Davis, Jonathan P; Weisleder, Noah; Györke, Sandor; Wehrens, Xander H; Hund, Thomas J; Mohler, Peter J

    2015-07-21

    Protein phosphatase 2A (PP2A) is a serine/threonine-selective holoenzyme composed of a catalytic, scaffolding, and regulatory subunit. In the heart, PP2A activity is requisite for cardiac excitation-contraction coupling and central in adrenergic signaling. We found that mice deficient in the PP2A regulatory subunit B56α (1 of 13 regulatory subunits) had altered PP2A signaling in the heart that was associated with changes in cardiac physiology, suggesting that the B56α regulatory subunit had an autoinhibitory role that suppressed excess PP2A activity. The increase in PP2A activity in the mice with reduced B56α expression resulted in slower heart rates and increased heart rate variability, conduction defects, and increased sensitivity of heart rate to parasympathetic agonists. Increased PP2A activity in B56α(+/-) myocytes resulted in reduced Ca(2+) waves and sparks, which was associated with decreased phosphorylation (and thus decreased activation) of the ryanodine receptor RyR2, an ion channel on intracellular membranes that is involved in Ca(2+) regulation in cardiomyocytes. In line with an autoinhibitory role for B56α, in vivo expression of B56α in the absence of altered abundance of other PP2A subunits decreased basal phosphatase activity. Consequently, in vivo expression of B56α suppressed parasympathetic regulation of heart rate and increased RyR2 phosphorylation in cardiomyocytes. These data show that an integral component of the PP2A holoenzyme has an important inhibitory role in controlling PP2A enzyme activity in the heart.

  1. Sensitivity, child regulatory processes, and naturally occurring declines in antisocial behavior across childhood.

    Science.gov (United States)

    Buck, Katharine Ann

    2014-12-01

    Despite considerable research on why antisocial behavior develops and interventions that reduce it, aspects of everyday family processes that may promote naturally occurring declines in antisocial behavior or that may result from such declines in most children without intervention are poorly understood. The current study explored family processes that may enable children to replace antisocial tendencies and the effects that declines in antisocial behavior may have on parenting and child regulatory processes. Longitudinal data from 1,022 children (54 months-6th grade) from the NICHD Study of Early Child Care and Youth Development were examined. Findings demonstrated that naturally occurring declines in antisocial behavior both predicted and were predicted by maternal sensitivity, emotion regulation, and social skills. These declines predicted but were not predicted by declines in hostile attributions. The data revealed multiple indirect paths, which highlight the complex nature of these variables across development.

  2. IMMUNOBIOLOGICAL ACTIVITY OF REGULATORY PEPTIDE FRACTIONS SYNTHESIZED BY NEUTROPHILS, AS TESTED IN A MACROPHAGE MODEL

    Directory of Open Access Journals (Sweden)

    G. I. Vasilieva

    2010-01-01

    Full Text Available The article presents experimental data on regulatory effect of neutrophilokine helper fractions on the macrophage (Mph functional activity in the course of antiplague immunity formation. It has revealed that these fractions content biologically active, low-molecular weight peptides. They stimulate Mph killing activity by increasing phagosome-lysosome fusion, thus boosting transformation of monocytes to Mph, and causing redistribution of macrophage subpopulations in the total cellular pool. The helper effect of neutrophilokine fractions upon functional activity of MPh is more pronounced during secondary immune response.

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

    International Nuclear Information System (INIS)

    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)

  4. Activation of protein phosphatase 1 by a small molecule designed to bind to the enzyme's regulatory site.

    Science.gov (United States)

    Tappan, Erin; Chamberlin, A Richard

    2008-02-01

    The activity of protein phosphatase 1 (PP1), a serine-threonine phosphatase that participates ubiquitously in cellular signaling, is controlled by a wide variety of regulatory proteins that interact with PP1 at an allosteric regulatory site that recognizes a "loose" consensus sequence (usually designated as RVXF) found in all such regulatory proteins. Peptides containing the regulatory consensus sequence have been found to recapitulate the binding and PP1 activity modulation of the regulatory proteins, suggesting that it might be possible to design small-molecule surrogates that activate PP1 rather than inhibiting it. This prospect constitutes a largely unexplored way of controlling signaling pathways that could be functionally complementary to the much more extensively explored stratagem of kinase inhibition. Based on these principles, we have designed a microcystin analog that activates PP1. PMID:18291321

  5. The safety and regulatory process for low calorie sweeteners in the United States.

    Science.gov (United States)

    Roberts, Ashley

    2016-10-01

    Low calorie sweeteners are some of the most thoroughly tested and evaluated of all food additives. Products including aspartame and saccharin, have undergone several rounds of risk assessment by the United States Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA), in relation to a number of potential safety concerns, including carcinogenicity and more recently, effects on body weight gain, glycemic control and effects on the gut microbiome. The majority of the modern day sweeteners; acesulfame K, advantame, aspartame, neotame and sucralose have been approved in the United States through the food additive process, whereas the most recent sweetener approvals for steviol glycosides and lo han guo have occurred through the Generally Recognized as Safe (GRAS) system, based on scientific procedures. While the regulatory process and review time of these two types of sweetener evaluations by the FDA differ, the same level of scientific evidence is required to support safety, so as to ensure a reasonable certainty of no harm.

  6. Panel discussion on 'the clearance of very low activity materials from regulatory control'

    International Nuclear Information System (INIS)

    'Full text:' Some activities on nuclear sites such as decommissioning generate large volumes of uncontaminated waste. What is an appropriate degree of rigour to apply to demonstrate that wastes are not contaminated, and are therefore suitable for release from regulatory control so they can be reused, recycled or disposed of in conventional waste facilities? Is there a level of demonstration that is practical to demonstrate on the scale required? If not, what are the practical alternatives for dealing with such wastes? (author)

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

    International Nuclear Information System (INIS)

    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

  8. Anticipated Activities in Maritime Work, Process Control, and Business Processes

    DEFF Research Database (Denmark)

    Andersen, Peter Bøgh

    2004-01-01

    Most activities are anticipated before they are executed. The paper presents methods for describing this anticipated state and the processes that may lead to a new state where the activities are executed. The method builds on linguistic case-theory....

  9. The Amino Acid Specificity for Activation of Phenylalanine Hydroxylase Matches the Specificity for Stabilization of Regulatory Domain Dimers.

    Science.gov (United States)

    Zhang, Shengnan; Hinck, Andrew P; Fitzpatrick, Paul F

    2015-08-25

    Liver phenylalanine hydroxylase is allosterically activated by phenylalanine. The structural changes that accompany activation have not been identified, but recent studies of the effects of phenylalanine on the isolated regulatory domain of the enzyme support a model in which phenylalanine binding promotes regulatory domain dimerization. Such a model predicts that compounds that stabilize the regulatory domain dimer will also activate the enzyme. Nuclear magnetic resonance spectroscopy and analytical ultracentrifugation were used to determine the ability of different amino acids and phenylalanine analogues to stabilize the regulatory domain dimer. The abilities of these compounds to activate the enzyme were analyzed by measuring their effects on the fluorescence change that accompanies activation and on the activity directly. At concentrations of 10-50 mM, d-phenylalanine, l-methionine, l-norleucine, and (S)-2-amino-3-phenyl-1-propanol were able to activate the enzyme to the same extent as 1 mM l-phenylalanine. Lower levels of activation were seen with l-4-aminophenylalanine, l-leucine, l-isoleucine, and 3-phenylpropionate. The ability of these compounds to stabilize the regulatory domain dimer agreed with their ability to activate the enzyme. These results support a model in which allosteric activation of phenylalanine hydroxylase is linked to dimerization of regulatory domains.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    Phan, Huy P

    2010-05-01

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

  12. Improving regulatory effectiveness in federal/state siting actions: water supplies and the nuclear licensing process

    International Nuclear Information System (INIS)

    The Interstate Conference on Water Problems (ICWP) is a national association of State, intrastate, and interstate officials concerned with water resources administration and related matters. The Conference was established in 1959 as an outgrowth of regional conferences on water problems as recognized in the same year by action of the General Assembly of the States. This report was produced by the Interstate Conference on Water Problems in an effort to provide a compilation and summary of the views of selected States regarding relationships of water supplies to the nuclear power plant licensing process. This publication does not represent the official position of the U.S Water Resources Council, or the U.S. Nuclear Regulatory Commission, nor does it represent the position of any single state or the ICWP

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

  20. Investigating relationship between self- and co-regulatory learning processes in a workplace e-learning system

    NARCIS (Netherlands)

    Rahimi, E.; Tampinongkol, S.; Sedighi, M.; Van den Berg, J.; Veen, W.

    2014-01-01

    While supporting regulatory learning processes in work environments is increasingly becoming important, there is not a clear picture of the interaction between self- and coregulatory processes performed by learners in workplace e-learning systems. In this paper, by following a design-based research

  1. Magnetohydrodynamic process in solar activity

    OpenAIRE

    Jingxiu Wang; Jie Jiang

    2014-01-01

    Magnetohydrodynamics is one of the major disciplines in solar physics. Vigorous magnetohydrodynamic process is taking place in the solar convection zone and atmosphere. It controls the generating and structuring of the solar magnetic fields, causes the accumulation of magnetic non-potential energy in the solar atmosphere and triggers the explosive magnetic energy release, manifested as violent solar flares and coronal mass ejections. Nowadays detailed observations in solar astrophysics from s...

  2. Distinct regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID.

    Science.gov (United States)

    Bhaumik, Sukesh R

    2011-02-01

    A growing number of human diseases are linked to abnormal gene expression which is largely controlled at the level of transcriptional initiation. The gene-specific activator promotes the initiation of transcription through its interaction with one or more components of the transcriptional initiation machinery, hence leading to stimulated transcriptional initiation or activation. However, all activator proteins do not target the same component(s) of the transcriptional initiation machinery. Rather, they can have different target specificities, and thus, can lead to distinct mechanisms of transcriptional activation. Two such distinct mechanisms of transcriptional activation in yeast are mediated by the SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID (Transcription factor IID) complexes, and are termed as "SAGA-dependent" and "TFIID-dependent" transcriptional activation, respectively. SAGA is the target of the activator in case of SAGA-dependent transcriptional activation, while the targeting of TFIID by the activator leads to TFIID-dependent transcriptional activation. Both the SAGA and TFIID complexes are highly conserved from yeast to human, and play crucial roles in gene activation among eukaryotes. The regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID are discussed here. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough!

  3. Perilipin-mediated lipid droplet formation in adipocytes promotes sterol regulatory element-binding protein-1 processing and triacylglyceride accumulation.

    Directory of Open Access Journals (Sweden)

    Yu Takahashi

    Full Text Available Sterol regulatory element-binding protein-1 (SREBP-1 has been thought to be a critical factor that assists adipogenesis. During adipogenesis SREBP-1 stimulates lipogenic gene expression, and peroxisome proliferator-activated receptor γ (PPARγ enhances perilipin (plin gene expression, resulting in generating lipid droplets (LDs to store triacylglycerol (TAG in adipocytes. Plin coats adipocyte LDs and protects them from lipolysis. Here we show in white adipose tissue (WAT of plin-/- mice that nuclear active SREBP-1 and its target gene expression, but not nuclear SREBP-2, significantly decreased on attenuated LD formation. When plin-/- mouse embryonic fibroblasts (MEFs differentiated into adipocytes, attenuated LDs were formed and nuclear SREBP-1 decreased, but enforced plin expression restored them to their original state. Since LDs are largely derived from the endoplasmic reticulum (ER, alterations in the ER cholesterol content were investigated during adipogenesis of 3T3-L1 cells. The ER cholesterol greatly reduced in differentiated adipocytes. The ER cholesterol level in plin-/- WAT was significantly higher than that of wild-type mice, suggesting that increased LD formation caused a change in ER environment along with a decrease in cholesterol. When GFP-SREBP-1 fusion proteins were exogenously expressed in 3T3-L1 cells, a mutant protein lacking the S1P cleavage site was poorly processed during adipogenesis, providing evidence of the increased canonical pathway for SREBP processing in which SREBP-1 is activated by two cleavage enzymes in the Golgi. Therefore, LD biogenesis may create the ER microenvironment favorable for SREBP-1 activation. We describe the novel interplay between LD formation and SREBP-1 activation through a positive feedback loop.

  4. The Swiss Modification Process in Nuclear Power Plants Regulatory Regime - Regulator/Operator process and Experience Related to Events with Safety Impact

    International Nuclear Information System (INIS)

    Modifications at NPPs are one of the important processes in regulatory and operator tasks for safe operation. Experience shows that many of the most significant Swiss events have their origin in previous modifications. Failures were sometimes latent, over a long time. Important elements of the whole quality chain are the Quality Management Systems of the operators. The latter has also to control the activity of suppliers and manufacturers. The other important element is the regulation and the supervision by the regulatory body (RB), and their related organisations. The paper outlines the main Swiss regulatory guidelines and the RB impact, which depends on the safety impact of modifications and on the type of modifications (large or small, new technology or known standard technology). Experience shows that large modifications performed by qualified suppliers have resulted in few events, small modifications by plant personnel have led to significant events. Derived from these events, the following proposals are made: - Applying Human Factor principles should be an integral element of all modifications. Such principles should be defined in an IAEA safety guide or TECDOC. - Using operating experience should also be a standard element in the modification process. A powerful computerised intelligent search tool to extract the relevant information from large databases (e.g. IRS) should be developed by related organisations. In conclusion: The Swiss contribution should support international discussions on implementing operating experience feedback in the modification process. Condition: a 'powerful intelligent computerized tool' should be developed to find quickly and easily the important related 'lesson learned' e.g. in the IRS database. The existing tool is not helpful in this respect. This may help to reduce the risk of MINIMs recurrence and may lead to better design reviews and an improvement of acceptance or commissioning tests. Experience has showed that missing

  5. Preserving the Environment of Outer Space - Legal, Regulatory and Institutional Aspects of Active Orbital Debris Removal

    Science.gov (United States)

    Mankata Nyampong, Y. O.

    2012-01-01

    In view of the massive quantities of space debris already deposited in outer space, any effort aimed at guaranteeing the sustainability of mankind's access to outer space and the continued safety of space operations must not be limited exclusively to mitigating the creation of new debris, but must also focus on the active removal of existing pieces of debris from space (remediation) as a matter of necessity. Presently, technologies that will enable active debris removal (ADR) are only just emerging. As the technology develops, however, several legal, regulatory and institutional issues that may hinder the conduct of ADR activities must also be addressed. This paper highlights and explores some of the foregoing issues in an effort to draw international attention to these matters and ultimately to pave the way for the smooth conduct of ADR activities once the technology matures.

  6. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation.

    Science.gov (United States)

    Izcue, Ana; Coombes, Janine L; Powrie, Fiona

    2006-08-01

    The gastrointestinal (GI) tract is the main interface where the body encounters exogenous antigens. It is crucial that the local response here is tightly regulated to avoid an immune reaction against dietary antigens and commensal flora while still mounting an efficient defense against pathogens. Faults in establishing intestinal tolerance can lead to disease, inducing local and often also systemic inflammation. Studies in human as well as in animal models suggest a role for regulatory T cells (Tregs) in maintaining intestinal homeostasis. Transfer of Tregs can not only prevent the development of colitis in animal models but also cure established disease, acting both systemically and at the site of inflammation. In this review, we discuss the major regulatory pathways, including transforming growth factor-beta (TGF-beta), interleukin-10 (IL-10), and cytotoxic T-lymphocyte antigen-4 (CTLA-4), and their role in Treg-mediated control of systemic and mucosal responses. In addition, we give an overview of the known mechanisms of lymphocyte migration to the intestine and discuss how CD103 expression can influence the balance between regulatory and effector T cells. Further understanding of the factors that control the activity of Tregs in different immune compartments may facilitate the design of strategies to target regulation in a tissue-specific way. PMID:16903919

  7. Nuclear Regulatory Commission activities to prepare for reviewing license applications and issuing licenses

    Energy Technology Data Exchange (ETDEWEB)

    Uleck, R.B.; DeFino, C.V. [Nuclear Regulatory Commission, Washington, DC (United States)

    1991-12-31

    The Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) assigned States the responsibility to provide for disposal of commercial low-level radioactive waste (LLRW) by 1993. The LLRWPAA also required the US Nuclear Regulatory Commission (NRC) to establish procedures and develop the technical review capability to process license applications for new LLRW disposal facilities. Under the LLRWPAA, NRC is required, to the extent practicable, to complete its review of an LLRW disposal facility license application within 15 months of its submittal by a State. This provision of the LLRWPAA helps ensure that NRC, in addition to protecting public health and safety and the environment, facilitates States` achievement of LLRWPAA milestones for new facility development. A timely NRC review is needed for States to accomplish their objective of having new disposal facilities in operation on the dates prescribed in the LLRWPAA. To help assure NRC and States` compliance with the provisions of the LLRWPAA, NRC has developed a licensing review strategy that includes: (1) the further development of regulatory guidance, (2) enhancement of licensing review capability, and (3) prelicensing regulatory consultation with potential applicants.

  8. Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus.

    Directory of Open Access Journals (Sweden)

    Alexis Mathian

    Full Text Available A slight increase in the proportion of circulating regulatory T (Treg cells has been reported in systemic lupus erythematosus (SLE patients taking oral prednisone. The effects of intravenous (IV high dose methylprednisolone (MP on Tregs have not yet been described, especially in active SLE.We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1 naïve Treg (nTreg FoxP3lowCD45RA+ cells; (2 effector Treg (eTreg FoxP3highCD45RA- cells; and (3 non-suppressive FoxP3lowCD45RA- cells (non-regulatory Foxp3low T cells. Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0 and the following days (day 1, day 2, ±day 3 and ±day 8. The activity of SLE was assessed by the SLEDAI score.Seventeen patients were included. Following MP infusions, the median (range percentage of eTregs significantly increased from 1.62% (0.53-8.43 at day 0 to 2.80% (0.83-14.60 at day 1 (p = 0.003 versus day 0, 4.64% (0.50-12.40 at day 2 (p = 0.06 versus day 1 and 7.50% (1.02-20.70 at day 3 (p = 0.008 versus day 2, and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20-17.70 at day 0 to 4.74% (1.03-9.72 at day 2 (p = 0.005; nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.

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

    International Nuclear Information System (INIS)

    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 coordination of this work is described in the paper and examples are given of inspection activities associated with the enforcement requirements of license conditions as well as those related to the inspection of the plant itself

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

    International Nuclear Information System (INIS)

    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)

  11. Improvements to the DOE low-level waste regulatory structure and process under recommendation 94-2 - progress to date

    Energy Technology Data Exchange (ETDEWEB)

    Regnier, E.

    1995-12-31

    Among the concerns expressed by the Defense Nuclear Facility Safety Board (DNFSB) in its Recommendation 94-2 was the lack of a clearly defined and effective internal Department of Energy (DOE) regulatory oversight and enforcement process for ensuring that low-level radioactive waste management health, safety, and environmental requirements are met. Therefore, part of the response to the DNFSB concern is a task to clarify and strengthen the low-level waste management regulatory structure. This task is being conducted in two steps. First, consistent with the requirements of the current DOE waste management order and within the framework of the current organizational structure, interim clarification of a review process and the associated organizational responsibilities has been issued. Second, in coordination with the revision of the waste management order and consistent with the organizational responsibilities resulting from the strategic alignment of DOE, a rigorous, more independent regulatory oversight structure will be developed.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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)

  16. Laboratory Exercise: Study of Digestive and Regulatory Processes through the Exploration of Fasted and Postprandial Blood Glucose

    Science.gov (United States)

    Hopper, Mari K.; Maurer, Luke W.

    2013-01-01

    Digestive physiology laboratory exercises often explore the regulation of enzyme action rather than systems physiology. This laboratory exercise provides a systems approach to digestive and regulatory processes through the exploration of postprandial blood glucose levels. In the present exercise, students enrolled in an undergraduate animal…

  17. Modelling non-stationary gene regulatory processes with a non-homogeneous Bayesian network and the allocation sampler

    NARCIS (Netherlands)

    Grzegorczyk, Marco; Husmeier, Dirk; Edwards, Kieron D.; Ghazal, Peter; Millar, Andrew J.

    2008-01-01

    Method: The objective of the present article is to propose and evaluate a probabilistic approach based on Bayesian networks for modelling non-homogeneous and non-linear gene regulatory processes. The method is based on a mixture model, using latent variables to assign individual measurements to diff

  18. Environmental radiological aspects of mining and processing of beach sand minerals: regulatory perspective

    International Nuclear Information System (INIS)

    The coastal sands of India have large reserves of valuable minerals namely titanium bearing minerals (ilmenite, rutile, leucoxene), zircon, garnet, sillimanite and monazite (which is a source of thorium and uranium). In 1998, a Policy on Exploitation of Beach Sand Minerals (BSM) was notified by the Government of India in 1998 which encouraged the participation of companies outside Department of Atomic Energy in the field of beach sand mining and mineral separation. Since the beach sand minerals remain invariably associated with the radioactive mineral monazite, preferential separation of other heavy minerals results in enhancement of the monazite content in the left over sands generally referred to as tailings. Atomic Energy Regulatory Board took an independent assessment of all these facilities and a special Committee was constituted in 2004 with experts from AERB and BARC to evaluate the radiological safety aspects in these facilities. AERB evaluates the design of engineered trenches for storage of radioactive solid wastes, treatment methodology of gaseous and liquid wastes and prescribes limits on the activity content and quantity of gaseous, liquid and solid wastes such that there is no adverse impact on the environment. Independent Environmental Survey Laboratories of Bhabha Atomic Research Centre are stationed at these sites to carry out periodic surveillance of the surrounding environment, which includes bore well monitoring, environmental radiation monitoring, air, water, soil, and vegetation sample analysis. AERB reviews the periodic reports of ESL to assess the radiological impact from these facilities

  19. 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.

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

    International Nuclear Information System (INIS)

    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

  1. 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

  2. Regulatory guidance document

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  3. Regulatory guidance document

    International Nuclear Information System (INIS)

    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

  4. Effects of self-regulatory strength depletion on muscular performance and EMG activation.

    Science.gov (United States)

    Bray, Steven R; Martin Ginis, Kathleen A; Hicks, Audrey L; Woodgate, Jennifer

    2008-03-01

    The purpose of the present study was to examine the effects of a self-regulatory strength depletion manipulation on performance of a physical endurance (isometric handgrip) task. In addition, the effect of depletion on EMG activity in the working forearm muscles during the endurance task was explored. Sedentary undergraduates (N=49) were randomly assigned to either a cognitive depletion condition (modified Stroop task) or a control (color word) group and completed two maximal isometric exercise endurance trials separated by the cognitive task. Participants in the depletion group showed significant (p<.05) degradations in performance and exhibited higher EMG activation on the second endurance trial (p<.05) compared to controls. Results are consistent with the limited strength model of self-regulation and are interpreted in light of the central fatigue hypothesis. PMID:17995906

  5. Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes

    OpenAIRE

    Lior Lobel; Herskovits, Anat A.

    2016-01-01

    Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was c...

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

    OpenAIRE

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

    2013-01-01

    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 fi...

  7. Status of PAR Installation in Korean NPPs and Experiences in Regulatory Activities

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Jae; Sung, Key Yong [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2010-10-15

    Following TMI-2 and Chernobyl accidents, concerns on the safety problems of nuclear power plants (NPPs) have been increased, especially for severe accident phenomena including hydrogen risk. To reduce the potential of hydrogen combustion, much of international efforts have been made for decades and it resulted in development of an innovative device, i.e. passive autocatalytic recombiner (PAR), for hydrogen removal in containment during an accident. On the designing and implementing a PAR, Bachellerie et al. provided a good instruction. Actually not only most new NPP designs but also NPPs to be refurbished are considering the installation of PARs for hydrogen control following a design basis accident (DBA) and severe accident (SA). For some Korean NPPs, the utility, KHNP, also has decided to equip PARs in containment and KINS has performed relevant regulatory reviews and preoperational inspections. In this paper, the status of PAR installation in Korean NPPs and KINS' experiences in regulatory activities including onsite findings as well as some recommendations, are described

  8. Review of regulatory activities associated with safety culture and management of safety at UK nuclear installations

    International Nuclear Information System (INIS)

    The management of health and safety and the culture of the people who participate in the process have been fundamental to the development of the United Kingdom's nuclear power programme. In the early years of development, the organizations and systems set up in companies which designed, manufactured, constructed and operated nuclear power stations were based upon the best practices needed to ensure, not only the operability of the plant, but also the safety of the workers at the power stations and the public. Over the years the nuclear industry in the UK has changed as has the regulatory body responsible for licensing. The economic environment within which the nuclear electricity generators operate has caused them to review their business and organizational structures. The UK nuclear industry has developed its approach to health and safety management and it is generally recognized that commercially successful companies have excellent health and safety records. This paper discusses the importance of effective health and safety management to the maintenance of high safety standards and the delivery of business goals. It also discusses the model that has been developed to help assess safety management in the changing UK nuclear industry. Finally, it comments upon regulatory developments in management of safety and safety culture. (author)

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Goldman, C.A. (Lawrence Berkeley Lab., CA (United States) National Association of Regulatory Utility Commissioners, Washington, DC (United States)); Hopkins, M.E. (Fleming Group, Washington, DC (United States))

    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.

  11. 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.

  12. Plasmacytoid dendritic cells are inefficient in activation of human regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Mario Hubo

    Full Text Available BACKGROUND: Dendritic cells (DC play a key role in initiation and regulation of immune responses. Plasmacytoid DC (pDC, a small subset of DC, characterized as type-I interferon producing cells, are critically involved in anti-viral immune responses, but also mediate tolerance by induction of regulatory T cells (Treg. In this study, we compared the capacity of human pDC and conventional DC (cDC to modulate T cell activity in presence of Foxp3(+ Treg. PRINCIPAL FINDINGS: In coculture of T effector cells (Teff and Treg, activated cDC overcome Treg anergy, abrogate their suppressive function and induce Teff proliferation. In contrast, pDC do not break Treg anergy but induce Teff proliferation even in coculture with Treg. Lack of Treg-mediated suppression is independent of proinflammatory cytokines like IFN-α, IL-1, IL-6 and TNF-α. Phenotyping of pDC-stimulated Treg reveals a reduced expression of Treg activation markers GARP and CTLA-4. Additional stimulation by anti-CD3 antibodies enhances surface expression of GARP and CTLA-4 on Treg and consequently reconstitutes their suppressive function, while increased costimulation with anti-CD28 antibodies is ineffective. CONCLUSIONS/SIGNIFICANCE: Our data show that activated pDC induce Teff proliferation, but are insufficient for functional Treg activation and, therefore, allow expansion of Teff also in presence of Treg.

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

    International Nuclear Information System (INIS)

    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

  14. China Bans Some Processing Trade Activities

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    <正>China’s Commerce Ministry and General Administration of Customs jointly issued a circular, which will ban the processing trade activities for some metals concentrates. According to the circular, the processing trade for a number of metals concentrates will be banned from August 22, 2005.

  15. 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.

  16. Managing Regulatory Body Competence

    International Nuclear Information System (INIS)

    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

  17. Antimutagenic and redox regulatory activities of curcumin in whole body γ - irradiated mice

    International Nuclear Information System (INIS)

    the aim of the current study is understanding the redox regulatory activity ( pro- and anti-oxidant properties) and mutagenic burden following whole body -irradiation with special reference to its control by curcumin in mice. the antimutagenic effects of curcumin; diferuloylmethane ( C21 H20 O6) were evaluated in vitro using chromosomal aberration assay in male mice,induced after-exposure to 3 Gy γ-rays that is a known mutagenic and carcinogenic agent, when curcumin was given at a dose of 400 mmol/kg body wt through gastric intubation for 5 following days either before-, after-or both before and after-exposure, the incidence of aberrant cells and aberration types (mostly chromatids, breaks and fragments) reduced with curcumin dosage as compared to irradiated group. the cellular biochemical changes were estimated using liver tissue damage marker enzymes: alkaline phosphatase (ALP) and γ -glutamyl transferase (GGT), pro-oxidant: xanthine oxidase (XO), lipid per oxidative indices: thiobarbituric acid reactive substances (TBARS) and hydroperoxide (HP. the non-enzymatic antioxidant : glutathione (GSH) and the enzymatic antioxidants: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). TBARS ,HP,XO and liver marker enzymes were increased significantly , whereas the levels of GSH and the enzymatic antioxidants were significantly depleted in -irradiated groups. curcumin-treatment either before-, after-or both before and after -irradiation has attenuated the liver toxic effects of radiation obvious by reducing the levels of tbars and HP and diminished the increases of the activity of XO and liver marker enzymes. it has also re sued the depletion of the non enzymatic -and the enzymatic-antioxidant status.conclusion:curcumin has anti-oxidant potential against -rays-induced chromosomal mutations and redox imbalance regulatory status

  18. CRIMINAL PROCESS AND OPERATIONAL AND INVESTIGATIVE ACTIVITY

    Directory of Open Access Journals (Sweden)

    Meretukov G. M.

    2016-01-01

    Full Text Available The authors of the article examine the relationship between the criminal process and investigative activity taking into consideration the requirements of the Criminal Procedure Law and the Law on Investigative Activities in the Russian Federation. Such important issues as main tasks and principles of the criminal process and investigative activity are considered in the article. The authors analyze interrelations of some investigative actions and operational search as well as the order of introduction and usage of the results of the investigative activities at the stage of criminal case initializing and in the course of investigative activities. The authors also pay attention to the data which must be submitted in the report or memorandum on the prepared or being committed crime giving grounds for criminal case initializing

  19. Physical activity (PA) and the disablement process

    DEFF Research Database (Denmark)

    Schultz-Larsen, Kirsten; Rahmanfard, Naghmeh; Holst, Claus

    2012-01-01

    . Among older women, the association between RPA and incidence of disability was attenuated in analyses that controlled for baseline mobility function. Thus, the association between physical activity and mortality reflected processes different from those underlying a simple relation between physical...... activity, disability and mortality. Physical activity was an ubiquitous predictor of longevity, but only for women....... community-living persons, aged 75-83 years, we evaluated the 1021 who reported no disability in basic activities of daily living. Participants were followed for a median of 8.34 years in public registers to determine onset of disability and mortality. RPA predicted mortality in older women (HR=1.77, 95%CI=1...

  20. Electroweak processes in external active media

    Energy Technology Data Exchange (ETDEWEB)

    Kuznetsov, Alexander; Mikheev, Nickolay [Yaroslavl State P.G. Demidov Univ. (Russian Federation). Theoretical Physics Dept.

    2013-06-01

    Covers new effects of a pure magnetic field on electroweak processes. Focus lays on the calculation technique for electroweak processes in external active media - hot dense plasma. Useful reference for researchers and for graduate students. Expanding on the concept of the authors' previous book ''Electroweak Processes in External Electromagnetic Fields,'' this new book systematically describes the investigation methods for the effects of external active media, both strong electromagnetic fields and hot dense plasma, in quantum processes. Solving the solar neutrino puzzle in a unique experiment conducted with the help of the heavy-water detector at the Sudbery Neutrino Observatory, along with another neutrino experiments, brings to the fore electroweak physics in an active external medium. It is effectively demonstrated that processes of neutrino interactions with active media of astrophysical objects may lead, under some physical conditions, to such interesting effects as neutrino-driven shockwave revival in a supernova explosion, a ''cherry stone shooting'' mechanism for pulsar natal kick, and a neutrino pulsar. It is also shown how poor estimates of particle dispersion in external active media sometimes lead to confusion. The book will appeal to graduate and post-graduate students of theoretical physics with a prior understanding of Quantum Field Theory (QFT) and the Standard Model of Electroweak Interactions, as well as to specialists in QFT who want to know more about the problems of quantum phenomena in hot dense plasma and external electromagnetic fields.

  1. Transcription factors GAF and HSF act at distinct regulatory steps to modulate stress-induced gene activation

    Science.gov (United States)

    Fuda, Nicholas J.; Mahat, Dig B.; Core, Leighton J.; Guertin, Michael J.

    2016-01-01

    The coordinated regulation of gene expression at the transcriptional level is fundamental to development and homeostasis. Inducible systems are invaluable when studying transcription because the regulatory process can be triggered instantaneously, allowing the tracking of ordered mechanistic events. Here, we use precision run-on sequencing (PRO-seq) to examine the genome-wide heat shock (HS) response in Drosophila and the function of two key transcription factors on the immediate transcription activation or repression of all genes regulated by HS. We identify the primary HS response genes and the rate-limiting steps in the transcription cycle that GAGA-associated factor (GAF) and HS factor (HSF) regulate. We demonstrate that GAF acts upstream of promoter-proximally paused RNA polymerase II (Pol II) formation (likely at the step of chromatin opening) and that GAF-facilitated Pol II pausing is critical for HS activation. In contrast, HSF is dispensable for establishing or maintaining Pol II pausing but is critical for the release of paused Pol II into the gene body at a subset of highly activated genes. Additionally, HSF has no detectable role in the rapid HS repression of thousands of genes. PMID:27492368

  2. A regulatory adjustment process for the determination of the optimal percentage requirement in an electricity market with Tradable Green Certificates

    International Nuclear Information System (INIS)

    A system of Tradable Green Certificates (TGCs) is a market-based subsidy scheme designed to promote electricity generation from renewable energy sources such as wind power. Under a TGC system, the principal policy instrument is the “percentage requirement,” which stipulates the percentage of total electricity production (“green” plus “black”) that must be obtained from renewable sources. In this paper, we propose a regulatory adjustment process that a regulator can employ to determine the socially optimal percentage requirement, explicitly accounting for environmental damages resulting from black electricity generation. - Highlights: • A Tradable Green Certificate (TGC) system promotes energy production from renewable sources. • We consider an electricity oligopoly operated under a TGC system. • Welfare analysis must account for damages from “black” electricity production. • We characterize the welfare maximizing (optimal) “percentage requirement.” • We present a regulatory adjustment process that computes the optimal percentage requirement iteratively

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

    International Nuclear Information System (INIS)

    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. Activation of regulatory T cells during inflammatory response is not an exclusive property of stem cells.

    Directory of Open Access Journals (Sweden)

    Jan-Hendrik Gosemann

    Full Text Available BACKGROUND: Sepsis and systemic-inflammatory-response-syndrome (SIRS remain major causes for fatalities on intensive care units despite up-to-date therapy. It is well accepted that stem cells have immunomodulatory properties during inflammation and sepsis, including the activation of regulatory T cells and the attenuation of distant organ damage. Evidence from recent work suggests that these properties may not be exclusively attributed to stem cells. This study was designed to evaluate the immunomodulatory potency of cellular treatment during acute inflammation in a model of sublethal endotoxemia and to investigate the hypothesis that immunomodulations by cellular treatment during inflammatory response is not stem cell specific. METHODOLOGY/PRINCIPAL FINDINGS: Endotoxemia was induced via intra-peritoneal injection of lipopolysaccharide (LPS in wild type mice (C3H/HeN. Mice were treated with either vital or homogenized amniotic fluid stem cells (AFS and sacrificed for specimen collection 24 h after LPS injection. Endpoints were plasma cytokine levels (BD™ Cytometric Bead Arrays, T cell subpopulations (flow-cytometry and pulmonary neutrophil influx (immunohistochemistry. To define stem cell specific effects, treatment with either vital or homogenized human-embryonic-kidney-cells (HEK was investigated in a second subset of experiments. Mice treated with homogenized AFS cells showed significantly increased percentages of regulatory T cells and Interleukin-2 as well as decreased amounts of pulmonary neutrophils compared to saline-treated controls. These results could be reproduced in mice treated with vital HEK cells. No further differences were observed between plasma cytokine levels of endotoxemic mice. CONCLUSIONS/SIGNIFICANCE: The results revealed that both AFS and HEK cells modulate cellular immune response and distant organ damage during sublethal endotoxemia. The observed effects support the hypothesis, that immunomodulations are not

  5. Improving regulatory effectiveness in Federal/State siting actions. Need for power: determinants in the state decisionmaking processes

    International Nuclear Information System (INIS)

    The Department of Energy's Nuclear Siting and Licensing Act of 1978 (S.2775; H.R.11704) proposes Federal/State coordination in need for facility decisionmaking for nuclear power stations. A prior study by the Nuclear Regulatory Commission's Office of State Programs, ''Improving Regulatory Effectiveness in Federal/State Siting Actions'', NUREG-0195, May 1977, considered the concept of need for power/facility. The present study expands the inquiry into need for power/facility by examining the decisionmaking criteria utilized by forty-four States in making a determination of need for power/facility. Specific criteria are identified along with the number of States which make those criteria a primary consideration or a secondary consideration in determining need for facility. Individual profiles of the studied States' decisionmaking criteria are provided. In addition, the study examines the different organizational and functional patterns found in the States' regulatory processes to certificate power stations. The coordination or lack of coordination of the issuance of associated environmental permits required for power stations is outlined for each State. Information concerning States' rate treatment of expenses associated with the construction and operation of a power station is provided. The relationship between the need for power decisionmaking process and the ratemaking process is explored

  6. FOXP3+Helios+ Regulatory T Cells, Immune Activation, and Advancing Disease in HIV-Infected Children.

    Science.gov (United States)

    Khaitan, Alka; Kravietz, Adam; Mwamzuka, Mussa; Marshed, Fatma; Ilmet, Tiina; Said, Swalehe; Ahmed, Aabid; Borkowsky, William; Unutmaz, Derya

    2016-08-15

    Regulatory T cells (Tregs) are functionally suppressive CD4 T cells, critical for establishing peripheral tolerance and controlling inflammatory responses. Previous reports of Tregs during chronic HIV disease have conflicting results with higher or lower levels compared with controls. Identifying true Tregs with suppressive activity proves challenging during HIV infection, as traditional Treg markers, CD25 and FOXP3, may transiently upregulate expression as a result of immune activation (IA). Helios is an Ikaros family transcription factor that marks natural Tregs with suppressive activity and does not upregulate expression after activation. Coexpression of FOXP3 and Helios has been suggested as a highly specific marker of "bona fide" Tregs. We evaluated Treg subsets by FOXP3 coexpressed with either CD25 or Helios and their association with HIV disease progression in perinatally infected HIV-positive children. Identifying Tregs by FOXP3 coexpression with Helios rather than CD25 revealed markedly higher Treg frequencies, particularly in HIV+ children. Regardless of antiretroviral therapy, HIV-infected children had a selective expansion of memory FOXP3+Helios+ Tregs. The rise in memory Tregs correlated with declining HIV clinical status, indicated by falling CD4 percentages and CD4:CD8 ratios and increasing HIV plasma viremia and IA. In addition, untreated HIV+ children exhibited an imbalance between the levels of Tregs and activated T cells. Finally, memory Tregs expressed IA markers CD38 and Ki67 and exhaustion marker, PD-1, that tightly correlated with a similar phenotype in memory CD4 T cells. Overall, HIV-infected children had significant disruptions of memory Tregs that associated with advancing HIV disease. PMID:27003495

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

    International Nuclear Information System (INIS)

    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

  8. Decreased Circulating T Regulatory Cells in Egyptian Patients with Nonsegmental Vitiligo: Correlation with Disease Activity.

    Science.gov (United States)

    Hegab, Doaa Salah; Attia, Mohamed Attia Saad

    2015-01-01

    Background. Vitiligo is an acquired depigmentary skin disorder resulting from autoimmune destruction of melanocytes. Regulatory T cells (Tregs), specifically CD4(+)CD25(+) and Forkhead box P3(+) (FoxP3(+)) Tregs, acquired notable attention because of their role in a variety of autoimmune pathologies. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to vitiligo pathogenesis. Methods. In order to sustain the role of Tregs in pathogenesis and disease activity of vitiligo, surface markers for CD4(+)CD25(+) and FoxP3(+) peripheral Tregs were evaluated by flow cytometry in 80 Egyptian patients with nonsegmental vitiligo in addition to 60 healthy control subjects and correlated with clinical findings. Results. Vitiligo patients had significantly decreased numbers of both peripheral CD4(+)CD25(+) and FoxP3(+) T cells compared to control subjects (11.49%  ± 8.58% of CD4(+) T cells versus 21.20%  ± 3.08%, and 1.09%  ± 0.96% versus 1.44%  ± 0.24%, resp., P nonsegmental vitiligo particularly in active cases. Effective Treg cell-based immunotherapies might be a future hope for patients with progressive vitiligo. PMID:26788051

  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. US Department of Energy wind turbine candidate site program: the regulatory process

    Energy Technology Data Exchange (ETDEWEB)

    Greene, M.R.; York, K.R.

    1982-06-01

    Sites selected in 1979 as tentative sites for installation of a demonstration MOD-2 turbine are emphasized. Selection as a candidate site in this program meant that the US Department of Energy (DOE) designated the site as eligible for a DOE-purchased and installed meteorological tower. The regulatory procedures involved in the siting and installation of these meteorological towers at the majority of the candidate sites are examined. An attempt is also made, in a preliminary fashion, to identify the legal and regulatory procedures that would be required to put up a turbine at each of these candidate sites. The information provided on each of these sites comes primarily from utility representatives, supplemented by conversations with state and local officials. The major findings are summarized on the following: federal requirements, state requirements, local requirements, land ownership, wind rights, and public attitudes.

  11. 75 FR 61483 - Agency Information Collection Activities; Proposed Collection; Comment Request; Regulatory Pilot...

    Science.gov (United States)

    2010-10-05

    ... solicited for pilot projects to test innovation in environmental permitting. Other parties affected by this... continue their commitments to monitor the results of remaining pilot tests of regulatory innovation... existing innovative regulatory pilot tests in projects funded by a State Innovation Grant are required...

  12. The additive effect of regulatory activities on top of intelligence in relation to academic performance in higher education

    NARCIS (Netherlands)

    Minnaert, A; Janssen, PJ

    1999-01-01

    This study investigated the additive, beneficial effect of regulatory activities on top of verbal, numerical, and diagrammatic intelligence in the prediction of academic performance. About 500 freshmen of different study domains participated in this research. The findings supported both the mixed an

  13. Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Wei Song; Jiguang Wang; Ying Yang; Naihe Jing; Xiangsun Zhang; Luonan Chen; Jiarui Wu

    2012-01-01

    Many of oncogenes and tumor suppressor genes have been found to exert variable and even opposing roles in different kinds of tumors or at different stages of cancer development.Here we showed that tumorigenic potential of mouse embryonic carcinoma P19 cells cultured in adherent plates (attached-P19-cells) was suppressed by a chemotherapeutic agent,5-aza-2'-deoxycytidine (ZdCyd),whereas the higher pro-tumorigenicity of P19 cells growing in suspension (detached-P19-cells) was generated by the ZdCyd treatment.Surprisingly,p53 activity was highly up-regulated by ZdCyd in both growing conditions.By our developed computational approaches,we revealed that there was a significant enrichment of apoptotic pathways in the ZdCyd-induced p53-dominant gene-regulatory network in attached P19 cells,whereas the pro-survival genes were significantly enriched in the ZdCyd-induced p53 network in detached P19 cells.The protein-protein interaction network of the ZdCyd-treated detached P19 cells was significantly different from that of ZdCyd-treated attached P19 cells.On the other hand,inhibition of pS3 expression by siRNA suppressed the ZdCyd-induced tumorigenesis of detached P19 cells,suggesting that the ZdCyd-activated p53 plays oncogenic function in detached P19 cells.Taken together,these results indicate a context-dependent role for the ZdCyd-activated p53-dominant network in tumorigenesis.

  14. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase

    Science.gov (United States)

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2016-01-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 μM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl− and the decreased HCO3− concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na–K–2Cl electroneutral cotransporter or Cl−/HCO3− anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  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. Immune regulatory activities of fowlicidin-1, a cathelicidin host defense peptide.

    Science.gov (United States)

    Bommineni, Yugendar R; Pham, Giang H; Sunkara, Lakshmi T; Achanta, Mallika; Zhang, Guolong

    2014-05-01

    Appropriate modulation of immunity is beneficial in antimicrobial therapy and vaccine development. Host defense peptides (HDPs) constitute critically important components of innate immunity with both antimicrobial and immune regulatory activities. We previously showed that a chicken HDP, namely fowlicidin-1(6-26), has potent antibacterial activities in vitro and in vivo. Here we further revealed that fowl-1(6-26) possesses strong immunomodulatory properties. The peptide is chemotactic specifically to neutrophils, but not monocytes or lymphocytes, after injected into the mouse peritoneum. Fowl-1(6-26) also has the capacity to activate macrophages by inducing the expression of inflammatory mediators including IL-1β, CCL2, and CCL3. However, unlike bacterial lipopolysaccharide that triggers massive production of inflammatory cytokines and chemokines, fowl-1(6-26) only marginally increased their expression in mouse RAW264.7 macrophages. Additionally, fowl-1(6-26) enhanced the surface expression of MHC II and CD86 on RAW264.7 cells, suggesting that it may facilitate development of adaptive immune response. Indeed, co-immunization of mice with chicken ovalbumin (OVA) and fowl-1(6-26) augmented both OVA-specific IgG1 and IgG2a titers, relative to OVA alone. We further showed that fowl-1(6-26) is capable of preventing a methicillin-resistant Staphylococcus aureus (MRSA) infection due to its enhancement of host defense. All mice survived from an otherwise lethal infection when the peptide was administered 1-2 days prior to MRSA infection, and 50% mice were protected if receiving the peptide 4 days before infection. Taken together, with a strong capacity to stimulate innate and adaptive immunity, fowl-1(6-26) may have potential to be developed as a novel antimicrobial and a vaccine adjuvant.

  17. FraTAct for Transforming A Nescient Process Activity Into an Intelligent Process Activity

    Directory of Open Access Journals (Sweden)

    Rafiqul Haque

    2014-03-01

    Full Text Available Existing business process technologies support defining only nescient activities. Currently there is no solution that underpins transforming a nescient activity into intelligent activity. In this paper, we address this shortcoming of the state of the art. We offer a framework ‘FraTAct’ for transforming regulation intensive nescient activities of a financial service business process into intelligent activities. Financial service industries has been experiencing enormous challenges since the last decade. A recent financial crisis has unearthed various weaknesses in terms of administering the financial service industries. In order to prevent the future crisis, the regulators are constantly formulating new rules and also forcing the financial service industry to enact financial regulations in their financial service based application which automates financial operations. A financial service application underpins the financial service business process that contains activities. A nescient activity within a financial service process is prone to the risk of producing an inconsistent outcome that results in severe legal consequences for a financial institute e.g., a bank. In order to avoid these legal consequences, a financial institute should develop their financial service processes by composing activities that should be intelligent to understand and comply with financial regulations. Intelligent activities will produce outcomes that are consistent to financial regulations. It will reduce the possibility of financial regulation noncompliance in financial service process based application.

  18. Speech perception as an active cognitive process

    Directory of Open Access Journals (Sweden)

    Shannon eHeald

    2014-03-01

    Full Text Available One view of speech perception is that acoustic signals are transformed into representations for pattern matching to determine linguistic structure. This process can be taken as a statistical pattern-matching problem, assuming realtively stable linguistic categories are characterized by neural representations related to auditory properties of speech that can be compared to speech input. This kind of pattern matching can be termed a passive process which implies rigidity of processingd with few demands on cognitive processing. An alternative view is that speech recognition, even in early stages, is an active process in which speech analysis is attentionally guided. Note that this does not mean consciously guided but that information-contingent changes in early auditory encoding can occur as a function of context and experience. Active processing assumes that attention, plasticity, and listening goals are important in considering how listeners cope with adverse circumstances that impair hearing by masking noise in the environment or hearing loss. Although theories of speech perception have begun to incorporate some active processing, they seldom treat early speech encoding as plastic and attentionally guided. Recent research has suggested that speech perception is the product of both feedforward and feedback interactions between a number of brain regions that include descending projections perhaps as far downstream as the cochlea. It is important to understand how the ambiguity of the speech signal and constraints of context dynamically determine cognitive resources recruited during perception including focused attention, learning, and working memory. Theories of speech perception need to go beyond the current corticocentric approach in order to account for the intrinsic dynamics of the auditory encoding of speech. In doing so, this may provide new insights into ways in which hearing disorders and loss may be treated either through augementation or

  19. The emerging regulatory potential of SCFMet30 -mediated polyubiquitination and proteolysis of the Met4 transcriptional activator

    Directory of Open Access Journals (Sweden)

    Chandrasekaran Srikripa

    2008-07-01

    Full Text Available Abstract The yeast SCFMet30 ubiquitin ligase plays a critical role in cell division by regulating the Met4 transcriptional activator of genes that control the uptake and assimilation of sulfur into methionine and S-adenosyl-methionine. The initial view on how SCFMet30 performs its function has been driven by the assumption that SCFMet30 acts exclusively as Met4 inhibitor when high levels of methionine drive an accumulation of cysteine. We revisit this model in light of the growing evidence that SCFMet30 can also activate Met4. The notion that Met4 can be inhibited or activated depending on the sulfur metabolite context is not new, but for the first time both aspects have been linked to SCFMet30, creating an interesting regulatory paradigm in which polyubiquitination and proteolysis of a single transcriptional activator can play different roles depending on context. We discuss the emerging molecular basis and the implications of this new regulatory phenomenon.

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

    International Nuclear Information System (INIS)

    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

  1. Enhanced multistatic active sonar signal processing.

    Science.gov (United States)

    Zhao, Kexin; Liang, Junli; Karlsson, Johan; Li, Jian

    2013-07-01

    Multistatic active sonar systems involve the transmission and reception of multiple probing sequences and can achieve significantly enhanced performance of target detection and localization through exploiting spatial diversity. This paper mainly focuses on two signal processing aspects of such systems, namely, enhanced range-Doppler imaging and improved target parameter estimation. The main contributions of this paper are (1) a hybrid dense-sparse method is proposed to generate range-Doppler images with both low sidelobe levels and high accuracy; (2) a generalized K-Means clustering (GKC) method for target association is developed to associate the range measurements from different transmitter-receiver pairs, which is actually a range fitting procedure; (3) the extended invariance principle-based weighted least-squares method is developed for accurate target position and velocity estimation. The effectiveness of the proposed multistatic active sonar signal processing techniques is verified using numerical examples.

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

    International Nuclear Information System (INIS)

    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.)

  3. 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.

  4. Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses.

    Science.gov (United States)

    Ambrozova, Gabriela; Martiskova, Hana; Koudelka, Adolf; Ravekes, Thorben; Rudolph, Tanja K; Klinke, Anna; Rudolph, Volker; Freeman, Bruce A; Woodcock, Steven R; Kubala, Lukas; Pekarova, Michaela

    2016-01-01

    Inflammation is an immune response triggered by microbial invasion and/or tissue injury. While acute inflammation is directed toward invading pathogens and injured cells, thus enabling tissue regeneration, chronic inflammation can lead to severe pathologies and tissue dysfunction. These processes are linked with macrophage polarization into specific inflammatory "M1-like" or regulatory "M2-like" subsets. Nitro-fatty acids (NO2-FAs), produced endogenously as byproducts of metabolism and oxidative inflammatory conditions, may be useful for treating diseases associated with dysregulated immune homeostasis. The goal of this study was to characterize the role of nitro-oleic acid (OA-NO2) in regulating the functional specialization of macrophages induced by bacterial lipopolysaccharide or interleukin-4, and to reveal specific signaling mechanisms which can account for OA-NO2-dependent modulation of inflammation and fibrotic responses. Our results show that OA-NO2 inhibits lipopolysaccharide-stimulated production of both pro-inflammatory and immunoregulatory cytokines (including transforming growth factor-β) and inhibits nitric oxide and superoxide anion production. OA-NO2 also decreases interleukin-4-induced macrophage responses by inhibiting arginase-I expression and transforming growth factor-β production. These effects are mediated via downregulation of signal transducers and activators of transcription, mitogen-activated protein kinase and nuclear factor-кB signaling responses. Finally, OA-NO2 inhibits fibrotic processes in an in vivo model of angiotensin II-induced myocardial fibrosis by attenuating expression of α-smooth muscle actin, systemic transforming growth factor-β levels and infiltration of both "M1-" and "M2-like" macrophage subsets into afflicted tissue. Overall, the electrophilic fatty acid derivative OA-NO2 modulates a broad range of "M1-" and "M2-like" macrophage functions and represents a potential therapeutic approach to target diseases

  5. The regulatory action in the problem of radioactive sources processed as scrap

    International Nuclear Information System (INIS)

    The loss of control of a radioactive source can result in a radiological emergency, especially if that source is treated as scrap. This paper presents a case registered in Argentina about discovery of a radioactive source of Kr-85, 9.25 GBq, used in a computer for industrial measurement of thickness. The radioactive source, without registration or identification, was registered by a portal for detection of radioactive material in the middle of the scrap that entered daily in the oven of a important steel company. From there, the Nuclear Regulatory Authority (RNA) conducted an investigation to determine the origin of the radioactive source, and in parallel made, in the laboratories of measurement, identification of radioactive material inside the source. This led to a company in financial and judicial bankruptcy, which had not notified the RNA about this situation, and also possessed, according to records, other eleven sources with similar characteristics. Finally the actions and regulatory effort allowed the localization of all the radioactive sources of this company, and its storage and deposit in an authorised repository

  6. Activation of Vago by interferon regulatory factor (IRF) suggests an interferon system-like antiviral mechanism in shrimp.

    Science.gov (United States)

    Li, Chaozheng; Li, Haoyang; Chen, Yixiao; Chen, Yonggui; Wang, Sheng; Weng, Shao-Ping; Xu, Xiaopeng; He, Jianguo

    2015-01-01

    There is a debate on whether invertebrates possess an antiviral immunity similar to the interferon (IFN) system of vertebrates. The Vago gene from arthropods encodes a viral-activated secreted peptide that restricts virus infection through activating the JAK-STAT pathway and is considered to be a cytokine functionally similar to IFN. In this study, the first crustacean IFN regulatory factor (IRF)-like gene was identified in Pacific white shrimp, Litopenaeus vannamei. The L. vannamei IRF showed similar protein nature to mammalian IRFs and could be activated during virus infection. As a transcriptional regulatory factor, L. vannamei IRF could activate the IFN-stimulated response element (ISRE)-containing promoter to regulate the expression of mammalian type I IFNs and initiate an antiviral state in mammalian cells. More importantly, IRF could bind the 5'-untranslated region of L. vannamei Vago4 gene and activate its transcription, suggesting that shrimp Vago may be induced in a similar manner to that of IFNs and supporting the opinion that Vago might function as an IFN-like molecule in invertebrates. These suggested that shrimp might possess an IRF-Vago-JAK/STAT regulatory axis, which is similar to the IRF-IFN-JAK/STAT axis of vertebrates, indicating that invertebrates might possess an IFN system-like antiviral mechanism.

  7. SOCIAL AND CULTURAL GROUNDS AND THE EFFICIENCY OF REGULATORY FUNCTIONS OF GOVERNMENT AUTHORITIES (ASSESSMENT IN THE DEVELOPMENT PROCESS OF LOCAL GOVERNMENT INSTITUTIONS IN RUSSIAN SOCIETY

    Directory of Open Access Journals (Sweden)

    Виктор Павлович Ляхов

    2014-06-01

    Full Text Available The article deals with the analyses of the regulatory role efficiency of the state in the process of local administration formation and development in Russia. The active position of the state in the formation of civil society and civil control structures in Russia has social and cultural grounds, it is adequate to the modern political reality.Local government efficiency is due to how much its structure is adequate to the conditions and opportunities of the society, its needs in self-organization and self-administration. In the course of the reforms in the sphere of local self-administration such factors as social and cultural features of Russian society, its self-management traditions and the authoritarian nature of all initiatives and innovations which have taken place in Russian.Present contradictions in the evaluating the essence of local government in Russia and the government authorities’ role in its functioning indicate the undeveloped institutionalization process of local administration system in Russian state.As its main factor of local administration transformations the state realizes its regulatory function absolutely ineffectively and contradictorily.DOI: http://dx.doi.org/10.12731/2218-7405-2013-11-12

  8. 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.

  9. 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)

    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.

  10. Modeling Aspects Of Activated Sludge Processes Part I: Process Modeling Of Activated Sludge Facilitation And Sedimentation

    International Nuclear Information System (INIS)

    Process modeling of activated sludge flocculation and sedimentation reviews consider the activated sludge floc characteristics such as: morphology viable and non-viable cell ratio density and water content, bio flocculation and its kinetics were studied considering the characteristics of bio flocculation and explaining theory of Divalent Cation Bridging which describes the major role of cations in bio flocculation. Activated sludge flocculation process modeling was studied considering mass transfer limitations from Clifft and Andrew, 1981, Benefild and Molz 1983 passing Henze 1987, until Tyagi 1996 and G. Ibrahim et aI. 2002. Models of aggregation and breakage of flocs were studied by Spicer and Pratsinis 1996,and Biggs 2002 Size distribution of floes influences mass transfer and biomass separation in the activated sludge process. Therefore, it is of primary importance to establish the role of specific process operation factors, such as sludge loading dynamic sludge age and dissolved oxygen, on this distribution with special emphasis on the formation of primary particles

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

    International Nuclear Information System (INIS)

    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)

  12. Active PZT fibers: a commercial production process

    Science.gov (United States)

    Strock, Harold B.; Pascucci, Marina R.; Parish, Mark V.; Bent, Aaron A.; Shrout, Thomas R.

    1999-07-01

    Lead Zirconate Titanate (PZT) active fibers, from 80 to 250 micrometers in diameter, are produced for the AFOSR/DARPA funded Active Fiber Composites Consortium (AFCC) Program and commercial customers. CeraNova has developed a proprietary ceramics-based technology to produce PZT mono-filaments of the required purity, composition, straightness, and piezoelectric properties for use in active fiber composite structures. CeraNova's process begins with the extrusion of continuous lengths of mono-filament precursor fiber from a plasticized mix of PZT-5A powder. The care that must be taken to avoid mix contamination is described using illustrations form problems experiences with extruder wear and metallic contamination. Corrective actions are described and example microstructures are shown. The consequences of inadequate lead control are also shown. Sintered mono- filament mechanical strength and piezoelectric properties data approach bulk values but the validity of such a benchmark is questioned based on variable correlation with composite performance measures. Comb-like ceramic preform structures are shown that are being developed to minimize process and handling costs while maintaining the required mono-filament straightness necessary for composite fabrication. Lastly, actuation performance data are presented for composite structures fabricated and tested by Continuum Control Corporation. Free strain actuation in excess of 2000 microstrain are observed.

  13. The Multifaceted Activity of the VirF Regulatory Protein in the Shigella Lifestyle

    Science.gov (United States)

    Di Martino, Maria Letizia; Falconi, Maurizio; Micheli, Gioacchino; Colonna, Bianca; Prosseda, Gianni

    2016-01-01

    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. PMID:27747215

  14. Degradation of corticosteroids during activated sludge processing.

    Science.gov (United States)

    Miyamoto, Aoi; Kitaichi, Yuko; Uchikura, Kazuo

    2014-01-01

    Laboratory tests of the decomposition of corticosteroids during activated sludge processing were investigated. Corticosteroid standards were added to activated sludge, and aliquots were regularly taken for analysis. The corticosteroids were extracted from the samples using a solid-phase extraction method and analyzed LC-MS. Ten types of corticosteroids were measured and roughly classified into three groups: 1) prednisolone, triamcinolone, betamethasone, prednisolone acetate, and hydrocortisone acetate, which decomposed within 4 h; 2) flunisolide, betamethasone valerate, and budesonide of which more than 50% remained after 4 h, but almost all of which decomposed within 24 h; and 3) triamcinolone acetonide, and fluocinolone acetonide of which more than 50% remained after 24 h. The decomposed ratio was correlated with each corticosteroid's Log P, especially groups 2) and 3). PMID:24390495

  15. Interactive Effects of Working Memory Self-Regulatory Ability and Relevance Instructions on Text Processing

    Science.gov (United States)

    Hamilton, Nancy Jo

    2012-01-01

    Reading is a process that requires the enactment of many cognitive processes. Each of these processes uses a certain amount of working memory resources, which are severely constrained by biology. More efficiency in the function of working memory may mediate the biological limits of same. Reading relevancy instructions may be one such method to…

  16. Activation of sterol regulatory element binding protein and NLRP3 inflammasome in atherosclerotic lesion development in diabetic pigs.

    Directory of Open Access Journals (Sweden)

    Yu Li

    Full Text Available BACKGROUND: Aberrantly elevated sterol regulatory element binding protein (SREBP, the lipogenic transcription factor, contributes to the development of fatty liver and insulin resistance in animals. Our recent studies have discovered that AMP-activated protein kinase (AMPK phosphorylates SREBP at Ser-327 and inhibits its activity, represses SREBP-dependent lipogenesis, and thereby ameliorates hepatic steatosis and atherosclerosis in insulin-resistant LDLR(-/- mice. Chronic inflammation and activation of NLRP3 inflammasome have been implicated in atherosclerosis and fatty liver disease. However, whether SREBP is involved in vascular lipid accumulation and inflammation in atherosclerosis remains largely unknown. PRINCIPAL FINDINGS: The preclinical study with aortic pouch biopsy specimens from humans with atherosclerosis and diabetes shows intense immunostaining for SREBP-1 and the inflammatory marker VCAM-1 in atherosclerotic plaques. The cleavage processing of SREBP-1 and -2 and expression of their target genes are increased in the well-established porcine model of diabetes and atherosclerosis, which develops human-like, complex atherosclerotic plaques. Immunostaining analysis indicates an elevation in SREBP-1 that is primarily localized in endothelial cells and in infiltrated macrophages within fatty streaks, fibrous caps with necrotic cores, and cholesterol crystals in advanced lesions. Moreover, concomitant suppression of NAD-dependent deacetylase SIRT1 and AMPK is observed in atherosclerotic pigs, which leads to the proteolytic activation of SREBP-1 by diminishing the deacetylation and Ser-372 phosphorylation of SREBP-1. Aberrantly elevated NLRP3 inflammasome markers are evidenced by increased expression of inflammasome components including NLPR3, ASC, and IL-1β. The increase in SREBP-1 activity and IL-1β production in lesions is associated with vascular inflammation and endothelial dysfunction in atherosclerotic pig aorta, as demonstrated

  17. 15 CFR 400.31 - Manufacturing and processing activity; criteria.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Manufacturing and processing activity... ZONES BOARD Manufacturing and Processing Activity-Reviews § 400.31 Manufacturing and processing activity....” When evaluating zone and subzone manufacturing and processing activity, either as proposed in...

  18. Safety assessment of cosmetic products, with emphasis on the ocular area: regulatory aspects and validation processes

    Directory of Open Access Journals (Sweden)

    Maythê de Lima Cancian

    2014-12-01

    Full Text Available Before marketing a cosmetic product, a series of biological assays, such as ocular irritation tests, must be conducted in order to prove that the product is safe. However, a few scientific articles mention the discussion and evolution of cosmetic products testing performed in the eyes area. The aim of this study was to review the available literature on the evolution of tests carried out with cosmetics, in the ocular area, as well as to describe the methodologies that have been used and that are currently accepted. In Brazil, tests performed on animals are still allowed. However, the international laws strongly recommend the use of alternative methods for evaluating the risk of cosmetic ingredients and products. Regulatory requirements involving the registration of these products also request safety support of them in human beings. To perform ocular tests in human beings, it is necessary to involve an ophthalmologist for conducting clinical protocols. These protocols signed by the expert physician are sent to the National Health Surveillance Agency in order to endorse the product manufacturer concerning its safety. The safety support of a cosmetic product is very important, taking into account that the consumer has free access to these products of widespread use in today's society.

  19. STAT6 Activation Confers upon T Helper Cells Resistance to Suppression by Regulatory T Cells

    NARCIS (Netherlands)

    Pillemer, Brendan B. L.; Qi, Zengbiao; Melgert, Barbro; Oriss, Timothy B.; Ray, Prabir; Ray, Anuradha

    2009-01-01

    Recent studies have highlighted characteristics of T regulatory cells (Tregs) that underlie their suppressive function. However, mechanisms that override their suppressive function in the context of an adaptive immune response are not well understood. In the lungs of mice undergoing allergic inflamm

  20. Photoprotection in changing times - UV filter efficacy and safety, sensitization processes and regulatory aspects.

    Science.gov (United States)

    Stiefel, C; Schwack, W

    2015-02-01

    As excessive sun exposure is tightly associated with different pathological changes of the skin, for example premature skin ageing or the development of skin cancer, an appropriate protection of the skin against UV radiation is of particular importance. Sun protection products and UV filter substances have evolved continuously in the past few decades. New developments and improved technical conditions of production have led to increasingly effective and efficient products with broadband protection ability. Accordingly, legal requirements have also changed and expanded. Although certain trends exist to harmonize the regulation of sunscreens at a global level, there are still large differences how UV absorbers are approved, which testing methods are prescribed, and which general requirements sun protection products must fulfil. Modern UV filters provide efficient protection against UVA and UVB radiation, are heat and photostable, user-friendly, cost-effective, water resistant and non-toxic. As inorganic and organic UV filters are topically applied to the skin in relatively high concentrations (up to 25%), especially the assessment of their (photo)sensitization potential is of particular importance. Accordingly, skin sensitization is a key endpoint for the legally required safety assessment of cosmetic ingredients in Europe and many other countries. This review will summarize the current regulatory status of different approved UV filters, will describe their beneficial and adverse properties and will give an overview of how the efficacy of sunscreens can be evaluated. Finally, an insight into the basic mechanism of (photo)allergic reactions and existing skin sensitization test methods will be provided. PMID:25256657

  1. Correlated activity supports efficient cortical processing

    Directory of Open Access Journals (Sweden)

    Chou Po Hung

    2015-01-01

    Full Text Available Visual recognition is a computational challenge that is thought to occur via efficient coding. An important concept is sparseness, a measure of coding efficiency. The prevailing view is that sparseness supports efficiency by minimizing redundancy and correlations in spiking populations. Yet, we recently reported that ‘choristers’, neurons that behave more similarly (have correlated stimulus preferences and spontaneous coincident spiking, carry more generalizable object information than uncorrelated neurons (‘soloists’ in macaque inferior temporal (IT cortex. The rarity of choristers (as low as 6% of IT neurons indicates that they were likely missed in previous studies. Here, we report that correlation strength is distinct from sparseness (choristers are not simply broadly tuned neurons, that choristers are located in non-granular output layers, and that correlated activity predicts human visual search efficiency. These counterintuitive results suggest that a redundant correlational structure supports efficient processing and behavior.

  2. hARACNe: improving the accuracy of regulatory model reverse engineering via higher-order data processing inequality tests.

    Science.gov (United States)

    Jang, In Sock; Margolin, Adam; Califano, Andrea

    2013-08-01

    A key goal of systems biology is to elucidate molecular mechanisms associated with physiologic and pathologic phenotypes based on the systematic and genome-wide understanding of cell context-specific molecular interaction models. To this end, reverse engineering approaches have been used to systematically dissect regulatory interactions in a specific tissue, based on the availability of large molecular profile datasets, thus improving our mechanistic understanding of complex diseases, such as cancer. In this paper, we introduce high-order Algorithm for the Reconstruction of Accurate Cellular Network (hARACNe), an extension of the ARACNe algorithm for the dissection of transcriptional regulatory networks. ARACNe uses the data processing inequality (DPI), from information theory, to detect and prune indirect interactions that are unlikely to be mediated by an actual physical interaction. Whereas ARACNe considers only first-order indirect interactions, i.e. those mediated by only one extra regulator, hARACNe considers a generalized form of indirect interactions via two, three or more other regulators. We show that use of higher-order DPI resulted in significantly improved performance, based on transcription factor (TF)-specific ChIP-chip data, as well as on gene expression profile following RNAi-mediated TF silencing.

  3. Comparative epigenomics in distantly related teleost species identifies conserved cis-regulatory nodes active during the vertebrate phylotypic period

    Science.gov (United States)

    Tena, Juan J.; González-Aguilera, Cristina; Fernández-Miñán, Ana; Vázquez-Marín, Javier; Parra-Acero, Helena; Cross, Joe W.; Rigby, Peter W.J.; Carvajal, Jaime J.; Wittbrodt, Joachim; Gómez-Skarmeta, José L.; Martínez-Morales, Juan R.

    2014-01-01

    The complex relationship between ontogeny and phylogeny has been the subject of attention and controversy since von Baer’s formulations in the 19th century. The classic concept that embryogenesis progresses from clade general features to species-specific characters has often been revisited. It has become accepted that embryos from a clade show maximum morphological similarity at the so-called phylotypic period (i.e., during mid-embryogenesis). According to the hourglass model, body plan conservation would depend on constrained molecular mechanisms operating at this period. More recently, comparative transcriptomic analyses have provided conclusive evidence that such molecular constraints exist. Examining cis-regulatory architecture during the phylotypic period is essential to understand the evolutionary source of body plan stability. Here we compare transcriptomes and key epigenetic marks (H3K4me3 and H3K27ac) from medaka (Oryzias latipes) and zebrafish (Danio rerio), two distantly related teleosts separated by an evolutionary distance of 115–200 Myr. We show that comparison of transcriptome profiles correlates with anatomical similarities and heterochronies observed at the phylotypic stage. Through comparative epigenomics, we uncover a pool of conserved regulatory regions (≈700), which are active during the vertebrate phylotypic period in both species. Moreover, we show that their neighboring genes encode mainly transcription factors with fundamental roles in tissue specification. We postulate that these regulatory regions, active in both teleost genomes, represent key constrained nodes of the gene networks that sustain the vertebrate body plan. PMID:24709821

  4. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    Science.gov (United States)

    Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

    2012-01-01

    Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

  5. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    Directory of Open Access Journals (Sweden)

    Joana P Gonçalves

    Full Text Available Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1 apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2 ignore local patterns, abundant in most interesting cases of transcriptional activity; (3 neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4 limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots. Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in

  6. The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests.

    Science.gov (United States)

    Mathaes, Roman; Mahler, Hanns-Christian; Buettiker, Jean-Pierre; Roehl, Holger; Lam, Philippe; Brown, Helen; Luemkemann, Joerg; Adler, Michael; Huwyler, Joerg; Streubel, Alexander; Mohl, Silke

    2016-02-01

    Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process.

  7. 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.

  8. Evolutionary dynamics and functional roles of regulatory systems in plants

    NARCIS (Netherlands)

    Berke, L.

    2015-01-01

    Transcription, the process of generating RNA copies of the genetic information stored in the DNA, is crucial for every organism. As with other essential processes in life, correct activation and repression of transcription is governed by complex regulatory mechanisms. These regulatory mechanisms ope

  9. Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes.

    Science.gov (United States)

    Lobel, Lior; Herskovits, Anat A

    2016-02-01

    Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes) and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY's regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA) under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes), integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner. PMID:26895237

  10. Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Lior Lobel

    2016-02-01

    Full Text Available Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY's regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes, integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner.

  11. HPA-axis stress reactivity in youth depression: evidence of impaired regulatory processes in depressed boys.

    Science.gov (United States)

    Lopez-Duran, Nestor L; McGinnis, Ellen; Kuhlman, Kate; Geiss, Elisa; Vargas, Ivan; Mayer, Stefanie

    2015-01-01

    Given the link between youth depression and stress exposure, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Despite these vast efforts, the underlying mechanisms at play, as well as factors that may explain heterogeneity of past findings, are not well understood. In this study, we simultaneously examined separate components of the HPA-axis response (e.g. activation intensity, peak levels, recovery) to the Socially Evaluated Cold-Pressor Test in a targeted sample of 115 youth (age 9-16), recruited to overrepresent youth with elevated symptoms of depression. Among youth who displayed a cortisol response to the task, depression symptoms were associated with higher peak responses but not greater rate of activation or recovery in boys only. Among those who did not respond to the task, depression symptoms were associated with greater cortisol levels throughout the visit in boys and girls. Results suggest that depression symptoms are associated with a more prolonged activation of the axis and impaired recovery to psychosocial stressors primarily in boys. We discussed two potential mechanistic explanations of the link between depression symptoms and the duration of activation: (1) inhibitory shift (i.e. point at which the ratio of inhibitory and excitatory input into the axis shifts from greater excitatory to greater inhibitory input) or (2) inhibitory threshold (i.e. level of cortisol exposure required to activate the axis' feedback inhibition system).

  12. The regulatory benefits of high levels of affect perception accuracy: a process analysis of reactions to stressors in daily life.

    Science.gov (United States)

    Robinson, Michael D; Moeller, Sara K; Buchholz, Maria M; Boyd, Ryan L; Troop-Gordon, Wendy

    2012-08-01

    Individuals attuned to affective signals from the environment may possess an advantage in the emotion-regulation realm. In two studies (total n = 151), individual differences in affective perception accuracy were assessed in an objective, performance-based manner. Subsequently, the same individuals completed daily diary protocols in which daily stressor levels were reported as well as problematic states shown to be stress-reactive in previous studies. In both studies, individual differences in affect perception accuracy interacted with daily stressor levels to predict the problematic outcomes. Daily stressors precipitated problematic reactions--whether depressive feelings (study 1) or somatic symptoms (study 2)--at low levels of affect perception accuracy, but did not do so at high levels of affect perception accuracy. The findings support a regulatory view of such perceptual abilities. Implications for understanding emotion regulation processes, emotional intelligence, and individual differences in reactivity are discussed. PMID:22775136

  13. Modeling Aspects of Activated Sludge Processes Part l l: Mathematical Process Modeling and Biokinetics of Activated Sludge Processes

    International Nuclear Information System (INIS)

    Mathematical process modeling and biokinetics of activated sludge process were reviewed considering different types of models. It has been evaluated the task group models of ASMI. and 2, and 3 versioned by Henze et al considering the conditions of each model and the different processes of which every model consists. It is revealed that ASMI contains some defects avoided in ASM3. Relied on homogeneity, Models can be classified into homogenous models characterized by taking the activated sludge process as one phase. In this type of models, the internal mass transfer inside the floes was neglected.. Hence, the kinetic parameter produces can be considered inaccurate. The other type of models is the heterogeneous model This type considers the mass transfer operations in addition to the biochemical reaction processes; hence, the resulted kinetic parameters can be considered more accurate than that of homogenous type

  14. Measuring Cognitive and Metacognitive Regulatory Processes during Hypermedia Learning: Issues and Challenges

    Science.gov (United States)

    Azevedo, Roger; Moos, Daniel C.; Johnson, Amy M.; Chauncey, Amber D.

    2010-01-01

    Self-regulated learning (SRL) with hypermedia environments involves a complex cycle of temporally unfolding cognitive and metacognitive processes that impact students' learning. We present several methodological issues related to treating SRL as an event and strengths and challenges of using online trace methodologies to detect, trace, model, and…

  15. Cell surface engineering of renal cell carcinoma with glycosylphosphatidylinositol-anchored TIMP-1 blocks TGF- β 1 activation and reduces regulatory ID gene expression.

    Science.gov (United States)

    Notohamiprodjo, Susan; Djafarzadeh, Roghieh; Rieth, Nicole; Hofstetter, Monika; Jaeckel, Carsten; Nelson, Peter J

    2012-12-01

    Tissue inhibitor of metalloproteinase 1 (TIMP-1) controls matrix metalloproteinase activity through 1:1stoichiometric binding. Human TIMP-1 fused to a glycosylphosphatidylinositol(GPI) anchor (TIMP-1 - GPI) shifts the activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1 - GPI treated renal cell carcinoma cells show increased apoptosis and reduced proliferation.Transcriptomic profiling and regulatory pathway mapping were used to identify the potential mechanisms driving these effects. Significant changes in the DNA binding inhibitors, TGF- β 1/SMAD and BMP pathways resulted from TIMP-1 - GPI treatment. These events were linked to reduced TGF- β 1 signaling mediated by inhibition of proteolytic processing of latent TGF- β 1 by TIMP-1 - GPI. PMID:23667903

  16. An Exploration of Activity Scheduling and Rescheduling Processes

    OpenAIRE

    Chen, Quizi

    2001-01-01

    The objective of this research is to examine processes of activity scheduling and rescheduling by experiments. Activity scheduling processes were examined by using a combination of mail surveys and telephone interviews. It was found that individuals’ schedules are hardly complete. Scheduled activities take place less than 50% of all executed activities. The incompleteness suggests that activity scheduling and execution are a concurrent process and the distiction between is vague. Activities w...

  17. CO2 – intrinsic product, essential substrate and regulatory trigger of microbial and mammalian production processes

    OpenAIRE

    Bastian eBlombach; Ralf eTakors

    2015-01-01

    Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. As a consequence CO2/HCO3- dissociation equilibria arise in fermenters by the growing culture. Anaplerotic reactions make use of the abundant CO2/HCO3- levels for refueling citric acid cycle demands and for enabling oxaloacetate derived products. At the same time CO2 is released manifold in metabolic reactions via decarboxylation activity. The levels of extracellular CO2/H...

  18. CO2 - intrinsic product, essential substrate and regulatory trigger of microbial and mammalian production processes

    OpenAIRE

    Blombach, Bastian; Takors, Ralf

    2015-01-01

    Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. As a consequence, CO 2 / HCO 3 − dissociation equilibria arise in fermenters by the growing culture. Anaplerotic reactions make use of the abundant CO 2 / HCO 3 − levels for refueling citric acid cycle demands and for enabling oxaloacetate-derived products. At the same time, CO2 is released manifold in metabolic reactions via decarboxylation activity. The levels of extrace...

  19. You've found a safety signal--now what?: regulatory implications of industry signal detection activities.

    Science.gov (United States)

    Kahn, Sidney N

    2007-01-01

    Signals detected by measuring disproportionality of drug-event combinations are only statistical indicators of possible real safety issues, and are not per se necessarily medically important. Nevertheless, once a signal is observed, sponsors are obligated by regulations and ethical considerations to determine whether it represents a new product-associated risk by additional analysis, validation and evaluation of its clinical relevance. Signal strength does not necessarily correlate with medical significance. Strong signals most often represent known, expected and/or medically trivial adverse reactions or confounding by treatment indication, common co-morbidities or other common concomitant treatments. Conversely, any product with reasonably extensive clinical use and reporting of suspected adverse reactions is likely to manifest many weak but clinically unimportant signals, creating significant background 'noise'. Since relatively rare, medically important adverse drug reactions are often likely to manifest as weak signals, sponsors face a potentially onerous burden of evaluating multiple signals in order to distinguish true, clinically important events of concern from spurious signals. This paper discusses the regulatory, clinical and potential legal liability issues that confront industry as a consequence of signal identification activities, including: current and anticipated regulatory requirements for detection, assessment and reporting; the reliability of the data used for signal generation; assessment of clinical relevance; organisational approaches and responses to observed signals; targeted clinical and scientific responses to observed signals; and potential regulatory, legal and commercial impact.

  20. p-process nucleosynthesis: Activation experiments

    Science.gov (United States)

    Glorius, J.; Knörzer, M.; Müller, S.; Pietralla, N.; Sauerwein, A.; Sonnabend, K.; Wälzlein, C.; Wiescher, M.

    2011-04-01

    For the astrophysical p process a complex reaction network has to be solved. In the order of 10,000 theoretically predicted reaction rates are needed for simulations of this network. For reactions involving α particles or protons, the predictions in the framework of the Hauser-Feshbach (HF) model were found to deviate from experimental results partially by a factor of 5 or even more. To optimize the predictive power of the applied HF codes, the nuclear physics input has to be improved. For this purpose, the reactions 166ErTm(p,n) as well as the reaction 170Yb(γ,n) have been measured with the activation method at low energies. The data can provide a further test of HF predictions but can also be used to optimize input parameters of the afore mentioned codes. Preliminary results of the experiments are presented and compared to theoretical predictions using the standard settings of the HF codes NON-SMOKER and TALYS.

  1. The Danish Regulatory Reform of Telecommunications

    DEFF Research Database (Denmark)

    Skouby, Knud Erik

    1998-01-01

    An overview of the liberalisation process and regulatory reform of telecommunications in Denmark......An overview of the liberalisation process and regulatory reform of telecommunications in Denmark...

  2. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages.

    Science.gov (United States)

    Clark, Kristopher; MacKenzie, Kirsty F; Petkevicius, Kasparas; Kristariyanto, Yosua; Zhang, Jiazhen; Choi, Hwan Geun; Peggie, Mark; Plater, Lorna; Pedrioli, Patrick G A; McIver, Ed; Gray, Nathanael S; Arthur, J Simon C; Cohen, Philip

    2012-10-16

    Macrophages acquire strikingly different properties that enable them to play key roles during the initiation, propagation, and resolution of inflammation. Classically activated (M1) macrophages produce proinflammatory mediators to combat invading pathogens and respond to tissue damage in the host, whereas regulatory macrophages (M2b) produce high levels of anti-inflammatory molecules, such as IL-10, and low levels of proinflammatory cytokines, like IL-12, and are important for the resolution of inflammatory responses. A central problem in this area is to understand how the formation of regulatory macrophages can be promoted at sites of inflammation to prevent and/or alleviate chronic inflammatory and autoimmune diseases. Here, we demonstrate that the salt-inducible kinases (SIKs) restrict the formation of regulatory macrophages and that their inhibition induces striking increases in many of the characteristic markers of regulatory macrophages, greatly stimulating the production of IL-10 and other anti-inflammatory molecules. We show that SIK inhibitors elevate IL-10 production by inducing the dephosphorylation of cAMP response element-binding protein (CREB)-regulated transcriptional coactivator (CRTC) 3, its dissociation from 14-3-3 proteins and its translocation to the nucleus where it enhances a gene transcription program controlled by CREB. Importantly, the effects of SIK inhibitors on IL-10 production are lost in macrophages that express a drug-resistant mutant of SIK2. These findings identify SIKs as a key molecular switch whose inhibition reprograms macrophages to an anti-inflammatory phenotype. The remarkable effects of SIK inhibitors on macrophage function suggest that drugs that target these protein kinases may have therapeutic potential for the treatment of inflammatory and autoimmune diseases.

  3. Relationship between regulatory T cells and immune activation in human immunodeficiency virus-infected patients interrupting antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Laurence Weiss

    Full Text Available UNLABELLED: Persistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV disease progression. Whether CD4+CD25+ regulatory T cells (Tregs are harmful by suppressing HIV-specific immune responses and/or beneficial through a decrease in immune activation remains debatable. We analysed the relationship between proportion and number of regulatory T cells (Tregs and immune activation in HIV-infected patients interrupting an effective antiretroviral therapy (ART. Twenty-five patients were included in a substudy of a prospective multicenter trial of treatment interruption (TI (ANRS 116. Proportions and numbers of Tregs and the proportion of activated CD4 and CD8 T cells were assessed at baseline and month 12 (M12 of TI. Specific anti-HIV CD4 and CD8 responses were investigated at baseline and M12. Non parametric univariate analyses and multivariate linear regression models were conducted. At baseline, the proportion of Tregs negatively correlated with the proportion of HLA-DR+CD8+T cells (r=-0.519. Following TI, the proportion of Tregs increased from 6.3% to 7.2% (p=0.029; absolute numbers of Tregs decreased. The increase in the proportion of HLA-DR+CD38+CD8+T cells was significantly related to the increase in proportion of Tregs (p=0.031. At M12, the proportion of Tregs did not negatively correlate with CD8 T-cell activation. Nevertheless, Tregs retain a suppressive function since depletion of Treg-containing CD4+CD25+ cells led to an increase in lymphoproliferative responses in most patients studied. Our data suggest that Tregs are efficient in controlling residual immune activation in patients with ART-mediated viral suppression. However, the insufficient increase in the proportion and/or the decrease in the absolute number of Tregs result in a failure to control immune activation following TI. TRIAL REGISTRATION: ClinicalTrials.gov NCT00118677.

  4. Gene expression during the generation and activation of mouse neutrophils: implication of novel functional and regulatory pathways.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Ericson

    Full Text Available As part of the Immunological Genome Project (ImmGen, gene expression was determined in unstimulated (circulating mouse neutrophils and three populations of neutrophils activated in vivo, with comparison among these populations and to other leukocytes. Activation conditions included serum-transfer arthritis (mediated by immune complexes, thioglycollate-induced peritonitis, and uric acid-induced peritonitis. Neutrophils expressed fewer genes than any other leukocyte population studied in ImmGen, and down-regulation of genes related to translation was particularly striking. However, genes with expression relatively specific to neutrophils were also identified, particularly three genes of unknown function: Stfa2l1, Mrgpr2a and Mrgpr2b. Comparison of genes up-regulated in activated neutrophils led to several novel findings: increased expression of genes related to synthesis and use of glutathione and of genes related to uptake and metabolism of modified lipoproteins, particularly in neutrophils elicited by thioglycollate; increased expression of genes for transcription factors in the Nr4a family, only in neutrophils elicited by serum-transfer arthritis; and increased expression of genes important in synthesis of prostaglandins and response to leukotrienes, particularly in neutrophils elicited by uric acid. Up-regulation of genes related to apoptosis, response to microbial products, NFkB family members and their regulators, and MHC class II expression was also seen, in agreement with previous studies. A regulatory model developed from the ImmGen data was used to infer regulatory genes involved in the changes in gene expression during neutrophil activation. Among 64, mostly novel, regulatory genes predicted to influence these changes in gene expression, Irf5 was shown to be important for optimal secretion of IL-10, IP-10, MIP-1α, MIP-1β, and TNF-α by mouse neutrophils in vitro after stimulation through TLR9. This data-set and its analysis using the

  5. Ribavirin Does Not Impair the Suppressive Activity of Foxp3+CD4+CD25+ Regulatory T Cells

    OpenAIRE

    Lee, Jeewon; CHOI, YOON SEOK; Shin, Eui-Cheol

    2013-01-01

    Ribavirin is an antiviral drug used in combination with pegylated interferon-α (IFN-α) for the treatment of hepatitis C virus (HCV) infection. Recently, ribavirin was reported to inhibit the suppressive activity of regulatory T (Treg) cells. In the present study, we re-evaluated the effect of ribavirin on Foxp3+CD4+CD25+ Treg cells from normal donors. First, we examined the expression of CTLA-4 and CD39, which are known to play a role in the suppressive function of Treg cells. We found that r...

  6. Flt3/Flt3L Participates in the Process of Regulating Dendritic Cells and Regulatory T Cells in DSS-Induced Colitis

    Directory of Open Access Journals (Sweden)

    Jing-Wei Mao

    2014-01-01

    Full Text Available The immunoregulation between dendritic cells (DCs and regulatory T cells (T-regs plays an important role in the pathogenesis of ulcerative colitis (UC. Recent research showed that Fms-like tyrosine kinase 3 (Flt3 and Flt3 ligand (Flt3L were involved in the process of DCs regulating T-regs. The DSS-induced colitis model is widely used because of its simplicity and many similarities with human UC. In this study, we observe the disease activity index (DAI and histological scoring, detect the amounts of DCs and T-regs and expression of Flt3/Flt3L, and investigate Flt3/Flt3L participating in the process of DCs regulating T-regs in DSS-induced colitis. Our findings suggest that the reduction of Flt3 and Flt3L expression may possibly induce colonic immunoregulatory imbalance between CD103+MHCII+DCs and CD4+CD25+FoxP3+T-regs in DSS-induced colitis. Flt3/Flt3L participates in the process of regulating DCS and T-regs in the pathogenesis of UC, at least, in the acute stage of this disease.

  7. 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)

    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.

  8. 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)

    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

  9. Establishment of the nuclear regulatory framework for the process of decommissioning of nuclear installations in Mexico; Establecimiento del marco regulador nuclear para el proceso de cierre de instalaciones nucleares en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Salmeron V, J. A.; Camargo C, R.; Nunez C, A., E-mail: juan.salmeron@cnsns.gob.mx [Comision Nacional de Seguridad Nuclear y Salvaguardias, Dr. Barragan 779, Col. Narvarte, 03020 Ciudad de Mexico (Mexico)

    2015-09-15

    Today has not managed any process of decommissioning of nuclear installations in the country; however because of the importance of the subject and the actions to be taken to long term, the Comision Nacional de Seguridad Nuclear y Salvaguardias (CNSNS) in Mexico, accordance with its objectives is developing a National Nuclear Regulatory Framework and defined requirements to ensure the implementation of appropriate safety standards when such activities are performed. In this regard, the national nuclear regulatory framework for nuclear installations and the particular case of nuclear power reactors is presented, as well as a proposed licensing process for the nuclear power plant of Laguna Verde based on international regulations and origin country regulations of the existing reactors in nuclear facilities in accordance with the license conditions of operation to allow to define and incorporate such regulation. (Author)

  10. Two new monoclonal antibodies for biochemical and flow cytometric analyses of human interferon regulatory factor-3 activation, turnover, and depletion.

    Science.gov (United States)

    Rustagi, Arjun; Doehle, Brian P; McElrath, M Juliana; Gale, Michael

    2013-02-01

    Interferon regulatory factor-3 (IRF-3) is a master transcription factor that drives the host intracellular innate immune response to virus infection. The importance of IRF-3 in innate immune responses is highlighted by the fact that pathogenic viruses have developed strategies for antagonism of IRF-3. Several tools exist for evaluation of viral regulation of IRF-3 activation and function, but high-quality monoclonal antibodies that mark the differential activation states of human IRF-3 are lacking. To study IRF-3 activation, turnover, and depletion in a high-throughput manner in the context of virus infection, we have developed two new monoclonal antibodies to human IRF-3. These antibodies detect IRF-3 in virus-infected cells in a wide variety of assays and provide a new tool to study virus-host interactions and innate immune signaling.

  11. Golden rice: scientific, regulatory and public information processes of a genetically modified organism.

    Science.gov (United States)

    Moghissi, A Alan; Pei, Shiqian; Liu, Yinzuo

    2016-01-01

    Historically, agricultural development evolved in three phases. During the first phase the plants were selected on the basis of the availability of a plant with desirable properties at a specific location. The second phase provided the agricultural community with crossbreeding plants to achieve improvement in agricultural production. The evolution of biological knowledge has provided the ability to genetically engineer (GE) crops, one of the key processes within genetically modified organisms (GMO). This article uses golden rice, a species of transgenic Asian rice which contains a precursor of vitamin A in the edible part of the plant as an example of GE/GMO emphasizing Chinese experience in agricultural evolution. It includes a brief review of agricultural evolution to be followed by a description of golden rice development. Golden rice was created as a humanitarian project and has received positive comments by the scientific community and negative voices from certain environmental groups. In this article, we use the Best Available Science (BAS) Concept and Metrics for Evaluation of Scientific Claims (MESC) derived from it to evaluate claims and counter claims on scientific aspects of golden rice. This article concludes that opposition to golden rice is based on belief rather than any of its scientifically derived nutritional, safety or environmental properties.

  12. Golden rice: scientific, regulatory and public information processes of a genetically modified organism.

    Science.gov (United States)

    Moghissi, A Alan; Pei, Shiqian; Liu, Yinzuo

    2016-01-01

    Historically, agricultural development evolved in three phases. During the first phase the plants were selected on the basis of the availability of a plant with desirable properties at a specific location. The second phase provided the agricultural community with crossbreeding plants to achieve improvement in agricultural production. The evolution of biological knowledge has provided the ability to genetically engineer (GE) crops, one of the key processes within genetically modified organisms (GMO). This article uses golden rice, a species of transgenic Asian rice which contains a precursor of vitamin A in the edible part of the plant as an example of GE/GMO emphasizing Chinese experience in agricultural evolution. It includes a brief review of agricultural evolution to be followed by a description of golden rice development. Golden rice was created as a humanitarian project and has received positive comments by the scientific community and negative voices from certain environmental groups. In this article, we use the Best Available Science (BAS) Concept and Metrics for Evaluation of Scientific Claims (MESC) derived from it to evaluate claims and counter claims on scientific aspects of golden rice. This article concludes that opposition to golden rice is based on belief rather than any of its scientifically derived nutritional, safety or environmental properties. PMID:25603722

  13. Basolateral Na+/HCO3– cotransport activity is regulated by the dissociable Na+/H+ exchanger regulatory factor

    Science.gov (United States)

    Bernardo, Angelito A.; Kear, Felicidad T.; Santos, Anna V.P.; Ma, Jianfei; Steplock, Debra; Robey, R. Brooks; Weinman, Edward J.

    1999-01-01

    In the renal proximal tubule, the activities of the basolateral Na+/HCO3– cotransporter (NBC) and the apical Na+/H+ exchanger (NHE3) uniformly vary in parallel, suggesting that they are coordinately regulated. PKA-mediated inhibition of NHE3 is mediated by a PDZ motif–containing protein, the Na+/H+ exchanger regulatory factor (NHE-RF). Given the common inhibition of these transporters after protein kinase A (PKA) activation, we sought to determine whether NHE-RF also plays a role in PKA-regulated NBC activity. Renal cortex immunoblot analysis using anti-peptide antibodies directed against rabbit NHE-RF demonstrated the presence of this regulatory factor in both brush-border membranes (BBMs) and basolateral membranes (BLMs). Using a reconstitution assay, we found that limited trypsin digestion of detergent solubilized rabbit renal BLM preparations resulted in NBC activity that was unaffected by PKA activation. Co-reconstitution of these trypsinized preparations with a recombinant protein corresponding to wild-type rabbit NHE-RF restored the inhibitory effect of PKA on NBC activity in a concentration-dependent manner. NBC activity was inhibited 60% by 10–8M NHE-RF; this effect was not observed in the absence of PKA. Reconstitution with heat-denatured NHE-RF also failed to attenuate NBC activity. To establish further a physiologic role for NHE-RF in NBC regulation, the renal epithelial cell line B-SC-1, which lacks detectable endogenous NHE-RF expression, was engineered to express stably an NHE-RF transgene. NHE-RF–expressing B-SC-1 cells (B-SC-RF) exhibited markedly lower basal levels of NBC activity than did wild-type controls. Inhibition of NBC activity in B-SC-RF cells was enhanced after 10 μM of forskolin treatment, consistent with a postulated role for NHE-RF in mediating the inhibition of NBC activity by PKA. These findings not only suggest NHE-RF involvement in PKA-regulated NBC activity, but also provide a unique molecular mechanism whereby

  14. A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers.

    Directory of Open Access Journals (Sweden)

    Peter W Hunt

    Full Text Available HIV-infected individuals maintaining undetectable viremia in the absence of therapy (HIV controllers often maintain high HIV-specific T cell responses, which has spurred the development of vaccines eliciting HIV-specific T cell responses. However, controllers also often have abnormally high T cell activation levels, potentially contributing to T cell dysfunction, CD4+ T cell depletion, and non-AIDS morbidity. We hypothesized that a weak T regulatory cell (Treg response might contribute to the control of viral replication in HIV controllers, but might also contribute to generalized immune activation, contributing to CD4+ T cell loss. To address these hypotheses, we measured frequencies of activated (CD38+ HLA-DR+, regulatory (CD4+CD25+CD127(dim, HIV-specific, and CMV-specific T cells among HIV controllers and 3 control populations: HIV-infected individuals with treatment-mediated viral suppression (ART-suppressed, untreated HIV-infected "non-controllers" with high levels of viremia, and HIV-uninfected individuals. Despite abnormally high T cell activation levels, controllers had lower Treg frequencies than HIV-uninfected controls (P = 0.014. Supporting the propensity for an unusually low Treg response to viral infection in HIV controllers, we observed unusually high CMV-specific CD4+ T cell frequencies and a strong correlation between HIV-specific CD4+ T cell responses and generalized CD8+ T cell activation levels in HIV controllers (P ≤ 0.001. These data support a model in which low frequencies of Tregs in HIV controllers may contribute to an effective adaptive immune response, but may also contribute to generalized immune activation, potentially contributing to CD4 depletion.

  15. Implementation of a Quality Management System in regulatory inspection activities; Implantacao de um sistema de gestao da qualidade em atividades de inspecao regulatoria

    Energy Technology Data Exchange (ETDEWEB)

    Pires do Rio, Monica; Ferreira, Paulo Roberto; Cunha, Paulo G. da; Acar, Maria Elizabeth [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2005-07-01

    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.

  16. A flexible regulatory framework

    International Nuclear Information System (INIS)

    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

  17. 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.

  18. The Creation of a French Basic Nuclear Installation - Description of the Regulatory Process - 13293

    International Nuclear Information System (INIS)

    CEA is a French government-funded technological research organization. It has to build a medium-level waste interim storage facility because the geological repository will not be available until 2025. This interim storage facility, called DIADEM, has to be available in 2017. These wastes are coming from the research facilities for spent fuel reprocessing and the dismantling of the most radioactive parts of nuclear facilities. The CEA handles the waste management by inventorying the needs and updating them regularly. The conception of the facility is mainly based on this inventory. It provides quantity and characteristics of wastes and it gives the production schedule until 2035. Beyond mass and volume, main characteristics of these radioactive wastes are chemical nature, radioisotopes, radioactivity, radiation dose, the heat emitted, corrosive or explosive gas production, etc. These characteristics provide information to study the repository safety. DIADEM mainly consists of a concrete cell, isolated from the outside, wherein stainless steel welded containers are stored, stacked in a vertical position in the racks. DIADEM is scheduled to store three types of 8 mm-thick, stainless steel cylindrical containers with an outside diameter 498 mm and height from 620 to 2120 mm. DIADEM will be a basic nuclear installation (INB in French) because of overall activity of radioactive substances stored. The creation of a French basic nuclear installation is subject to authorization according to the French law No. 2006-686 of 13 June 2006 on Transparency and Security in the Nuclear Field. The authorization takes into account the technical and financial capacities of the licensee which must allow him to conduct his project in compliance with these interests, especially to cover the costs of decommissioning the installation and conduct remediation work, and to monitor and maintain its location site or, for radioactive waste disposal installations, to cover the definitive shut

  19. The Creation of a French Basic Nuclear Installation - Description of the Regulatory Process - 13293

    Energy Technology Data Exchange (ETDEWEB)

    Mahe, Carole [CEA Marcoule - BP17171 - 30207 Bagnols-Sur-Ceze (France); Leroy, Christine [CEA Cadarache - 13108 Saint Paul-Lez-Durance (France)

    2013-07-01

    CEA is a French government-funded technological research organization. It has to build a medium-level waste interim storage facility because the geological repository will not be available until 2025. This interim storage facility, called DIADEM, has to be available in 2017. These wastes are coming from the research facilities for spent fuel reprocessing and the dismantling of the most radioactive parts of nuclear facilities. The CEA handles the waste management by inventorying the needs and updating them regularly. The conception of the facility is mainly based on this inventory. It provides quantity and characteristics of wastes and it gives the production schedule until 2035. Beyond mass and volume, main characteristics of these radioactive wastes are chemical nature, radioisotopes, radioactivity, radiation dose, the heat emitted, corrosive or explosive gas production, etc. These characteristics provide information to study the repository safety. DIADEM mainly consists of a concrete cell, isolated from the outside, wherein stainless steel welded containers are stored, stacked in a vertical position in the racks. DIADEM is scheduled to store three types of 8 mm-thick, stainless steel cylindrical containers with an outside diameter 498 mm and height from 620 to 2120 mm. DIADEM will be a basic nuclear installation (INB in French) because of overall activity of radioactive substances stored. The creation of a French basic nuclear installation is subject to authorization according to the French law No. 2006-686 of 13 June 2006 on Transparency and Security in the Nuclear Field. The authorization takes into account the technical and financial capacities of the licensee which must allow him to conduct his project in compliance with these interests, especially to cover the costs of decommissioning the installation and conduct remediation work, and to monitor and maintain its location site or, for radioactive waste disposal installations, to cover the definitive shut

  20. Hydrodynamic Limit For An Active Exclusion Process

    OpenAIRE

    Clément, Erignoux

    2016-01-01

    Collective dynamics can be observed among many animal species, and have given rise in the last decades to an active and interdisciplinary field of study. Such behaviors are often modeled by active matter, in which each individual is self-driven and tends to update its velocity depending on the one of its neighbors. In a classical model introduced by Vicsek \\and al., as well as in numerous related active matter models, a phase transition between chaotic behavior at high temperature and global ...

  1. 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.; Hanna, Luke A.; Judd, Chaeli R.; Blake, Kara M.

    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. Objectives for 2.1.7 are the following: • To work with stakeholders to streamline the MHK regulatory permitting process. • To work with stakeholders to gather information on needs and priorities for environmental assessment of MHK development. • To communicate research findings and directions to the MHK industry and stakeholders. • To engage in spatial planning processes in order to further the development of the MHK industry. These objectives are met through three subtasks, each of which are described in this report: • 2.1.7.1—Regulatory Assistance • 2.1.7.2—Stakeholder Outreach • 2.1.7.3—Coastal and Marine Spatial Planning As the MHK industry works with the regulatory community and stakeholders to plan, site, permit and license MHK technologies they have an interest in a predictable, efficient, and transparent process. Stakeholders and regulators have an interest in processes that result in sustainable use of ocean space with minimal effects to existing ocean users. Both stakeholders and regulators have an interest in avoiding legal challenges by meeting the intent of federal, state, and local laws that govern siting and operation of MHK technologies. The intention of work under 2.1.7 is to understand these varied interests, explore mechanisms to reduce conflict, identify efficiencies, and ultimately identify pathways to reduce the regulatory costs, time, and potential environmental impacts associated with developing, siting, permitting, and deploying MHK systems.

  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)

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

    International Nuclear Information System (INIS)

    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)

  4. Regulatory review of safety cases and safety assessments for near surface

    International Nuclear Information System (INIS)

    The activities of the ASAM Regulatory Review Working Group are presented. Regulatory review of the safety assessment is made. It includes the regulatory review of post-closure safety assessment; safety case development and confidence building. The ISAM methodology is reviewed and SA system description is presented. Recommendations on the review process management are given

  5. 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)

    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

  6. 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)

    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.

  7. Regulatory Competition in Global Financial Markets

    DEFF Research Database (Denmark)

    Ringe, Georg

    2016-01-01

    Regulatory arbitrage in financial markets refers to a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of moving trading abroad or relocating activities or operations of financial institutions to other jurisdictions. Where this happens......, such arbitrage can trigger regulatory competition between jurisdictions that may respond to the relocation of financial services (or threats to relocate) by moderating their regulatory standards. This study develops a framework for the assessment of both phenomena in the context of financial regulation...... and the evaluation of their merits. I argue that regulatory competition has many advantages over alternative global approaches, notably international harmonization of regulation, by offering a dynamic process for the discovery of efficient regulatory standards. However, the risk is that countries lower...

  8. Low Activity Waste Feed Process Control Strategy

    International Nuclear Information System (INIS)

    The primary purpose of this document is to describe the overall process control strategy for monitoring and controlling the functions associated with the Phase 1B high-level waste feed delivery. This document provides the basis for process monitoring and control functions and requirements needed throughput the double-shell tank system during Phase 1 high-level waste feed delivery. This document is intended to be used by (1) the developers of the future Process Control Plan and (2) the developers of the monitoring and control system

  9. Low Activity Waste Feed Process Control Strategy

    Energy Technology Data Exchange (ETDEWEB)

    STAEHR, T.W.

    2000-06-14

    The primary purpose of this document is to describe the overall process control strategy for monitoring and controlling the functions associated with the Phase 1B high-level waste feed delivery. This document provides the basis for process monitoring and control functions and requirements needed throughput the double-shell tank system during Phase 1 high-level waste feed delivery. This document is intended to be used by (1) the developers of the future Process Control Plan and (2) the developers of the monitoring and control system.

  10. LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages.

    Science.gov (United States)

    Ruggiero, Tina; Trabucchi, Michele; De Santa, Francesca; Zupo, Simona; Harfe, Brian D; McManus, Michael T; Rosenfeld, M Geoff; Briata, Paola; Gherzi, Roberto

    2009-09-01

    The importance of post-transcriptional mechanisms for the regulation of the homoeostasis of the immune system and the response to challenge by microorganisms is becoming increasingly appreciated. We investigated the contribution of microRNAs (miRNAs) to macrophage activation induced by lipopolysaccharide (LPS). We first observed that Dicer knockout in bone marrow-derived macrophages (BMDMs) increases the LPS-induced expression of some inflammation mediators. miRNA microarray analysis in BMDMs revealed that LPS significantly induces the expression of a single miRNA, miR-155, and this induction depends on enhanced miR-155 maturation from its precursors. The single-strand RNA-binding protein KH-type splicing regulatory protein (KSRP) binds to the terminal loop of miR-155 precursors and promotes their maturation. Both inhibition of miR-155 and KSRP knockdown enhance the LPS-induced expression of select inflammation mediators, and the effect of KSRP knockdown is reverted by mature miR-155. Our studies unveil the existence of an LPS-dependent post-transcriptional regulation of miR-155 biogenesis. Once induced, miR-155 finely tunes the expression of select inflammation mediators in response to LPS. PMID:19423639

  11. Modulation of Pantothenate Kinase 3 Activity by Small Molecules that Interact with the Substrate/Allosteric Regulatory Domain

    Energy Technology Data Exchange (ETDEWEB)

    Leonardi, Roberta; Zhang, Yong-Mei; Yun, Mi-Kyung; Zhou, Ruobing; Zeng, Fu-Yue; Lin, Wenwei; Cui, Jimmy; Chen, Taosheng; Rock, Charles O.; White, Stephen W.; Jackowski, Suzanne (SJCH)

    2010-09-27

    Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis of site-directed mutants indicates that pantothenate binds in a tunnel adjacent to the active site that is occupied by the pantothenate moiety of the acetyl-CoA regulator in the PanK3 acetyl-CoA binary complex. A high-throughput screen for PanK3 inhibitors and activators was applied to a bioactive compound library. Thiazolidinediones, sulfonylureas and steroids were inhibitors, and fatty acyl-amides and tamoxifen were activators. The PanK3 activators and inhibitors either stimulated or repressed CoA biosynthesis in HepG2/C3A cells. The flexible allosteric acetyl-CoA regulatory domain of PanK3 also binds the substrates, pantothenate and pantetheine, and small molecule inhibitors and activators to modulate PanK3 activity.

  12. Treatment and conditioning processes for low and medium activity waste

    International Nuclear Information System (INIS)

    This chapter reports on experimental studies of precipitation and membrane processes, exchange processes, particular techniques, and immobilization methods. Topics considered include the separation of actinides and fission products from medium activity waste (MAW) concentrate, the decontamination of low activity liquid wastes from fuel fabrication plants by ultrafiltration, active liquid treatment by a combination of precipitation and membrane processes, the treatment of liquid wastes by flocculation, the denitration and chemical precipitation of MAW concentrate, inorganic ion-exchangers prepared via a sol-gel process, liquid waste treatment by electrical processes, the incorporation of low and medium activity wastes in cement, and the conditioning of highly radioactive residues by utilizing a drum-dryer

  13. 23 CFR 450.208 - Coordination of planning process activities.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Coordination of planning process activities. 450.208... Coordination of planning process activities. (a) In carrying out the statewide transportation planning process... CFR part 500. (e) States may apply asset management principles and techniques in establishing...

  14. Human regulatory T cell suppressive function is independent of apoptosis induction in activated effector T cells.

    Directory of Open Access Journals (Sweden)

    Yvonne Vercoulen

    Full Text Available BACKGROUND: CD4(+CD25(+FOXP3(+ Regulatory T cells (Treg play a central role in the immune balance to prevent autoimmune disease. One outstanding question is how Tregs suppress effector immune responses in human. Experiments in mice demonstrated that Treg restrict effector T cell (Teff responses by deprivation of the growth factor IL-2 through Treg consumption, resulting in apoptosis of Teff. PRINCIPAL FINDINGS: In this study we investigated the relevance of Teff apoptosis induction to human Treg function. To this end, we studied naturally occurring Treg (nTreg from peripheral blood of healthy donors, and, to investigate Treg function in inflammation in vivo, Treg from synovial fluid of Juvenile Idiopathic Arthritis (JIA patients (SF-Treg. Both nTreg and SF-Treg suppress Teff proliferation and cytokine production efficiently as predicted. However, in contrast with murine Treg, neither nTreg nor SF-Treg induce apoptosis in Teff. Furthermore, exogenously supplied IL-2 and IL-7 reverse suppression, but do not influence apoptosis of Teff. SIGNIFICANCE: Our functional data here support that Treg are excellent clinical targets to counteract autoimmune diseases. For optimal functional outcome in human clinical trials, future work should focus on the ability of Treg to suppress proliferation and cytokine production of Teff, rather than induction of Teff apoptosis.

  15. Overcoming regulatory, political and operational challenges to boost Alaska E and P and pipeline activity

    International Nuclear Information System (INIS)

    This presentation addressed a range of issues associated with the development of the Alaska Highway Gas Pipeline, including fundamentals regarding North American gas supply and demand for power generation, industrial use and residential and commercial use; pipeline routing. It also addressed issues regarding the United States Energy Bill and Alaska readiness in terms of regulatory approvals and right-of-way applications, TransCanada readiness, and other key issues. Natural gas supply from the East Coast, Western Canadian Sedimentary Basin, United States Rockies, Gulf of Mexico and other localities in the United States were illustrated in a graph along with natural gas market prices and a comparison of recent NYMEX gas price forecasts. The author indicates that 10 to 15 billion cubic feet per day of new supply will be needed. The Mackenzie project continues to work towards an in-service date of 2009. However, a strong competitor and alternative to northern gas is liquefied natural gas (LNG). The issue of integrating Alaskan gas into the existing Alberta pipeline grid was also discussed along with technologies to improve pipeline costs and issues regarding First Nation consultations. TransCanada believes that Alaskan gas can be delivered to markets in the United States by 2012 if existing pipeline infrastructures are used as well as existing legislation in Canada. 4 figs

  16. Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes.

    Science.gov (United States)

    Infante, Carlos R; Mihala, Alexandra G; Park, Sungdae; Wang, Jialiang S; Johnson, Kenji K; Lauderdale, James D; Menke, Douglas B

    2015-10-12

    The amniote phallus and limbs differ dramatically in their morphologies but share patterns of signaling and gene expression in early development. Thus far, the extent to which genital and limb transcriptional networks also share cis-regulatory elements has remained unexplored. We show that many limb enhancers are retained in snake genomes, suggesting that these elements may function in non-limb tissues. Consistent with this, our analysis of cis-regulatory activity in mice and Anolis lizards reveals that patterns of enhancer activity in embryonic limbs and genitalia overlap heavily. In mice, deletion of HLEB, an enhancer of Tbx4, produces defects in hindlimbs and genitalia, establishing the importance of this limb-genital enhancer for development of these different appendages. Further analyses demonstrate that the HLEB of snakes has lost hindlimb enhancer function while retaining genital activity. Our findings identify roles for Tbx4 in genital development and highlight deep similarities in cis-regulatory activity between limbs and genitalia.

  17. 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.

  18. The changing regulatory environment

    International Nuclear Information System (INIS)

    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

  19. Antibacterial and quorum sensing regulatory activities of some traditional Eastern-European medicinal plants

    Directory of Open Access Journals (Sweden)

    Tolmacheva Anna A.

    2014-06-01

    Full Text Available The objective of this study was to screen extracts of twenty Eastern European medicinal plants, using wild-type and reporter Chromobacterium violaceum bioassays, for novel components that target bacterial cells and their quorum sensing (QS communication systems. Three types of activity and their combinations were revealed: (i direct antimicrobial growth-inhibitory activity, (ii non-specific and specific pro-QS activities, (iii anti-QS activity. Among seven plant extracts showing direct growth-inhibitory activity, the strongest effect was shown by Arctostaphylos uva- -ursi (bearberry leaves. Many plants stimulated violacein production by wild-type C. violaceum ATCC 31532 in a non-specific manner, and only the herb Bidens tripartita (three-lobe beggarticks contained compounds that mimic acyl-homoserine lactone and operated as a QS agonist. Anti-QS activity was found in eleven plants including Quercus robur (oak cortex, Betula verrucosa (birch buds and Eucalyptus viminalis (Manna Gum leaves. Subsequent statistical analysis showed differences between antimicrobial and anti-QS activities, whereas both activities were defined by phylogenetic position of medical resource plant. Finally, extract from Quercus robur cortex revealed at least two fractions, showing different anti-QS mechanisms. These data confirm that multicomponent anti-infectious mechanisms are used by plants, which may be useful for drug development

  20. Modelling the Active Hearing Process in Mosquitoes

    Science.gov (United States)

    Avitabile, Daniele; Homer, Martin; Jackson, Joe; Robert, Daniel; Champneys, Alan

    2011-11-01

    A simple microscopic mechanistic model is described of the active amplification within the Johnston's organ of the mosquito species Toxorhynchites brevipalpis. The model is based on the description of the antenna as a forced-damped oscillator coupled to a set of active threads (ensembles of scolopidia) that provide an impulsive force when they twitch. This twitching is in turn controlled by channels that are opened and closed if the antennal oscillation reaches a critical amplitude. The model matches both qualitatively and quantitatively with recent experiments. New results are presented using mathematical homogenization techniques to derive a mesoscopic model as a simple oscillator with nonlinear force and damping characteristics. It is shown how the results from this new model closely resemble those from the microscopic model as the number of threads approach physiologically correct values.

  1. LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity.

    Directory of Open Access Journals (Sweden)

    Roberta Bertelli

    Full Text Available Immunosuppressive regulatory T cells (Tregs have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna and/or drug induced (Adriamycin nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg was given as single shot in C57BL/6, p2rx7⁻/⁻ and Foxp3EGFP; free IL-2 (18.000 U or, in alternative, IL-2 coupled with JES6-1 mAb (IL-2/anti-IL-2 were injected before LPS. Peripheral and tissue Tregs/total CD4+ cell ratio, urinary parameters and renal histology were evaluated for 15 days. IL-2 administration to wild type mice had no effect on peripheral Tregs number, whereas a significant increase was induced by the IL-2/anti-IL-2 immunocomplex after 5 days. Spleen and lymph nodes Tregs were comparably increased. In p2rx7⁻/⁻ mice, IL-2/anti-IL-2 treatment resulted in increase of peripheral Tregs but did not modify the spleen and lymph nodes quota. LPS induced comparable and transient proteinuria in both wild type and p2rx7⁻/⁻ mice. Proteinuria was inhibited by co-infusion of human IL-2, with reduction at each phase of the disease (24 -48 and 72 hours whereas IL-2/anti-IL-2 produced weaker effects. In all mice (wild type and p2rx7⁻/⁻ and irrespective of treatment (IL-2, IL-2/anti-IL-2, LPS was associated with progressive signs of renal pathologic involvement resulting in glomerulosclerosis. In conclusion, IL-2 plays a transient protective effect on proteinuria induced by LPS independent of circulating or tissue Tregs but does not modify the outcome of renal degenerative renal lesions.

  2. 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.

  3. Non-hypoxic activation of the negative regulatory feedback loop of prolyl-hydroxylase oxygen sensors.

    Science.gov (United States)

    Tug, Suzan; Delos Reyes, Buena; Fandrey, Joachim; Berchner-Pfannschmidt, Utta

    2009-07-10

    Hypoxia inducible factors (HIF) coordinate cellular responses towards hypoxia. HIFs are mainly regulated by a group of prolyl-hydroxylases (PHDs) that in the presence of oxygen, target the HIFalpha subunit for degradation. Herein, we studied the role of nitric oxide (NO) in regulating PHD activities under normoxic conditions. In the present study we show that different NO-donors initially inhibited endogenous PHD2 activity which led to accumulation of HIF-1alpha subsequently to enhance HIF-1 dependent increased PHD2 promoter activity. Consequently PHD2 abundance and activity were strongly induced which caused downregulation of HIF-1alpha. Interestingly, upregulation of endogenous PHD2 activity by NO was not found in cells that lack an intact pVHL dependent degradation pathway. Recovery of PHD activity required intact cells and was not observed in cell extracts or recombinant PHD2. In conclusion induction of endogenous PHD2 activity by NO is dependent on a feedback loop initiated despite normoxic conditions. PMID:19427832

  4. Regulatory aspects of NPP safety in Ukraine

    International Nuclear Information System (INIS)

    After a short overview of the Ukrainian nuclear power program, detailed information is presented describing the organisation, activity, responsibility and tasks of the Ukrainian regulatory authority, including its interactions with central executive authorities involved in nuclear and radiation safety. Main activities described include: inspection of nuclear installations i.e. in-service inspection of the equipment, licensing of NPPs especially when large-scale modernisation is concerned. Principles of the Regulatory Authority in consideration and assessment process of Safety Analysis report are listed as a legislative basis applied during the licensing process

  5. [Life as regulatory activity and self-realization: debate surrounding the concept of biological regulation in Goldstein and Canguilhem].

    Science.gov (United States)

    Ostachuk, Agustín

    2015-12-01

    The influence of Kurt Goldstein on the thinking of Georges Canguilhem extended throughout his entire work. This paper seeks to examine this relationship in order to conduct a study of the norm as a nexus or connection between the concept and life. Consequently, this work will be a reflection on the approach to life as a regulatory activity and self-realization. For this, it will be necessary to redefine the concepts of health and disease, and make a crossover between the two. At the end of this trajectory, it will be found that these concepts can explain the identity between the concept and life, which leads to the unexpected conclusion that the cure is ultimately self-healing. PMID:25807361

  6. HLA Class II Antibody Activation of Endothelial Cells Promotes Th17 and Disrupts Regulatory T Lymphocyte Expansion.

    Science.gov (United States)

    Lion, J; Taflin, C; Cross, A R; Robledo-Sarmiento, M; Mariotto, E; Savenay, A; Carmagnat, M; Suberbielle, C; Charron, D; Haziot, A; Glotz, D; Mooney, N

    2016-05-01

    Kidney transplantation is the most successful treatment option for patients with end-stage renal disease, and chronic antibody-mediated rejection is the principal cause of allograft loss. Predictive factors for chronic rejection include high levels of HLA alloantibodies (particularly HLA class II) and activation of graft endothelial cells (ECs). The mechanistic basis for this association is unresolved. We used an experimental model of HLA-DR antibody stimulation of microvascular ECs to examine the mechanisms underlying the association between HLA class II antibodies, EC activation and allograft damage. Activation of ECs with the F(Ab')2 fragment of HLA-DR antibody led to phosphorylation of Akt, ERK and MEK and increased IL-6 production by ECs cocultured with allogeneic peripheral blood mononuclear cells (PBMCs) in an Akt-dependent manner. We previously showed that HLA-DR-expressing ECs induce polarization of Th17 and FoxP3(bright) regulatory T cell (Treg) subsets. Preactivation of ECs with anti-HLA-DR antibody redirected EC allogenicity toward a proinflammatory response by decreasing amplification of functional Treg and by further increasing IL-6-dependent Th17 expansion. Alloimmunized patient serum containing relevant HLA-DR alloantibodies selectively bound and increased EC secretion of IL-6 in cocultures with PBMCs. These data contribute to understanding of potential mechanisms of antibody-mediated endothelial damage independent of complement activation and FcR-expressing effector cells. PMID:26614587

  7. 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

  8. 3 CFR - Regulatory Review

    Science.gov (United States)

    2010-01-01

    ... transparency; encourage public participation in agency regulatory processes; offer suggestions on the role of cost-benefit analysis; address the role of distributional considerations, fairness, and concern for the... delay; clarify the role of the behavioral sciences in formulating regulatory policy; and identify...

  9. ACTIVE FRONT STEERING DURING BRAKING PROCESS

    Institute of Scientific and Technical Information of China (English)

    CHEN Deling; CHEN Li; YIN Chengliang; ZHANG Yong

    2008-01-01

    An active front steering (AFS) intervention control during braking for vehicle stability is presented. Based on the investigation of AFS mechanism, a simplified model of steering system is established and integrated with vehicle model. Then the AFS control on vehicle handling dynamics during braking is designed. Due to the difficulties associated with the sideslip angle measurement of vehicle, a state observer is designed to provide real time estimation. Thereafter, the controller with the feedback of both sideslip and yaw angle is implemented. To evaluate the system control, the proposed AFS controlled vehicle has been tested in the Hardware-in-the-loop-simulation (HILS) system and compared with that of conventional vehicle. Results show that AFS can improve vehicle lateral stability effectively without reducing the braking performance.

  10. Regulatory Activity of Polyunsaturated Fatty Acids in T-Cell Signaling

    Science.gov (United States)

    Kim, Wooki; Khan, Naim A.; McMurray, David N.; Prior, Ian A.; Wang, Naisyin; Chapkin, Robert S.

    2010-01-01

    n-3 polyunsaturated fatty acids (PUFA) are considered to be authentic immunosuppressors and appear to exert beneficial effects with respect to certain immune-mediated diseases. In addition to promoting T-helper 1 (Th1) cell to T-helper 2 (Th2) cell effector T-cell differentiation, n-3 PUFA may also exert anti-inflammatory actions by inducing apoptosis in Th1 cells. With respect to mechanisms of action, effects range from the modulation of membrane receptors to gene transcription via perturbation of a number of second messenger cascades. In this review, the putative targets of anti-inflammatory n-3 PUFA, activated during early and late events of T-cell activation will be discussed. Studies have demonstrated that these fatty acids alter plasma membrane micro-organization (lipid rafts) at the immunological synapse, the site where T-cells and antigen presenting cells (APC) form a physical contact for antigen initiated T-cell signaling. In addition, the production of diacylglycerol and the activation of different isoforms of protein kinase C (PKC), mitogen activated protein kinase (MAPK), calcium signaling, and nuclear translocation/activation of transcriptional factors, can be modulated by n-3 PUFA. Advantages and limitations of diverse methodologies to study the membrane lipid raft hypothesis, as well as apparent contradictions regarding the effect of n-3 PUFA on lipid rafts will be critically presented. PMID:20176053

  11. 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.

  12. Human Blood and Mucosal Regulatory T Cells Express Activation Markers and Inhibitory Receptors in Inflammatory Bowel Disease.

    Directory of Open Access Journals (Sweden)

    James D Lord

    Full Text Available FOXP3+ regulatory T cells (Tregs are critical for preventing intestinal inflammation. However, FOXP3+ T cells are paradoxically increased in the intestines of patients with the inflammatory bowel disease (IBD ulcerative colitis (UC or Crohn's disease (CD. We determined whether these FOXP3+ cells in IBD patients share or lack the phenotype of such cells from patients without IBD.We quantified and characterized FOXP3+ Treg populations, as well as FOXP3- CD4+ T cells, in the lamina propria lymphocytes (LPL of intestine surgically resected from patients with and without IBD, and in the blood of controls or Crohn's patients with or without disease activity.In all samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg marker Helios, suggesting that, in IBD, these cells are not entirely "induced" Tregs (iTregs derived from activated effector T cells. Helios+ and Helios- FOXP3+ T cells demonstrated similar expression of maturation markers, activation markers, and inhibitory molecules between IBD patients and controls, while FOXP3- cells paradoxically expressed more of the inhibitory receptors CD39, CTLA4, and PD-1 in inflamed mucosa. Greater expression of activation markers was also seen in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients and controls, indicating that Tregs are effectively activated by antigen in IBD.Extensive immunophenotyping revealed that Helios+ and Helios- mucosal Tregs exist at a similar frequency, and have a similar expression of inhibitory molecules and activation markers in patients with IBD as in healthy controls.

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

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2013-10-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2013-05-01

    Full Text Available 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.

  15. 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.

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

    International Nuclear Information System (INIS)

    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

  17. 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)

    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

  18. Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Marco Tucci

    2010-01-01

    Full Text Available Lupus nephritis (LN occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th- 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role. These cytokines are locally produced by both macrophages and dendritic cells (DCs which attract other inflammatory cells leading to maintenance of the kidney inflammation. However, other populations including T-cells and B-cells are integral for the development and worsening of renal damage. T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping with defective T-regulatory (Treg cell function regards as further event contributing to the glomerular damage. These populations also activate B-cells to produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic mechanism that involves different players and the evaluation of their activity may provide an effective tool for monitoring the onset of the disease.

  19. ppGpp controlled by the Gac/Rsm regulatory pathway sustains biocontrol activity in Pseudomonas fluorescens CHA0.

    Science.gov (United States)

    Takeuchi, Kasumi; Yamada, Kosumi; Haas, Dieter

    2012-11-01

    In Pseudomonas fluorescens CHA0 and other fluorescent pseudomonads, the Gac/Rsm signal transduction pathway is instrumental for secondary metabolism and biocontrol of root pathogens via the expression of regulatory small RNAs (sRNAs). Furthermore, in strain CHA0, an imbalance in the Krebs cycle can affect the strain's ability to produce extracellular secondary metabolites, including biocontrol factors. Here, we report the metabolome of wild-type CHA0, a gacA-negative mutant, which has lost Gac/Rsm activities, and a retS-negative mutant, which shows strongly enhanced Gac/Rsm-dependent activities. Capillary electrophoresis-based metabolomic profiling revealed that the gacA and retS mutations had opposite effects on the intracellular levels of a number of central metabolites, suggesting that the Gac/Rsm pathway regulates not only secondary metabolism but also primary metabolism in strain CHA0. Among the regulated metabolites identified, the alarmone guanosine tetraphosphate (ppGpp) was characterized in detail by the construction of relA (for ppGpp synthase) and spoT (for ppGpp synthase/hydrolase) deletion mutants. In a relA spoT double mutant, ppGpp synthesis was completely abolished, the expression of Rsm sRNAs was attenuated, and physiological functions such as antibiotic production, root colonization, and plant protection were markedly diminished. Thus, ppGpp appears to be essential for sustaining epiphytic fitness and biocontrol activity of strain CHA0.

  20. Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3' regulatory region.

    Science.gov (United States)

    Gostissa, Monica; Yan, Catherine T; Bianco, Julia M; Cogné, Michel; Pinaud, Eric; Alt, Frederick W

    2009-12-10

    B-cell malignancies, such as human Burkitt's lymphoma, often contain translocations that link c-myc or other proto-oncogenes to the immunoglobulin heavy chain locus (IgH, encoded by Igh). The nature of elements that activate oncogenes within such translocations has been a long-standing question. Translocations within Igh involve DNA double-strand breaks initiated either by the RAG1/2 endonuclease during variable, diversity and joining gene segment (V(D)J) recombination, or by activation-induced cytidine deaminase (AID, also known as AICDA) during class switch recombination (CSR). V(D)J recombination in progenitor B (pro-B) cells assembles Igh variable region exons upstream of mu constant region (Cmu) exons, which are the first of several sets of C(H) exons ('C(H) genes') within a C(H) locus that span several hundred kilobases (kb). In mature B cells, CSR deletes Cmu and replaces it with a downstream C(H) gene. An intronic enhancer (iEmu) between the variable region exons and Cmu promotes V(D)J recombination in developing B cells. Furthermore, the Igh 3' regulatory region (Igh3'RR) lies downstream of the C(H) locus and modulates CSR by long-range transcriptional enhancement of C(H) genes. Transgenic mice bearing iEmu or Igh3'RR sequences fused to c-myc are predisposed to B lymphomas, demonstrating that such elements can confer oncogenic c-myc expression. However, in many B-cell lymphomas, Igh-c-myc translocations delete iEmu and place c-myc up to 200 kb upstream of the Igh3'RR. Here we address the oncogenic role of the Igh3'RR by inactivating it in two distinct mouse models for B-cell lymphoma with Igh-c-myc translocations. We show that the Igh3'RR is dispensable for pro-B-cell lymphomas with V(D)J recombination-initiated translocations, but is required for peripheral B-cell lymphomas with CSR-associated translocations. As the Igh3'RR is not required for CSR-associated Igh breaks or Igh-c-myc translocations in peripheral B-cell lymphoma progenitors, we conclude that

  1. Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment.

    Science.gov (United States)

    Kueh, Hao Yuan; Yui, Mary A; Ng, Kenneth K H; Pease, Shirley S; Zhang, Jingli A; Damle, Sagar S; Freedman, George; Siu, Sharmayne; Bernstein, Irwin D; Elowitz, Michael B; Rothenberg, Ellen V

    2016-08-01

    During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation. PMID:27376470

  2. Synergistic transcriptional activation by one regulatory protein in response to two metabolites

    OpenAIRE

    Bundy, Becky M.; Collier, Lauren S.; Hoover, Timothy R.; Neidle, Ellen L.

    2002-01-01

    BenM is a LysR-type bacterial transcriptional regulator that controls aromatic compound degradation in Acinetobacter sp. ADP1. Here, in vitro transcription assays demonstrated that two metabolites of aromatic compound catabolism, benzoate and cis,cis-muconate, act synergistically to activate gene expression. The level of BenM-regulated benA transcription was significantly higher in response to both compounds than the combined levels due to each alone. These compounds also were more effective ...

  3. Activation and Recruitment of Regulatory T Cells via Chemokine Receptor Activation in Trichinella spiralis-Infected Mice

    OpenAIRE

    Ahn, Jeong-Bin; Kang, Shin Ae; Kim, Dong-Hee; Yu, Hak Sun

    2016-01-01

    As most infections by the helminth parasite elicit the recruitment of CD4+CD25+Foxp3+ T (Treg) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated Treg cells, we compared the expression levels of Treg cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of Treg cells was monitore...

  4. Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation.

    Science.gov (United States)

    Masters, Seth L; Lagou, Vasiliki; Jéru, Isabelle; Baker, Paul J; Van Eyck, Lien; Parry, David A; Lawless, Dylan; De Nardo, Dominic; Garcia-Perez, Josselyn E; Dagley, Laura F; Holley, Caroline L; Dooley, James; Moghaddas, Fiona; Pasciuto, Emanuela; Jeandel, Pierre-Yves; Sciot, Raf; Lyras, Dena; Webb, Andrew I; Nicholson, Sandra E; De Somer, Lien; van Nieuwenhove, Erika; Ruuth-Praz, Julia; Copin, Bruno; Cochet, Emmanuelle; Medlej-Hashim, Myrna; Megarbane, Andre; Schroder, Kate; Savic, Sinisa; Goris, An; Amselem, Serge; Wouters, Carine; Liston, Adrian

    2016-03-30

    Pyrin responds to pathogen signals and loss of cellular homeostasis by forming an inflammasome complex that drives the cleavage and secretion of interleukin-1β (IL-1β). Mutations in the B30.2/SPRY domain cause pathogen-independent activation of pyrin and are responsible for the autoinflammatory disease familial Mediterranean fever (FMF). We studied a family with a dominantly inherited autoinflammatory disease, distinct from FMF, characterized by childhood-onset recurrent episodes of neutrophilic dermatosis, fever, elevated acute-phase reactants, arthralgia, and myalgia/myositis. The disease was caused by a mutation in MEFV, the gene encoding pyrin (S242R). The mutation results in the loss of a 14-3-3 binding motif at phosphorylated S242, which was not perturbed by FMF mutations in the B30.2/SPRY domain. However, loss of both S242 phosphorylation and 14-3-3 binding was observed for bacterial effectors that activate the pyrin inflammasome, such as Clostridium difficile toxin B (TcdB). The S242R mutation thus recapitulated the effect of pathogen sensing, triggering inflammasome activation and IL-1β production. Successful therapy targeting IL-1β has been initiated in one patient, resolving pyrin-associated autoinflammation with neutrophilic dermatosis. This disease provides evidence that a guard-like mechanism of pyrin regulation, originally identified for Nod-like receptors in plant innate immunity, also exists in humans. PMID:27030597

  5. 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.

  6. Board composition, process, and activism: evidence within American firms

    OpenAIRE

    Scott SCARBOROUGH; Jeffrey J. HAYNIE; Christopher SHOOK

    2010-01-01

    This study provided an empirical test of the effects of compositional and process variables on board activism. The attributes examined were functional area knowledge, independence, duality, and effort norms. The findings from this study provided support for the positive relationships between both functional area knowledge and effort norms and board activism. The strong relationship between effort norms and activism indicates the importance of process variables in board research and the need f...

  7. Quality Management Activities for Software Architecture and Software Architecture Process

    OpenAIRE

    Hämäläinen, Niina

    2008-01-01

    Architecture processes are considerably new parts of organisations’ processes. These processes have the responsibility to aim at high quality and financially successful architectures. However, the activities which promote this aim are not clearly defined yet. This study reviews literature and practitioners’ experiences on quality management activities that could be suggested to promote the achievement of high quality software architectures and a good quality software a...

  8. Activated Sludge and other Aerobic Suspended Culture Processes.

    Science.gov (United States)

    Li, Chunying; Wei, Li; Chang, Chein-Chi; Zhang, Yuhua; Wei, Dong

    2016-10-01

    This is a literature review for the year 2015 and contains information specifically associated with suspended growth processes including activated sludge, upflow anaerobic sludge blanket, and sequencing batch reactors. The review encompasses modeling and kinetics, nutrient removal, system design and operation. Compared to past reviews, many topics show increase in activity in 2015. These include, fate and effect of xenobiotics, industrial wastes treatment with sludge, and pretreatment for the activated sludge. These topics are referred to the degradation of constituents in activated sludge. Other sections include population dynamics, process microbiology give an insight into the activated sludge. The subsection in industrial wastes: converting sewage sludge into biogases was also mentioned. PMID:27620082

  9. 77 FR 33253 - Regulatory Guide 8.24, Revision 2, Health Physics Surveys During Enriched Uranium-235 Processing...

    Science.gov (United States)

    2012-06-05

    ...- 8040 on March 22, 2010 (75 FR 13599). This guide specifies the types and frequencies of surveys that... March 22, 2010, DG-8040 was published with a request for public comments (75 FR 13599). The public... COMMISSION Regulatory Guide 8.24, Revision 2, Health Physics Surveys During Enriched Uranium-235...

  10. Self-Regulatory Processes Mediating between Career Calling and Perceived Employability and Life Satisfaction in Emerging Adults

    Science.gov (United States)

    Praskova, Anna; Creed, Peter A.; Hood, Michelle

    2015-01-01

    We tested a cross-sectional, mediation model of career calling, in which career calling was associated positively with life satisfaction and perceptions of future employability, and these relationships were explained by the self-regulatory mechanisms of work effort, career strategies, and emotional regulation. Using a sample of 664 emerging adults…

  11. The Integration of Cognition and Emotion during Infancy and Early Childhood: Regulatory Processes Associated with the Development of Working Memory

    Science.gov (United States)

    Wolfe, Christy D.; Bell, Martha Ann

    2007-01-01

    This study was an attempt to integrate cognitive development (i.e., cognitive control) and emotional development (i.e., emotion regulation) in the first years of life. The construct of temperament was used to unify cognition and emotion because of its focus on attentional and regulatory behaviors. Children were seen at 8 months and 4 1/2-years of…

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

    International Nuclear Information System (INIS)

    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.)

  13. Nitric Oxide Mediated Transcriptome Profiling Reveals Activation of Multiple Regulatory Pathways in Arabidopsis thaliana.

    Science.gov (United States)

    Hussain, Adil; Mun, Bong-Gyu; Imran, Qari M; Lee, Sang-Uk; Adamu, Teferi A; Shahid, Muhammad; Kim, Kyung-Min; Yun, Byung-Wook

    2016-01-01

    Imbalance between the accumulation and removal of nitric oxide and its derivatives is a challenge faced by all plants at the cellular level, and is especially important under stress conditions. Exposure of plants to various biotic and abiotic stresses causes rapid changes in cellular redox tone potentiated by the rise in reactive nitrogen species that serve as signaling molecules in mediating defensive responses. To understand mechanisms mediated by these signaling molecules, we performed a large-scale analysis of the Arabidopsis transcriptome induced by nitrosative stress. We generated an average of 84 and 91 million reads from three replicates each of control and 1 mM S-nitrosocysteine (CysNO)-infiltrated Arabidopsis leaf samples, respectively. After alignment, more than 95% of all reads successfully mapped to the reference and 32,535 genes and 55,682 transcripts were obtained. CysNO infiltration caused differential expression of 6436 genes (3448 up-regulated and 2988 down-regulated) and 6214 transcripts (3335 up-regulated and 2879 down-regulated) 6 h post-infiltration. These differentially expressed genes were found to be involved in key physiological processes, including plant defense against various biotic and abiotic stresses, hormone signaling, and other developmental processes. After quantile normalization of the FPKM values followed by student's T-test (P level and would prove helpful in understanding and incorporating mechanisms associated with nitrosative stress responses in plants. PMID:27446194

  14. 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.

  15. Dynamics and control at feedback vertex sets. II: a faithful monitor to determine the diversity of molecular activities in regulatory networks.

    Science.gov (United States)

    Mochizuki, Atsushi; Fiedler, Bernold; Kurosawa, Gen; Saito, Daisuke

    2013-10-21

    Modern biology provides many networks describing regulations between many species of molecules. It is widely believed that the dynamics of molecular activities based on such regulatory networks are the origin of biological functions. However, we currently have a limited understanding of the relationship between the structure of a regulatory network and its dynamics. In this study we develop a new theory to provide an important aspect of dynamics from information of regulatory linkages alone. We show that the "feedback vertex set" (FVS) of a regulatory network is a set of "determining nodes" of the dynamics. The theory is powerful to study real biological systems in practice. It assures that (i) any long-term dynamical behavior of the whole system, such as steady states, periodic oscillations or quasi-periodic oscillations, can be identified by measurements of a subset of molecules in the network, and that (ii) the subset is determined from the regulatory linkage alone. For example, dynamical attractors possibly generated by a signal transduction network with 113 molecules can be identified by measurement of the activity of only 5 molecules, if the information on the network structure is correct. Our theory therefore provides a rational criterion to select key molecules to control a system. We also demonstrate that controlling the dynamics of the FVS is sufficient to switch the dynamics of the whole system from one attractor to others, distinct from the original.

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

    International Nuclear Information System (INIS)

    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 226RaT228Ra 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 m3 of crude per day, rising to around 2,500 m3 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 (Safety

  17. Direct interaction of FliX and FlbD is required for their regulatory activity in Caulobacter crescentus

    Directory of Open Access Journals (Sweden)

    Dutton Rachel J

    2011-05-01

    Full Text Available Abstract Background The temporal and spatial expression of late flagellar genes in Caulobacter crescentus is activated by the transcription factor FlbD and its partner trans-acting factor FliX. The physical interaction of these two proteins represents an alternative mechanism for regulating the activity of σ54 transcription factors. This study is to characterize the interaction of the two proteins and the consequences of the interaction on their regulatory activity. Results FliX and FlbD form stable complexes, which can stand the interference of 2.65 M NaCl. The stability of FliX and FlbD was affected by the co-existence of each other. Five FliX mutants (R71A, L85K, Δ117-118, T130L, and L136K were created by site-directed mutagenesis in conserved regions of the protein. All mutants were successfully expressed in both wild-type and ΔfliX Caulobacter strains. All but FliXL85K could rescue the motility and cell division defects of a ΔfliX mutant strain. The ability of FliX to regulate the transcription of class II and class III/IV flagellar promoters was fully diminished due to the L85K mutation. Co-immunoprecipitation experiment revealed that FliXL85K was unable to physically interact with FlbD. Conclusions FliX interacts with FlbD and thereby directly regulates the activity of FlbD in response to flagellar assembly. Mutations in highly conserved regions of FliX could severely affect the recognition between FliX and FlbD and hence interrupt the normal progression of flagellar synthesis and other developmental events in Caulobacter.

  18. Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens

    Science.gov (United States)

    Rodi, Maria; Dimisianos, Nikolaos; de Lastic, Anne-Lise; Sakellaraki, Panagiota; Deraos, George; Matsoukas, John; Papathanasopoulos, Panagiotis; Mouzaki, Athanasia

    2016-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4+CD25highFoxp3+ (nTregs), CD3+CD4+HLA−G+, CD3+CD8+CD28−, CD3+CD56+, and CD56bright cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3+CD4+HLA−G+ and CD3+CD8+CD28− RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3+CD56+, and patients in remission + natalizumab the highest levels of CD56bright cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction. PMID:27571060

  19. Ginsenoside Rp1 Exerts Anti-inflammatory Effects via Activation of Dendritic Cells and Regulatory T Cells.

    Science.gov (United States)

    Bae, Jingyu; Koo, Jihye; Kim, Soochan; Park, Tae-Yoon; Kim, Mi-Yeon

    2012-10-01

    Ginsenoside Rp1 (G-Rp1) is a saponin derivate that provides anti-metastatic activities through inhibition of the NF-κB pathway. In this study, we examined the effects of G-Rp1 on regulatory T cell (Treg) activation. After treatment of splenocytes with G-Rp1, Tregs exhibited upregulation of IL-10 expression, and along with dendritic cells (DCs), these Tregs showed increased cell number compared to other cell populations. The effect of G-Rp1 on Treg number was augmented in the presence of lipopolysaccharide (LPS), which mimics pathological changes that occur during inflammation. However, depletion of DCs prevented the increase in Treg number in the presence of G-Rp1 and/or LPS. In addition, G-Rp1 promoted the differentiation of the memory types of CD4(+)Foxp3(+)CD62L(low) Tregs rather than the generation of new Tregs. In vivo experiments also demonstrated that Tregs and DCs from mice that were fed G-Rp1 for 7 d and then injected with LPS exhibited increased activation compared with those from mice that were injected with LPS alone. Expression of TGF-β and CTLA4 in Tregs was increased, and upregulation of IL-2 and CD80/ CD86 expression by DCs affected the suppressive function of Tregs through IL-2 receptors and CTLA4. These data demonstrate that G-Rp1 exerts anti-inflammatory effects by activating Tregs in vitro and in vivo. PMID:23717139

  20. Nitric Oxide Mediated Transcriptome Profiling Reveals Activation of Multiple Regulatory Pathways in Arabidopsis thaliana.

    Science.gov (United States)

    Hussain, Adil; Mun, Bong-Gyu; Imran, Qari M; Lee, Sang-Uk; Adamu, Teferi A; Shahid, Muhammad; Kim, Kyung-Min; Yun, Byung-Wook

    2016-01-01

    Imbalance between the accumulation and removal of nitric oxide and its derivatives is a challenge faced by all plants at the cellular level, and is especially important under stress conditions. Exposure of plants to various biotic and abiotic stresses causes rapid changes in cellular redox tone potentiated by the rise in reactive nitrogen species that serve as signaling molecules in mediating defensive responses. To understand mechanisms mediated by these signaling molecules, we performed a large-scale analysis of the Arabidopsis transcriptome induced by nitrosative stress. We generated an average of 84 and 91 million reads from three replicates each of control and 1 mM S-nitrosocysteine (CysNO)-infiltrated Arabidopsis leaf samples, respectively. After alignment, more than 95% of all reads successfully mapped to the reference and 32,535 genes and 55,682 transcripts were obtained. CysNO infiltration caused differential expression of 6436 genes (3448 up-regulated and 2988 down-regulated) and 6214 transcripts (3335 up-regulated and 2879 down-regulated) 6 h post-infiltration. These differentially expressed genes were found to be involved in key physiological processes, including plant defense against various biotic and abiotic stresses, hormone signaling, and other developmental processes. After quantile normalization of the FPKM values followed by student's T-test (P pathways were verified using quantitative real-time PCR. This study provides comprehensive information about plant responses to nitrosative stress at transcript level and would prove helpful in understanding and incorporating mechanisms associated with nitrosative stress responses in plants.

  1. 77 FR 70846 - Regulatory Guide 1.182, “Assessing and Managing Risk Before Maintenance Activities at Nuclear...

    Science.gov (United States)

    2012-11-27

    ... 21, 2012 (77 FR 30030). Therefore, RG 1.182 is no longer needed, as the guidance in Regulatory Guide..., MD 20852. FOR FURTHER INFORMATION CONTACT: Aron Lewin, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone: 301-415-2259, email to Aron.Lewin@nrc.gov or Rick Jervey, telephone:...

  2. Defective jejunal and colonic salt absorption and alteredNa +/H+ exchanger 3 (NHE3) activity in NHE regulatory factor 1 (NHERF1) adaptor protein-deficient mice

    NARCIS (Netherlands)

    N. Broere (Nellie); M. Chen (Min); A. Cinar (Ayhan); A.K. Singh (Arbind); J. Hillesheim (Jutta); B. Riederer (Beat Michel); M. Lunnemann; I. Rottinghaus (Ingrid); A. Krabbenhöft (Anja); R. Engelhardt (Regina); B. Rausch; E.J. Weinman (Edward); M. Donowitz (Mark); A. Hubbard; O. Kocher (Olivier); H.R. de Jonge (Hugo); B.M. Hogema (Boris); U. Seidler (Ursula)

    2009-01-01

    textabstractWe investigated the role of the Na+/H+ exchanger regulatory factor 1 (NHERF1) on intestinal salt and water absorption, brush border membrane (BBM) morphology, and on the NHE3 mRNA expression, protein abundance, and transport activity in the murine intestine. NHERF1-deficient mice display

  3. Nuclear legislation. Analytical study: regulatory and institutional framework for nuclear activities

    International Nuclear Information System (INIS)

    This study is part of the series of analytical studies of the major aspects of nuclear legislation in OECD Member countries, prepared by the OECD Nuclear Energy Agency (NEA) with the co-operation of the appropriate services of countries concerned. The first study, published in 1967, dealt with national legislations concerning nuclear third party liability. Since then, several studies on other aspects of nuclear law (e.g., transport, radiation protection, trade, etc) in Member countries have been issued. Each study is based, to the extent possible, on a standardised plan of all countries, allowing an easier retrieval and comparison of the information contained. Periodical updates are also issued in order to help the reader keep abreast of amendments in national nuclear laws and regulations, such s the revision of the study on nuclear third party liability, in 1990. The reader will find a revised and expanded version of the 1983-1984 study reflecting new changes in nuclear law and encompassing new Member countries to the OECD since then. This new version reviews the body of regulations governing nuclear activities in the OECD area as well as the institutional framework in which such regulations are applied in each country. This study is based on information available to the NEA Secretariat as of May 1995, and neither the Secretariat nor national authorities concerned assume any liability for it. It is published under the responsibility of the Secretary-General of the OECD. (author)

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

    International Nuclear Information System (INIS)

    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

  5. Acyl-homoserine Lactone from Saccharum × officinarum with Stereochemistry-Dependent Growth Regulatory Activity.

    Science.gov (United States)

    Olher, Vanessa G A; Ferreira, Nagela P; Souza, Alan G; Chiavelli, Lucas U R; Teixeira, Aline F; Santos, Wanderley D; Santin, Silvana M O; Ferrarese Filho, Osvaldo; Silva, Cleuza C; Pomini, Armando M

    2016-05-27

    Acyl-homoserine lactones (AHLs) are a class of compounds produced by Gram-negative bacteria that are used in a process of chemical communication called quorum sensing. Much is known about how bacteria use these chemical compounds to control the expression of important factors; however, there have been few reports about the presence and effects of AHLs in plants. In this study, the phytochemical study of leaves and culms of sugar cane (Saccharum × officinarum) led to the identification of N-(3-oxo-octanoyl)homoserine lactone. Since the absolute configuration of the natural product could not be determined, both R and S enantiomers of N-(3-oxo-octanoyl)homoserine lactone were synthesized and tested in sugar cane culms. The enantiomers caused changes in the mass and length of buds and roots when used at micromolar concentrations. Using the sugar cane RB96-6928 variety, the S enantiomer increased sprouting of roots more effectively than the R enantiomer. Furthermore, scanning electron microscopy showed that both the R and S enantiomers led to more stretched root cells compared with the control. PMID:27192014

  6. Process of activation of a palladium catalyst system

    Science.gov (United States)

    Sobolevskiy, Anatoly; Rossin, Joseph A.; Knapke, Michael J.

    2011-08-02

    Improved processes for activating a catalyst system used for the reduction of nitrogen oxides are provided. In one embodiment, the catalyst system is activated by passing an activation gas stream having an amount of each of oxygen, water vapor, nitrogen oxides, and hydrogen over the catalyst system and increasing a temperature of the catalyst system to a temperature of at least 180.degree. C. at a heating rate of from 1-20.degree./min. Use of activation processes described herein leads to a catalyst system with superior NOx reduction capabilities.

  7. Activation and Recruitment of Regulatory T Cells via Chemokine Receptor Activation in Trichinella spiralis-Infected Mice.

    Science.gov (United States)

    Ahn, Jeong-Bin; Kang, Shin Ae; Kim, Dong-Hee; Yu, Hak Sun

    2016-04-01

    As most infections by the helminth parasite elicit the recruitment of CD4(+)CD25(+)Foxp3(+) T (Treg) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated Treg cells, we compared the expression levels of Treg cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of Treg cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated Treg cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of Treg cells in the muscle tissue. PMID:27180574

  8. XCL1 Enhances Regulatory Activities of CD4+CD25highCD127low/− T Cells in Human Allergic Asthma1

    OpenAIRE

    Nguyen, Khoa D.; Fohner, Alison; Booker, Jerome D.; Dong, Chen; Krensky, Alan M.; Nadeau, Kari C.

    2008-01-01

    Chemokine-mediated recruitment of regulatory cell subsets to the airway during inflammation and enhancement of their activities are potential strategies for therapeutic development in allergic asthma (AA). In this study, we aim to explore the role of XCL1, a chemokine associated with immune suppression and allergy, on CD4+CD25highCD127low/− regulatory T cell (Treg) function in AA. Flow cytometry and PCR analysis showed a reduction in XCL1 and XCR1 expression in AA Treg compared with healthy c...

  9. 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.

  10. Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation.

    Directory of Open Access Journals (Sweden)

    Andrea Mencarelli

    Full Text Available BACKGROUND: Adipocytes from mesenteric white adipose tissue amplify the inflammatory response and participate in inflammation-driven immune dysfunction in Crohn's disease by releasing proinflammatory mediators. Peroxisome proliferator-activated receptors (PPAR-α and -γ, pregnane x receptor (PXR, farnesoid x receptor (FXR and liver x-receptor (LXR are ligand-activated nuclear receptor that provide counter-regulatory signals to dysregulated immunity and modulates adipose tissue. AIMS: To investigate the expression and function of nuclear receptors in intestinal and adipose tissues in a rodent model of colitis and mesenteric fat from Crohn's patients and to investigate their modulation by probiotics. METHODS: Colitis was induced by TNBS administration. Mice were administered vehicle or VSL#3, daily for 10 days. Abdominal fat explants obtained at surgery from five Crohn's disease patients and five patients with colon cancer were cultured with VSL#3 medium. RESULTS: Probiotic administration attenuated development of signs and symptoms of colitis, reduced colonic expression of TNFα, IL-6 and IFNγ and reserved colonic downregulation of PPARγ, PXR and FXR caused by TNBS. Mesenteric fat depots isolated from TNBS-treated animals had increased expression of inflammatory mediators along with PPARγ, FXR, leptin and adiponectin. These changes were prevented by VSL#3. Creeping fat and mesenteric adipose tissue from Crohn's patients showed a differential expression of PPARγ and FXR with both tissue expressing high levels of leptin. Exposure of these tissues to VSL#3 medium abrogates leptin release. CONCLUSIONS: Mesenteric adipose tissue from rodent colitis and Crohn's disease is metabolically active and shows inflammation-driven regulation of PPARγ, FXR and leptin. Probiotics correct the inflammation-driven metabolic dysfunction.

  11. Report on activities of Nuclear Regulatory Authority of the Slovak Republic and safety of nuclear installations in the Slovak Republic in 1997. Annual report 1997

    International Nuclear Information System (INIS)

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (NRA SR) in 1997 is presented. These activities are reported under the headings: (1) Foreword; (2) Role of the Nuclear Regulatory Authority of the Slovak Republic; (3) Supervisory and assessment activities in activities; (3.1) NPP V-1 Bohunice; (3.2) NPP V-2 Bohunice; (3.3) NPP Mochovce; (3.4) NPP A-1 Bohunice; (3.5) Radioactive wastes repository in Mochovce; (3.6) Interim spent fuel storage in Jaslovske Bohunice; (4) Nuclear materials and physical protection; (5) Radioactive wastes; (6) Quality assurance; (7) Personnel qualification and training; (8) Emergency management; (9) Legislation; (10) International co-operation; (11) Public information; (12) Conclusions; (13) Appendices

  12. Short Horizon Control Strategies for an Alternating Activated Sludge Process

    DEFF Research Database (Denmark)

    Isaacs, Steven Howard

    1996-01-01

    Three control strategies allowing improved operational flexibility of an alternating type activated sludge process are presented in a unified model based framework. The control handles employed are the addition rate of an external carbon source to denitrification, the cycle length...

  13. Campylobacter jejuni adenosine triphosphate phosphoribosyltransferase is an active hexamer that is allosterically controlled by the twisting of a regulatory tail.

    Science.gov (United States)

    Mittelstädt, Gerd; Moggré, Gert-Jan; Panjikar, Santosh; Nazmi, Ali Reza; Parker, Emily J

    2016-08-01

    Adenosine triphosphate phosphoribosyltransferase (ATP-PRT) catalyzes the first committed step of the histidine biosynthesis in plants and microorganisms. Here, we present the functional and structural characterization of the ATP-PRT from the pathogenic ε-proteobacteria Campylobacter jejuni (CjeATP-PRT). This enzyme is a member of the long form (HisGL ) ATP-PRT and is allosterically inhibited by histidine, which binds to a remote regulatory domain, and competitively inhibited by AMP. In the crystalline form, CjeATP-PRT was found to adopt two distinctly different hexameric conformations, with an open homohexameric structure observed in the presence of substrate ATP, and a more compact closed form present when inhibitor histidine is bound. CjeATP-PRT was observed to adopt only a hexameric quaternary structure in solution, contradicting previous hypotheses favoring an allosteric mechanism driven by an oligomer equilibrium. Instead, this study supports the conclusion that the ATP-PRT long form hexamer is the active species; the tightening of this structure in response to remote histidine binding results in an inhibited enzyme. PMID:27191057

  14. Integrative analysis of the transcriptome and targetome identifies the regulatory network of miR-16: an inhibitory role against the activation of hepatic stellate cells.

    Science.gov (United States)

    Pan, Qin; Guo, Canjie; Sun, Chao; Fan, Jiangao; Fang, Chunhua

    2014-01-01

    Hepatic stellate cell (HSC) activation is the critical event of liver fibrosis. Abnormality of miR-16 expression induces their activation. However, the action model of miR-16 remains to be elucidated because of its multiple-targeted manner. Here, we report that miR-16 restoration exerted a wide-range impact on transcriptome (2,082 differentially expressed transcripts) of activated HSCs. Integrative analysis of both targetome (1,195 targets) and transcriptome uncovered the miR-16 regulatory network based upon bio-molecular interaction databases (BIND, BioGrid, Tranfac, and KEGG), cross database searching with iterative algorithm, Dijkstra's algorithm with greedy method, etc. Eight targets in the targetome (Map2k1, Bmpr1b, Nf1, Pik3r3, Ppp2r1a, Prkca, Smad2, and Sos2) served as key regulatory network nodes that mediate miR-16 action. A set of TFs (Sp1, Jun, Crebl, Arnt, Fos, and Nf1) was recognized to be the functional layer of key nodes, which mapped the signal of miR-16 to transcriptome. In result, the comprehensive action of miR-16 abrogated transcriptomic characteristics that determined the phenotypes of activated HSCs, including active proliferation, ECM deposition, and apoptosis resistance. Therefore, a multi-layer regulatory network based upon the integration of targetome and transcriptome may underlie the global action of miR-16, which suggesting it plays an inhibitory role in HSC activation. PMID:25227104

  15. Formal Verification of Effectiveness of Control Activities in Business Processes

    Science.gov (United States)

    Arimoto, Yasuhito; Iida, Shusaku; Futatsugi, Kokichi

    It has been an important issue to deal with risks in business processes for achieving companies' goals. This paper introduces a method for applying a formal method to analysis of risks and control activities in business processes in order to evaluate control activities consistently, exhaustively, and to give us potential to have scientific discussion on the result of the evaluation. We focus on document flows in business activities and control activities and risks related to documents because documents play important roles in business. In our method, document flows including control activities are modeled and it is verified by OTS/CafeOBJ Method that risks about falsification of documents are avoided by control activities in the model. The verification is done by interaction between humans and CafeOBJ system with theorem proving, and it raises potential to discuss the result scientifically because the interaction gives us rigorous reasons why the result is derived from the verification.

  16. Improvement of enterprise activities based on process management

    OpenAIRE

    Łuczak, Ja.

    2015-01-01

    Process management has been increasingly popular for several years now, yet most frequently it is limited to fragmentary actions, at times even to declarative activity. Few organizations have brought their management systems in conformity with the idea of process management; more frequently some particular actions within the range of process approach may be observed. Specialization allows efficient realizations of tasks; however, it separates individual organizational unities and amount...

  17. Process technology activities at the Software Engineering Institute

    Energy Technology Data Exchange (ETDEWEB)

    Christie, A.M. [Carnegie Mellon Univ., Pittsburgh, PA (United States)

    1996-12-31

    This paper provides a brief overview of the rationale for, and direction of the software process technology work being pursued at the Software Engineering Institute. The paper then describes some of the activities that the SEI has recently been involved in. Finally, it relates in more detail an example of one specific effort; namely the development of a process modeling formalism and its use in process simulation.

  18. ChIP-Seq-Annotated Heliconius erato Genome Highlights Patterns of cis-Regulatory Evolution in Lepidoptera.

    Science.gov (United States)

    Lewis, James J; van der Burg, Karin R L; Mazo-Vargas, Anyi; Reed, Robert D

    2016-09-13

    Uncovering phylogenetic patterns of cis-regulatory evolution remains a fundamental goal for evolutionary and developmental biology. Here, we characterize the evolution of regulatory loci in butterflies and moths using chromatin immunoprecipitation sequencing (ChIP-seq) annotation of regulatory elements across three stages of head development. In the process we provide a high-quality, functionally annotated genome assembly for the butterfly, Heliconius erato. Comparing cis-regulatory element conservation across six lepidopteran genomes, we find that regulatory sequences evolve at a pace similar to that of protein-coding regions. We also observe that elements active at multiple developmental stages are markedly more conserved than elements with stage-specific activity. Surprisingly, we also find that stage-specific proximal and distal regulatory elements evolve at nearly identical rates. Our study provides a benchmark for genome-wide patterns of regulatory element evolution in insects, and it shows that developmental timing of activity strongly predicts patterns of regulatory sequence evolution.

  19. Regulatory Models and the Environment: Practice, Pitfalls, and Prospects

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, K. John; Graham, Judith A.; McKone, Thomas; Whipple, Chris

    2008-06-01

    Computational models support environmental regulatory activities by providing the regulator an ability to evaluate available knowledge, assess alternative regulations, and provide a framework to assess compliance. But all models face inherent uncertainties, because human and natural systems are always more complex and heterogeneous than can be captured in a model. Here we provide a summary discussion of the activities, findings, and recommendations of the National Research Council's Committee on Regulatory Environmental Models, a committee funded by the US Environmental Protection Agency to provide guidance on the use of computational models in the regulatory process. Modeling is a difficult enterprise even outside of the potentially adversarial regulatory environment. The demands grow when the regulatory requirements for accountability, transparency, public accessibility, and technical rigor are added to the challenges. Moreover, models cannot be validated (declared true) but instead should be evaluated with regard to their suitability as tools to address a specific question. The committee concluded that these characteristics make evaluation of a regulatory model more complex than simply comparing measurement data with model results. Evaluation also must balance the need for a model to be accurate with the need for a model to be reproducible, transparent, and useful for the regulatory decision at hand. Meeting these needs requires model evaluation to be applied over the"life cycle" of a regulatory model with an approach that includes different forms of peer review, uncertainty analysis, and extrapolation methods than for non-regulatory models.

  20. Cascading activation from lexical processing to letter-level processing in written word production.

    Science.gov (United States)

    Buchwald, Adam; Falconer, Carolyn

    2014-01-01

    Descriptions of language production have identified processes involved in producing language and the presence and type of interaction among those processes. In the case of spoken language production, consensus has emerged that there is interaction among lexical selection processes and phoneme-level processing. This issue has received less attention in written language production. In this paper, we present a novel analysis of the writing-to-dictation performance of an individual with acquired dysgraphia revealing cascading activation from lexical processing to letter-level processing. The individual produced frequent lexical-semantic errors (e.g., chipmunk → SQUIRREL) as well as letter errors (e.g., inhibit → INBHITI) and had a profile consistent with impairment affecting both lexical processing and letter-level processing. The presence of cascading activation is suggested by lower letter accuracy on words that are more weakly activated during lexical selection than on those that are more strongly activated. We operationalize weakly activated lexemes as those lexemes that are produced as lexical-semantic errors (e.g., lethal in deadly → LETAHL) compared to strongly activated lexemes where the intended target word (e.g., lethal) is the lexeme selected for production. PMID:25163539

  1. Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens.

    Science.gov (United States)

    Rodi, Maria; Dimisianos, Nikolaos; de Lastic, Anne-Lise; Sakellaraki, Panagiota; Deraos, George; Matsoukas, John; Papathanasopoulos, Panagiotis; Mouzaki, Athanasia

    2016-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4⁺CD25(high)Foxp3⁺ (nTregs), CD3⁺CD4⁺HLA(-)G⁺, CD3⁺CD8⁺CD28(-), CD3⁺CD56⁺, and CD56(bright) cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3⁺CD4⁺HLA(-)G⁺ and CD3⁺CD8⁺CD28(-) RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3⁺CD56⁺, and patients in remission + natalizumab the highest levels of CD56(bright) cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction. PMID:27571060

  2. The regulatory dynamic

    International Nuclear Information System (INIS)

    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

  3. Use of probabilistic safety assessment in the regulatory process. Report of the technical committee meeting. Working material

    International Nuclear Information System (INIS)

    A Technical Committee Meeting (TCM) was organized between 5-8 December 1994 to discuss and review the international situation in connection with the use made, whether formally or informally, by regulatory bodies of probabilistic safety assessment (PSA) in the course of their work, and the related question of the use and value of adopting probabilistic safety criteria (PSC) as an aid to judging the results of PSAs. The document includes the output from the four working groups, as well as 11 papers from the 12 papers presented to the TCM. A separate abstract was prepared for each paper. Refs, figs, tabs

  4. 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)

    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

  5. Regulatory Effect of Low-Intensity Optical Radiation on Oxygenation of Blood Irradiated In Vivo and Metabolic Processes

    Science.gov (United States)

    Zalesskaya, G. A.; Laskina, O. V.

    2016-03-01

    For three series of blood samples, we have studied the effect of therapeutic doses of low-intensity optical radiation (LOR) on oxygenation parameters of blood irradiated in vivo, and also on the levels of some metabolites: lactate, glucose, cholesterol. The quality of blood oxygenation was assessed using three parameters: the partial pressure of oxygen pVO2, the oxygen saturation of hemoglobin SVO2, and the oxygen level in arterial and venous blood, varying under the influence of low-intensity optical radiation due to photodissociation of hemoglobin/ligand complexes. We have established that during photohemotherapy (PHT), including extracorporeal, supravascular, and intravenous blood irradiation, positive changes occur in the oxygenation parameters and the metabolite levels, while after the courses of PHT have been completed, the individual changes in such parameters in individual patients were both positive and negative. The regulatory effect of PHT was apparent in the tendency toward a decrease in high initial values and an increase in low initial values both for the oxygenation parameters and for the metabolites; but at the doses recommended for use, PHT had a regulatory but still not a normalizing effect.

  6. 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

  7. 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

    2001-01-01

    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...

  8. Active Shop Scheduling Of Production Process Based On RFID Technology

    Directory of Open Access Journals (Sweden)

    Cuihua Chao

    2016-01-01

    Full Text Available In industry 4.0 environment, intelligent technology is almost applied to all parts of the manufacturing process, such as process design, job shop scheduling, etc.. This paper presents an efficient approach to job shop scheduling actively by using RFID to collect real-time manufacturing data. Identified the workpiece by RFID which needs to be machined, it can “ask for” the resource actively for the following process. With these active asking-for strategy, a double genetically encoded improved genetic algorithm is proposed for achieving active job shop scheduling solution during the actual manufacturing process. A case was used to evaluate its effectiveness. Meanwhile, , it can effectively and actively carry out job shop scheduling and has much better convergence effect comparing with basic genetic algorithm. And the job shop scheduler in management center can use the proposed algorithm to get the satisfied scheduling result timely by reducing waiting time and making begin time earlier during transmission between manufacturing process, which makes the scheduling result feasible and accurate.

  9. Aerobic storage under dynamic conditions in activated sludge processes

    DEFF Research Database (Denmark)

    Majone, M.; Dircks, K.

    1999-01-01

    In activated sludge processes, several plant configurations (like plug-flow configuration of the aeration tanks, systems with selectors, contact-stabilization processes or SBR processes) impose a concentration gradient of the carbon sources to the biomass. As a consequence, the biomass grows under...... mechanisms can also contribute to substrate removal, depending on the microbial composition and the previous "history" of the biomass. In this paper the type and the extent of this dynamic response is discussed by review of experimental studies on pure cultures, mixed cultures and activated sludges...... and with main reference to its relevance on population dynamics in the activated sludge. Possible conceptual approaches to storage modelling are also presented, including both structured and unstructured modelling. (C) 1999 IAWQ Published by Elsevier Science Ltd. All rights reserved....

  10. Impact of activation process on fog life cycle

    Science.gov (United States)

    Mazoyer, Marie; Burnet, Frédéric; Lac, Christine; Roberts, Greg; Dupont, Jean-Charles; Haeffelin, Martial; Elias, Thierry

    2015-04-01

    Fogs are complex meteorological system dealing with fine scale processes. Subtle interaction between radiative, dynamic, turbulent and microphysic processes can lead to different fog life cycle, which make prediction difficult. The droplets that composed fogs are formed trough the activation of aerosol particles called CCN (cloud condensation nuclei) described by the Köhler theory (Köhler, 1936). The number and distribution of the droplets activated during fog formation is determined by the aerosols particles properties and number and the ambient vapor supersaturation of the atmosphere. In the frame of the PreViBOSS project, an in-situ measurement platform of fog properties at ground level was deployed at SIRTA (Instrumented Site for Atmospheric Remote Sensing Research) during winter 2010 to 2013. Microphysics data supply a detailed characterization of number size spectrum from dry to wet aerosols particles and inform on the abilities of the aerosols particles to act as a CCN. 48 fog events have been studied. Supersaturation critical values and concentrations of CCN have been determined and linked to aerosols properties. The main impact of aerosols size distribution on activation have been pointed out. The study of droplets spectra evolution reveals the major physical processes into fogs and suggests that even if thermodynamic dominates the fog life cycle, activation process seems to have a significant effect. Large eddy simulation of fog run with Meso-NH model allow to explore precisely the interaction between fog physical processes and to quantify activation impact. Supersaturation modelling is a key point, a new pseudo-prognostic scheme (Thouron et al., 2012) is used. Confrontation between a detailed experimental study and three-dimensional fine scale simulation in LES provides an accurate investigation of the impact of activation process on fog life cycle.

  11. Clearance of Apoptotic Cells by Macrophages Induces Regulatory Phenotype and Involves Stimulation of CD36 and Platelet-Activating Factor Receptor

    Directory of Open Access Journals (Sweden)

    Matheus Ferracini

    2013-01-01

    Full Text Available Phagocytosis of apoptotic cells (efferocytosis induces macrophage differentiation towards a regulatory phenotype (IL-10high/IL-12p40low. CD36 is involved in the recognition of apoptotic cells (AC, and we have shown that the platelet-activating factor receptor (PAFR is also involved. Here, we investigated the contribution of PAFR and CD36 to efferocytosis and to the establishment of a regulatory macrophage phenotype. Mice bone marrow-derived macrophages were cocultured with apoptotic thymocytes, and the phagocytic index was determined. Blockage of PAFR with antagonists or CD36 with specific antibodies inhibited the phagocytosis of AC (~70–80%. Using immunoprecipitation and confocal microscopy, we showed that efferocytosis increased the CD36 and PAFR colocalisation in the macrophage plasma membrane; PAFR and CD36 coimmunoprecipitated with flotillin-1, a constitutive lipid raft protein, and disruption of these membrane microdomains by methyl-β-cyclodextrin reduced AC phagocytosis. Efferocytosis induced a pattern of cytokine production, IL-10high/IL-12p40low, that is, characteristic of a regulatory phenotype. LPS potentiated the efferocytosis-induced production of IL-10, and this was prevented by blocking PAFR or CD36. It can be concluded that phagocytosis of apoptotic cells engages CD36 and PAFR, possibly in lipid rafts, and this is required for optimal efferocytosis and the establishment of the macrophage regulatory phenotype.

  12. Impaired NK cells' activity and increased numbers of CD4 + CD25+ regulatory T cells in multidrug-resistant Mycobacterium tuberculosis patients.

    Science.gov (United States)

    Fan, Renhua; Xiang, Yangen; Yang, Li; Liu, Yanke; Chen, Pingsheng; Wang, Lei; Feng, Wenjun; Yin, Ke; Fu, Manjiao; Xu, Yixin; Wu, Jialin

    2016-05-01

    Multidrug-resistant tuberculosis (MDR-TB) often causes persistent infection and chemotherapy failure, which brings heavy burden of society and family. Many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. The presence of regulatory T cells (Tregs) is thought to be an important mechanism that TB successfully evades the immune system. Tregs play a central role in the prevention of autoimmunity and in the control of immune responses. The role of Tregs in MDR-TB infection and persistence is inadequately documented. The current study was designed to determine whether CD4 + CD25+ regulatory T cells may modulate innate immunity (such as NK cells) against human tuberculosis. Our results indicated that the numbers of CD4 + CD25+ Treg cells increased in MDR-TB patients' blood, and the cytokine production of IL-10 increased from MDR-patients compared with healthy subjects, along with the lower activity and low CD69 expression of NK cells in patients. These results suggested that immunity to MDR-TB patients induced circulating CD4 + CD25+ T regulatory cells expansion, which may be related to the persistence of Mycobacterium tuberculosis (M. tb) infection, and to the balance between effectors immune responses and suppression immune responses. PMID:27156613

  13. 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

  14. Low and medium activity solid wastes processing and encapsulation

    International Nuclear Information System (INIS)

    This work, carried out under contract with the European Atomic Energy Community, describes the techniques in use for waste management. The activity of low and medium activity solid wastes is from few curies to few tens of curies per cubic meter, they are produced by nuclear facilities and are often complex mixtures. Radioactive wastes are characterized and processing and conditioning are described. Leaching, stability, mechanical resistance and radiolysis of encapsulated wastes are examined. Handling, storage and disposal are treated

  15. Activated sludge process based on artificial neural network

    Institute of Scientific and Technical Information of China (English)

    张文艺; 蔡建安

    2002-01-01

    Considering the difficulty of creating water quality model for activated sludge system, a typical BP artificial neural network model has been established to simulate the operation of a waste water treatment facilities. The comparison of prediction results with the on-spot measurements shows the model, the model is accurate and this model can also be used to realize intelligentized on-line control of the wastewater processing process.

  16. Murine CD4+CD25- cells activated in vitro with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis in vivo

    OpenAIRE

    Majowicz Anna; van der Marel Sander; te Velde Anje A; Meijer Sybren L; Petry Harald; van Deventer Sander J; Ferreira Valerie

    2012-01-01

    Abstract Background Induced regulatory T (iTreg) lymphocytes show promise for application in the treatment of allergic, autoimmune and inflammatory disorders. iTreg cells demonstrate advantages over natural Treg (nTreg) cells in terms of increased number of starting population and greater potential to proliferate. Different activation methods to generate iTreg cells result in iTreg cells that are heterogeneous in phenotype and mechanisms of suppression. Therefore it is of interest to explore ...

  17. High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Lu-WenWang; Hui Chen; Zuo-Jiong Gong

    2010-01-01

    BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4+CD25+CD127low Treg cells among CD4+cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4+CD25+CD127low Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CD4+ cells were found in liver failure patients than in CHB patients (82.6±20.1 μg/L vs. 34.2±13.7 μg/L; 4.55±1.34% vs. 9.52± 3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection

  18. 76 FR 33181 - Regulatory Review Schedule

    Science.gov (United States)

    2011-06-08

    ... processes. (76 FR 18457, April 4, 2011). The Commission's regulatory review process establishes a detailed... National Indian Gaming Commission 25 CFR Chapter III Regulatory Review Schedule AGENCY: National Indian... Regulatory Review Schedule setting out detailed consultation schedules and review processes. NIGC divided...

  19. Optimized operation and design of alternating activated sludge processes

    NARCIS (Netherlands)

    Lukasse, L.J.S.; Keesman, K.J.

    1999-01-01

    This paper presents a simulation study with the scope to optimise the plant design and operation strategy of 2-reactors alternating activated sludge processes with only flow schedule and aeration on/off as control inputs. The methodology is to simulate the application of receding horizon optimal con

  20. Flow Velocity Measurement by Image Processing of Optically Activated Tracers

    OpenAIRE

    Gharib, M.; Hernan, M. A.; Yavrouian, A. H.; Sarohia, V.

    1985-01-01

    A computerized flow visualization technique capable of quantifying the flow field automatically has been developed. This technique uses afterglowing effect of optically activated phosphorescent particles to retrieve vectorial information on each trace. By using this information, in conjunction with computer image processing, the flow field of a free surface transient vortex was investigated.

  1. Activated Sludge and Other Aerobic Suspended Culture Processes

    Directory of Open Access Journals (Sweden)

    Yung-Tse Hung

    2011-08-01

    Full Text Available A review of the literature published in 2008, 2009 and 2010 relating to activated sludge treatment of wastewater is presented. The review considers information on the topics of modeling and kinetics; process microbiology; nitrogen and phosphorus removal; treatment and effects of xenobiotics; oxygen transfer; and solids separation.

  2. TLR-2 Activation Induces Regulatory T Cells and Long-Term Suppression of Asthma Manifestations in Mice

    NARCIS (Netherlands)

    Nawijn, Martijn C.; Motta, Alexandre C.; Gras, Renee; Shirinbak, Soheila; Maazi, Hadi; van Oosterhout, Antoon J. M.

    2013-01-01

    Asthma is a chronic inflammatory disease of the airways characterized by variable airway obstruction and airway hyperresponsiveness (AHR). The T regulatory (Treg) cell subset is critically important for the regulation of immune responses. Adoptive transfer of Treg cells has been shown to be sufficie

  3. The Land Processes Distributed Active Archive Center (LP DAAC)

    Science.gov (United States)

    Golon, Danielle K.

    2016-10-03

    The Land Processes Distributed Active Archive Center (LP DAAC) operates as a partnership with the U.S. Geological Survey and is 1 of 12 DAACs within the National Aeronautics and Space Administration (NASA) Earth Observing System Data and Information System (EOSDIS). The LP DAAC ingests, archives, processes, and distributes NASA Earth science remote sensing data. These data are provided to the public at no charge. Data distributed by the LP DAAC provide information about Earth’s surface from daily to yearly intervals and at 15 to 5,600 meter spatial resolution. Data provided by the LP DAAC can be used to study changes in agriculture, vegetation, ecosystems, elevation, and much more. The LP DAAC provides several ways to access, process, and interact with these data. In addition, the LP DAAC is actively archiving new datasets to provide users with a variety of data to study the Earth.

  4. From molecule to market access: drug regulatory science as an upcoming discipline.

    Science.gov (United States)

    Gispen-de Wied, Christine C; Leufkens, Hubertus G M

    2013-11-01

    Regulatory science as a discipline has evolved over the past years with the object to boost and promote scientific rationale behind benefit/risk and decision making by regulatory authorities. The European Medicines Agency, EMA, the Food and Drug Administration, FDA, and the Japanese Pharmaceutical and Medical Devices Agency, PMDA, highlighted in their distinct ways the importance of regulatory science as a basis of good quality assessment in their strategic plans. The Medicines Evaluation Board, MEB, states: 'regulatory science is the science of developing and validating new standards and tools to evaluate and assess the benefit/risk of medicinal products, facilitating sound and transparent regulatory decision making'. Through analysis of regulatory frameworks itself and their effectiveness, however, regulatory science can also advance knowledge of these systems in general. The comprehensive guidance that is issued to complete an application dossier for regulatory product approval has seldomly been scrutinized for its efficiency. Since it is the task of regulatory authorities to protect and promote public health, it is understood that they take a cautious approach in regulating drugs prior to market access. In general, the authorities are among the first to be blamed if dangerous or useless drugs were allowed to the market. Yet, building a regulatory framework that is not challenged continuously in terms of deliverables for public health and cost-effectiveness, might be counterproductive in the end. Regulatory science and research can help understand how and why regulatory decisions are made, and where renewed discussions may be warranted. The MEB supports regulatory science as an R&D activity to fuel primary regulatory processes on product evaluation and vigilance, but also invests in a 'looking into the mirror' approach. Along the line of the drug life-cycle, publicly available data are reviewed and their regulatory impact highlighted. If made explicit

  5. Pro-protein convertases control the maturation and processing of the iron-regulatory protein, RGMc/hemojuvelin

    Directory of Open Access Journals (Sweden)

    Rotwein Peter

    2008-04-01

    Full Text Available Abstract Background Repulsive guidance molecule c (RGMc or hemojuvelin, a glycosylphosphatidylinositol-linked glycoprotein expressed in liver and striated muscle, plays a central role in systemic iron balance. Inactivating mutations in the RGMc gene cause juvenile hemochromatosis (JH, a rapidly progressing iron storage disorder with severe systemic manifestations. RGMc undergoes complex biosynthetic steps leading to membrane-bound and soluble forms of the protein, including both 50 and 40 kDa single-chain species. Results We now show that pro-protein convertases (PC are responsible for conversion of 50 kDa RGMc to a 40 kDa protein with a truncated COOH-terminus. Unlike related molecules RGMa and RGMb, RGMc encodes a conserved PC recognition and cleavage site, and JH-associated RGMc frame-shift mutants undergo COOH-terminal cleavage only if this site is present. A cell-impermeable peptide PC inhibitor blocks the appearance of 40 kDa RGMc in extra-cellular fluid, as does an engineered mutation in the conserved PC recognition sequence, while the PC furin cleaves 50 kDa RGMc in vitro into a 40 kDa molecule with an intact NH2-terminus. Iron loading reduces release of RGMc from the cell membrane, and diminishes accumulation of the 40 kDa species in cell culture medium. Conclusion Our results define a role for PCs in the maturation of RGMc that may have implications for the physiological actions of this critical iron-regulatory protein.

  6. 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.

  7. A comparison of United States and Japanese regulatory requirements at the time of Fukushima accident and updates of USNRC post-Fukushima activities

    International Nuclear Information System (INIS)

    This paper discusses the similarities and differences between the United States (US) and Japan on nuclear reactor regulations based on a Nuclear Regulatory Commission (NRC) study after the Fukushima Dai-ichi accident. The US and Japan had many similarities in design basis requirements and guidance at the time of the event. There were also differences between the US and Japan in the approach to beyond design basis events and severe accidents. This paper also discusses the NRC's post-Fukushima activities and US industry’s responses. This paper will give the most recent updates on these activities and path forward. (author)

  8. Report on activities of Nuclear Regulatory Authority of the Slovak Republic and safety of nuclear installations in the Slovak Republic in 1996. Annual report 1996

    International Nuclear Information System (INIS)

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (NRA SR) in 1996 is presented. These activities are reported under the headings: (1) Foreword; (2) NPP V-1 Bohunice; (3) NPP V-2 Bohunice; (4) NPP Mochovce; (5) Nuclear materials; ((6) NPP A-1 Bohunice; (7) Treatment; (8) Qualification and personnel training; (9) Emergency management; (10) Legislation; (11) Quality assurance; (12) International cooperation; (13) Public relations; (14) Organization structure of the NRA SR; (15) Conclusions; (16) Appendices

  9. The waste isolation pilot plant regulatory compliance program

    International Nuclear Information System (INIS)

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

  10. Competition between activating and inhibitory processes in photobiology

    Science.gov (United States)

    Friedmann, Harry; Lubart, Rachel

    1996-01-01

    We discuss light-induced stimulation and inhibition of biological activity by means of three types of competing processes. In the visible region, these competing processes are the formation by photosensitization of reactive oxygen species (ROS) which stimulate the redox activity of the respiratory chain (RC) on the one hand, and intramolecular electronic- vibrational energy transfer from an endogenous photosensitizer to an enzyme of the RC, thereby bringing this enzyme into an inactive configuration and paralyzing the RC, on the other hand. Moreover, there is competition between stimulation of the redox activity of the RC by the ROS and a slower process where the enzymes of the RC react with the ROS, again paralyzing the RC. This paralysis of the RC plays a dominant role in photodynamic therapy, where exogenous photosensitizers together with a sufficiently large visible light-energy dose lead to overproduction of ROS. Finally, in the far-red region, there is competition between reactivation of the ATPase ion pumps in the cell membrane and inhibition of the enzymes in the RC as a result of vibrational overtone excitation. Photobioactivation is shown to lead to enhanced transient Ca2+ concentration increase (calcium oscillations) in the cytosol, thereby triggering further biological activity such as afflux of intercellular messengers which open gated ion channels in neighboring cells, producing calcium waves. Addition of ROS scavengers or quenchers such as SOD in the presence of catalase neutralizes photobiomodulation induced by visible light.

  11. Dempster-Shafer theory applied to regulatory decision process for selecting safer alternatives to toxic chemicals in consumer products.

    Science.gov (United States)

    Park, Sung Jin; Ogunseitan, Oladele A; Lejano, Raul P

    2014-01-01

    Regulatory agencies often face a dilemma when regulating chemicals in consumer products-namely, that of making decisions in the face of multiple, and sometimes conflicting, lines of evidence. We present an integrative approach for dealing with uncertainty and multiple pieces of evidence in toxics regulation. The integrative risk analytic framework is grounded in the Dempster-Shafer (D-S) theory that allows the analyst to combine multiple pieces of evidence and judgments from independent sources of information. We apply the integrative approach to the comparative risk assessment of bisphenol-A (BPA)-based polycarbonate and the functionally equivalent alternative, Eastman Tritan copolyester (ETC). Our results show that according to cumulative empirical evidence, the estimated probability of toxicity of BPA is 0.034, whereas the toxicity probability for ETC is 0.097. However, when we combine extant evidence with strength of confidence in the source (or expert judgment), we are guided by a richer interval measure, (Bel(t), Pl(t)). With the D-S derived measure, we arrive at various intervals for BPA, with the low-range estimate at (0.034, 0.250), and (0.097,0.688) for ETC. These new measures allow a reasonable basis for comparison and a justifiable procedure for decision making that takes advantage of multiple sources of evidence. Through the application of D-S theory to toxicity risk assessment, we show how a multiplicity of scientific evidence can be converted into a unified risk estimate, and how this information can be effectively used for comparative assessments to select potentially less toxic alternative chemicals.

  12. Remission of systemic lupus erythematosus disease activity with regulatory cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice.

    Science.gov (United States)

    Cai, Z; Wong, C K; Dong, J; Chu, M; Jiao, D; Kam, N W; Lam, C W K; Tam, L S

    2015-08-01

    The immunological mechanisms mediated by regulatory cytokine interleukin (IL)-35 are unclear in systemic lupus erythematosus (SLE). We investigated the frequency of CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) regulatory T (Treg ) and IL-10(+) regulatory B (Breg ) cells and related immunoregulatory mechanisms in a female Murphy Roths Large (MRL)/lpr mouse model of spontaneous lupus-like disease, with or without IL-35 treatment. A remission of histopathology characteristics of lupus flare and nephritis was observed in the MRL/lpr mice upon IL-35 treatment. Accordingly, IL-35 and IL-35 receptor subunits (gp130 and IL-12Rβ2) and cytokines of MRL/lpr and BALB/c mice (normal controls) were measured. The increased anti-inflammatory cytokines and decreased proinflammatory cytokines were possibly associated with the restoration of Treg and Breg frequency in MRL/lpr mice with IL-35 treatment, compared to phosphate-buffered saline (PBS) treatment. mRNA expressions of Treg -related FoxP3, IL-35 subunit (p35 and EBI3) and soluble IL-35 receptor subunit (gp130 and IL12Rβ2) in splenic cells were up-regulated significantly in IL-35-treated mice. Compared with the PBS treatment group, IL-35-treated MRL/lpr mice showed an up-regulation of Treg -related genes and the activation of IL-35-related intracellular Janus kinase/signal transducer and activator of transcription signal pathways, thereby indicating the immunoregulatory role of IL-35 in SLE. These in vivo findings may provide a biochemical basis for further investigation of the regulatory mechanisms of IL-35 for the treatment of autoimmune-mediated inflammation.

  13. Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function

    Directory of Open Access Journals (Sweden)

    Godder Kamar

    2009-10-01

    Full Text Available Abstract Background Foxp3 has been suggested to be a standard marker for murine Tregs whereas its role as marker for human Tregs is controversial. While some reports have shown that human Foxp3+ T cells had no regulatory function others have shown their role in the inhibition of T cell proliferation. Methods T cell activation was performed by means of brayostatin-1/ionomycin (B/I, mixed lymphocyte reaction (MLR, and CD3/CD28 activation. T cell proliferation was performed using BrdU and CFSE staining. Flow cytometry was performed to determine Foxp3 expression, cell proliferation, viabilities and phenotype analyses of T cells. Results Both CD4+ and CD8+ T cells expressed Foxp3 upon activation in vitro. Expression of Foxp3 remained more stable in CD4+CD25+ T cells compared to that in CD8+CD25+ T cells. The CD4+CD25+Foxp3+ T cells expressed CD44 and CD62L, showing their effector and memory phenotypes. Both FoxP3- responder T cells and CD4+FoxP3+ T cells underwent proliferation upon CD3/CD28 activation. Conclusion Expression of Foxp3 does not necessarily convey regulatory function in human CD4+CD25+ T cells. Increased FoxP3 on CD44+ effector and CD44+CD62L+ memory T cells upon stimulation suggest the activation-induced regulation of FoxP3 expression.

  14. Processing Chinese hand-radicals activates the medial frontal gyrus

    Institute of Scientific and Technical Information of China (English)

    Qing-Lin Wu; Yu-Chen Chan; Joseph P. Lavallee; Hsueh-Chin Chen; Kuo-En Chang; Yao-Ting Sung

    2013-01-01

    Embodied semantics theory asserts that the meaning of action-related words is neural y represented through networks that overlap with or are identical to networks involved in sory-motor processing. While some studies supporting this theory have focused on Chinese cha-racters, less attention has been paid to their semantic radicals. Indeed, there is stil disagreement about whether these radicals are processed independently. The present study investigated whether radicals are processed separately and, if so, whether this processing occurs in sensory-motor gions. Materials consisted of 72 high-frequency Chinese characters, with 18 in each of four ries:hand-action verbs with and without hand-radicals, and verbs not related to hand actions, with and without hand-radicals. Twenty-eight participants underwent functional MRI scans while reading the characters. Compared to characters without hand-radicals, reading characters with hand-radicals activated the right medial frontal gyrus. Verbs involving hand-action activated the left inferior parietal lobule, possibly reflecting integration of information in the radical with the semantic meaning of the verb. The findings may be consistent with embodied semantics theory and suggest that neural representation of radicals is indispensable in processing Chinese characters.

  15. Human Blood and Mucosal Regulatory T Cells Express Activation Markers and Inhibitory Receptors in Inflammatory Bowel Disease

    OpenAIRE

    Lord, James D.; Shows, Donna M.; Chen, Janice; Thirlby, Richard C.

    2015-01-01

    Background FOXP3+ regulatory T cells (Tregs) are critical for preventing intestinal inflammation. However, FOXP3+ T cells are paradoxically increased in the intestines of patients with the inflammatory bowel disease (IBD) ulcerative colitis (UC) or Crohn’s disease (CD). We determined whether these FOXP3+ cells in IBD patients share or lack the phenotype of such cells from patients without IBD. Methods We quantified and characterized FOXP3+ Treg populations, as well as FOXP3- CD4+ T cells, in ...

  16. Impact of independent directors and the regulatory environment on bank merger prices: evidence from takeover activity in the 1990s

    OpenAIRE

    Elijah Brewer; Jackson, William E.; Julapa Jagtiani

    2000-01-01

    This article examines the primary motivation of the bank merger waves in the 1990s. Our investigation of the factors that determine bid premiums paid for target banks focuses on the importance of the financial characteristics of the targets, composition of their boards of directors, and the regulatory environment. ; The value of the target bank to the acquiring bank should reflect its present discounted value of future net cash flows. Thus, at a minimum, the bid price should be a combination ...

  17. TLR-2 Activation Induces Regulatory T Cells and Long-Term Suppression of Asthma Manifestations in Mice

    OpenAIRE

    Nawijn, Martijn C.; Motta, Alexandre C; Renée Gras; Soheila Shirinbak; Hadi Maazi; van Oosterhout, Antoon J. M.

    2013-01-01

    Asthma is a chronic inflammatory disease of the airways characterized by variable airway obstruction and airway hyperresponsiveness (AHR). The T regulatory (Treg) cell subset is critically important for the regulation of immune responses. Adoptive transfer of Treg cells has been shown to be sufficient for the suppression of airway inflammation in experimental allergic asthma. Intervention strategies aimed at expanding the Treg cell population locally in the airways of sensitized individuals a...

  18. Northwestern profiling of potential translation-regulatory proteins in human breast epithelial cells and malignant breast tissues: evidence for pathological activation of the IGF1R IRES.

    Science.gov (United States)

    Blume, Scott W; Jackson, Nateka L; Frost, Andra R; Grizzle, William E; Shcherbakov, Oleg D; Choi, Hyoungsoo; Meng, Zheng

    2010-06-01

    Genes involved in the control of cell proliferation and survival (those genes most important to cancer pathogenesis) are often specifically regulated at the translational level, through RNA-protein interactions involving the 5'-untranslated region of the mRNA. IGF1R is a proto-oncogene strongly implicated in human breast cancer, promoting survival and proliferation of tumor cells, as well as metastasis and chemoresistance. Our lab has focused on the molecular mechanisms regulating IGF1R expression at the translational level. We previously discovered an internal ribosome entry site (IRES) within the 5'-untranslated region of the human IGF1R mRNA, and identified and functionally characterized two individual RNA-binding proteins, HuR and hnRNP C, which bind the IGF1R 5'-UTR and differentially regulate IRES activity. Here we have developed and implemented a high-resolution northwestern profiling strategy to characterize, as a group, the full spectrum of sequence-specific RNA-binding proteins potentially regulating IGF1R translational efficiency through interaction with the 5'-untranslated sequence. The putative IGF1R IRES trans-activating factors (ITAFs) are a heterogeneous group of RNA-binding proteins including hnRNPs originating in the nucleus as well as factors tightly associated with ribosomes in the cytoplasm. The IGF1R ITAFs can be categorized into three distinct groups: (a) high molecular weight external ITAFs, which likely modulate the overall conformation of the 5'-untranslated region of the IGF1R mRNA and thereby the accessibility of the core functional IRES; (b) low molecular weight external ITAFs, which may function as general chaperones to unwind the RNA, and (c) internal ITAFs which may directly facilitate or inhibit the fundamental process of ribosome recruitment to the IRES. We observe dramatic changes in the northwestern profile of non-malignant breast cells downregulating IGF1R expression in association with acinar differentiation in 3-D culture

  19. Transcriptional Regulatory Networks Activated by PI3K and ERK Transduced Growth Signals in Human Glioblastoma Cells

    Institute of Scientific and Technical Information of China (English)

    Peter M. Haverty; Zhi-Ping Weng; Ulla Hansen

    2005-01-01

    Determining how cells regulate their transcriptional response to extracellular signals is key to the understanding of complex eukaryotic systems. This study was initiated with the goals of furthering the study of mammalian transcriptional regulation and analyzing the relative benefits of related computational methodologies. One dataset available for such an analysis involved gene expression profiling of the early growth factor response to platelet derived growth factor (PDGF)in a human glioblastoma cell line; this study differentiated genes whose expression was regulated by signaling through the phosphoinositide-3-kinase (PI3K) versus the extracellular-signal regulated kinase (ERK) pathways. We have compared the inferred transcription factors from this previous study with additional predictions of regulatory transcription factors using two alternative promoter sequence analysis techniques. This comparative analysis, in which the algorithms predict overlapping,although not identical, sets of factors, argues for meticulous benchmarking of promoter sequence analysis methods to determine the positive and negative attributes that contribute to their varying results. Finally, we inferred transcriptional regulatory networks deriving from various signaling pathways using the CARRIE program suite. These networks not only included previously described transcriptional features of the response to growth signals, but also predicted new regulatory features for the propagation and modulation of the growth signal.

  20. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2016-01-01

    Full Text Available The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin’s related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71 and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed.

  1. Enhancement of activated sludge disintegration and dewaterability by Fenton process

    Science.gov (United States)

    Heng, G. C.; Isa, M. H.

    2016-06-01

    Municipal and industrial wastewater treatment plants produce large amounts of sludge. This excess sludge is an inevitable drawback inherent to the activated sludge process. In this study, the waste activated sludge was obtained from the campus wastewater treatment plant at Universiti Teknologi PETRONAS (UTP), Malaysia. Fenton pretreatment was optimized by using the response surface methodology (RSM) to study the effects of three operating conditions including the dosage of H2O2 (g H2O2/kg TS), the molar ratio of H2O2/Fe2+ and reaction time. The optimum operating variables to achieve MLVSS removal 65%, CST reduction 28%, sCOD 11000 mg/L and EPS 500 mg/L were: 1000 g H2O2/kg TS, H2O2/Fe2+ molar ratio 70 and reaction time 45 min. Fenton process was proved to be able to enhance the sludge disintegration and dewaterability.

  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. Processed Vietnamese ginseng: Preliminary results in chemistry and biological activity

    OpenAIRE

    Le, Thi Hong Van; Lee, Seo Young; Kim, Tae Ryong; Kim, Jae Young; Kwon, Sung Won; NGUYEN, NGOC KHOI; Park, Jeong Hill; Nguyen, Minh Duc

    2013-01-01

    Background This study was carried out to investigate the effect of the steaming process on chemical constituents, free radical scavenging activity, and antiproliferative effect of Vietnamese ginseng. Methods Samples of powdered Vietnamese ginseng were steamed at 120°C for various times and their extracts were subjected to chemical and biological studies. Results Upon steaming, contents of polar ginsenosides, such as Rb1, Rc, Rd, Re, and Rg1, were rapidly decreased, whereas less polar ginsenos...

  4. Multimodal Hierarchical Dirichlet Process-based Active Perception

    OpenAIRE

    Taniguchi, Tadahiro; Takano, Toshiaki; Yoshino, Ryo

    2015-01-01

    In this paper, we propose an active perception method for recognizing object categories based on the multimodal hierarchical Dirichlet process (MHDP). The MHDP enables a robot to form object categories using multimodal information, e.g., visual, auditory, and haptic information, which can be observed by performing actions on an object. However, performing many actions on a target object requires a long time. In a real-time scenario, i.e., when the time is limited, the robot has to determine t...

  5. Government Regulatory

    Science.gov (United States)

    Becker, Katie

    Government regulation of food products, food processing, and food preparation is imperative in bringing an unadulterated, nonmisleading, and safe food product to market and is relevant to all areas of food science, including engineering, processing, chemistry, and microbiology. The liability associated with providing consumers with an adulterated or substandard product cannot only tarnish a company's name and reputation, but also impose substantial financial repercussions on the company and those individuals who play an active role in the violation. In order for a company to fully comply with the relevant food laws (both federal and state), an intimate knowledge of food science is required. Individuals knowledgeable in food science play an integral role not only in implementing and counseling food companies/processors to ensure compliance with government regulations, but these individuals are also necessary to the state and federal governments that make and enforce the relevant laws and regulators.

  6. Controlled movement processing: superior colliculus activity associated with countermanded saccades.

    Science.gov (United States)

    Paré, Martin; Hanes, Doug P

    2003-07-23

    We investigated whether the monkey superior colliculus (SC), an important midbrain structure for the regulation of saccadic eye movements, contains neurons with activity patterns sufficient to control both the cancellation and the production of saccades. We used a countermanding task to manipulate the probability that, after the presentation of a stop signal, the monkeys canceled a saccade that was planned in response to an eccentric visual stimulus. By modeling each animal's behavioral responses, with a race between GO and STOP processes leading up to either saccade initiation or cancellation, we estimated that saccade cancellation took on average 110 msec. Neurons recorded in the superior colliculus intermediate layers during this task exhibited the discharge properties expected from neurons closely involved in behavioral control. Both saccade- and fixation-related discharged differently when saccades were counter-manded instead of executed, and the time at which they changed their activity preceded the behavioral estimate of saccade cancellation obtained from the same trials by 10 and 13 msec, respectively. Furthermore, these intervals exceed the minimal amount of time needed for SC activity to influence eye movements. The additional observation that saccade-related neurons discharged significantly less when saccades were countermanded instead of executed suggests that saccades are triggered when these neurons reach a critical activation level. Altogether, these findings provide solid evidence that the superior colliculus contains the necessary neural signals to be directly involved in the decision process that regulates whether a saccade is to be produced. PMID:12878689

  7. Final disposal of spent nuclear fuel - regulatory system and roles of different actors during the decision process

    Energy Technology Data Exchange (ETDEWEB)

    2009-03-15

    In November 2006 Swedish Nuclear Fuels Co. applied for a license to build a plant for encapsulation of spent nuclear fuels at Oskarshamn, Sweden. The company also have plans to apply, in 2009, for a license to construct a underground repository for spent nuclear fuels. KASAM arranged a seminar in November 2006 in order to describe and discuss the licensing rules and regulations and the roles of different parties in the decision making. Another objective of the seminar was to point out possible ambiguities in this process. Another interesting question under discussion was in what ways the basic data for the decision should be produced. The seminar covered the part of the process beginning with the application for a license and ending with the government approval/rejection of the application. Most time was spent on the legal aspects of the process

  8. Materials and Process Activities for NASA's Composite Crew Module

    Science.gov (United States)

    Polis, Daniel L.

    2012-01-01

    In January 2007, the NASA Administrator and Associate Administrator for the Exploration Systems Mission Directorate chartered the NASA Engineering and Safety Center (NESC) to design, build, and test a full-scale Composite Crew Module (CCM). The overall goal of the CCM project was to develop a team from the NASA family with hands-on experience in composite design, manufacturing, and testing in anticipation of future space exploration systems being made of composite materials. The CCM project was planned to run concurrently with the Orion project s baseline metallic design within the Constellation Program so that features could be compared and discussed without inducing risk to the overall Program. The materials and process activities were prioritized based on a rapid prototype approach. This approach focused developmental activities on design details with greater risk and uncertainty, such as out-of-autoclave joining, over some of the more traditional lamina and laminate building block levels. While process development and associated building block testing were performed, several anomalies were still observed at the full-scale level due to interactions between process robustness and manufacturing scale-up. This paper describes the process anomalies that were encountered during the CCM development and the subsequent root cause investigations that led to the final design solutions. These investigations highlight the importance of full-scale developmental work early in the schedule of a complex composite design/build project.

  9. FAME: Freeform Active Mirrors Experiment: manufacturing process development

    Science.gov (United States)

    Challita, Zalpha; Hugot, Emmanuel; Venema, Lars; Schnetler, Hermine; Ferrari, Marc; Cuby, Jean-Gabriel

    2014-07-01

    Extreme freeform mirrors couple a non-axisymmetrical shape and an extreme asphericity, i.e. more than one millimeter of deviation from the best fit sphere. In astronomical instrumentation, such a large asphericity allows compact instruments, using less optical components. However, the lack of freeform mirrors manufacturing facilities is a real issue. We present the concept and development of an innovative manufacturing process based on plasticity forming which allow imprinting permanent deformations on mirrors, following a pre-defined mold. The aim of this activity, pursued in the frame of the OPTICON-FAME (Freeform Active Mirrors Experiment) project, is to demonstrate the suitability of this method for VIS/NIR/MIR applications. The process developed can operate on thin and flat polished initial substrates. Three study cases have been highlighted by FEA (Finite Element Analysis) and the real tests associated were performed on thin substrates in AISI420b stainless steel with 100 mm optical diameter. A comparison between FEA and tests is performed to study the evolution of the mechanical behaviour and the optical quality. The opto-mechanical results will allow a fine tuning of FEA parameters to optimize the residual form errors obtained through this process to converge toward an innovative and recurrent process.

  10. Land processes distributed active archive center product lifecycle plan

    Science.gov (United States)

    Daucsavage, John C.; Bennett, Stacie D.

    2014-01-01

    The U.S. Geological Survey (USGS) Earth Resources Observation and Science (EROS) Center and the National Aeronautics and Space Administration (NASA) Earth Science Data System Program worked together to establish, develop, and operate the Land Processes (LP) Distributed Active Archive Center (DAAC) to provide stewardship for NASA’s land processes science data. These data are critical science assets that serve the land processes science community with potential value beyond any immediate research use, and therefore need to be accounted for and properly managed throughout their lifecycle. A fundamental LP DAAC objective is to enable permanent preservation of these data and information products. The LP DAAC accomplishes this by bridging data producers and permanent archival resources while providing intermediate archive services for data and information products.

  11. Internationalization of regulatory requirements.

    Science.gov (United States)

    Juillet, Y

    2003-02-01

    The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

  12. 76 FR 54408 - Regulatory Review Schedule

    Science.gov (United States)

    2011-09-01

    ... Regulatory Review Schedule in the Federal Register setting out consultation schedules and review processes. (76 FR 18457, April 4, 2011). The Commission's regulatory review process established a tribal... National Indian Gaming Commission 25 CFR Chapter III Regulatory Review Schedule AGENCY: National...

  13. 76 FR 57683 - Regulatory Review Schedule

    Science.gov (United States)

    2011-09-16

    ... Regulatory Review Schedule in the Federal Register setting out consultation schedules and review processes. (76 FR 18457, April 4, 2011). The Commission's regulatory review process established a Tribal... National Indian Gaming Commission 25 CFR Chapter III Regulatory Review Schedule AGENCY: National...

  14. Toxicogenomics in Regulatory Ecotoxicology

    Science.gov (United States)

    The potential utility of toxicogenomics in toxicological research and regulatory activities has been the subject of scientific discussions, and as with any new technology, there is a wide range of opinion. The purpose of this feature article is to consider roles of toxicogenomic...

  15. Modeling Nonalcoholic Fatty Liver Disease with Human Pluripotent Stem Cell-Derived Immature Hepatocyte-Like Cells Reveals Activation of PLIN2 and Confirms Regulatory Functions of Peroxisome Proliferator-Activated Receptor Alpha

    Science.gov (United States)

    Graffmann, Nina; Ring, Sarah; Kawala, Marie-Ann; Wruck, Wasco; Ncube, Audrey; Trompeter, Hans-Ingo

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD/steatosis) is a metabolic disease characterized by the incorporation of fat into hepatocytes. In this study, we developed an in vitro model for NAFLD based on hepatocyte-like cells (HLCs) differentiated from human pluripotent stem cells. We induced fat storage in these HLCs and detected major expression changes of metabolism-associated genes, as well as an overall reduction of liver-related microRNAs. We observed an upregulation of the lipid droplet coating protein Perilipin 2 (PLIN2), as well as of numerous genes of the peroxisome proliferator-activated receptor (PPAR) pathway, which constitutes a regulatory hub for metabolic processes. Interference with PLIN2 and PPARα resulted in major alterations in gene expression, especially affecting lipid, glucose, and purine metabolism. Our model recapitulates many metabolic changes that are characteristic for NAFLD. It permits the dissection of disease-promoting molecular pathways and allows us to investigate the influences of distinct genetic backgrounds on disease progression. PMID:27308945

  16. Regulatory focus in groupt contexts

    NARCIS (Netherlands)

    Faddegon, Krispijn Johannes

    2009-01-01

    The thesis examines the influence of group processes on the regulatory focus of individual group members. It is demonstrated that the group situation can affect group members' regulatory focus both in a top-down fashion (via the identitiy of the group) and in a bottom-up fashion (emerging from the g

  17. Rho family GTP binding proteins are involved in the regulatory volume decrease process in NIH3T3 mouse fibroblasts

    DEFF Research Database (Denmark)

    Pedersen, Stine F; Beisner, Kristine H; Willumsen, Berthe M;

    2002-01-01

    kinase inhibitor Y-27632 and the phosphatidyl-inositol 3 kinase (PI3K) inhibitor wortmannin. The maximal rates of swelling-activated K+ (86 Rb+ as tracer) and taurine ([3H]taurine as tracer) efflux after a 30 % reduction in extracellular osmolarity were increased about twofold in cells with maximal Rho......AV14 expression compared to wild-type cells, but were unaffected by Y-27632. The volume set points for activation of release of both osmolytes appeared to be reduced by RhoAV14 expression. The maximal taurine efflux rate constant was potentiated by the tyrosine phosphatase inhibitor Na(3)VO(4), and...... inhibited by the tyrosine kinase inhibitor genistein. The magnitude of the swelling-activated Cl- current (I(Cl,swell) ) was higher in RhoAV14 than in wild-type cells after a 7.5 % reduction in extracellular osmolarity, but, in contrast to 86Rb+ and [3H]taurine efflux, similar in both strains after a 30...

  18. The two positively acting regulatory proteins PHO2 and PHO4 physically interact with PHO5 upstream activation regions.

    OpenAIRE

    Vogel, K.; Hörz, W; Hinnen, A

    1989-01-01

    The repressible acid phosphatase gene PHO5 of Saccharomyces cerevisiae requires the two positively acting regulatory proteins PHO2 and PHO4 for expression. pho2 or pho4 mutants are not able to derepress the PHO5 gene under low-Pi conditions. Here we show that both PHO2 and PHO4 bind specifically to the PHO5 promoter in vitro. Gel retardation assays using promoter deletions revealed two regions involved in PHO4 binding. Further characterization by DNase I footprinting showed two protected area...

  19. Acute HIV Seroconversion Presenting with Active Tuberculosis and Associated with High Levels of T-Regulatory Cells

    Science.gov (United States)

    Sued, Omar; Quiroga, María Florencia; Socías, María Eugenia; Turk, Gabriela; Salomón, Horacio

    2011-01-01

    Abstract A patient with well-defined acute HIV infection who developed concomitant pulmonary tuberculosis during the retroviral acute syndrome is reported here. In this patient high levels of T-regulatory cells (Tregs) and a low proliferation response to M. tuberculosis were initially detected, which normalized throughout follow-up. This case calls for the consideration of tuberculosis in patients in the early stages of HIV, and emphasizes the need for further study of the potential causal relationship between Treg cells and the risk of TB reactivation in HIV patients. PMID:21774688

  20. CsrA (BB0184) Is Not Involved in Activation of the RpoN-RpoS Regulatory Pathway in Borrelia burgdorferi

    OpenAIRE

    Ouyang, Zhiming; Zhou, Jianli; Norgard, Michael V.

    2014-01-01

    Borrelia burgdorferi encodes a homologue of the bacterial carbon storage regulator A (CsrA). Recently, it was reported that CsrA contributes to B. burgdorferi infectivity and is required for the activation of the central RpoN-RpoS regulatory pathway. However, many questions concerning the function of CsrA in B. burgdorferi gene regulation remain unanswered. In particular, there are conflicting reports concerning the molecular details of how CsrA may modulate rpoS expression and, thus, how Csr...

  1. Drilling to investigate processes in active tectonics and magmatism

    Science.gov (United States)

    Shervais, J.; Evans, J.; Toy, V.; Kirkpatrick, J.; Clarke, A.; Eichelberger, J.

    2014-12-01

    Coordinated drilling efforts are an important method to investigate active tectonics and magmatic processes related to faults and volcanoes. The US National Science Foundation (NSF) recently sponsored a series of workshops to define the nature of future continental drilling efforts. As part of this series, we convened a workshop to explore how continental scientific drilling can be used to better understand active tectonic and magmatic processes. The workshop, held in Park City, Utah, in May 2013, was attended by 41 investigators from seven countries. Participants were asked to define compelling scientific justifications for examining problems that can be addressed by coordinated programs of continental scientific drilling and related site investigations. They were also asked to evaluate a wide range of proposed drilling projects, based on white papers submitted prior to the workshop. Participants working on faults and fault zone processes highlighted two overarching topics with exciting potential for future scientific drilling research: (1) the seismic cycle and (2) the mechanics and architecture of fault zones. Recommended projects target fundamental mechanical processes and controls on faulting, and range from induced earthquakes and earthquake initiation to investigations of detachment fault mechanics and fluid flow in fault zones. Participants working on active volcanism identified five themes: the volcano eruption cycle; eruption sustainability, near-field stresses, and system recovery; eruption hazards; verification of geophysical models; and interactions with other Earth systems. Recommended projects address problems that are transferrable to other volcanic systems, such as improved methods for identifying eruption history and constraining the rheological structure of shallow caldera regions. Participants working on chemical geodynamics identified four major themes: large igneous provinces (LIPs), ocean islands, continental hotspot tracks and rifts, and

  2. Locating Melody Processing Activity in Auditory Cortex with Magnetoencephalography.

    Science.gov (United States)

    Patterson, Roy D; Andermann, Martin; Uppenkamp, Stefan; Rupp, André

    2016-01-01

    This paper describes a technique for isolating the brain activity associated with melodic pitch processing. The magnetoencephalograhic (MEG) response to a four note, diatonic melody built of French horn notes, is contrasted with the response to a control sequence containing four identical, "tonic" notes. The transient response (TR) to the first note of each bar is dominated by energy-onset activity; the melody processing is observed by contrasting the TRs to the remaining melodic and tonic notes of the bar (2-4). They have uniform shape within a tonic or melodic sequence which makes it possible to fit a 4-dipole model and show that there are two sources in each hemisphere--a melody source in the anterior part of Heschl's gyrus (HG) and an onset source about 10 mm posterior to it, in planum temporale (PT). The N1m to the initial note has a short latency and the same magnitude for the tonic and the melodic sequences. The melody activity is distinguished by the relative sizes of the N1m and P2m components of the TRs to notes 2-4. In the anterior source a given note elicits a much larger N1m-P2m complex with a shorter latency when it is part of a melodic sequence. This study shows how to isolate the N1m, energy-onset response in PT, and produce a clean melody response in the anterior part of auditory cortex (HG).

  3. Regulatory aspects of NPP safety

    International Nuclear Information System (INIS)

    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)

  4. Process for processing and conditioning radioactive effluents of low and medium activity

    International Nuclear Information System (INIS)

    Preferably continuous process for processing radioactive effluents of low and medium activity, comprising an effluent pre-treatment: precipitation of radioactive compounds to form a stable suspension that can be concentrated. Then a mix is made of 0.6 to 2 parts of cement by weight for one part by weight of suspension, from 0.5 to 5% by weight, in relation to the cement, of asbestos fibre and, if necessary, added water for the cement to set, this suspension containing from 15 to 75% by weight of dry extract and a suspension agent. The homogeneous mix achieved is poured into a container

  5. The insulin receptor activation process involves localized conformational changes.

    Science.gov (United States)

    Baron, V; Kaliman, P; Gautier, N; Van Obberghen, E

    1992-11-15

    The molecular process by which insulin binding to the receptor alpha-subunit induces activation of the receptor beta-subunit with ensuing substrate phosphorylation remains unclear. In this study, we aimed at approaching this molecular mechanism of signal transduction and at delineating the cytoplasmic domains implied in this process. To do this, we used antipeptide antibodies to the following sequences of the receptor beta-subunit: (i) positions 962-972 in the juxtamembrane domain, (ii) positions 1247-1261 at the end of the kinase domain, and (iii) positions 1294-1317 and (iv) positions 1309-1326, both in the receptor C terminus. We have previously shown that insulin binding to its receptor induces a conformational change in the beta-subunit C terminus. Here, we demonstrate that receptor autophosphorylation induces an additional conformational change. This process appears to be distinct from the one produced by ligand binding and can be detected in at least three different beta-subunit regions: the juxtamembrane domain, the kinase domain, and the C terminus. Hence, the cytoplasmic part of the receptor beta-subunit appears to undergo an extended conformational change upon autophosphorylation. By contrast, the insulin-induced change does not affect the juxtamembrane domain 962-972 nor the kinase domain 1247-1261 and may be limited to the receptor C terminus. Further, we show that the hormone-dependent conformational change is maintained in a kinase-deficient receptor due to a mutation at lysine 1018. Therefore, during receptor activation, the ligand-induced change could precede ATP binding and receptor autophosphorylation. We propose that insulin binding leads to a transient receptor form that may allow ATP binding and, subsequently, autophosphorylation. The second conformational change could unmask substrate-binding sites and stabilize the receptor in an active conformation. PMID:1331080

  6. CAN ACTIVE EXPERIMENTS BE USED IN WOODWORKING PROCESSES?

    Directory of Open Access Journals (Sweden)

    Wilhelm LAURENZI

    2014-12-01

    Full Text Available The experiments conducted during scientific research can be very simple or very complex. It is widely known that the classic (passive experiments, consisting of 5 tests at every point of the experiment, are the most precise, but also expensive experiments. In order to reduce the cost of experiments, many researchers use different types of active experiments. These experiments are cheaper than the classical experiments, but no so precise (up to 95%. The number of tests that are necessary can be reduced by designing the experiments (DOE experiments. If we take into account that the structure of wood (depending on its type is non-uniform, it is possible that the results of the experimental research conducted with active experiments are inaccurate. In order to confirm or invalidate these hypothesis, this paper presents a simulation program that allows simulations of a milling process for different types of experiments

  7. 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)

    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

  8. Role of sympathetic nerve activity in the process of fainting

    Directory of Open Access Journals (Sweden)

    Satoshi eIwase

    2014-09-01

    Full Text Available Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery, and the process of syncope progression will be described with two types of sympathetic change. Simultaneous recordings of microneurographically recorded MSNA and continuous and noninvasive blood pressure measurement have disclose what is going on in the course of progression of the syncope. Vasovagal or neurally mediated syncope, three stages are identified in the course of syncope onset, oscillation, imbalance, and catastrophe phases. The vasovagal syncope is characterized by the sympathoexcitation, followed by vagal overcome via the Bezold-Jarisch reflex. Orthostatic syncope is caused by the response failure or lack of sympathetic nerve activity toward the orthostatic challenge followed by the fluid shift, and subsequent cerebral low perfusion. Four causes are considered for the compensatory failure, which triggers the orthostatic syncope; hypovolemia, increased pooling in the lower body, failure to activate the sympathetic activity, and failure of vasoconstriction against sympathetic vasoconstrictive stimulation. Many pathophysiological conditions were described in the viewpoint of 1 exaggerated sympathoexcitation and 2 failure to activate the sympathetic nerve. We conclude that the sympathetic nervous system can control the cardiovascular function, and its failure resulted syncope, however, responses of the system by microneurographically recorded MSNA would determine the pathophysiology of the onset and progression of syncope, explaining the treatment effect that could be achieved by the analysis of this mechanism.

  9. Hydration process in Portland cement blended with activated coal gangue

    Institute of Scientific and Technical Information of China (English)

    Xian-ping LIU; Pei-ming WANG; Min-ju DING

    2011-01-01

    This paper deals with the hydration of a blend of Portland cement and activated coal gangue in order to determine the relationship between the degree of hydration and compressive strength development.The hydration process was investigated by various means:isothermal calorimetry,thermal analysis,non-cvaporable water measurement,and X-ray diffraction analysis.The results show that the activated coal gangue is a pozzolanic material that contributes to the hydration of the cement blend.The pozzolanic reaction occurs over a period of between 7 and 90 d,consuming portlandite and forming both crystal hydrates and ill-crystallized calcium silicate hydrates.These hydrates are similar to those found in pure Portland cement.The results show that if activated coal gangue is substituted for cement at up to 30% (w/w),it does not significantly affect the final compressive strength of the blend.A long-term compressive strength improvement can in fact be achieved by using activated coal gangue as a supplementary cementing material.The relationship between compressive strength and degree of hydration for both pure Portland cement and blended cement can be described with the same equation.However,the parameters are different since blended cement produces fewer calcium silicate hydrates than pure Portland cement at the same degree of hydration.

  10. Web Refinding Support System Based on Process Recollective Activity

    Directory of Open Access Journals (Sweden)

    Masashi Toda

    2012-05-01

    Full Text Available The recent growth of search technology has enabled people to find information more easily. However, most people need to refind information on a daily basis. Finding and refinding are different activities and require different types of support. However, current refinding support systems don't consider this point. This has caused several problems: PVR, loss of contextual information, and difference in search experiences. We discuss these problems and their solutions from a cognitive perspective. We propose a process-recollective refinding support system based on this discussion. We demonstrate a novel approach to refinding information on the web and a specific system as an example.

  11. Active Chemical Sensing With Partially Observable Markov Decision Processes

    Science.gov (United States)

    Gosangi, Rakesh; Gutierrez-Osuna, Ricardo

    2009-05-01

    We present an active-perception strategy to optimize the temperature program of metal-oxide sensors in real time, as the sensor reacts with its environment. We model the problem as a partially observable Markov decision process (POMDP), where actions correspond to measurements at particular temperatures, and the agent is to find a temperature sequence that minimizes the Bayes risk. We validate the method on a binary classification problem with a simulated sensor. Our results show that the method provides a balance between classification rate and sensing costs.

  12. Process for reduction of the volume of low activity waste

    International Nuclear Information System (INIS)

    The invention concerns a process for the reduction of the volume of low activity waste in a plant equipped with separate solid and liquid inputs, where the liquid is taken via a filter to a waste water container and the dry solids are taken to a solid container. Plant of this type should be used in hospitals and university clinics etc. It is an important aim of the invention to describe a process, which makes a particularly compact layout of such a plant possible. The solids are taken to a pulverizer and after passing through this, the dry material is separated from the process and taken to the solid container, while the wet material is dried in a flushing drying system and then also taken to the solid container. The humidity carried off with the hot air is condensed and the condensate is taken to the waste water container. The material taken to the solid container is compacted in a press, preferably adding glue. By separating the pulverized already dry solid material from the pulverized wet material, the plant itself can be made considerably smaller, as one does not have to take the whole volume of solids into account for further processing. (orig./HP)

  13. Leachate Treatment by Batch Decant Activated Sludge Process and Powdered Activated Carbon Addition

    OpenAIRE

    Y Hashempur; R Rezaei Kalantary; Jaafarzadeh, N.; Jorfi, S.

    2009-01-01

    "n "nBackgrounds and Objectives: Direct biodegradation of landfill leachate is too difficult because of high concentrations of COD and NH3 and also the presence of toxic compounds. The main objective of this study was to application of Strurvite precipitation as a pretreatment stage, in order to remove inhibitors of biodegradation before the batch decant activated sludge process with addition of powdered activated carbon (PAC)."nMaterials and Methods: Strurvite precipitated leachate was intro...

  14. Behavioral activation system modulation on brain activation during appetitive and aversive stimulus processing

    OpenAIRE

    Barrós-Loscertales, Alfonso; Ventura-Campos, Noelia; Sanjuán-Tomás, Ana; Belloch, Vicente; Parcet, Maria-Antònia; Ávila, César

    2010-01-01

    The reinforcement sensitivity theory (RST) proposed the behavioral activation system (BAS) as a neurobehavioral system that is dependent on dopamine-irrigated structures and that mediates the individual differences in sensitivity and reactivity to appetitive stimuli associated with BAS-related personality traits. Theoretical developments propose that high BAS sensitivity is associated with both enhanced appetitive stimuli processing and the diminished processing of aversive stimuli. The objec...

  15. Transiently reduced PI3K/Akt activity drives the development of regulatory function in antigen-stimulated Naive T-cells.

    Directory of Open Access Journals (Sweden)

    Eloho Etemire

    Full Text Available Regulatory T-cells (Tregs are central for immune homeostasis and divided in thymus-derived natural Tregs and peripherally induced iTreg. However, while phenotype and function of iTregs are well known, a remarkable lack exists in knowledge about signaling mechanisms leading to their generation from naïve precursors in peripheral tissues. Using antigen specific naïve T-cells from mice, we investigated CD4+ CD25+ FoxP3- iTreg induction during antigen-specific T-cell receptor (TCR stimulation with weak antigen presenting cells (APC. We show that early signaling pathways such as ADAM-17-activation appeared similar in developing iTreg and effector cells (Teff and both initially shedded CD62-L. But iTreg started reexpressing CD62-L after 24 h while Teff permanently downmodulated it. Furthermore, between 24 and 72 hours iTreg presented with significantly lower phosphorylation levels of Akt-S473 suggesting lower activity of the PI3K/Akt-axis. This was associated with a higher expression of the Akt hydrophobic motif-specific phosphatase PHLPP1 in iTreg. Importantly, the lack of costimulatory signals via CD28 from weak APC was central for the development of regulatory function in iTreg but not for the reappearance of CD62-L. Thus, T-cells display a window of sensitivity after onset of TCR triggering within which the intensity of the PI3K/Akt signal controls entry into either effector or regulatory pathways.

  16. Continuous activation of the CD122/STAT-5 signaling pathway during selection of antigen-specific regulatory T cells in the murine thymus.

    Directory of Open Access Journals (Sweden)

    Jérémie D Goldstein

    Full Text Available Signaling events affecting thymic selection of un-manipulated polyclonal natural CD25(+foxp3(+ regulatory T cells (nTreg have not been established ex vivo. Here, we report a higher frequency of phosphorylated STAT-5 (pSTAT-5 in nTreg cells in the adult murine thymus and to a lesser extent in the periphery, compared to other CD4(+CD8(- subsets. In the neonatal thymus, the numbers of pSTAT-5(+ cells in CD25(+foxp3(- and nTreg cells increased in parallel, suggesting that pSTAT-5(+CD25(+foxp3(- cells might represent the precursors of foxp3(+ regulatory T cells. This "specific" pSTAT-5 expression detected in nTreg cells ex vivo was likely due to a very recent signal given by IL-2/IL-15 cytokines in vivo since (i it disappeared rapidly if cells were left unstimulated in vitro and (ii was also observed if total thymocytes were stimulated in vitro with saturating amounts of IL-2 and/or IL-15 but not IL-7. Interestingly, STAT-5 activation upon IL-2 stimulation correlated better with foxp3 and CD122 than with CD25 expression. Finally, we show that expression of an endogenous superantigen strongly affected the early Treg cell repertoire but not the proportion of pSTAT-5(+ cells within this repertoire. Our results reveal that continuous activation of the CD122/STAT-5 signaling pathway characterize regulatory lineage differentiation in the murine thymus.

  17. Phosphorylation-dephosphorylation process as a probable mechanism for the diurnal regulatory changes of phosphoenolpyruvate carboxylase in CAM plants.

    Science.gov (United States)

    Brulfert, J; Vidal, J; Le Marechal, P; Gadal, P; Queiroz, O; Kluge, M; Kruger, I

    1986-04-14

    Day and night forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) (PEPC) were extracted from leaves of the CAM plants Kalanchoe daigremontiana, K. tubiflora and K. blossfeldiana previously fed with [32P] labelled phosphate solution. A one-step immunochemical purification followed by SDS polyacrylamide gel electrophoresis and autoradiography showed that, in all species, the night form of the enzyme was phosphorylated and not the day form. Limited acid hydrolysis of the night form and two-dimensional separation identified predominantly labelled phosphoserine and phosphothreonine. In vitro addition of exogenous acid phosphatase (EC 3.1.3.2) to desalted night form-containing extracts resulted within 30 min in a shift in PEPC enzymic properties similar to the in vivo changes from night to day form. It is suggested that phosphorylation-dephosphorylation of the enzyme could be the primary in vivo process which might explain the observed rhythmicity of enzymic properties. PMID:3707571

  18. 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

  19. Molecular chaperone activity and biological regulatory actions of the TPR-domain immunophilins FKBP51 and FKBP52.

    Science.gov (United States)

    Erlejman, Alejandra G; Lagadari, Mariana; Harris, Diondra C; Cox, Marc B; Galigniana, Mario D

    2014-05-01

    Immunophilins comprise a family of intracellular proteins with peptidyl-prolyl-(cis/trans)-isomerase activity. These foldases are abundant, ubiquitous, and able to bind immunosuppressant drugs, from which the term immunophilin derives. Family members are found in abundance in virtually all organisms and subcellular compartments, and their amino acid sequences are conserved phylogenetically. Immunophilins possess the ability to function as molecular chaperones favoring the proper folding and biological regulation of their biological actions. Their ability to interact via their TPR domains with the 90-kDa heat-shock protein, and through this chaperone, with several signalling cascade factors is of particular importance. Among the family members, the highly homologous proteins FKBP51 and FKBP52 were first characterized due to their ability to interact with steroid hormone receptors. Since then, much progress has been made in understanding the mechanisms by which they regulate receptor signaling and the resulting roles they play not only in endocrine processes, but also in cell architecture, neurodifferentiation, and tumor progression. In this article we review the most relevant features of these two immunophilins and their potential as pharmacologic targets.

  20. Assessment of regulatory effectiveness. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    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

  1. Cloud condensation nuclei activity and droplet activation kinetics of wet processed regional dust samples and minerals

    Directory of Open Access Journals (Sweden)

    P. Kumar

    2011-08-01

    Full Text Available This study reports laboratory measurements of particle size distributions, cloud condensation nuclei (CCN activity, and droplet activation kinetics of wet generated aerosols from clays, calcite, quartz, and desert soil samples from Northern Africa, East Asia/China, and Northern America. The dependence of critical supersaturation, sc, on particle dry diameter, Ddry, is used to characterize particle-water interactions and assess the ability of Frenkel-Halsey-Hill adsorption activation theory (FHH-AT and Köhler theory (KT to describe the CCN activity of the considered samples. Wet generated regional dust samples produce unimodal size distributions with particle sizes as small as 40 nm, CCN activation consistent with KT, and exhibit hygroscopicity similar to inorganic salts. Wet generated clays and minerals produce a bimodal size distribution; the CCN activity of the smaller mode is consistent with KT, while the larger mode is less hydrophilic, follows activation by FHH-AT, and displays almost identical CCN activity to dry generated dust. Ion Chromatography (IC analysis performed on regional dust samples indicates a soluble fraction that cannot explain the CCN activity of dry or wet generated dust. A mass balance and hygroscopicity closure suggests that the small amount of ions (from low solubility compounds like calcite present in the dry dust dissolve in the aqueous suspension during the wet generation process and give rise to the observed small hygroscopic mode. Overall these results identify an artifact that may question the atmospheric relevance of dust CCN activity studies using the wet generation method.

    Based on the method of threshold droplet growth analysis, wet generated mineral aerosols display similar activation kinetics compared to ammonium sulfate calibration aerosol. Finally, a unified CCN activity framework that accounts for concurrent effects of solute and adsorption is developed to

  2. Improved cosmetic activity by optimizing the Lithospermum erythrorhizon extraction process.

    Science.gov (United States)

    Kim, Ji Seon; Seo, Yong Chang; No, Ra Hwan; Lee, Hyeon Yong

    2015-01-01

    This study was conducted to expand the use of Lithospermum erythrorhizon, which is a good source of natural dye, in skin whitening and immune activation cosmetics. The goal was to provide cosmeceutical data about the extraction yield and shikonin contents of this plant by optimizing the ultrasonic extraction and high pressure extraction conditions. Under optimal extraction conditions, which consisted of 500 MPa for 60 min and 120 kHz for 90 min, 27.49 and 3.19 % (w/w) of the highest extraction yield and shikonin contents were obtained, compared to 16.32 and 1.81 % from a conventional ethanol extract (EE) control. Hyaluronidase inhibition activity was measured as 44.24 % after adding 1.0 mg/ml of ethanol extract, but it was as high as 64.19 % when using extract produced by ultrasonication with high pressure extraction (UE + HPE). The MMP-1 expression levels from skin fibroblast cells (CCD-986sk) treated with or without UV irradiation were also lowered by as much as 110.6 % after adding 1.0 mg/ml of the UE + HPE extract, relative to 126.9 % from the EE. After UVA exposure, prostaglandin E2 production from RAW 264.7 was also lower, at 110.6 %, which also indicates that the extract from the UE + HPE process enhanced skin immune activation activities. For the skin whitening activity, tyrosinase inhibitory activity was observed at 67.15 % in the HPE + UE extract, which was ca. 20 % higher than that of the EE extract (57.48 %). To reduce melanin production in Clone M-3 cells, 79.5 % of the melanin production was estimated after adding 1.0 mg/ml of the UE + HPE extract compared to that of the control (no treatment), which was similar to the 77.4 % result found in an ascorbic acid positive control. The highest shikonin secretion was conclusively obtained under the optimal conditions and resulted in a significant improvement of the cosmetic activities of L. erythrorhizon extracts. PMID:24287611

  3. Quality assurance within regulatory bodies

    International Nuclear Information System (INIS)

    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

  4. Inspection and enforcement by the regulatory body for nuclear power plants. A safety guide. A publication within the NUSS programme

    International Nuclear Information System (INIS)

    The purpose of this Safety Guide is to provide guidance on fulfilling the requirements for inspection and enforcement by the regulatory body, as set out in the Code on the Safety of Nuclear Power Plants; Governmental Organization. This Safety Guide deals with the responsibilities of the regulatory body, the organization of inspection programmes, the inspection resources of the regulatory body, methods of inspection, requirements on the applicant/licensee in regard to regulatory inspection, inspection reports, and regulatory action and enforcement. It is recognized that many of the provisions of this Safety Guide may be applicable to the regulations of other nuclear facilities and related activities including research reactors, fuel processing and manufacturing plants, irradiated fuel processing plants and radioactive waste management facilities. This Safety Guide does not deal specifically with the functions of a regulatory body responsible for such matters; however, the guidance presented here may be applied as appropriate to these activities. 11 refs, 1 fig

  5. Nitrogen in the Process of Waste Activated Sludge Anaerobic Digestion

    Directory of Open Access Journals (Sweden)

    Suschka Jan

    2014-07-01

    Full Text Available Primary or secondary sewage sludge in medium and large WWTP are most often processed by anaerobic digestion, as a method of conditioning, sludge quantity minimization and biogas production. With the aim to achieve the best results of sludge processing several modifications of technologies were suggested, investigated and introduced in the full technical scale. Various sludge pretreatment technologies before anaerobic treatment have been widely investigated and partially introduced. Obviously, there are always some limitations and some negative side effects. Selected aspects have been presented and discussed. The problem of nitrogen has been highlighted on the basis of the carried out investigations. The single and two step - mesophilic and thermophilic - anaerobic waste activated sludge digestion processes, preceded by preliminary hydrolysis were investigated. The aim of lab-scale experiments was pre-treatment of the sludge by means of low intensive alkaline and hydrodynamic disintegration. Depending on the pretreatment technologies and the digestion temperature large ammonia concentrations, up to 1800 mg NH4/dm3 have been measured. Return of the sludge liquor to the main sewage treatment line means additional nitrogen removal costs. Possible solutions are discussed.

  6. Different Head Environments in Tarantula Thick Filaments Support a Cooperative Activation Process

    OpenAIRE

    Sulbarán, Guidenn; Biasutto, Antonio; Alamo, Lorenzo; Riggs, Claire; Pinto, Antonio; Méndez, Franklin; Craig, Roger; Padrón, Raúl

    2013-01-01

    Myosin filaments from many muscles are activated by phosphorylation of their regulatory light chains (RLCs). Structural analysis of relaxed tarantula thick filaments shows that the RLCs of the interacting free and blocked myosin heads are in different environments. This and other data suggested a phosphorylation mechanism in which Ser-35 of the free head is exposed and constitutively phosphorylated by protein kinase C, whereas the blocked head is hidden and unphosphorylated; on activation, my...

  7. A Framework for Integrating Environmental Justice in Regulatory Analysis

    Directory of Open Access Journals (Sweden)

    Onyemaechi C. Nweke

    2011-06-01

    Full Text Available With increased interest in integrating environmental justice into the process for developing environmental regulations in the United States, analysts and decision makers are confronted with the question of what methods and data can be used to assess disproportionate environmental health impacts. However, as a first step to identifying data and methods, it is important that analysts understand what information on equity impacts is needed for decision making. Such knowledge originates from clearly stated equity objectives and the reflection of those objectives throughout the analytical activities that characterize Regulatory Impact Analysis (RIA, a process that is traditionally used to inform decision making. The framework proposed in this paper advocates structuring analyses to explicitly provide pre-defined output on equity impacts. Specifically, the proposed framework emphasizes: (a defining equity objectives for the proposed regulatory action at the onset of the regulatory process, (b identifying specific and related sub-objectives for key analytical steps in the RIA process, and (c developing explicit analytical/research questions to assure that stated sub-objectives and objectives are met. In proposing this framework, it is envisioned that information on equity impacts informs decision-making in regulatory development, and that this is achieved through a systematic and consistent approach that assures linkages between stated equity objectives, regulatory analyses, selection of policy options, and the design of compliance and enforcement activities.

  8. 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

  9. 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

  10. Regulatory review of probabilistic safety assessment (PSA) Level 2

    International Nuclear Information System (INIS)

    Probabilistic safety assessment (PSA) is increasingly being used as part of the decision making process to assess the level of safety of nuclear power plants. The methodologies in use are maturing and the insights gained from the PSAs are being used along with those from deterministic analysis. Many regulatory authorities consider the current state of the art in PSA to be sufficiently well developed for results to be used centrally in the regulatory decision making process-referred to as risk informed regulation. For these applications to be successful, it will be necessary for the regulatory authority to have a high degree of confidence in the PSA. However, at the 1994 IAEA Technical Committee Meeting on Use of PSA in the Regulatory Process and at the OECD Nuclear Energy Agency Committee for Nuclear Regulatory Activities (CNRA) 'Special Issues' meeting in 1997 on Review Procedures and Criteria for Different Regulatory Applications of PSA, it was recognized that formal regulatory review guidance for PSA did not exist. The senior regulators noted that there was a need to produce some international guidance for reviewing PSAs to establish an agreed basis for assessing whether important technological and methodological issues in PSAs are treated adequately and to verify that conclusions reached are appropriate. In 1997, the IAEA and OECD Nuclear Energy Agency agreed to produce, in cooperation, guidance on Regulatory Review of PSA. This led to the publication of IAEA-TECDOC-1135 on the Regulatory Review of Probabilistic Safety Assessment (PSA) Level 1, which gives advice for the review of Level 1 PSA for initiating events occurring at power plants. This TECDOC extends the coverage to address the regulatory review of Level 2 PSA.These publications are intended to provide guidance to regulatory authorities on how to review the PSA for a nuclear power plant to gain confidence that it has been carried out to an acceptable level of quality so that it can be used as the

  11. Contagion processes on the static and activity driven coupling networks

    CERN Document Server

    Lei, Yanjun; Guo, Quantong; Ma, Yifang; Li, Meng; Zheng, Zhiming

    2015-01-01

    The evolution of network structure and the spreading of epidemic are common coexistent dynamical processes. In most cases, network structure is treated either static or time-varying, supposing the whole network is observed in a same time window. In this paper, we consider the epidemic spreading on a network consisting of both static and time-varying structures. At meanwhile, the time-varying part and the epidemic spreading are supposed to be of the same time scale. We introduce a static and activity driven coupling (SADC) network model to characterize the coupling between static (strong) structure and dynamic (weak) structure. Epidemic thresholds of SIS and SIR model are studied on SADC both analytically and numerically with various coupling strategies, where the strong structure is of homogeneous or heterogeneous degree distribution. Theoretical thresholds obtained from SADC model can both recover and generalize the classical results in static and time-varying networks. It is demonstrated that weak structure...

  12. Enhanced 3D face processing using an active vision system

    DEFF Research Database (Denmark)

    Lidegaard, Morten; Larsen, Rasmus; Kraft, Dirk;

    2014-01-01

    We present an active face processing system based on 3D shape information extracted by means of stereo information. We use two sets of stereo cameras with different field of views (FOV): One with a wide FOV is used for face tracking, while the other with a narrow FOV is used for face identification...... of the narrow FOV camera. We substantiate these two observations by qualitative results on face reconstruction and quantitative results on face recognition. As a consequence, such a set-up allows to achieve better and much more flexible system for 3D face reconstruction e.g. for recognition or emotion....... We argue for two advantages of such a system: First, an extended work range, and second, the possibility to place the narrow FOV camera in a way such that a much better reconstruction quality can be achieved compared to a static camera even if the face had been fully visible in the periphery...

  13. Dual Control with Active Learning using Gaussian Process Regression

    CERN Document Server

    Alpcan, Tansu

    2011-01-01

    In many real world problems, control decisions have to be made with limited information. The controller may have no a priori (or even posteriori) data on the nonlinear system, except from a limited number of points that are obtained over time. This is either due to high cost of observation or the highly non-stationary nature of the system. The resulting conflict between information collection (identification, exploration) and control (optimization, exploitation) necessitates an active learning approach for iteratively selecting the control actions which concurrently provide the data points for system identification. This paper presents a dual control approach where the information acquired at each control step is quantified using the entropy measure from information theory and serves as the training input to a state-of-the-art Gaussian process regression (Bayesian learning) method. The explicit quantification of the information obtained from each data point allows for iterative optimization of both identifica...

  14. Mapping the Regulatory Network for Salmonella enterica Serovar Typhimurium Invasion

    Science.gov (United States)

    Smith, Carol; Stringer, Anne M.; Mao, Chunhong; Palumbo, Michael J.

    2016-01-01

    ABSTRACT Salmonella enterica pathogenicity island 1 (SPI-1) encodes proteins required for invasion of gut epithelial cells. The timing of invasion is tightly controlled by a complex regulatory network. The transcription factor (TF) HilD is the master regulator of this process and senses environmental signals associated with invasion. HilD activates transcription of genes within and outside SPI-1, including six other TFs. Thus, the transcriptional program associated with host cell invasion is controlled by at least 7 TFs. However, very few of the regulatory targets are known for these TFs, and the extent of the regulatory network is unclear. In this study, we used complementary genomic approaches to map the direct regulatory targets of all 7 TFs. Our data reveal a highly complex and interconnected network that includes many previously undescribed regulatory targets. Moreover, the network extends well beyond the 7 TFs, due to the inclusion of many additional TFs and noncoding RNAs. By comparing gene expression profiles of regulatory targets for the 7 TFs, we identified many uncharacterized genes that are likely to play direct roles in invasion. We also uncovered cross talk between SPI-1 regulation and other regulatory pathways, which, in turn, identified gene clusters that likely share related functions. Our data are freely available through an intuitive online browser and represent a valuable resource for the bacterial research community. PMID:27601571

  15. COMPUTER AIDED DESIGN OF WASTE WATER TREATMENT PLANT WITH ACTIVATED SLUDGE PROCESS

    Directory of Open Access Journals (Sweden)

    K. SUNDARA KUMAR

    2011-04-01

    Full Text Available There are two fundamental reasons for treatment of wastewater viz., prevention of pollution and thereby protecting the environment, and protecting the public health by safe guarding water supplies andpreventing the spread of water borne diseases. Proper design, construction together with good operation and maintenance are essential for waste water treatment plants (WWTP, in order to produce effluents which are satisfying the safe disposal standards prescribed by the regulatory authorities. In this work a computer program in C++ has been developed for comprehensive design of wastewater treatment plant which incorporates activated sludge process as biological treatment method. All the units of WWTP areincluded in the design and the program is developed in a very user friendly manner by referring various standard procedures and manuals. The validity of the software has been verified by test running andcomparison with an existing plant data. This program not only helps in sizing the treatment units but also helps in understanding the plant’s capacity as well as in deciding the future expansion works needed for increased hydraulic and organic loadings.

  16. Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, Wendy R.; Roy, Monideepa; Vardar-Ulu, Didem; Garfinkel, Megan; Mansour, Marc R.; Aster, Jon C.; Blacklow, Stephen C.; (BWH); (Wellesley); (UCL)

    2009-09-02

    Proteolytic resistance of Notch prior to ligand binding depends on the structural integrity of a negative regulatory region (NRR) of the receptor that immediately precedes the transmembrane segment. The NRR includes the 3 Lin12/Notch repeats and the juxtamembrane heterodimerization domain, the region of Notch1 most frequently mutated in T-cell acute lymphoblastic leukemia lymphoma (T-ALL). Here, we report the x-ray structure of the Notch1 NRR in its autoinhibited conformation. A key feature of the Notch1 structure that maintains its closed conformation is a conserved hydrophobic plug that sterically occludes the metalloprotease cleavage site. Crystal packing interactions involving a highly conserved, exposed face on the third Lin12/Notch repeat suggest that this site may normally be engaged in intermolecular or intramolecular protein-protein interactions. The majority of known T-ALL-associated point mutations map to residues in the hydrophobic interior of the Notch1 NRR. A novel mutation (H1545P), which alters a residue at the crystal-packing interface, leads to ligand-independent increases in signaling in reporter gene assays despite only mild destabilization of the NRR, suggesting that it releases the autoinhibitory clamp on the heterodimerization domain imposed by the Lin12/Notch repeats. The Notch1 NRR structure should facilitate a search for antibodies or compounds that stabilize the autoinhibited conformation.

  17. Electrical processes for the treatment of medium active liquid wastes

    International Nuclear Information System (INIS)

    Cross-flow electrokinetic dewatering has been developed on a lab-scale into an effective process for the treatment of such wastes as gravity-settled flocs, or sludges arising from fuel storage. The product may be concentrated to 25-42% solids while still remaining fluid, prior to immobilization - e.g. by addition of cement powder. Complete retention of activity in the concentrate was observed during the treatment of Harwell low-level waste sludges due to the high solids separation factor ( > 104). It is a low pressure, low temperature process - consuming only 0.03-0.13 kWh/L at permeation rates of 0.3-1.5 m/h (depending on the stream), corresponding to 1/67 - 1/15 that needed for evaporation. An advanced electrochemical ion-exchange system has been developed in which ionic material can be electrically adsorbed and eluted by polarity reversal > 1000 times, without any change in performance. Decontamination factors of about 2000 were achieved for Cs removal, up to 75% loading of the exchanger at flow rates of 8 bed volumes/h. Elution into water can give concentrates of >= 0.25 M - with consequent high volume reduction factors. Inorganic ion-exchangers have also demonstrated system selectivity for the removal of specific cations. Overall energy consumption is 3 (1/400 evaporation). Significant cost savings over conventional ion-exchange may accrue from the improved performance under electrical control, and the reduced volumes of waste requiring disposal. (author)

  18. Remedial action plan for the inactive uranium processing site at Naturita, Colorado. DOE responses to comments from U.S. Nuclear Regulatory Commission and Colorado Department of Public Health and Environment

    International Nuclear Information System (INIS)

    This report contains responses by the US Department of Energy to comments from the US Nuclear Regulatory Commission and the Colorado Department of Public Health and Environment on the Naturita remedial action plan. This was done in an attempt to clarify information. The site is an inactive uranium processing site at Naturita, Colorado

  19. Adenosine prevents TNFα-induced decrease in endothelial mitochondrial mass via activation of eNOS-PGC-1α regulatory axis.

    Directory of Open Access Journals (Sweden)

    Theodore J Kalogeris

    Full Text Available We tested whether adenosine, a cytoprotective mediator and trigger of preconditioning, could protect endothelial cells from inflammation-induced deficits in mitochondrial biogenesis and function. We examined this question using human microvascular endothelial cells exposed to TNFα. TNFα produced time and dose-dependent decreases in mitochondrial membrane potential, cellular ATP levels, and mitochondrial mass, preceding an increase in apoptosis. These effects were prevented by co-incubation with adenosine, a nitric oxide (NO donor, a guanylate cyclase (GC activator, or a cell-permeant cyclic GMP (cGMP analog. The effects of adenosine were blocked by a nitric oxide synthase inhibitor, a soluble guanylate cyclase inhibitor, a morpholino antisense oligonucleotide to endothelial nitric oxide synthase (eNOS, or siRNA knockdown of the transcriptional coactivator, PGC-1α. Incubation with exogenous NO, a GC activator, or a cGMP analog reversed the effect of eNOS knockdown, while the effect of NO was blocked by inhibition of GC. The protective effects of NO and cGMP analog were prevented by siRNA to PGC-1α. TNFα also decreased expression of eNOS, cellular NO levels, and PGC-1α expression, which were reversed by adenosine. Exogenous NO, but not adenosine, rescued expression of PGC-1α in cells in which eNOS expression was knocked down by eNOS antisense treatment. Thus, TNFα elicits decreases in endothelial mitochondrial function and mass, and an increase in apoptosis. These effects were reversed by adenosine, an effect mediated by eNOS-synthesized NO, acting via soluble guanylate cyclase/cGMP to activate a mitochondrial biogenesis regulatory program under the control of PGC-1α. These results support the existence of an adenosine-triggered, mito-and cytoprotective mechanism dependent upon an eNOS-PGC-1α regulatory pathway, which acts to preserve endothelial mitochondrial function and mass during inflammatory challenge.

  20. Murine CD4+CD25- cells activated in vitro with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis in vivo

    Directory of Open Access Journals (Sweden)

    Majowicz Anna

    2012-12-01

    Full Text Available Abstract Background Induced regulatory T (iTreg lymphocytes show promise for application in the treatment of allergic, autoimmune and inflammatory disorders. iTreg cells demonstrate advantages over natural Treg (nTreg cells in terms of increased number of starting population and greater potential to proliferate. Different activation methods to generate iTreg cells result in iTreg cells that are heterogeneous in phenotype and mechanisms of suppression. Therefore it is of interest to explore new techniques to generate iTreg cells and to determine their physiological relevance. Methods Using phorbol myristate acetate (PMA/ionomycin and anti-CD3 activation of CD4+CD25- cells we generated in vitro functional CD4+CD25+ iTreg (TregPMA cells. Functionality of the generated TregPMA cells was tested in vivo in a mouse model of inflammatory bowel disease (IBD - CD45RB transfer colitis model. Results TregPMA cells expressed regulatory markers and proved to ameliorate the disease phenotype in murine CD45RB transfer colitis model. The body weight loss and disease activity scores for TregPMA treated mice were reduced when compared to diseased control group. Histological assessment of colon sections confirmed amelioration of the disease phenotype. Additionally, cytokine analysis showed decreased levels of proinflammatory colonic and plasma IL-6, colonic IL-1 β and higher levels of colonic IL-17 when compared to diseased control group. Conclusions This study identifies a new method to generate in vitro iTreg cells (TregPMA cells which physiological efficacy has been demonstrated in vivo.

  1. Regulatory processes in Aspergillus niger

    DEFF Research Database (Denmark)

    Poulsen, Lars

    Filamentous fungi are extensively used in the fermentation industry for synthesis of numerous products. One of the most important, is the fungus Aspergillus niger, used industrially for production of organic acids, and homologous as well as heterologous enzymes. This fungus has numerous of advant......Filamentous fungi are extensively used in the fermentation industry for synthesis of numerous products. One of the most important, is the fungus Aspergillus niger, used industrially for production of organic acids, and homologous as well as heterologous enzymes. This fungus has numerous...

  2. Independent technical and scientific advice for regulatory decision making

    International Nuclear Information System (INIS)

    Technical and scientific support organizations (TSOs) dedicated to supporting national regulatory authorities need comprehensive know-how and know-why concerning nuclear science and technology, and all the technical aspects of a given nuclear installation. This comprehensive knowledge can only be obtained if a TSO is involved in the nuclear licensing and supervision process, and if R and D activities are continuously sponsored to maintain the institutional knowledge base and to contribute to the development of nuclear safety. The R and D activities need not be directly connected to current regulatory requirements, but could serve for developing the state of the art in view of long term regulatory considerations. The TSOs need their independent knowledge to be able to provide technically correct insights and reactions to various regulatory requests and to define their research topics. The Convention on Nuclear Safety and other international agreements, as well as national acts and ordinances, set out the responsibilities of licensing and supervisory authorities. Some requirements of the Convention on Nuclear Safety are used here as examples for the various regulatory aspects that underline the variety of technical support provided to regulatory authorities by TSOs. The areas of support include siting assessments, design assessments, evaluations of operating experience and the development of different aspects of emergency preparedness. The issues of decommissioning and waste disposal are also taken into account. Technical and scientific support organizations support the regulatory authorities in the decision making process by providing technical advice in all these areas. Doing so requires the cooperation of experts from various technical and scientific disciplines, including neutron physics, thermo-hydraulics, material science, civil engineering, process engineering, human and organizational factors, health physics and many more. The requests of regulatory

  3. The immunosuppressive drug FK778 induces regulatory activity in stimulated human CD4+ CD25- T cells.

    NARCIS (Netherlands)

    Kreijveld, E.; Koenen, H.J.P.M.; Hilbrands, L.B.; Hooff, H.J. van; Joosten, I.

    2007-01-01

    The induction of transplantation tolerance involves a T-cell-mediated process of immune regulation. In clinical transplantation, the use of immunosuppressive drugs that promote or facilitate this process would be highly desirable. Here, we investigated the tolerance-promoting potential of the immuno

  4. TLR-2 activation induces regulatory T cells and long-term suppression of asthma manifestations in mice.

    Directory of Open Access Journals (Sweden)

    Martijn C Nawijn

    Full Text Available Asthma is a chronic inflammatory disease of the airways characterized by variable airway obstruction and airway hyperresponsiveness (AHR. The T regulatory (Treg cell subset is critically important for the regulation of immune responses. Adoptive transfer of Treg cells has been shown to be sufficient for the suppression of airway inflammation in experimental allergic asthma. Intervention strategies aimed at expanding the Treg cell population locally in the airways of sensitized individuals are therefore of high interest as a potential therapeutic treatment for allergic airway disease. Here, we aim to test whether long-term suppression of asthma manifestations can be achieved by locally expanding the Treg cell subset via intranasal administration of a TLR-2 agonist. To model therapeutic intervention aimed at expanding the endogenous Treg population in a sensitized host, we challenged OVA-sensitized mice by OVA inhalation with concomitant intranasal instillation of the TLR-2 agonist Pam3Cys, followed by an additional series of OVA challenges. Pam3Cys treatment induced an acute but transient aggravation of asthma manifestations, followed by a reduction or loss of AHR to methacholine, depending on the time between Pam3Cys treatment and OVA challenges. In addition, Pam3Cys-treatment induced significant reductions of eosinophils and increased numbers of Treg cells in the lung infiltrates. Our data show that, despite having adverse acute effects, TLR2 agonist treatment as a therapeutic intervention induces an expansion of the Treg cell population in the lungs and results in long-term protection against manifestation of allergic asthma upon subsequent allergen provocation. Our data indicate that local expansion of Tregs in allergic airway disease is an interesting therapeutic approach that warrants further investigation.

  5. The RafC1 cysteine-rich domain contains multiple distinct regulatory epitopes which control Ras-dependent Raf activation.

    Science.gov (United States)

    Daub, M; Jöckel, J; Quack, T; Weber, C K; Schmitz, F; Rapp, U R; Wittinghofer, A; Block, C

    1998-11-01

    Activation of c-Raf-1 (referred to as Raf) by Ras is a pivotal step in mitogenic signaling. Raf activation is initiated by binding of Ras to the regulatory N terminus of Raf. While Ras binding to residues 51 to 131 is well understood, the role of the RafC1 cysteine-rich domain comprising residues 139 to 184 has remained elusive. To resolve the function of the RafC1 domain, we have performed an exhaustive surface scanning mutagenesis. In our study, we defined a high-resolution map of multiple distinct functional epitopes within RafC1 that are required for both negative control of the kinase and the positive function of the protein. Activating mutations in three different epitopes enhanced Ras-dependent Raf activation, while only some of these mutations markedly increased Raf basal activity. One contiguous inhibitory epitope consisting of S177, T182, and M183 clearly contributed to Ras-Raf binding energy and represents the putative Ras binding site of the RafC1 domain. The effects of all RafC1 mutations on Ras binding and Raf activation were independent of Ras lipid modification. The inhibitory mutation L160A is localized to a position analogous to the phorbol ester binding site in the protein kinase C C1 domain, suggesting a function in cofactor binding. Complete inhibition of Ras-dependent Raf activation was achieved by combining mutations K144A and L160A, which clearly demonstrates an absolute requirement for correct RafC1 function in Ras-dependent Raf activation.

  6. 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.

  7. MalT, the regulatory protein of the Escherichia coli maltose system, is an ATP-dependent transcriptional activator.

    OpenAIRE

    Richet, E; Raibaud, O

    1989-01-01

    We show that MalT, the transcriptional activator of the Escherichia coli maltose regulon, specifically binds ATP and dATP with a high affinity (Kd = 0.4 microM) and exhibits a weak ATPase activity. Using an abortive initiation assay, we further show that activation of open complex formation by MalT depends on the presence of ATP in addition to that of maltotriose, the inducer of the maltose system. Similar experiments in which ATP was replaced by ADP or AMP-PNP, a non-hydrolysable analogue of...

  8. Leachate Treatment by Batch Decant Activated Sludge Process and Powdered Activated Carbon Addition

    Directory of Open Access Journals (Sweden)

    Y Hashempur

    2009-07-01

    Full Text Available "n "nBackgrounds and Objectives: Direct biodegradation of landfill leachate is too difficult because of high concentrations of COD and NH3 and also the presence of toxic compounds. The main objective of this study was to application of Strurvite precipitation as a pretreatment stage, in order to remove inhibitors of biodegradation before the batch decant activated sludge process with addition of powdered activated carbon (PAC."nMaterials and Methods: Strurvite precipitated leachate was introduced to a bench scale batch decant activated sludge reactor with hydraulic retention times of 6 and 12 hour. PAC was added to aeration tank directly at the rate of 3.5 g/L."nResults:TCOD, SCOD, NH3 and P removal efficiency with addition of PAC in HRT of 6 h were 90,87, 98.3 and 94 % respectively and 96, 95, 99.2 and 98.7 5 in HRT of 12 h."nConcusion:According to obtained data from this work, it can be concluded that Strurvite precipitation before batch decant activated sludge process and simultaneous addition of PAC is promising technology for leachate treatment and can meet effluent standards for discharge to the receiving waters.

  9. The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis

    OpenAIRE

    Cripps, Richard M.; Black, Brian L.; Zhao, Bin; Lien, Ching-Ling; Schulz, Robert A.; Olson, Eric N.

    1998-01-01

    MEF2 is a MADS-box transcription factor required for muscle development in Drosophila. Here, we show that the bHLH transcription factor Twist directly regulates Mef2 expression in adult somatic muscle precursor cells via a 175-bp enhancer located 2245 bp upstream of the transcriptional start site. Within this element, a single evolutionarily conserved E box is essential for enhancer activity. Twist protein can bind to this E box to activate Mef2 transcription, and ectopic expression of twist ...

  10. A critical appraisal of the process of regulatory implementation of novel in vivo and in vitro methods for chemical hazard and risk assessment.

    Science.gov (United States)

    Piersma, Aldert H; Ezendam, Janine; Luijten, Mirjam; Muller, J J Andre; Rorije, Emiel; van der Ven, Leo T M; van Benthem, Jan

    2014-11-01

    Regulatory toxicology urgently needs applicable alternative test systems that reduce animal use, testing time, and cost. European regulation on cosmetic ingredients has already banned animal experimentation for hazard identification, and public awareness drives toward additional restrictions in other regulatory frameworks as well. In addition, scientific progress stimulates a more mechanistic approach of hazard identification. Nevertheless, the implementation of alternative methods is lagging far behind their development. In search for general bottlenecks for the implementation of alternative methods, this manuscript reviews the state of the art as to the development and implementation of 10 diverse test systems in various areas of toxicological hazard assessment. They vary widely in complexity and regulatory acceptance status. The assays are reviewed as to parameters assessed, biological system involved, standardization, interpretation of results, extrapolation to human hazard, position in testing strategies, and current regulatory acceptance status. Given the diversity of alternative methods in many aspects, no common bottlenecks could be identified that hamper implementation of individual alternative assays in general. However, specific issues for the regulatory acceptance and application were identified for each assay. Acceptance of one-in-one replacement of complex in vivo tests by relatively simple in vitro assays is not feasible. Rather, innovative approaches using test batteries are required together with metabolic information and in vitro to in vivo dose extrapolation to convincingly provide the same level of information of current in vivo tests. A mechanistically based alternative approach using the Adverse Outcome Pathway concept could stimulate further (regulatory) acceptance of non-animal tests. PMID:25058877

  11. 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.

  12. Physicochemical and porosity characteristics of thermally regenerated activated carbon polluted with biological activated carbon process.

    Science.gov (United States)

    Dong, Lihua; Liu, Wenjun; Jiang, Renfu; Wang, Zhansheng

    2014-11-01

    The characteristics of thermally regenerated activated carbon (AC) polluted with biological activated carbon (BAC) process were investigated. The results showed that the true micropore and sub-micropore volume, pH value, bulk density, and hardness of regenerated AC decreased compared to the virgin AC, but the total pore volume increased. XPS analysis displayed that the ash contents of Al, Si, and Ca in the regenerated AC respectively increased by 3.83%, 2.62% and 1.8%. FTIR spectrum showed that the surface functional groups of virgin and regenerated AC did not change significantly. Pore size distributions indicated that the AC regeneration process resulted in the decrease of micropore and macropore (D>10 μm) volume and the increase of mesopore and macropore (0.1 μmprocess.

  13. Replacement of the C-terminal tetrapeptide (314PAPV317 to 314SSSM317) in interferon regulatory factor-2 alters its N-terminal DNA-binding activity

    Indian Academy of Sciences (India)

    Krishna Prakash; Pramod C Rath

    2010-12-01

    Interferon regulatory factor-2 (IRF-2) is an important transcription factor involved in cell growth regulation, immune response and cancer. IRF-2 can function as a transcriptional repressor and activator depending on its DNA-binding activity and protein–protein interactions. We compared the amino acid sequences of IRF-2 and found a C-terminal tetrapeptide (314PAPV317) of mouse IRF-2 to be different (314SSSM317) from human IRF-2. Recombinant GST-IRF-2 with 314PAPV317 (wild type) and 314SSSM317 (mutant) expressed in Escherichia coli were assessed for DNA-binding activity with 32P-(GAAAGT)4 by electrophoretic mobility shift assay (EMSA). Wild type- and mutant GST-IRF-2 showed similar expression patterns and immunoreactivities but different DNA-binding activities. Mutant (mt) IRF-2 formed higher-molecular-mass, more and stronger DNA–protein complexes in comparison to wild type (wt) IRF-2. Anti-IRF-2 antibody stabilized the DNA–protein complexes formed by both wt IRF-2 and mt IRF-2, resolving the differences. This suggests that PAPV and SSSM sequences at 314-317 in the C-terminal region of mouse and human IRF-2 contribute to conformation of IRF-2 and influence DNA-binding activity of the N-terminal region, indicating intramolecular interactions. Thus, evolution of IRF-2 from murine to human genome has resulted in subtle differences in C-terminal amino acid motifs, which may contribute to qualitative changes in IRF-2-dependent DNA-binding activity and gene expression.

  14. α-Synuclein vaccination modulates regulatory T cell activation and microglia in the absence of brain pathology

    DEFF Research Database (Denmark)

    Christiansen, Josefine R; Olesen, Mads N; Otzen, Daniel E;

    2016-01-01

    BACKGROUND: Passive and active immunization with α-synuclein has been shown to be neuroprotective in animal models of Parkinson's disease. We have previously shown that vaccination with α-synuclein, long before α-synuclein-induced brain pathology, prevents striatal degeneration by inducing regula...

  15. In Vitro Metabolism and Bioavailability Test for Endocrine Active Substances: What is Needed Next for Regulatory Purposes?

    NARCIS (Netherlands)

    Jacobs, M.N.; Laws, S.C.; Willett, K.; Schmieder, P.; Odum, B.; Bovee, T.F.H.

    2013-01-01

    Legislation 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 putative endocrine disrup

  16. Modulation of glucokinase by glucose, small-molecule activator and glucokinase regulatory protein: steady-state kinetic and cell-based analysis.

    Science.gov (United States)

    Bourbonais, Francis J; Chen, Jing; Huang, Cong; Zhang, Yanwei; Pfefferkorn, Jeffrey A; Landro, James A

    2012-02-01

    GK (glucokinase) is an enzyme central to glucose metabolism that displays positive co-operativity to substrate glucose. Small-molecule GKAs (GK activators) modulate GK catalytic activity and glucose affinity and are currently being pursued as a treatment for Type 2 diabetes. GK progress curves monitoring product formation are linear up to 1 mM glucose, but biphasic at 5 mM, with the transition from the lower initial velocity to the higher steady-state velocity being described by the rate constant kact. In the presence of a liver-specific GKA (compound A), progress curves at 1 mM glucose are similar to those at 5 mM, reflecting activation of GK by compound A. We show that GKRP (GK regulatory protein) is a slow tight-binding inhibitor of GK. Analysis of progress curves indicate that this inhibition is time dependent, with apparent initial and final Ki values being 113 and 12.8 nM respectively. When GK is pre-incubated with glucose and compound A, the inhibition observed by GKRP is time dependent, but independent of GKRP concentration, reflecting the GKA-controlled transition between closed and open GK conformations. These data are supported by cell-based imaging data from primary rat hepatocytes. This work characterizes the modulation of GK by a novel GKA that may enable the design of new and improved GKAs.

  17. Developing effective consultation programs for regulatory development

    Energy Technology Data Exchange (ETDEWEB)

    Paulson, K.F. [National Energy Board, Ottawa, ON (Canada)

    2003-07-01

    Canada's National Energy Board promotes safety, environmental protection and economic efficiency in the regulation of pipelines, energy development and trade. The Board regulates the design, construction, operation and abandonment of interprovincial and international pipelines within Canada. It also holds regulatory control over tolls and tariffs of interprovincial and international pipelines as well as the export, exploration and development of natural gas and oil resources. Regulatory authorities are required to consult with stakeholders whenever new regulations or amendments to existing regulations are proposed. The Board has launched new initiatives for compliance with Damage Prevention Regulations. Stakeholders were advised through consultative processes such as plain language drafts, open houses, focus meetings and newsletters. The proposed Damage Prevention Regulation will govern activities that have the potential to damage a pipeline. The regulations will apply to pipeline operators, excavators, landowners, municipal planners, emergency responders, and utility companies dealing with federally regulated pipelines. 7 refs., 1 tab.

  18. Tumor-Derived Microvesicles Induce, Expand and Up-Regulate Biological Activities of Human Regulatory T Cells (Treg)

    OpenAIRE

    Marta Szajnik; Malgorzata Czystowska; Szczepanski, Miroslaw J.; Magis Mandapathil; Whiteside, Theresa L.

    2010-01-01

    BACKGROUND: Tumor-derived microvesicles (TMV) or exosomes are present in body fluids of patients with cancer and might be involved in tumor progression. The frequency and suppressor functions of peripheral blood CD4(+)CD25(high)FOXP3(+) Treg are higher in patients with cancer than normal controls. The hypothesis is tested that TMV contribute to induction/expansion/and activation of human Treg. METHODOLOGY/PRINCIPAL FINDINGS: TMV isolated from supernatants of tumor cells but not normal cells i...

  19. Activation of a Ca(2+)-dependent protein kinase involves intramolecular binding of a calmodulin-like regulatory domain

    Science.gov (United States)

    Huang, J. F.; Teyton, L.; Harper, J. F.; Evans, M. L. (Principal Investigator)

    1996-01-01

    Ca(2+)-dependent protein kinases (CDPKs) are regulated by a C-terminal calmodulin-like domain (CaM-LD). The CaM-LD is connected to the kinase by a short junction sequence which contains a pseudosubstrate autoinhibitor. To understand how the CaM-LD regulates a CDPK, a recombinant CDPK (isoform CPK-1 from Arabidopsis, accession no. L14771) was made as a fusion protein in Escherichia coli. We show here that a truncated CDPK lacking a CaM-LD (e.g. mutant delta NC-26H) can be activated by exogenous calmodulin or an isolated CaM-LD (Kact approximately 2 microM). We propose that Ca2+ activation of a CDPK normally occurs through intramolecular binding of the CaM-LD to the junction. When the junction and CaM-LD are made as two separate polypeptides, the CaM-LD can bind the junction in a Ca(2+)-dependent fashion with a dissociation constant (KD) of 6 x 10(-6) M, as determined by kinetic binding analyses. When the junction and CaM-LD are tethered in a single polypeptide (e.g. in protein JC-1), their ability to engage in bimolecular binding is suppressed (e.g. the tethered CaM-LD cannot bind a separate junction). A mutation which disrupts the putative CaM-LD binding sequence (e.g. substitution LRV-1444 to DLPG) appears to block intramolecular binding, as indicated by the restored ability of a tethered CaM-LD to engage in bimolecular binding. This mutation, in the context of a full-length enzyme (mutant KJM46H), appears to block Ca2+ activation. Thus, a disruption of intramolecular binding correlates with a disruption of the Ca2+ activation mechanism. CDPKs provide the first example of a member of the calmodulin superfamily where a target binding sequence is located within the same polypeptide.

  20. Plant growth regulatory effect and insecticidal activity of the extracts of the Tree of Heaven (Ailanthus altissima L.

    Directory of Open Access Journals (Sweden)

    Peterson Chris J

    2002-02-01

    Full Text Available Abstract Background There is an urgent need to explore and utilize naturally occurring products for combating harmful agricultural and public health pests. Secondary metabolites in the leaves of the Tree of Heaven, Ailanthus altissima L. have been reported to be herbicidal and insecticidal. The mode of action, however, of the active compounds in A. altissima are not understood. In this paper, we report the chemical characteristics of the herbicidal and insecticidal components in this tree, and will discuss the effect of light on the bioactivity of the active components. Results Extracts from the fresh leaves of A. altissima showed a strong plant germination/growth inhibitory effect in laboratory bioassays against alfalfa (Medicago sativa. The effect was dose-dependent. The growth inhibitory components were in the methylene chloride soluble fraction of the extract. The effect was greater in the light than in the dark. Other fractions had plant growth enhancing effect at lower concentrations. The extract was slightly insecticidal against yellow fever mosquito larvae (Aedes aegypti. Conclusions The extract or its semi-purified fractions of A. altissima were strong plant growth inhibitors, therefore good candidates as potential environmentally safe and effective agricultural pest management agents. The finding that light affects the activity will be useful in the application of such natural products.

  1. Advanced Reactor Technology -- Regulatory Technology Development Plan (RTDP)

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

    This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However, it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory

  2. Annual Report 2008. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    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.

  3. Annual Report 2007. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    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.

  4. Annual Report 2009. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    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.

  5. Characterization and functional studies of forkhead box protein 3(-) lymphocyte activation gene 3(+) CD4(+) regulatory T cells induced by mucosal B cells.

    Science.gov (United States)

    Chu, K-H; Chiang, B-L

    2015-05-01

    The induction of mucosal tolerance has been demonstrated to be an effective therapeutic approach for the treatment of allergic diseases. Our previous study demonstrated that Peyer's patch B cells could convert naive T cells into regulatory T cells (so-called Treg -of-B(P) cells); however, it is important to characterize this particular subset of Treg -of-B cells for future applications. This study aimed to investigate the role of lymphocyte activating gene 3 (LAG3) in mediating the regulatory function of Treg -of-B(P) cells induced by mucosal follicular B (FOB) cells. Microarray analysis and real-time polymerase chain reaction (PCR) were used to assess the gene expression pattern of Treg -of-B(P) cells. To evaluate the role of LAG3, the in-vitro suppressive function and the alleviation of airway inflammation in a murine model of asthma was assessed. Our data indicated that FOB cells isolated from Peyer's patches had the ability to generate more suppressive Treg -of-B cells with LAG3 expression, compared with CD23(lo) CD21(lo) B cells. LAG3 is not only a marker for Treg -of-B(P) cells, but also participate in the suppressive ability. Moreover, CCR4 and CCR6 could be detected on the LAG3(+) , not LAG3(-) , Treg -of-B(P) cells and would help cells homing to allergic lung. In the murine model of asthma, the adoptive transfer of LAG3(+) Treg -of-B(P) cells was able to sufficiently suppress T helper type 2 (Th2) cytokine production, eosinophil infiltration and alleviate asthmatic symptoms. LAG3 was expressed in Treg -of-B(P) cells and was also involved in the function of Treg -of-B(P) cells. In the future, this particular subset of Treg -of-B cells might be used to alleviate allergic symptoms. PMID:25581421

  6. A global regulatory science agenda for vaccines.

    Science.gov (United States)

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

    2013-04-18

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

  7. Physiological and receptor-selective retinoids modulate interferon gamma signaling by increasing the expression, nuclear localization, and functional activity of interferon regulatory factor-1.

    Science.gov (United States)

    Luo, Xin M; Ross, A Catharine

    2005-10-28

    Synergistic actions between all-trans-retinoic acid (atRA) and interferon gamma (IFNgamma) on modulation of cellular functions have been reported both in vitro and in vivo. However, the mechanism of atRA-mediated regulation of IFNgamma signaling is poorly understood. In this study, we have used the human lung epithelial cell line A549 to examine the effect of atRA on IFNgamma-induced expression of IFN regulatory factor-1 (IRF-1), an important transcription factor involved in cell growth and apoptosis, differentiation, and antiviral and antibacterial immune responses. At least 4 h of pretreatment with atRA followed by suboptimal concentrations of IFNgamma induced a faster, higher, and more stable expression of IRF-1 than IFNgamma alone. Actinomycin D completely blocked the induction of IRF-1 by the combination, suggesting regulation at the transcriptional level. Further, we found that activation of signal transducer and activator of transcription-1 was induced more dramatically by atRA and IFNgamma than by IFNgamma alone. Expression of IFNgamma receptor-1 on the cell surface was also increased upon atRA pretreatment. Experiments using receptor-selective retinoids revealed that ligands for retinoic acid receptor-alpha (RARalpha), including atRA, 9-cis-retinoic acid, and Am580, sequentially increased the levels of IFNgamma receptor-1, activated signal transducer and activator of transcription-1, and IRF-1 and that an RARalpha antagonist was able to inhibit the effects of atRA and Am580. In addition, atRA pretreatment affected the transcriptional functions of IFNgamma-induced IRF-1, increasing its nuclear localization and DNA binding activity as well as the transcript levels of IRF-1 target genes. These results suggest that atRA, an RARalpha ligand, regulates IFNgamma-induced IRF-1 by affecting multiple components of the IFNgamma signaling pathway, from the plasma membrane to the nuclear transcription factors.

  8. 15 CFR 400.33 - Restrictions on manufacturing and processing activity.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Restrictions on manufacturing and...-TRADE ZONES BOARD Manufacturing and Processing Activity-Reviews § 400.33 Restrictions on manufacturing and processing activity. (a) In general. In approving manufacturing or processing activity for a...

  9. Blogs and Social Network Sites as Activity Systems: Exploring Adult Informal Learning Process through Activity Theory Framework

    Science.gov (United States)

    Heo, Gyeong Mi; Lee, Romee

    2013-01-01

    This paper uses an Activity Theory framework to explore adult user activities and informal learning processes as reflected in their blogs and social network sites (SNS). Using the assumption that a web-based space is an activity system in which learning occurs, typical features of the components were investigated and each activity system then…

  10. 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

    Full Text Available UNLABELLED: 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

  11. Evaluation of regulatory guides potentially useful to geologic repository development

    International Nuclear Information System (INIS)

    The US Regulatory Commission Regulatory Guide series provides a set of regulatory and technical guidelines for achieving and demonstrating regulatory compliance for various segments of the nuclear fuel cycle. Of these regulatory guides only few specifically pertain to high-level waste repository activities. The overwhelming majority pertain to other, more mature aspects of the nuclear cycle. It is believed that conscientious, reasoned application of the fundamental regulatory bases underlying the positions in these other regulatory guides could provide a solid regulatory starting point for repository development activities. This information report provides a summary screening of regulatory guides published as of September 1983 and provides an initial assessment of the potential usefulness of these regulatory guides to repository design and operation activities

  12. Cholesterol regulatory effects and antioxidant activities of protein hydrolysates from zebra blenny (Salaria basilisca) in cholesterol-fed rats.

    Science.gov (United States)

    Ktari, Naourez; Belguith-Hadriche, Olfa; Ben Amara, Ibtissem; Ben Hadj, Aïda; Turki, Mouna; Makni-Ayedi, Fatma; Boudaouara, Tahia; El Feki, Abdelfattah; Boualga, Ahmed; Ben Salah, Riadh; Nasri, Moncef

    2015-07-01

    This study aims to explore the hypocholesterolemic effects and antioxidative activities of zebra blenny protein hydrolysates (ZBPHs) in rats fed with a hypercholesterolemic diet. The rats were fed during eight weeks a standard laboratory diet (normal rats), a high-cholesterol diet (HCD) (1%) or a HCD and orally treated with ZBPHs or undigested zebra blenny proteins (UZBPs) (400 mg per kg per day). Results showed that a hypercholesterolemic diet induced the increase of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Treatment with ZBPHs increased the level of high-density lipoprotein cholesterol (HDL-C) and decreased significantly the levels of TC, TG, and LDL-C. In addition, ZBPH treatment showed significant normalization of thiobarbituric acid-reactive substance (TBARS) levels as well as catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in renal and hepatic tissues. Furthermore, ZBPHs may also exert significant protective effects on liver and kidney functions, evidenced by a marked decrease in the level of serum urea, uric acid, creatinine, alkaline phosphatase (ALP), and alanine aminotransferase (ALAT). Histological studies confirmed that ZBPHs effectively protected the livers and kidneys against hypercholesterolemia-mediated oxidative damage. Therefore, the study strengthens the hypothesis that ZBPHs can be used as novel antioxidants and hypocholesterolemic compounds against hyperlipidemia induced atherosclerosis. PMID:26065510

  13. Regulatory review of probabilistic safety assessment (PSA) level 1

    International Nuclear Information System (INIS)

    Probabilistic safety assessment (PSA) is increasingly being used as part of the decision making process to assess the level of safety of nuclear power plants. The methodologies in use are maturing and the insights gained from the PSAs are being used along with those from the deterministic analysis. Many regulatory authorities consider that the current state of the art in PSA (especially Level 1 PSA) is sufficiently well developed that it can be used centrally in the regulatory decision making process - referred to as 'risk informed regulation'. For these applications to be successful, it will be necessary for regulatory authorities to have a high degree of confidence in PSA. However, at the IAEA Technical Committee Meeting on Use of PSA in the Regulatory Process in 1994 and at the OECD Nuclear Energy Agency Committee for Nuclear Regulatory Activities (CNRA) 'Special Issues' Meeting in 1997 on Review Procedures and Criteria for Different Regulatory Applications of PSA, it was recognized that formal regulatory review guidance for PSA did not exist. The senior regulators noted that there was a need to produce some international guidance for reviewing PSAs to establish an agreed basis for assessing whether important technological and methodological issues in PSAs are treated adequately and to verify that conclusions reached are appropriate. In 1997 the IAEA and OECD Nuclear Energy Agency agreed to produce in co-operation a technical document on the regulatory review of PSA. This publication is intended to provide guidance to regulatory authorities on how to review the PSA for a nuclear power plant to gain confidence that it has been carried out to an acceptable standard so that it can be used as the basis for taking risk informed decisions within a regulatory decision making process. The document gives guidance on how to set about reviewing a PSA and on the technical issues that need to be addressed. This publication gives guidance for the review of Level 1 PSA for

  14. Carbon Capture and Storage Legal and Regulatory Review. Edition 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    The International Energy Agency (IEA) estimates that 100 carbon capture and storage (CCS) projects must be implemented by 2020 and over 3000 by 2050 if CCS is to fully contribute to the least-cost technology portfolio for CO2 mitigation. To help countries address the many legal and regulatory issues associated with such rapid deployment, the IEA launched the Carbon Capture and Storage Legal and Regulatory Review (CCS Review) in October 2010. The CCS Review gathers contributions by national and regional governments, as well as leading organisations engaged in CCS regulatory activities, to provide a knowledge-sharing forum that supports national-level CCS regulatory development. Each contribution provides a short summary of recent and anticipated developments and highlights a particular regulatory theme (such as financial contributions to long-term stewardship). To introduce each edition, the IEA provides a brief analysis of key advances and trends. Produced bi-annually, the CCS Review provides an up-to-date snapshot of global CCS regulatory developments. The theme for the second edition of the CCS Review, released in May 2011, is long-term liability for stored CO2. Other key issues addressed include: national progress towards implementation of the EU CCS Directive; developments in marine treaties relevant to CCS; international climate change negotiations; and the development process for CCS regulation.

  15. 75 FR 13599 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-03-22

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of issuance and availability of Draft Regulatory Guide, DG-8040, ``Health Physics Surveys During Enriched Uranium-235 Processing and...

  16. 78 FR 1574 - Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ... antiseptic products. Timetable: Action Date FR Cite NPRM (Healthcare) 06/17/94 59 FR 31402 Comment Period End... public more effectively participate in the Department's regulatory activity, and the Department welcomes... underlying medicine, public health, and social services. This agenda presents the rulemaking activities...

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

    Directory of Open Access Journals (Sweden)

    Monica A McArthur

    2015-05-01

    Full Text Available 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 human challenge study. Peripheral blood mononuclear cells were obtained from volunteers pre- and at multiple time-points post-challenge with wild-type S. Typhi. We identified differing patterns of S. Typhi-specific modulation of the homing potential of circulating Treg between volunteers diagnosed with typhoid (TD and those who were not (No TD. TD volunteers demonstrated up-regulation of the gut homing molecule integrin α4ß7 pre-challenge, followed by a significant down-regulation post-challenge consistent with Treg homing to the gut. Additionally, S. Typhi-specific Treg from TD volunteers exhibited up-regulation of activation molecules post-challenge (e.g., HLA-DR, LFA-1. We further demonstrate that depletion of Treg results in increased S. Typhi-specific cytokine production by CD8+ TEM in vitro. These results suggest that the tissue distribution of activated Treg, their characteristics and activation status may play a pivotal role in typhoid fever, possibly through suppression of S. Typhi-specific effector T cell responses. These studies provide important novel insights into the regulation of immune responses that are likely to be critical in protection against typhoid and other enteric infectious diseases.

  18. HLA-DR expression on regulatory T cells is closely associated with the global immune activation in HIV-1 infected subjects na(i)ve to antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    XIAO Jian; LI Ming-yuan; WANG Ying; QIAN Ke-lei; CAO Qing-hua; QIU Chen-li; QIU Cao; XUE Yi-le; ZHANG Xiao-yan; ZHONG Ping; XU Jian-qing

    2011-01-01

    Background The frequencies of regulatory T cells (Tregs) increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4+CD25+CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. ResultsCompared to HIV-1 seronegative donors, the levels of HLA-DR on CD4+CD25+CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads (r=0.3163,P=0.004) and negatively with CD4 T-cell counts (r=-0.4153, P<0.0001). In addition, significant associations between HLA-DR expression on CD4+CD25+CD127lo/-Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4+ and CD8+ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.

  19. Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells

    Institute of Scientific and Technical Information of China (English)

    Qi Cao; Dangsheng Li; Ningli Li; Li Wang; Fang Du; Huiming Sheng; Yan Zhang; Juanjuan Wu; Baihua Shen; Tianwei Shen; Jingwu Zhang

    2007-01-01

    Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Thl immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Thl responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4+CD25+ T cells from the immunized mice. Moreover, CD4+CD25+Foxp3+ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high level of anti-CD25 antibody (about 30 ng/ml,/K0.01 vs controls). Consistent with a role of anti-CD25 response in the down-regulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4+CD25+Foxp3+ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.

  20. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation

    Science.gov (United States)

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  1. RNA Interference of Interferon Regulatory Factor-1 Gene Expression in THP-1 Cell Line Leads to Toll-Like Receptor-4 Overexpression/Activation As Well As Up-modulation of Annexin-II

    Directory of Open Access Journals (Sweden)

    Christos I. Maratheftis

    2007-12-01

    Full Text Available Interferon regulatory factor-1 (IRF-1 is a candidate transcription factor for the regulation of the Toll-like receptor-4 (TLR-4 gene. Using a small interfering RNAbased (siRNA process to silence IRF-1 gene expression in the leukemic monocytic cell line THP-1, we investigated whether such a modulation would alter TLR-4 expression and activation status in these cells. The siIRF-1 cells expressed elevated levels of TLR-4 mRNA and protein compared to controls by 90% and 77%, respectively. ICAM.1 protein expression and apoptosis levels were increased by 8.35- and 4.25-fold, respectively. The siIRF-1 cells overexpressed Bax mRNA compared to controls. Proteomic analysis revealed upmodulation of the Annexin-II protein in siIRF-1 THP-1 cells. Myelodysplastic syndrome (MDS patients with an absence of full-length IRF-1 mRNA also overexpressed Annexin-II. It is plausible that this overexpression may lead to the activation of TLR-4 contributing to the increased apoptosis characterizing MDS.

  2. PASS-GP: Predictive active set selection for Gaussian processes

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2010-01-01

    available in GPs to make a common ranking for both active and inactive points, allowing points to be removed again from the active set. This is important for keeping the complexity down and at the same time focusing on points close to the decision boundary. We lend both theoretical and empirical support...

  3. 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...

  4. Regulatory physiology discipline science plan

    Science.gov (United States)

    1991-01-01

    The focus of the Regulatory Physiology discipline of the Space Physiology and Countermeasures Program is twofold. First, to determine and study how microgravity and associated factors of space flight affect the regulatory mechanisms by which humans adapt and achieve homeostasis and thereby regulate their ability to respond to internal and external signals; and, second, to study selected physiological systems that have been demonstrated to be influenced by gravity. The Regulatory Physiology discipline, as defined here, is composed of seven subdisciplines: (1) Circadian Rhythms, (2) Endocrinology, (3) Fluid and Electrolyte Regulation, (4) Hematology, (5) Immunology, (6) Metabolism and Nutrition, and (7) Temperature Regulation. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the area of regulatory physiology. It covers the research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in regulatory physiology. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

  5. 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

  6. 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

    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 endosomal

  7. Regulatory T cells with multiple suppressive and potentially pro-tumor activities accumulate in human colorectal cancer.

    Science.gov (United States)

    Timperi, Eleonora; Pacella, Ilenia; Schinzari, Valeria; Focaccetti, Chiara; Sacco, Luca; Farelli, Francesco; Caronna, Roberto; Del Bene, Gabriella; Longo, Flavia; Ciardi, Antonio; Morelli, Sergio; Vestri, Anna Rita; Chirletti, Piero; Barnaba, Vincenzo; Piconese, Silvia

    2016-07-01

    Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor. Ex vivo, those Tregs suppressed the proliferation of tumor-infiltrating CD8(+) and CD4(+) T cells. A differential compartmentalization was detected between Helios(high) and Helios(low) Treg subsets (thymus-derived versus peripherally induced): while Helios(low) Tregs were enriched in both sites, only Helios(high) Tregs accumulated significantly and specifically in tumors, displayed a highly demethylated TSDR region and contained high proportions of cells expressing CD39 and OX40, markers of activation and suppression. Besides the suppression of T cells, Tregs may contribute to CRC progression also through releasing IL-17, or differentiating into Tfr cells that potentially antagonize a protective Tfh response, events that were both detected in tumor-associated Tregs. Overall, our data indicate that Treg accumulation may contribute through multiple mechanisms to CRC establishment and progression. PMID:27622025

  8. Investigating Task Understanding in Online Repositories Equipped with Topic Map Indexes : Implications for Improving Self-Regulatory Processes in Graduate Learners

    Directory of Open Access Journals (Sweden)

    Kamran Shaikh

    2008-01-01

    Full Text Available [Français] Les modèles de recherche d’information cognitive et de la psychologie de l’éducation peuvent travailler de pair pour mieux formaliser les processus reliés à l’autorégulation, comme la compréhension des tâches, dans un contexte d’apprentissage virtuel. Les résultats d’une étude antérieure de 38 élèves de maîtrise et de doctorat, lesquels utilisaient une carte thématique (ISO 13250 pour parcourir un ensemble d’épreuves écrites annotées et ainsi compléter une épreuve écrite mal structurée, semblent indiquer un rendement et une compréhension accrus de leurs tâches. Dans cette étude complémentaire, l’analyse inductive des entrevues et des fichiers journaux traces d’un échantillon théorique de 12 de ces 38 élèves montre comment la nature sémantique de la carte thématique a permis aux élèves de suivre des cheminements distincts en parcourant les épreuves écrites annotées selon leur degré de compréhension des tâches et leur besoin d’information. [English] Theories of cognitive information retrieval can work in concert with those of educational psychology to better formalize self-regulatory processes, such as task understanding, in online learning. Results from a prior statistical exploration of 38 graduate learners using a topic map (ISO 13250 index to browse an online repository of instructorannotated essays in order to complete an ill-structured essay task indicate improved performance and task understanding. This follow-up study analyzes the inductive content of interviews and computer-based user traces for a theoretical sample of 12 of these 38 learners, showing how the semantic nature of the topic map enabled them to pursue distinct paths to browse essays according to individual task understanding and information need.

  9. Studies on gene structure, enzymatic activity and regulatory mechanism of acetohydroxy acid isomeroreductase from G2 pea

    Institute of Scientific and Technical Information of China (English)

    XU Yunjian (徐云剑); GU Xuesong (顾雪松); LI Jun (李珺); LI Qing (李 晴); Peter J. Davies; ZHU Yuxian (朱玉贤)

    2003-01-01

    The AAIR genomic DNA of G2 pea (Pisum sativum L.) was amplified by PCR method. Sequence analysis showed that it was composed of 8 introns and 9 exons with three of the introns containing specific A/T-rich endogenous promoter regions. Molecular hybridization experiments revealed that the expression of AAIR remained at a high level before and after flowering if grown in short day growth chambers. However, when grown under long day conditions, the level of AAIR expression declined very rapidly after flowering. This variation of AAIR expression is consistent with the change of enzymatic activity of acetohydroxy acid isomeroreductase. Functional complementation experiments carried out using an acetohydroxy acid isomeroreductase deficient E. coli strain showed that these cells could not grow on M9 medium without addition of branched-chain amino acids unless they were transformed with the AAIR expression vector. Further study revealed that overexpression of the pea AAIR cDNA in acetohydroxy acid isomeroreductase deficient E. coli strain enhanced significantly its branched-chain amino acid biosynthetic capacity. Results from gel shift experiments showed that fractions of pea nuclear protein extracts could bind specifically to some A/T rich regions present in introns of the AAIR gene. The A/T-rich-region-binding proteins remained at a steady level in the non-senescing apical buds of short-day grown G2 pea. In the rapid-senescing apical buds of long-day grown G2 pea, the levels of these proteins declined rapidly after flower initiation. Therefore, the nuclear protein binding capacities to endogenous promoter regions may constitute an important mechanism to regulate AAIR gene expression.

  10. A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

    Directory of Open Access Journals (Sweden)

    Maitraye Sen

    2014-05-01

    Full Text Available In this work, a hybrid MPC (model predictive control-PID (proportional-integral-derivative control system has been designed for the continuous purification and processing framework of active pharmaceutical ingredients (APIs. The specific unit operations associated with the purification and processing of API have been developed from first-principles and connected in a continuous framework in the form of a flowsheet model. These integrated unit operations are highly interactive along with the presence of process delays. Therefore, a hybrid MPC-PID is a promising alternative to achieve the desired control loop performance as mandated by the regulatory authorities. The integrated flowsheet model has been simulated in gPROMSTM (Process System Enterprise, London, UK. This flowsheet model has been linearized in order to design the control scheme. The ability to track the set point and reject disturbances has been evaluated. A comparative study between the performance of the hybrid MPC-PID and a PID-only control scheme has been presented. The results show that an enhanced control loop performance can be obtained under the hybrid control scheme and demonstrate that such a scheme has high potential in improving the efficiency of pharmaceutical manufacturing operations.

  11. 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.

  12. Substrate utilization and VSS relations in activated sludge processes

    Energy Technology Data Exchange (ETDEWEB)

    Droste, R.L.; Fernandes, L.; Sun, X. [Ottawa Univ., ON (Canada). Dept. of Civil Engineering

    1993-12-31

    A new empirical substrate removal model for activated sludge in continuous flow stirred tank reactor (CFSTR) and sequencing batch reactor (SBR) was developed in this study. This model includes an exponential function of volatile suspended solids to express the active biomass which is actually involved in substrate utilization. Results indicate that the proposed exponential models predict more accurately effluent COD in CFSTR and SBR systems than the first or zero order models. (author). 7 refs., 1 fig., 4 tabs.

  13. Fur is required for the activation of virulence gene expression through the induction of the sae regulatory system in Staphylococcus aureus.

    Science.gov (United States)

    Johnson, Miranda; Sengupta, Mrittika; Purves, Joanne; Tarrant, Emma; Williams, Peter H; Cockayne, Alan; Muthaiyan, Arunachalam; Stephenson, Robert; Ledala, Nagender; Wilkinson, Brian J; Jayaswal, Radheshyam K; Morrissey, Julie A

    2011-01-01

    Our previous studies showed that both Sae and Fur are required for the induction of eap and emp expression in low iron. In this study, we show that expression of sae is also iron-regulated, as sae expression is activated by Fur in low iron. We also demonstrate that both Fur and Sae are required for full induction of the oxidative stress response and expression of non-covalently bound surface proteins in low-iron growth conditions. In addition, Sae is required for the induced expression of the important virulence factors isdA and isdB in low iron. Our studies also indicate that Fur is required for the induced expression of the global regulators Agr and Rot in low iron and a number of extracellular virulence factors such as the haemolysins which are also Sae- and Agr-regulated. Hence, we show that Fur is central to a complex regulatory network that is required for the induced expression of a number of important S. aureus virulence determinants in low iron.

  14. Vancomycin susceptibility in methicillin-resistant Staphylococcus aureus is mediated by YycHI activation of the WalRK essential two-component regulatory system.

    Science.gov (United States)

    Cameron, David R; Jiang, Jhih-Hang; Kostoulias, Xenia; Foxwell, Daniel J; Peleg, Anton Y

    2016-01-01

    The treatment of infections caused by methicillin-resistant Staphylococcus aureus is complicated by the emergence of strains with intermediate-level resistance to vancomycin (termed VISA). We have characterised a molecular pathway involved in the in vivo evolution of VISA mediated by the regulatory proteins YycH and YycI. In contrast to their function in other bacterial species, we report a positive role for these auxiliary proteins in regulation of the two-component regulator WalRK. Transcriptional profiling of yycH and yycI deletion mutants revealed downregulation of the 'WalRK regulon' including cell wall hydrolase genes atlA and sle1, with functional autolysis assays supporting these data by showing an impaired autolytic phenotype for each deletion strain. Using bacterial-two hybrid assays, we showed that YycH and YycI interact, and that YycHI also interacts with the sensor kinase WalK, forming a ternary protein complex. Mutation to YycH or YycI associated with clinical VISA strains had a deleterious impact on the YycHI/WalK complex, suggesting that the interaction is important for the regulation of WalRK. Taken together, we have described a novel antibiotic resistance strategy for the human pathogen S. aureus, whereby YycHI mutations are selected for in vivo leading to reduced WalRK activation, impaired cell wall turnover and ultimately reduced vancomycin efficacy. PMID:27600558

  15. Studies on gene structure, enzymatic activity and regulatory mechanism of acetohydroxy acid isomeroreductase from G2 pea

    Institute of Scientific and Technical Information of China (English)

    XU; Yunjian; (

    2003-01-01

    , P., Smith, J. K. et al., Regulation of tobacco acetolactate synthase gene expression, Plant Physiol., 1993, 102: 1009-1018.[21]Singh, B. K., Newhouse, K. E., Stidham, M. A. et al., Actohydroxyacid synthase-imidazolinone interaction, in Biosynthesis of Branched Chain Amino Acids (eds. Barak, Z., Chipman, D. M., Schloss, J. V.), Weinheim: VCH, 1990, 357-372.[22]Stidham, M. A., Singh, B. K., Imidazolinone-acetohydroxyacid synthase interactions, in The Imidazolinone Herbicides (eds. Shaner, L. L., O'Connor, S. L.), Boca Raton, F L: CRC Press, 1991, 71-90.[23]Szamosi, I. T., Shaner, D. L., Singh, B. K., Identification and characterization of a biodegradative form of threonine deghdratase in senescing tomato leaf, Plant Physiol., 1993, 101: 999-1004.[24]Hofgen, R., Laber, B., Schuttke, I. et al., Repression of acetolactate synthase activity through antisense inhibition: Molecular and biochemical analysis of transgenic potato (Solanum tuberosum L. cv Desiree) plants, Plant Physiol., 1995, 107: 469-477.

  16. Angiotensin processing activities in the venom of Thalassophryne nattereri.

    Science.gov (United States)

    Tenório, Humberto de Araújo; Marques, Maria Elizabeth da Costa; Machado, Sonia Salgueiro; Pereira, Hugo Juarez Vieira

    2015-05-01

    The venom of marine animals is a rich source of compounds with remarkable functional specificity and diversity. Thalassophryne nattereri is a small venomous fish inhabiting the northern and northeastern coast of Brazil, and represents a relatively frequent cause of injuries. Its venom causes severe inflammatory response followed frequently by the necrosis of the affected area. This venom presents characterized components such as proteases (Natterins 1-4) and a lectin (Nattectin) with complex effects on the human organism. A specific inhibitor of tissue kallikrein (TKI) reduces the nociception and the edema caused by the venom in mice. Our study sought to investigate the proteolytic activities against vasopeptides Angiotensin I, Angiotensin II, Angiotensin 1-9 and Bradykinin. The venom indicated angiotensin conversion against angiotensin I, as well as kininase against bradykinin. Captopril conducted the total inhibition of the converting activity, featuring the first report of ACE activity in fish venoms. PMID:25702959

  17. Saharan Dust, Transport Processes, and Possible Impacts on Hurricane Activities

    Science.gov (United States)

    Lau, William K. M.; Kim, K. M.

    2010-01-01

    In this paper, we present observational evidence of significant relationships between Saharan dust outbreak, and African Easterly wave activities and hurricane activities. We found two dominant paths of transport of Saharan dust: a northern path, centered at 25degN associated with eastward propagating 6-19 days waves over northern Africa, and a southern path centered at 15degN, associated with the AEW, and the Atlantic ITCZ. Seasons with stronger dust outbreak from the southern path are associated with a drier atmosphere over the Maximum Development Region (MDR) and reduction in tropical cyclone and hurricane activities in the MDR. Seasons with stronger outbreak from the northern path are associated with a cooler N. Atlantic, and suppressed hurricane in the western Atlantic basin.

  18. Activity Specific Knowledge Characteristics in the Internationalization Process

    DEFF Research Database (Denmark)

    Søberg, Peder Veng

    2012-01-01

    /methodology/approach – The paper presents a framework primarily based on knowledge management theory, which is illustrated in relation to interesting cases of four companies that are global leaders. Findings – An R&D knowledge gap still exists in China and India. Differences across business activities exist in terms......Purpose – The purpose of this paper is to investigate differences in the characteristics of knowledge, which is very important for the internationalization of different business activities. In particular, the focus is on internationalization in emerging markets such as China and India. Design...... is developed that illustrates differences between the most important knowledge for the internationalization of key business activities within MNCs. It is proposed that the technical dimension of tacit knowledge is more easily codified than the cognitive dimension of tacit knowledge. The cognitive dimension...

  19. Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice

    Institute of Scientific and Technical Information of China (English)

    PAN Xu-dong; MAO Yan-qing; ZHU Li-jing; LI Jie; XIE Yan; WANG Ling; ZHANG Guang-bo

    2012-01-01

    Background Immunosuppressive regulatory T cells (Tregs) participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process,but it is not clear whether such change leads to a higher incidence of tumors in the elderly.To this end,we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 (FoxP3) in the aging process and its relationship with lung tumors in humans and mice.Methods The percentage of CD4+CD25+CD127lowTregs and expression of FoxP3 mRNA were analyzed using flow cytometry (FCM) and real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR).Markers were analyzed in the peripheral blood (PB) of 65 elderly patients (age ≥65 years) with primary non-small cell lung cancer (NSCLC),20 younger patients (aged <55 years) with NSCLC,30 elderly healthy individuals and 30 young healthy individuals.Furthermore,we set up the Lewis lung cancer model with C57BL/6 female mice.Thirty-six mice were divided into a young healthy group,a middle-aged healthy group,an elderly healthy group,a young tumor group,a middle-aged tumor group,and an elderly tumor group.The percentage of CD4+CD25+FoxP3+ Tregs and the expression level of FoxP3mRNA in splenocytes were determined in the six groups.Results The percentage of peripheral CD4+CD25+CD127low Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals.Further analysis showed that the percentage of CD4+CD25+CD127low Tregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis (TNM) staging in elderly patients with NSCLC.In the mouse model,the percentage of CD4+CD25+FoxP3+ Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups,with the highest expression in the elderly tumor group.In the

  20. CD4+FoxP3+ regulatory T cells from Gαi2-/- mice are functionally active in vitro, but do not prevent colitis.

    Directory of Open Access Journals (Sweden)

    Yu-Yuan C Götlind

    Full Text Available BACKGROUND: Mice deficient in the inhibitory G protein subunit Gαi2 spontaneously develop a T helper 1 dominated colitis. We examined whether a defect in CD4(+FoxP3(+ regulatory T cells (Treg underpins the pathogenesis of colitis in the Gαi2(-/- (Gαi2-deficient colitis model. METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometry, we found that thymus and colonic lamina propria, but not spleen and mesenteric lymph nodes, of colitic Gαi2(-/- mice contained increased frequencies of Treg, whereas FoxP3 expression intensity was similar in Gαi2(-/- compared to Gαi2(+/- or Gαi2(+/+ wild type (WT mice. The frequency of CD4(+FoxP3(+ T cells expressing CD103 was significantly increased in Gαi2(-/- compared to WT mice. Treg in colons from WT mice clustered in the T cell areas of colonic lymphoid patches (CLP, with relatively few Treg in the lamina propria, as demonstrated by immunohistochemistry. In Gαi2(-/- mice, CLP were not observed but lamina propria Treg were increased in number and frequency within the CD4(+ infiltrate, compared to WT mice. Using an in vitro co-culture system and flow cytometric analysis of cell division we could demonstrate that the in vitro suppressive function of WT and Gαi2(-/- CD4(+FoxP3(+ regulatory T cells (WT-Treg and KO-Treg was indistinguishable, but that T effector cells (CD4(+25(- T cells from Gαi2(-/- mice were less readily suppressed than WT effectors (WT-Teff by Treg from either source. However, neither WT nor Gαi2(-/- Treg was able to suppress colitis induced by adoptive transfer of Gαi2(-/- effector T cells (KO-Teff to RAG2(-/- recipients. The enhanced inflammatory activity of Gαi2(-/- effectors was accompanied by increased expression of an effector/memory T cell phenotype and increased cytokine secretion, especially IL-4, IL-6 and IFN-γ. CONCLUSIONS: There is an increased frequency of Gαi2(-/- Treg in the colon, and they demonstrate no endogenous functional defect. However, Gαi2(-/- T effector cells

  1. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity

    Science.gov (United States)

    Azevedo, Michelle de C. S.; Rosa, Patricia S.; Soares, Cleverson T.; Fachin, Luciana R. V.; Baptista, Ida Maria F. D.; Woods, William J.; Garlet, Gustavo P.

    2015-01-01

    Jorge Lobo’s disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  2. Phosphoproteomic analysis of induced resistance reveals activation of signal transduction processes by beneficial and pathogenic interaction in grapevine.

    Science.gov (United States)

    Perazzolli, Michele; Palmieri, Maria Cristina; Matafora, Vittoria; Bachi, Angela; Pertot, Ilaria

    2016-05-20

    Protein phosphorylation regulates several key processes of the plant immune system. Protein kinases and phosphatases are pivotal regulators of defense mechanisms elicited by resistance inducers. However, the phosphorylation cascades that trigger the induced resistance mechanisms in plants have not yet been deeply investigated. The beneficial fungus Trichoderma harzianum T39 (T39) induces resistance against grapevine downy mildew (Plasmopara viticola), but its efficacy could be further improved by a better understanding of the cellular regulations involved. We investigated quantitative changes in the grapevine phosphoproteome during T39-induced resistance to get an overview of regulatory mechanisms of downy mildew resistance. Immunodetection experiments revealed activation of the 45 and 49kDa kinases by T39 treatment both before and after pathogen inoculation, and the phosphoproteomic analysis identified 103 phosphopeptides that were significantly affected by the phosphorylation cascades during T39-induced resistance. Peptides affected by T39 treatment showed comparable phosphorylation levels after P. viticola inoculation, indicating activation of the microbial recognition machinery before pathogen infection. Phosphorylation profiles of proteins related to photosynthetic processes and protein ubiquitination indicated a partial overlap of cellular responses in T39-treated and control plants. However, phosphorylation changes of proteins involved in response to stimuli, signal transduction, hormone signaling, gene expression regulation, and RNA metabolism were exclusively elicited by P. viticola inoculation in T39-treated plants. These results highlighted the relevance of phosphorylation changes during T39-induced resistance and identified key regulator candidates of the grapevine defense against downy mildew. PMID:27010348

  3. High Resolution Processing with an Active Phased Array SAR

    NARCIS (Netherlands)

    Nijenboer, F.J.; Otten, M.P.G.

    1999-01-01

    The Dutch PHARUS system is a polarimetric active phased array SAR capable of performing advanced SAR modes. Advanced SAR modes that are being investigated are: spotlight SAR, sliding spotlight SAR, stepped frequency SAR and interferometric SAR. The flight experiments and automatic beam steering impl

  4. Brain activity related to integrative processes in visual object recognition

    DEFF Research Database (Denmark)

    Gerlach, Christian; Aaside, C T; Humphreys, G W;

    2002-01-01

    We report evidence from a PET activation study that the inferior occipital gyri (likely to include area V2) and the posterior parts of the fusiform and inferior temporal gyri are involved in the integration of visual elements into perceptual wholes (single objects). Of these areas, the fusiform a...

  5. Theoretical and practical aspects of modelling activated sludge processes

    NARCIS (Netherlands)

    Meijer, S.C.F.

    2004-01-01

    This thesis describes the full-scale validation and calibration of a integrated metabolic activated sludge model for biological phosphorus removal. In chapters 1 and 2 the metabolic model is described, in chapters 3 to 6 the model is tested and in chapters 7 and 8 the model is put into practice. Cha

  6. CONDITIONING PROCESS AND CHARACTERIZATION OF FRESH ACTIVATED SLUDGE

    Directory of Open Access Journals (Sweden)

    SALAM K. AL-DAWERY

    2015-05-01

    Full Text Available Fresh activated sludge in many wastewater treatment plants may be considered unhealthy due to the large amount of organic and organism content. Due to the lack of research on municipal sludge, there is an apparent scarcity of actual data. Thus, this work will focus on the characterization of fresh activated sludge. The effect of dosage of different polyelectrolytes and coagulants has been investigated at pH level in a comparative fashion that is commonly associated with fresh activated sludge. The results indicated that the cationic polyelectrolytes had significant effluence on the sludge properties, degree of flocculation and water quality. With respect to the optical analyses, it was observed that the floc sizes and densities were increased with rise concentrations of both types of cationic polyelectrolytes. It was found that the cationic CPAM-80 was the most effective chemical among other six used chemicals especially for solutions with pH near neutrality despite of the variations in feed properties of the fresh activated sludge. This polyelectrolyte gave lower turbidity, lower sludge volume index, faster zone settling rate and large floc density.

  7. Neural activities during affective processing in people with Alzheimer's disease

    NARCIS (Netherlands)

    Lee, Tatia M. C.; Sun, Delin; Leung, Mei-Kei; Chu, Leung-Wing; Keysers, Christian

    2013-01-01

    This study examined brain activities in people with Alzheimer's disease when viewing happy, sad, and fearful facial expressions of others. A functional magnetic resonance imaging and a voxel-based morphometry methodology together with a passive viewing of emotional faces paradigm were employed to co

  8. An Activity to Teach Students about Schematic Processing

    Science.gov (United States)

    Isbell, Linda M.; Tyler, James M.; Burns, Kathleen C.

    2007-01-01

    We designed a classroom activity to foster students' understanding of what schemas are and how they function. We used a video of the instructor as an infant to illustrate how schemas influence gender stereotyping. Before the video, we told students that the baby was either a boy or a girl. After the video, students rated whether the baby would…

  9. Effects of language processing on spontaneous muscle activity

    NARCIS (Netherlands)

    Stins, J.F.; Beek, P.J.

    2013-01-01

    There is evidence of the crucial involvement of the motor system in language understanding and production. We tested whether reading verbs that symbolized various actions would lead to an effector-specific modulation in subliminal muscle activity. Participants were lying in a relaxed position, and r

  10. Stochastic Greybox Modeling of an Alternating Activated Sludge Process

    DEFF Research Database (Denmark)

    Halvgaard, Rasmus Fogtmann; Munk-Nielsen, T.; Tychsen, P.;

    Summary of key findings We found a greybox model for state estimation and control of the BioDenitro process based on a reduced ASM1. We then applied Maximum Likelihood Estimation on measurements from a real full-scale waste water treatment plant to estimate the model parameters. The estimation...

  11. 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)

    (Changes to site evaluation reports); Nuclear safety and radiation protection (Amendments to various laws relating to nuclear safety, Revised requirements relating to modifications of nuclear installations, New safety reporting requirements, New requirements relating to releases of radionuclides, New conditions for removal of items from regulatory control, New radiation protection requirements, New inspection procedure requirements, New procedure for compliance enforcement); Nuclear security (Establishment of a design basis threat review process). Moldova: General legislation (Co-operation with the International Atomic Energy Agency). Poland: General legislation (Amendments to the Atomic Law Act); Liability and compensation (New requirements for civil liability insurance); Organisation and structure (New advisory council established); Nuclear safety and radiation protection (New requirements for employees working at nuclear power plants). Portugal: General legislation (Integration of the Nuclear Technological Institute into the Technical University of Lisbon); Nuclear safety and radiation protection (Creation of the Regulatory Commission for the Safety of Nuclear Facilities). Romania: Environmental protection (Changes to fuel production regulations). Slovenia: Nuclear safety and radiation protection (New rules governing worker qualification); Sweden: Nuclear safety and radiation protection (New regulation on clearance from regulation). Ukraine: General legislation (New requirements relating to the purchase of fuel elements); Nuclear safety and radiation protection (New plans for a comprehensive safety upgrade, New community outreach requirements, New transparency and information availability requirements); Nuclear security (Changes to the state-level physical protection regime); Radioactive waste management (New centralised repository planned) United States: Radioactive waste management (Status of the high-level waste repository programme, Issuance of the Final Report of

  12. Technical support for the Ohio Clean Coal Technology Program. Volume 2, Baseline of knowledge concerning process modification opportunities, research needs, by-product market potential, and regulatory requirements: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Olfenbuttel, R.; Clark, S.; Helper, E.; Hinchee, R.; Kuntz, C.; Means, J.; Oxley, J.; Paisley, M.; Rogers, C.; Sheppard, W.; Smolak, L. [Battelle, Columbus, OH (United States)

    1989-08-28

    This report was prepared for the Ohio Coal Development Office (OCDO) under Grant Agreement No. CDO/R-88-LR1 and comprises two volumes. Volume 1 presents data on the chemical, physical, and leaching characteristics of by-products from a wide variety of clean coal combustion processes. Volume 2 consists of a discussion of (a) process modification waste minimization opportunities and stabilization considerations; (b) research and development needs and issues relating to clean coal combustion technologies and by-products; (c) the market potential for reusing or recycling by-product materials; and (d) regulatory considerations relating to by-product disposal or reuse.

  13. Controlling Methane Emissions in the Natural Gas Sector. A Review of Federal and State Regulatory Frameworks Governing Production, Gathering, Processing, Transmission, and Distribution

    Energy Technology Data Exchange (ETDEWEB)

    Paranhos, Elizabeth [Energy Innovation Partners, Seoul (South Korea); Kozak, Tracy G. [Energy Innovation Partners, Seoul (South Korea); Boyd, William [Univ. of Colorado, Boulder, CO (United States); Bradbury, James [U.S. Department of Energy, Washington, DC (United States); Steinberg, D. C. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Arent, D. J. [Joint Inst. for Strategic Energy Alaysis, Washington, DC (United States)

    2015-04-23

    This report provides an overview of the regulatory frameworks governing natural gas supply chain infrastructure siting, construction, operation, and maintenance. Information was drawn from a number of sources, including published analyses, government reports, in addition to relevant statutes, court decisions and regulatory language, as needed. The scope includes all onshore facilities that contribute to methane emissions from the natural gas sector, focusing on three areas of state and federal regulations: (1) natural gas pipeline infrastructure siting and transportation service (including gathering, transmission, and distribution pipelines), (2) natural gas pipeline safety, and (3) air emissions associated with the natural gas supply chain. In addition, the report identifies the incentives under current regulatory frameworks to invest in measures to reduce leakage, as well as the barriers facing investment in infrastructure improvement to reduce leakage. Policy recommendations regarding how federal or state authorities could regulate methane emissions are not provided; rather, existing frameworks are identified and some of the options for modifying existing regulations or adopting new regulations to reduce methane leakage are discussed.

  14. Environmental regulatory update table, July 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-08-01

    This Environmental Regulatory Update Table (July 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  15. Environmental Regulatory Update Table, December 1989

    International Nuclear Information System (INIS)

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  16. Environmental Regulatory Update Table, April 1989

    International Nuclear Information System (INIS)

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  17. Environmental Regulatory Update Table, October 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  18. Environmental Regulatory Update Table, December 1989

    Energy Technology Data Exchange (ETDEWEB)

    Houlbert, L.M.; Langston, M.E. (Tennessee Univ., Knoxville, TN (USA)); Nikbakht, A.; Salk, M.S. (Oak Ridge National Lab., TN (USA))

    1990-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  19. Environmental regulatory update table, March 1989

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-04-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  20. Environmental Regulatory Update Table, April 1989

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.