WorldWideScience

Sample records for european commission erk6-1999-00001

  1. Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells

    Czech Academy of Sciences Publication Activity Database

    Kyjacová, Lenka; Hubáčková, Soňa; Krejčíková, Kateřina; Strauss, R.; Hanzlíková, Hana; Dzijak, Rastislav; Imrichová, Terezie; Šímová, Jana; Reiniš, Milan; Bartek, Jiří; Hodný, Zdeněk

    2015-01-01

    Roč. 22, č. 6 (2015), s. 898-911 ISSN 1350-9047 R&D Projects: GA ČR GA13-17658S; GA MZd NT14461 EU Projects: European Commission 259893 Institutional support: RVO:68378050 Keywords : Radiotherapy-induced plasticity * prostate cancer * Erk signaling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.218, year: 2015

  2. European commission research activities on iodine

    Energy Technology Data Exchange (ETDEWEB)

    Loggia, E della [European Commission, Brussels (Belgium)

    1996-12-01

    The research on iodine, as on other important fission products which would be released during a severe accident, carried out directly or organized by the European Commission stems from the Euratom Treaty, namely from Chapter III of the treaty which deals with the protection of the health of the population against radiations and from Chapter I which deals with research. In this paper we do not consider the Commission radiological protection programme: we limit ourselves to the presentation of the research carried out on Iodine as part of the most recent source term studies within the framework Programmes as are called the research programme of the European Commission, usually valid for a 4 year periods. The research activities are carried out by the European Commission either directly through the Joint Research Centres (JRC) or indirectly through collaboration with research organizations of Member States. Concerning the iodine research carried out as Direct Action in the Joint Research Centres, are mentioned here the most relevant activities carried out in this field at the JRC of Ispra and Karlsruhe (TUI). As Indirect Action, we present here the results of some studies allocated by the European Commission to experts of research organizations of Member Countries, followed by a short description of the main results achieved by the Reinforced Concerted Action, within the III Framework Programme (1992-1995). At the end of the paper are described the research on iodine being carried out or proposed within the IV Framework Programme (1995-1998). Mention is also done of the Commission participation, relevant in terms of financial and human efforts, to the PHEBUS FP Project. (author) refs.

  3. European commission research activities on iodine

    International Nuclear Information System (INIS)

    Loggia, E. della

    1996-01-01

    The research on iodine, as on other important fission products which would be released during a severe accident, carried out directly or organized by the European Commission stems from the Euratom Treaty, namely from Chapter III of the treaty which deals with the protection of the health of the population against radiations and from Chapter I which deals with research. In this paper we do not consider the Commission radiological protection programme: we limit ourselves to the presentation of the research carried out on Iodine as part of the most recent source term studies within the framework Programmes as are called the research programme of the European Commission, usually valid for a 4 year periods. The research activities are carried out by the European Commission either directly through the Joint Research Centres (JRC) or indirectly through collaboration with research organizations of Member States. Concerning the iodine research carried out as Direct Action in the Joint Research Centres, are mentioned here the most relevant activities carried out in this field at the JRC of Ispra and Karlsruhe (TUI). As Indirect Action, we present here the results of some studies allocated by the European Commission to experts of research organizations of Member Countries, followed by a short description of the main results achieved by the Reinforced Concerted Action, within the III Framework Programme (1992-1995). At the end of the paper are described the research on iodine being carried out or proposed within the IV Framework Programme (1995-1998). Mention is also done of the Commission participation, relevant in terms of financial and human efforts, to the PHEBUS FP Project. (author) refs

  4. Status and functioning of the European Commission's major accident reporting system

    International Nuclear Information System (INIS)

    Kirchsteiger, C.

    1999-01-01

    This paper describes the background, functioning and status of the European Commission's Major Accident Reporting System (MARS), dedicated to collect, in a consistent way, data on major industrial accidents involving dangerous substances from the Member States of the European Union, to analyse and statistically process them, and to create subsets of all non-confidential accidents data and analysis results for export to all Member States. This modern information exchange and analysis tool is made up of two connected parts: one for each local unit (i.e., for the Competent Authority of each EU Member State), and one central part for the European Commission. The local, as well as the central parts of this information network, can serve both as data logging systems and, on different levels of complexity, as data analysis tools. The central database allows complex cluster and pattern analysis, identifying and analysing the succession of the disruptive factors leading to an accident. On this basis, 'lessons learned' can be formulated for the industry for the purposes of further accident prevention. Further, results from analysing data of major industrial accidents reported to MARS are presented. It can be shown that some of the main assumptions in the new 'Seveso II Directive' can directly be validated from MARS data. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. Radiological emergency preparedness arrangements in the European Commission

    International Nuclear Information System (INIS)

    Tanner, V.

    2002-01-01

    The purpose of this paper is to give an overview of the different procedures established within the European Commission, which are relevant to radiological emergency planning and response. Although emergency preparedness is a national responsibility within the European Union, the Commission has clearly defined operational tasks in terms of emergency information exchange and community foodstuff regulations. In addition the Commission promotes research programmes and training courses in the field

  6. Decommissioning and radioactive waste management. The European Commission overview

    International Nuclear Information System (INIS)

    Rehak, M

    2010-01-01

    In this lecture author deals with the European Commission overview on the decommissioning and radioactive waste management. Financial support of European Commission of decommissioning of the Ignalina NPP, Bohunice V1 NPP and Kozloduy Units 1 and 2 is presented.

  7. European Union energy policy integration: A case of European Commission policy entrepreneurship and increasing supranationalism

    International Nuclear Information System (INIS)

    Maltby, Tomas

    2013-01-01

    Focusing on gas, this article explores the role of the European Commission in the process of European Union energy security policy development, and the extent to which the policy area is becoming increasingly supranational. Situating the article within the literature on agenda-setting and framing, it is argued that a policy window was opened as a result of: enlargement to include more energy import dependent states, a trend of increasing energy imports and prices, and gas supply disruptions. From the mid-2000s, the Commission contributed to a shift in political norms, successfully framing import dependency as a problem requiring an EU-level solution, based on the institution’s pre-existing preferences for a diversified energy supply and internal energy market. Whilst Member States retain significant sovereignty, the Commission has achieved since 2006 creeping competencies in the internal, and to a lesser extent external, dimensions of EU energy policy. - Highlights: ► We examine the development of EU energy security policy, focusing on gas. ► We examine changes in European Commission competence in energy policy. ► The European Commission has gained increased competence in the internal market. ► In the external dimension of EU energy policy Member States retain competence. ► The European Commission has had qualified success as a policy entrepreneur

  8. Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells

    Czech Academy of Sciences Publication Activity Database

    Kyjacová, Lenka; Hubáčková, Soňa; Krejčíková, Kateřina; Strauss, R; Hanzlíková, Hana; Dzijak, Rastislav; Imrichová, Terezie; Šímová, Jana; Reiniš, Milan; Bartek, Jiří; Hodný, Zdeněk

    -, July (2014) ISSN 1350-9047 R&D Projects: GA ČR GA13-17658S; GA MZd NT14461 Grant - others:Danish Research Council(DK) DFF-1331-00262B; Lundbeck Foundation(DK) (R93-A8990; European Commission DDResponse 259893 Institutional support: RVO:68378050 Keywords : Radiotherapy * induced plasticity * prostate cancer * Erk Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.184, year: 2014

  9. Changes in physical performance in elderly Europeans. SENECA 1993-1999

    NARCIS (Netherlands)

    Schroll Bjornsbo, K.; Ferry, M.; Groot, de C.P.G.M.; Schlienger, J.L.

    2002-01-01

    OBJECTIVE: To assess longitudinal changes in subjective and objective measures of physical performance in elderly Europeans. DESIGN: Longitudinal study including SENECA measurements 1993-1999. SETTING: Data were collected in 9 'traditional' European towns. SUBJECTS AND METHODS: In total 444 men and

  10. Nuclear safety research at the European Commission's Joint Research Centre

    International Nuclear Information System (INIS)

    Toerroenen, K.

    2003-01-01

    Nuclear power plants currently generate some 35 % of electricity used in the European Union and applicant countries. Nuclear safety will therefore remain a priority for the EU, particularly in view of enlargement, the need to monitor ageing nuclear installations and the licencing of advanced new reactor systems. The European Commission's Joint Research Centre (JRC), with its long involvement and recognised competence in nuclear safety related activities, provides direct support to the European Commission services responsible for nuclear safety and civil protection. (author)

  11. Radiation research within the framework programmes of the European Commission

    Energy Technology Data Exchange (ETDEWEB)

    Karaoglou, A.; Kelly, G.N.; Desmet, G.; Menzel, H.G.; Schibilla, H.; Olast, M.; Gasperini, F.; Chadwick, K.H.; Sinnave, J. [European Commission Directorate General science, Brussels (Belgium). Research and Development, Radiation Protection Research Action

    1997-09-01

    The background to the radiation protection research and training programme of the European Commission is described in the presentation. The objectives and achievements of the third framework programme are summarised together with a description of how the achievements led to the establishment of the priorities for the fourth framework programme. Indications on the preliminary prospects for the fifth framework programme, 1998-2002 are also given. (6 refs.).

  12. Discussion: European Commission policy

    International Nuclear Information System (INIS)

    Coldwell, R.

    1993-01-01

    This paper documents the debate which arose following two papers presented to a seminar run by the Centre for the Study of Regulated Industries, on 11th November 1992, on European Commission (EC) energy policies. The issues raised cover how an internal market for electricity and natural gas will be implemented under a proposed EC directive, bearing in mind the level of opposition from a number of Member States. How this Directive will apply to vertically integrated structures, such as Scottish Electricity Industry, is also considered. (UK)

  13. The European Commission proposes changes to the directive on nuclear safety

    International Nuclear Information System (INIS)

    Anon.

    2013-01-01

    The European Commission proposes changes in the ancient European directive on nuclear safety in order to europeanize nuclear safety. The first proposal is to submit all European nuclear facilities to a control every 6 years by a board of foreign experts. Another proposal is to impose that every new power plant should be designed so that the radiological impact of an accident should be limited to the facility itself. The same proposal would impose for every nuclear plant the presence of an emergency center resistant to radiation, earthquakes and floods. The reporting of any incident occurring in a nuclear plant would be made compulsory. The decision to extend the operating life of a nuclear plant would be suspended to the results of a compulsory safety test. (A.C.)

  14. European Commission research on aircraft impacts in the atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Amanatidis, G T; Angeletti, G [European Commission (CEC), Brussels (Belgium)

    1998-12-31

    Aircraft engines release in the troposphere and lower stratosphere a number of chemical compounds (NO{sub x}, CO{sub 2}, CO, H{sub 2}O, hydrocarbons, sulphur, soot, etc.) which could potentially affect the ozone layer and the climate through chemical, dynamical and radiative changes. The global amount of gases and particles emitted by current subsonic and projected supersonic aircraft fleets can be estimated, but significant uncertainties remain about the fate of these emissions in the atmosphere. The European efforts concerning these potential atmospheric impacts of aircraft emissions are conducted by the Environment and Climate Research Programme of the European Commission (EC) as well as by national programmes of the Member States of the European Union (EU). The European research activities in this field, are described, divided for practical reasons in two periods. The first includes activities supported under the 3. Framework Programme for R and D activities which covered the period from 1992 up to 1996, while the second period has started in early 1996 and is supported under the 4. Framework Programme. (R.P.) 6 refs.

  15. European Commission research on aircraft impacts in the atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Amanatidis, G.T.; Angeletti, G. [European Commission (CEC), Brussels (Belgium)

    1997-12-31

    Aircraft engines release in the troposphere and lower stratosphere a number of chemical compounds (NO{sub x}, CO{sub 2}, CO, H{sub 2}O, hydrocarbons, sulphur, soot, etc.) which could potentially affect the ozone layer and the climate through chemical, dynamical and radiative changes. The global amount of gases and particles emitted by current subsonic and projected supersonic aircraft fleets can be estimated, but significant uncertainties remain about the fate of these emissions in the atmosphere. The European efforts concerning these potential atmospheric impacts of aircraft emissions are conducted by the Environment and Climate Research Programme of the European Commission (EC) as well as by national programmes of the Member States of the European Union (EU). The European research activities in this field, are described, divided for practical reasons in two periods. The first includes activities supported under the 3. Framework Programme for R and D activities which covered the period from 1992 up to 1996, while the second period has started in early 1996 and is supported under the 4. Framework Programme. (R.P.) 6 refs.

  16. Appraisal of the European Commission's Energy Roadmap 2050

    International Nuclear Information System (INIS)

    Meeus, L.

    2012-01-01

    What is the European energy strategy for 2050? How different is it from the 2020 energy strategy? What are the technology options? What are the policy options? The European Commission provided a first answer to these questions in its Energy Roadmap 2050. This article gives an appraisal of that answer based on the recommendations we made during the preparation of the roadmap.

  17. Commissioning for the European XFEL facility

    Science.gov (United States)

    Nölle, D.

    2017-06-01

    The European XFEL is a 4th generation light source based on the Self Amplified Spontaneous Emission (SASE) FreeElectron-Laser concept. It is currently being commissioned in North- Germany. The core installation is a 17.5 GeV superconducting accelerator driving 3 SASE lines with photon energies from 1 to beyond 20 keV range with a maximum of 27.000 pulses per second. The international facility is organized as a limited liability company with shareholders from the contributing countries. DESY has taken over the leadership of the accelerator construction consortium, and will be in charge of the operation of the accelerator complex. The facility was set up with contributions from the 11 shareholder countries, either being hardware systems and/or staff or cash contributions. The construction is almost complete, and the commissioning phase has started by the end of 2015. This contribution will report the status of the accelerator complex with emphasis on the commissioning of the accelerator and an outlook to the commissioning of the SASE 1 FEL line.

  18. The debate on law propositions about energy by the European Commission

    International Nuclear Information System (INIS)

    Kerebel, C.

    2008-01-01

    After a presentation of the third Energy Package put forward by the European Commission on the 19 September 2007, and a presentation of the European Strategic Energy Technology Plan (SET-Plan) presented by the Commission on the 22 November 2007, the author more precisely presents the contents of the European Union Energy and Climate Package of January 2008. Several aspects are addressed: renewable energies, greenhouse gas emissions, carbon capture and storage, and public aids for these different themes. A graph gives a description of the co-decision procedure

  19. The European carbon tax: an assessment of the European Commission's proposals

    International Nuclear Information System (INIS)

    Pearson, M.; Smith, Stephen.

    1991-12-01

    After a lengthy internal debate within the European Commission, the Environment Commissioner announced the broad structure of the Commission's proposals for a European carbon tax towards the end of September. The proposed tax would be a combination of a tax on the carbon content of fossil fuels, and a tax on all non-renewable forms of energy. Thus, fossil fuels such as gas, coal and oil would bear a tax comprising two components, one related to their carbon content, the other related to their energy content. Non-renewable forms of energy other than fossil fuels (mainly nuclear power) would be subject to the energy-related part of the tax, but would not bear the carbon component. Overall, the two components would be combined in equal proportions, in the sense that half of the tax on a typical barrel of oil would be related to the carbon component and half to the energy component. (author)

  20. The European Commission 2008 Directive Proposal on Biofuels - Comment

    Directory of Open Access Journals (Sweden)

    Florent Pelsy

    2008-09-01

    Full Text Available This article focuses on the 2008 Directive Proposal of the European Commission on biofuels. The development of biofuels as a renewable energy source has been perceived as a priority by the European Union. Indeed biofuels are approached by the EU as a new 'win-win' solution that could both reduce emission of greenhouses gases in the context of climate change and improve energy security while not affecting the European economic growth. The 2008 Directive Proposal of the Commission requires an objective of ten per cent of biofuels in the EU Transport in 2020. In order to qualify within that target biofuels shall be produced according to certain environmental criteria. This article points out the tremendous negative impacts on food security and the environment both in the developed and in the developing world of such a large-scale consumption of biofuels. It then considers that the environmental criteria required by the Directive Proposal of the Commission are not likely to be the adequate response to tackle the negative consequences of the implementation of that ten per cent target. It, thus, suggests the application of the precautionary principle as sketched out by the European Court of Justice in the case Pfizer - Alpharma to that ten per cent target and a moratorium on biofuels at the EU level.

  1. Research on nuclear energy within the European Commission Research Framework Programme

    International Nuclear Information System (INIS)

    Forsstroem, H.

    2000-01-01

    The strategic goal of the 5 th EURATOM RTD Framework Programme (FP5) is to help exploit the full potential of nuclear energy in a sustainable manner, by making current technologies even safer and more economical and by exploring promising new concepts. The programme covers nuclear fusion, nuclear fission and radiation protection. Part of the programme on nuclear fission and radiation protection is being implemented through ''indirect actions'', i.e. research co-sponsored (up to 50% of total costs) and co-ordinated by DG RESEARCH of the European Commission (EC) but carried out by external public and private organisations as multi-partner projects. The budget available for these indirect actions during FP5 (1998-2002) is 191 MEuro. The programme covers four different areas: safety of existing reactors, including plant life management, severe accident management and development of evolutionary systems; safety of the fuel cycle, including radioactive waste management and disposal, partitioning and transmutation and decommissioning of nuclear installation; safety of future systems, including new or revisited reactor or fuel cycle concepts; radiation protection and radiological sciences, including both basic radiobiology and radiophysics and issues connected to the application of radiation protection. After the first calls for proposals of FP5, which were evaluated in 1999 about 140 research projects have been selected for funding and is now in the process of starting. In parallel the research projects that were supported in the 4th Framework Programme (1994 - 1998) are coming to an end, and being reported, at the same time as the first thoughts on the 6 t h FP are discussed.An important new component for the future research in Europe is the concept of a European Research Area (ERA). The purpose of ERA is to create better overall framework conditions for research in Europe. Some of the concepts being discussed in this context are networking of centres of excellence, a

  2. The review of constitutional norms concerning local public administration in the view of the European Commission for Democracy through Law (Venice Commission)

    OpenAIRE

    Apostolache, Mihai

    2015-01-01

    The proposals of the Commission to review the Constitution of Romania were subject to the analysis of experts from the European Commission for Democracy through Law (the Venice Commission), who expressed their opinion in a report adopted at the 98th plenary session of the European body. The article analyzes the recommendations of the Venice Commission regarding the proposed changes to the constitutional norms governing local public administration, comprising some general aspects concern...

  3. Abatement cost of SF6 emissions from medium voltage switchgear. Validation of recent studies for the European Commission

    Energy Technology Data Exchange (ETDEWEB)

    Benner, J.; Van Lieshout, M.; Croezen, H.

    2012-05-15

    Sulphur hexafluoride (SF6) is a gas with applications including use as an insulator and switching medium in medium voltage (MV) switchgear. While having certain unique properties, it is also a greenhouse gas, with a 22,800 times greater impact than CO2 and an atmospheric lifetime of over 3,000 years. Although the use of SF6 in MV switchgear can be avoided, according to recent studies for the European Commission, the abatement costs are high. This study validates the calculated cost levels as well as the general feasibility of determining a fixed cost figure for this purpose. This analysis yields a result which differs from the earlier studies, particularly with respect to the cost aspect, but also in other areas. CE Delft concludes that for the majority of applications cost-effective SF6-free options are available, leading to abatement costs for the use of SF6 in MV switchgear that range from - 40 to 0 euro/tCO2 eq., for all types of switchgear, with voltage levels below 25 kV and situated on relatively dry locations.

  4. Interest group satisfaction with the European Commission's consultation agendas

    DEFF Research Database (Denmark)

    Hermansson, Henrik Alf Jonas

    2016-01-01

    Interest groups exist largely to raise awareness of particular problems or to avoid regulation by keeping items off the political agenda, it is a major component of their raison d'être. At the earliest stages of the European policy process, the European Commission presents an agenda in the form...... of a "call for consultation" which interest groups attempt to influence. Groups that have had a role in setting the Commission's agenda will likely show most satisfaction with the agenda, used here as a way to examine their agenda-setting power. Based on a novel dataset covering 190 policy issues and 469...... interest groups, unique issue-level data on the expertise held by interest groups, their privileged access and their resources, this paper evaluates whether it is the technical information provided by groups, their insider status or their ability to put pressure on the European institutions that form...

  5. Open Letter to the European Commission

    DEFF Research Database (Denmark)

    Savin, Andrej; Schwemer, Sebastian Felix

    2016-01-01

    to the information society. A key component of this acquis is the prohibition of general monitoring obligations to the benefit of providers of intermediary services. It is a means to achieve at least two central objectives: the encouragement of innovation as well as the protection of fundamental rights of all...... Internet users, namely the rights protected by Articles 8 and 11 of the European Convention of Human Rights. Yet, the proposed Copyright Directive, in particular, seems to negatively affect both the domain and effect of Article 15 of the E-commerce Directive. The signatories of this open letter therefore...... urge the European Commission to take into account the human rights dimension of Article 15 of the E-commerce Directive, as made explicit by the Court of the Justice of the European Union, and to make sure its implications are carefully examined across sectors. Authors: Sophie Stalla-Bourdillon Eleonora...

  6. Impact assessment and policy learning in the European Commission

    International Nuclear Information System (INIS)

    Ruddy, Thomas F.; Hilty, Lorenz M.

    2008-01-01

    Governance for sustainable development requires policy coherence and Environmental Policy Integration, which are being hindered by difficulties coordinating the two separate impact assessment processes being conducted in the European Commission. One of them, the Commission-wide Impact Assessment process, looks primarily at EU-internal impacts, whereas the other one, Sustainability Impact Assessment (SIA) in DG Trade, looks outward to other countries and intergovernmental organizations. Ideally, the two processes should complement one another, especially as the two are set to continue being done in parallel. The paper uses a case study of the reform of the European sugar regime under a World Trade Organization ruling to demonstrate how the two impact assessment processes could better complement one another. Feedback from the experience had with existing trade agreements could then promote policy learning and inform the negotiations on new agreements. The number of new bilateral and Regional Trade Agreements is expected to continue rising, thus increasing the importance of the Commission-wide Impact Assessment process required for them

  7. European antitrust policy 1957-2004: an analysis of Commission decisions

    NARCIS (Netherlands)

    Carree, M.; Günster, A.; Schinkel, M.P.

    2010-01-01

    This paper provides a survey of European antitrust law enforcement since its foundation in the Treaty of Rome of 1957 up to and including 2004. We present a complete overview and statistical analysis of all 538 formal Commission decisions under Articles 81, 82, and 86 of the European Community

  8. European commission report on market opening

    International Nuclear Information System (INIS)

    Anon.

    2005-01-01

    Governments must step up their effort to implement measures relating to market opening within the framework of the directives on gas and electricity. Only greater integration of national markets will produce the improvements required from a competitive point of view on the domestic energy market. These are the main conclusions of the annual report on domestic electricity and gas market operation adopted by the European Commission at the beginning of January 2005. (author)

  9. PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.

    Directory of Open Access Journals (Sweden)

    Hiroaki Ono

    Full Text Available Protein Tyrosine Kinase 6 (PTK6 is a non-receptor type tyrosine kinase that may be involved in some cancers. However, the biological role and expression status of PTK6 in pancreatic cancer is unknown. Therefore in this study, we evaluated the functional role of PTK6 on pancreatic cancer invasion. Five pancreatic cancer cell lines expressed PTK6 at varying levels. PTK6 expression was also observed in human pancreatic adenocarcinomas. PTK6 suppression by siRNA significantly reduced both cellular migration and invasion (0.59/0.49 fold for BxPC3, 0.61/0.62 for Panc1, 0.42/0.39 for MIAPaCa2, respectively, p<0.05 for each. In contrast, forced overexpression of PTK6 by transfection of a PTK6 expression vector in Panc1 and MIAPaCa2 cells increased cellular migration and invasion (1.57/1.67 fold for Panc1, 1.44/1.57 for MIAPaCa2, respectively, p<0.05. Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation. U0126, a specific inhibitor of ERK1/2, completely abolished the effect of PTK6 overexpression on cellular migration and invasion. These results suggest that PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer.

  10. European Commission - 7th Framework Programme

    International Nuclear Information System (INIS)

    Fiorini, G.L.; Vasile, A.

    2011-01-01

    Highlights: → Core safety optimisation through a set of reactivity feedback coefficients allowing to cope with accidental transients. → Reactor optimisation by exploring innovative options for intermediate circuits and steam generators. → Reactor behaviour under accidental conditions including severe accidents to improve the robustness. → Waste management options having both characteristics of efficiency and economics viability. → Promoting European young human resources skills on sodium fast reactors by means of dedicated workshops and doctoral dissertations. - Abstract: Fast Reactors have a unique capability as sustainable energy source; the closed fuel cycle allows significantly improving the usage of natural resources and the minimisation of volume and heat load of high-level waste. Among the fast reactor systems, the sodium-cooled fast reactor has the most comprehensive technological basis, thanks to the experience gained internationally from operating experimental, prototype and commercial size reactors. The paper summarizes the key characteristics of the four years large Collaborative Project on European Sodium Fast Reactor (CP ESFR - 2009-2012); the CP ESFR follows the 6th FP project named 'Roadmap for a European Innovative SOdium cooled FAst Reactor - EISOFAR' further identifying, organizing and implementing a significant part of the needed R and D effort. The CP ESFR merges the contribution of 25 European partners; it is performed under the aegis of the 7th FP under the Area - Advanced Nuclear Systems with a refund from the European Commission of 5.8 M Euro (11.55 M Euro total budget). It is a key component of the European Sustainable Nuclear Energy Technology Platform (SNE TP) and its Strategic Research Agenda (SRA). The inputs for the project are the key research goals for fourth generation of European sodium cooled fast reactors which can be summarized as follows: an improved safety with in particular the achievement of a robust architecture

  11. European commission - 7th framework programme. The collaborative project on European sodium fast reactor (CP ESFR)

    International Nuclear Information System (INIS)

    Fiorini, G.L.

    2009-01-01

    The paper summarizes the key characteristics of the four years large Collaborative Project on European Sodium Fast Reactor (CP ESFR - 2009-2012); the CP ESFR follows the 6th FP project named 'Roadmap for a European Innovative SOdium cooled FAst Reactor - EISOFAR' further identifying, organizing and implementing a significant part of the needed R and D effort. The CP ESFR merges the contribution of 25 european partners; it will be realized under the aegis of the 7th FP under the Area - Advanced Nuclear Systems with a refund from the European Commission of 5.8 M euro (11.55 M euro total budget). It will be a key component of the European Sustainable Nuclear Energy Technology Platform (SNE TP) and its Strategic Research Agenda (SRA). The inputs for the project are the key research goals for fourth generation of European sodium cooled fast reactors which can be summarized as follow: an improved safety with in particular the achievement of a robust architecture vis a vis of abnormal situations and the robustness of the safety demonstrations; the guarantee of a financial risk comparable to that of the other means of energy production; a flexible and robust management of the nuclear materials and especially the waste reduction through the Minor Actinides burning. (author)

  12. European antitrust policy 1957-2004: An analysis of Commission decisions

    NARCIS (Netherlands)

    Carree, M.; Günster, A.; Schinkel, M.P.

    2008-01-01

    This paper provides a survey of European antitrust law enforcement since its foundation in the Treaty of Rome of 1957. We present a complete overview and statistical analysis of all 538 formal Commission decisions adopted up to 2004 under Articles 81, 82 and 86 of the European Community Treaty. We

  13. Motivation and values of European Commission staff. Paper

    NARCIS (Netherlands)

    Vandenabeele, W.V.; Ban, C.

    2009-01-01

    The concept of public service motivation has been central to the discussion of motivation in the field of public management but has never been studied in international organizations. This paper reports on a preliminary study of motivational issues within the European Commission, including motivation

  14. Basic Fibroblast Growth Factor Regulates Persistent ERK Osciliations in Premaligant but not Malignant JB6 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Thomas J.; Shankaran, Harish; Wiley, H. S.; Opresko, Lee K.; Chrisler, William B.; Quesenberry, Ryan D.

    2010-05-02

    basic fibroblast growth factor (bFGF or FGF2) plays an important role in epidermal wound healing in vivo and is associated with a persistent increased in the extracellular signal-regulated kinase (ERK) pathway in vitro. Here we have examined whether bFGF induces the closure of an experimental scratch wound in JB6 mouse epidermal cells and have explored the regulation of the ERK pathway by bFGF in the context of kinase oscillations. bFGF stimulation is associated with increases in cellular phospho-ERK and phospho-c-Jun levels. In addition, bFGF increases cell proliferation and a change in cell morphology (stellate appearance) in a dose-dependent fashion (0.1 – 100 ng/ml). bFGF treatment also promoted the closure of an experimental scratch wound in vitro. JB6 cells were stably transfected with an ERK1-GFP chimera to follow temporal ERK subcellular distribution patterns. We observe a persistent upregulation of the ERK pathway, as evidenced by a significant increase in nuclear ERK1-GFP levels at time points up to 24 hr after bFGF treatment. Interestingly, at the single cell level, ERK is observed to oscillate between nuclear and cytosolic compartments in response to bFGF treatment. Because this oscillatory behavior is asynchronous in the cell population, it is only clearly resolved at the single cell level. Collectively, data presented here are consistent with an important role for bFGF in wound healing and suggest a more complex regulation of the ERK pathway by bFGF than has previously been appreciated.

  15. Experts Networks and the European Commission on Demographic Change

    DEFF Research Database (Denmark)

    Seabrooke, Leonard; Tsingou, Eleni; Willers, Johann Ole

    experts on demographic change. Our findings suggest that on demographic change issues at the EU level, DG EMPL has taken the lead, while DG ECFIN is the secondary actor. Still, internal European Commission dynamics mean that the lead actor on demographic issues has less autonomy in articulating a funded......This paper examines who populates the expert and policy network around demographic change issues in Europe. We examine how competing policy departments in the European Commission Directorates-General (DGs) deal with the issue of Europe’s changing demography, as well as discuss the role of external...... and clear policy position on how to address them. As a consequence, there is little institutional memory and hardly a depository of activity on demographic change. While outside expertise comes primarily from demographers, and other scholars concerned with demographic change, they are primarily an academic...

  16. Drug: D00001 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00001 Drug Water (JP17/USP); Purified water (JP17); Purified water in containers ...(JP17); Water, purified (USP); Sterile purified water in containers (JP17); Water for injection (JP17); Water for injection in contai...ners (JP17); Sterile water (TN) ... H2O D00001.gif ... Same as: C00001 Therapeutic cat

  17. Agmatine Protects Against 6-OHDA-Induced Apoptosis, and ERK and Akt/GSK Disruption in SH-SY5Y Cells.

    Science.gov (United States)

    Amiri, Esmat; Ghasemi, Rasoul; Moosavi, Maryam

    2016-08-01

    6-Hydroxydopamine (6-OHDA), a metabolite of dopamine is known to induce dopaminergic cell toxicity which makes that a suitable agent inducing an experimental model of Parkinson's disease (PD). Agmatine has been shown to protect against some cellular and animal PD models. This study was aimed to assess whether agmatine prevents 6-OHDA-induced SH-SY5Y cell death and if yes, then how it affects Akt/glycogen synthesis kinase-3β (GSK-3β) and extracellular signal-regulated kinases (ERK) signals. The cells were treated with different drugs, and their viability was examined via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay and morphological observation. Western blot studies were done to assess cleaved caspase-3, Akt/GSK-3β, and ERK proteins. 6-OHDA-induced cell death and caspase-3 cleavage, while agmatine prevented those changes. 6-OHDA also decreased the amount of phosphorylated Akt (pAkt)/Akt while increased GSK-3β activity which was prevented by agmatine. Additionally, this toxin increased pERK/ERK ratio which was averted again by agmatine. The PI3/Akt inhibitor, LY294002, impeded the changes induced by agmatine, while ERK inhibitor (PD98059) did not disturb the effects of agmatine, and by itself, it preserved the cells against 6-OHDA toxicity. This study revealed that agmatine is protective in 6-OHDA model of PD and affects Akt/GSK-3β and ERK pathways.

  18. Government Performance and Results Act: Performance plan FY 1999, U.S. Nuclear Regulatory Commission. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Fuches, J.L.

    1998-02-01

    The Nuclear Regulatory Commission`s (NRC) strategic plan [NUREG-1614, Vol. 1, September 1997] establishes a strategic framework that will guide future decision-making and will help the NRC continue to meet its responsibility for protecting public health and safety, promoting the common defense and security, and protecting the environment. This performance plan complements the agency`s strategic plan by setting annual goals with measurable target levels of performance for FY 1999, as required by the Government Performance and Results Act. No significant contribution was made to the preparation of the performance plan by any non-Federal entity. However, a contractor was used to help facilitate discussions and resolution of issues. Within six months after the close of FY 1999, the NRC will submit to the President and the Congress a report on program performance for FY 1999. This performance report will review the success of the agency in achieving the performance goals established for FY 1999. Where those goals have been achieved, the underlying assumptions and strategies will be examined to ensure that continued applicability is warranted in the future. If any of the FY 1999 performance goals are not met, the agency will conduct a thorough analysis of why it did not meet the goal and the actions necessary to meet-the goal in the future. One result of this analysis will be the documentation of plans and schedules for achieving the established performance goal. If the analysis should indicate that the performance goal is impractical or infeasible, the performance report will document why that is the case and what action is recommended.

  19. Off-site emergency preparedness activities within the European Commission

    International Nuclear Information System (INIS)

    Kelly, G.N.

    1998-01-01

    Increasing attention is being given by the European Commission to off-site emergency preparedness as part of its broader contribution to improving nuclear safety in Eastern Europe. The main initiatives being taken or planned by the Commission in this area are summarised. Particular attention is given to two topics: Firstly, the development of the RODOS (Real-time On-line DecisiOn Support) system for supporting off-site emergency management in the event of a nuclear accident; and, secondly, the work of an Inter-Service Group on nuclear Off-Site Emergency Preparedness (OSEP) in Eastern Europe that has been established within the Commission. The contribution that each is making to improving emergency preparedness, both in Eastern Europe and in Europe more widely, is described. (orig.)

  20. European commission contribution to improving off-site emergency preparedness

    International Nuclear Information System (INIS)

    Kelly, G.N.

    1996-01-01

    Increasing attention is being given by the European Commission to off-site emergency preparedness as part of its broader contribution to improving nuclear safety in Eastern Europe. The main initiatives being taken or planned by the Commission in this area are summarized. Particular attention is given to two topics: firstly, the development of the RODOS (Real-time On-line Decision Support) system for supporting off-site emergency management in the event of a nuclear accident; and, secondly, the work of an Inter-Service Group on nuclear Off-Site Emergency Preparedness (OSEP) in Eastern Europe that has recently been established within the Commission. The contribution that each is making to improving emergency preparedness, both in Eastern Europe and in Europe more widely, is described

  1. British Columbia Oil and Gas Commission 2. annual report (1999/2000)

    International Nuclear Information System (INIS)

    2001-01-01

    The British Columbia Oil and Gas Commission (OGC) is a regulatory agency which was created in 1998 to oversee oil and gas industry operations in the province including exploration, development, reclamation and pipeline transportation systems. In addition, the OGC resolves industry land use and economic issues related to Aboriginal Lands on behalf of the province. This annual report highlights the operational performance and outlines business priorities and initiatives. Environmental Fund and Advisory Committee activity were also presented along with financial data for fiscal 1999-2000. Given that the OGC is a young agency, it took the year to stabilize its organization and finalize primary recruitment. Its business processes were also reorganized and streamlined. The year also saw an increase in oil and gas activity in Northeast British Columbia. The process to improve relationships with First Nations was initiated. All of the operations and application functions in Fort St. John were consolidated. Applications received during 1999-2000 were 63 per cent higher than the previous year. The OGC also conducted more than 2500 consultations with Treaty 8 First Nations on various applications. The future will focus on innovation and the effective use of technology with a leading edge workforce. 1999/2000 saw record rig activity for the province. In January 2000 there were more than 120 rigs operating in the province. tabs

  2. International network non-energy use and CO2 emissions (NEU-CO2). An activity within the European Commission's ENRICH programme, DG RTD, 'Environment and Climate'. Final report of the first phase of the network (January 1999 - June 2000)

    International Nuclear Information System (INIS)

    Patel, M.; Gielen, D.; Kilde, N.; Simmons, T.

    2000-07-01

    This report concludes the first phase of the NEU-CO 2 network, covering the period from January 1999 to June 2000. Within this period, two workshops were held, one in Paris in September 1999 and the other in Brussels in April 2000. The results of these workshops represent the basis of this report. The workshop papers have also been compiled in workshop proceedings which are publicly available. Due to the success of the NEU-CO 2 network, the partners decided to apply for the continuation of this activity which was recently accepted by the European Commission. The second phase of the of the NEU-CO 2 network will start in Fall 2000 and will continue for 18 months. This will allow the NEU-CO 2 network to improve the methods applied, to close data gaps, to check the preliminary conclusions given in this report and to provide consolidated results and recommendations by mid 2002. The ultimate goal of the NEU-CO 2 network is to contribute to an improvement of the IPCC guidelines in the area of non-energy use and to provide inventorists with tools and methods to estimate more accurately non-energy CO 2 emissions. (orig.)

  3. Replacement, Reduction, Refinement - Animal welfare progress in European Pharmacopoeia monographs: activities of the European Pharmacopoeia Commission from 2007 to 2017.

    Science.gov (United States)

    Lang, C; Kolaj-Robin, O; Cirefice, G; Taconet, L; Pel, E; Jouette, S; Buda, M; Milne, C; Charton, E

    2018-01-01

    Since the opening for signature of the European Convention for the Protection of Animals Used for Experimental and Other Scientific Purposes in 1986, the European Pharmacopoeia Commission and its experts have carried out a programme of work committed to Replacing, Reducing and Refining (3Rs) the use of animals for test purposes. While updates on achievements in the field of the 3Rs are regularly provided, this article summarises the activities of the Ph. Eur. Commission in this field within the last decade.

  4. Nuclear power and sustainable energy supply for Europe. European Commission

    International Nuclear Information System (INIS)

    Hilden, W.

    2005-01-01

    The right energy mix is decisive. The European Commission feels that nuclear power can make an important contribution towards sustainable energy supply in Europe. Nuclear power should keep its place in the European energy mix. One important aspect in this regard is improved public acceptance through communication, transparency, and confidence building. High safety standards and a credible approach to the safe long-term management of radioactive waste are major components of this sustainable energy source. (orig./GL)

  5. Commission of the European Communities - Review of fast reactor activities, March 1979

    International Nuclear Information System (INIS)

    Balz, W.

    1979-01-01

    The Commission of the European Communities pursued its activities on the lines described earlier. Besides the execution of a research programme in its Joint Research Centre the Commission endeavoured to support the development and demonstration of fast reactors. Most of the latter activities were performed in the frame of the Fast Reactor Coordinating Committee

  6. The European Commission's light bulb decree: Another costly regulation?

    International Nuclear Information System (INIS)

    Frondel, Manuel; Lohmann, Steffen

    2011-01-01

    Since September 2009, Regulation 244/2009 of the European Commission enforces the gradual phase-out of incandescent light bulbs. As of September 2012, only energy-efficient lighting sources will be allowed for sale. Among these are halogen light bulbs, light-emitting diodes (LED), or compact fluorescent light bulbs-often referred to as energy-saving light bulbs. The Commission's justification for the phase-out of conventional light bulbs maintains that a reduction in the electricity consumed will not only lead to lower energy cost for private households and industrial consumers, but at the same time lead to a decrease in greenhouse gas emissions. This article discusses possible reasons for the slow market diffusion of energy-saving light bulbs and shows that the investment in energy-efficient light bulbs does not necessarily lead to significant cost reductions. Drawing on some illustrative examples, we demonstrate that the use of cheaper incandescent bulbs instead of energy-saving light bulbs can be economically rational in cases of rather low usage times, in which the higher initial purchasing price might only pay off after very long time spans. Furthermore, due to the coexistence with the European Emissions Trading Scheme (ETS), this regulation attains no additional emission reductions beyond those achieved by the ETS alone. We thus conclude that the general ban of incandescent light bulbs is inappropriate and should be abolished by the Commission. - Research highlights: → This article discusses reasons for the slow market diffusion of energy-saving light bulbs. → We show that using incandescent bulbs can be rational in cases of rather low usage times. → We conclude that the general ban of incandescent light bulbs should be abolished by the Commission.

  7. Different associations of CD45 isoforms with STAT3, PKC and ERK regulate IL-6-induced proliferation in myeloma.

    Directory of Open Access Journals (Sweden)

    Xu Zheng

    Full Text Available In response to interleukin 6 (IL-6 stimulation, both CD45RO and CD45RB, but not CD45RA, translocate to lipid rafts. However, the significance of this distinct translocation and the downstream signals in CD45 isoforms-participated IL-6 signal are not well understood. Using sucrose fractionation, we found that phosphorylated signal transducer and activator of transcription (STAT3 and STAT1 were mainly localized in lipid rafts in response to IL-6 stimulation, despite both STAT3 and STAT1 localizing in raft and non-raft fractions in the presence or absence of IL-6. On the other hand, extracellular signal-regulated kinase (ERK, and phosphorylated ERK were localized in non-raft fractions regardless of the existence of IL-6. The rafts inhibitor significantly impeded the phosphorylation of STAT3 and STAT1 and nuclear translocation, but had little effect on (and only postponing the phosphorylation of ERK. This data suggests that lipid raft-dependent STAT3 and STAT1 pathways are dominant pathways of IL-6 signal in myeloma cells. Interestingly, the phosphorylation level of STAT3 but not STAT1 in CD45+ cells was significantly higher compared to that of CD45- cells, while the phosphorylation level of ERK in CD45+ myeloma cells was relatively low. Furthermore, exogenously expressed CD45RO/RB significantly enhanced STAT3, protein kinase C (PKC and downstream NF-κB activation; however, CD45RA/RB inhibited IL-6-induced ERK phosphorylation. CD45 also enhanced the nuclear localization of STAT3 but not that of STAT1. In response to IL-6 stimulation, CD45RO moved into raft compartments and formed a complex with STAT3 and PKC in raft fraction, while CD45RA remained outside of lipid rafts and formed a complex with ERK in non-raft fraction. This data suggests a different role of CD45 isoforms in IL-6-induced signaling, indicating that while CD45RA/RB seems inhibit the rafts-unrelated ERK pathway, CD45RO/RB may actually work to enhance the rafts-related STAT3 and PKC

  8. Charities' response to the European Commission call of interest for their involvement in the European Research Area

    CERN Document Server

    Sessano, D.

    2003-01-01

    This paper presents an exploratory study to investigate what could be the role of the charities concerned with scientific research in the European Research Area (ERA). The analysis particularly concentrates on UK and Italy. The questions on which the exploratory study was developed are: 1. “In what specific areas of the ERA did the European Commission (EC) for the involvement of charities? And could there be other areas in which charities might participate?” 2. “Given the role and situation of charities in UK and Italy, what role, if any, could they be willing to play in the ERA? Is it the same as the one proposed by the Commission or not?” In order to answer these questions, the following discussion will focus at first on a short overview of the charity sector, both at the general level and at the national level in UK and Italy. Then a brief presentation of the European Research Area will be given. The hypotheses of the study will then be presented, followed by a methodological section. Results wi...

  9. Monitoring and analysis of technology transfer and intellectual property regimes and their use results of a study carried out on behalf of the European Commission (DG Research)

    CERN Document Server

    Van Eecke, Patrick; Bolger, P; Truyens, M

    2008-01-01

    This report presents the results of a three-year study commissioned by the European Commission (DG Research) regarding the monitoring, analysis and use of technology transfer and intellectual property regimes in the European Union. This study was organised in the context of the 6th Framework Programme for R&D, and was jointly carried out by law firms Mason Hayes+Curran (Dublin) and DLA Piper (Brussels).

  10. CRASH - Community Road Accident System Homepage : feasibility study on a European Road Safety Information System, financially supported by the European Commission.

    NARCIS (Netherlands)

    Brouwer, M. Poppe, F. Blokpoel, A. & Kars, V.

    2000-01-01

    This report is the result of a feasibility study, financially supported by the European Commission. The study investigated the possibilities for the development and maintenance of a European Road Safety Information System with relevant and internationally comparable information. Recommendations on

  11. Measuring the Extent of European State Aid Control : An Econometric Analysis of the European Commission Decisions

    NARCIS (Netherlands)

    Brouwer, E.; Ozbugday, F.C.

    2011-01-01

    This paper provides an analysis of the European Commission (EC) decisions on state aid control using data on 550 state aid cases approved by the EC between 1998 and 2009. More specifically, we measure the determinants of the duration of state aid, total budget of state aid and daily budget of state

  12. Measuring the Extent of European State Aid Control : An Econometric Analysis of the European Commission Decisions

    NARCIS (Netherlands)

    Brouwer, E.; Ozbugday, F.C.

    2010-01-01

    This paper provides an analysis of the European Commission (EC) decisions on state aid control using data on 550 state aid cases approved by the EC between 1998 and 2009. More specifically, we measure the determinants of the duration of state aid, total budget of state aid and daily budget of state

  13. Commission of the European Communities review of fast reactor activities, March 1981

    Energy Technology Data Exchange (ETDEWEB)

    Balz, W [Commission of the European Communities, Brussels (Belgium)

    1981-05-01

    The Commission of the European Communities continued its activities in the field of fast reactors development essentially in the frame of the Fast Reactor Coordinating Committee (FRCC) and by execution of a Reactor Programme at its Joint Research Center (JRC). The study was concerned with introducing fast reactors into European Community, elaboration of preliminary safety criteria and guidelines for typical fast reactor accidents; codes and standards; LMFBR safety, fuel, fuel cycle safety.

  14. Commission of the European Communities review of fast reactor activities, March 1981

    International Nuclear Information System (INIS)

    Balz, W.

    1981-01-01

    The Commission of the European Communities continued its activities in the field of fast reactors development essentially in the frame of the Fast Reactor Coordinating Committee (FRCC) and by execution of a Reactor Programme at its Joint Research Center (JRC). The study was concerned with introducing fast reactors into European Community, elaboration of preliminary safety criteria and guidelines for typical fast reactor accidents; codes and standards; LMFBR safety, fuel, fuel cycle safety

  15. Commission of the European Communities. Review of fast reactor activities - April 1984

    International Nuclear Information System (INIS)

    Balz, W.

    1984-01-01

    The frame in which the activities of the Commission of the European Communities in the field of fast breeders are executed was described at earlier meetings. The present review is therefore limited to a brief report on same highlights

  16. Information report by the Commission for European Affairs on the second Energy-Climate Package - Nr 2294

    International Nuclear Information System (INIS)

    Leroy, Arnaud

    2014-01-01

    This report first recalls the objectives of the first Energy-Climate package and outlines that its implementation revealed some gaps despite some promising results. The author then notices that the current context requires new efforts, and that new objectives have been defined to promote energy transition: propositions of the European Commission are recalled as well as the opinions of the European Parliament and European Council. The author discusses the ambition of this second package as a lever for a transition towards a new growth model. He discusses divergence issues between countries, and the triple challenge (emission reduction, share of renewable energy, energy efficiency), and outlines that energy transition represents a new industrial project for Europe, and that the evolution towards a Union of energy is needed. Works of the French Commission for European Affairs are briefly reported, and the proposal for a European resolution is given

  17. 36 CFR 401.6 - Approval by National Commission of Fine Arts.

    Science.gov (United States)

    2010-07-01

    ... Commission of Fine Arts. 401.6 Section 401.6 Parks, Forests, and Public Property AMERICAN BATTLE MONUMENTS COMMISSION MONUMENTS AND MEMORIALS § 401.6 Approval by National Commission of Fine Arts. A design for a... Commission of Fine Arts before the Commission can accept it. ...

  18. Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

    Science.gov (United States)

    Zhang, Hui; Guo, Qiufen; Wang, Chong; Yan, Lei; Fu, Yibing; Fan, Mingjun; Zhao, Xingbo; Li, Mingjiang

    2013-08-25

    Dual-specificity phosphatase 6 (Dusp6) is a negative feedback mechanism of fibroblast growth factors (FGFs)/mitogen-activated protein kinase (MAPK)/ERK1/2 signaling. The aim of this study was to explore the expression of Dusp6 in human endometrial adenocarcinomas and the role of Dusp6 expression in the growth regulation of endometrial adenocarcinoma cell. We found that Dusp6 was over-expressed in human endometrial adenocarcinomas. In Ishikawa cells, plasmid-driven Dusp6 expression efficiently blocked the activity of FGF2-induced MAPK/ERK1/2 signaling. Unexpectedly, Dusp6 expression significantly enhanced the growth of Ishikawa cells. In Dusp6 forced-expression cells, 17β-estradiol stimulation increased the cell growth by all most threefolds. In addition, progesterone treatment reduced the cell growth to about half both in Ishikawa cells with and without forced-Dusp6-expression. Dusp6 over-expression is involved in the pathogenesis and development of human endometrial adenocarcinomas. Dusp6 functions as a negative regulator of FGF2/ERK1/2 signaling but enhances the growth and 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell. Copyright © 2013. Published by Elsevier Ireland Ltd.

  19. Feedback from European Social Partners as Part of the Consultation on the Commission's Memorandum on Lifelong Learning. Supporting Document to the Communication from the Commission Making a European Area of Lifelong Learning a Reality.

    Science.gov (United States)

    Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

    This document provides European social partners' responses to the Commission's memorandum on lifelong learning. Part 1, Opinion of the European Center of Enterprises, makes comments and proposals related to the memorandum's six key messages, which are new basic skills for all; more investment in human resources; innovation in teaching and…

  20. The European Commission's light bulb decree: Another costly regulation?

    Energy Technology Data Exchange (ETDEWEB)

    Frondel, Manuel, E-mail: frondel@rwi-essen.de [Ruhr-University Bochum (RUB), Ruhr-Graduate School in Economics (RGS Econ) (Germany); Rheinisch-Westfaelisches Institut fuer Wirtschaftsforschung (RWI), Hohenzollernstr. 1-3, 45128 Essen (Germany); Lohmann, Steffen [Rheinisch-Westfaelisches Institut fuer Wirtschaftsforschung (RWI), Hohenzollernstr. 1-3, 45128 Essen (Germany); Tinbergen Institute (Netherlands)

    2011-06-15

    Since September 2009, Regulation 244/2009 of the European Commission enforces the gradual phase-out of incandescent light bulbs. As of September 2012, only energy-efficient lighting sources will be allowed for sale. Among these are halogen light bulbs, light-emitting diodes (LED), or compact fluorescent light bulbs-often referred to as energy-saving light bulbs. The Commission's justification for the phase-out of conventional light bulbs maintains that a reduction in the electricity consumed will not only lead to lower energy cost for private households and industrial consumers, but at the same time lead to a decrease in greenhouse gas emissions. This article discusses possible reasons for the slow market diffusion of energy-saving light bulbs and shows that the investment in energy-efficient light bulbs does not necessarily lead to significant cost reductions. Drawing on some illustrative examples, we demonstrate that the use of cheaper incandescent bulbs instead of energy-saving light bulbs can be economically rational in cases of rather low usage times, in which the higher initial purchasing price might only pay off after very long time spans. Furthermore, due to the coexistence with the European Emissions Trading Scheme (ETS), this regulation attains no additional emission reductions beyond those achieved by the ETS alone. We thus conclude that the general ban of incandescent light bulbs is inappropriate and should be abolished by the Commission. - Research Highlights: > This article discusses reasons for the slow market diffusion of energy-saving light bulbs. > We show that using incandescent bulbs can be rational in cases of rather low usage times. > We conclude that the general ban of incandescent light bulbs should be abolished by the Commission.

  1. Ethical evaluation of research proposals by ethics panels advising the European Commission.

    Science.gov (United States)

    Kolar, Roman

    2004-06-01

    Ethical principles with regard to animal experimentation are referred to in European Union (EU) legislation and other official documents. Therefore, applications for funding of research under the EU's research programme may undergo an ethical review that is carried out by so-called ethics panels, consisting of experts chosen by the European Commission. The work of these panels differs substantially from that of other ethical committees, as they exist on the institutional, local, regional or national level. Their main purpose is not to decide whether a proposed research can be regarded legal, and therefore should be endorsed or licensed; instead, it is to help the Commission in prioritising its funding. The panels may examine other ethical aspects than those of animal experimentation or animal welfare alone, such as the use of human volunteers. This is reflected by the composition of the panels. Their decisions are normally based on consensus. Even though these decisions may refer to EU legislation, the criteria applied are not restricted to those provided by this legislation. Nevertheless, the various aspects of the Commission's ethical evaluation system (e.g. formal and practical basic conditions, information content of applications, type of decisions taken, lacking of any quality control) offers opportunities for improvement.

  2. The position of petroleum industry on the European Commission strategy against acidification; Position de l`industrie petroliere sur la communication de la commission europeenne sur la strategie acidificaiton

    Energy Technology Data Exchange (ETDEWEB)

    Canton-Lauga, P. [Union Francaise des Industries Petrolieres (UFIP), 75 - Paris (France)

    1997-12-31

    The French Petroleum industry presents several objections to the projected European Commission program concerning the reduction of air pollution and acidification: the limitation levels which are set for 2010 are practically impossible to sustain, and will induce a considerable cost for the european countries; the models that were used (Rains) by the Commission are not sufficiently precise and taking 1990 as a reference year does not take into consideration the important pollution emission reduction achieved by France before 1990; the Commission seems to consider mainly sulfur contained in liquid fuels, although coal represents 62 pc of sulfur dioxide emission in Europe. Amendment propositions are presented

  3. Government Performance and Results Act: Performance plan FY 1999, U.S. Nuclear Regulatory Commission. Volume 1

    International Nuclear Information System (INIS)

    Fuches, J.L.

    1998-02-01

    The Nuclear Regulatory Commission's (NRC) strategic plan [NUREG-1614, Vol. 1, September 1997] establishes a strategic framework that will guide future decision-making and will help the NRC continue to meet its responsibility for protecting public health and safety, promoting the common defense and security, and protecting the environment. This performance plan complements the agency's strategic plan by setting annual goals with measurable target levels of performance for FY 1999, as required by the Government Performance and Results Act. No significant contribution was made to the preparation of the performance plan by any non-Federal entity. However, a contractor was used to help facilitate discussions and resolution of issues. Within six months after the close of FY 1999, the NRC will submit to the President and the Congress a report on program performance for FY 1999. This performance report will review the success of the agency in achieving the performance goals established for FY 1999. Where those goals have been achieved, the underlying assumptions and strategies will be examined to ensure that continued applicability is warranted in the future. If any of the FY 1999 performance goals are not met, the agency will conduct a thorough analysis of why it did not meet the goal and the actions necessary to meet-the goal in the future. One result of this analysis will be the documentation of plans and schedules for achieving the established performance goal. If the analysis should indicate that the performance goal is impractical or infeasible, the performance report will document why that is the case and what action is recommended

  4. Beam commission of the high intensity proton source developed at INFN-LNS for the European Spallation Source

    Science.gov (United States)

    Neri, L.; Celona, L.; Gammino, S.; Miraglia, A.; Leonardi, O.; Castro, G.; Torrisi, G.; Mascali, D.; Mazzaglia, M.; Allegra, L.; Amato, A.; Calabrese, G.; Caruso, A.; Chines, F.; Gallo, G.; Longhitano, A.; Manno, G.; Marletta, S.; Maugeri, A.; Passarello, S.; Pastore, G.; Seminara, A.; Spartà, A.; Vinciguerra, S.

    2017-07-01

    At the Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (INFN-LNS) the beam commissioning of the high intensity Proton Source for the European Spallation Source (PS-ESS) started in November 2016. Beam stability at high current intensity is one of the most important parameter for the first steps of the ongoing commissioning. Promising results were obtained since the first source start with a 6 mm diameter extraction hole. The increase of the extraction hole to 8 mm allowed improving PS-ESS performances and obtaining the values required by the ESS accelerator. In this work, extracted beam current characteristics together with Doppler shift and emittance measurements are presented, as well as the description of the next phases before the installation at ESS in Lund.

  5. Functional Redundancy of ERK1 and ERK2 MAP Kinases during Development

    Directory of Open Access Journals (Sweden)

    Christophe Frémin

    2015-08-01

    Full Text Available ERK1 and ERK2 are the effector kinases of the ERK1/2 MAP-kinase signaling pathway, which plays a central role in transducing signals controlling cell proliferation, differentiation, and survival. Deregulated activity of the ERK1/2 pathway is linked to a group of developmental syndromes and contributes to the pathogenesis of various human diseases. One fundamental question that remains unaddressed is whether ERK1 and ERK2 have evolved unique physiological functions or whether they are used redundantly to reach a threshold of global ERK activity. Here, we show that the extent of development of the mouse placenta and embryo bearing different combinations of Erk1 and Erk2 alleles is strictly correlated with total ERK1/2 activity. We further demonstrate that transgenic expression of ERK1 fully rescues the embryonic and placental developmental defects associated with the loss of ERK2. We conclude that ERK1 and ERK2 exert redundant functions in mouse development.

  6. The european ALARA network

    International Nuclear Information System (INIS)

    Croueail, P.; Lefaure, C.; Croft, J.

    2000-01-01

    Throughout the 1980s and early 1990s the European Commission sponsored projects on the understanding and practical implementation of the ALARA principle. These projects helped ensure that ALARA was integrated into many organisations radiation protection programmes, particularly in the nuclear industry. However there was still much to be done in the non-nuclear sector, as well as for the management of internal exposure. Therefore, the European Commission decided to set up, as of the first January 1996, a European ALARA Network (EAN) whose main goals are to: Further promote ALARA within non nuclear industry, research and the nuclear cycle; Provide a means for feedback experience and the exchange and dissemination of good radiological protection practices in these areas; Initiate proposals for research projects and workshops on topics dealing with optimisation of radiological protection for all types of occupational exposure. The Network has a Steering Committee of experts from 11 countries, with CEPN being the co-ordinator. Twice yearly, the EAN products for the international community a European ALARA Newsletter that reaches several thousand individuals or institutions, mainly in Europe. Each year since 1997, the EAN has organised an ALARA workshop attended by 60 to 80 experts from about ten countries. The first three Workshops were devoted to: ALARA and Decommissioning (1997, Saclay, France), Good Radiation Practices in Industry and Research (1998, Chilton, United Kingdam), and ALARA and Internal Exposure (1999, Munich, Germany). Each of these Workshops gave rise to sets of recommendations to the European Commission which included proposals for further research, modification of regulations, and actions to support feedback experience within the member states. (author)

  7. Direct-to-consumer advertising of prescription drugs: European Commission persists in putting industry's interests first.

    Science.gov (United States)

    2013-01-01

    In late September 2010, Members of the European Parliament (MEPs) issued their verdict on European Commission proposals aimed at lifting the ban on pharmaceutical companies communicating directly with the general public about prescription drugs. The MEPs were able to limit the scope of some of the more harmful aspects of these proposals, in particular by proposing that drug regulatory agencies should pre-screen the "information" produced by drug companies before it is made available to the public. In December 2010, faced with ongoing opposition from European Member States, the Commission appeared to back down, announcing that it was drawing up "amended proposals". They were publicly released in February 2012 but still leave the door open to direct-to-consumer advertising of prescription drugs, particularly "reminder advertising". As of 4 July 2012, the amended proposals had not yet been examined by Member States, thus obstructing the legislative process. Public health and management of the costs of social services for Member States are at stake. The Medicines in Europe Forum (MiEF) and the International Society of Drug Bulletins (ISDB) urge Member States to continue to refuse to examine the Commission's proposals, and have drawn up concrete counterproposals that would enable the general public to obtain relevant health information.

  8. Scenarios for the implementation of daytime running lights in the European Union : study in the framework of a European Commission project, Work Package 4.

    NARCIS (Netherlands)

    Commandeur, J.J.F. Mathijssen, M.P.M. Elvik, R. Janssen, W. & Kallberg, V.-P.

    2004-01-01

    This report is the last part of the documentation of a project funded by the European Commission, designed to assess the effects of Daytime Running Lights (DRL) and possible strategies for implementing the use of DRL in the European Union (EU). The general objective of the present report is to

  9. Information report by the Commission for European Affairs about energy transition in the European Union. Nr 596

    International Nuclear Information System (INIS)

    Michels, Thierry

    2018-01-01

    In order to deal with the issue of energy transition, the European Commission has implemented a complete reworking of the European climate and energy framework, by updating certain existing legislative texts and by putting forward several new ones. In this context, this report first gives an overview of the issue of climate change, and outlines that the struggle against it is a necessity and an obligation, and even a moral one after the US withdrawal from the Paris agreement. In the second part, the author discusses the perfectible efficiency of European regulations related to energy and climate issues, and outlines remaining obstacles and weaknesses for the implementation of an efficient policy. In the third part, he defines a set of axes of action aimed at improving European objectives and make them in compliance with the Paris agreement: to define a floor price for carbon, to strengthen solidarity between member States, to introduce a framework which would suit innovation development and would make citizen empowerment possible, to ensure a financing which would match challenges, and to systematically integrate renewable energies into negotiations

  10. Updated European Union Risk Assessment Report of Alkanes, C10-13, Chloro

    OpenAIRE

    2008-01-01

    A risk assessment of alkanes, C10-13, chloro (short-chain chlorinated paraffins or SCCPs) produced in accordance with Council Regulation (EEC) 793/93 was published in October 1999 . Subsequent marketing and use restrictions for two uses (metal working and use for fat liquoring of leather) have come into force in the European Union through Directive 2002/45/EC . This Directive also states that all remaining uses of short-chain chlorinated paraffins will be reviewed by the European Commission ...

  11. EDITORIAL: The 15th Central European Workshop on Quantum Optics The 15th Central European Workshop on Quantum Optics

    Science.gov (United States)

    Bozic, Mirjana; Man'ko, Margarita; Arsenovic, Dusan

    2009-07-01

    The development of quantum optics was part and parcel of the formation of modern physics following the fundamental work of Max Planck and Albert Einstein, which gave rise to quantum mechanics. The possibility of working with pure quantum objects, like single atoms and single photons, has turned quantum optics into the main tool for testing the fundamentals of quantum physics. Thus, despite a long history, quantum optics nowadays remains an extremely important branch of physics. It represents a natural base for the development of advanced technologies, like quantum information processing and quantum computing. Previous Central European Workshops on Quantum Optics (CEWQO) took place in Palermo (2007), Vienna (2006), Ankara (2005), Trieste (2004), Rostock (2003), Szeged (2002), Prague (2001), Balatonfüred (2000), Olomouc (1999), Prague (1997), Budmerice (1995, 1996), Budapest (1994) and Bratislava (1993). Those meetings offered excellent opportunities for the exchange of knowledge and ideas between leading scientists and young researchers in quantum optics, foundations of quantum mechanics, cavity quantum electrodynamics, photonics, atom optics, condensed matter optics, and quantum informatics, etc. The collaborative spirit and tradition of CEWQO were a great inspiration and help to the Institute of Physics, Belgrade, and the Serbian Academy of Sciences and Arts, as the organizers of CEWQO 2008. The 16th CEWQO will take place in 2009 in Turku, Finland, and the 17th CEWQO will be organized in 2010 in St Andrews, United Kingdom. The 15th CEWQO was organized under the auspices and support of the Ministry of Science of the Republic of Serbia, the Serbian Physical Society, the European Physical Society with sponsorship from the University of Belgrade, the Central European Initiative, the FP6 Program of the European Commission under INCO project QUPOM No 026322, the FP7 Program of the European Commission under project NANOCHARM, Europhysics Letters (EPL), The European

  12. The financial incentives of European Commission to renewable energies

    International Nuclear Information System (INIS)

    Thomas, A.

    2000-01-01

    The European Commission has an active policy of favoring renewable energies but despite that, only one European program (ALTENER program) is completely dedicated to that topic, in fact various other programs allows the financing of projects concerning renewable energies. This article reviews various current programs that can offer such opportunities. ALTENER-1 was launched in 1993 and ALTENER-2 took over in 1998. ALTENER-2 is funded with 74 millions Euros for 5 years and can finance studies, pilot installations, information and training actions. 2 other programs ETAP and SYNERGY are also concerned by renewable or alternative energies. The fifth PCRD (research and development framing plan) is dedicated to problems of society and then can concern energy. PCRD is made up of 3 major programs (1-the international role of European research, 2-human potential and socio-economic research, 3-innovation and small and medium-scale enterprises) and 4 theme programs (1-energy, environment and durable development, 2-quality of life and management of life resources, 3-friendly information technologies and 4-growth and competitiveness. Each one of these 7 programs can finance actions concerning renewable energies but the first of the theme program is the best opportunity, it is funded with 2 milliards Euros for 5 years. (A.C.)

  13. Rehabilitation robotics in robotics for healthcare ; a roadmap study for the European Commission

    NARCIS (Netherlands)

    Gelderblom, G.J.; Wilt, M.de; Cremers, G.; Rensma, A.R.

    2009-01-01

    To gain understanding in the current status of Robotics in healthcare the European Commission issued a roadmap study into this domain. This paper reports on the main characteristics and results of this study. The study covered the wide domain of Healthcare and in this paper the domains relevant for

  14. The Commission of European Communities project 'mirage' (migration of radionuclides in the geosphere)

    International Nuclear Information System (INIS)

    Come, B.

    1984-01-01

    The co-ordinated project 'MIRAGE' on Migration of Radionuclides in the Geosphere corresponds to the follow-up, from 1983 onwards, of the present activities of the laboratories of the Member States, up to the end of 1984, and of the Joint Research Centre at Ispra, up to the end of 1983. It is concentrated upon the study of the transfer of radioactivity from conditioned waste through the different barriers up to the interface between the geosphere and the biosphere. The MIRAGE project is performed in the framework of the Commission of European Communities (CEC) indirect action programme on Management and Storage of Radioactive Waste, sub-programme Undergound Disposal, and of the CEC direct action programme on Safety of Nuclear Materials at the Joint Research Centre, Ispra Establishment. The total financial commitment in this project is at present 6,384,000 ECU for 1983 and 1984 and the Commission participates financially in each study selected on a cost-sharing basis to a level of about 40% of the total cost. The costs of the studies performed at JRC-Ispra are not included in this amount. The number of organizations, firms and laboratories involved in this project comes to about 40

  15. From use cases of the Joint European Torus towards integrated commissioning requirements of the ITER tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Neto, A.C. [Fusion for Energy, 08019 Barcelona (Spain); Stephen, A. [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Sartori, F.; Cavinato, M. [Fusion for Energy, 08019 Barcelona (Spain); Farthing, J.W. [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Ranz, R.; Saibene, G. [Fusion for Energy, 08019 Barcelona (Spain); Winter, A. [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 St. Paul Lez Durance Cedex (France); Arnoux, G. [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Alves, D. [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa (Portugal); Blackman, T.; Boboc, A.; Card, P.J.; Dalley, S.; Day, I.E. [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); De Tommasi, G. [Consorzio CREATE/Dipartimento di Ingegneria Elettrica e delle Tecnologie dell’Informazione, Università degli Studi di Napoli Federico II, Via Claudio 21, 80125 Napoli (Italy); Drewelow, P.; Elsmore, C.; Ivings, E.; Felton, R. [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); and others

    2015-10-15

    The Joint European Torus (JET) is the largest tokamak currently in operation in the world. One of the greatest challenges of JET is the integrated commissioning of all its major plant systems. This is driven, partially, by the size and complexity of its operational infrastructure and also by the fact that, being an international environment, it has to address the issues of integrating, commissioning and maintaining plant systems developed by third parties. The ITER tokamak, now in construction, is a fusion device twice the size of JET and, being a joint effort between the European Union, China, India, Japan, South Korea, the Russian Federation and the USA, it will share on a wider scale all of the JET challenges regarding integration and integrated commissioning of very large and complex plant systems. With the scope of taking advantage from the history and experience of JET, Fusion for Energy (F4E) has worked together with the Culham Centre for Fusion Energy (CCFE), the host and operator of JET, for the provision of ITER relevant user experiences related to the integrated commissioning of the tokamak. This work presents and discusses the main results and the methods that were used to extract and translate the commissioning experience information into ITER requirements.

  16. Trends in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma Incidence, Vermont 1999-2013.

    Science.gov (United States)

    Owosho, Adepitan A; Wiley, Rashidah; Stansbury, Tessie; Gbadamosi, Semiu O; Ryder, Jon S

    2018-02-09

    This study examines trends in age-adjusted incidence rates of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) in comparison to oral cavity proper squamous cell carcinoma (OSCC) in the population of Vermont from 1999 to 2013. Data on cases of oral and pharynx cancers diagnosed in Vermont between 1999 and 2013 were obtained from the Vermont cancer registry. The age-adjusted incidence rates and annual percentage change of HPV-related OPSCC and OSCC were calculated using Joinpoint trend analysis. Four hundred and thirty-one cases of HPV-related OPSCC were diagnosed from 1999 to 2013. Males constituted 83% (P < 0.0001) of the cases and the 6th decade of life marked the highest incidence. The overall age-adjusted incidence rates for HPV-related OPSCC significantly increased (from 2.39 to 3.86 per 100,000, P < 0.0001). In males, it significantly increased (from 3.62 to 6.93 per 100,000, P < 0.0001), while in females it remained stable (from 1.18 to 1.02 per 100,000, P = 0.28) during 1999-2013. The average rate of HPV-related OPSCC significantly increased by 4.4% annually (P = 0.004). In males the average rate significantly increased by 5.3% annually (P = 0.001) and in females the rate increased by 0.37% annually (P = 0.87). In contrast, age-adjusted overall incidence rates for OSCC significantly decreased (from 3.99 to 3.35 per 100,000, P = 0.018). The overall rate of OSCC decreased by 0.96% annually (P = 0.37) and the highest incidence of cases was in the 7th decade of life. In conclusion, there was an increasing trend of HPV-related OPSCC, specifically in males, and there appears to be a decreasing trend of OSCC in Vermont.

  17. Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

    International Nuclear Information System (INIS)

    Carpenter, Richard L.; Jiang, Yue; Jing, Yi; He, Jun; Rojanasakul, Yon; Liu, Ling-Zhi; Jiang, Bing-Hua

    2011-01-01

    Highlights: ► Chronic exposure to arsenite induces cell proliferation and transformation. ► Arsenite-induced transformation increases ROS production and downstream signalings. ► Inhibition of ROS levels via catalase reduces arsenite-induced cell transformation. ► Interruption of AKT, ERK, or p70S6K1 inhibits arsenite-induced cell transformation. -- Abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidence suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.

  18. THE EUROPEAN COMMISSION – THE EXERCISE OF THE POWERS OF CONTROL AND MONITORING OF THE ENFORCEMENT OF THE LEGISLATION OF THE EUROPEAN UNION IN THE MOLDOVA NOUA CASE

    Directory of Open Access Journals (Sweden)

    Adriana Deac

    2014-11-01

    Full Text Available One of the competencies that the EU Treaties confer to the European Commission is the control and supervision of the application of primary and secondary law and the enforcement of this legislation so it is observed by private persons, Member States and EU institutions2 . Further to an official communiqué in October 2014, the European Commission has announced that it sued Romania at the European Union Court of Justice concerning the failure to observe EU legislation on the treatment of extractive industry waste. Namely, it refers to the Moldova Noua case, in which toxic waste from the zinc and copper mines were discharged into the Bosneag pond. This paper means to present the regulations in the field of extractive industry, the competence of the European Commission regarding the enforcement of EU legislation and the ability to sue a Member State at the EU Court of Justice, when the entity exploiting the zinc and copper deposits is not the Romanian state, but a private law legal person.

  19. Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6

    International Nuclear Information System (INIS)

    Chen, Y.-C.; Chow, J.-M.; Lin, C.-W.; Wu, C.-Y.; Shen, S.-C.

    2006-01-01

    In the present study, we examined the protective mechanism of baicalein (BE) and its glycoside, baicalin (BI), on hydrogen-peroxide (H 2 O 2 )-induced cell death in rat glioma C6 cells. Results of the MTT assay, LDH release assay, and morphological observation showed that H 2 O 2 addition reduced the viability of C6 cells, and this was prevented by the addition of BE but not BI. Incubation of C6 cells with BE significantly decreased the intracellular peroxide level induced by H 2 O 2 according to flow cytometric analysis using DCHF-DA as a fluorescent substrate. Suppression of H 2 O 2 -induced apoptotic events including DNA ladders, hypodiploid cells, and activation of caspases 3, 8, and, 9 by BE but not BI was identified in C6 cells. The cytotoxicity and phosphorylation of ERK proteins induced by H 2 O 2 were blocked by the ERK inhibitor PD98059. Catalase addition prevented H 2 O 2 -induced ROS production, ERKs protein phosphorylation, and cell death, and BE dose-dependently inhibited H 2 O 2 -induced ERK protein phosphorylation in C6 cells. These data suggest that ROS-scavenging activity is involved in BE prevention of H 2 O 2 -induced cell death via blocking ERKs activation. Additionally, BE but not BI induced heat shock protein 32 (HSP32; HO-1) protein expression in both time- and dose-dependent manners, but not heme oxygenase 2 (HO-2), heat shock protein 70 (HSP70), or heat shock protein 90 (HSP90) protein expression. In the absence of H 2 O 2 , BE induces ERKs protein phosphorylation, and HO-1 protein expression induced by BE was blocked by the addition of cycloheximide, actinomycin D, and the ERK inhibitor PD98059. The addition of the HO inhibitor ZnPP inhibited the protective effect of BE against H 2 O 2 -induced cytotoxicity in C6 cells according to the MTT assay and apoptotic morphology under microscopic observation, accompanied by blocking the ROS-scavenging activity of BE in C6 cells. However, BE treatment was unable to protect C6 cells from C2-ceramide

  20. The European Commission Proposal for a Directive on Antitrust Damages: A First Assessment

    NARCIS (Netherlands)

    Cauffman, C.

    2013-01-01

    On 11 June 2013 the European Commission adopted a package of instruments to facilitate damages claims by victims of antitrust damages. The main element of the package is a proposal for a directive on antitrust damages. The aim of this article is to give an overview of the content of the proposed

  1. A critical analysis of political conditionality: political transformation in Turkey from 1999 to 2016

    OpenAIRE

    Sarı, Özge; Sari, Ozge

    2017-01-01

    The thesis applies the external incentives model to the Turkish transformation, by analysing the effectiveness and credibility of political conditionality. The main empirical data used is drawn from the Regular Progress Reports that the European Commission prepared for the period of 1999 when Turkey was granted the status of candidate at the Helsinki Summit until 2016 when the most recent Progress Report was released. The thesis examines that to which extent and under which conditions politic...

  2. Several roads lead to international norms, but few via international socialization. A case study of the European Commission

    NARCIS (Netherlands)

    Hooghe, E.A.E.B.

    2005-01-01

    Can an international organization socialize those who work within it? The European Commission of the European Union is a crucial case because it is an autonomous international organization with a vocation to defend supranational norms. If this body cannot socialize its members, which international

  3. Commission of the European Communities - Activities in the field of fast reactors

    International Nuclear Information System (INIS)

    Balz, W.

    1977-01-01

    The Commission of the European Communities is performing activities in the field of fast reactor on two lines: a) activities aiming to prepare the commercialization of fast reactors by coordination and collaboration between national programmes. b) the execution of an own programme in the Joint Research Centre at Ispra (Italy) and Karlsruhe (Federal Republic of Germany) in the field of FBR safety and research on Pu-bearing fuel

  4. Raising Competitiveness for Tourist Destinations through Information Technologies within the Newest Tourism Action Framework Proposed by the European Commission

    Directory of Open Access Journals (Sweden)

    Ray F. Iunius

    2015-09-01

    Full Text Available Several challenges regarding the European tourism industry were recently identified at EU level which the experts of the European Commission tried to meet, thus formulating several priorities within the newest Tourism Action Framework: Stimulate long-term competitiveness in the European tourism sector, promote the development of sustainable and high-quality tourism, and consolidate the image and promotion of European tourist destinations. Due to the new generational context, information and communications technology ICT and innovation became keywords within the most recent European Tourism Policy. Considering the symbiotic relationship that exists at the European tourism level between sustainable development, innovative ICT solutions, and long-term competitiveness, the decision-makers in European destinations should focus on identifying innovative ways to implement the new Tourism Action Framework adopted by the European Commission, through ICT applications, in order to support long-term competitiveness achievement. Two such authentic proposals are formulated within the present discussion paper: the creation of a decision support system for the management of sustainable European destinations and the development of a trip-planner for quality-sensitive tourists based on an umbrella European certification/labeling system for tourism quality. There is still a fertile field in these areas and, therefore, more innovative ICT tools to support the long-term competitiveness of European tourist destinations can be developed.

  5. How to opt into the Common European Sales Law? Brief comments on the Commission's proposal for a regulation

    NARCIS (Netherlands)

    Hesselink, M.

    2012-01-01

    Unlike the actual text for the proposed Common European Sales Law (CESL), which is based on extensive preparatory work by academics, the regime for opting into the instrument, which is set out in the main text of the proposed regulation, is entirely of the European Commission's own making. The

  6. How to opt into the Common European Sales Law? Brief comments on the Commission's proposal for a regulation

    NARCIS (Netherlands)

    Hesselink, M.W.; Claeys, I.; Feltkamp, R.

    2013-01-01

    Unlike the actual text for the proposed Common European Sales Law (CESL), which is based on extensive preparatory work by academics, the regime for opting into the instrument, which is set out in the main text of the proposed regulation, is entirely of the European Commission's own making. The

  7. The European Federation of Organisations for Medical Physics Policy Statement No. 6.1: Recommended Guidelines on National Registration Schemes for Medical Physicists

    OpenAIRE

    Christofides, S; Isidoro, J; Pesznyak, C; Bumbure, L; Cremers, Fn; Schmidt, WF

    2016-01-01

    This EFOMP Policy Statement is an update of Policy Statement No. 6 first published in 1994. The present version takes into account the European Union Parliament and Council Directive 2013/55/EU that amends Directive 2005/36/EU on the recognition of professional qualifications and the European Union Council Directive 2013/59/EURATOM laying down the basic safety standards for protection against the dangers arising from exposure to ionising radiation. The European Commission Radiation Protection...

  8. European Commission action aimed at constructing a European regulatory framework

    International Nuclear Information System (INIS)

    Ristori, D.

    2010-01-01

    The challenge of a low-carbon economy provides a new incentive for the development of renewable energies as well as of nuclear energy. The latter calls for a high level of safety and security. The EU has a role in providing a legal framework for this purpose as well as ensuring that these standards are respected internationally. For over 50 years the EURATOM Treaty has offered the legal basis for a wide range of initiatives supporting this policy. The EU has competences under chapter 3, 'Health and Safety', for the establishment of basic safety standards for the protection against ionizing radiation. These have extended beyond the scope of nuclear energy and now include medical exposures as well as natural radiation sources. The latest revision of the BSS-Directive, to be proposed in 2011, was an opportunity for the consolidation of all Community legislation. A ruling of the Court of Justice in 1999 paved the way for the establishment of standards on the safety of nuclear installations. A common vision on this matter was achieved through the creation of a body of European Safety Regulators (ENSREG) and the adoption of a specific Safety Directive in 2009. This new Directive translates internationally agreed safety standards into legally binding EU legislation and strengthens the position of national Regulators. (author)

  9. [Effects of electromagnetic radiation on RAF/MEK/ERK signaling pathway in rats hippocampus].

    Science.gov (United States)

    Zuo, Hong-yan; Wang, De-wen; Peng, Rui-yun; Wang, Shui-ming; Gao, Ya-bing; Xu, Xin-ping; Ma, Jun-Jie

    2009-05-01

    To study the development of changes for signaling molecules related to Raf/MEK/ERK pathway in hippocampus of rats after electromagnetic radiation, and investigate the mechanisms of radiation injury. Rats were exposed to X-HPM, S-HPM and EMP radiation source respectively, and animal model of electromagnetic radiation was established. Western blot was used to detect the expression of Raf-1, phosphorylated Raf-1 and phospholylated ERK. The expression of Raf-1 down-regulated during 6 h-14 d after radiation, most significantly at 7 d, and recovered at 28 d. There was no significant difference between the radiation groups. The expression of phosphorylated Raf-1 and phosphorylated ERK both up-regulated at 6 h and 7 d after radiation, more significantly at 6 h, and the two microwave groups were more serious for phosphorylated ERK. During 6 h-14 d after S-HPM radiation, the expression of phosphorylated Raf-1 increased continuously, but phosphorylated ERK changed wavily, 6 h and 7 d were expression peak. Raf/MEK/ERK signaling pathway participates in the hippocampus injury induced by electromagnetic radiation. The excessive activation of ERK pathway may result in the apoptosis and death of neurons, which is the important mechanism of recognition disfunction caused by electromagnetic radiation.

  10. BMP6 down-regulates GDNF expression through SMAD1/5 and ERK1/2 signaling pathways in human granulosa-lutein cells.

    Science.gov (United States)

    Zhang, Xin-Yue; Chang, Hsun-Ming; Taylor, Elizabeth L; Leung, Peter C K; Liu, Rui-Zhi

    2018-05-09

    Bone morphogenetic protein 6 (BMP6) is a critical regulator of follicular development that is expressed in mammalian oocytes and granulosa cells. Glial cell line-derived neurotrophic factor (GDNF) is an intraovarian neurotrophic factor that plays an essential role in regulating mammalian oocyte maturation. The aim of this study was to investigate the effect of BMP6 on the regulation of GDNF expression and the potential underlying mechanisms. We used an established immortalized human granulosa cell line (SVOG cells) and primary human granulosa-lutein cells as in vitro cell models. Our results showed that BMP6 significantly down-regulated the expression of GDNF in both SVOG and primary human granulosa-lutein cells. Using dual inhibition approaches (kinase receptor inhibitor and small interfering RNA knockdown), our results showed that both ALK2 and ALK3 are involved in BMP6-induced down-regulation of GDNF. In addition, BMP6 induced the phosphorylation of SMAD1/5/8 and ERK1/2 but not AKT or p38. Among three downstream mediators, both SMAD1 and SMAD5 are involved in BMP6-induced down-regulation of GDNF. Moreover, concomitant knockdown of endogenous SMAD4 and inhibition of ERK1/2 activity completely reversed BMP6-induced down-regulation of GDNF, indicating that both SMAD and ERK1/2 signaling pathways are required for the regulatory effect of BMP6 on GDNF expression. Our findings suggest an additional role for an intrafollicular growth factor in regulating follicular function through their paracrine interactions in human granulosa cells.

  11. Dietary carbohydrates and change in physical performance of elderly Europeans. SENECA 1993 and 1999

    DEFF Research Database (Denmark)

    Kynde, I; Schroll, K; Tetens, Inge

    2010-01-01

    scores indicate a better physical performance. Habitual diets were measured using diet history interviews and dietary GI and GL were estimated from table values. Setting Eight towns/centres from the Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA) in 1993 and 1999. Subjects...... Seven hundred and sixty-five men and women, 75–80 years old, were examined in 1993; of these, 357 (47 %) were followed up in 1999, at age 80–85 years. Results At baseline, both dietary GI and GL were significantly inversely associated with PPT scores (P = 0·03 and P = 0·05, respectively). When adjusted......Objective To study dietary glycaemic index (GI) and glycaemic load (GL) in association with physical performance in elderly Europeans. Design Cross-sectional and prospective study. Physical performance was measured using the Physical Performance Test (PPT) score on a scale from 0 to 27, where high...

  12. [The EU law on genetically modified organisms: the European Commission changes the strategy in order to allow, restrict, or prohibit its culture].

    Science.gov (United States)

    González Vaqué, Luis

    2010-01-01

    On July 13 2010, the European Commission adopted a series of measures which outline a new approach on Genetically Modified Organisms (GMOs) cultivation in the Member States. This proposal, which still retains the basis of the existing science-based GMO authorisation system, will be implemented through: a Communication from the Commission, explaining the new approach on the freedom for Member States to decide on the cultivation of genetically modified crops; the "Proposal for a Regulation of the European Parliament and of the Council amending Directive 2001/18/EC as regards the possibility for the Member States to restrict or prohibit the cultivation of GMOs in their territory"; and a new "European Commission Recommendation (2010/C 200/01) of 13 July 2010 on guidelines for the development of national co-existence measures to avoid the unintended presence of GMOs in conventional and organic crops".

  13. EC4IT - A Guide to European Commission Projects for CERN/IT department

    CERN Document Server

    Jones, R

    2012-01-01

    European Commission (EC) projects represent an important source of external funding for a number of activities in which IT department is involved. The EC has a set of procedures and formalities for the preparation, negotiation, execution and completion of projects that are different to those normally used at CERN. This document gives an overview of the administrative, financial, reporting and managerial steps involved in participating in an EC project.

  14. Contact Allergy to Preservatives—Is the European Commission a Commendable Risk Manager?

    Directory of Open Access Journals (Sweden)

    Jakob Ferløv Schwensen

    2016-08-01

    Full Text Available Although preservatives are necessary to prevent deterioration by microbial growth in cosmetic products, daily skin contact with preserved cosmetic products may cause a preservative contact allergy. Only preservatives with sufficient pre-market risk assessment, presumably being safe for the consumer from a public health point of view, are permitted for use in cosmetic products in the European Union. Notwithstanding the efforts by the European Commission (EC to avoid epidemics of contact allergy, the former epidemic of contact allergy to methyldibromo glutaronitrile and the unprecedented epidemic of contact allergy to methylisothiazolinone show the procrastination of the European Union risk management process for cosmetic ingredients. Timely risk management is of the utmost importance to avoid rapidly increasing numbers of contact allergy to turn into full-blown epidemics. It is therefore proposed that in order to avoid future epidemics of contact allergy to preservatives, the allowed preservatives in cosmetic products should be entered onto Annex V on a time-limited basis only, and they must be re-evaluated in order to stay on Annex V.

  15. Gaz de France and Ruhrgas have made commitments towards the European commission

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    The European Commission's DG Competition has decided to close its investigation into the alleged refusal by the French and German gas companies Gaz de France and Ruhrgas to grant the Norwegian subsidiary of the US gas producer Marathon access to their gas networks. Both companies have offered commitments to improve third party access to their respective transport networks in order to allow customers in France and Germany to benefit more effectively from the opening of the gas markets to competition. (author)

  16. GEP100/Arf6 is required for epidermal growth factor-induced ERK/Rac1 signaling and cell migration in human hepatoma HepG2 cells.

    Directory of Open Access Journals (Sweden)

    ZhenZhen Hu

    Full Text Available BACKGROUND: Epidermal growth factor (EGF signaling is implicated in the invasion and metastasis of hepatoma cells. However, the signaling pathways for EGF-induced motility of hepatoma cells remain undefined. METHODOLOGY/PRINCIPAL FINDINGS: We found that EGF dose-dependently stimulated the migration of human hepatoma cells HepG2, with the maximal effect at 10 ng/mL. Additionally, EGF increased Arf6 activity, and ectopic expression of Arf6 T27N, a dominant negative Arf6 mutant, largely abolish EGF-induced cell migration. Blocking GEP100 with GEP100 siRNA or GEP100-△PH, a pleckstrin homology (PH domain deletion mutant of GEP100, blocked EGF-induced Arf6 activity and cell migration. EGF also increased ERK and Rac1 activity. Ectopic expression GEP100 siRNA, GEP100-△PH, or Arf6-T27N suppressed EGF-induced ERK and Rac1 activity. Furthermore, blocking ERK signaling with its inhibitor U0126 remarkably inhibited both EGF-induced Rac1 activation as well as cell migration, and ectopic expression of inactive mutant form of Rac1 (Rac1-T17N also largely abolished EGF-induced cell migration. CONCLUSIONS/SIGNIFICANCE: Taken together, this study highlights the function of the PH domain of GEP100 and its regulated Arf6/ERK/Rac1 signaling cascade in EGF-induced hepatoma cell migration. These findings could provide a rationale for designing new therapy based on inhibition of hepatoma metastasis.

  17. Transcriptional Regulation of Δ6-Desaturase by Peroxisome Proliferative-Activated Receptor δ Agonist in Human Pancreatic Cancer Cells: Role of MEK/ERK1/2 Pathway

    Directory of Open Access Journals (Sweden)

    Maryam Darabi

    2013-01-01

    Full Text Available The Δ6-desaturase (Δ6D, also known as fatty acid desaturase 2, is a regulatory enzyme in de novo fatty acid synthesis, which has been linked to obesity and diabetes. The aim of the present study was to investigate the effect of peroxisome proliferative-activated receptor δ (PPARδ agonist and MEK/ERK1/2-dependent pathway on the expression of Δ6D in human pancreatic carcinoma cell line PANC-1. PANC-1 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPARδ agonist GW0742. Changes in mRNA and protein expression of Δ6D were then determined using real-time RT-PCR and Western blot, respectively. The expression of Δ6D (P40%, P25%, P<0.05 pretreatment. PPARδ and MEK/ERK1/2 signaling pathways affect differentially the expression of Δ6D in pancreatic cancer cells. Furthermore, there may be an inhibitory crosstalk between these two regulatory pathways on the mRNA expression of Δ6D and subsequently on Δ6D protein expression.

  18. Commission of the European Communities: Review of fast reactor activities performed during 1990

    International Nuclear Information System (INIS)

    Balz, W.

    1991-01-01

    In the field of fast reactors the Commission of the European Communities (CEC) is conducting coordination and harmonization activities at the Brussels headquarters and performing research in its Joint Research Center. The Fast Reactor Coordinating Committee (FRCC) is performing coordination and harmonization activities taking account of the collaboration agreements within the European Fast Reactor (EFR) context. Since the EFR collaboration does not involve all Member States of the European Community the FRCC should establish a link between the EFR countries and other countries. The FRCC discussed R and D activities suitable for a concerted action in a community frame. The Committee also discussed actinide transmutation aspects in LMFBRs. The discussions were based on the results of a study sponsored by the CEC to assess the characteristics of a large core (3600 MWth) with variable actinide content (3-15%). The FRCC received regularly reports on results from current R and D programmes, especially from those related to EFR. (author). 2 figs, 2 tabs

  19. The European Commission: nuclear power has an important role to play

    International Nuclear Information System (INIS)

    Anon.

    2008-01-01

    The European Commission (E.C.) thinks that nuclear power has an important role to play: first to reduce CO 2 emissions and secondly to reinforce energy self-reliance of the member states. The decision to introduce nuclear power in their energy mix belongs to every state but the E.C. has also highlighted that if adequate investment are quickly made 2 thirds of the electricity produced in the European Union in 2010 could by from low-carbon-emitting sources. Today with 148 reactors operating in 15 member countries nuclear power contributes to 1 third of the electricity produced. Another issue that is looming is the security of electricity supplying. A study has shown that the security level is worsening (particularly in winter) because of the greater part of wind energy in the energy mix as wind energy is not necessarily available when energy demand is peaking. The E.C. has proposed a new directive drawing a common standard frame for nuclear safety requirements concerning design, site selection, maintenance, operation and decommissioning of nuclear facilities. Each member state will have the choice to implement stiffer regulations. The European Union must reduce its dependency on Russian gas by increasing its storing capacities, by easing gas exchanges between member states and by importing more liquefied natural gas. European member states will have to invert 1000*10 9 euros in gas and electrical power infrastructures in the next 25 years. (A.C.)

  20. Status report 1999; Rapport Annuel 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-01

    This 1999 annual report of the french Commissariat a l'Energie Atomique (Cea), gives a general overview of its activities, organization and international relations. The main subjects presented are: the energy policy in the nuclear energy (fuel cycle, reactors, management,thermonuclear fusion) the national defense contribution, the research program, the nuclear safety, the technology assessment, the valorization and transfer of knowledge, the scientific prices and the committees, councils and commissions. (A.L.B.)

  1. Status report 1999; Rapport Annuel 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-01

    This 1999 annual report of the french Commissariat a l'Energie Atomique (Cea), gives a general overview of its activities, organization and international relations. The main subjects presented are: the energy policy in the nuclear energy (fuel cycle, reactors, management,thermonuclear fusion) the national defense contribution, the research program, the nuclear safety, the technology assessment, the valorization and transfer of knowledge, the scientific prices and the committees, councils and commissions. (A.L.B.)

  2. European Commission and IAEA Celebrate 30 Years Co-operation on Nuclear Safeguards

    International Nuclear Information System (INIS)

    2011-01-01

    Full text: Today the European Commission and the International Atomic Energy Agency (IAEA) celebrate 30 years of cooperation in the safeguarding of nuclear materials and facilities. This anniversary is marked by an event at the AEA Headquarters in Vienna. The Joint Research Centre (JRC) of the European Commission has provided scientific and echnical support to the work of IAEA since 1981, with over 100 scientists and technicians working on more than 25 projects. The anniversary is also an opportunity for both parties to plan their future joint activities. ''Nuclear safety and security are absolute priorities for the EU and in this context expertise on nuclear safeguards is extremely important for global security,'' says Dominique Ristori, Director General of the Joint Research Centre. ''The JRC is constantly at work on state-of-the-art technologies for nuclear safeguards and training of nuclear inspectors to stay ahead of the evolving challenges, in its long-standing cooperation in support of the Agency's mission.'' ''The JRC has provided us with vital scientific and technical support which has helped us to implement safeguards more effectively,'' said Herman Nackaerts, Deputy Director General for Safeguards at the IAEA. ''This has had a positive impact on the security of all the citizens of the European Union and beyond.'' An important chapter in the collaboration between the two organisations is training: high-quality training programmes are provided by the JRC for the next generation of IAEA and EURATOM Inspectors. Other examples of cooperation include special tools to improve environmental particle analysis, a 3D laser-based verification system of nuclear facilities, new nuclear reference materials, and secure sealing for underwater nuclear spent fuel assemblies. Future cooperation between the JRC and IAEA will be in line with the new priorities of the IAEA to further increase the safeguards' effectiveness and efficiency, through a customized approach

  3. New body starts independent advisory work for EU Commission

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    The new European Science and Technology Assembly (ESTA) had its first General Assembly on 6-7 September in Brussels. According to Commissioner A. Ruberti, the European Union's 'Minister' for science, technology and higher education, who has been largely responsible for ESTA's creation, the tasks of the new and independent Assembly of Scientists are to give opinions and advice and to help the European Commission implement the EU research policy

  4. Point Climat no. 17 'The role of the forestry sector in reducing European emissions: the European Commission starts with a tally'

    International Nuclear Information System (INIS)

    Bellassen, Valentin; Deheza, Mariana

    2012-01-01

    Among the publications of CDC Climat Research, 'Climate Briefs' presents, in a few pages, hot topics in climate change policy. This issue addresses the following points: On March 12 2012, after two years of consultations and reviews, the European Commission published a decision proposal regarding the inclusion of the land use and forestry sector in European climate policy. The aim of this proposal is to impose accounting rules that are consistent with the decisions of the United Nations Framework Convention on Climate Change (UNFCCC), and to harmonise them between Member States. Meanwhile, the issue of economic incentives aimed at guaranteeing the sector's contribution to climate mitigation is postponed until a later date

  5. The ERK5 and ERK1/2 signaling pathways play opposing regulatory roles during chondrogenesis of adult human bone marrow-derived multipotent progenitor cells.

    Science.gov (United States)

    Bobick, Brent E; Matsche, Alexander I; Chen, Faye H; Tuan, Rocky S

    2010-07-01

    Adult human bone marrow-derived multipotent progenitor cells (MPCs) are able to differentiate into a variety of specialized cell types, including chondrocytes, and are considered a promising candidate cell source for use in cartilage tissue engineering. In this study, we examined the regulation of MPC chondrogenesis by mitogen-activated protein kinases in an attempt to better understand how to generate hyaline cartilage in the laboratory that more closely resembles native tissue. Specifically, we employed the high-density pellet culture model system to assess the roles of ERK5 and ERK1/2 pathway signaling in MPC chondrogenesis. Western blotting revealed that high levels of ERK5 phosphorylation correlate with low levels of MPC chondrogenesis and that as TGF-beta 3-enhanced MPC chondrogenesis proceeds, phospho-ERK5 levels steadily decline. Conversely, levels of phospho-ERK1/2 paralleled the progression of MPC chondrogenesis. siRNA-mediated knockdown of ERK5 pathway components MEK5 and ERK5 resulted in increased MPC pellet mRNA transcript levels of the cartilage-characteristic marker genes SOX9, COL2A1, AGC, L-SOX5, and SOX6, as well as enhanced accumulation of SOX9 protein, collagen type II protein, and Alcian blue-stainable proteoglycan. In contrast, knockdown of ERK1/2 pathway members MEK1 and ERK1 decreased expression of all chondrogenic markers tested. Finally, overexpression of MEK5 and ERK5 also depressed MPC chondrogenesis, as indicated by diminished activity of a co-transfected collagen II promoter-luciferase reporter construct. In conclusion, our results suggest a novel role for the ERK5 pathway as an important negative regulator of adult human MPC chondrogenesis and illustrate that the ERK5 and ERK1/2 kinase cascades play opposing roles regulating MPC cartilage formation. (c) 2010 Wiley-Liss, Inc.

  6. The position of Electricite de France (EDF) on the European Commission strategy against acidification; Position de l`Electricite de France (EDF) sur la strategie de lutte contre l`acidification de la commission europeenne

    Energy Technology Data Exchange (ETDEWEB)

    Bartaire, J.G. [Electricite de France (EDF), 94 - Vitry-sur-Seine (France)

    1997-12-31

    Electricite de France (EDF), the French national power utility, presents several observations on the European Union 1997 project for the reduction of air pollution and acidification in Europe. Although EDF is globally approving the European Commission determination for a common strategy, several points are pinned, which are related to the necessity of technical-economical impact analysis of the strategy, the synchronization with the sulfur protocol and the projected United Nation protocol, a stronger consideration of emission sources others than power plants, the consideration of national specificities, situation in Eastern Europe, and limitations in the reliability of models and tools used by the Commission

  7. The security of energy supply. The European Commission's Green Paper stimulates debate

    International Nuclear Information System (INIS)

    2000-01-01

    The growing dependence of the European Union (EU) on external supplies of energy is the central focus of a ''Green Paper'' issued in late November 2000 by the Commission of the European Communities in Brussels. Entitled ''Towards a European Strategy for the Security of Energy Supply'', the Green Paper is intended to stimulate debate on the EU's energy policies and strategies. European member States are ''interdependent'', the Green Paper states, ''both because of climate change issues and the creation of the internal energy market. Any energy policy decision taken by a Member State will inevitably have repercussions on the functioning of the market in other Member States. Energy policy has assumed a new, Community dimension.'' Three main points emerge from the Green Paper: The EU will become increasingly dependent on external energy sources; its enlargement will not change this situation. Based on current forecasts, energy dependence will reach 70% by the year 2030. - The EU has very limited scope to influence energy supply conditions; it is essentially on the demand side that the EU can intervene, mainly by promoting energy saving in buildings and the transport sector. - The EU presently is not in a position to respond to the challenge of climate change and to meet its commitments, notably under the Kyoto Protocol. Featured here is the Executive Summary of the Green Paper

  8. Ghrelin promotes human non-small cell lung cancer A549 cell proliferation through PI3K/Akt/mTOR/P70S6K and ERK signaling pathways.

    Science.gov (United States)

    Zhu, Jianhua; Yao, Jianfeng; Huang, Rongfu; Wang, Yueqin; Jia, Min; Huang, Yan

    2018-04-06

    Ghrelin is a gastric acyl-peptide that plays an important role in cell proliferation. In the present study, we explored the role of ghrelin in A549 cell proliferation and the possible molecular mechanisms. We found that ghrelin promotes A549 cell proliferation, knockdown of the growth hormone secretagogue receptor (GHSR) attenuated A549 cell proliferation caused by ghrelin. Ghrelin induced the rapid phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, ERK, mammalian target of rapamycin (mTOR) and P70S6K. PI3K inhibitor (LY 294002), ERK inhibitor (PD98059) and mTOR inhibitor (Rapamycin) inhibited ghrelin-induced A549 cell proliferation. Moreover, GHSR siRNA inhibited phosphorylation of PI3K, Akt, ERK, mTOR and P70S6K induced by ghrelin. Akt and mTOR/P70S6K phosphorylation was inhibited by LY 294002 but not by PD98059. These results indicate that ghrelin promotes A549 cell proliferation via GHSR-dependent PI3K/Akt/mTOR/P70S6K and ERK signaling pathways. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Erk5 inhibits endothelial migration via KLF2-dependent down-regulation of PAK1.

    Science.gov (United States)

    Komaravolu, Ravi K; Adam, Christian; Moonen, Jan-Renier A J; Harmsen, Martin C; Goebeler, Matthias; Schmidt, Marc

    2015-01-01

    The MEK5/Erk5 pathway mediates beneficial effects of laminar flow, a major physiological factor preventing vascular dysfunction. Forced Erk5 activation induces a protective phenotype in endothelial cell (EC) that is associated with a dramatically decreased migration capacity of those cells. Transcriptional profiling identified the Krüppel-like transcription factors KLF2 and KLF4 as central mediators of Erk5-dependent gene expression. However, their downstream role regarding migration is unclear and relevant secondary effectors remain elusive. Here, we further investigated the mechanism underlying Erk5-dependent migration arrest in ECs. Our experiments reveal KLF2-dependent loss of the pro-migratory Rac/Cdc42 mediator, p21-activated kinase 1 (PAK1), as an important mechanism of Erk5-induced migration inhibition. We show that endothelial Erk5 activation by expression of a constitutively active MEK5 mutant, by statin treatment, or by application of laminar shear stress strongly decreased PAK1 mRNA and protein expression. Knockdown of KLF2 but not of KLF4 prevented Erk5-mediated PAK1 mRNA inhibition, revealing KLF2 as a novel PAK1 repressor in ECs. Importantly, both PAK1 re-expression and KLF2 knockdown restored the migration capacity of Erk5-activated ECs underscoring their functional relevance downstream of Erk5. Our data provide first evidence for existence of a previously unknown Erk5/KLF2/PAK1 axis, which may limit undesired cell migration in unperturbed endothelium and lower its sensitivity for migratory cues that promote vascular diseases including atherosclerosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  10. Nuclear energy and the Green Paper of the European Commission 'An European strategy for sustainable, competitive and secure energy'

    International Nuclear Information System (INIS)

    Metes, Mircea

    2006-01-01

    At present the energy is for European Union officials an issue of top priority. In the beginning of 2006 the natural gas crisis between Russia and Ukraine remembered menacingly to the Europeans that energy supply of the continent depends decisively on importation from other geographic areas and that these importation raise risks of a great variety. In addition to the power problems, disastrous effects on the economy, human life and eco-systems appeared to have the climate changes produced by fossil fuel burning. Consequently, a common energetic policy of Europe should be targeted at three main objectives: sustainability, competitiveness and security of supply. Six directions of action were identified: 1. EU must finalize the construction of internal European gas and electricity market; 2. EU should ensure that its energy market guaranties the security of supply under a solidary policy of the member states; 3. It is necessary that a large debate to have place about different sources of energy including the problems of costs and impact on climatic change, security and supply competitiveness and sustainability; 4. EU should approach the climatic change issues in agreement with the objectives established at Lisbon conference aiming at placing EU in the forefront of technological and scientific progress; 5. A strategic plan concerning the energy technology; 6. A common foreign policy in the field of energy. It is worthy to stress that the present Green Paper of EU has a manifestly different position concerning the nuclear energy with respect to the prior Green Paper of November 2000. While, in 2000 the EU Commission viewed the nuclear energy as being 'in limbo', in the 2006 version the Commission declared the nuclear energy as the most important source of power in Europe without CO 2 emissions. It is stated that all the energy options should be kept open while the Europe states have the right to establish their own energy mix, which they consider optimal, and in which

  11. Radioactive waste management: outline of the research programme of the Commission of the European Communities

    International Nuclear Information System (INIS)

    Bresesti, M.

    1980-01-01

    The lines of activity, the main achievements and the perspectives of the research programme of the Commission of the European Communities on radioactive waste management, are presented. In particular an overall view of the activity on chemical separation and nuclear transmutation of actinides is given, as introduction to the various presentations of the JRC staff on specific aspects of this waste management strategy

  12. Preparing Teachers for Diversity: The Role of Initial Teacher Education. Annex 1 to the Final Report to DG Education, Youth, Sport and Culture of the European Commission

    Science.gov (United States)

    European Commission, 2017

    2017-01-01

    This document, "Annex 1 to the Final Report to DG Education, Youth, Sport and Culture of the European Commission" is intended as a companion piece to European Commission report "Preparing Teachers for Diversity: The Role of Initial Teacher Education. Final Report". It contains country fiches which are overviews of available…

  13. The epidemiology of HIV and AIDS reports in migrants in the 27 European Union countries, Norway and Iceland: 1999-2006.

    Science.gov (United States)

    Del Amo, Julia; Likatavičius, Giedrius; Pérez-Cachafeiro, Santiago; Hernando, Victoria; González, Cristina; Jarrín, Inma; Noori, Teymur; Hamers, Françoise F; Bolúmar, Francisco

    2011-10-01

    To describe the epidemiology of HIV and AIDS by geographical origin in the EU, 1999-2006. AIDS and HIV cases from the EU 27, Norway and Iceland reported to European Centre for Epidemiological Monitoring of AIDS were analysed. Of 75,021 AIDS reports over 1999-2006, 35% were migrants. Of 2988 heterosexual AIDS reports in 2006, 50% were migrants, largely from Sub-Saharan Africa (SSA), 20% of 1404 AIDS cases in men who have sex with men (MSM) were migrants from Latin-America and Western Europe. Of 57 mother-to-child transmission (MTCT) AIDS cases, 23% were from SSA. AIDS cases decreased from 1999 to 2006 in natives (42%), Western Europeans (40%) and North Africa and Middle East (34%), but increased in people from SSA (by 89%), Eastern Europe (by 200%) and Latin-America (50%). Of 17,646 HIV infections in men and 9066 in females in 2006, 49 and 76% were migrants, largely from SSA. Of 169 MTCT infections, 41% were from SSA. Migrants, largely from SSA, represent a considerable proportion of AIDS and HIV reports in EU, especially among heterosexual and MTCT infections. Their contribution is higher among female reports. A substantial percentage of diagnoses in MSM are migrants, largely from Western Europe and Latin-America.

  14. Conference "Internet, Web, What's next?" on 26 June 1998 at CERN : Robert Verrue, Director general of the DGXIII of the European Commission, responsible for telecommunication in Europe, outlines the Commission's vision on the Information Society in Europe

    CERN Multimedia

    1998-01-01

    Conference "Internet, Web, What's next?" on 26 June 1998 at CERN : Robert Verrue, Director general of the DGXIII of the European Commission, responsible for telecommunication in Europe, outlines the Commission's vision on the Information Society in Europe

  15. Comparative decline in funding of European Commission malaria vaccine projects: what next for the European scientists working in this field?

    Directory of Open Access Journals (Sweden)

    Imoukhuede Egeruan B

    2011-09-01

    Full Text Available Abstract Since 2000, under the Fifth and subsequent Framework Programmes, the European Commission has funded research to spur the development of a malaria vaccine. This funding has contributed to the promotion of an integrated infrastructure consisting of European basic, applied and clinical scientists in academia and small and medium enterprises, together with partners in Africa. Research has added basic understanding of what is required of a malaria vaccine, allowing selected candidates to be prioritized and some to be moved forward into clinical trials. To end the health burden of malaria, and its economic and social impact on development, the international community has now essentially committed itself to the eventual eradication of malaria. Given the current tentative advances towards elimination or eradication of malaria in many endemic areas, malaria vaccines constitute an additional and almost certainly essential component of any strategic plan to interrupt transmission of malaria. However, funding for malaria vaccines has been substantially reduced in the Seventh Framework Programme compared with earlier Framework Programmes, and without further support the gains made by earlier European investment will be lost.

  16. Energy regulation at EU level. The role of the European Commission and ACER in the context of REMIT

    International Nuclear Information System (INIS)

    Konar, Selma

    2015-01-01

    The regulatory act of promulgating REMIT, the Regulation on Wholesale Market Integrity and Transparency, has highlighted the commanding position of both the European Commission and ACER, the Agency for the Cooperation of Energy Regulators, in the regulation of energy affairs in the European Union. Furthermore it has led to major changes in how surveillance is organized at the national level. The first part of this publication is dedicated to the organization of market surveillance following the promulgation of REMIT. It depicts the tasks of the European Commission and ACER in this context. The Regulation has accorded the authorities a central role in managing the European Union's responsibilities with regard to energy wholesale trade. The act of delegating such far-reaching competence to the authorities deserves careful review however. The article shows how, given ACER's lack of practical experience in market surveillance, as well as its lack of human resources, the task of surveilling the European energy wholesale market confronts the agency with a significant challenge. How successfully the EU energy agency will master this challenge will depend on a number of different factors. Stringent requirements will be needed for the data registration offices in order to ensure optimal data processing. National authorities and supervisory bodies should be made to participate in the data monitoring process. ACER's efficiency in surveilling the market will furthermore depend decisively on its IT infrastructure.

  17. The role of the Joint Research Centre from the European Commission in the European Structural Integrity Networks AMES, ENIQ and NESC

    International Nuclear Information System (INIS)

    Estorff, U. von; Torronen, K.

    1999-01-01

    Due to the reduction in many countries of the research budget for nuclear safety several European institutions and organisations and the Institute for Advanced Materials (IAM) of the Joint Research Centre (JRC) of the European Commission (EC) have developed co-operative programmes now organised into 'Networks' for mutual benefit. They include utilities, engineering companies, research and development (R and D) laboratories and regulatory bodies. These Networks are all organised and managed in a similar way, i.e. like the successful Programme for the Inspection of Steel Components (PISC). The IAM plays the role of Operating Agent, Reference Laboratory and Network Manager of these Networks: European Network on Ageing Materials Evaluation and Studies (AMES), European Network for Inspection Qualification (ENIQ) and Network for Evaluating Steel Components (NESC), each of them dealing with a specific aspect of fitness for purpose of materials in structural components. This article will describe how the network organisation works, which was the positive experience from the past, why the networks are a tool for integrating fragmented research in Europe and how they fit into the mission of the JRC and therefore follow the EC policy. (orig.)

  18. Removal of radon by aeration testing of various aeration techniques for small water works. For European Commission under Contract No FI4PCT960054 TENAWA project

    CERN Document Server

    Salonen, L; Mehtonen, J; Mjoenes, L; Raff, O; Turunen, H

    2002-01-01

    Capability of various aeration techniques to remove radon from water in small waterworks was studied as a part of project (Treatment Techniques for Removing Natural Radionuclides from Drinking Water), which was carried out during 1997-1999 on a cost-shared basis (contract No. F14PCT960054) with The European Commission (CEC) under the supervision of the Directorate-General XII Radiation Protection Research Unit. In TENAWA project both laboratory and field experiments were performed in order to find reliable methods and equipment for removing natural radionuclides from ground water originating either from private wells or small waterworks. Because such techniques are more often needed in private households than at waterworks, the main emphasis of the research was aimed to solve the water treatment problems related to the private water supplies, especially bedrock wells. Radon was the most important radionuclide to be removed from water at waterworks whereas the removal of other radionuclides ( sup 2 sup 3 sup 4...

  19. The design of European energy markets by means of decisions of commitment acceptance of the European Commission. Pt. 1; Die Gestaltung der europaeischen Energiemaerkte durch Verpflichtungszusagenentscheidungen der Kommission. T. 1

    Energy Technology Data Exchange (ETDEWEB)

    Gussone, Peter [Bundeskartellamt, Bonn (Germany). ECN-Koordinationsstelle

    2011-03-10

    The compartmentalization of national energy markets is the leitmotif of anti-trust against the greatest European energy utilities. With far-reaching commitments of the utilities the European Commission attempted a rapid end of abusive practices and a market opening. A discouragement of claim for damages under private law from customers has been accepted. There is a lack of a final reasoned statement of the behavior being in violation with competition law with a binding effect also for the courts. The impressive balance of the European Commission shows a partial failure of the regulation in the grid operation. E.ON (Munich, Federal Republic of Germany) has sold its high voltage network. RWE AG (Essen, Federal Republic of Germany) sold its transmission system. Eni Gas and Power GmbH (Duesseldorf, Federal Republic of Germany) will sell large portions of its international transmission system. The large vertically integrated utilities may not agree on long-term supply and resale restrictions.

  20. CacyBP/SIP binds ERK1/2 and affects transcriptional activity of Elk-1

    International Nuclear Information System (INIS)

    Kilanczyk, Ewa; Filipek, Slawomir; Jastrzebska, Beata; Filipek, Anna

    2009-01-01

    In this work we showed for the first time that mouse CacyBP/SIP interacts with extracellular signal regulated kinases 1 and 2 (ERK1/2). We also established that a calcium binding protein, S100A6, competes for this interaction. Moreover, the E217K mutant of CacyBP/SIP does not bind significantly to ERK1/2 although it retains the ability to interact with S100A6. Molecular modeling shows that the E217K mutation in the 189-219 CacyBP/SIP fragment markedly changes its electrostatic potential, suggesting that the binding with ERK1/2 might have an electrostatic character. We also demonstrate that CacyBP/SIP-ERK1/2 interaction inhibits phosphorylation of the Elk-1 transcription factor in vitro and in the nuclear fraction of NB2a cells. Altogether, our data suggest that the binding of CacyBP/SIP with ERK1/2 might regulate Elk-1 phosphorylation/transcriptional activity and that S100A6 might further modulate this effect via Ca 2+ -dependent interaction with CacyBP/SIP and competition with ERK1/2.

  1. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Chen, Qing-wen; Edvinsson, Lars; Xu, Cang-Bao

    2009-01-01

    muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate...... agonist, Sarafotoxin 6c (S6c) caused a time-dependent ERK1/2 activation with a maximal effect by less than 20% of the ET-1-induced activation of ERK1/2. Increase in bosentan concentration up to 10 microM further inhibited ET-1-induced activation of ERK1/2 and had a stronger inhibitory effect than BQ123...

  2. Consolidated results 1999 outlook for 2000

    International Nuclear Information System (INIS)

    Gadonneix, P.

    2000-01-01

    This document presents an economic analysis of the consolidated results 1999 for the Group Gaz De France for the year 1999, showing a radical change for the gas industry. The main topics discussed are: a growth market for natural gas, a highly de-compartmentalized market, a market in which the Gaz de France group is an European leader and a market marked in 1999 by a sharp rise in oil prices. (A.L.B.)

  3. Consolidated results 1999 outlook for 2000

    Energy Technology Data Exchange (ETDEWEB)

    Gadonneix, P. [Gaz de France (GDF), 75 - Paris (France)

    2000-07-01

    This document presents an economic analysis of the consolidated results 1999 for the Group Gaz De France for the year 1999, showing a radical change for the gas industry. The main topics discussed are: a growth market for natural gas, a highly de-compartmentalized market, a market in which the Gaz de France group is an European leader and a market marked in 1999 by a sharp rise in oil prices. (A.L.B.)

  4. Godiva, a European Project for Ozone and Trace Gas Measurements from GOME

    Science.gov (United States)

    Goede, A. P. H.; Tanzi, C. P.; Aben, I.; Burrows, J. P.; Weber, M.; Perner, D.; Monks, P. S.; Llewellyn-Jones, D.; Corlett, G. K.; Arlander, D. W.; Platt, U.; Wagner, T.; Pfeilsticker, K.; Taalas, P.; Kelder, H.; Piters, A.

    GODIVA (GOME Data Interpretation, Validation and Application) is a European Commission project aimed at the improvement of GOME (Global Ozone Monitoring Experiment) data products. Existing data products include global ozone, NO2 columns and (ir)radiances. Advanced data products include O3 profiles, BrO, HCHO and OCIO columns. These data are validated by ground-based and balloon borne instruments. Calibration issues are investigated by in-flight monitoring using several complementary calibration sources, as well as an on-ground replica of the GOME instrument. The results will lead to specification of operational processing of the EUMETSAT ozone Satellite Application Facility as well as implementation of the improved and new GOME data products in the NILU database for use in the European THESEO (Third European Stratospheric Experiment on Ozone) campaign of 1999

  5. Regulatory requirements for biocides on the market in the European Union according to Directive 98/8/EC.

    Science.gov (United States)

    Rasmussen, K; Chemin, P; Haastrup, P

    1999-06-30

    In early 1998, the European Commission and Parliament adopted a new Directive concerning the placing on the market of biocidal products. The Directive is to be implemented in the member states by May 2000. The member states are currently concerned with the national implementation into legislation whereas the Commission is setting up the proposal for a review programme for the existing active substances and the products in which they are used. This paper describes the effort currently undertaken (up to the end of December 1998) to define the procedures to be used and characterise the substances covered. Copyright 1999 Elsevier Science B.V.

  6. [6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway

    Directory of Open Access Journals (Sweden)

    Sung Ok Kim

    2013-01-01

    Full Text Available To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP activities; transepithelial electrical resistance (TER and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO- 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.

  7. Communication from the commission to the council and the European parliament. Final report on the green paper: towards a European strategy for the security of energy supply

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-06-15

    energy saving in buildings, which provides a precise legislative framework for limiting energy consumption in this sector, representing 40% of the energy consumed in the European Union. Finally, the Commission has also made regulatory and fiscal proposals to promote biofuels. A wide debate also developed around the Green Paper proposal for a new approach to oil stocks. The debate on the Green Paper has shown the need to develop a Europe-wide security of supply concept which alone will enable Europe to control its energy future. Efforts to promote new and renewable energy sources, representing only 6% of the EU energy balance, have been too feeble so far: on present trends they will account for only 9% of total European consumption by 2030. The Green Paper's proposal for the development of these sources to be financed by conventional energy sources prompted a mitigated response. The nuclear factor remains an inseparable part of the debate. One major lesson to be drawn from the Green Paper debate is that the future of this industry depends on finding a clear and unequivocal answer to the question of the processing and transportation of radioactive waste. (A.L.B.)

  8. Communication from the commission to the council and the European parliament. Final report on the green paper: towards a European strategy for the security of energy supply

    International Nuclear Information System (INIS)

    2002-06-01

    energy saving in buildings, which provides a precise legislative framework for limiting energy consumption in this sector, representing 40% of the energy consumed in the European Union. Finally, the Commission has also made regulatory and fiscal proposals to promote biofuels. A wide debate also developed around the Green Paper proposal for a new approach to oil stocks. The debate on the Green Paper has shown the need to develop a Europe-wide security of supply concept which alone will enable Europe to control its energy future. Efforts to promote new and renewable energy sources, representing only 6% of the EU energy balance, have been too feeble so far: on present trends they will account for only 9% of total European consumption by 2030. The Green Paper's proposal for the development of these sources to be financed by conventional energy sources prompted a mitigated response. The nuclear factor remains an inseparable part of the debate. One major lesson to be drawn from the Green Paper debate is that the future of this industry depends on finding a clear and unequivocal answer to the question of the processing and transportation of radioactive waste. (A.L.B.)

  9. The MAPK ERK5, but not ERK1/2, inhibits the progression of monocytic phenotype to the functioning macrophage

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xuening [Department of Pathology and Laboratory Medicine, Rutgers, NJ Medical School, 185 South Orange Ave, Newark, NJ 07103 (United States); Pesakhov, Stella [Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 653, 84105 Beer-Sheva (Israel); Harrison, Jonathan S [Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); Kafka, Michael; Danilenko, Michael [Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 653, 84105 Beer-Sheva (Israel); Studzinski, George P, E-mail: studzins@njms.rutgers.edu [Department of Pathology and Laboratory Medicine, Rutgers, NJ Medical School, 185 South Orange Ave, Newark, NJ 07103 (United States)

    2015-01-01

    Intracellular signaling pathways present targets for pharmacological agents with potential for treatment of neoplastic diseases, with some disease remissions already recorded. However, cellular compensatory mechanisms usually negate the initial success. For instance, attempts to interrupt aberrant signaling downstream of the frequently mutated ras by inhibiting ERK1/2 has shown only limited usefulness for cancer therapy. Here, we examined how ERK5, that overlaps the functions of ERK1/2 in cell proliferation and survival, functions in a manner distinct from ERK1/2 in human AML cells induced to differentiate by 1,25D-dihydroxyvitamin D{sub 3} (1,25D). Using inhibitors of ERK1/2 and of MEK5/ERK5 at concentrations specific for each kinase in HL60 and U937 cells, we observed that selective inhibition of the kinase activity of ERK5, but not of ERK1/2, in the presence of 1,25D resulted in macrophage-like cell morphology and enhancement of phagocytic activity. Importantly, this was associated with increased expression of the macrophage colony stimulating factor receptor (M-CSFR), but was not seen when M-CSFR expression was knocked down. Interestingly, inhibition of ERK1/2 led to activation of ERK5 in these cells. Our results support the hypothesis that ERK5 negatively regulates the expression of M-CSFR, and thus has a restraining function on macrophage differentiation. The addition of pharmacological inhibitors of ERK5 may influence trials of differentiation therapy of AML. - Highlights: • ERK5 has at least some functions in AML cells which are distinct from those of ERK1/2. • ERK5 activity negatively controls the expression of M-CSFR. • ERK5 retards the progression of differentiation from monocyte to functional macrophage.

  10. The European Commission: nuclear power has an important role to play; Commission Europeenne: le nucleaire a un role important a jouer

    Energy Technology Data Exchange (ETDEWEB)

    Anon

    2008-11-15

    The European Commission (E.C.) thinks that nuclear power has an important role to play: first to reduce CO{sub 2} emissions and secondly to reinforce energy self-reliance of the member states. The decision to introduce nuclear power in their energy mix belongs to every state but the E.C. has also highlighted that if adequate investment are quickly made 2 thirds of the electricity produced in the European Union in 2010 could by from low-carbon-emitting sources. Today with 148 reactors operating in 15 member countries nuclear power contributes to 1 third of the electricity produced. Another issue that is looming is the security of electricity supplying. A study has shown that the security level is worsening (particularly in winter) because of the greater part of wind energy in the energy mix as wind energy is not necessarily available when energy demand is peaking. The E.C. has proposed a new directive drawing a common standard frame for nuclear safety requirements concerning design, site selection, maintenance, operation and decommissioning of nuclear facilities. Each member state will have the choice to implement stiffer regulations. The European Union must reduce its dependency on Russian gas by increasing its storing capacities, by easing gas exchanges between member states and by importing more liquefied natural gas. European member states will have to invert 1000*10{sup 9} euros in gas and electrical power infrastructures in the next 25 years. (A.C.)

  11. ERF is a Potential ERK Modulated Tumor Suppressor in Prostate Cancer

    Science.gov (United States)

    2016-10-01

    6/27/2016 - 6/27/2019 1.20 calendar Prostate Cancer Foundation (formerly CaP CURE) $ 75,000 Epigenetic ...AWARD NUMBER: W81XWH-15-1-0277 TITLE: ERF is a Potential ERK-Modulated Tumor Suppressor in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rohit...4. TITLE AND SUBTITLE ERF is a Potential ERK-Modulated Tumor Suppressor in Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0277

  12. Impact Assessment Road Safety Action Programme : assessment for mid term review : final report. Report on behalf of the European Commission, Directorate-General Energy and Transport.

    OpenAIRE

    ECORYS Transport & SWOV Institute for Road Safety Research

    2006-01-01

    In 2003 the Commission published Saving 20000 lives on our roads, a shared responsibility, also known as the third European Road Safety Action Programme (RSAP). The RSAP describes concrete actions and proposals for actions by the Commission aimed at realising the target for improving road safety as set in the White Paper (European Transport Policy for 2010: time to decide, 2001), namely halving the number of road deaths by 2010. Improving road safety in the EU is clearly a joint responsibilit...

  13. Ionizing radiation-induced MEK and Erk activation does not enhance survival of irradiated human squamous carcinoma cells

    International Nuclear Information System (INIS)

    Bonner, James A.; Vroman, Benjamin T.; Christianson, Teresa J.H.; Karnitz, Larry M.

    1998-01-01

    Purpose: Ionizing radiation (IR) triggers several intracellular signaling cascades that have commonly been regarded as mitogenic, including the Raf-MEK-Erk kinase cascade. In addition to promoting proliferation, activated MEK and Erk may also prevent cell death induced by cytotoxic stimuli. Because Raf, MEK, and Erk are activated by IR in some tumor cell lines, this suggests that IR-induced activation of the kinase cascade may enhance the survival of irradiated cells. Methods and Materials: IR-induced activation of MEK and Erk was assessed in irradiated UM-SCC-6 cells, a human squamous carcinoma cell line. Activation of MEK and Erk was blocked with the pharmacological inhibitor of MEK activation, PD098059. Clonogenic survival was assessed in irradiated UM-SCC-6 cells that were pretreated with nothing or with the MEK inhibitor. Results: In UM-SCC-6 cells, IR doses as low as 2 Gy rapidly activated MEK and Erk. Pretreatment of the cells with the pharmacological inhibitor of MEK activation, PD098059, effectively blocked IR-induced activation of MEK and Erk. However, inhibition of the kinase cascade did not affect the clonogenic survival of irradiated cells in either early or delayed-plating experiments. Conclusion: Taken together, these results suggest that although MEK and Erk are rapidly activated by IR treatment, these protein kinases do not affect the clonogenic survival of irradiated UM-SCC6 cells

  14. CRE answer to the European Commission public consultation on the new electricity market design

    International Nuclear Information System (INIS)

    Ladoucette, Philippe de

    2015-01-01

    On July 15, 2015, the European Commission launched a public consultation on the new Electricity Market Design. All National Regulatory Authorities (NRAs), and CRE in particular, contributed to the joint ACER-CEER response to the consultation. CRE supports this joint response, and further develops some topics in this document, building on its particular experience in the implementation of the internal energy market: implementation of the network codes, in particular those regarding the markets, development of demand-side flexibility, development of interconnections, and alignment of fragmented balancing markets

  15. Activities of the Commission of the European Communities in the field of codes and standards for FBRs

    International Nuclear Information System (INIS)

    Terzaghi, A.

    1987-01-01

    A description of the organization set up by the Commission of European Communities to study problems, compare information within the member nations, and with other industrial nations for the preparation of guides and codes for the components of the LMFBR is given. Work performed and currently in progress is given on structural analysis, materials, and classification of components. (orig.)

  16. BAG3 controls angiogenesis through regulation of ERK phosphorylation.

    Science.gov (United States)

    Falco, A; Festa, M; Basile, A; Rosati, A; Pascale, M; Florenzano, F; Nori, S L; Nicolin, V; Di Benedetto, M; Vecchione, M L; Arra, C; Barbieri, A; De Laurenzi, V; Turco, M C

    2012-12-13

    BAG3 is a co-chaperone of the heat shock protein (Hsp) 70, is expressed in many cell types upon cell stress, however, its expression is constitutive in many tumours. We and others have previously shown that in neoplastic cells BAG3 exerts an anti-apoptotic function thus favoring tumour progression. As a consequence we have proposed BAG3 as a target of antineoplastic therapies. Here we identify a novel role for BAG3 in regulation of neo-angiogenesis and show that its downregulation results in reduced angiogenesis therefore expanding the role of BAG3 as a therapeutical target. In brief we show that BAG3 is expressed in endothelial cells and is essential for the interaction between ERK and its phosphatase DUSP6, as a consequence its removal results in reduced binding of DUSP6 to ERK and sustained ERK phosphorylation that in turn determines increased levels of p21 and p15 and cell-cycle arrest in the G1 phase.

  17. Participatory approaches to environmental policy-making. The European Commission Climate Policy Process as a case study

    International Nuclear Information System (INIS)

    Van den Hove, S.

    2000-01-01

    The paper investigates the relevance of participatory approaches to environmental policy-making when sustainable development is taken as the encompassing normative basis for environmental governance. In the first section, we illustrate the frequent references to participatory approaches in environmental decision-making. We then look at environmental issue attributes as determinants of the problem-solving requirements for environmental decision-making. We conclude the section by investigating whether and how participatory approaches could answer some of these requirements. In the second section, an illustration is proposed with the presentation of a participatory process that took place in 1997, during the last phase of the international negotiations that led to the Kyoto Conference of the Parties to the UN Framework Convention on Climate Change, and in 1998 in the preparation of the post-Kyoto phase. The process, organised by the European Commission, consisted of a series of workshops whose objective was to furnish timely inputs responding to the European Commission's information needs for climate policy formation in the pre- and post-Kyoto periods. This was to be achieved through the establishment of interfaces between: (1) the research community; (2) the EC Climate negotiation team and through it the EU Member States representatives; (3) other Commission interests (the 'inside stakeholders'); (4) a range of 'outside' stakeholders including industry, finance and commerce, employment, environment, consumer and citizen interests. We reflect on the participatory nature of the process and show how the process met some of the decision-making requirements identified in the first section. 27 refs

  18. The European Commission and IEA highlight the importance of diversifying energy sources

    International Nuclear Information System (INIS)

    Anon.

    2008-01-01

    Europe will become more and more dependent on foreign sources for its energy supply because of the growing demand for energy. As a consequence Europe must diversify both its supplying countries and its energy sources. In this way the Nabucco gas pipeline project is important because it will link the Caspian sea to Europe by avoiding Russia, the main gas supplier of Europe. Other sources of energy like renewable energies or nuclear energy or carbon sequestration must be developed in Europe. Another point is to give more power to the European Commission to deal directly with energy exporting countries to get more favourable contracts, till now each member state has favored its own bi-lateral talks. (A.C.)

  19. The History of Soil Mapping and Classification in Europe: The role of the European Commission

    Science.gov (United States)

    Montanarella, Luca

    2014-05-01

    Early systematic soil mapping in Europe dates back to the early times of soil science in the 19th Century and was developed at National scales mostly for taxation purposes. National soil classification systems emerged out of the various scientific communities active at that time in leading countries like Germany, Austria, France, Belgium, United Kingdom and many others. Different scientific communities were leading in the various countries, in some cases stemming from geological sciences, in others as a branch of agricultural sciences. Soil classification for the purpose of ranking soils for their capacity to be agriculturally productive emerged as the main priority, allowing in some countries for very detailed and accurate soil maps at 1:5,000 scale and larger. Detailed mapping was mainly driven by taxation purposes in the early times but evolved in several countries also as a planning and management tool for farms and local administrations. The need for pan-European soil mapping and classification efforts emerged only after World War II in the early 1950's under the auspices of FAO with the aim to compile a common European soil map as a contribution to the global soil mapping efforts of FAO at that time. These efforts evolved over the next decades, with the support of the European Commission, towards the establishment of a permanent network of National soil survey institutions (the European Soil Bureau Network). With the introduction of digital soil mapping technologies, the new European Soil Information System (EUSIS) was established, incorporating data at multiple scales for the EU member states and bordering countries. In more recent years, the formal establishment of the European Soil Data Centre (ESDAC) hosted by the European Commission, together with a formal legal framework for soil mapping and soil classification provided by the INSPIRE directive and the related standardization and harmonization efforts, has led to the operational development of advanced

  20. SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation

    International Nuclear Information System (INIS)

    Huang Lin; Gotoh, Noriko; Zhang Shengliang; Shibuya, Masabumi; Yamamoto, Tadashi; Tsuchida, Nobuo

    2004-01-01

    The control of cellular responses with fibroblast growth factors and neurotrophins is mediated through membrane-linked docking proteins, SNT (suc1-binding neurotrophic target)-1/FRS2α and SNT-2/FRS2β. ERK1/2 are members of the mitogen-activated protein kinase family that regulate diverse cellular activities in response to various stimuli. Here, we demonstrate that SNT-2 does not become tyrosine phosphorylated significantly in response to EGF but forms a complex with ERK2 via the region of 186-252 amino acid residues, and the complex formation is enhanced upon EGF stimulation. SNT-2 downregulates ERK2 phosphorylation, suppresses and delays ERK2 nuclear accumulation which occurs following EGF stimulation. In contrast, the mutant SNT-2 which carries deletion of 186-252 amino acids and lacks ERK2 binding does not have these effects. These observations suggest that SNT-2 negatively regulates ERK2 signaling activated via EGF stimulation through direct binding to ERK2

  1. Jacques Delors - President de la Commission Europeenne

    Directory of Open Access Journals (Sweden)

    Dacian Graţian GAL

    2005-02-01

    Full Text Available This article refers to the President of the European Commission between 1985- 1995, Jacques Delors. He was the single person who exercised the presidency of the European Commission during 10 years and this period was one of the most important for the European construction: the achievement of the Single Market, the development of the Single Currency Unit project, of the new common politics, the enlargement of the European Union from 12 members to 15 members etc. Due the contribution of his presidency to the European construction, Jacques Delors is one of the parents of the European construction and one of the most important political men of the XX century.  

  2. Evaluation report no. 6

    International Nuclear Information System (INIS)

    2000-06-01

    The French national commission of evaluation was settled in 1994 when the survey work of the feasibility study for the disposal of radioactive wastes in the deep underground started up again. This document presents a mid-way evaluation of the progress of researches and includes also the main conclusions of the 1999-2000 audits. The content is presented as follows: 1 - the activities of the commission: activities during the 1999-2000 period (scientific audits, audit reports, study travel in Sweden and Finland), events in relation with the law, members of the commission; 2 - consequences of the recommendations of the commission: method of analysis, analysis of answers given by the law actors (modeling and numerical simulation, feasibility study for the recovery of conditioned calcinates and glasses, wastes toxicology, inventory, other actions); 3 - evaluation of the strategy and research programs: general considerations, 1999 acquired knowledge, comments, industrial strategy; 4 - methodology of the inventory of radioactive wastes: mission of the ANDRA, report provided by the ANDRA to the commission on May 4, 2000 (origin and classifying of wastes, inventory needs, foreign experience, principles of the proposed national inventory); 5 - researches on advanced separation and transmutation: chemical separations (1999 acquired knowledge, Puretex and Actinex programs, separation of long-life activation and fission products, pyro-chemistry, recommendations), transmutation and hybrid systems (1999-2000 knowledge, transmutation in critical reactors, basic research on hybrid systems, projects of hybrid system demonstrators, scenarios study), progresses made; 6 - researches for underground laboratories and geological disposal: research program at the Eastern site (ANDRA's planning, experimental program in underground laboratory, other associated researches), selection of granitic massifs prior to the dialogue, long-term behaviour of confinement matrices and containers, status

  3. 1999 world energy consumption (ENERDATA)

    International Nuclear Information System (INIS)

    Martin, J.M.

    2000-01-01

    Here is given a compilation of detailed statistical tables on various aspects of world energy production and consumption over the years 1994 to 1999. The present tables indicate the production, trade and consumption of crude oil, liquefied natural gas, oil products, natural gas, coal, lignite, electric power; the energy balance for the year 1999; the total energy consumption in European Union, Western Europe, North America, Japan and Pacific, CIS and Central Europe, Latin America, Asia, Middle East and Africa for the years 1994 to 1999. The CO 2 emissions for these countries are also given. These data are an extraction of the energy statistics yearbook, ENERDATA, June 2000. They are commented by Mr J.M. Martin. According to ENERDATA, the 1999 world energy consumption stagnates. (O.M.)

  4. Environment in the European Union 1995

    DEFF Research Database (Denmark)

    The update to the 1992 report on the state of the environment in the European Union requested by the European Commission......The update to the 1992 report on the state of the environment in the European Union requested by the European Commission...

  5. From Access to Documents to Consumption of Information: The European Commission Transparency Policy for the TTIP Negotiations

    Directory of Open Access Journals (Sweden)

    Evelyn Coremans

    2017-09-01

    Full Text Available To increase transparency of the Transatlantic Trade and Investment Partnership (TTIP negotiations, the European Commission has reformed existing information sharing systems for trade policy. The Commission has moved from a strategy of providing transparency in the form of access to documents to one of access to information, geared specifically towards enhancing consumption of the available information. In both public and institutional transparency policy, the width of the target audience and the depth of the information have increased, and the manner of provision has shifted from reactive to proactive provision of information. As a result, the TTIP is now being coined as the most transparent trade negotiation ever in the EU’s history and a pilot project for transparency policy in future trade negotiations. The article adopts a supply-centred perspective to explain a transparency policy that goes beyond the legal minimum imposed by formal requirements. It relies on interview data of the changes brought about in inter-institutional relations since 2014, basic quantitative and qualitative analysis of document material, and a five-month participatory observation by the author in the secretariat of the European Parliament’s Committee on International Trade.

  6. Impact Assessment Road Safety Action Programme : assessment for mid term review : final report. Report on behalf of the European Commission, Directorate-General Energy and Transport.

    NARCIS (Netherlands)

    ECORYS Transport & SWOV Institute for Road Safety Research

    2006-01-01

    In 2003 the Commission published Saving 20000 lives on our roads, a shared responsibility, also known as the third European Road Safety Action Programme (RSAP). The RSAP describes concrete actions and proposals for actions by the Commission aimed at realising the target for improving road safety as

  7. Case note: ECJ (case C-28/08 P, European Commission v. The Bavarian Lager Co. Ltd, not yet reported: privacy of EU government data)

    NARCIS (Netherlands)

    Curtin, D.M.

    2011-01-01

    The Bavarian Lager Company challenged the Commission's refusal to grant it full access tot the minutes of a meeting in Brussels with national and European civil servants as well as representatives of the European Beer Brewing Federation, including the names of all those who attended. The Court of

  8. The security of energy supply. The European seminar. The green book of the Commission. The IEA judgment. The strategic oil stocks

    International Nuclear Information System (INIS)

    Rose, D.; Burucoa, X.

    2001-01-01

    This issue of Energies et Matieres Premieres journal comprises five articles about the security of energy supplies in Europe and France. The first article is the opening talk given by Christian Pierret at the European seminar on the security of energy supplies (Paris-Bercy, France, Nov. 24 2000). The article gives a broad presentation of the French energy policy in the worldwide economical, political and environmental context of energy. The second article is the concluding talk given by Jean-Michel Charpin at the seminar. The third article reports on some excerpts of the technical summary that was used to elaborate the green book of the European commission about the security of energy supplies. The fourth article is a summary written in collaboration with the IEA about the French policy of security of energy supplies. The last article gives a presentation of the role and management of strategic oil stocks (historical aspects, rules and legal aspects, management of crises, economical impact of the US destocking of September 2000, proposal of the European Commission's green book). (J.S.)

  9. Metallothionein-III protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a PI3K and ERK/Nrf2-dependent manner

    International Nuclear Information System (INIS)

    Hwang, Yong Pil; Kim, Hyung Gyun; Han, Eun Hee; Jeong, Hye Gwang

    2008-01-01

    The zinc-binding protein metallothionein-III (MT-III) is associated with resistance to neuronal injury. However, the underlying mechanism for its effects is unclear. In this study, we demonstrate that MT-III prevents the accumulation of reactive oxygen species (ROS) in dopaminergic SH-SY5Y cells challenged with the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA) by a mechanism that involves phosphatidylinositol 3-kinase (PI3K) and ERK kinase/NF-E2-related factor 2 (Nrf2) dependent induction of the stress response protein heme oxygenase-1 (HO-1). Pretreatment of SH-SY5Y cells with MT-III significantly reduced 6-OHDA-induced generation of ROS, caspase-3 activation, and subsequent cell death. Also, MT-III up-regulates HO-1 expression and this expression confers neuroprotection against oxidative injury induced by 6-OHDA. Moreover, MT-III induces Nrf2 nuclear translocation, which is upstream of MT-III-induced HO-1 expression, and PI3K and ERK1/2 activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and neuroprotection. Taken together, these results suggest that the PI3K and ERK/Nrf2 signaling pathway controls the intracellular levels of ROS by regulating the expression of the antioxidant enzyme HO-1

  10. Trends in acceptance of euthanasia among the general public in 12 European countries (1981-1999).

    Science.gov (United States)

    Cohen, Joachim; Marcoux, Isabelle; Bilsen, Johan; Deboosere, Patrick; van der Wal, Gerrit; Deliens, Luc

    2006-12-01

    We wanted to examine how the acceptance of euthanasia among the general public in Western Europe has changed in the last decades, and we wanted to look for possible explanations. We analysed data from the European Values Surveys, held in 1981, 1990, and 1999-2000 in 12 West European countries. In each country, representative samples of the general public were interviewed using the same structured questionnaire in all countries. Euthanasia was explained in the questionnaires as 'terminating the life of the incurably sick'. A total of 46 199 respondents participated in the surveys. A significant increase in acceptance of euthanasia could be observed in all countries except (West) Germany. While the average increase in euthanasia acceptance was 22%, the increase was particularly obvious in Belgium, Italy, Spain, and Sweden. Although changes in several characteristics of respondents, such as decrease in religious beliefs, rising belief in the right to self-determination, and (to a lesser extent) rise in levels of education, were associated with growing acceptance of euthanasia, they could only partly explain the increase of euthanasia acceptance over the years. An increase of euthanasia acceptance among the general public took place over the last two decades in almost all West European countries, possibly indicating a growing support for personal autonomy regarding medical end-of-life decisions. If this trend continues, it is likely to increase the public and political debate about the (legal) regulation of euthanasia under certain conditions of careful medical practice in several West European countries.

  11. GenHyPEM: A research program on PEM water electrolysis supported by the European Commission

    Energy Technology Data Exchange (ETDEWEB)

    Millet, Pierre; Dragoe, Diana [Institut de Chimie Moleculaire et des Materiaux d' Orsay, UMR CNRS no 8182, Universite Paris-Sud 11, 15 rue Georges Clemenceau, 91405 Orsay Cedex (France); Grigoriev, Serguey; Fateev, Vladimir [Hydrogen Energy and Plasma Technology, Institute of Russian Research Center, Kurchatov Institute, 1, Kurchatov sq., 123182 Moscow (Russian Federation); Etievant, Claude [Compagnie Europeenne des Technologies de l' Hydrogene (CETH), Innov' Valley Entreprise, Batiment D0, Route de Nozay, 91461 Marcoussis Cedex (France)

    2009-06-15

    GenHyPEM (Generateur d'Hydrogene par electrolyse de l'eau PEM <>) is an STREP programme (no 019802) supported by the European Commission in the course of the 6th framework research programme. This R and D project which started in October 2005, is a 2.6 MEUR research effort over three years. It gathers partners from Belgium, Germany, Romania, Federation of Russia, Armenia and France. The main goal of the project is to develop low-cost and high pressure (50 bar) PEM water electrolysers for the production of up to several Nm{sup 3} H{sub 2}/h. The purpose of this communication is to present the current status of GenHyPEM. Major results and technological achievements obtained so far in the fields of academic (electrocatalysis, polymer electrolyte) and applied (stack development and performances) research are presented. Non-noble electrocatalysts have been identified to replace platinum for the HER and stable performances have been obtained during operation at high (1 A cm{sup -2}) current density, paving the way to substantial cost reductions. Prototype electrolysers producing from 0.1 to 5 Nm{sup 3} H{sub 2}/h have been successfully developed. (author)

  12. European Commission policies

    International Nuclear Information System (INIS)

    Coldwell, R.

    1993-01-01

    This debate discusses the debate surrounding the proposed European Community (EC) Directive on the completion of the internal energy market for natural gas and electric power. The context in which the liberalisation program is proposed is described for electricity, considering political issues, international ownership patterns and trade between Eastern and Western Europe. The author then argues for Member States to be consistent and fair, bearing in mind existing variations in liberalisation of national energy markets. Finally the components of the directive are examined. The United Kingdom, with its already liberalised electricity industry has much to gain from the Directive, while other countries which oppose it, are seen as protecting the vested interests of their own utilities. (UK)

  13. Division B Commission 6: Astronomical Telegrams

    Science.gov (United States)

    Yamaoka, H.; Green, D. W. E.; Samus, N. N.; Aksnes, K.; Gilmore, A. C.; Nakano, S.; Sphar, T.; Tichá, J.; Williams, G. V.

    2016-04-01

    IAU Commission 6 ``Astronomical Telegrams'' had a single business meeting during Honolulu General Assembly of the IAU. It took place on Tuesday, 11 August 2015. The meeting was attended by Hitoshi Yamaoka (President), Daniel Green (Director of the Central Bureau for Astronomical Telegrams, CBAT, via Skype), Steven Chesley (JPL), Paul Chodas (JPL), Alan Gilmore (Canterbury University), Shinjiro Kouzuma (Chukyo University), Paolo Mazzali (Co-Chair of the Supernova Working Group), Elena Pian (Scuola Normale Superiore di Pisa), Marion Schmitz (chair IAU Working Group Designations + NED), David Tholen (University of Hawaii), Jana Ticha (Klet Observatory), Milos Tichy (Klet Observatory), Giovanni Valsecchi (INAF\\slash Italy), Gareth Williams (Minor Planet Center). Apologies: Nikolai Samus (General Catalogue of Variable Stars, GCVS).

  14. Trihydrophobin 1 Phosphorylation by c-Src Regulates MAPK/ERK Signaling and Cell Migration

    Science.gov (United States)

    Wu, Weibin; Sun, Zhichao; Wu, Jingwen; Peng, Xiaomin; Gan, Huacheng; Zhang, Chunyi; Ji, Lingling; Xie, Jianhui; Zhu, Haiyan; Ren, Shifang

    2012-01-01

    c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. Further study reveals that Tyr-6 phosphorylation of TH1 reduces its inhibition on MAPK/ERK signaling, enhances c-Src mediated cell migration. Moreover, induced tyrosine phosphorylation of TH1 has been found by EGF and estrogen treatments. Taken together, our findings demonstrate a novel mechanism for the comprehensive regulation of Ras/Raf/MEK/ERK signaling and cell migration involving tyrosine phosphorylation of TH1 by c-Src. PMID:22238675

  15. 1. European conference on local democracies and nuclear power plants. Conference proceedings

    International Nuclear Information System (INIS)

    2000-01-01

    The Group of European Municipalities with Nuclear Facilities (GMF) was constituted in 1999. Its basic objectives are to keep and strengthen the relations between municipalities with the aim of consolidating a European network of municipalities with common problems; and to participate in European forums on the future of nuclear energy, contributing and helping in decision making processes. The GMF wants to become a support element to the local authorities of nuclear areas in order to foster their participation in the decision making processes, working continuously in collaboration with other agents of the nuclear sector, especially with the authorities of the European Commission, assuming that its major contribution is the knowledge of the everyday territorial reality, as a fundamental element that should be born in mind in all defined policies, whether on european or national level. It is stated that the debate on the future of nuclear energy represents a new era for the municipalities with nuclear facilities across Europe and that international cooperation will open the way for a better use of nuclear energy in Europe

  16. Status report 1999

    International Nuclear Information System (INIS)

    1999-01-01

    This 1999 annual report of the french Commissariat a l'Energie Atomique (Cea), gives a general overview of its activities, organization and international relations. The main subjects presented are: the energy policy in the nuclear energy (fuel cycle, reactors, management,thermonuclear fusion) the national defense contribution, the research program, the nuclear safety, the technology assessment, the valorization and transfer of knowledge, the scientific prices and the committees, councils and commissions. (A.L.B.)

  17. Action by the European Commission to promote nuclear safety outside the territory of the Union

    International Nuclear Information System (INIS)

    Joulia, J.P.

    2010-01-01

    The TACIS programme to improve nuclear safety in Central and Eastern Europe and the former USSR has now entered its final phase. A new programme 'the Instrument for Nuclear Safety Cooperation (INSC)' has been launched and its aim is to promote nuclear safety in all third-party countries. Support for improvement of the regulatory framework and the effectiveness of the bodies in charge of nuclear safety is a key element. Within the European Commission, the 'Europe, Southern Mediterranean, Middle East and Neighbourhood policy' Directorate, belonging to the AIDCO General Directorate, is tasked with implementation. (author)

  18. The European Federation of Organisations for Medical Physics Policy Statement No. 6.1: Recommended Guidelines on National Registration Schemes for Medical Physicists.

    Science.gov (United States)

    Christofides, Stelios; Isidoro, Jorge; Pesznyak, Csilla; Bumbure, Lada; Cremers, Florian; Schmidt, Werner F O

    2016-01-01

    This EFOMP Policy Statement is an update of Policy Statement No. 6 first published in 1994. The present version takes into account the European Union Parliament and Council Directive 2013/55/EU that amends Directive 2005/36/EU on the recognition of professional qualifications and the European Union Council Directive 2013/59/EURATOM laying down the basic safety standards for protection against the dangers arising from exposure to ionising radiation. The European Commission Radiation Protection Report No. 174, Guidelines on Medical Physics Expert and the EFOMP Policy Statement No. 12.1, Recommendations on Medical Physics Education and Training in Europe 2014, are also taken into consideration. The EFOMP National Member Organisations are encouraged to update their Medical Physics registration schemes where these exist or to develop registration schemes taking into account the present version of this EFOMP Policy Statement (Policy Statement No. 6.1"Recommended Guidelines on National Registration Schemes for Medical Physicists"). Copyright © 2016. Published by Elsevier Ltd.

  19. The European Commission in the power relations of the European Union after the 2004–07 enlargement

    Directory of Open Access Journals (Sweden)

    Ekaterina Ostrovskaya

    2014-05-01

    Full Text Available pplying a comparative perspective, this article argues that the current crisis of European Union integration cannot be resolved by member states either transferring additional competences to the EU level or strengthening the intergovernmental dimension of integration. The systemic character of the ongoing process is weakening the institutional structure, which affects both the institutions and their power relations. The European Commission (EC, once a highly independent supranational actor on the eve of the integration process in the 1950s, now faces growing competition from intergovernmental elements in the institutional balance. The theoretical approach of historical neo-institutionalism offers new, useful insights into this research area. The articles uses this theory to analyze the EC’s evolution since the time of its creation in the form of the High Authority of the European Coal and Steel Community, focusing on the links between the gradual changes in its internal structure and its institutional position. Although the phenomenon of “path dependence” was initially present in the EC’s internal systems, the later development of its competences in the institutional balance provoked member states to limit the commission’s activities in the second half of the 1960s. First attempts were made mainly by appointing weak presidents, but the later reform of the EC’s internal structure, undertaken by Neil Kinnock in the beginning of the 21st centry, directed its further structural development as a more technocratic institution. Consequently, the EC was not able to pursue its aims effectively in preparing for its enlargement to include Central and Eastern Europe. The increased heterogeneity of the member states after the 2004–07 enlargement also weakened the EC’s position in the institutional balance, diminishing its traditional function as the “engine of integration.”

  20. More planned economy than market economy in the energy policy strategy for 2020 of the European Commission; Mehr Plan- als Marktwirtschaft in der energiepolitischen Strategie 2020 der Europaeischen Kommission

    Energy Technology Data Exchange (ETDEWEB)

    Haucap, Justus; Coenen, Michael

    2011-04-15

    The Europeanization of energy policies is desirable because the three main objectives of energy policy (climate protection, security of supply and competitiveness) have cross-border impacts. Hence, it is good that the European Union has been granted a competence for energy policy in the article 194 of the Lisbon treaty. In addition, it is good that the European Commission has published its long-term strategy to stabilize expectations which is important for infrastructure investment. It is regrettable though that price signals, competition and market principles only play a minor role for the Commission while rather doubtful objectives such as fostering energy efficiency and promoting renewable dominate the agenda. The Commission's strategy is mainly characterized by bureaucratic dirigisme, intense regulation, state planning and public subsidies. The road to a centrally planned energy industry is being walked down fast.

  1. ERK phosphorylation regulates sleep and plasticity in Drosophila.

    Directory of Open Access Journals (Sweden)

    William M Vanderheyden

    Full Text Available Given the relationship between sleep and plasticity, we examined the role of Extracellular signal-regulated kinase (ERK in regulating baseline sleep, and modulating the response to waking experience. Both sleep deprivation and social enrichment increase ERK phosphorylation in wild-type flies. The effects of both sleep deprivation and social enrichment on structural plasticity in the LNvs can be recapitulated by expressing an active version of ERK (UAS-ERK(SEM pan-neuronally in the adult fly using GeneSwitch (Gsw Gsw-elav-GAL4. Conversely, disrupting ERK reduces sleep and prevents both the behavioral and structural plasticity normally induced by social enrichment. Finally, using transgenic flies carrying a cAMP response Element (CRE-luciferase reporter we show that activating ERK enhances CRE-Luc activity while disrupting ERK reduces it. These data suggest that ERK phosphorylation is an important mediator in transducing waking experience into sleep.

  2. New nuclear legislation proposals from the European Commission funds to cover nuclear liabilities

    International Nuclear Information System (INIS)

    Taylor, Derek M.

    2003-01-01

    On 30 January 2003, the European Commission adopted two proposals for new Directives in the area of nuclear safety: - a proposal for a Council Directive defining the basic obligations and the general principles on the safety of nuclear installations; - a proposal for a Council Directive on the management of spent nuclear fuel and radioactive waste. The first of these includes a requirement for the setting up of 'decommissioning funds'. However, this is a 'short-hand' title as the funds must cover all nuclear liabilities that remain after the end of operation of a nuclear installation, not just its closure and dismantling. The liabilities that remain following the closure of a nuclear installation need to be managed safely. They also need to be managed over a period that ranges from decades to centuries. It is vitally important that the financial resources for the safe management of these liabilities can be guaranteed over the full period. In the Commission's view, this can be best achieved by establishing a segregated fund that is built up over the operating life of the facility and by placing clear limitations on how the fund may be used. Ideally the segregated fund should be 'external' to the company and managed in such a way to ensure that it retains its value. The funds should not be spent on anything other than their identified purpose. The fund should be sufficient to cover all liabilities that remain once a facility stops generating revenue. These liabilities would include long-term management of spent nuclear fuel and all radioactive waste (including its disposal), not already paid for during operation, and the full dismantling of the facility. The Directive should cover all nuclear installations, not just nuclear power plants. It would not be logical to require a fund to cover reactor decommissioning, but not for a reprocessing plant. Special provisions will have to be made for those installations, such as some research reactors, that do not generate

  3. Constitutive activation of the ERK pathway in melanoma and skin melanocytes in Grey horses.

    Science.gov (United States)

    Jiang, Lin; Campagne, Cécile; Sundström, Elisabeth; Sousa, Pedro; Imran, Saima; Seltenhammer, Monika; Pielberg, Gerli; Olsson, Mats J; Egidy, Giorgia; Andersson, Leif; Golovko, Anna

    2014-11-21

    Constitutive activation of the ERK pathway, occurring in the vast majority of melanocytic neoplasms, has a pivotal role in melanoma development. Different mechanisms underlie this activation in different tumour settings. The Grey phenotype in horses, caused by a 4.6 kb duplication in intron 6 of Syntaxin 17 (STX17), is associated with a very high incidence of cutaneous melanoma, but the molecular mechanism behind the melanomagenesis remains unknown. Here, we investigated the involvement of the ERK pathway in melanoma development in Grey horses. Grey horse melanoma tumours, cell lines and normal skin melanocytes were analyzed with help of indirect immunofluorescence and immunoblotting for the expression of phospho-ERK1/2 in comparison to that in non-grey horse and human counterparts. The mutational status of BRAF, RAS, GNAQ, GNA11 and KIT genes in Grey horse melanomas was determined by direct sequencing. The effect of RAS, RAF and PI3K/AKT pathways on the activation of the ERK signaling in Grey horse melanoma cells was investigated with help of specific inhibitors and immunoblotting. Individual roles of RAF and RAS kinases on the ERK activation were examined using si-RNA based approach and immunoblotting. We found that the ERK pathway is constitutively activated in Grey horse melanoma tumours and cell lines in the absence of somatic activating mutations in BRAF, RAS, GNAQ, GNA11 and KIT genes or alterations in the expression of the main components of the pathway. The pathway is mitogenic and is mediated by BRAF, CRAF and KRAS kinases. Importantly, we found high activation of the ERK pathway also in epidermal melanocytes, suggesting a general predisposition to melanomagenesis in these horses. These findings demonstrate that the presence of the intronic 4.6 kb duplication in STX17 is strongly associated with constitutive activation of the ERK pathway in melanocytic cells in Grey horses in the absence of somatic mutations commonly linked to the activation of this

  4. Is "Better Regulation" Possible? Formal and Substantive Quality in the Impact Assessments in Education and Culture of the European Commission

    Science.gov (United States)

    Souto-Otero, Manuel

    2013-01-01

    This article explores the initial results produced by the European Commission's "better regulation agenda", which aims to stimulate productivity and employment, on the use of evidence and its potential to enhance democratic governance. The article finds that implausible rational models of policy making dictate the ways in which the…

  5. The European Commission's environmental stakeholder consultations: Is lobbying success based on what you know, what you own or who you know?

    DEFF Research Database (Denmark)

    Hermansson, Henrik Alf Jonas

    2015-01-01

    measures of expertise and privileged access than previously available, this paper evaluates whether the European Commission listens to stakeholder because of the expertise they provide, because of their influence at later legislative stages or because of their Brussels insider status. The paper also...

  6. Policy implementation for methicillin-resistant Staphylococcus aureus in seven European countries: a comparative analysis from 1999 to 2015.

    Science.gov (United States)

    Kinoshita, Takuya; Tokumasu, Hironobu; Tanaka, Shiro; Kramer, Axel; Kawakami, Koji

    2017-01-01

    Background : Policies to reduce methicillin-resistant Staphylococcus aureus (MRSA) infections, both healthcare-acquired (HA-MRSA) and livestock-associated (LA-MRSA) are implemented Europe-wide, but evaluations are difficult for countries yet to implement such policies. A descriptive study was conducted, describing multinational MRSA rates and policy implementation, focusing on MRSA mandatory surveillance. We also investigated antibiotic use and MRSA rates and the use of veterinary antibiotics. Methods : This study used Europe-wide surveillance data on infectious diseases (EARS-Net), antibiotic consumption (ESAC-Net), and veterinary medicine (ESVAC). We visualized LA- and HA-MRSA related policies and MRSA rates from 1999 to 2015 in seven European countries. Changes in MRSA rates after implementation of an MRSA mandatory surveillance policy were investigated by setting each country as rate of 1.0 and compared countries with and without such policy. Correlations between antibiotic use and MRSA rates from 1999 to 2012 were investigated using defined daily dose. Sales data were used to investigate veterinary antibiotic use. Results : MRSA rates were 1-45.4% across the seven countries between 1999 and 2015. MRSA rates changed between 0.61 and 0.24 after the implementation of mandatory surveillance policies within a 6-12 year span. The rate of decrease rate in implemented and non-implemented countries ranged from 10% in Spain to 76% in the UK. The correlation between MRSA rate and cephalosporin consumption was r  = 0.419, and for fluoroquinolones r  = 0.305. Mean annual sales of veterinary cephalosporin and quinolone antibiotics were lowest in the UK (0.8 mg/PCU) and highest in Spain (9.7 mg/PCU) between 2009 and 2014. Conclusions : There were similar but different health policy implications in the seven countries regarding LA- and HA-MRSA. Although causation could not be defined, some policies such as mandatory surveillance may be helpful for countries that have

  7. First annual report, 1998/1999

    International Nuclear Information System (INIS)

    1999-01-01

    The British Columbia Oil and Gas Commission was established in 1998 to regulate the crude oil, natural gas and pipeline activities within the province. In this first annual report the Commission reports significant progress in completing a multi-year business improvement plan designed to identify opportunities to streamline regulatory delivery and enhance the Commission's operations through strategies that will maintain a stable regulatory environment, thus increasing stakeholder confidence. Stakeholder cooperation is seen as the key to growth of the oil and gas industry in the province. To this end, the Commission places high priority on consultation and cooperation from the oil and gas industry, First Nations, local and regional governments, environmental organizations and the public. A review of activities to date include accounts of over 500 applications and approvals for drilling, seismic surveys, 575 applications for pipelines and facilities, over 1500 inspections to ensure regulatory compliance, signing of Memoranda of Understanding with five First Nations communities, and consideration of over 90 geology applications. The report also contains the Commissions audited financial statement for the October 23, 1998 - March 31, 1999 period

  8. European Commission study on energy costs and subsidies in the EU. Report for EDF

    International Nuclear Information System (INIS)

    Roques, Fabien; Perekhodtsev, Dmitri; Verhaeghe, Charles

    2014-01-01

    The European Commission (EC) has launched a study in order to provide a complete and consistent view on the subsidies and external costs associated with different power generation technologies. Such study is expected to provide input for policy making in years to come. FTI CL Energy has been mandated by EDF to provide a critical review of the methodology developed in the EC study, and to identify potential gaps in coverage and/or contestable assumptions. The study provides a description of best practice to improve the methodology and surveys the literature to provide a range of estimates for critical assumptions on costs and subsidies

  9. The programme and objectives of the Commission of the European Communities concerning radioactive wastes

    International Nuclear Information System (INIS)

    Orlowski, S.; Cricchio, A.; Girardi, F.

    1984-01-01

    The radioactive waste management programme of the Commission of the European Communities offers a good opportunity for co-operation between Member States. The Commission's principal objectives are: (1) to implement a Community action plan adopted in 1980 for a twelve-year period; (2) to promote research and development; (3) to ensure that radioactive waste management is conducted in conformity with environmental concerns and radiation protection norms. Under the action plan the current situation and prospects for radioactive waste management in the Community were evaluated in 1981-82. Other activities under the plan relate to the promotion of Community co-operation in final disposal and to the institution of a mechanism for Community consultations on criteria for the acceptance of conditioned wastes. The promotion of research and development involves a high degree of co-operation and effort to optimize or select procedures and to establish pilot or demonstration facilities. A budget of US$ 20 million at present supports these activities. With regard to radiation protection, in 1982 the Commission issued a recommendation for an investigation, at Community level, into the impact on all the Member States of operations such as waste treatment, dumping at sea, burial in the ground and storage of radioactive wastes. These objectives suggest that the solutions now under consideration for the management of high-level and long-lived wastes will by the end of this century be introduced alongside those already adopted in practice for low- and medium-level wastes. (author)

  10. European Union

    International Nuclear Information System (INIS)

    Schaller, K.

    1995-01-01

    Different instruments used by European Commission of the European Union for financial support radioactive waste management activities in the Russian Federation are outlined. Three particular programmes in the area are described

  11. Is Gender Mainstreamed? : A study of the European Commission's use of gender mainstreaming in development policies

    OpenAIRE

    Karlsson, Sophie

    2016-01-01

    The EU has long expressed a will to be a normative power and to externally promote the values it views as important. Seeing as the EU collectively is the largest donor of foreign aid in the world, development policies are a perfect platform for doing this. One value that has gained ground in recent years is the notion of gender equality. Bearing this in mind, this thesis explores how the EU’s largest institutional donor of foreign aid, the European Commission, has chosen to promote the value ...

  12. ISOLDE 1996-1999: Preparing for new science opportunities

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    1996-1999 was a time in which ISOLDE saw important changes. In order to make space for REX-ISOLDE the experimental hall saw its first extension and first equipment for REX-ISOLDE was installed and commissioned.

  13. The European Commission as Network Broker

    DEFF Research Database (Denmark)

    Borrás, Susana

    2007-01-01

    after the year 2000. Developing a conceptual framework about brokerage roles in EU policy, the article uses a combination of quantitative and qualitative data in an empirical analysis of two very different cases where the Commission has been embattled the past years. The article argues that previous...

  14. EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 李柏林; 宋敏; 宋继谒

    2004-01-01

    Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

  15. A European Commission software tool for radon risk calculation and evaluation of countermeasures

    Energy Technology Data Exchange (ETDEWEB)

    Degrange, J.P.; Levy, F.P. [CEPN, Fontenay-aux-Roses Cedex (France); Birchall, A.; Haylock, R.; Marsh, J.; Muirhead, C. [National Radiological Protection Board, Chilton (United Kingdom); Janssens, A. [European Commission, DG XI (Luxembourg)

    2000-05-01

    The effects of exposure to radon on workers and members of the public have been examined for many years. Recent advances have been made in evaluating the risk associated with radon exposure and in implementing remediation programmes in dwellings. However, decisions about whether to implement countermeasures to reduce radon exposures may benefit from an enhanced capability to evaluate and understand the associated health risk. In this context, the European Commission has launched a project to develop a user friendly software package based upon current information on radon epidemiology, radon dosimetry, demography, and countermeasure efficiency. The software has been designed to perform lung cancer risk calculations specific to European populations for various exposure profiles and to evaluate, in terms of risk reduction, the efficiency of various countermeasures in dwellings. This paper presents an overview of the general structure of the software and outlines its most important modelling approaches. The software is able to evaluate the risk of fatal lung cancer associated with individual or collective exposure to radon. The individual risk calculation module determines, for an individual of given age, sex and tobacco consumption, the excess risk for a given exposure (past or future exposure) time-profile, on the basis of demographic data (WHO, 1996 and 1998) specific to the selected population. The collective risk calculation module determines the excess risk for each occupant of a dwelling, for an exposure time-profile derived from data describing the dwelling, its occupancy, and the chosen countermeasures. These calculations may be done using one of two classical approaches: 1) The epidemiological approach in which the risk is obtained directly from the radon exposure data using a risk model (BEIR IV, 1988; BEIR VI, 1999) derived from epidemiological studies of uranium miners; 2) The dosimetric approach in which the risk is derived from the radon exposure data

  16. A European Commission software tool for radon risk calculation and evaluation of countermeasures

    International Nuclear Information System (INIS)

    Degrange, J.P.; Levy, F.P.; Birchall, A.; Haylock, R.; Marsh, J.; Muirhead, C.; Janssens, A.

    2000-01-01

    The effects of exposure to radon on workers and members of the public have been examined for many years. Recent advances have been made in evaluating the risk associated with radon exposure and in implementing remediation programmes in dwellings. However, decisions about whether to implement countermeasures to reduce radon exposures may benefit from an enhanced capability to evaluate and understand the associated health risk. In this context, the European Commission has launched a project to develop a user friendly software package based upon current information on radon epidemiology, radon dosimetry, demography, and countermeasure efficiency. The software has been designed to perform lung cancer risk calculations specific to European populations for various exposure profiles and to evaluate, in terms of risk reduction, the efficiency of various countermeasures in dwellings. This paper presents an overview of the general structure of the software and outlines its most important modelling approaches. The software is able to evaluate the risk of fatal lung cancer associated with individual or collective exposure to radon. The individual risk calculation module determines, for an individual of given age, sex and tobacco consumption, the excess risk for a given exposure (past or future exposure) time-profile, on the basis of demographic data (WHO, 1996 and 1998) specific to the selected population. The collective risk calculation module determines the excess risk for each occupant of a dwelling, for an exposure time-profile derived from data describing the dwelling, its occupancy, and the chosen countermeasures. These calculations may be done using one of two classical approaches: 1) The epidemiological approach in which the risk is obtained directly from the radon exposure data using a risk model (BEIR IV, 1988; BEIR VI, 1999) derived from epidemiological studies of uranium miners; 2) The dosimetric approach in which the risk is derived from the radon exposure data

  17. Commission of the european communities. Joint research centre. Petten Establishment. Annual Report 1977

    International Nuclear Information System (INIS)

    1977 marked the beginning of a new multiannual research programme for the European Commission's Joint research Centre. Regarding the exploitation of HFR (High Flux Reactor), the year was one of steady, on-schedule operation with high utilization, although this fell off slightly in the autumn due to overloading of our capsule project engineering team and manufacturing services. We are pleased to note that the HFR Users' Meeting, held in October, drew about 100 participants from Europe and America and demonstrated a lively interest in the Commission's materials testing reactor. Technical improvements to the plant are being examined as one means of maintaining or even increasing this interest in the 1980's. Following the wishes of the Council of Ministers, new Advisory Committees for Programme Management have been set up for all the Joint Research Centre's activities and those for HFR and High Temperature Materials Programmes have met at Petten. This latter Committee is entirely new to its task, the programme having been served until 1977 by a number of ad hoc meetings of national experts. The work of the Organic Chemistry Laboratory falls under the wings of the Community Reference Bureau Advisory Committee, who have met in Brussels and strongly encouraged the development of the activity

  18. The mechanism by which MEK/ERK regulates JNK and p38 activity in polyamine depleted IEC-6 cells during apoptosis

    Science.gov (United States)

    Bavaria, Mitul N.; Jin, Shi; Ray, Ramesh M.; Johnson, Leonard R.

    2014-01-01

    Polyamine-depletion inhibited apoptosis by activating ERK1/2, while, preventing JNK1/2 activation. MKP-1 knockdown by SiRNA increased ERK1/2, JNK1/2, and p38 phosphorylation and apoptosis. Therefore, we predicted that polyamines might regulate MKP1 via MEK/ERK and thereby apoptosis. We examined the role of MEK/ERK in the regulation of MKP1 and JNK, and p38 activities and apoptosis. Inhibition of MKP-1 activity with a pharmacological inhibitor, sanguinarine (SA), increased JNK1/2, p38, and ERK1/2 activities without causing apoptosis. However, pre-activation of these kinases by SA significantly increased camptothecin (CPT)-induced apoptosis suggesting different roles for MAPKs during survival and apoptosis. Inhibition of MEK1 activity prevented the expression of MKP-1 protein and augmented CPT-induced apoptosis, which correlated with increased activities of JNK1/2, caspases, and DNA fragmentation. Polyamine depleted cells had higher levels of MKP-1 protein and decreased JNK1/2 activity and apoptosis. Inhibition of MEK1 prevented MKP-1 expression and increased JNK1/2 and apoptosis. Phospho-JNK1/2, phospho-ERK2, MKP-1, and the catalytic subunit of protein phosphatase 2A (PP2Ac) formed a complex in response to TNF/CPT. Inactivation of PP2Ac had no effect on the association of MKP-1 and JNK1. However, inhibition of MKP-1 activity decreased the formation of the MKP-1, PP2Ac and JNK complex. Following inhibition by SA, MKP-1 localized in the cytoplasm, while basal and CPT-induced MKP-1 remained in the nuclear fraction. These results suggest that nuclear MKP-1 translocates to the cytoplasm, binds phosphorylated JNK and p38 resulting in dephosphorylation and decreased activity. Thus, MEK/ERK activity controls the levels of MKP-1 and, thereby, regulates JNK activity in polyamine-depleted cells. PMID:24253595

  19. The D Domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits MEK/ERK activation in glioma cells

    Directory of Open Access Journals (Sweden)

    Zeyou Wang

    2016-11-01

    Full Text Available Abstract Background As a well-characterized key player in various signal transduction networks, extracellular-signal-regulated kinase (ERK1/2 has been widely implicated in the development of many malignancies. We previously found that Leucine-rich repeat containing 4 (LRRC4 was a tumor suppressor and a negative regulator of the ERK/MAPK pathway in glioma tumorigenesis. However, the precise molecular role of LRRC4 in ERK signal transmission is unclear. Methods The interaction between LRRC4 and ERK1/2 was assessed by co-immunoprecipitation and GST pull-down assays in vivo and in vitro. We also investigated the interaction of LRRC4 and ERK1/2 and the role of the D domain in ERK activation in glioma cells. Results Here, we showed that LRRC4 and ERK1/2 interact via the D domain and CD domain, respectively. Following EGF stimuli, the D domain of LRRC4 anchors ERK1/2 in the cytoplasm and abrogates ERK1/2 activation and nuclear translocation. In glioblastoma cells, ectopic LRRC4 expression competitively inhibited the interaction of endogenous mitogen-activated protein kinase (MEK and ERK1/2. Mutation of the D domain decreased the LRRC4-mediated inhibition of MAPK signaling and its anti-proliferation and anti-invasion roles. Conclusions Our results demonstrated that the D domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits MEK/ERK activation in glioma cells. These findings identify a new mechanism underlying glioblastoma progression and suggest a novel therapeutic strategy by restoring the activity of LRRC4 to decrease MAPK cascade activation.

  20. Variations in the pace of old-age mortality decline in seven European countries, 1950-1999 : the role of smoking and other factors earlier in life

    NARCIS (Netherlands)

    Janssen, Fanny; Kunst, Anton; Mackenbach, Johan

    We examine the variations in the pace of old-age (80+) mortality decline in seven European countries, from 1950 to 1999. Marked variations were found between countries, periods and sexes. While mortality declines were strong in France and England and Wales, modest or no mortality declines were seen

  1. Erk1 positively regulates osteoclast differentiation and bone resorptive activity.

    Directory of Open Access Journals (Sweden)

    Yongzheng He

    Full Text Available The extracellular signal-regulated kinases (ERK1 and 2 are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/- bone marrow mononuclear cells (BMMNCs demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/- BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

  2. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a population-based study.

    Science.gov (United States)

    De Angelis, Roberta; Sant, Milena; Coleman, Michel P; Francisci, Silvia; Baili, Paolo; Pierannunzio, Daniela; Trama, Annalisa; Visser, Otto; Brenner, Hermann; Ardanaz, Eva; Bielska-Lasota, Magdalena; Engholm, Gerda; Nennecke, Alice; Siesling, Sabine; Berrino, Franco; Capocaccia, Riccardo

    2014-01-01

    Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE-the largest cooperative study of population-based cancer survival in Europe-has shown persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries. In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000-07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999-2001, 2002-04, and 2005-07). 5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999-2001 to 2005-07 were for prostate cancer (73.4% [95% CI 72.9-73.9] vs 81.7% [81.3-82.1]), non-Hodgkin lymphoma (53.8% [53.3-54.4] vs 60.4% [60.0-60.9]), and rectal cancer (52.1% [51.6-52.6] vs 57.6% [57.1-58.1]). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although

  3. SEEWIND - South-East European Wind Energy Exploitation. Wind energy research in South East Europe under the EC FP6 programme; SEEWIND - South-East European Wind Energy Exploitation. Windenergieforschung im 6. Rahmenprogramm der Europaeischen Union in Suedosteuropa

    Energy Technology Data Exchange (ETDEWEB)

    Winkelmeier, H. [Verein Energiewerkstatt (Austria)

    2008-08-15

    Large areas in South East Europe offer perfect conditions for the Utilisation of Wind Energy. Local wind systems like ''Bora'', which occurs along the Adriatic Sea, or ''Koshava'', which flows between the ridge of the Carpathian Mountains and the Balkan Mountains from Romania over to Serbia, are generated through differences in pressure and temperature between the adjacent regions. Those wind systems therefore can be described as 'home made' and have very individual characteristics. Despite the excellent wind conditions of those locations, the mainly cliffy and complex terrain and the extreme wind conditions with turbulences and strong gusts make great demands on the design and operation of the wind turbines. Exactly those problems the European Commission asked to be investigated and therefore defined 'Complex terrain and local wind systems' as one of the research topics in the last call of the 6th Framework Programme. Under the lead management of Verein Energiewerkstatt, a consortium of ten partners from seven middle- and southeast European countries took part in this call for proposals and received acceptance for the submitted Project ''SEEWIND - South-East European Wind Energy Exploitation''. (orig.)

  4. Histone Deacetylase 3 Suppresses Erk Phosphorylation and Matrix Metalloproteinase (Mmp)-13 Activity in Chondrocytes

    Science.gov (United States)

    Carpio, Lomeli R.; Bradley, Elizabeth W.; Westendorf, Jennifer J.

    2017-01-01

    Histone deacetylase inhibitors are emerging therapies for many diseases including cancers and neurological disorders; however, these drugs are teratogens to the developing skeleton. Hdac3 is essential for proper endochondral ossification as its deletion in chondrocytes increases cytokine signaling and the expression of matrix remodeling enzymes. Here we explored the mechanism by which Hdac3 controls Mmp13 expression in chondrocytes. In Hdac3-depleted chondrocytes, Erk1/2 as well as its downstream substrate, Runx2, were hyperphosphorylated as a result of decreased expression and activity of the Erk1/2 specific phosphatase, Dusp6. Erk1/2 kinase inhibitors and Dusp6 adenoviruses reduced Mmp13 expression and partially rescued matrix production in Hdac3-deficient chondrocytes. Postnatal chondrocyte-specific deletion of Hdac3 with an inducible Col2a1-Cre caused premature production of pErk1/2 and Mmp13 in the growth plate. Thus, Hdac3 controls the temporal and spatial expression of tissue-remodeling genes in chondrocytes to ensure proper endochondral ossification during development. PMID:27662443

  5. Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors

    Science.gov (United States)

    Papale, Alessandro; Morella, Ilaria Maria; Indrigo, Marzia Tina; Bernardi, Rick Eugene; Marrone, Livia; Marchisella, Francesca; Brancale, Andrea; Spanagel, Rainer; Brambilla, Riccardo; Fasano, Stefania

    2016-01-01

    Ras-ERK signalling in the brain plays a central role in drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested in experimental models of addiction, a necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 - that penetrate the brain and, in the micromolar range, inhibit phosphorylation of ERK, histone H3 and S6 ribosomal protein in striatal slices. Furthermore, a screening of small therapeutics currently in clinical trials for cancer therapy revealed PD325901 as a brain-penetrating drug that blocks ERK signalling in the nanomolar range. All three compounds have an inhibitory effect on cocaine-induced ERK activation and reward in mice. In particular, PD325901 persistently blocks cocaine-induced place preference and accelerates extinction following cocaine self-administration. Thus, clinically relevant, systemically administered drugs that attenuate Ras-ERK signalling in the brain may be valuable tools for the treatment of cocaine addiction. DOI: http://dx.doi.org/10.7554/eLife.17111.001 PMID:27557444

  6. The politics of a European civil code

    NARCIS (Netherlands)

    Hesselink, M.W.

    2004-01-01

    Last year the European Commission published its Action Plan on European contract law. That plan forms an important step towards a European Civil Code. In its Plan, the Commission tries to depoliticise the codification process by asking a group of academic experts to prepare what it calls a 'common

  7. 18 CFR 39.6 - Conflict of a Reliability Standard with a Commission Order.

    Science.gov (United States)

    2010-04-01

    ... Reliability Standard with a Commission Order. 39.6 Section 39.6 Conservation of Power and Water Resources..., APPROVAL, AND ENFORCEMENT OF ELECTRIC RELIABILITY STANDARDS § 39.6 Conflict of a Reliability Standard with... Transmission Organization determines that a Reliability Standard may conflict with a function, rule, order...

  8. 20 April 2011 - President of the European Commission J.M. Barroso visiting the LHC tunnel at Point 5 and CMS experimental cavern.

    CERN Document Server

    Maximilien Brice

    2011-01-01

    CERN-HI-1104125 02 - 18: President Barroso is welcomed in the French territory by the Representative of the French Republic O. Laurens-Bernard, Sous-Préfet de Gex, then, in the welcome line, CERN Director General introduces: Director for Research and Scientific Computing S. Bertolucci Portuguese Delegate to CERN Council G. Barreira Head of International Relations F. Pauss Head of Physics Department P. Bloch Head of Technology Department F. Bordry Head of Beams Department P. Collier Head of Information Technology Department F. Hemmer CMS Collaboration Spokesperson G. Tonelli Project Coordinator of FP7 EuCARD J.-P. Koutchouk and CERN EU Projects Leader S. Stavrev. From left to right on CERN-HI-1104125 91: Head of the EU Delegation to the WTO A. Pangratis;General Director, DG Research and Innovation, European Commission R. J. Smits; CERN Director for Research and Scientific Computing S. Bertolucci; Head of International Relations F. Pauss; President of the European Commission J. M. Barroso;CERN Director-Genera...

  9. European Commission Initiatives to Promote Social Concern on the Market: a Counterbalance to Fiscal Discipline?

    Directory of Open Access Journals (Sweden)

    Laura Gómez Urquijo

    2014-03-01

    Full Text Available The aim of this article is to analyse the significance of recent European Commission initiatives in the face of evidence of non-compliance with the social objectives targeted in the EU 2020 Strategy. In the midst of the ongoing debate regarding austerity and growth, we stress the need to further the EU trend toward differentiated growth-friendly fiscal consolidation. Given that “conditionality” is a new keystone of economic governance and cohesion policy, the difficulties that the Member States encounter and the diversity of their social protections give a new meaning to the European coordination policies that are intended to promote social cohesion. By analysing EU proposals and official documents, we will show how the Commission’s initiatives have introduced diverse elements that are intended to address the social consequences of the economic crisis and reveal how new ideas of growth and new ways to deepen the internal market have been promoted. We will also determine whether we can consider these ideas to be a valid response to current social challenges.

  10. The Institutional vs. the Academic Definition of the Quality of Work Life. What Is the Focus of the European Commission?

    Science.gov (United States)

    Royuela, Vicente; Lopez-Tamayo, Jordi; Surinach, Jordi

    2008-01-01

    In recent years, we have seen how the quality of work life has been focused and defined by the European Commission (EC). In our study we compare the EC definition with the academic one and try to see how close they are. We also analyse the possibility of applying the institutional definition to the Spanish case through the development of specific…

  11. ATF2 Commissioning

    Energy Technology Data Exchange (ETDEWEB)

    Seryi, A.; /SLAC; Christian, G.; /KLTE-ATOMKI; Parker, B.; /BNL; Schulte, D.; Delahaye, J.-P.; Tomas, R.; Zimmermann, F.; /CERN; Wolski, A.; Elsen, E.; /Cockcroft Inst. /DESY; Sanuki, T.; /Tohoku U.; Gianfelice-Wendt, E.; Ross, M.; Wendt, M.; /Fermilab; Takahashi, T.; /Hiroshima U.; Bai, S.; Gao, J.; /Beijing, Inst. High Energy Phys.; Bolzon, B.; Geffroy, N.; Jeremie, A.; /Annecy, LAPP; Apsimon, R.; Burrows, P.; /Oxford U., JAI /Kyoto U., Inst. Chem. Res. /Kyungpook Natl. U. /Orsay, LAL /Phang Accelerator Lab /Royal Holloway, U. of London /SLAC /Daresbury /University Coll. London /Manchester U. /Univ. of Tokyo U.

    2009-10-30

    ATF2 is a final-focus test beam line that aims to focus the low-emittance beam from the ATF damping ring to a beam size of about 37 nm, and at the same time to demonstrate nm beam stability, using numerous advanced beam diagnostics and feedback tools. The construction has been finished at the end of 2008 and the beam commissioning of ATF2 has started in December of 2008. ATF2 is constructed and commissioned by ATF international collaborations with strong US, Asian and European participation.

  12. ATF2 COMMISSIONING

    CERN Document Server

    Seryi, A; Parker, B; Schulte, D; Delahaye, J P; Tomas, R; Zimmermann, F; Wolski, A; Elsen, E; Sanuki, T; Gianfelice-Wendt, E; Ross, M; Wendt, M; Takahashi, T; Bai, S; Gao, J; Bolzon, B; Geffroy, N; Jeremie, A; Apsimon, R; Burrows, P; Constance, B; Perry, C; Resta-Lopez, J; Swinson, C; Araki, S; Aryshev, A; Hayano, H; Honda, Y; Kubo, K; Kume, T; Kuroda, S; Masuzawa, M; Naito, T; Okugi, T; Sugahara, R; Tauchi, T; Terunuma, N; Urakawa, J; Yokoya, K; Iwashita, Y; Sugimoto, T; Heo, A Y; Kim, E S; Kim, H S; Bambade, P; Renier, Y; Rimbault, C; Huang, J Y; Kim, S H; Park, Y J; Hwang, W H; Blair, G; Boogert, S; Karataev, P; Molloy, S; Amann, J; Bellomo, P; Lam, B; McCormick, D; Nelson, J; Paterson, E; Pivi, M; Raubenheimer, T; Spencer, C; Wang, M H; White, G; Wittmer, W; Woodley, M; Yan, Y; Zhou, F; Angal-Kalinin, D; Jones, J; Lyapin, A; Scarfe, A; Kamiya, Y; Komamiya, S; Oroku, M; Suehara, T; Yamanaka, T

    2010-01-01

    ATF2 is a final-focus test beam line that aims to focus the low-emittance beam from the ATF damping ring to a beam size of about 37 nm, and at the same time to demonstrate nm beam stability, using numerous advanced beam diagnostics and feedback tools. The construction has been finished at the end of 2008 and the beam commissioning of ATF2 has started in December of 2008. ATF2 is constructed and commissioned by ATF international collaborations with strong US, Asian and European participation.

  13. The second pillar of the CAP: the role of Commission policy learning in the creation and reform of EU rural development policy (1968-1999)

    DEFF Research Database (Denmark)

    Steffensen, Jonny Trapp

    argument advanced in this thesis is that policy learning is a multifaceted phenomenon that can most reliably be examined employing 'method pluralism' (documentary analysis, elite interviews, and survey techniques). A second theoretical assertion is that policy learning can change the beliefs - termed......This thesis examines the concept of 'policy learning' and explores its applicability to the European Commission's role in EU policymaking. Policy learning refers to 'knowledge-based' policy formulation, where content of policy proposals is shaped to a 'non-trivial' extent by administrative...... 'policy strategy' - of political actors. A third theoretical contribution is the concept of 'bureaucratic policy learning capability' (BPLC) which refers to an organisation's ability and inclination to utilise available policy-relevant knowledge. I assess the Commission's BPLC through a survey, designed...

  14. European internal electricity market. What next?

    International Nuclear Information System (INIS)

    Petrov, K.; Hewicker, C.; Boisseleau, F.; Nabuurs, P.

    2007-01-01

    2006 has been a very active year in the development of electricity markets worldwide. In Europe the liberalisation process was moving forward driven by the European Directives implemented in the EU states. Together with security of supply and environmental protection, implementation of competitive energy markets has also been one of the main objectives of EU energy policy. A competitive internal market for electricity has been progressively implemented across the European Union since 1999-2000. This process aims at increasing competition in electricity generation and supply leading to enhanced efficiency, which is closely associated with lower production costs and ultimately lower electricity prices. The sector inquiry and the country reviews conducted by the European Commission (EC) during 2006 showed that progress has been achieved. However, there are still a number of issues that need to be resolved in order to achieve an adequately operating internal electricity market. The EC energy package from 10th January 2007 is a set of concrete proposals for action in the energy field and arises in reaction to the Green Paper published on 8th March 2006. The Green Paper 'A European Strategy for Sustainable, Competitive and Secure Energy', on the one hand, identified the main problems that the European energy sector faces and, on the other hand, suggested possible actions to meet key objectives, including security of supply, environmental sustainability and competitiveness towards a unified European Energy Policy. The motivation of the EC package is the need to identify new measures or a strengthening of existing measures to reach the targets and their underlying objectives. The EC package deals with the main issues on energy policy (renewable electricity, internal electricity and gas market, sector competition, sustainable power generation from fossil fuels, nuclear energy, gas and electricity infrastructures and energy technology) and an action plan for energy

  15. Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

  16. The radioactive waste management program of The Commission of the European Communities: Past, present, and future trends

    International Nuclear Information System (INIS)

    Orlowski, S.M.

    1983-01-01

    The radioactive waste management program started in the mid-1970s is being carried out by the Commission of European Communities (CEC) Joint Research Centre and by research bodies within the European community under CEC coordination and partial financing. The program deals with the management of the radioactive waste resulting from uranium-plutonium fuel cycle. During its first phase (1973-1979), various treatment and conditioning processes were investigated; high temperature incineration and acid digestion of alpha-bearing waste, immobilization of highly active waste in borosilicate glasses, inter alia, appeared promising. Geological disposal was recognized as a feasible option; transmutation of long-lived products did not appear to be an advantageous alternative to geological disposal, and the studies were discontinued. The second phase (1980-1984) of the program is a followup to the first. The needs of the European nuclear industry and of the national radioactive waste agencies or operators recently created are, however, taken into account. The continuity of the RandD effort is ensured by a ''Community plan of action on waste management,'' (1980-1992). A third phase, 1984-1989, should demonstrate the availability and validity of the waste management techniques and be convincing about their safety

  17. Differential phosphorylation of Smad1 integrates BMP and neurotrophin pathways through Erk/Dusp in axon development.

    Science.gov (United States)

    Finelli, Mattéa J; Murphy, Kevin J; Chen, Lei; Zou, Hongyan

    2013-05-30

    Sensory axon development requires concerted actions of growth factors for the precise control of axonal outgrowth and target innervation. How developing sensory neurons integrate different cues is poorly understood. We demonstrate here that Smad1 activation is required for neurotrophin-mediated sensory axon growth in vitro and in vivo. Through differential phosphorylation, Smad1 exerts transcriptional selectivity to regulate the expression and activity of Erk1 and Erk2-two key neurotrophin effectors. Specifically, bone morphogenetic proteins (BMPs) signal through carboxy-terminal phosphorylation of Smad1 (pSmad1C) to induce Erk1/2 transcription for enhanced neurotrophin responsiveness. Meanwhile, neurotrophin signaling results in linker phosphorylation of Smad1 (pSmad1L), which in turn upregulates an Erk-specific dual-specificity phosphatase, Dusp6, leading to reduced pErk1/2 and constituting a negative-feedback loop for the prevention of axon overgrowth. Together, the BMP and neurotrophin pathways form a tightly regulated signaling network with a balanced ratio of Erk1/2 and pErk1/2 to direct the precise connections between sensory neurons and peripheral targets. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Cobenefits of climate and air pollution regulations. The context of the European Commission Roadmap for moving to a low carbon economy in 2050

    Energy Technology Data Exchange (ETDEWEB)

    Koelemeijer, R.; Eerens, H.; Van Velze, K. [Netherlands Environmental Assessment Agency PBL, Den Haag (Netherlands); Colette, A.; Schucht, S.; Pere, J.C.; Bessagnet, B.; Rouil, L. [Institut National de l' Environnement Industriel et des Risques INERIS, Verneuil-en-Halatte (France); Mellios, G. [EMISIA, Thessaloniki (Greece)

    2012-03-15

    In 2011, the European Commission published its roadmap towards a competitive low-carbon economy for 2050. For this roadmap the possibilities of a far-reaching reduction in greenhouse gas emissions in Europe were assessed (a decrease of 80% by 2050 compared to 1990 levels). This report was written at the request of the European Environment Agency and examines the effects of such a reduction on air quality. Analysis of several existing scenarios indicates that climate policy, in general, leads to a decrease in air pollution in Europe.

  19. StreamNet; 1999 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Columbia River Inter-Tribal Fish Commission

    2000-01-01

    This report was funded by the Bonneville Power Administration (BPA), US Department of Energy, as part of BPA's program to protect, mitigate, and enhance fish and wildlife affected by the development and operation of hydroelectric facilities on the Columbia River and its tributaries. The views of this report are the author's and do not necessarily represent the views of BPA. This annual report covers progress made by: Columbia River Inter-Tribal Fish Commission Idaho; Department of Fish and Game; Montana Department of Fish, Wildlife and Parks; Oregon Department of Fish and Wildlife; Pacific States Marine Fisheries Commission; Shoshone-Bannock Tribes; US Fish and Wildlife Service; Washington Department of Fish and Wildlife; and FY1999 StreamNet Quickplan.

  20. GLP-1 Treatment Improves Diabetic Retinopathy by Alleviating Autophagy through GLP-1R-ERK1/2-HDAC6 Signaling Pathway.

    Science.gov (United States)

    Cai, Xiangsheng; Li, Jingjing; Wang, Mingzhu; She, Miaoqin; Tang, Yongming; Li, Jinlong; Li, Hongwei; Hui, Hongxiang

    2017-01-01

    Objective: Apoptosis and autophagy of retinal cells, which may be induced by oxidative stress, are tightly associated with the pathogenesis of diabetic retinopathy (DR). The autophagy induced by oxidative stress is considered as excessively stimulated autophagy, which accelerates the progression of DR. This study aims to investigate the protective effect of GLP-1 treatment on alleviating apoptosis and autophagy of retinal cells in type 2 diabetic rats and reveals its possible mechanism. Methods: Type 2 diabetic rats were induced by fed with high sugar, high fat diet and followed with streptozotocin injection. GLP-1 was applied to treat the diabetic rats for one week after the onset of diabetes. The expressions of oxidative stress-related enzymes, retinal GLP-1R, mitochondria-dependent apoptosis- related genes, autophagy markers, and autophagy-associated pathway genes were studied by Western blotting or immunohistochemistry analysis. Results: GLP-1treatment reduced the levels of NOX3 and SOD2 in DR. The expression of BCL2 was increased, while the levels of caspase3 and LC3B were reduced through GLP-1 treatment in DR . GLP-1 treatment restored the GLP-1R expression and decreased the levels of phosphorylated AKT and phosphorylated ERK1/2, which was accompanied with the reduction of the HDAC6 levels in DR. Conclusions: GLP-1 treatment can alleviate autophagy which may be induced by oxidative stress; this protective effect is likely through GLP-1R-ERK1/2-HDAC6 signaling pathway.

  1. Some THINKing on European energy policy

    OpenAIRE

    GLACHANT, Jean-Michel; MEEUS, Leonardo; RUESTER, Sophia

    2013-01-01

    QM-02-13-166-EN-C QM-02-13-166-EN-N Energy regulation and policy currently belong to the most important and developing areas in the European Union. THINK, the Florence School of Regulation’s think tank was running from June 2010 to May 2013. THINK advised the European Commission (DG Energy) on Energy Policy and presented policy options each semester. This booklet gives an overview of the THINK output published in the second half of the project and focuses on 6 topics: How to Refurbish A...

  2. ERK5 and cell proliferation: nuclear localization is what matters

    Directory of Open Access Journals (Sweden)

    Nestor Gomez

    2016-09-01

    Full Text Available ERK5, the last MAP kinase family member discovered, is activated by the upstream kinase MEK5 in response to growth factors and stress stimulation. MEK5-ERK5 pathway has been associated to different cellular processes, playing a crucial role in cell proliferation in normal and cancer cells by mechanisms that are both dependent and independent of its kinase activity. Thus, nuclear ERK5 activates transcription factors by either direct phosphorylation or acting as co-activator thanks to a unique transcriptional activation TAD domain located at its C-terminal tail. Consequently, ERK5 has been proposed as an interesting target to tackle different cancers, and either inhibitors of ERK5 activity or silencing the protein have shown antiproliferative activity in cancer cells and to block tumour growth in animal models. Here, we review the different mechanisms involved in ERK5 nuclear translocation and their consequences. Inactive ERK5 resides in the cytosol, forming a complex with Hsp90-Cdc37 superchaperone. In a canonical mechanism, MEK5-dependent activation results in ERK5 C-terminal autophosphorylation, Hsp90 dissociation and nuclear translocation. This mechanism integrates signals such as growth factors and stresses that activate the MEK5-ERK5 pathway. Importantly, two other mechanisms, MEK5-independent, have been recently described. These mechanisms allow nuclear shuttling of kinase-inactive forms of ERK5. Although lacking kinase activity, these forms activate transcription by interacting with transcription factors through the TAD domain. Both mechanisms also require Hsp90 dissociation previous to nuclear translocation. One mechanism involves phosphorylation of the C-terminal tail of ERK5 by kinases that are activated during mitosis, such as Cyclin-dependent kinase-1. The second mechanism involves overexpression of chaperone Cdc37, an oncogene that is overexpressed in cancers such as prostate adenocarcinoma, where it collaborates with ERK5 to promote

  3. ERα and ERK1/2 MAP kinase expression in microdissected stromal and epithelial endometrial cells

    Directory of Open Access Journals (Sweden)

    Said Abu Alkhair Mohamed

    2014-03-01

    Total and phosphorylated levels for ERK1/2 and ERα were measured by quantitation of signals from Western blots using specific antibodies against the active and total forms of ERK1/2 and against ERα. When the level of the proteins was quantitated and normalized to β actin from microdissected stroma and epithelium, no significant difference was detected in the levels of these proteins between the two tissue compartments. There was a trend toward higher expression in the stroma vs. epithelium, respectively (active ERK1/2 0.45 ± 0.17 vs. 0.2 ± 0.65; total ERK1/2 0.54 ± 0.35 vs. 0.28 ± 0.23; ERα 0.82 ± 0.28 vs. 0.54 ± 0.18; n = 6. These data demonstrate that there are comparable levels of ERα (P = 0.41, total ERK1/2 (P = 0.18 and active ERK1/2 (P = 0.13 in the stroma and epithelium of proliferative phase endometrium with a trend toward higher expression of these proteins in the stromal compartment.

  4. 00001:Airline Service Quality Performance 234 (On-Time performance data).

    Science.gov (United States)

    2011-11-01

    00001:This CD presents data reported by U.S. certificated air carriers so that information on the air carriers' quality of service can be made available to consumers of air transportation. Carriers within 1% or more of the total domestic scheduled se...

  5. 00001:Airline Service Quality Performance 234 (On-Time performance data).

    Science.gov (United States)

    2014-02-01

    00001:This CD presents data reported by U.S. certificated air carriers so that information on the air carriers' quality of service can be made available to consumers of air transportation. Carriers within 1% or more of the total domestic scheduled se...

  6. Drought footprint on European ecosystems between 1999 and 2010 assessed by remotely sensed vegetation phenology and productivity

    DEFF Research Database (Denmark)

    Ivits, Eva; Horion, Stéphanie Marie Anne F; Fensholt, Rasmus

    2014-01-01

    bioclimatic zones. The Standardized Precipitation and Evapotranspiration Index (SPEI) was used as drought indicator whereas changes in growing season length and vegetation productivity were assessed using remote sensing time-series of Normalized Difference Vegetation Index (NDVI). Drought spatio...... length, indicating that these ecosystems did not buffer the effects of drought well. In a climate change perspective, increase in drought frequency or intensity may result in larger impacts over these ecosystems, thus management and adaptation strategies should be strengthened in these areas of concerns.......Drought affects more people than any other natural disaster but there is little understanding of how ecosystems react to droughts. This study jointly analyzed spatio-temporal changes of drought patterns with vegetation phenology and productivity changes between 1999 and 2010 in major European...

  7. 26th May 2011 -Delegate to CERN Open Council sessions and European Commission Head of Unit for Joint Programming European Research Area, DG Research and Innovation R. Lečbychová visiting the CERN Control Centre with M. Pojer, accompanied by CERN S. Stavrev.

    CERN Multimedia

    Maximilien Brice

    2011-01-01

    26th May 2011 -Delegate to CERN Open Council sessions and European Commission Head of Unit for Joint Programming European Research Area, DG Research and Innovation R. Lečbychová visiting the CERN Control Centre with M. Pojer, accompanied by CERN S. Stavrev.

  8. Amitriptyline induces early growth response-1 gene expression via ERK and JNK mitogen-activated protein kinase pathways in rat C6 glial cells.

    Science.gov (United States)

    Chung, Eun Young; Shin, Soon Young; Lee, Young Han

    2007-07-05

    Astrocytes play important roles in guiding the construction of the nervous system, controlling extracellular ions and neurotransmitters, and regulating CNS synaptogenesis. Egr-1 is a transcription factor involved in neuronal differentiation and astrocyte cell proliferation. In this study, we investigated whether the tricyclic antidepressant (TCA) amitriptyline induces Egr-1 expression in astrocytes using rat C6 glioma cells as a model. We found that amitriptyline increased the expression of Egr-1 in a dose- and time-dependent manner. The amitriptyline-induced Egr-1 expression was mediated through serum response elements (SREs) in the Egr-1 promoter. SREs were activated by the Ets-domain transcription factor Elk-1 through the ERK and JNK mitogen-activated protein (MAP) kinase pathways. The inhibition of the ERK and JNK MAP kinase signals attenuated amitriptyline-induced transactivation of Gal4-Elk-1 and Egr-1 promoter activity. Our findings suggest that the induction of Egr-1 expression in astrocytes may be required to attain the therapeutic effects of antidepressant drugs.

  9. A European Master's Programme in Public Health Nutrition.

    Science.gov (United States)

    Yngve, A; Warm, D; Landman, J; Sjöström, M

    2001-12-01

    Effective population-based strategies require people trained and competent in the discipline of Public Health Nutrition. Since 1997, a European Master's Programme in Public Health Nutrition has been undergoing planning and implementation, by establishing initial quality assurance systems with the aid of funding from the European Commission (DG SANCO/F3). Partners from 17 European countries have been involved in the process. A European Network of Public Health Nutrition has been developed and accredited by the European Commission.

  10. ERK mutations confer resistance to mitogen-activated protein kinase pathway inhibitors.

    Science.gov (United States)

    Goetz, Eva M; Ghandi, Mahmoud; Treacy, Daniel J; Wagle, Nikhil; Garraway, Levi A

    2014-12-01

    The use of targeted therapeutics directed against BRAF(V600)-mutant metastatic melanoma improves progression-free survival in many patients; however, acquired drug resistance remains a major medical challenge. By far, the most common clinical resistance mechanism involves reactivation of the MAPK (RAF/MEK/ERK) pathway by a variety of mechanisms. Thus, targeting ERK itself has emerged as an attractive therapeutic concept, and several ERK inhibitors have entered clinical trials. We sought to preemptively determine mutations in ERK1/2 that confer resistance to either ERK inhibitors or combined RAF/MEK inhibition in BRAF(V600)-mutant melanoma. Using a random mutagenesis screen, we identified multiple point mutations in ERK1 (MAPK3) and ERK2 (MAPK1) that could confer resistance to ERK or RAF/MEK inhibitors. ERK inhibitor-resistant alleles were sensitive to RAF/MEK inhibitors and vice versa, suggesting that the future development of alternating RAF/MEK and ERK inhibitor regimens might help circumvent resistance to these agents. ©2014 American Association for Cancer Research.

  11. 6th European symposium on uroradiology

    International Nuclear Information System (INIS)

    Bujlov, V.M.

    1999-01-01

    Materials of the 6th European symposium on uroradiology held in Strasbourg (France) in September, 1998. Symposium topics included problems of radiological diagnosis of kidneys, renovascular hypertension, man and woman sterility, pelvis organs of men and women, functional studies of lower urinary tract, pediatric and interventional uroradiology. Great attention is paid to magnetic resonance tomography, ultrasonography and conventional biomedical radiography [ru

  12. The Harmonization of Public Sector Accounting in European Union

    DEFF Research Database (Denmark)

    Pontoppidan, Caroline Aggestam; Alijarde, Isabel Brusca; Chow, Danny

    accounting standards in Member States. The suitability of IPSAS for the Member States” (European Commission, 2013b). This report takes into account the Public Consultation on the suitability of the IPSAS for EU Member States. The European Commission (2013b, p. 8) considers that IPSASs cannot easily......The European Commission is working on several fronts to achieve the implementation of uniform and comparable accruals-based accounting practices for the European Union Member States and for all the sectors of General Government, that is, Central Government, State Government, Local Government...... and Social Security, considering that at the same time it can help ensure high quality statistics (European Commission, 2013a). In 2012 Eurostat issued a Public Consultation on the suitability of the IPSAS for EU Member States, later publishing the report “Towards implementing harmonised public sector...

  13. Commission for Energy regulation (CRE) - Activity report june 2008

    International Nuclear Information System (INIS)

    2008-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

  14. Chronic tooth pulp inflammation induces persistent expression of phosphorylated ERK (pERK) and phosphorylated p38 (pp38) in trigeminal subnucleus caudalis

    Science.gov (United States)

    Worsley, M.A.; Allen, C.E.; Billinton, A.; King, A.E.; Boissonade, F.M.

    2014-01-01

    Background Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase are transiently phosphorylated (activated) in the spinal cord and trigeminal nucleus by acute noxious stimuli. Acute stimulation of dental pulp induces short-lived ERK activation in trigeminal subnucleus caudalis (Vc), and p38 inhibition attenuates short-term sensitization in Vc induced by acute pulpal stimulation. We have developed a model to study central changes following chronic inflammation of dental pulp that induces long-term sensitization. Here, we examine the effects of chronic inflammation and acute stimulation on the expression of phosphorylated ERK (pERK), phosphorylated p38 (pp38) and Fos in Vc. Results Chronic inflammation alone induced bilateral expression of pERK and pp38 in Vc, but did not induce Fos expression. Stimulation of both non-inflamed and inflamed pulps significantly increased pERK and pp38 bilaterally; expression was greatest in inflamed, stimulated animals, and was similar following 10-min and 60-min stimulation. Stimulation for 60 min, but not 10 min, induced Fos in ipsilateral Vc; Fos expression was significantly greater in inflamed, stimulated animals. pERK was present in both neurons and astrocytes; pp38 was present in neurons and other non-neuronal, non-astrocytic cell types. Conclusions This study provides the first demonstration that chronic inflammation of tooth pulp induces persistent bilateral activation of ERK and p38 within Vc, and that this activation is further increased by acute stimulation. This altered activity in intracellular signaling is likely to be linked to the sensitization that is seen in our animal model and in patients with pulpitis. Our data indicate that pERK and pp38 are more accurate markers of central change than Fos expression. In our model, localization of pERK and pp38 within specific cell types differs from that seen following acute stimulation. This may indicate specific roles for different cell types in

  15. An Optional Instrument for European Insurance Contract Law

    Directory of Open Access Journals (Sweden)

    Helmut Heiss

    2010-08-01

    Full Text Available The Principles of European Insurance Contract Law, also referred tousing the acronym PEICL, were published in September 2009. They are the result of ten years of academic work undertaken by the"Restatement of European Insurance Contract Law" Project Group. In the time since its establishment in 1999, the project has been transformed from being a stand-alone project to a part of the CoPECL (Common Principles of European Insurance Contract Law network, drafting a specific part of the Common Frame of Reference. Having continually worked under the guiding principle that "the law of insurance [in Europe] must be one," it now represents a serious option for providing Europe with a single legal framework for insurance contracts.Despite the European Council's proclamations that the Common Frame of Reference will remain a non-binding instrument, the implementation of one or more optional instruments in the future does not appear to beimprobable considering recent developments. The possibility of anoptional instrument has been expressed more than once by the European Commission in its Action Plan and Communication on European Contract Law. Other indications in favour of an optional instrument include the European Parliament's repeated references to the Common Frame of Reference as providing, at the very least, a model for a futureoptional instrument, as well as the EESC's earlier proposal of anoptional instrument as an alternative to standardising insurancecontract law. The preparation by the EESC of another (own-initiative opinion on European contract law is underway, and its presentation is anticipated in 2010. Hence, the optional instrument is evidently the subject of serious political deliberation. Using Article 1:102, the Principles of European Insurance Contract Law represent a prototype for such an instrument.

  16. An Optional Instrument for European Insurance Contract Law

    Directory of Open Access Journals (Sweden)

    Mandeep Lakhan

    2010-08-01

    Full Text Available The Principles of European Insurance Contract Law, also referred tousing the acronym PEICL, were published in September 2009. They are the result of ten years of academic work undertaken by the"Restatement of European Insurance Contract Law" Project Group. In the time since its establishment in 1999, the project has been transformed from being a stand-alone project to a part of the CoPECL (Common Principles of European Insurance Contract Law network, drafting a specific part of the Common Frame of Reference. Having continually worked under the guiding principle that "the law of insurance [in Europe] must be one," it now represents a serious option for providing Europe with a single legal framework for insurance contracts. Despite the European Council's proclamations that the Common Frame of Reference will remain a non-binding instrument, the implementation of one or more optional instruments in the future does not appear to beimprobable considering recent developments. The possibility of anoptional instrument has been expressed more than once by the European Commission in its Action Plan and Communication on European Contract Law. Other indications in favour of an optional instrument include the European Parliament's repeated references to the Common Frame of Reference as providing, at the very least, a model for a futureoptional instrument, as well as the EESC's earlier proposal of anoptional instrument as an alternative to standardising insurancecontract law. The preparation by the EESC of another (own-initiative opinion on European contract law is underway, and its presentation is anticipated in 2010. Hence, the optional instrument is evidently the subject of serious political deliberation. Using Article 1:102, the Principles of European Insurance Contract Law represent a prototype for such an instrument.

  17. Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate

  18. Annual Report 1999-2000

    International Nuclear Information System (INIS)

    2000-01-01

    Research / development and other activities of various PAEC (Pakistan Atomic Energy Commission) Departments for the year 1999-2000 are presented in this report. The various constituent unit of PAEC nuclear research centres, nuclear power plants, biotechnology, nuclear medical sciences, nuclear materials etc. These activities are described under the headings: highlights of various projects, nuclear power plants, physical sciences and engineering, biosciences, nuclear minerals, human resource development, projects, international relations. At the end of this report financial position of PAEC and list of publication is also available. (A.B.)

  19. Annual Report 1999-2000

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    Research / development and other activities of various PAEC (Pakistan Atomic Energy Commission) Departments for the year 1999-2000 are presented in this report. The various constituent unit of PAEC nuclear research centres, nuclear power plants, biotechnology, nuclear medical sciences, nuclear materials etc. These activities are described under the headings: highlights of various projects, nuclear power plants, physical sciences and engineering, biosciences, nuclear minerals, human resource development, projects, international relations. At the end of this report financial position of PAEC and list of publication is also available. (A.B.)

  20. Guidelines for residential commissioning

    Energy Technology Data Exchange (ETDEWEB)

    Wray, Craig P.; Walker, Iain S.; Sherman, Max H.

    2003-01-31

    Currently, houses do not perform optimally or even as many codes and forecasts predict, largely because they are field assembled and there is no consistent process to identify problems or to correct them. Residential commissioning is a solution to this problem. This guide is the culmination of a 30-month project that began in September 1999. The ultimate objective of the project is to increase the number of houses that undergo commissioning, which will improve the quality, comfort, and safety of homes for California citizens. The project goal is to lay the groundwork for a residential commissioning industry in California focused on end-use energy and non-energy issues. As such, we intend this guide to be a beginning and not an end. Our intent is that the guide will lead to the programmatic integration of commissioning with other building industry processes, which in turn will provide more value to a single site visit for people such as home energy auditors and raters, home inspectors, and building performance contractors. Project work to support the development of this guide includes: a literature review and annotated bibliography, which facilitates access to 469 documents related to residential commissioning published over the past 20 years (Wray et al. 2000), an analysis of the potential benefits one can realistically expect from commissioning new and existing California houses (Matson et al. 2002), and an assessment of 107 diagnostic tools for evaluating residential commissioning metrics (Wray et al. 2002). In this guide, we describe the issues that non-experts should consider in developing a commissioning program to achieve the benefits we have identified. We do this by providing specific recommendations about: how to structure the commissioning process, which diagnostics to use, and how to use them to commission new and existing houses. Using examples, we also demonstrate the potential benefits of applying the recommended whole-house commissioning approach to

  1. A Market for Company Incorporations in the European Union?

    DEFF Research Database (Denmark)

    Birkmose, Hanne Søndergaard

    2005-01-01

    The article discuss the European market for company incorporation in light of the recent decisions of the European Court of Justice; Centros (1999 E.C.R. at I-1487), Überseering (2002 E.C.R. at I-9919) and Inspire Art (2003 E.C.R. at I-10155)......The article discuss the European market for company incorporation in light of the recent decisions of the European Court of Justice; Centros (1999 E.C.R. at I-1487), Überseering (2002 E.C.R. at I-9919) and Inspire Art (2003 E.C.R. at I-10155)...

  2. First steps towards a European atlas of natural radiation: status of the European indoor radon map

    International Nuclear Information System (INIS)

    Dubois, G.; Bossew, P.; Tollefsen, T.; De Cort, M.

    2010-01-01

    Within the context of its institutional scientific support to the European Commission, in 2005 the Radioactivity Environmental Monitoring (REM) group at the Joint Research Centre of the European Commission, started to explore the possibility of mapping indoor radon in European houses as a first step towards preparing a European Atlas of Natural Radiations. The main objective of such an atlas is to contribute to familiarizing the public with its naturally radioactive environment. The process of preparing the atlas should also provide the scientific community with a database of information that can be used for further studies and for highlighting regions with elevated levels of natural radiation. This document presents the status of the European indoor radon (Rn) map, first statistical results, and outlines of forthcoming challenges.

  3. Active Erk Regulates Microtubule Stability in H-ras-Transformed Cells

    Directory of Open Access Journals (Sweden)

    Rene E. Harrison

    2001-01-01

    Full Text Available Increasing evidence suggests that activated erk regulates cell functions, at least in part, by mechanisms that do not require gene transcription. Here we show that the map kinase, erk, decorates microtubules (MTs and mitotic spindles in both parental and mutant active rastransfected 10T1 /2 fibroblasts and MCF10A breast epithelial cells. Approximately 20% of total cellular erk decorated MTs in both cell lines. A greater proportion of activated erk was associated with MTs in the presence of mutant active H-ras than in parental cells. Activation of erk by the ras pathway coincided with a decrease in the stability of MT, as detected by a stability marker. The MKK1 inhibitor, PD98059 and transfection of a dominant negative MKK1 blocked ras-induced instability of MTs but did not modify the association of erk with MTs or affect MT stability of the parental cells. These results indicate that the subset of active erk kinase that associates with MTs contributes to their instability in the presence of a mutant active ras. The MT-associated subset of active erk likely contributes to the enhanced invasive and proliferative abilities of cells containing mutant active H-ras.

  4. Turkey European Union Relations: Great Expectations

    National Research Council Canada - National Science Library

    Aydin, Hanifi

    2000-01-01

    .... Applications submitted prior to December 1999, were rejected by the EU Commission on the basis of poor democracy, human rights abuses, restrictions on political and cultural rights, a high level...

  5. National choices in a European perspective. Proceedings of the European Forum 2003

    International Nuclear Information System (INIS)

    Sido, Bruno; Lamoureux, Francois; ); Herzog, Philippe; ); Barre, Bertrand; Bataille, Christian; Colombani, Pascal; Gonzalez Gomez, Jose Luis; Lescoeur, DBruno; Perez, Serge; Weh, Rudolf; Westerlind, Magnus; Houssin, Didier; Nagashima, Hideo; Pavlopoulos, Panagiotis; Linkohr, Rolf; ); Allemeersch, Antoine; Beveridge, George; Bonnemains, Jacky; Fritschi, Markus; Piguet, Jack-Pierre; Rigny, Paul; Streydio, Jean-Marie; Tallec, Michele; Vasa, Ivo; Pancher, Bertrand

    2003-01-01

    In 2003, the 'Entretiens europeens' engaged a dialogue between stakeholders of various socio-professional backgrounds from several countries and with the European Commission, in order to compare the selected options of management of radioactive waste and materials and to emphasize the best experiments, which could inspire an innovating European policy in the world. This document is the proceedings of this first European Forum on this topic. Content: 1 - Introduction by Bruno Sido, senator and chairman of the County Council of Haute-Marne; 2 - talk by Francois Lamoureux, General Director of DG TREN, European Commission. 3 - Debate with the audience. 4 - First round table chaired by Philippe Herzog, Member of the European Parliament and President of Confrontations Europe: Is a European directive feasible? Within what time frame? What flexibility is required? What democratic process is needed? With the contributions from: Bertrand Barre, Manager in charge of Scientific Communications (AREVA), Christian Bataille, Member of the French Parliament, author of the 'Bataille Law', Pascal Colombani, Administrator, British Energy (nuclear power producer in UK), Jose Luis Gonzalez Gomez, ENRESA (Spain), Bruno Lescoeur, Director of the Energy sector, EDF, Serge Perez, Trade Unionist, Member of the National Bureau, FNME CGT (France), Rudolf Weh, Head of Department Spent Fuel and Waste Management Services/Interim Storage, GNS Gesellschaft fuer Nuklear-Service mbH (Germany), Magnus Westerlind, Manager Nuclear Security, SKI (Sweden). 5 - Hearing Didier Houssin, Director, Raw Materials and Hydrocarbons, DGEMP. 6 - Interventions of Hideo Nagashima, Executive Director, NUMO (Japan) and of Panagiotis Pavlopoulos, Research Director CERN, Geneva. 7 - Second round table chaired by Rolf Linkohr, Member of the European Parliament and chairman of European Energy Foundation: 'The scientific and social importance of the various options for the management of nuclear waste' With the contributions

  6. Validation of commercial ERK antibodies against the ERK orthologue of the scleractinian coral Stylophora pistillata [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Lucile Courtial

    2017-04-01

    Full Text Available The extracellular signal-regulated protein kinase (ERK signalling pathway controls key cellular processes, such as cell cycle regulation, cell fate determination and the response to external stressors. Although ERK functions are well studied in a variety of living organisms ranging from yeast to mammals, its functions in corals are still poorly known. The present work aims to give practical tools to study the expression level of ERK protein and the activity of the ERK signalling pathway in corals. The antibody characterisation experiment was performed five times and identical results were obtained. The present study validated the immune-reactivity of commercially available antibodies directed against ERK and its phosphorylated/activated forms on protein extracts of the reef-building coral Stylophora pistillata.

  7. The EFQM excellence model: European and Dutch experiences with the EFQM approach in health care. European Foundation for Quality Management.

    Science.gov (United States)

    Nabitz, U; Klazinga, N; Walburg, J

    2000-06-01

    One way to meet the challenges in creating a high performance organization in health care is the approach of the European Foundation for Quality Management (EFQM). The Foundation is in the tradition of the American Malcolm Baldrige Award and was initiated by the European Commission and 14 European multi-national organizations in 1988. The essence of the approach is the EFQM Model, which can be used as a self-assessment instrument on all levels of a health care organization and as an auditing instrument for the Quality Award. In 1999 the EFQM Model was revised but its principles remained the same. In The Netherlands many health care organizations apply the EFQM Model. In addition to improvement projects, peer review of professional practices, accreditation and certification, the EFQM Approach is used mainly as a framework for quality management and as a conceptualization for organizational excellence. The Dutch National Institute for Quality, the Instituut Nederlandse Kwaliteit, delivers training and supports self-assessment and runs the Dutch quality award programme. Two specific guidelines for health care organizations, 'Positioning and Improving' and 'Self-Assessment', have been developed and are used frequently. To illustrate the EFQM approach in The Netherlands, the improvement project of the Jellinek Centre is described. The Jellinek Centre conducted internal and external assessments and received in 1996, as the first health care organization, the Dutch Quality Prize.

  8. FY 1999 annual work plan for infrastructure program WBS 6

    Energy Technology Data Exchange (ETDEWEB)

    Donley, C.D.

    1998-08-27

    The Fiscal Year (FY) 1999 DynCorp Annual Work Plan (AWP) relates DOE-RL work breakdown structure (WBS) to Cost Accounts and to Organizational Structure. Each Cost Account includes a workscope narrative and justification performance and service standards, goals, and deliverables. Basis of estimates are included within each Cost Account to demonstrate the relationship of budget to defined workscope. The FY 1999 AWP reflects the planning assumptions and initiatives that are included in the PHMC Strategic Plan for Infrastructure Optimization which was established in FY 1998. Development of the FY 1999 AWP was in accordance with a sequential series of events and efforts described in the Infrastructure Annual Work Planning and Budget Cycle which was developed and established in conjunction with the Strategic Plan. The Strategic Plan covers a rolling five year span of time and is updated at the start of each fiscal year as the beginning of the annual work planning and budget cycle for the following fiscal year. Accordingly the planning for the FY 1999 AWP began in January 1998. Also included in the annual work planning and budget cycle, and the basis for the budget in this AWP, is the development of a requirements-based budget.

  9. European Analytical Column

    DEFF Research Database (Denmark)

    Karlberg, B.; Grasserbauer, M.; Andersen, Jens Enevold Thaulov

    2009-01-01

    for European analytical chemistry. During the period 2002–07, Professor Grasserbauer was Director of the Institute for Environment and Sustainability, Joint Research Centre of the European Commission (EC), Ispra, Italy. There is no doubt that many challenges exist at the present time for all of us representing...

  10. The EIROforum Collaboration Agreement with the European Union

    CERN Document Server

    2003-01-01

    Collaboration between CERN and the European Union has extended over many years, and the European Commission were granted Observer Status in the CERN Council in 1985 already. In 1994, an Administrative Arrangement was signed between CERN's Director-General, Professor C.H. Llewellyn Smith, and the Commissioner of the European Communities, Professor Antonio Ruberti, "to promote co-operation between the Commission of the European Communities and CERN in research and technological development". (See Annex I). In 2000, the EIROforum was set up composed of the Directors-General of the seven organisations - CERN, EFDA, EMBL, ESA, ESO, ESRF and ILL - whom now meet regularly twice per year. More information is available at the Web site www.eiroforum.org. On 27 October 2003, the EIROforum members signed a joint "Statement of Intent" with the European Commission, represented by Commissioner Philippe Busquin, confirming their common commitment to developing the European Research Area. The goal is to work together to estab...

  11. Realizing the European Higher Education Area: Berlin Conference of European Higher Education Ministers

    Science.gov (United States)

    European Education, 2004

    2004-01-01

    The Bologna Declaration of June 1999 has put in motion a series of reforms needed to make European higher education more compatible and comparable, more competitive and attractive for European citizens and for citizens and scholars from other continents. In Prague, in May 2001, the ministers took note of the progress so far and added three new…

  12. StreamNet: FY 1999 annual progress report

    International Nuclear Information System (INIS)

    Columbia River Inter-Tribal Fish Commission

    2000-01-01

    This report was funded by the Bonneville Power Administration (BPA), US Department of Energy, as part of BPA's program to protect, mitigate, and enhance fish and wildlife affected by the development and operation of hydroelectric facilities on the Columbia River and its tributaries. The views of this report are the author's and do not necessarily represent the views of BPA. This annual report covers progress made by: Columbia River Inter-Tribal Fish Commission Idaho; Department of Fish and Game; Montana Department of Fish, Wildlife and Parks; Oregon Department of Fish and Wildlife; Pacific States Marine Fisheries Commission; Shoshone-Bannock Tribes; US Fish and Wildlife Service; Washington Department of Fish and Wildlife; and FY1999 StreamNet Quickplan

  13. IP FUNMIG: The European far-field project

    International Nuclear Information System (INIS)

    Kienzler, B.; Buckau, G.

    2007-01-01

    The fundamental processes of radionuclide migration (the FUNMIG) is the subject matter for the Integral Project in terms of the European Commission 6-th Frame Programme (the FP6). Within the frameworks of the Project one focuses on the processes of the hot radionuclide interaction with various rocks associated with the migration of the hot radionuclides from the deep underground storage. Paper describes the Project objectives, arrangement and implementation. One highlights the German involvement in the Project [ru

  14. The Analysis of Public Administration Reforms in Macedonia and the Evaluation of the Performance of Public Administration by the European Commission

    OpenAIRE

    Abdula Azizi

    2011-01-01

    The objective of this paper is to underline the deficiencies in the funcioning of Public Administration in the Republic of Macedonia. The issue of Public Administration reforms in Macedonia has been dealt with by other scholars, but the European Commission reports have not been analyzed years after receiving the status of candidate country for EU membership. The results will reflect the realistic assessments and objective perceptions of citizens about the functioning of Public Administration,...

  15. AVS-1357 inhibits melanogenesis via prolonged ERK activation.

    Science.gov (United States)

    Kim, Dong-Seok; Lee, Hyun-Kyung; Park, Seo-Hyoung; Chae, Chong Hak; Park, Kyoung-Chan

    2009-08-01

    In this study, we demonstrated that a derivative of imidazole, AVS-1357, is a novel skin-whitening compound. AVS-1357 was found to significantly inhibit melanin production in a dose-dependent manner; however, it did not directly inhibit tyrosinase. Furthermore, we found that AVS-1357 induced prolonged activation of extracellular signal-regulated kinase (ERK) and Akt, while it downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase. It has been reported that the activation of ERK and/or Akt is involved in melanogenesis. Therefore, we examined the effects of AVS-1357 on melanogenesis in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway) and/or LY294002 (a specific inhibitor of the Akt pathway). PD98059 dramatically increased melanogenesis, whereas LY294002 had no effect. Furthermore, PD98059 attenuated AVS-1357 induced ERK activation, as well as the downregulation of MITF and tyrosinase. These findings suggest that the effects of AVS-1357 occur via downregulation of MITF and tyrosinase, which is caused by AVS-1357-induced prolonged ERK activation. Taken together, our results indicate that AVS-1357 has the potential as a new skin whitening agent.

  16. Towards the development of European networks

    International Nuclear Information System (INIS)

    Hanreich, G.

    2004-01-01

    The second AFG (French Gas Association) forum, held on June 17, addressed the issue of links between European networks with presentations by Guenther Hainreich, Director of Trans-European Networks for the European Commission Energy and Transport DG, and Loannis Galanis, Assistant Unit Director for the European Commission Energy and Transport DG. The choice for this topic has been influenced by the opening of gas markets in Europe which supposes that two conditions are fulfilled: first, the existence of gas availabilities, and second, the development of transportation, storage and LNG terminal infrastructures. In this context, the national policies are today the regional variations of a European policy at the service of the reinforcement of isolated areas and of the sustain of expanding areas. It is thus necessary to consider the European point-of-view about the existing infrastructures, their development and their financing means

  17. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Voss, Kelsey; Amaya, Moushimi [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Mueller, Claudius [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Roberts, Brian [Leidos Health Life Sciences, 5202 Presidents Court, Suite 110, Frederick, MD (United States); Kehn-Hall, Kylene; Bailey, Charles [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Petricoin, Emanuel [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Narayanan, Aarthi, E-mail: anaraya1@gmu.edu [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States)

    2014-11-15

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.

  18. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    International Nuclear Information System (INIS)

    Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius; Roberts, Brian; Kehn-Hall, Kylene; Bailey, Charles; Petricoin, Emanuel; Narayanan, Aarthi

    2014-01-01

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells

  19. Evaluation of the European Commission's proposal to set aside emission allowances. Effects on the EU carbon price and Dutch ETS companies

    Energy Technology Data Exchange (ETDEWEB)

    Verdonk, M.; Vollebergh, H.

    2012-11-15

    A set-aside of CO2 allowances would reduce the current oversupply in the European Emissions Trading System (ETS). This would result in temporary higher CO2 prices. However, a literature study has shown that the impact of the European Commission's proposal on CO2 prices is likely to be limited, because the total amount of allowances up to 2020 would remain unchanged. However, the proposal sends out a signal to investors that the functioning of the ETS is a priority for politicians, and increases the likelihood of further reforms. Any negative impact of back loading on ETS companies in the Netherlands is likely to be limited.

  20. Global Warming: Will the European Commission Choose Impotency?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    The authors aim to answer this question with a presentation of two main propositions: the objectives of the green book are insufficient and the absence of an ambitious reduction goal by the EU is due, in part, to objective factors, in part to ideology. They then propose some recommendation to the European Union. Citations on energy production, energy market and diagrams for the energy versus carbon intensities (for the European Union countries) are also provided to illustrate the analysis. (A.L.B.)

  1. Global Warming: Will the European Commission Choose Impotency?

    International Nuclear Information System (INIS)

    2008-01-01

    The authors aim to answer this question with a presentation of two main propositions: the objectives of the green book are insufficient and the absence of an ambitious reduction goal by the EU is due, in part, to objective factors, in part to ideology. They then propose some recommendation to the European Union. Citations on energy production, energy market and diagrams for the energy versus carbon intensities (for the European Union countries) are also provided to illustrate the analysis. (A.L.B.)

  2. Sulforaphane inhibits invasion via activating ERK1/2 signaling in human glioblastoma U87MG and U373MG cells.

    Directory of Open Access Journals (Sweden)

    Chunliu Li

    Full Text Available Glioblastoma has highly invasive potential, which might result in poor prognosis and therapeutic failure. Hence, the key we study is to find effective therapies to repress migration and invasion. Sulforaphane (SFN was demonstrated to inhibit cell growth in a variety of tumors. Here, we will further investigate whether SFN inhibits migration and invasion and find the possible mechanisms in human glioblastoma U87MG and U373MG cells.First, the optimal time and dose of SFN for migration and invasion study were determined via cell viability and cell morphological assay. Further, scratch assay and transwell invasion assay were employed to investigate the effect of SFN on migration and invasion. Meanwhile, Western blots were used to detect the molecular linkage among invasion related proteins phosphorylated ERK1/2, matrix metalloproteinase-2 (MMP-2 and CD44v6. Furthermore, Gelatin zymography was performed to detect the inhibition of MMP-2 activation. In addition, ERK1/2 blocker PD98059 (25 µM was integrated to find the link between activated ERK1/2 and invasion, MMP-2 and CD44v6.The results showed that SFN (20 µM remarkably reduced the formation of cell pseudopodia, indicating that SFN might inhibit cell motility. As expected, scratch assay and transwell invasion assay showed that SFN inhibited glioblastoma cell migration and invasion. Western blot and Gelatin zymography showed that SFN phosphorylated ERK1/2 in a sustained way, which contributed to the downregulated MMP-2 expression and activity, and the upregulated CD44v6 expression. These molecular interactions resulted in the inhibition of cell invasion.SFN inhibited migration and invasion processes. Furthermore, SFN inhibited invasion via activating ERK1/2 in a sustained way. The accumulated ERK1/2 activation downregulated MMP-2 expression and decreased its activity and upregulated CD44v6. SFN might be a potential therapeutic agent by activating ERK1/2 signaling against human glioblastoma.

  3. Activity report 2015 Commission Perspectives du Reseau

    International Nuclear Information System (INIS)

    Ricour, Olivia

    2016-01-01

    This document contains the activity report for 2015 of the Commission Perspectives du Reseau which has been set up by RTE to be the main body for organising a dialogue with all the actors of the energy sector and civil society about challenges and stakes of the electric power system on the medium and on the long term. It describes how this body aims at sharing knowledge and expertise of all stakeholders (publications, European platform for data transparency), at being a place for debating and enriching the understanding of tomorrow's important stakes for the power system (discussion of the issue of greenhouse gas emissions with an analysis of the impact of the CO 2 price signal on emissions by the European electricity system and results of the e-Highway 2050 European project). The road-map of the Commission works for 2016 is provided, as well as a list of members

  4. Elements of Social Security in 6 European Countries

    DEFF Research Database (Denmark)

    Hansen, Hans

    Elements of Social Security in 6 European Countries contains an overview of important benefit schemes in Denmark, Sweden, Finland, Germany, Great Britain and the Nether-lands. The schemes are categorized according to common sets of criteria and compared. Stylized cases illustrate the impact...

  5. Molecular mechanism of ERK dephosphorylation by striatal-enriched protein tyrosine phosphatase (STEP)

    Science.gov (United States)

    Li, Hui; Li, Kang-shuai; Su, Jing; Chen, Lai-Zhong; Xu, Yun-Fei; Wang, Hong-Mei; Gong, Zheng; Cui, Guo-Ying; Yu, Xiao; Wang, Kai; Yao, Wei; Xin, Tao; Li, Min-Yong; Xiao, Kun-Hong; An, Xiao-fei; Huo, Yuqing; Xu, Zhi-gang; Sun, Jin-Peng; Pang, Qi

    2013-01-01

    Striatal-enriched tyrosine phosphatase (STEP) is an important regulator of neuronal synaptic plasticity, and its abnormal level or activity contributes to cognitive disorders. One crucial downstream effector and direct substrate of STEP is extracellular signal-regulated protein kinase (ERK), which has important functions in spine stabilisation and action potential transmission. The inhibition of STEP activity toward phospho-ERK has the potential to treat neuronal diseases, but the detailed mechanism underlying the dephosphorylation of phospho-ERK by STEP is not known. Therefore, we examined STEP activity toward pNPP, phospho-tyrosine-containing peptides, and the full-length phospho-ERK protein using STEP mutants with different structural features. STEP was found to be a highly efficient ERK tyrosine phosphatase that required both its N-terminal regulatory region and key residues in its active site. Specifically, both KIM and KIS of STEP were required for ERK interaction. In addition to the N-terminal KIS region, S245, hydrophobic residues L249/L251, and basic residues R242/R243 located in the KIM region were important in controlling STEP activity toward phospho-ERK. Further kinetic experiments revealed subtle structural differences between STEP and HePTP that affected the interactions of their KIMs with ERK. Moreover, STEP recognised specific positions of a phospho-ERK peptide sequence through its active site, and the contact of STEP F311 with phospho-ERK V205 and T207 were crucial interactions. Taken together, our results not only provide the information for interactions between ERK and STEP, but will also help in the development of specific strategies to target STEP-ERK recognition, which could serve as a potential therapy for neurological disorders. PMID:24117863

  6. Road tunnels safety according to European legislation

    Directory of Open Access Journals (Sweden)

    Fedor KÁLLAY

    2008-01-01

    Full Text Available The article deals with safety of European road tunnels in accordance with actual European legislation. Standards and recommendations of European Commission, PIARC and other professional bodies of the European Union define minimal technological requirements for equipment and operation of the tunnels in scope of Trans-European Road Network.

  7. Report made on the behalf of the Commission for Sustainable Development et Land Planning on European resolution proposition on the second Energy-Climate package (nr 2295) - Nr 2309

    International Nuclear Information System (INIS)

    Leroy, Arnaud

    2014-01-01

    After having noticed that, once again, the objective of reduction of world carbon intensity (greenhouse gas emissions per dollar of GDP) will not be reached, this report outlines the importance of this now undisputed environmental, strategic and economic challenge, and that the definition of objectives by the European Union of its energy and climate policy is a critical milestone before the Paris conference on Climate of 2015. It comments the content of the Energy-Climate 2030 package proposed by the European Commission in January 2014. It also recalls the content of the 2020 package which was adopted in 2008. It recalls and comments the content of the resolution proposition of the French National Assembly, the opinions stated by the Assembly, and reports the discussion of the Commission for Sustainable development, and the discussion about the bill articles

  8. Report on the behalf of the economy, sustainable development and land planning commission of the European resolution proposition by Mr Ladislas Poniatowski on the directive proposition by the European Parliament and Council related to energy efficiency

    International Nuclear Information System (INIS)

    Poniatowski, L.

    2011-01-01

    In its first part, this report outlines the interest of the directive proposition as energy efficiency and energy savings must be a priority for the European energy policy, that important energy saving fields are still to be explored, and that this directive is an ambitious and multi-sector oriented arrangement. The second part deals with the resolution proposition (the version proposed by M. Poniatowski and that of the commission). These propositions present the general objectives, comment the rules concerning public bodies, discuss obligation mechanisms regarding energy savings, discuss the issue of energy counting and billing, and the development of cogeneration and networks. The discussion of the commission is reported

  9. ERK2-Mediated Phosphorylation of Transcriptional Coactivator Binding Protein PIMT/NCoA6IP at Ser298 Augments Hepatic Gluconeogenesis

    Science.gov (United States)

    Parsa, Kishore V. L.; Kain, Vasundhara; Behera, Soma; Suraj, Sashidhara Kaimal; Babu, Phanithi Prakash; Kar, Anand; Panda, Sunanda; Zhu, Yi-jun; Jia, Yuzhi; Thimmapaya, Bayar; Reddy, Janardan K.; Misra, Parimal

    2013-01-01

    PRIP-Interacting protein with methyl transferase domain (PIMT) serves as a molecular bridge between CREB-binding protein (CBP)/ E1A binding protein p300 (Ep300) -anchored histone acetyl transferase and the Mediator complex sub-unit1 (Med1) and modulates nuclear receptor transcription. Here, we report that ERK2 phosphorylates PIMT at Ser298 and enhances its ability to activate PEPCK promoter. We observed that PIMT is recruited to PEPCK promoter and adenoviral-mediated over-expression of PIMT in rat primary hepatocytes up-regulated expression of gluconeogenic genes including PEPCK. Reporter experiments with phosphomimetic PIMT mutant (PIMTS298D) suggested that conformational change may play an important role in PIMT-dependent PEPCK promoter activity. Overexpression of PIMT and Med1 together augmented hepatic glucose output in an additive manner. Importantly, expression of gluconeogenic genes and hepatic glucose output were suppressed in isolated liver specific PIMT knockout mouse hepatocytes. Furthermore, consistent with reporter experiments, PIMTS298D but not PIMTS298A augmented hepatic glucose output via up-regulating the expression of gluconeogenic genes. Pharmacological blockade of MAPK/ERK pathway using U0126, abolished PIMT/Med1-dependent gluconeogenic program leading to reduced hepatic glucose output. Further, systemic administration of T4 hormone to rats activated ERK1/2 resulting in enhanced PIMT ser298 phosphorylation. Phosphorylation of PIMT led to its increased binding to the PEPCK promoter, increased PEPCK expression and induction of gluconeogenesis in liver. Thus, ERK2-mediated phosphorylation of PIMT at Ser298 is essential in hepatic gluconeogenesis, demonstrating an important role of PIMT in the pathogenesis of hyperglycemia. PMID:24358311

  10. Endothelial ERK signaling controls lymphatic fate specification

    Science.gov (United States)

    Deng, Yong; Atri, Deepak; Eichmann, Anne; Simons, Michael

    2013-01-01

    Lymphatic vessels are thought to arise from PROX1-positive endothelial cells (ECs) in the cardinal vein in response to induction of SOX18 expression; however, the molecular event responsible for increased SOX18 expression has not been established. We generated mice with endothelial-specific, inducible expression of an RAF1 gene with a gain-of-function mutation (RAF1S259A) that is associated with Noonan syndrome. Expression of mutant RAF1S259A in ECs activated ERK and induced SOX18 and PROX1 expression, leading to increased commitment of venous ECs to the lymphatic fate. Excessive production of lymphatic ECs resulted in lymphangiectasia that was highly reminiscent of abnormal lymphatics seen in Noonan syndrome and similar “RASopathies.” Inhibition of ERK signaling during development abrogated the lymphatic differentiation program and rescued the lymphatic phenotypes induced by expression of RAF1S259A. These data suggest that ERK activation plays a key role in lymphatic EC fate specification and that excessive ERK activation is the basis of lymphatic abnormalities seen in Noonan syndrome and related diseases. PMID:23391722

  11. ETUDE - European Trade Union Distance Education.

    Science.gov (United States)

    Creanor, Linda; Walker, Steve

    2000-01-01

    Describes transnational distance learning activities among European trade union educators carried out as part of the European Trade Union Distance Education (ETUDE) project, supported by the European Commission. Highlights include the context of international trade union distance education; tutor training course; tutors' experiences; and…

  12. Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions

    Directory of Open Access Journals (Sweden)

    Salvadore Christopher

    2004-09-01

    Full Text Available Abstract Background The mitogen-activated protein kinases (MAPKs have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2 has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6, were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE binding (CREB protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3 were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold. Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex areas. Conclusions Swim stress specifically and markedly

  13. Concerns of European Commission for small and medium size enterprises development

    Directory of Open Access Journals (Sweden)

    Mircea Muntean

    2009-12-01

    by means of national programs, will support the SMEs development by offering the possibility of attendance to cross-border transactions with European Single Market. European Commission’s programs were supported by European Council and approved by European Parliament, following that every Member State will establish programs and initiatives on national level. European Commission’s strategy concerning SMEs  development is the increase of their number, labour force absorption and a faster economic and financial crisis traversing.

  14. Third single energy market package of the EU Commission

    International Nuclear Information System (INIS)

    Heller, W.

    2008-01-01

    In adopting the so-called Third Single Energy Market Package on September 9, 2007, the European Commission has initiated a comprehensive reform of the single energy market. The main item of the package is the separation of generation and supply from the transmission grids and transport networks in the electricity and gas sectors (ownership unbundling), an approach favored by the Commission. On the other hand, the Commission wants to advance protection of the European market in case firms from third countries, to the extent in which they do not comply with the EU unbundling requirements, would want to assume control over an EU grid or network. The key points of the package are presented. The legal and entrepreneurial ramifications are discussed, for instance, under the aspect of protection of ownership, and concrete as well as potential concerns about ownership unbundling are voiced. (orig.)

  15. A CRITICAL ASSESSMENT OF THE EUROPEAN COMMISSION’S CIVIL SOCIETY DISCOURSE AND SOCIAL PLATFORM OF EUROPEAN NGOs

    DEFF Research Database (Denmark)

    KUTAY, RIZA ACAR

    2011-01-01

    European NGO network, the Social Platform of European NGOs. The common understanding conceives of these organizations as conducive to democratization of EU governance within the scope of participatory democracy. However, I endeavour to argue that the Commission has had an aim to make use of the civil...... society discourse for its institutional interests, while intentionally and unintentionally shaping (and reshaping) civic action in Europe. Participatory democracy project, which is promoted by the Commission, can be seen as a deliberate venture of shaping civic action and state-society relationships......, which has been particularly created by the Commission to disperse the participatory democracy and good governance discourse in Europe....

  16. EUROPEAN UNION SUPPORT AND TRANSITIONAL JUSTICE PROCESSES IN KOSOVO

    OpenAIRE

    Remzije Istrefi

    2017-01-01

    The legacy of systematic human rights violations committed during 1999 violent conflict and the previous repressive rule still impact the everyday life of Kosovo citizens. That is why transitional justice processes are a necessary component in Kosovo’s state building efforts. With the end of the 1999 conflict, Kosovo has been administered by the United Nations Mission in Kosovo (UNMIK) and also supported by European Union (EU) presences: the EU Special Representative in Kosovo, and European U...

  17. Introduction: European climate leadership

    NARCIS (Netherlands)

    Wurzel, R.K.W.; Liefferink, J.D.; Connelly, J.; Wurzel, R.K.W.; Connelly, J.; Liefferink, D.

    2017-01-01

    There is no shortage of would-be leaders in EU climate change politics. The EU institutions (e.g. European Council, Council of the EU, Commission and the European Parliament (EP)), member states and societal actors have all, though to varying degrees and at different time periods, tried to offer

  18. 1999 scientific evaluation at the CEA; L'evaluation scientifique 1999 au CEA

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-01

    This report presents a statement of the scientific and technical activity of the French atomic energy commission (CEA) for the year 1999. This evaluation is made by external and independent experts and requires some specific dispositions for the nuclear protection and safety institute (IPSN) and for the direction of military applications (DAM). The report is divided into 4 parts dealing successively with: 1)the CEA, a public research organization (strategy, research programs, new organization of the CEA activities, civil nuclear research, technology research and transfer, defence activities, transfer of knowledge) 2)the scientific evaluation at the CEA (evaluations of the civil applications of the CEA, IPSN, DAM, INSTN (national institute for nuclear sciences and techniques) 3)synthesis of the 1999 scientific and technical evaluation for each operational directions of the CEA (directions of fuel cycle, of nuclear reactors, of advanced technologies, of materials sciences, of life sciences, of military applications, of the nuclear protection and safety institute and of the national institute for nuclear sciences and techniques) 4)the corresponding members of the evaluation and the list of scientific and technical councils and members.

  19. Different Expression of Extracellular Signal-Regulated Kinases (ERK) 1/2 and Phospho-Erk Proteins in MBA-MB-231 and MCF-7 Cells after Chemotherapy with Doxorubicin or Docetaxel.

    Science.gov (United States)

    Taherian, Aliakbar; Mazoochi, Tahereh

    2012-01-01

    Curative treatment of breast cancer patients using chemotherapy often fails as a result of intrinsic or acquired resistance of the tumor to the drug. ERK is one of the main components of the Ras/Raf/MEK/ERK cascade, which mediates signal from cell surface receptors to transcription factors to regulate different gene expression. In this study, cytotoxicity and the expression of Erk1/2 and phospho-ERK was compared in MDA-MB-231 (ER-) and MCF-7 (ER+) cell lines after treatment with doxorubicin (DOX) or docetaxel (DOCT). Cell cytotoxicity of DOX or DOCT was calculated using MTT assay. Immonofluorescent technique was used to show MDR-1 protein in MDA-MB-231 and MCF-7 cells after treatment with DOX or DOCT. The expression of ERK1/2 and phpspho-ERK was assayed with immunoblotting. Comparing IC50 values showed that MDA-MB-231 cells are more sensitive than MCF-7 cells to DOX or DOCT. Immonofluorescent results confirmed the expression of MDR-1 in these two cell lines after DOX or DOCT treatment. In MDA-MB-231 cells the expression of ERK1/2 and phospho-ERK was decreased after DOX treatment in a dose-dependent manner. In contrast in MCF-7 cells the expression of ERK1/2 and phospho-ERK was increased after DOX treatment. DOCT treatment demonstrated the same result with less significant differences than DOX. The heterogeneity seen in cell lines actually reflects the heterogeneity of breast cancers. That is why, patients categorized in one group respond differently to a single treatment. These results emphasize the importance of a more accurate classification and a more specific treatment of breast cancer subtypes.

  20. Natalidad y riesgo reproductivo en adolescentes de Chile, 1990­1999 Birth rates and reproductive risk in adolescents in Chile, 1990­1999

    Directory of Open Access Journals (Sweden)

    Enrique Donoso Siña

    2003-07-01

    ía volumes published by Chile's National Institute of Statistics (Instituto Nacional de Estadísticas for 1990­1999. From that database we calculated the trends in the number of live births and in the rates of maternal mortality, late fetal mortality, neonatal mortality, and infant mortality among the teenage mothers under 15 and from 15 to 19 years old. We calculated the risk odds ratio (OR for both of those age groups in comparison with women from 20 to 34 years old. The groups were compared using Fisher's exact test or the chi-square test, and the analysis of trends in the period studied was carried out with Pearson's correlation, with an alpha level of 0.05. RESULTS: In the period studied, for the teenage mothers under age 15, the respective rates for maternal mortality, late fetal mortality, neonatal mortality, and infant mortality were 41.9 per 100 000 live births, 5.1 per 1 000 live births, 15.2 per 1 000 live births, and 27.4 per 1 000 live births. For the adolescents from 15 to 19 years, the corresponding rates were 19.3, 4.1, 8.1, and 16.6; for the women 20­34 years old, they were 26.8, 5.0, 6.7, and 12.1. The adolescents under 15 had higher risks of maternal mortality (OR = 1.56; 95% confidence interval (CI: 0.50 to 4.31; P = 0.372 and of fetal mortality (OR = 1.02; 95% CI: 0.76 to 1.36; P = 0.890, but those differences were not statistically significant. However, the younger adolescents did have significantly higher risks of neonatal mortality (OR = 2.27; 95% CI: 1.92­2.68; P < 0.0001 and of infant mortality (OR = 2.39; 95% CI: 2.04 to 2.62; P < 0.0001. In comparison to the women 20­34 years old, the teenage mothers from 15 to 19 years old had significantly lower risks of maternal mortality (OR = 0.72; 95% CI: 0.56 to 0.92; P < 0.008 and of fetal mortality (OR = 0.81; 95% CI: 0.77 to 0.86; P < 0.0001 but significantly higher risks of neonatal mortality (OR = 1.20; 95% CI: 1.16 to 1.25; P < 0.0001 and of infant mortality (OR = 1.38; 95% CI: 1.35 to 1.42; P < 0.0001

  1. Experience gained during commissioning and trial operation of Mochovce Nuclear Power Plant

    International Nuclear Information System (INIS)

    GaL, P.; Adamica, T.; Marosik, V.; Rehak, A.

    2000-01-01

    In this paper authors describe the experience gained during commissioning and trial operation of Mochovce NPP (EMO). The first year of EMO operation from the point of view of safety and reliability was successful. Evidently we were challenged with certain problems characteristic to this stage of operation which resulted in automatic reactor shutdown. There were 11 automatic shutdowns in 1998 by action of the quick emergency protection AO-1 and two manual shutdowns by the AO-1 key. In 1999, there were 6 automatic shutdowns by action of the quick emergency protection AO-1. Three of them was connected to the falsely activated binary signal of MCP switch of, in two cases the reason came out from the turbo-generator (TG) cooling water system. Very positive trend in the operation of both units shows the fact that during all commissioning period of the second unit there were only three automatic reactor shutdowns by the signal AO-1. All these actions were done in frame of commissioning tests. All causes which activated the automatic unit shutdowns were found out and rectified, the overall tuning of the cooling water system is on the process now. The solution of this problem is possible only power commissioning, and in the stage of the trial operation had no direct impacts on the nuclear, radiation, or technical safety respectively. In 1998 two events according to the INES scale after second unit commissioning because of two unit links of the cooling water system. The operational events during the commissioning tests, start-up tests, physical commissioning, were ranked the category 1 ('Action of SIS U040 p po <8,34 MPa at the system 2 and 3' and 'Breaching the L and C'). In 1999 only events occurred that were ranked in the category safety insignificant events and lower (category 0, or off the scale respectively). In the frame of the safety culture principles adopted, such as critical attitude, exact and careful approach, and communication, these problems were given the

  2. Annual report 1999

    International Nuclear Information System (INIS)

    2000-01-01

    basis for their decisions. The Government has decided the fees and guarantees which will apply to cover future expenses, largely on the basis of the proposals made by SKI following its review of the industry's cost-estimates. 6. Decision-makers and the general public must be well informed of nuclear risks and safety as well as of the handling and final disposal of spent nuclear fuel and nuclear waste; SKI has aimed to be a reliable information provider that maintains considerable openness and provides a high level of service to the media, politicians and the general public. SKI has also been able to meet the need for information in the municipalities participating in feasibility studies prior to the selection of a site for a spent nuclear fuel repository. 7. SKI must actively contribute to the development and reinforcement of international nuclear safety and proliferation work, especially within the framework of the European Union; Together with other regulatory authorities within the EU, SKI has evaluated the reactor safety situation within the countries that have applied for EU membership. SKI has also participated in the European Commission's evaluation of forms of co-operation within the EU within reactor safety and has actively worked for more effective co-operation. In summary, it can be said that much has been achieved during 1999 to attain the performance goals for SKI's regulatory and supervisory activities. The regulatory and supervisory strategy has been further developed and regulatory and supervisory work and other tasks are continuously being developed through the SKIQ quality assurance system

  3. Radioactivity in the Baltic Sea, 1999-2006 HELCOM thematic assessment

    International Nuclear Information System (INIS)

    Herrmann, J.; Ikaeheimonen, T.K.; Ilus, E.; Kanisch, G.; Luning, M.; Mattila, J.; Nielsen, S.P.; Osvath, I.; Outola, I.

    2009-01-01

    The report describes work carried out by HELCOM's (Helsinki Commission, Baltic Marine Environment Commission) project on the Monitoring of Radioactive Substances in the Baltic Sea (MORS-PRO) during the period 1999-2006. The main topics include: sources of man-made radioactivity in the Baltic Sea; levels of man-made radionuclides in seawater, sediments and biota; work on modelling and evaluations of the riks to man caused by radioactivity in the Baltic Sea; comparison of man-made radionuclides in the Baltic Sea with levels in other sea regions. The concequent recommendations and work on data quality are presented in the Appendix

  4. Report on the behalf of the Commission for economic affairs on the proposition of European resolution presented by MM. Jean BIZET and Michel DELEBARRE on the behalf of the Commission for European affairs in application of article 73 quarter of the Regulation, on renewable energies and capacity mechanisms. Nr 435

    International Nuclear Information System (INIS)

    Poniatowski, Ladislas

    2017-01-01

    In the main part of this report, the author first proposes an overview of the energy policy as a shared competence and priority of the Junker Commission: this competence is shared between the European Union and member States, and a Union of energy is a political priority at the service of economic growth and of commitments for the climate. The author also proposes an overview of the main legal measures present in the fourth energy package: energy efficiency and energetic performance of buildings, development of renewable energies, organisation of the electric power market and security of supply, governance of the Union of energy and sector regulation. He discusses the position of the French Senate Commission for economic affairs: a general agreement (notably about energy efficiency, renewable energies, central role awarded to consumers, industrial and social support for energy transition) with some reservations on some proposed action modalities (notably with respect to the principles of subsidiarity, proportionality, sovereignty and responsibility of member states). A transcription of Commission debates, a list of hearings, and a comparative version of the text are provided

  5. World: 2508 nuclear tera-watts hour in 1999

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    In 1999, the nuclear power plants have produced 2508 tera-watts hour, that is to say 16% of the normal electricity production or 35% of the European electric production. At the end of 1999, 443 reactors were in operation, 53 were in building and 13 put in an order in the world. 5 reactors have been coupled to the network in South Korea, in France, in India, in Slovakia and 2 have been definitively stopped (Kazakhstan and Sweden). 1999 has seen the beginning of construction for 8 reactors (China, South Korea, Japan and Taiwan). The nuclear power has covered 40 % of needs for 8 countries: France (75%), Lithuania (73%) Belgium (58%), Sweden (46%), Slovakia (45%), Ukraine (43.5%), South Korea ( 43%), Bulgaria ( 41.5%). 18 countries have used nuclear energy to cover at least 25% of their needs. (N.C.)

  6. A global strategy for the European PV industry

    International Nuclear Information System (INIS)

    Viaud, M.; Despotou, E.; Latour, M.; Hoffmann, W.; Macias, E.; Cameron, M.; Laborde, E.

    2004-01-01

    The objective was to develop a comprehensive strategy that answers to the need of today European PV industry. Namely: - Develop PV markets in Europe - Develop export markets. - Position the European PV industry within the European political environment and support the effort of national actors in their local objectives. This method lends itself to brainstorming to create actions and synergies, on order to achieve strategy objectives. The whole work is based on working groups clearly defined on the purpose, where all EPIA members are invited to participate. The overall first results are presented during the 19. EU PV Conference in Paris and EPIA will do recommendations on actions to be undertaken in the future. This strategy is co-financed by EPIA members and the 6. Framework Programme for research of the European Commission through the PV Catapult project. (authors)

  7. [Effect of ERK1/2 Signaling Pathway Inhibitor PD98059 on the Expression of Ras, BRaf, MEK, ERK1/2 in Marrow Nucleated Red Blood Cells of CMS Patients].

    Science.gov (United States)

    Han, Yuan-Fang; Ji, Lin-Hua; Feng, Ting-Ting; Liu, Fang; Cui, Sen; Su, Juan

    2017-10-01

    To investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS). Sixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA, the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in nucleated red blood cells, and the Western blot method was used to detect expression of BRaf, MEK, ERK1, ERK2 protein. PD98059 had no effect on the level of Ras-GTP in each groups. Compared with the blank control group, the expression levels of BRaf, MEK mRNA in DMSO group were not statistically significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L group, the expression level of ERK1/2 mRNA was statistically significant (P=0.001, 0.002). Compared with the blank control group, expression levels of p-BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370, 0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2 protein level in other 4 groups were statistically significant (P values were <0.001, 0.007). PD98059 can up-regulate the expressions of ERK1/2 miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras / Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2 pathway may be involved in the pathogenesis of chronic mountain sickness process.

  8. Health status in 1040 adults with disorders of sex development (DSD: a European multicenter study

    Directory of Open Access Journals (Sweden)

    Henrik Falhammar

    2018-03-01

    Full Text Available Objective: The knowledge about health status in adults with disorder of sex development (DSD is scarce. Design and methods: A cross-sectional observational study in 14 European tertiary centers recruited 1040 participants (717 females, 311 males, 12 others with DSD. Mean age was 32.4 ± 13.6 year (range 16–75. The cohort was divided into: Turner (n = 301, Klinefelter (n = 224, XY-DSD (n = 222, XX-DSD (excluding congenital adrenal hyperplasia (CAH and 46,XX males (n = 21, 46,XX-CAH (n = 226 and 45,X/46,XY (n = 45. Perceived and objective health statuses were measured and compared to European control data. Results: In DSD, fair to very good general health was reported by 91.4% and only 8.6% reported (very bad general health (controls 94.0% and 6.0%, P < 0.0001. Longstanding health issues other than DSD and feeling limited in daily life were reported in 51.0% and 38.6%, respectively (controls 24.5% and 13.8%, P < 0.0001 both. Any disorder except DSD was present in 84.3% (controls 24.6%, P < 0.0001. Males reported worse health than females. In the subgroup analysis, Klinefelter and 46, XX-DSD patients reported bad general health in 15.7% and 16.7%, respectively (Turner 3.2% and CAH 7.4%. Comorbidities were prevalent in all DSD subgroups but Klinefelter and Turner were most affected. Early diagnosis of DSD and a healthy lifestyle were associated with less comorbidities. Conclusions: Overall, general health appeared to be good but a number of medical problems were reported, especially in Klinefelter and Turner. Early diagnosis of DSD and a healthy lifestyle seemed to be important. Lifelong follow-up at specialized centers is necessary.

  9. Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

    Directory of Open Access Journals (Sweden)

    Shih-Hung Yang

    2014-01-01

    Full Text Available Background. Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND, a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo. Methods. Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model. Results and Conclusion. In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.

  10. The ERK1/2 Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina

    Directory of Open Access Journals (Sweden)

    Ghulam Mohammad

    2013-01-01

    Full Text Available This study was conducted to determine the expression of matrix metalloproteinase-9 (MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in a time-dependent manner and the effect of extracellular-signal-regulated kinases-1/2 (ERK1/2 inhibition on the expressions of MMP-9, TIMP-1, and inflammatory biomarkers in the retinas of diabetic rats. The expression of MMP-9 was quantified by zymography, and the mRNA level of MMP-9 and TIMP-1 was quantified by RT-PCR. The expression of inducible nitric oxide synthase (iNOS, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α was examined by Western blot analysis. MMP-9 expression was significantly higher in diabetic rat retinas compared to controls at all time points.TIMP-1 expression was nonsignificantly upregulated at 1week of diabetes and was significantly downregulated at 4 and 12 weeks of diabetes. Intravitreal administration of the ERK1/2 inhibitor U0126 prior to induction of diabetes decreased ERK1/2 activation, attenuated diabetes-induced upregulation of MMP-9, iNOS, IL-6, and TNF-α and upregulated TIMP-1 expression. In MMP-9 knockout mice, diabetes had no effect on retinal iNOS expression and its level remained unchanged. These data provide evidence that ERK1/2 signaling pathway is involved in MMP-9, iNOS, IL-6, and TNF-α induction in diabetic retinas and suggest that ERK1/2 can be a novel therapeutic target in diabetic retinopathy.

  11. 1999 Annual report: compression + power + service

    International Nuclear Information System (INIS)

    2000-01-01

    Enerflex manufactures, services and leases compression systems for the production and processing of natural gas and gas-fueled power generation systems. Design, engineering, project management, financing, installation commissioning and after-sales service are also part of Enerflex's arsenal of tools to ensure innovation, and high standards of quality and service. In 1999, Enerflex suffered an 18 per cent decline in revenues from $315 million in 1998 to $257 million in 1999, entirely due to lower sales of big ticket compression equipment in Canada. At the same time, revenues from international sales and service increased to $ 61.8 million in 1999, from $ 53 million in 1998. The company successfully completed the move to a new 328,000 sq. ft state-of-the-art manufacturing facility, and made its first significant sale to the United States in 1999 in the form of delivering a coal bed methane project in the Powder River area of Wyoming, and power generation equipment to Massachusetts. Although in the short term unusually warm average temperatures, industry cash flows, and access to capital may determine demand for the company's products and services, the long-term fundamentals are positive and demand for compression equipment and power generation systems is likely to grow. Indeed, in the fourth quarter of 1999, market conditions improved significantly and the company recorded its highest quarterly revenues and earnings during the last quarter. The annual review provides further details about the operations of the company's various divisions, (Compression and Power Systems, Parts and Compression Services, Leasing and Financing), management's review of the company's overall operations and finances, audited financial statements, and shareholders' information

  12. Critical outlook and trends for environmental reference materials at the Measurements & Testing Generic Activity (European Commission).

    Science.gov (United States)

    Quevauviller, P; Bennink, D; Bøwadt, S

    2001-05-01

    It is now well recognised that the quality control (QC) of all types of analyses, including environmental analyses depends on the appropriate use of reference materials. One of the ways to check the accuracy of methods is based on the use of Certified Reference Materials (CRMs), whereas other types of (not certified) Reference Materials (RMs) are used for routine quality control (establishment of control charts) and interlaboratory testing (e.g. proficiency testing). The perception of these materials, in particular with respect to their production and use, differs widely according to various perspectives (e.g. RM producers, routine laboratories, researchers). This review discusses some critical aspects of RM use and production for the QC of environmental analyses and describes the new approach followed by the Measurements & Testing Generic Activity (European Commission) to tackle new research and production needs.

  13. Report from the 2012 European Gender Summit

    CERN Document Server

    European Gender Summit, 2012

    2012-01-01

    Report from the 2012 European Gender Summit to the European Parliament and the Council, the European Commission, the Council of Europe, EU Member and Associate States, Science Institutions. Developing Systematic Implementation Strategy to Advance EU Policy on Gender Equality in Science, as part of HORIZON 2020, European Research Area and Innovation Union.

  14. Temperature Dependences for Air-broadened Widths and Shift Coefficients in the 30013 - 00001 and 30012 - 00001 Bands of Carbon Dioxide near 1600 nm

    Science.gov (United States)

    Devi, M.; Predoi-Cross, A.; McKellar, R.; Benner, C.; Miller, C. E.; Toth, R. A.; Brown, L. R.

    2008-12-01

    Nearly 40 high resolution spectra of air-broadened CO2 recorded at temperatures between 215 and 294 K were analyzed using a multispectrum nonlinear least squares technique to determine temperature dependences of air-broadened half width and air-induced pressure shift coefficients in the 30013-00001 and 30012-00001 bands of 12CO2. Data were recorded with two different Fourier transform spectrometers (Kitt Peak FTS at the National Solar Observatory in Arizona and the Bomem FTS at NRC, Ottawa) with optical path lengths ranging between 25 m and 121 m. The sample pressures varied between 11 torr (pure CO2) and 924 torr (CO2-air) with volume mixing ratios of CO2 in air between ~ 0.015 and 0.11. To minimize systematic errors and increase the accuracy of the retrieved parameters, we constrained the multispectrum nonlinear least squares fittings to use quantum mechanical expressions for the rovibrational energies and intensities rather than retrieving the individual positions and intensities line-by-line. The results suggest minimal vibrational dependence for the temperature dependence coefficients.1 1 A. Predoi-Cross and R. Mckellar are grateful for financial support from the National Sciences and Engineering Research Council of Canada. The research at the Jet Propulsion laboratory (JPL), California Institute of Technology, was performed under contract with National Aeronautics and Space Administration. The support received from the National Science Foundation under Grant No. ATM-0338475 to the College of William and Mary is greatly appreciated. The authors thank Mike Dulick of the National Solar Observatory for his assistance in obtaining the data recorded at Kitt Peak.

  15. Flood Risk Research and Warning Tools at the European Scale

    NARCIS (Netherlands)

    Roo, A.P.J. de; Thielen, J.; Feyen, L.; Burek, P.; Salamon, P.

    2012-01-01

    The floods in the rivers Meuse and Rhine in 1993 and 1995 made the European Commission realize that also at Commission level further research on floods – especially in transboundary river catchments - was necessary. This led to the start of a dedicated research project on floods at the European

  16. Novel Reporter for Faithful Monitoring of ERK2 Dynamics in Living Cells and Model Organisms

    Science.gov (United States)

    Sipieter, François; Cappe, Benjamin; Gonzalez Pisfil, Mariano; Spriet, Corentin; Bodart, Jean-François; Cailliau-Maggio, Katia; Vandenabeele, Peter; Héliot, Laurent; Riquet, Franck B.

    2015-01-01

    Uncoupling of ERK1/2 phosphorylation from subcellular localization is essential towards the understanding of molecular mechanisms that control ERK1/2-mediated cell-fate decision. ERK1/2 non-catalytic functions and discoveries of new specific anchors responsible of the subcellular compartmentalization of ERK1/2 signaling pathway have been proposed as regulation mechanisms for which dynamic monitoring of ERK1/2 localization is necessary. However, studying the spatiotemporal features of ERK2, for instance, in different cellular processes in living cells and tissues requires a tool that can faithfully report on its subcellular distribution. We developed a novel molecular tool, ERK2-LOC, based on the T2A-mediated coexpression of strictly equimolar levels of eGFP-ERK2 and MEK1, to faithfully visualize ERK2 localization patterns. MEK1 and eGFP-ERK2 were expressed reliably and functionally both in vitro and in single living cells. We then assessed the subcellular distribution and mobility of ERK2-LOC using fluorescence microscopy in non-stimulated conditions and after activation/inhibition of the MAPK/ERK1/2 signaling pathway. Finally, we used our coexpression system in Xenopus laevis embryos during the early stages of development. This is the first report on MEK1/ERK2 T2A-mediated coexpression in living embryos, and we show that there is a strong correlation between the spatiotemporal subcellular distribution of ERK2-LOC and the phosphorylation patterns of ERK1/2. Our approach can be used to study the spatiotemporal localization of ERK2 and its dynamics in a variety of processes in living cells and embryonic tissues. PMID:26517832

  17. 7-Chloro-6-piperidin-1-yl-quinoline-5,8-dione (PT-262), a novel synthetic compound induces lung carcinoma cell death associated with inhibiting ERK and CDC2 phosphorylation via a p53-independent pathway.

    Science.gov (United States)

    Hsu, Tzu-Sheng; Chen, Chinpiao; Lee, Pei-Ting; Chiu, Shu-Jun; Liu, Huei-Fang; Tsai, Chih-Chien; Chao, Jui-I

    2008-10-01

    The derivatives of 5,8-quinolinedione have been shown to exert anticancer activities. A new synthetic compound 7-chloro-6-piperidin-1-yl-quinoline-5,8-dione (designed as PT-262) derived from 6,7-dichloroquinoline-5,8-dione on its anticancer activity was investigated in this study. PT-262 was synthesized as the following: triethylamine (0.56 ml, 5.1 mmol) was added dropwise to a solution of 6,7-dichloroquinoline-5,8-dione (1.00 g, 4.4 mmol) and piperidine (0.50 ml, 5.1 mmol) in 150 ml of benzene with stirring at room temperature for 5 min, and the solvent was removed using rotary evaporator to give a dark brown solid. PT-262 was purified by flash chromatography using 50% ethyl acetate/hexanes to elute that displayed as brown solids. To examine the induction of apoptosis following PT-262 treatment, the lung cancer cells were subjected to apoptotic cell observation, caspase activation, and mitochondrial functional assays. The protein levels of phosphorylated ERK and CDC2 after treatment with PT-262 were analyzed by Western blot. Treatment with 1-20 microM PT-262 for 24 h induced cytotoxicity via a concentration-dependent manner in human lung cancer cells. PT-262 induced the loss of mitochondrial membrane potential and elevated the caspase-3 activation and apoptosis. Interestingly, the phosphorylation of ERK was inhibited by PT-262. The IC50 value of ERK phosphorylation inhibition was approximate around 5 microM. Treatment with a specific MEK1/2 (the upstream of ERK) inhibitor, PD98059, increased the PT-262-induced cytotoxicity in lung cancer cells. Moreover, PT-262 did not alter the protein expression of tumor suppressor p53. PT-262 elicited the cytotoxicity and accumulated the G2/M fractions in both the p53-wild type and p53-null lung cancer cells. The mitosis-regulated protein levels of cyclin B1 and phospho-CDC2 at Thr14, Tyr15, and Thr161 were repressed by PT-262 in these cells. PT-262 suppresses the phosphorylation of ERK and CDC2 associated with proliferation

  18. [Effects of bushen jiannao recipe on the content of acetylcholine and the hippocampal ERK1 and ERK2 protein expressions of vascular dementia rats].

    Science.gov (United States)

    Liu, Yong-Hui; Li, Shao-Wei; Zheng, Qing-Lian

    2012-04-01

    To explore the effects of Bushen Jiannao Recipe (BJR) on the content of acetylcholine (Ach) and ERK1 and ERK2 protein expressions in the hippocampal CA1 region of vascular dementia (VD) rats, and to explore its possible mechanisms for treating VD. Eighty-three rats were selected. The VD model was established by permanent bilateral occlusion of both common carotid arteries (2-VO). Then the modeled rats were randomly divided into 5 groups, i. e., the memory deficit model group, the donepezil group, and the positive drug control groups [including high (n = 13), middle (n = 13), and low (n = 12) dose BJR group]. Besides, another 13 rats were chosen as the sham-operative group. The distilled water was given by gastrogavage to rats in the sham-operative group and the memory deficit model group (5 mL/kg). The donepezil hydrochloride suspension was given to rats in the donepezil group by gastrogavage (0.52 mg/kg). High (56 g/kg), middle (28 g/kg), and low (14 g/kg) dose of BJR were respectively given to rats in the other three groups. After 30 days of intervention, the escape latency period and platform crossing times were determined using Morris water maze experiment. The contents of Ach in the hippocampus and cortex were determined using colorimetry. The expressions of ERK1 and ERK2 in the CA1 region of the hippocampus were detected using immunohistochemical assay. The average escape latency of intervened rats showed an overall decreasing trend. From the third to the fifth day, the escape latency period was prolonged, the platform crossing times were reduced, the contents of Ach in the cortex and the hippocampus were lowered, the numbers of positive stained neuron of ERK1 and ERK2 in the hippocampus CA1 region were reduced, showing statistical difference when compared with the sham-operative group (P<0.01). Compared with the model group, the 4th day escape latency of the donepezil group and the high dose BJR group was shortened. The escape latency was shortened, and the

  19. PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway

    Directory of Open Access Journals (Sweden)

    H. Wang

    Full Text Available This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2 in chondrogenic differentiation of mesenchymal stem cells (MSCs. MSCs were isolated from femurs and tibias of Sprague-Dawley rats, weighing 300-400 g (5 females and 5 males. Overexpression and knockdown of PDK2 were transfected into MSCs and then cell viability, adhesion and migration were assessed. Additionally, the roles of aberrant PDK2 in chondrogenesis markers SRY-related high mobility group-box 6 (Sox6, type ΙΙ procollagen gene (COL2A1, cartilage oligomeric matrix protein (COMP, aggrecan (AGC1, type ΙX procollagen gene (COL9A2 and collagen type 1 alpha 1 (COL1A1 were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR. The expressions of c-Jun N-terminal kinase (JNK, p38 mitogen-activated protein kinase (MAPK and extracellular regulated protein kinase (ERK were measured. Overexpressing PDK2 promoted cell viability, adhesion and inhibited cell migration in MSCs (all P<0.05. qRT-PCR assay showed a potent increase in the mRNA expressions of all chondrogenesis markers in response to overexpressing PDK2 (P<0.01 or P<0.05. PDK2 overexpression also induced a significant accumulation in mRNA and protein expressions of JNK, p38MAPK and ERK in MSCs compared to the control (P<0.01 or P<0.05. Meanwhile, silencing PDK2 exerted the opposite effects on MSCs. This study shows a preliminary positive role and potential mechanisms of PDK2 in chondrogenic differentiation of MSCs. It lays the theoretical groundwork for uncovering the functions of PDK2 and provides a promising basis for repairing cartilage lesions in osteoarthritis.

  20. Amorce. Activity report 1999; Amorce. Rapport d'activite 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-01

    Amorce is a French association which groups 173 organizations and 95 professionals. Its domain of activity concerns the district heating networks, the energy management by territorial organizations and the management of municipal wastes. This activity report presents the highlights of the 1999 year in the life of the association (growth of the association, personnel, reputation, financial situation, European activity, training, development of a database on wastes), and in each domain of activity: district heating and energy (deregulation of the electricity market, difficulties encountered in the domain of district heating networks, greenhouse effect, energy service schemes, renewable energies), and wastes (technical choices, reduction of government helps, ecological packaging, non-addressed mail, legal problems..). (J.S.)

  1. LULI 1999 activity report; LULI rapport annuel 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-01

    This document gathers the main results obtained by scientists from the LULI (laboratory for the use of intense lasers) unit in 1999. It is made up of 55 short articles and is organized into 6 topics: 1) laser-matter interaction, 2) hydrodynamics, shocks, equations of state, 3) atom physics, X-ray lasers, 4) material treatment, 5) progress in optics for power lasers, and 6) instrumentation and other advances.

  2. Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli

    KAUST Repository

    Suen, KinMan

    2013-05-01

    Control mechanisms that prevent aberrant signaling are necessary to maintain cellular homeostasis. We describe a new mechanism by which the adaptor protein Shc directly binds the MAP kinase Erk, thus preventing its activation in the absence of extracellular stimuli. The Shc-Erk complex restricts Erk nuclear translocation, restraining Erk-dependent transcription of genes, including those responsible for oncogenic growth. The complex forms through unique binding sites on both the Shc PTB domain and the N-terminal lobe of Erk. Upon receptor tyrosine kinase stimulation, a conformational change within Shc - induced through interaction with the phosphorylated receptor - releases Erk, allowing it to fulfill its role in signaling. Thus, in addition to its established role in promoting MAP kinase signaling in stimulated cells, Shc negatively regulates Erk activation in the absence of growth factors and thus could be considered a tumor suppressor in human cells. © 2013 Nature America, Inc. All rights reserved.

  3. Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli

    KAUST Repository

    Suen, KinMan; Lin, Chichuan; George, Roger R.; Melo, Fernando A.; Biggs, Eleanor R.; Ahmed, Zamal; Drake, Melanie N.; Arur, Swathi; Arold, Stefan T.; Ladbury, John E S D

    2013-01-01

    Control mechanisms that prevent aberrant signaling are necessary to maintain cellular homeostasis. We describe a new mechanism by which the adaptor protein Shc directly binds the MAP kinase Erk, thus preventing its activation in the absence of extracellular stimuli. The Shc-Erk complex restricts Erk nuclear translocation, restraining Erk-dependent transcription of genes, including those responsible for oncogenic growth. The complex forms through unique binding sites on both the Shc PTB domain and the N-terminal lobe of Erk. Upon receptor tyrosine kinase stimulation, a conformational change within Shc - induced through interaction with the phosphorylated receptor - releases Erk, allowing it to fulfill its role in signaling. Thus, in addition to its established role in promoting MAP kinase signaling in stimulated cells, Shc negatively regulates Erk activation in the absence of growth factors and thus could be considered a tumor suppressor in human cells. © 2013 Nature America, Inc. All rights reserved.

  4. Disruption of MEK/ERK/c-Myc signaling radiosensitizes prostate cancer cells in vitro and in vivo.

    Science.gov (United States)

    Ciccarelli, Carmela; Di Rocco, Agnese; Gravina, Giovanni Luca; Mauro, Annunziata; Festuccia, Claudio; Del Fattore, Andrea; Berardinelli, Paolo; De Felice, Francesca; Musio, Daniela; Bouché, Marina; Tombolini, Vincenzo; Zani, Bianca Maria; Marampon, Francesco

    2018-06-29

    Prostate cancer (PCa) cell radioresistance causes the failure of radiation therapy (RT) in localized or locally advanced disease. The aberrant accumulation of c-Myc oncoprotein, known to promote PCa onset and progression, may be due to the control of gene transcription and/or MEK/ERK-regulated protein stabilization. Here, we investigated the role of MEK/ERK signaling in PCa. LnCAP, 22Rv1, DU145, and PC3 PCa cell lines were used in in vitro and in vivo experiments. U0126, trametinib MEK/ERK inhibitors, and c-Myc shRNAs were used. Radiation was delivered using an x-6 MV photon linear accelerator. U0126 in vivo activity alone or in combination with irradiation was determined in murine xenografts. Inhibition of MEK/ERK signaling down-regulated c-Myc protein in PCa cell lines to varying extents by affecting expression of RNA and protein, which in turn determined radiosensitization in in vitro and in vivo xenograft models of PCa cells. The crucial role played by c-Myc in the MEK/ERK pathways was demonstrated in 22Rv1 cells by the silencing of c-Myc by means of short hairpin mRNA, which yielded effects resembling the targeting of MEK/ERK signaling. The clinically approved compound trametinib used in vitro yielded the same effects as U0126 on growth and C-Myc expression. Notably, U0126 and trametinib induced a drastic down-regulation of BMX, which is known to prevent apoptosis in cancer cells. The results of our study suggest that signal transduction-based therapy can, by disrupting the MEK/ERK/c-Myc axis, reduce human PCa radioresistance caused by increased c-Myc expression in vivo and in vitro and restores apoptosis signals.

  5. The role of nuclear energy in the European Community

    International Nuclear Information System (INIS)

    Maniatopoulos, C.S.; Gmelin, W.; Schenkel, R.

    1991-01-01

    The overall objective of the energy policy of the European Community is to achieve a secure supply of energy at reasonable cost and low environmental impact. This overall objective is embedded in the steps taken by the European Community towards the Single European Market. This subject will be addressed briefly, as well as the developments in Eastern Europe including the European Energy Charter. With regard to nuclear energy in the community, facts and issues related to electricity production, the front end and back end of the nuclear fuel cycle and current environmental and safety issues will be presented. A common industrial strategy is required in the community including safety regulations, technical specifications and products for international markets. Concerning safeguards, the Commission is fully committed to the obligations from Chapter VII of the Treaty and to any relevant international agreements concluded by the Community. This is reflected in the close cooperation of the Commission with the IAEA and in the increase of resources, both in staff and budget, which the Commission has allocated to the Safeguards Directorate to cope with the increasing requirements, for example for bulk handling facilities. Based on a request from the European Parliament, the Commission has issued in 1989 a first report on the operation of Euratom Safeguards. The Commission services are currently preparing the second report of this type. Finally, some remarks with regard to the future of nuclear energy and challenges of safeguards in the Community will be made

  6. 1999 scientific evaluation at the CEA; L'evaluation scientifique 1999 au CEA

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-01

    This report presents a statement of the scientific and technical activity of the French atomic energy commission (CEA) for the year 1999. This evaluation is made by external and independent experts and requires some specific dispositions for the nuclear protection and safety institute (IPSN) and for the direction of military applications (DAM). The report is divided into 4 parts dealing successively with: 1)the CEA, a public research organization (strategy, research programs, new organization of the CEA activities, civil nuclear research, technology research and transfer, defence activities, transfer of knowledge) 2)the scientific evaluation at the CEA (evaluations of the civil applications of the CEA, IPSN, DAM, INSTN (national institute for nuclear sciences and techniques) 3)synthesis of the 1999 scientific and technical evaluation for each operational directions of the CEA (directions of fuel cycle, of nuclear reactors, of advanced technologies, of materials sciences, of life sciences, of military applications, of the nuclear protection and safety institute and of the national institute for nuclear sciences and techniques) 4)the corresponding members of the evaluation and the list of scientific and technical councils and members.

  7. Status report on research programmes of the Commission of European Communities related to risk evaluation of geological disposal of radioactive waste

    International Nuclear Information System (INIS)

    Girardi, F.

    1977-01-01

    The programmes of the Commission of European Communities related to risk evaluation of geological disposal of radioactive waste are presented. The Joint Research Centre carries out theoretical modelling activities and a few selected experimental activities which are related to model development and verification. A set of contractual research activities, coordinated by the General Directorate of Research, Scientific Affairs and Education and set up primarily to encourage development of optimised waste management strategies will provide the many additional experimental data which are necessary for a realistic evaluation of long term hazard to man and the environment

  8. ERK-dependent and -independent pathways trigger human neural progenitor cell migration

    International Nuclear Information System (INIS)

    Moors, Michaela; Cline, Jason E.; Abel, Josef; Fritsche, Ellen

    2007-01-01

    Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways

  9. An ERK/Cdk5 axis controls the diabetogenic actions of PPARγ.

    Science.gov (United States)

    Banks, Alexander S; McAllister, Fiona E; Camporez, João Paulo G; Zushin, Peter-James H; Jurczak, Michael J; Laznik-Bogoslavski, Dina; Shulman, Gerald I; Gygi, Steven P; Spiegelman, Bruce M

    2015-01-15

    Obesity-linked insulin resistance is a major precursor to the development of type 2 diabetes. Previous work has shown that phosphorylation of PPARγ (peroxisome proliferator-activated receptor γ) at serine 273 by cyclin-dependent kinase 5 (Cdk5) stimulates diabetogenic gene expression in adipose tissues. Inhibition of this modification is a key therapeutic mechanism for anti-diabetic drugs that bind PPARγ, such as the thiazolidinediones and PPARγ partial agonists or non-agonists. For a better understanding of the importance of this obesity-linked PPARγ phosphorylation, we created mice that ablated Cdk5 specifically in adipose tissues. These mice have both a paradoxical increase in PPARγ phosphorylation at serine 273 and worsened insulin resistance. Unbiased proteomic studies show that extracellular signal-regulated kinase (ERK) kinases are activated in these knockout animals. Here we show that ERK directly phosphorylates serine 273 of PPARγ in a robust manner and that Cdk5 suppresses ERKs through direct action on a novel site in MAP kinase/ERK kinase (MEK). Importantly, pharmacological inhibition of MEK and ERK markedly improves insulin resistance in both obese wild-type and ob/ob mice, and also completely reverses the deleterious effects of the Cdk5 ablation. These data show that an ERK/Cdk5 axis controls PPARγ function and suggest that MEK/ERK inhibitors may hold promise for the treatment of type 2 diabetes.

  10. Report realized in the name of the economic, environment and territory commission, on the resolution proposition (n. 1261) of Messrs Bernard Deflesselles and Jerome Lambert, reporters of the commission in charge of the european affairs, on the program energy-climate

    International Nuclear Information System (INIS)

    2008-01-01

    This report aims to evaluate a resolution proposition on five texts presented by the European Commission the 23 January 2008: the enhancement of the quotas emission system, the greenhouse gases effect reduction, the renewable energies development, the juridical aspects of the carbon sequestration and storage and the financial assistance of the governments for the environment. 12 propositions are provided. (A.L.B.)

  11. Annual Report 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-01-01

    will be updated as the nuclear safety work in the applicant countries is developed. SKI has also participated in the European Commission's evaluation of forms of co-operation within the EU within reactor safety and has actively worked for more effective co-operation. In April 1999, the first review meeting was held under the international nuclear safety convention, under the chairmanship of SKI's Director General. The evaluation was a major success. All of the countries expressed their commitment to the continued improvement of safety, in accordance with the purpose of the convention. Actual measures implemented will be followed up at the next review meeting in three years' time and this will be a means of putting international pressure on further safety work. This pressure is also reflected in the resolutions following the review meeting which were adopted by the General Congresses of the IAEA and the UN. (abstract truncated)

  12. European union contribution to the solution of the Chornobyl problems

    International Nuclear Information System (INIS)

    Djuglaris, D.; Konstantinov, N.

    2001-01-01

    The European Union has been the driving force in the development and implementation of the 1995 Memorandum of Understanding between the Governments of the G-7 countries and the European Commission and the Government of Ukraine on the closure of the Chornobyl NPP. Today, it is possible to summarize the past and current European Commission involvement into the solution of this huge problem and to see what the EC can do in future

  13. Rapid and Sustained Nuclear-Cytoplasmic ERK Oscillations Induced by Epidermal Growth Factor

    Energy Technology Data Exchange (ETDEWEB)

    Shankaran, Harish; Ippolito, Danielle L.; Chrisler, William B.; Resat, Haluk; Bollinger, Nikki; Opresko, Lee K.; Wiley, H. S.

    2009-12-01

    Mathematical modeling has predicted that ERK activity should oscillate in response to cell stimulation, but this has never been observed. To explore this inconsistency, we expressed an ERK1-GFP fusion protein in mammary epithelial cells. Following EGF stimulation, we observed rapid and continuous ERK oscillations between the nucleus and cytoplasm with a periodicity of approximately 15 minutes. These oscillations were remarkably persistent (>45 cycles), displayed an asymmetric waveform, and were highly dependent on cell density, essentially disappearing at confluency. We conclude that the ERK pathway is an intrinsic oscillator. Although the functional implications of the observed oscillations are uncertain, this property can be used to continuously monitor ERK activity in single cells.

  14. The Future of the European Security and Defence Policy

    National Research Council Canada - National Science Library

    Alt, Josef

    2006-01-01

    ...) at the European Union's (EU's) Helsinki summit in December 1999. They created the ESDP to allow the European Union to play a more comprehensive role in civilian and military international crisis management backed by credible military power...

  15. Combining ISO/IEC 17025:2005 and European Commission Decision 2002/657 audit requirements: a practical way forward.

    Science.gov (United States)

    Kay, Jack F

    2012-08-01

    Laboratories involved in the analyses of veterinary drug residues are under increasing pressure to demonstrate that they produce meaningful and reliable data. Quality assurance and quality control systems are implemented in laboratories to provide evidence of this and these are subject to external assessment to ensure that they are effective. Audits to ISO/IEC 17025:2005, an internationally accepted standard, and subsequent accreditation provide laboratories and their customers with a degree of assurance that the laboratories are operating in control and the data they report can be relied on. However, national or regional authorities may place additional requirements on laboratories to ensure quality data are reported. For example, in the European Union, all official control laboratories involved in veterinary drug residue analyses must also meet the requirements of European Commission Decision 2002/657/EC which sets performance criteria for analytical methods used in this area and these are subject to additional audits by national or regional authorities. All audits place considerable time and resource demands on laboratories and this paper discusses the burden audits place on laboratories and describes a UK initiative to combine these audits to the benefit of both the regulatory authority and the laboratory. © 2012 John Wiley & Sons, Ltd.

  16. New green paper on European energy policy

    International Nuclear Information System (INIS)

    Heller, W.

    2006-01-01

    On March 8, 2006, EU Commission president Jose Manuel Barroso and Energy Commissioner Andris Piebalgs presented to the public the Green Paper on 'A European Strategy for a Sustainable, Competitive, and Secure Energy', which had been expected for some time. The authors thus underscore the great importance for European development of energy policy. However, the European treaties restrict the competence of the EU in matters of energy policy. The Green Paper is to spark off a broad consultation and discussion process about the potential design of a comprehensive European energy policy. 6 main areas are mentioned in which action needs to be taken: - Energy for growth and employment. - Single energy market and continuity of supply. - Mix of energy resources: sustainable, efficient, divers. - Climate protection. - Innovation in energy technologies. - Coherent foreign policy in matters of energy. 3 key objectives are identified: - Development of renewable and other energy sources also with low CO 2 emissions. - Opening of markets, promotion of investments, energy efficiency. - Continuity of supply. (orig.)

  17. The R and D program on geothermal energy of the commission of the European communities results and future

    International Nuclear Information System (INIS)

    Louwrier, K.P.; Garnish, J.D.; Staroste, E.

    1992-01-01

    DGXII of the Commission of the European Communities has supported research and development in the field of the geothermal energy since 1975, and has just begun the fifth, and probably final, four year program. The first program concentrated on the data collection in order to establish the geothermal potential of the Community. This work resulted in the drafting and publication of two Atlases, one dealing with sub-surface temperatures and one with geothermal resources. Three multidisciplinary studies were undertaken on three known geothermal reservoirs with different characteristics, in order to test the validity of various exploration methods. A major element in recent years has been Hot Dry Rock studies, which have evolved during the course of the various program s from laboratory experiments and work in shallow holes towards a European test site where an international team of scientists coordinates research teams from different Member States. Basic scientific support to exploitation of geothermal energy has been given by geochemistry. The present R and D program centers on HDR research and abatement of corrosion and scaling in geothermal systems. Besides the geothermal work the program also supports studies in deep reservoir geology

  18. Contribution of the European Commission to a European Strategy for HLW Management through Partitioning and Transmutation: Presentation of MYRRHA and its Role in the European P and T Strategy

    International Nuclear Information System (INIS)

    Abderrahim, H.A.; Van den Eynde, G.; Baeten, P.; Schyns, M.; Vandeplassche, D.; Kochetkov, A.

    2015-01-01

    To be able to answer the world's increasing demand for energy, nuclear energy must be part of the energy mix. As a consequence of the nuclear electricity generation, high-level nuclear waste (HLW) is produced. The HLW is presently considered to be managed through its burying in geological storage. Partitioning and transmutation (P and T) has been pointed out as the strategy to reduce the radiological impact of HLW. Transmutation can be achieved in an efficient way in fast neutron spectrum facilities, both in critical fast reactors as well as in accelerator driven systems (ADSs). For more than two decades, the European Commission has been co-funding various research and development projects conducted in many European research organisations and industries related to P and T as a complementary strategy for high-level waste management to the geological disposal. In 2005, a European strategy for the implementation of P and T for a large part of the HLW in Europe indicated the need for the demonstration of its feasibility at an 'engineering' level. The R and D activities of this strategy were arranged in four 'building blocks': 1. Demonstration of the capability to process a sizable amount of spent fuel from commercial light water reactors (LWRs) in order to separate plutonium, uranium and minor actinides. 2. Demonstration of the capability to fabricate at a semi-industrial level the dedicated fuel needed as load in a dedicated transmuter. 3. Design and construction of one or more dedicated transmuters. 4. Provision of a specific installation for processing of the dedicated fuel unloaded from the transmuter, which can be of a different type than the one used to process the original spent fuel unloaded from the commercial power plants, together with the fabrication of new dedicated fuel. MYRRHA contributes to the third building block. MYRRHA is an ADS under development at SCK.CEN in collaboration with a large number of European partners. One of

  19. 4 July 2013- European Commission DG CONNECT Director-General R. Madelin, signing the guest book with CERN Director-General R. Heuer and visiting CMS experimental area with Collaboration Deputy Spokesperson J. Varela.

    CERN Multimedia

    Maximilien Brice

    2013-01-01

    4 July 2013- European Commission DG CONNECT Director-General R. Madelin, signing the guest book with CERN Director-General R. Heuer and visiting CMS experimental area with Collaboration Deputy Spokesperson J. Varela.

  20. Evidence for Elevated Cerebrospinal Fluid ERK1/2 Levels in Alzheimer Dementia

    Directory of Open Access Journals (Sweden)

    Philipp Spitzer

    2011-01-01

    Full Text Available Cerebrospinal fluid (CSF samples from 33 patients with Alzheimer dementia (AD, 21 patients with mild cognitive impairment who converted to AD during followup (MCI-AD, 25 patients with stable mild cognitive impairment (MCI-stable, and 16 nondemented subjects (ND were analyzed with a chemiluminescence immunoassay to assess the levels of the mitogen-activated protein kinase ERK1/2 (extracellular signal-regulated kinase 1/2. The results were evaluated in relation to total Tau (tTau, phosphorylated Tau (pTau, and beta-amyloid 42 peptide (Aβ42. CSF-ERK1/2 was significantly increased in the AD group as compared to stable MCI patients and the ND group. Western blot analysis of a pooled cerebrospinal fluid sample revealed that both isoforms, ERK1 and ERK2, and low amounts of doubly phosphorylated ERK2 were detectable. As a predictive diagnostic AD biomarker, CSF-ERK1/2 was inferior to tTau, pTau, and Aβ42.

  1. Characterization of genome sequences and clinical features of coxsackievirus A6 strains collected in Hyogo, Japan in 1999-2013.

    Science.gov (United States)

    Ogi, Miki; Yano, Yoshihiko; Chikahira, Masatsugu; Takai, Denshi; Oshibe, Tomohiro; Arashiro, Takeshi; Hanaoka, Nozomu; Fujimoto, Tsuguto; Hayashi, Yoshitake

    2017-08-01

    Coxsackievirus A6 (CV-A6) is an enterovirus, which is known to cause herpangina. However, since 2009 it has frequently been isolated from children with hand, foot, and mouth disease (HFMD). In Japan, CV-A6 has been linked to HFMD outbreaks in 2011 and 2013. In this study, the full-length genome sequencing of CV-A6 strains were analyzed to identify the association with clinical manifestations. Five thousand six hundred and twelve children with suspected enterovirus infection (0-17 years old) between 1999 and 2013 in Hyogo Prefecture, Japan, were enrolled. Enterovirus infection was confirmed with reverse transcriptase-PCR in 753 children (791 samples), 127 of whom (133 samples) were positive for CV-A6 based on the direct sequencing of the VP4 region. The complete genomes of CV-A6 from 22 positive patients with different clinical manifestations were investigated. A phylogenetic analysis divided these 22 strains into two clusters based on the VP1 region; cluster I contained strains collected in 1999-2009 and mostly related to herpangina, and cluster II contained strains collected in 2011-2013 and related to HFMD outbreak. Based on the full-length polyprotein analysis, the amino acid differences between the strains in cluster I and II were 97.7 ± 0.28%. Amino acid differences were detected in 17 positions within the polyprotein. Strains collected in 1999-2009 and those in 2011-2013 were separately clustered by phylogenetic analysis based on 5'UTR and 3Dpol region, as well as VP1 region. In conclusion, HFMD outbreaks by CV-A6 were recently frequent in Japan and the accumulation of genomic change might be associated with the clinical course. © 2017 Wiley Periodicals, Inc.

  2. Impact of European policy trends on bio-energy in the Netherlands

    International Nuclear Information System (INIS)

    Ruijgrok, W.; Erbrink, J.J.

    2000-03-01

    Energy extraction from biomass and waste is intended to account for a significant portion of the long-term objective of the Dutch government concerning sustainable energy. A major part of the task for energy from biomass and waste still has to come about, however. In the practical situation, the various parties in the Netherlands are experiencing different kinds of problems with this. In January 1999, the Ministry of Economic Affairs and Novern organised a round table conference concerning these bottlenecks with the participants representing a wide field of activity. The participants of this round table conference stated that insight into European policy developments is very important for the further market introduction of bio-energy in the Netherlands. Commissioned by Novem, this study surveys the consequences of the differences between European policy and Dutch policy in realising the target for energy from biomass and waste in the Netherlands in the medium term (2007). In addition, the following items were considered: sustainable energy; emission policy concerning waste, energy and biomass; waste policy and liberalisation of this market; energy policy and liberalisation of this market; agricultural policy; andfinancing of sustainable energy

  3. Sustainable introduction of GM crops into european agriculture: a summary report of the FP6 SIGMEA research project*

    Directory of Open Access Journals (Sweden)

    Messéan Antoine

    2009-01-01

    Full Text Available In 2003, the European Commission established the principle of coexistence which refers to “the ability of farmers to make a practical choice between conventional, organic and GM-crop production, in compliance with the legal obligations for labelling and/or purity standards” and laid down guidelines defining the context of this coexistence1. In order to determine what is needed for the sustainable introduction of GM crops in Europe, the cross-disciplinary SIGMEA Research Project was set up to create a science-based framework to inform decision-makers. SIGMEA has (i collated and analysed European data on gene flow and the environmental impacts of the major crop species which are likely to be transgenic in the future (maize, rapeseed, sugar beet, rice, and wheat, (ii designed predictive models of gene flow at the landscape level, (iii analysed the technical feasibility and economic impacts of coexistence in the principal farming regions of Europe, (iv developed novel GMO detection methods, (v addressed legal issues related to coexistence, and (vi proposed public and farm scale decisionmaking tools, as well as guidelines regarding management and governance. This publishable version of the final activity report of the FP6 SIGMEA research project, covers the fourteen major issues under investigation.

  4. International co-operation in safety matters within the framework of the Commission of the European Communities

    International Nuclear Information System (INIS)

    Vinck, W.; Balz, W.; Essler, W.; Tolley, B.; Gabolde, J.

    1981-01-01

    European Community (EC) countries realize that their energy demand cannot be met without a nuclear component, which is almost a necessity owing to its major economic advantages. Two typical areas where the Commission has stimulated intense international co-operation are as follows: The first broad area deals with efforts towards a gradual harmonization of regulatory health and safety practices and requirements for reactors of an industrially developed type, more specifically (light) water-cooled reactors. The second area concerns joint research programmes and co-ordination activities in research on nuclear safety (LWRs and LMFBRs). These two broad areas are closely interconnected. Information is also given on the existing network of bilateral and multilateral arrangements for the exchange of information of interest to the EC. In conclusion, some problems are highlighted where improvements could be made or where it seems crucial that increased international co-operation and especially agreement should come about. (author)

  5. The European network of excellence Emil

    International Nuclear Information System (INIS)

    2006-01-01

    The network of excellence EMIL (European Molecular Imaging Laboratories ) is the only European network of excellence in molecular imaging for oncology. It was set up and is coordinated by the 'in vivo imaging of gene expression' group of CEA Orsay. Included in Priority Thematic Area 1 (life sciences, genomics and biotechnology for health) of the European Commission's 6. Framework Programme for Research and Technological Development (FP6), this five-year project (2004-2009) aims t o merge the leading European research teams in molecular imaging, in universities, research centres and small and medium enterprises, to focus on early diagnosis, prognosis and therapeutic evaluation of cancer. The EMIL network brings together 58 partners representing 43 bodies in 13 European countries, and integrates 6 technological facilities: Orsay (France), Turin (Italy), Cologne (Germany), Leiden (Netherlands), Milan (Italy) and Antwerpen (Belgium).The research and training activities of the EMIL network are based on 9 thematic working groups or 'work packages' (wp), forming a common activity programme including : Integration activities: creation of a network of technological and training facilities favouring the mobility of researchers and the integration of small and medium enterprises into the EMIL network. Dissemination of expertise activities: training, communication, common knowledge management and intellectual property rights. Research activities: a common research programme with a horizontal dimension, making use of methodological tools of physics, biology and chemistry necessary for the further development of molecular imaging (instrument techniques, molecular probes, biological engineering), and a vertical integrative dimension, bringing together cancer imaging applications (early diagnostic imaging, development of new therapies imaging for drug development). (author)

  6. ERK2 dependent signaling contributes to wound healing after a partial-thickness burn

    International Nuclear Information System (INIS)

    Satoh, Yasushi; Saitoh, Daizoh; Takeuchi, Atsuya; Ojima, Kenichiro; Kouzu, Keita; Kawakami, Saki; Ito, Masataka; Ishihara, Masayuki; Sato, Shunichi; Takishima, Kunio

    2009-01-01

    Burn healing is a complex physiological process involving multiple cell activities, such as cell proliferation, migration and differentiation. Although extracellular signal-regulated kinases (ERK) have a pivotal role in regulating a variety of cellular responses, little is known about the individual functions of ERK isoform for healing in vivo. This study investigated the role of ERK2 in burn healing. To assess this, Erk2 +/- mice generated by gene targeting were used. The resultant mice exhibited significant delay in re-epithelization of partial-thickness burns in the skin in comparison to wild-type. An in vitro proliferation assay revealed that keratinocytes from Erk2 +/- mice grew significantly slower than those prepared from wild-type. These results highlight the importance of ERK2 in the process of burn healing.

  7. [6]-Shogaol Inhibits α-MSH-Induced Melanogenesis through the Acceleration of ERK and PI3K/Akt-Mediated MITF Degradation

    Directory of Open Access Journals (Sweden)

    Huey-Chun Huang

    2014-01-01

    Full Text Available [6]-Shogaol is the main biologically active component of ginger. Previous reports showed that [6]-shogaol has several pharmacological characteristics, such as antioxidative, anti-inflammatory, antimicrobial, and anticarcinogenic properties. However, the effects of [6]-shogaol on melanogenesis remain to be elucidated. The study aimed to evaluate the potential skin whitening mechanisms of [6]-shogaol. The effects of [6]-shogaol on cell viability, melanin content, tyrosinase activity, and the expression of the tyrosinase and microphthalmia-associated transcription factor (MITF were measured. The results revealed that [6]-shogaol effectively suppresses tyrosinase activity and the amount of melanin and that those effects are more pronounced than those of arbutin. It was also found that [6]-shogaol decreased the protein expression levels of tyrosinase-related protein 1 (TRP-1 and microphthalmia-associated transcriptional factor (MITF. In addition, the MITF mRNA levels were also effectively decreased in the presence of 20 μM [6]-shogaol. The degradation of MITF protein was inhibited by the MEK 1-inhibitor (U0126 or phosphatidylinositol-3-kinase inhibitor (PI3K inhibitor (LY294002. Further immunofluorescence staining assay implied the involvement of the proteasome in the downregulation of MITF by [6]-shogaol. Our confocal assay results also confirmed that [6]-shogaol inhibited α-melanocyte stimulating hormone- (α-MSH- induced melanogenesis through the acceleration of extracellular responsive kinase (ERK and phosphatidylinositol-3-kinase- (PI3K/Akt- mediated MITF degradation.

  8. Structure-Guided Strategy for the Development of Potent Bivalent ERK Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lechtenberg, Bernhard C. [Cancer; Mace, Peter D. [Cancer; Sessions, E. Hampton [Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827, United States; Williamson, Robert [Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827, United States; Stalder, Romain [Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827, United States; Wallez, Yann [Cancer; Roth, Gregory P. [Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827, United States; Riedl, Stefan J. [Cancer; Pasquale, Elena B. [Cancer; Pathology

    2017-06-13

    ERK is the effector kinase of the RAS-RAF-MEK-ERK signaling cascade, which promotes cell transformation and malignancy in many cancers and is thus a major drug target in oncology. Kinase inhibitors targeting RAF or MEK are already used for the treatment of certain cancers, such as melanoma. Although the initial response to these drugs can be dramatic, development of drug resistance is a major challenge, even with combination therapies targeting both RAF and MEK. Importantly, most resistance mechanisms still rely on activation of the downstream effector kinase ERK, making it a promising target for drug development efforts. Here, we report the design and structural/functional characterization of a set of bivalent ERK inhibitors that combine a small molecule inhibitor that binds to the ATP-binding pocket with a peptide that selectively binds to an ERK protein interaction surface, the D-site recruitment site (DRS). Our studies show that the lead bivalent inhibitor, SBP3, has markedly improved potency compared to the small molecule inhibitor alone. Unexpectedly, we found that SBP3 also binds to several ERK-related kinases that contain a DRS, highlighting the importance of experimentally verifying the predicted specificity of bivalent inhibitors. However, SBP3 does not target any other kinases belonging to the same CMGC branch of the kinome. Additionally, our modular click chemistry inhibitor design facilitates the generation of different combinations of small molecule inhibitors with ERK-targeting peptides.

  9. MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma

    Science.gov (United States)

    Ranjan, Atul; Iyer, Swathi V.; Ward, Christopher; Link, Tim; Diaz, Francisco J.; Dhar, Animesh; Tawfik, Ossama W.; Weinman, Steven A.; Azuma, Yoshiaki; Izumi, Tadahide; Iwakuma, Tomoo

    2018-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases. MTBP also inhibits phosphorylation of Elk-1 and decreases mRNA expression of Elk-1 target genes. Reduced Elk-1 activity is caused by inhibited nuclear translocation of phosphorylated Erk1/2 (p-Erk) by MTBP and subsequent inhibition of Elk-1 phosphorylation. We also reveal that MTBP inhibits the interaction of p-Erk with importin-7/RanBP7 (IPO7), an importin family member which shuttles p-Erk into the nucleus, by binding to IPO7. Moreover, high levels of MTBP in human HCC tissues are correlated with cytoplasmic localization of p-Erk1/2. Our study suggests that MTBP suppresses metastasis, at least partially, by down-modulating the Erk1/2-Elk-1 signaling pathway, thus identifying a novel regulatory mechanism of HCC metastasis by regulating the subcellular localization of p-Erk. PMID:29765550

  10. European vehicle passive safety network

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Janssen, E.G.

    1999-01-01

    The general objective of the European Vehicle Passive Safety Network is to contribute to the reduction of the number of road traffic victims in Europe by passive safety measures. The aim of the road safety policy of the European Commission is to reduce the annual total of fatalities to 18000 in

  11. Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Jan Kučera

    2017-01-01

    Full Text Available Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1 is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES cell maintenance. We employed wild-type and HIF-1α-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected. Downregulation of ERK could not be mimicked either by pharmacologically induced hypoxia or by the overexpression. Dual-specificity phosphatases (DUSP 1, 5, and 6 are hypoxia-sensitive MAPK-specific phosphatases involved in ERK downregulation, and protein phosphatase 2A (PP2A regulates both ERK and Akt. However, combining multiple approaches, we revealed the limited significance of DUSPs and PP2A in the hypoxia-mediated attenuation of ERK signaling. Interestingly, we observed a decreased reactive oxygen species (ROS level in hypoxia and a similar phosphorylation pattern for ERK when the cells were supplemented with glutathione. Therefore, we suggest a potential role for the ROS-dependent attenuation of ERK signaling in hypoxia, without the involvement of HIF-1.

  12. Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan; Reddy, Kanamata; Kurinov, Igor; Carper, Andria; Langfald, Alyssa; Oi, Naomi; Kim, Myoung Ok; Zhu, Feng; Sosa, Carlos P.; Zhou, Keyuan; Bode, Ann M.; Dong, Zigang (Cornell); (Guangdong); (UMM)

    2012-06-27

    Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.

  13. Benchmarking European Gas Transmission System Operators

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter; Trinkner, Urs

    This is the final report for the pan-European efficiency benchmarking of gas transmission system operations commissioned by the Netherlands Authority for Consumers and Markets (ACM), Den Haag, on behalf of the Council of European Energy Regulators (CEER) under the supervision of the authors....

  14. The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: Code of Conduct, Version 2--2008.

    LENUS (Irish Health Repository)

    McMurray, Janet

    2009-01-01

    In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 10 years, more than 2000 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Federation of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). A Code of Conduct was adopted in 2003 and a revised and updated version, taking account particularly of the guidelines of the Conseil Européen des Professions Libérales (CEPLIS) of which EFCC is a member, is presented in this article. The revised version was approved by the EC4 Register Commission and by the EFCC Executive Board in Paris on 6 November, 2008.

  15. Commissioning of Temelin NPP as seen by scientific supervisory group

    International Nuclear Information System (INIS)

    Svoboda, C.

    2003-01-01

    Scientific Supervisory Group worked during the Temelin NPP commissioning process as an independent supervisor. The main tasks and main results of its activity are described in this contribution. The characteristic common features of commissioning process and most important events from the Scientific Supervisory Group point of view are presented. In April 1999 the Czech Power Utility with the objective to achieve maximum level of nuclear safety and quality within the NPP Temelin commissioning procedures has established a special body / Scientific Supervisory Group and requested Nuclear Research Institute Rez plc to perform the required function. The Scientific Supervisory Group proceeds in accordance with its Statute and provides an independent specialised professional and expert work focused on nuclear safety assurance, assesment of the selected documentation related to plant preparedness for the individual commissioning stages, and, of course. on assessment of the commissioning tests results. While performing its function the Scientific Supervisory Group is guided by the Atomic Act and the relevant Directives of State Office for Nuclear Safety; its activities are in compliance with the applicable IAEA recommendations (Authors)

  16. Sodium Ferulate Prevents Daunorubicin - Induced Apoptosis in H9c2 Cells via Inhibition of the ERKs Pathway

    Directory of Open Access Journals (Sweden)

    Zhi-Juan Wu

    2015-07-01

    Full Text Available Background: Daunorubicin (DNR-induced cardiotoxicity, which is closely associated with cardiomyocyte apoptosis, limits the drug's clinical application. The activation of the extracellular regulated protein kinases (ERKs pathway is responsible for the pro-apoptosis effect of DNR Sodium ferulate (SF has recently been found to attenuate both DNR-induced cardiotoxicity and mitochondrial apoptosis in juvenile rats. Nonetheless, the precise mechanism underlying SF-induced cardio-protection remains unclear. Methods: The DNR-injured H9c2 cell model was prepared by incubating the cells in 1 µM DNR for 24 h. Amounts of 15.6, 31.3 or 62.5 µM SF were simultaneously added to the cells. The effect of SF on the cytotoxic and apoptotic parameters of the cells was studied by monitoring apoptosis regulation via the ERKs pathway. Results: SF attenuated DNR-induced cell death (particularly apoptotic death, cTnI and β-tubulin degradation, and cellular morphological changes. SF reduced mitochondrial membrane potential depolarization, cytochrome c leakage, and caspase-9 and caspase-3 activation. SF also decreased ERK1/2, phospho-ERK1/2, p53 and Bax expression and increased Bcl-2 expression. These effects were similar to the results observed when using the pharmacological ERKs phosphorylation inhibitor, AZD6244. Conclusion: We determined that SF protects H9c2 cells from DNR-induced apoptosis through a mechanism that involves the interruption of the ERKs signaling pathway.

  17. Photovoltaic module with integrated power conversion and interconnection system - the European project PV-MIPS

    OpenAIRE

    Henze, N.; Engler, A.; Zacharias, P.

    2006-01-01

    Within the 6th framework program funded by the European Commission the project PV-MIPS (Photovoltaic Module with Integrated Power Conversion System) was launched in November 2004. Together with eleven European partners from Germany, Austria, Greece and the Netherlands a solar module with integrated in-verter shall be developed that can feed solar electricity directly into the grid. The challenging objective of the project is to reduce the total costs of a PV system. At the same time lifetime ...

  18. [Electroacupuncture Intervention Enhances Splenic Natural Killer Cell Activity via Inhibiting Phosphorylation of ERK 5 in the Hypothalamus of Surgically Traumatized Rats].

    Science.gov (United States)

    Chen, Yan; Li, Jing; Zhu, Ke-ying; Xiao, Sheng; Wang, Yan-qing; Wu, Gen-cheng; Wang, Jun

    2015-06-01

    To observe the effect of electroacupuncture (EA) on cytotoxic activity of splenic natural killer (NK) cells after surgical trauma via extracellular signal-regulated kinase (ERK) 5 pathway in the rats' hypothalamus, so as to explore its mechanism underlying improving immune disorders after surgery. Sprague-Dawley rats were randomly divided into the following 6 groups: control, trauma model, EA, sham EA, 4 nmol-BIX 02188 (an inhibitor for ERK 5 catalytic activity) and 20 nmol-BIX 02188 (n = 6 rats per group). The surgical trauma model was established by making a longitudinal incision (6 cm in length) along the median line of the back to expose the spinal column and another longitudinal incision along the abdominal median line. EA (2 Hz/15 Hz, 1 - 2 mA) was applied to bilateral "Zusanli" (ST 36) for 30 min immediately after surgery. For rats of the BIX groups, intra-lateral ventricular microinjection of BIX 02188 (10 µL, 4 nmol or 20 nmol, or saline for control rats) was conducted 30 min before the surgery. The expression level and protein of phosphorylated ERK 5 (p-ERK 5) and corticotropin-releasing factor (CRF) protein were measured by immunohistochemistry and Western blot, respectively. The cytotoxicity of splenic NK cells and the expression of splenic Perforin and Granzyme-B genes were measured by lactate dehydrogenase (LDH) release assay and real-time PCR, respectively. In comparison with the control group, hypothalamic p-ERK 5 immunoactivity, p-ERK 5 protein and CRF protein expression levels were significantly up-regulated in the model group (Psplenic NK cell cytotoxicity and Perforin mRNA and Granzyme-B mRNA expression levels were notably down-regulated in the model group (P 0. 05) except the increased p-ERK 5 protein in the 4 nmol-BIX 02188 group. In addition, the down-regulated NK cell activity, Perforin mRNA and Granzyme-B mRNA expression levels were significantly reversed in the EA and 20 nmol-BIX 02188 groups (Psplenic NK cytotoxicity and Perforin and

  19. The EFQM excellence model: European and Dutch experiences with the EFQM approach in health care. European Foundation for Quality Management

    NARCIS (Netherlands)

    Nabitz, U.; Klazinga, N.; Walburg, J.

    2000-01-01

    One way to meet the challenges in creating a high performance organization in health care is the approach of the European Foundation for Quality Management (EFQM). The Foundation is in the tradition of the American Malcolm Baldrige Award and was initiated by the European Commission and 14 European

  20. Quality of SME Business Transfers Matching Platforms: Research Outcomes of 12 European Countries

    NARCIS (Netherlands)

    Oriol Alba; Edwin Weesie; Marie Depelssemaker; Lex van Teeffelen; Nicolas Pirotte

    2016-01-01

    From the preface : The European Commission supports Member States by providing them with recommendations, guidelines, information and good practices. For years, the European Commission has stimulated Member States to develop matching platforms to efficiently support sellers and buyers of SMEs in

  1. 6-Alkyl-, 6-aryl- or 6-hetaryl-7-deazapurine ribonucleosides as inhibitors of human or MTB adenosine kinase and potential antimycobacterial agents

    Czech Academy of Sciences Publication Activity Database

    Perlíková, Pavla; Konečný, P.; Nauš, Petr; Snášel, Jan; Votruba, Ivan; Džubák, P.; Pichová, Iva; Hajdúch, M.; Hocek, Michal

    2013-01-01

    Roč. 4, č. 11 (2013), s. 1497-1500 ISSN 2040-2503 R&D Projects: GA ČR GAP207/11/0344 EU Projects: European Commission(XE) 241587 - SYSTEMTB Grant - others:Operational Programme Research and Development for Innovations(XE) CZ.1.05/2.1.00/01.0030 Institutional support: RVO:61388963 Keywords : mycobacterium- tuberculosis * enzyme-inhibition * 6-(het)aryl-7-deazapurine ribonucleosides Subject RIV: CC - Organic Chemistry Impact factor: 2.626, year: 2013

  2. Preparing accelerator systems for the RHIC sextant commissioning

    International Nuclear Information System (INIS)

    Trbojevic, D.; Pilat, F.; Ahrens, L.

    1997-01-01

    The Relativistic Heavy Ion Collider (RHIC) construction is progressing steadily towards completion in 1999 when beams will circulate in both collider rings. One of the major tests of the RHIC project was the commissioning of the first sextant with gold ion beams in early 1997. This is a report on preparation of the RHIC accelerator systems for the first sextant test. It includes beam position monitors, timing, injection correction through the magnetic septum and kickers, current transformers, flags and the ionization beam profile monitors, beam loss monitors, beam and quench permit link system, power supply controls, and the configuration database system. The software and hardware development and coordination of the different systems before commissioning were regularly checked during bi-weekly, and (later) weekly, progress report meetings

  3. Nuclear Regulatory Commission issuances: Volume 39, Number 6

    International Nuclear Information System (INIS)

    1994-06-01

    This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judges (ALJ), the Directors' Decisions (DD), and the Denials of Petitions for Rulemaking (DPRM). Issuances of the Nuclear Regulatory Commission include: (1) Advanced Medical Systems, Inc.; (2) Henry Allen, Diane Marrone, and Susan Settino; and (3) Westinghouse Electric Corporation. Issuances of the Atomic Safety and Licensing Boards include: (1) Sequoyah Fuels Corporation and General Atomics Corporation and (2) Umetco Minerals Corporation. Issuances of Director's Decisions include: (1) Advanced Medical Systems, Inc., and (2) Boston Edison Company and all boiling water reactors. The summaries and headnotes preceding the opinions reported herein are not to be deemed a part of those opinions or have any independent legal significance

  4. DA-Raf-Mediated Suppression of the Ras--ERK Pathway Is Essential for TGF-β1-Induced Epithelial-Mesenchymal Transition in Alveolar Epithelial Type 2 Cells.

    Science.gov (United States)

    Watanabe-Takano, Haruko; Takano, Kazunori; Hatano, Masahiko; Tokuhisa, Takeshi; Endo, Takeshi

    2015-01-01

    Myofibroblasts play critical roles in the development of idiopathic pulmonary fibrosis by depositing components of extracellular matrix. One source of lung myofibroblasts is thought to be alveolar epithelial type 2 cells that undergo epithelial-mesenchymal transition (EMT). Rat RLE-6TN alveolar epithelial type 2 cells treated with transforming growth factor-β1 (TGF-β1) are converted into myofibroblasts through EMT. TGF-β induces both canonical Smad signaling and non-canonical signaling, including the Ras-induced ERK pathway (Raf-MEK-ERK). However, the signaling mechanisms regulating TGF-β1-induced EMT are not fully understood. Here, we show that the Ras-ERK pathway negatively regulates TGF-β1-induced EMT in RLE-6TN cells and that DA-Raf1 (DA-Raf), a splicing isoform of A-Raf and a dominant-negative antagonist of the Ras-ERK pathway, plays an essential role in EMT. Stimulation of the cells with fibroblast growth factor 2 (FGF2), which activated the ERK pathway, prominently suppressed TGF-β1-induced EMT. An inhibitor of MEK, but not an inhibitor of phosphatidylinositol 3-kinase, rescued the TGF-β1-treated cells from the suppression of EMT by FGF2. Overexpression of a constitutively active mutant of a component of the Ras-ERK pathway, i.e., H-Ras, B-Raf, or MEK1, interfered with EMT. Knockdown of DA-Raf expression with siRNAs facilitated the activity of MEK and ERK, which were only weakly and transiently activated by TGF-β1. Although DA-Raf knockdown abrogated TGF-β1-induced EMT, the abrogation of EMT was reversed by the addition of the MEK inhibitor. Furthermore, DA-Raf knockdown impaired the TGF-β1-induced nuclear translocation of Smad2, which mediates the transcription required for EMT. These results imply that intrinsic DA-Raf exerts essential functions for EMT by antagonizing the TGF-β1-induced Ras-ERK pathway in RLE-6TN cells.

  5. ERK Regulates Renal Cell Proliferation and Renal Cyst Expansion in inv Mutant Mice

    International Nuclear Information System (INIS)

    Okumura, Yasuko; Sugiyama, Noriyuki; Tanimura, Susumu; Nishida, Masashi; Hamaoka, Kenji; Kohno, Michiaki; Yokoyama, Takahiko

    2009-01-01

    Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage kidney disease in children and young adults. Inv mice are a model for human nephronophthisis type 2 (NPHP2) and characterized by multiple renal cysts and situs inversus. Renal epithelial cells in inv cystic kidneys show increased cell proliferation. We studied the ERK pathway to understand the mechanisms that induce cell proliferation and renal cyst progression in inv kidneys. We studied the effects of ERK suppression by administering PD184352, an oral mitogen-activated protein kinase kinase (MEK) inhibitor on renal cyst expansion, extracellular signal-regulated protein kinase (ERK) activity, bromo-deoxyuridine (BrdU) incorporation and expression of cell-cycle regulators in invΔC kidneys. Phosphorylated ERK (p-ERK) level increased along with renal cyst enlargement. Cell-cycle regulators showed a high level of expression in invΔC kidneys. PD184352 successfully decreased p-ERK level and inhibited renal cyst enlargement. The inhibitor also decreased expression of cell-cycle regulators and BrdU incorporation in renal epithelial cells. The present results showed that ERK regulated renal cell proliferation and cyst expansion in inv mutants

  6. Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex

    Science.gov (United States)

    Xing, Lei; Larsen, Rylan S; Bjorklund, George Reed; Li, Xiaoyan; Wu, Yaohong; Philpot, Benjamin D; Snider, William D; Newbern, Jason M

    2016-01-01

    Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2+ neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability. DOI: http://dx.doi.org/10.7554/eLife.11123.001 PMID:26848828

  7. 76 FR 18198 - European Union-United States Atlantis Program

    Science.gov (United States)

    2011-04-01

    ... DEPARTMENT OF EDUCATION European Union-United States Atlantis Program AGENCY: Office of...)--Special Focus Competition: European Union-(EU) United States (U.S.) Atlantis Program Notice inviting... and Culture, European Commission for funding under a separate but parallel EU competition. Within this...

  8. Different trends in euthanasia acceptance across Europe. A study of 13 western and 10 central and eastern European countries, 1981-2008.

    Science.gov (United States)

    Cohen, Joachim; Van Landeghem, Paul; Carpentier, Nico; Deliens, Luc

    2013-06-01

    We examined how acceptance of euthanasia among the general public has changed between 1981 and 2008 in western and central and eastern European (CEE) countries using data of the European Values Surveys. Data were collected in 1981, 1990, 1999 and 2008 for 13 western European countries and in 1990, 1999 and 2008 for 10 CEE countries. Euthanasia acceptance increased each decade up until 2008 in 11 of 13 western European countries; in CEE countries, it decreased or did not increase between 1999-2008 in 8 of 10 countries. A number of explanations for and implications of this apparent east-west polarization are suggested.

  9. Enresa's Participation in the Technical Assistance Programmes to the Eastern European Countries

    International Nuclear Information System (INIS)

    Beceiro, A. R.; Vico, E.

    2000-01-01

    This article briefly describes the participation of ENRESA in the technical assistance programmes to the Central and Eastern European countries (PHARE) and to the New Independent States (TACIS) as well as in the co-operation programmes all of them established by the European Commission. It is worth to point out the active role of ENRESA within the European Consortium CASSIOPEE, formed in 1993 by the six radioactive waste management companies in existence in the European Union at that time. CASSIOPEE was created to assist the European Commission in the area of radioactive waste management of the PHARE and TACIS technical assistance programmes. (Author)

  10. Ectopic ERK Expression Induces Phenotypic Conversion of C10 Cells and Alters DNA Methyltransferase Expression

    Energy Technology Data Exchange (ETDEWEB)

    Sontag, Ryan L.; Weber, Thomas J.

    2012-05-04

    In some model systems constitutive extracellular signal regulated kinase (ERK) activation is sufficient to promote an oncogenic phenotype. Here we investigate whether constitutive ERK expression influences phenotypic conversion in murine C10 type II alveolar epithelial cells. C10 cells were stably transduced with an ERK1-green fluorescent protein (ERK1-GFP) chimera or empty vector and ectopic ERK expression was associated with the acquisition of soft agar focus-forming potential in late passage, but not early passage cells. Late passage ERK1-GFP cells exhibited a significant increase in the expression of DNA methyl transferases (DNMT1 and 3b) and a marked increase in sensitivity to 5-azacytidine (5-azaC)-mediated toxicity, relative to early passage ERK1-GFP cells and vector controls. The expression of xeroderma pigmentosum complementation group A (XPA) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) were significantly increased in late passage cells, suggesting enhanced DNA damage recognition and repair activity which we interpret as a reflection of genomic instability. Phospho-ERK levels were dramatically decreased in late passage ERK1-GFP cells, relative to early passage and vector controls, and phospho-ERK levels were restored by treatment with sodium orthovanadate, indicating a role for phosphatase activity in this response. Collectively these observations suggest that ectopic ERK expression promotes phenotypic conversion of C10 cells that is associated with latent effects on epigenetic programming and phosphatase activities.

  11. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    International Nuclear Information System (INIS)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae

    2012-01-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  12. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae, E-mail: chidkim@pusan.ac.kr

    2012-04-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  13. INSTITUTIONAL MANAGEMENT OF EUROPEAN STATISTICS AND OF THEIR QUALITY - CURRENT CONCERNS AT EUROPEAN LEVEL

    Directory of Open Access Journals (Sweden)

    Daniela ŞTEFĂNESCU

    2011-08-01

    Full Text Available The issues referring to official statistics quality and reliability became the main topics of debates as far as statistical governance in Europe is concerned. The Council welcomed the Commission Communication to the European Parliament and to the Council « Towards robust quality management for European Statistics » (COM 211, appreciating that the approach and the objective of the strategy would confer the European Statistical System (ESS the quality management framework for the coordination of consolidated economic policies. The Council pointed out that the European Statistical System management was improved during recent years, that progress was noticed in relation with high quality statistics production and dissemination within the European Union, but has also noticed that, in the context of recent financial crisis, certain weaknesses were identified, particularly related to quality management general framework.„Greece Case” proved that progresses were not enough for guaranteeing the complete independence of national statistical institutes and entailed the need for further consolidating ESS governance. Several undertakings are now in the preparatory stage, in accordance with the Commission Communication; these actions are welcomed, but the question arise: are these sufficient for definitively solving the problem?The paper aims to go ahead in the attempt of identifying a different way, innovative (courageous! on the long run, towards an advanced institutional structure of ESS, by setting up the European System of Statistical Institutes, similar to the European System of Central Banks, that would require a change in the Treaty.

  14. Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice.

    Science.gov (United States)

    Shiokawa, Moe; Lu, Xiuyuan; Miyake, Yasunobu; Ishikawa, Eri; Pagès, Gilles; Pouysségur, Jacques; Ogata, Masato; Yamasaki, Sho

    2017-12-18

    Lineage-specific Cre Tg mice are widely used to delineate the functions of genes in a tissue-specific manner. Several T-cell-specific promoter cassettes have been developed; however, the activities of those promoters in non-T cells have not been investigated extensively. Here, we report that CD2-Cre-mediated deletion of Erk proteins by generating CD2-Cre × Erk1-/-Erk2flox/flox (Erk∆CD2-Cre) mice results in abnormal cartilage hyperplasia. Histological analysis revealed that this abnormality is caused by aberrant hyperplasia of chondrocytes. The presence of Erk-deficient T cells is not required for this chondroma formation, as it was similarly observed in the absence of T cells in a CD3ε-deficient background. In addition, adoptive transfer of bone marrow cells from Erk∆CD2-Cre mice to wild-type recipients did not cause chondroma formation, suggesting that Erk-deficient non-immune cells are responsible for this abnormality. By tracing Cre-expressed tissues using a ROSA26-STOP-RFP allele, we found that the chondroma emitted RFP fluorescence, indicating that functional Cre is expressed in hyperplastic chondrocytes in Erk∆CD2-Cre mice. Furthermore, RFP+ chondrocytes were also found in an Erk-sufficient background, albeit without aberrant growth. These results suggest that unexpected expression of CD2-driven Cre in chondrocytes generates Erk-deficient chondrocytes, resulting in hyperplastic cartilage formation. Recently, two independent reports showed that CD4-Cre-mediated Ras-Erk signaling ablation led to similar abnormal cartilage formation (Guittard, G., Gallardo, D. L., Li, W. et al. 2017. Unexpected cartilage phenotype in CD4-Cre-conditional SOS-deficient mice. Front. Immunol. 8:343; Wehenkel, M., Corr, M., Guy, C. S. et al. 2017. Extracellular signal-regulated kinase signaling in CD4-expressing cells inhibits osteochondromas. Front. Immunol. 8:482). Together with these reports, our study suggests that an unexpected link exists between T-like cell and

  15. The accession to the European Union. The nuclear safety issue

    International Nuclear Information System (INIS)

    Mayer, S.; Tomic, B.; Goldemund, M.; Van der Mheen, W.; Johanson, G.

    2000-01-01

    Since mid 1999, a project based on an initiative by the European Commission has been conducted with the primary objective to develop a comprehensive, consistent, and wellbalanced methodology for the evaluation of the status of nuclear safety in countries with operating nuclear power plants, and to perform a preliminary assessment for Bulgaria, Czech Republic, Hungary, Lithuania, Romania, Slovak Republic, and Slovenia. In addition to the safety status of nuclear power plants, emphasis is placed on nuclear regulation, both on organisational and legislative aspects, and on the practice of performing safety assessment. A brief overview will also be given on the nuclear safety situation in the Newly Independent States (NIS). During the course of the project, a Performance Evaluation Guide was developed with the objective to establish a sound methodology for evaluating safety of nuclear reactors in different countries in a consistent manner. The project is performed by a Consortium led by ENCONET Consulting (Austria), with participation of NNC (United Kingdom), NRG (Netherlands), and ES-konsult (Sweden). (author)

  16. The European network of excellence Emil

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    The network of excellence EMIL (European Molecular Imaging Laboratories ) is the only European network of excellence in molecular imaging for oncology. It was set up and is coordinated by the 'in vivo imaging of gene expression' group of CEA Orsay. Included in Priority Thematic Area 1 (life sciences, genomics and biotechnology for health) of the European Commission's 6. Framework Programme for Research and Technological Development (FP6), this five-year project (2004-2009) aims t o merge the leading European research teams in molecular imaging, in universities, research centres and small and medium enterprises, to focus on early diagnosis, prognosis and therapeutic evaluation of cancer. The EMIL network brings together 58 partners representing 43 bodies in 13 European countries, and integrates 6 technological facilities: Orsay (France), Turin (Italy), Cologne (Germany), Leiden (Netherlands), Milan (Italy) and Antwerpen (Belgium).The research and training activities of the EMIL network are based on 9 thematic working groups or 'work packages' (wp), forming a common activity programme including : Integration activities: creation of a network of technological and training facilities favouring the mobility of researchers and the integration of small and medium enterprises into the EMIL network. Dissemination of expertise activities: training, communication, common knowledge management and intellectual property rights. Research activities: a common research programme with a horizontal dimension, making use of methodological tools of physics, biology and chemistry necessary for the further development of molecular imaging (instrument techniques, molecular probes, biological engineering), and a vertical integrative dimension, bringing together cancer imaging applications (early diagnostic imaging, development of new therapies imaging for drug development). (author)

  17. Nuclear Regulatory Commission issuances. Volume 42, No. 6

    International Nuclear Information System (INIS)

    1995-12-01

    This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judges (AU), the Directors' Decisions (DD), and the Decisions on Petitions for Rulemaking (DPRM)

  18. Elevated activation of ERK1 and ERK2 accompany enhanced liver injury following alcohol binge in chronically ethanol-fed rats.

    Science.gov (United States)

    Aroor, Annayya R; Jackson, Daniel E; Shukla, Shivendra D

    2011-12-01

    Binge drinking after chronic ethanol consumption is one of the important factors contributing to the progression of steatosis to steatohepatitis. The molecular mechanisms of this effect remain poorly understood. We have therefore examined in rats the effect of single and repeat ethanol binge superimposed on chronic ethanol intake on liver injury, activation of mitogen-activated protein kinases (MAPKs), and gene expression. Rats were chronically treated with ethanol in liquid diet for 4 weeks followed by single ethanol binge (5 gm/kg body weight) or 3 similar repeated doses of ethanol. Serum alcohol and alanine amino transferase (ALT) levels were determined by enzymatic methods. Steatosis was assessed by histology and hepatic triglycerides. Activation of MAPK, 90S ribosomal kinase (RSK), and caspase 3 were evaluated by Western blot. Levels of mRNA for tumor necrosis factor alpha (TNFα), early growth response-1 (egr-1), and plasminogen activator inhibitor-1 (PAI-1) were measured by real-time qRT-PCR. Chronic ethanol treatment resulted in mild steatosis and necrosis, whereas chronic ethanol followed by binge group exhibited marked steatosis and significant increase in necrosis. Chronic binge group also showed significant increase (compared with chronic ethanol alone) in the phosphorylation of extracellular regulated kinase 1 (ERK1), ERK2, and RSK. Phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK did not increase by the binge. Ethanol binge, after chronic ethanol intake, caused increase in mRNA for egr-1 and PAI-1, but not TNFα. Chronic ethanol exposure increases the susceptibility of rat liver to increased injury by 1 or 3 repeat binge. Among other alterations, the activated levels of ERK1, and more so ERK2, were remarkably amplified by binge suggesting a role of these isotypes in the binge amplification of the injury. In contrast, p38 MAPK and JNK1/2 activities were not amplified. These binge-induced changes were also reflected in the increases in the

  19. Priority for import capacity. The fear of the European Union for a free European energy market

    International Nuclear Information System (INIS)

    Roggen, M.

    2002-01-01

    Brussels (the seat of the European Union in Belgium) is worried about the performance of the liberalized European energy market. The natural gas and electricity networks are suffering from chronic congestion. Some areas are largely or even entirely cut off from the European energy infrastructure. Those problems must be addressed to realize the internal market. A package of reforms has been put forward by the European Commission the end of 2001 and 12 priority projects are identified and briefly discussed in this article [nl

  20. Analysis of the European Food Industry

    OpenAIRE

    Banse, Martin; McDonald, Scott; Joint Research Centre; Institute for Prospective Technological Studies; Kaditi, Eleni

    2008-01-01

    This report is based on a study assigned to the Centre for European Policy Studies (CEPS) by the European Commission¿s Joint Research Centre, Institute for Prospective Technological Studies (JRC-IPTS) to investigate recent developments in the European food industry and the impact of foreign direct investment (FDI) and trade flows on the food industry in the EU-25. The report illustrates trends in and the structure of the European food industry. Past and possible future developments are ana...

  1. European Sustainable Construction Regulation : Homogeneity and Attention

    NARCIS (Netherlands)

    Van der Heijden, J.; Van Bueren, E.M.

    2011-01-01

    Understanding the negative impact of the construction industry and the built environment on the ecological environment, the European Commission (EC) aims to harmonise and improve sustainable construction regulatory frameworks in Member States of the European Union. This paper discusses the topics of

  2. The radiological exposure of the population of the European Community from radioactivity in North European marine waters Project 'Marina'

    International Nuclear Information System (INIS)

    1990-01-01

    Project Marina was set up by the Commission of the European Communities in 1985 to look at the radiological impact of radionuclides, both natural and anthropogenic, in northern European marine waters. This paper is a summary of project Marina's work and its conclusions

  3. FGFR2c-mediated ERK-MAPK activity regulates coronal suture development

    Science.gov (United States)

    Pfaff, Miles J.; Xue, Ke; Li, Li; Horowitz, Mark C.; Steinbacher, Derek M.; Eswarakumar, Jacob V.P.

    2017-01-01

    Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor’s gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK-MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis. PMID:27034231

  4. Building the European Research Area in nuclear fission pioneering steps in actinide science

    International Nuclear Information System (INIS)

    Forsstroem, Hans

    2004-01-01

    The concept of the European Research Area (ERA) aims at closer development of research policies in Europe and closer networking of research capacities, to reduce fragmentation of research in Europe. The goal is to make European research more effective and competitive. Several approaches are made to create ERA. The European Research Framework Programme is one tool in this context, with the introduction of the new instruments, Integrated Projects, Networks of Excellence and Integrated Infrastructure Initiatives. Actinide science is one area that could benefit from better coordination and more effective use of the research capacities, both human and physical. The European Commission is thus funding a Network of Excellence (ACTINET-6) and an Integrated Project (EUROPART) in this area within the sixth EURATOM Framework Programme. (author)

  5. Investigation report from the commission for energy regulation about the outage of Saturday November 4, 2006

    International Nuclear Information System (INIS)

    2007-01-01

    On November 4, 2006, a large-scale incident occurred on the European high-voltage interconnected power network which left 15 million people without electricity in Western Europe during about 2 hours. Considering the European dimension of the outage, the European Regulators Group for Electricity and Gas (ERGEG) conducted an investigation, the final report of which being made publically available on February 6, 2007. Considering the impact of this incident on the French territory, the French commission for energy regulation (CRE) decided as soon as November 5, 2006 to carry out its own investigation in order to inform the French consumers about the chronology of facts and the precise causes of this incident. This document summarises the CRE's report and presents its conclusions and recommendations as well as the technical report of the incident

  6. Optimizing an Intermittent Stretch Paradigm Using ERK1/2 Phosphorylation Results in Increased Collagen Synthesis in Engineered Ligaments

    Science.gov (United States)

    Paxton, Jennifer Z.; Hagerty, Paul; Andrick, Jonathan J.

    2012-01-01

    Dynamic mechanical input is believed to play a critical role in the development of functional musculoskeletal tissues. To study this phenomenon, cyclic uniaxial mechanical stretch was applied to engineered ligaments using a custom-built bioreactor and the effects of different stretch frequency, amplitude, and duration were determined. Stretch acutely increased the phosphorylation of p38 (3.5±0.74-fold), S6K1 (3.9±0.19-fold), and ERK1/2 (2.45±0.32-fold). The phosphorylation of ERK1/2 was dependent on time, rather than on frequency or amplitude, within these constructs. ERK1/2 phosphorylation was similar following stretch at frequencies from 0.1 to 1 Hz and amplitudes from 2.5% to 15%, whereas phosphorylation reached maximal levels at 10 min of stretch and returned toward basal within 60 min of stretch. Following a single 10-min bout of cyclic stretch, the cells remained refractory to a second stretch for up to 6 h. Using the phosphorylation of ERK1/2 as a guide, the optimum stretch paradigm was hypothesized to be 10 min of stretch at 2.5% of resting length repeated every 6 h. Consistent with this hypothesis, 7 days of stretch using this optimized intermittent stretch program increased the collagen content of the grafts more than a continuous stretch program (CTL=3.1%±0.44%; CONT=4.8%±0.30%; and INT=5.9%±0.56%). These results suggest that short infrequent bouts of loading are optimal for improving engineered tendon and ligament physiology. PMID:21902469

  7. Angiotensin II modulates interleukin-1β-induced inflammatory gene expression in vascular smooth muscle cells via interfering with ERK-NF-κB crosstalk

    International Nuclear Information System (INIS)

    Xu, Shanqin; Zhi, Hui; Hou, Xiuyun; Jiang, Bingbing

    2011-01-01

    Highlights: → We examine how angiotensin II modulates ERK-NF-κB crosstalk and gene expression. → Angiotensin II suppresses IL-1β-induced prolonged ERK and NF-κB activation. → ERK-RSK1 signaling is required for IL-1β-induced prolonged NF-κB activation. → Angiotensin II modulates NF-κB responsive genes via regulating ERK-NF-κB crosstalk. → ERK-NF-κB crosstalk is a novel mechanism regulating inflammatory gene expression. -- Abstract: Angiotensin II is implicated in cardiovascular diseases, which is associated with a role in increasing vascular inflammation. The present study investigated how angiotensin II modulates vascular inflammatory signaling and expression of inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1. In cultured rat aortic vascular smooth muscle cells (VSMCs), angiotensin II suppressed interleukin-1β-induced prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and ribosomal S6 kinase (RSK)-1, and nuclear translocation of nuclear factor (NF)-κB, leading to decreased iNOS but enhanced VCAM-1 expression, associated with an up-regulation of mitogen-activated protein kinase phosphatase-1 expression. Knock-down of RSK1 selectively down regulated interleukin-1β-induced iNOS expression without influencing VCAM-1 expression. In vivo experiments showed that interleukin-1β, iNOS, and VCAM-1 expression were detectable in the aortic arches of both wild-type and apolipoprotein E-deficient (ApoE -/- ) mice. VCAM-1 and iNOS expression were higher in ApoE -/- than in wild type mouse aortic arches. Angiotensin II infusion (3.2 mg/kg/day, for 6 days, via subcutaneous osmotic pump) in ApoE -/- mice enhanced endothelial and adventitial VCAM-1 and iNOS expression, but reduced medial smooth muscle iNOS expression associated with reduced phosphorylation of ERK and RSK-1. These results indicate that angiotensin II can differentially modulate inflammatory gene expression in aortic smooth muscle cells

  8. Improving the profile of the European tourist destinations through the European tourism indicators system

    Directory of Open Access Journals (Sweden)

    Laura CISMARU

    2015-06-01

    Full Text Available Within the most recent European Policy for Tourism, the competitiveness of the European tourism industry is directly linked to the image of Europe and to its perception, as a collection of sustainable and high-quality tourist destinations. In such context, improving the profile of the European tourist destinations has become a main target. During the last years, the European Commission focused on the sustainable development of tourist destinations. Several projects were developed, the most recent one introducing a practical tool - the European Tourism Indicators System (ETIS for the sustainable development of destinations. The present paper advances the idea that such tool can be successfully used in order to achieve the goal of improving the profile of the European tourist destinations.

  9. Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways.

    Science.gov (United States)

    Li, Xuelian; Wang, GuoYuan; QiLi, MuGe; Liang, HaiHai; Li, TianShi; E, XiaoQiang; Feng, Ying; Zhang, Ying; Liu, Xiao; Qian, Ming; Xu, BoZhi; Shen, ZhiHang; Gitau, Samuel Chege; Zhao, DanDan; Shan, HongLi

    2018-01-01

    Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg-1·day-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways. © 2018 The Author(s). Published by S. Karger AG, Basel.

  10. Commission for Energy regulation (CRE) - Activity report June 2007

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets

  11. Commission for Energy regulation (CRE) - Activity report June 2007

    International Nuclear Information System (INIS)

    2007-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets, Natural gas

  12. Benchmarking Promotion and Deployment Activities Regarding Intelligent Vehicle Safety Systems in the European Union

    NARCIS (Netherlands)

    de Kievit, M.; Malone, K.M.; Zwijnenberg, H.; van Arem, B.

    2008-01-01

    This paper presents the results of a Benchmarking study performed in the European Union on Awareness and Promotion & Deployment activities related to Intelligent Vehicle Safety (IVS) systems (1). The study, commissioned by the European Commission under the Intelligent Car Initiative (a i2010

  13. Preparing Teachers for Diversity: The Role of Initial Teacher Education. Annex 2 To the Final Report to DG Education, Youth, Sport and Culture of the European Commission. Case Study Summaries

    Science.gov (United States)

    European Commission, 2017

    2017-01-01

    "Preparing Teachers for Diversity: The Role of Initial Teacher Education. Annex 2 To the Final Report to DG Education, Youth, Sport and Culture of the European Commission. Case Study Summaries" is designed as a companion document to the final report "Preparing Teachers for Diversity: The Role of Initial Teacher Education. Final…

  14. The expression of ER, PR in endometrial cancer and analysis of their correlation with ERK signaling pathway.

    Science.gov (United States)

    Luo, Lan; Xu, Lina; Tang, Liang

    2017-12-12

    Endometrial carcinoma (EC) is a common malignant tumor in gynecology. Its incidence and development are closely associated with the levels of estrogenic and progesterone hormone. Extracellular signal-regulated kinase (ERK) signaling pathway abnormity is associated with a variety of tumors. This study detected estrogen receptor (ER), progesterone receptor (PR), ERK1, and ERK2 expression in EC and analyzed their correlations. A total of 40 EC patients in our hospital were selected as test group, while another 40 healthy volunteers were enrolled as control group. ER, PR, ERK1, and ERK2 expression in EC tissue, para-carcinoma tissue, and normal endometrial tissue were detected by immunohistochemistry and Western blot. The positive rate of ER, PR, ERK1, and ERK2 in the test group was 50%, 40%, 60%, and 65%, respectively, which were significantly higher than those in the control (PPR, ERK1, and ERK2 protein expressions in EC cell were significantly higher than those in the control (PPR (PPR, which were correlated with higher levels of ERK1 and ERK2, suggesting they might be involved in the pathogenesis of EC.

  15. Energy regulation at EU level. The role of the European Commission and ACER in the context of REMIT; Energieregulierung auf Unionsebene. Die Rolle der Europaeischen Kommission und der ACER nach der REMIT-VO

    Energy Technology Data Exchange (ETDEWEB)

    Konar, Selma [Sozietaet Becker Buettner Held, Muenchen (Germany). Energie- und Infrastrukturrecht

    2015-03-15

    The regulatory act of promulgating REMIT, the Regulation on Wholesale Market Integrity and Transparency, has highlighted the commanding position of both the European Commission and ACER, the Agency for the Cooperation of Energy Regulators, in the regulation of energy affairs in the European Union. Furthermore it has led to major changes in how surveillance is organized at the national level. The first part of this publication is dedicated to the organization of market surveillance following the promulgation of REMIT. It depicts the tasks of the European Commission and ACER in this context. The Regulation has accorded the authorities a central role in managing the European Union's responsibilities with regard to energy wholesale trade. The act of delegating such far-reaching competence to the authorities deserves careful review however. The article shows how, given ACER's lack of practical experience in market surveillance, as well as its lack of human resources, the task of surveilling the European energy wholesale market confronts the agency with a significant challenge. How successfully the EU energy agency will master this challenge will depend on a number of different factors. Stringent requirements will be needed for the data registration offices in order to ensure optimal data processing. National authorities and supervisory bodies should be made to participate in the data monitoring process. ACER's efficiency in surveilling the market will furthermore depend decisively on its IT infrastructure.

  16. Environmental NGOs : Channels of democracy for the European Union

    DEFF Research Database (Denmark)

    Guasco, Clement Nicolas

    The notion of democratic deficit has been at the centre of many debates on the European Union for the last 30 years. The reason is, to a certain degree, linked to the lack of legitimacy of the European Commission, which is not elected and remote from the European citizens. However, the Commission...... seems to have found a positive way to increase its legitimacy by the inclusion of civil-society in the decision-making process. The interaction between the Commission and two Environmental NGOs will therefore be analysed in order to make a constructive contribution to the debate. The present paper does...... not limit itself to normative statements on reality and considers that there is more to socio political relations than “true” verifiable facts. Therefore, it is not limited to the formal decision-making process, and goes deeper into the socialisation process at play between the different actors. The outcome...

  17. Nuclear energy: the European way

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The dossier published in this issue deals with the present and future situation of nuclear energy in Europe. What could be the trends of the nuclear development in the Europe of tomorrows. That global question is answered by pointing out the different data related to the present state of european nuclear programmes. Such an overview is followed by a serie of articles dealing with definite items: the actions implemented by the European Communities Commission: the electricity market and EDF policy in the field of european electric grids; the trends of nuclear cycle industry and the perfecting of the future european nuclear reactor

  18. Network of Research Infrastructures for European Seismology (NERIES)—Web Portal Developments for Interactive Access to Earthquake Data on a European Scale

    OpenAIRE

    A. Spinuso; L. Trani; S. Rives; P. Thomy; F. Euchner; Danijel Schorlemmer; Joachim Saul; Andres Heinloo; R. Bossu; T. van Eck

    2009-01-01

    The Network of Research Infrastructures for European Seismology (NERIES) is European Commission (EC) project whose focus is networking together seismological observatories and research institutes into one integrated European infrastructure that provides access to data and data products for research. Seismological institutes and organizations in European and Mediterranean countries maintain large, geographically distributed data archives, therefore this scenario suggested a design approach bas...

  19. Nuclear Regulatory Commission issuances. Volume 22, No. 6

    International Nuclear Information System (INIS)

    1985-12-01

    This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Appeal Boards (ALAB), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judge (ALJ), the Directors' Decisions (DD), and the Denials of Petitions for Rulemaking (DPRM)

  20. Nuclear Regulatory Commission issuances. Volume 21, No. 6

    International Nuclear Information System (INIS)

    1985-06-01

    This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Appeal Boards (ALAB), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judge (ALJ), the Directors' Decisions (DD), and the Denials of Petitions for Rulemaking (DPRM)

  1. Conceptual basis for the european sustainability footprint

    OpenAIRE

    PELLETIER NATHANIEL; MAAS Rob; GORALCZYK MALGORZATA; WOLF Marc-Andree

    2012-01-01

    Sustainability is central to the policy objectives of the European Commission (EC), but a widely accepted integrated sustainability assessment framework in support of policy analysis and development is currently lacking. Here, we describe the conceptual basis for the proposed European Sustainability Footprint (ESF) - an integrated sustainability assessment framework for establishing a baseline and tracking trends with respect to the sustainability of European production and consumption. This ...

  2. European Union, 2017

    OpenAIRE

    Malone Margaret Mary

    2018-01-01

    The year 2017 was eventful for the EU and its member states. Given the widespread Euroscepticism and populism which appeared to be on the rise last year, election results in the Netherlands, France and Germany were greeted with relief and hope for the future. The EU was in an optimistic mood. European Commission President Jean- Claude Juncker used his State of the European Union speech in September to note that the EU had the ‘wind in its sails’ (Juncker, 2017). At the same time, he cautioned...

  3. Codes and standards an European point of view

    International Nuclear Information System (INIS)

    Roche, R.L.; Corsi, F.

    1987-01-01

    The first part of this paper is related to the European situation in which Construction Codes for FBR components are developed. Attention is given to the different agreements between European Countries. After a description of the present state of Codes development, indications are given on the future work in this field. Several appendix are devoted to the state of Codes in different European Countries and to the action of European Commission

  4. European Non Destructive Examination Forum (ENDEF)

    International Nuclear Information System (INIS)

    Deffrennes, M.; Engl, G.; Estorff, U. von

    1998-01-01

    Non destructive examination (NDE) during fabrication, Pre-service inspection (PSI) and In service inspection (ISI) are considered key issues for the safe use of nuclear energy. They are important elements of plant lifetime management which is a critical item in decision making on nuclear policies. The European non destructive examination forum (ENDEF) founded by European Commission provides a platform for open discussion between representatives of the European industries with the purpose to establish cooperation between EU, Central and Eastern European Countries and New Independent States in the field of NDE and ISI

  5. Controlling Delegated Powers in the Post-Lisbon European Union

    DEFF Research Database (Denmark)

    Brandsma, Gijs Jan; Blom-Hansen, Jens

    2016-01-01

    Most European Union rules are made by the Commission, not the Council of Ministers or the European Parliament. But although the Commission is an important rule-maker, it is not autonomous. The member states have always taken care to install committees to control the Commission (comitology). However......, the Lisbon Treaty introduced alternative control mechanisms (delegated acts) and a reform of the comitology system (implementing acts). This article investigates how the post-Lisbon control system works in daily legislative practice. It represents the first investigation of the institutional preferences...... of the Council, the Parliament and the Commission in the new system. Further, it utilizes better data than previous studies. The analysis is based on data on the control preferences of all actors before the first trilogue meeting for a large number of cases in the period 2010–13. The results indicate...

  6. Training Issues for the European Automotive Industry

    NARCIS (Netherlands)

    Dankbaar, B.

    1996-01-01

    Provides an overview of the results of an investigation carried out for the European Commission. Aims to identify themes and issues in the field of continuing training in the European automotive industry. A large number of interviews were carried out in all the major car manufacturing countries of

  7. Training issues for the European automotive industry

    NARCIS (Netherlands)

    Dankbaar, B.

    1999-01-01

    Provides an overview of the results of an investigation carried out for the European Commission. Aims to identify themes and issues in the field of continuing training in the European automotive industry. A large number of interviews were carried out in all the major car manufacturing countries of

  8. Erk signaling suppresses embryonic stem cell self-renewal to specify endoderm

    DEFF Research Database (Denmark)

    Hamilton, William B; Brickman, Joshua M

    2014-01-01

    Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To dissect the role of Erk in both ESC self-renewal and lineage specification, we explored...

  9. MAPK/ERK and Wnt/β-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

    International Nuclear Information System (INIS)

    Jin, Caixia; Samuelson, Lisa; Cui, Cai-Bin; Sun, Yangzhong; Gerber, David A.

    2011-01-01

    Highlights: → Activation of MAPK/ERK pathway with epidermal growth factor (EGF) significantly increased Sca-1 + HPC proliferation and colony formation. → Activation of either IL-6/STAT3 or Wnt/β-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. → Wnt/β-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation and maintain long-term HPCs in vitro. -- Abstract: Hepatic progenitor cells (HPCs) persist in adulthood and have the potential to play a major role in regenerating diseased liver. However, the signaling pathways that both directly and indirectly regulate HPCs' self-renewal and differentiation remain elusive. Previously, we identified a bipotent, stem cell antigen-1 (Sca-1) positive HPC population from naive adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1 + HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1 + HPC proliferation and colony formation while stimulating phosphorylation of ERK1/2 and activating the induction of Cyclin D1. There were no demonstrable effects of EGF on Akt. The MEK inhibitor, PD0325901, inhibits proliferation and ERK1/2 phosphorylation while also suppressing the expression of Cyclin D1. In addition, activation of either IL-6/STAT3 or Wnt/β-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/β-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation ratio and maintain long-term HPC in vitro. The data indicates that the MAPK/ERK pathway is both essential and critical for HPC proliferation, and the Wnt signaling pathway is not sufficient, while it works synergistically with the MAPK/ERK signaling pathway to promote HPC proliferation.

  10. MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Caixia [Department of Surgery, University of North Carolina at Chapel Hill (United States); Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan 750004 (China); Samuelson, Lisa; Cui, Cai-Bin; Sun, Yangzhong [Department of Surgery, University of North Carolina at Chapel Hill (United States); Gerber, David A., E-mail: david_gerber@med.unc.edu [Department of Surgery, University of North Carolina at Chapel Hill (United States); Lineberger Cancer Center, University of North Carolina at Chapel Hill (United States)

    2011-06-17

    Highlights: {yields} Activation of MAPK/ERK pathway with epidermal growth factor (EGF) significantly increased Sca-1{sup +} HPC proliferation and colony formation. {yields} Activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. {yields} Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation and maintain long-term HPCs in vitro. -- Abstract: Hepatic progenitor cells (HPCs) persist in adulthood and have the potential to play a major role in regenerating diseased liver. However, the signaling pathways that both directly and indirectly regulate HPCs' self-renewal and differentiation remain elusive. Previously, we identified a bipotent, stem cell antigen-1 (Sca-1) positive HPC population from naive adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1{sup +} HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1{sup +} HPC proliferation and colony formation while stimulating phosphorylation of ERK1/2 and activating the induction of Cyclin D1. There were no demonstrable effects of EGF on Akt. The MEK inhibitor, PD0325901, inhibits proliferation and ERK1/2 phosphorylation while also suppressing the expression of Cyclin D1. In addition, activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation ratio and maintain long-term HPC in vitro. The data indicates that the MAPK/ERK pathway is both essential and critical for HPC proliferation, and the Wnt signaling pathway is not sufficient, while it works synergistically with the MAPK/ERK signaling pathway to promote HPC proliferation.

  11. European visit

    CERN Multimedia

    2006-01-01

    The European Commissioner for Science and Research, Janez Potočnik, (on the right) visited the CMS assembly hall accompanied by Jim Virdee, Deputy Spokesman of CMS (on the left), and Robert Aymar, Director-General of CERN. The European Commissioner for Science and Research, Janez Potočnik, visited CERN on Tuesday 31 January. He was welcomed by the Director-General, Robert Aymar, who described the missions and current activities of CERN to him, in particular the realisation of the LHC with its three components: accelerator, detectors, storage and processing of data. The European Commissioner then visited the CMS assembly hall, then the hall for testing the LHC magnets and the ATLAS cavern. During this first visit since his appointment at the end of 2004, Janez Potočnik appeared very interested by the operation of CERN, an example of successful scientific co-operation on a European scale. The many projects (30 on average) that CERN and the European Commission carry out jointly for the benefit of res...

  12. Variations in Tropospheric Submicron Particle Size Distributions Across the European Continent 2008–2009

    Czech Academy of Sciences Publication Activity Database

    Beddows, D.C.S.; Dall’Osto, M.; Harrison, R. M.; Kulmala, M.; Asmi, A.; Wiedensohler, A.; Laj, P.; Fjaeraa, A.M.; Sellegri, K.; Birmili, W.; Bukowiecki, N.; Weingartner, E.; Baltensperger, U.; Ždímal, Vladimír; Zíková, Naděžda; Putaud, J.-P.; Marinoni, A.; Tunved, P.; Hansson, H.-C.; Feibig, M.; Kivekäs, N.; Swietlicki, E.; Lihavainen, H.; Asmi, E.; Ulevicius, V.; Aalto, P.P.; Mihalopoulos, N.; Kalivitis, N.; Kalapov, I.; Kiss, G.; de Leeuw, G.; Henzing, B.; O'Dowd, C.; Jennings, S.G.; Flentje, H.; Meinhardt, F.; Ries, L.; Denier van der Gon19, H.A.C.; Visschedijk, A.J.H.; Swietlicki, E.

    2014-01-01

    Roč. 14, č. 8 (2014), s. 4327-4348 ISSN 1680-7316 EU Projects: European Commission(XE) 36833 - EUCAARI; European Commission(XE) 26140 - EUSAAR Institutional support: RVO:67985858 Keywords : particle size distribution * clusters * aerosol size distribution Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.053, year: 2014

  13. Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells.

    Science.gov (United States)

    Ku, H; Meier, K E

    2000-04-14

    Intracellular signals can regulate cell adhesion via several mechanisms in a process referred to as "inside-out" signaling. In phorbol ester-sensitive EL4 thymoma cells, phorbol-12-myristate 13-acetate (PMA) induces activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases and promotes cell adhesion. In this study, clonal EL4 cell lines with varying abilities to activate ERKs in response to PMA were used to examine signaling events occurring downstream of ERK activation. Paxillin, a multifunctional docking protein involved in cell adhesion, was phosphorylated on serine/threonine residues in response to PMA treatment. This response was correlated with the extent and time course of ERK activation. PMA-induced phosphorylation of paxillin was inhibited by compounds that block the ERK activation pathway in EL4 cells, primary murine thymocytes, and primary murine splenocytes. Paxillin was phosphorylated in vitro by purified active ERK2. Two-dimensional electrophoresis revealed that PMA treatment generated a complex pattern of phosphorylated paxillin species in intact cells, some of which were generated by ERK-mediated phosphorylation in vitro. An ERK pathway inhibitor interfered with PMA-induced adhesion of sensitive EL4 cells to substrate. These findings describe a novel inside-out signaling pathway by which the ERK cascade may regulate events involved in adhesion.

  14. 17 October 2013 - C. Ashton High Representative of the European Union for Foreign Affairs and Security Policy, Vice-President of the European Commission visiting the ATLAS cavern with ATLAS Collaboration Spokesperson D. Charlton; visiting the LHC tunnel at Point 1 with Technology Department Head F. Bordry and signing the Guest book with CERN Director-General R. Heuer.

    CERN Multimedia

    Maximilien Brice

    2013-01-01

    17 October 2013 - C. Ashton High Representative of the European Union for Foreign Affairs and Security Policy, Vice-President of the European Commission visiting the ATLAS cavern with ATLAS Collaboration Spokesperson D. Charlton; visiting the LHC tunnel at Point 1 with Technology Department Head F. Bordry and signing the Guest book with CERN Director-General R. Heuer.

  15. An Optional Instrument for European Insurance Contract Law

    OpenAIRE

    Mandeep Lakhan; Helmut Heiss

    2010-01-01

    The Principles of European Insurance Contract Law, also referred tousing the acronym PEICL, were published in September 2009. They are the result of ten years of academic work undertaken by the"Restatement of European Insurance Contract Law" Project Group. In the time since its establishment in 1999, the project has been transformed from being a stand-alone project to a part of the CoPECL (Common Principles of European Insurance Contract Law) network, drafting a specific part of the Common Fr...

  16. The European Synchrotron Radiation Facility - an overview of planned diffraction capability

    International Nuclear Information System (INIS)

    Kvick, A.

    1991-01-01

    The European Synchrotron Radiation Facility (ESRF) is a third generation synchrotron radiation facility presently being built as a joint venture between 12 European countries in Grenoble, France. The ESRF will be a low emittance 6 GeV storage ring aimed at producing high-brilliance synchrotron radiation from 29 insertion devices and from 27 bending magnet ports. The general user program will start in the middle of 1994 with seven ESRF beam-lines. By 1999, 30 facility beam-lines as well as beam-lines built and financed by Collaborating Research Groups are scheduled to be in operation. The guidelines for the first beam-lines to be constructed as well as a survey of the diffraction oriented beam-lines built by the ESRF are given in the article. (author)

  17. 1999 scientific evaluation at the CEA

    International Nuclear Information System (INIS)

    1999-01-01

    This report presents a statement of the scientific and technical activity of the French atomic energy commission (CEA) for the year 1999. This evaluation is made by external and independent experts and requires some specific dispositions for the nuclear protection and safety institute (IPSN) and for the direction of military applications (DAM). The report is divided into 4 parts dealing successively with: 1)the CEA, a public research organization (strategy, research programs, new organization of the CEA activities, civil nuclear research, technology research and transfer, defence activities, transfer of knowledge) 2)the scientific evaluation at the CEA (evaluations of the civil applications of the CEA, IPSN, DAM, INSTN (national institute for nuclear sciences and techniques) 3)synthesis of the 1999 scientific and technical evaluation for each operational directions of the CEA (directions of fuel cycle, of nuclear reactors, of advanced technologies, of materials sciences, of life sciences, of military applications, of the nuclear protection and safety institute and of the national institute for nuclear sciences and techniques) 4)the corresponding members of the evaluation and the list of scientific and technical councils and members

  18. European virtual campus for biomedical engineering EVICAB.

    Science.gov (United States)

    Malmivuo, Jaakko A; Nousiainen, Juha O; Lindroos, Kari V

    2007-01-01

    European Commission has funded building a curriculum on Biomedical Engineering to the Internet for European universities under the project EVICAB. EVICAB forms a curriculum which will be free access and available free of charge. Therefore, in addition to the European universities, it will be available worldwide. EVICAB will make high quality education available for everyone, not only for the university students, and facilitate the development of the discipline of Biomedical Engineering.

  19. Safety effects of road design standards : a study commissioned by the European Commission DG VII of the situation in the European Union.

    NARCIS (Netherlands)

    Ruyters, H.G.J.C.M. Slop, M. & Wegman, F.C.M. (eds.)

    1994-01-01

    This report describes the results of a study carried out for the European Union. The report uses the safety principle that: (i) proper road design is crucial to prevent human errors in traffic; and (ii) less human errors will result in less accidents. The study contains the following parts: (1)

  20. Electronic signatures and their specificity in national and European regulations

    Directory of Open Access Journals (Sweden)

    R. MATEFI

    2017-07-01

    Full Text Available The paper aims to emphasize the particularities of the electronic signature by reference to the national as well as to the European legislation, trying to point out its utility in the business environment as well as the controversies in this matter. The starting point of this analysis was the Directive 1999/93/EC of the European Parliament and of the Council of 13 December 1999 on a Community framework for electronic signatures, which establishes the legal framework for electronic signatures and the recognition of certification-service providers. Its main aim was to ease its use and help it become legally recognized within all EU countries.

  1. ERK activation is required for hydrostatic pressure induced-tensile changes in engineered articular cartilage

    Science.gov (United States)

    DuRaine, G D; Athanasiou, K A

    2015-01-01

    The objective of this study was to identify the ERK 1/2 involvement in the changes in compressive and tensile mechanical properties associated with hydrostatic pressure treatment of self-assembled cartilage constructs. In study 1, ERK 1/2 phosphorylation was detected by immunoblot following application of hydrostatic pressure (1 hour of static 10MPa) applied at day 10-14 of self-assembly culture. In study 2, ERK 1/2 activation was blocked during hydrostatic pressure application on days 10-14. With pharmacological inhibition of the ERK pathway by the MEK1/ERK inhibitor U0126 during hydrostatic pressure application on days 10-14, the increase in Young’s modulus induced by hydrostatic pressure was blocked. Furthermore, this reduction in Young’s modulus with U0126 treatment during hydrostatic pressure application corresponded with a decrease in total collagen expression. However, U0126 did not inhibit the increase in aggregate modulus or GAG induced by hydrostatic pressure. These findings demonstrate a link between hydrostatic pressure application, ERK signaling, and changes in biomechanical properties of a tissue engineered construct. PMID:23255524

  2. ERK activation is required for hydrostatic pressure-induced tensile changes in engineered articular cartilage.

    Science.gov (United States)

    DuRaine, G D; Athanasiou, K A

    2015-04-01

    The objective of this study was to identify ERK 1/2 involvement in the changes in compressive and tensile mechanical properties associated with hydrostatic pressure treatment of self-assembled cartilage constructs. In study 1, ERK 1/2 phosphorylation was detected by immunoblot, following application of hydrostatic pressure (1 h of static 10 MPa) applied at days 10-14 of self-assembly culture. In study 2, ERK 1/2 activation was blocked during hydrostatic pressure application on days 10-14. With pharmacological inhibition of the ERK pathway by the MEK1/ERK inhibitor U0126 during hydrostatic pressure application on days 10-14, the increase in Young's modulus induced by hydrostatic pressure was blocked. Furthermore, this reduction in Young's modulus with U0126 treatment during hydrostatic pressure application corresponded to a decrease in total collagen expression. However, U0126 did not inhibit the increase in aggregate modulus or GAG induced by hydrostatic pressure. These findings demonstrate a link between hydrostatic pressure application, ERK signalling and changes in the biomechanical properties of a tissue-engineered construct. Copyright © 2012 John Wiley & Sons, Ltd.

  3. The 6th European metallurgical conference EMC 2011: Proceedings review

    Directory of Open Access Journals (Sweden)

    Srećko R. Stopić

    2011-10-01

    Full Text Available The GDMB Society for Mining, Metallurgy, Resource and Environmental Technology organized the 6th European Metallurgical Conference (2011 in Duesseldorf from June 26 to 29, 2011. The same venue hosted the most important international metallurgical trade fairs for metallurgy of iron and steel, new casting and thermochemical processes METEC, GIFA, THERMOPROCESS and NEWCAST. The previous European metallurgical conferences were organized by GDMB in Friedrichshafen (2001, Hanover (2003, Leipzig (2005, Duesseldorf (2007, Innsbruck (2009. The GDMB is a non-profit organization situated in Clausthal in Germany, which is related to combining science with the practical experience in metallurgy, mining, materials engineering, mineral processing, recycling and refining of metals, and manufacturing of semi- and finishing products. The European Metallurgical conference EMC is one of the most known conferences worldwide in the field of non-ferrous metallurgy and is attended regularly by the decision makers from the industry and universities. The scientific program contained 6 plenary lectures and more than 160 presentations from 40 countries in 5 parallel series. An extensive poster exhibition was held, during which the authors had an opportunity to introduce their posters to the entire plenum as a part of a brief presentation. The best poster from the Montan-University in Leoben, Austria, was awarded the € 500 'Poster Award EMC 2011'. Not only were the most important European countries represented here, more than one third of the lecturers were from the non-European countries (Canada, Japan, China, USA, South Africa, Australia. The origin of the participants reflects the aim of the organizers: to make this conference a worldwide platform for the scientific exchange of experience and information. More than 400 participants from all over the world participated at this conference. The scientific presentations of the conference are presented in five Proceedings

  4. Recovery of acidified European surface waters

    Czech Academy of Sciences Publication Activity Database

    Wright, R. F.; Larssen, T.; Camarero, L.; Cosby, B. J.; Ferrier, R. C.; Helliwell, R.; Forsius, M.; Jenkins, A.; Kopáček, Jiří; Majer, V.; Moldan, F.; Posch, M.; Rogora, M.; Schöpp, W.

    2005-01-01

    Roč. 39, č. 3 (2005), 64A-72A ISSN 0013-936X. [ Acid Rain 2005. International Conference on Acid Deposition /7./. Prague, 12.06.2005-17.06.2005] Grant - others:EC(XE) EMERGE EVK1-CT-1999-00032; EC(XE) RECOVER:2010 EVK1-CT-1999-00018; DEFRA(GB) EPG 1/3/194; ICST(ES) REN2000-0889/GLO Institutional research plan: CEZ:AV0Z60170517 Keywords : acid ification * recovery * European lake districts Subject RIV: DJ - Water Pollution ; Quality Impact factor: 4.054, year: 2005

  5. An emergent proposal on the Committee of Uranium Processing Factory Criticality Accident Survey of the Nuclear Safety Commission. A meantime report dated on November 5, 1999

    International Nuclear Information System (INIS)

    2000-01-01

    The Nuclear Safety Commission was received a decision on thorough investigations of accident reason on criticality accident at the Tokai-mura uranium processing factory of the JCO Incorporation occurred on September 30, 1999, to establish the Committee of Uranium Processing Factory Criticality Accident Survey to elucidate its reason thoroughly and contribute to set up a sufficient reforming prevention countermeasure. This Committee judged that it was important to propose a countermeasure directly obtainable by grasping some fact relations clarified before now as soon as possible and intended to conduct this meantime report of 'emergent proposal' by arrangement of such fact relations. Here were described on accidental conditions and their effects, response to the accident (on prevention of the accident), its reasons and their relating conditions, and some emergent proposals. In the last items, safety security at accidental site, health countermeasures to residents and others, establishment of safety security for nuclear business workers and others, and reconstruction on safety regulation in national government. (G.K.)

  6. The STOA experiment in the European Parliament

    International Nuclear Information System (INIS)

    Lake, G.

    1989-01-01

    The European Parliament, like the US Congress before it, has recognized a need for independent advice on scientific and technological policy issues, being hitherto over-dependent on Commission expertise in its examination of Commission proposals. Accordingly, it established the STOA Project (Scientific and Technological Options Assessment) in March 1987. The first major STOA study, Criteria for the Assessment of European Fusion Research, is described and analysed. A contrast is drawn between consensual and adversarial approaches to technology assessment and the importance of open, critical debate is stressed. In conclusion, it is the social character of technology which underlies the importance of parliamentary technology assessment. (author)

  7. Principles of European Contract Law

    DEFF Research Database (Denmark)

    Lando, Ole; Beale, Hugh

    This text provides a comprehensive guide to the principles of European contract law. They have been drawn up by an independent body of experts from each Member State of the EU, under a project supported by the European Commission and many other organizations. The principles are stated in the form...... of articles, with a detailed commentary explaining the purpose and operation of each article and its relation to the remainder. Each article also has extensive comparative notes surveying the national laws and other international provisions on the topic. "The Principles of European Contract Law Parts I &...... in developing a common European legal culture. The European Parliament has twice called for the creation of a European Civil Code. The principles of European contract law are essential steps in these projects. This text provides a comprehensive guide to the Principles of European contract law. They have been...

  8. Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway

    International Nuclear Information System (INIS)

    Lee, Cheol-Jung; Lee, Mee-Hyun; Yoo, Sun-Mi; Choi, Kyung-Il; Song, Ji-Hong; Jang, Jeong-Hoon; Oh, Sei-Ryang; Ryu, Hyung-Won; Lee, Hye-Suk; Surh, Young-Joon; Cho, Yong-Yeon

    2015-01-01

    Magnolin is a natural compound abundantly found in Magnolia flos, which has been traditionally used in oriental medicine to treat headaches, nasal congestion and anti-inflammatory reactions. Our recent results have demonstrated that magnolin targets the active pockets of ERK1 and ERK2, which are important signaling molecules in cancer cell metastasis. The aim of this study is to evaluate the effects of magnolin on cell migration and to further explore the molecular mechanisms involved. Magnolin-mediated signaling inhibition was confirmed by Western blotting using RSK2 +/+ and RSK2 −/− MEFs, A549 and NCI-H1975 lung cancer cells, and by NF-κB and Cox-2 promoter luciferase reporter assays. Inhibition of cell migration by magnolin was examined by wound healing and/or Boyden Chamber assays using JB6 Cl41 and A549 human lung cancer cells. The molecular mechanisms involved in cell migration and epithelial-to-mesenchymal transition were determined by zymography, Western blotting, real-time PCR and immunocytofluorescence. Magnolin inhibited NF-κB transactivation activity by suppressing the ERKs/RSK2 signaling pathway. Moreover, magnolin abrogated the increase in EGF-induced COX-2 protein levels and wound healing. In human lung cancer cells such as A549 and NCI-H1975, which harbor constitutive active Ras and EGFR mutants, respectively, magnolin suppressed wound healing and cell invasion as seen by a Boyden chamber assay. In addition, it was observed that magnolin inhibited MMP-2 and −9 gene expression and activity. The knockdown or knockout of RSK2 in A549 lung cancer cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling suppressed epithelial-to-mesenchymal transition by modulating EMT marker proteins such as N-cadherin, E-cadherin, Snail, Vimentin and MMPs. These results demonstrate that magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway. The online version of this article (doi:10.1186/s12885-015-1580-7) contains

  9. The European fusion technology programme

    International Nuclear Information System (INIS)

    Goedkoop, J.A.

    1984-01-01

    With the 1982-86 pluriannual programme, reactor technology became a separate chapter in the fusion research programme of the European Commission. It comprises work on materials, the breeder blanket, tritium management, magnet coils, maintenance and the safety and environmental aspects. After an overview of the programme each of these areas is discussed briefly and some remarks are made on the role played by the European fission energy and magnet laboratories. (author)

  10. Penanaman Modal Asing Dan Pertumbuhan Industri Di Asean(6), China, India, Dan Korea Selatan 1999-20041

    OpenAIRE

    Kusumastuti, Sri Yani

    2008-01-01

    The objective of this study is to shed light on the determinants of foreign direct investment (FDI) in Asian developing countries and their impact on industrial growth. In order to undertake it, we perform an econometric model based in panel data analysis for 9 countries (such as ASEAN 6, China, India, and Korea) for the 1999-2004 periods. Weestimate the simultaneous equation using panel data estimation with fixed effect and random effect. Among the major conclusions we have that the FDI is d...

  11. An expert consortium review of the EC-commissioned report "alternative (Non-Animal) methods for cosmetics testing: current status and future prospects - 2010"

    DEFF Research Database (Denmark)

    Hartung, Thomas; Blaauboer, Bas J; Bosgra, Sieto

    2011-01-01

    The European cosmetics legislation foresees a review in 2011 and possible postponement of the 2013 marketing ban to enforce the testing ban for systemic and repeated-dose animal tests. For this purpose, a 119-page report commissioned by the European Commission was published recently. Here, a group...... industry sectors....

  12. Commission of energy regulation. 2004 activity report; Commission de regulation de l'energie. Rapport d'activite 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  13. Electromagnetic Field Evaluation: Assessment of exclusion areas

    International Nuclear Information System (INIS)

    Duque, J.P.V.

    2009-01-01

    This work presents simulations done using the AWAS tool for the definition of areas that exceed reference levels, within the context of the implementation of Recommendation 1999/519/CE of the European Commission

  14. European Union and oil

    International Nuclear Information System (INIS)

    Paillard, Christophe Alexandre

    2004-01-01

    In a context of oil price increase, problems about a Russian oil company (Loukos), and uncertainties in the Middle-East, the possibility of a new oil shock is a threat for Europe, and raises the issue of a true European energy policy which would encompass, not only grid development, environmental issues or market regulation issues, but also strategic issues related to energy supply security. This article proposes an overview of the European policy: first steps for a future European energy and oil policy in the green paper of the European Commission published in November 2000, issues of pollution and safety for hydrocarbon maritime transport. The article then examines the possibility of a third oil shock due to a crisis in the Middle East, and discusses whether European must have strategic stocks to face an outage of oil supplies

  15. Corporate Political Strategies related to Decisions of European Competition Commission on Regulatory Issues in the European Telecommunications Industry

    NARCIS (Netherlands)

    Kranenburg, H.L. van; Ross, T.

    2014-01-01

    The European regulatory institution has the tasks to protect fair competition and equal opportunities for all companies in the European telecommunications industry and to protect the welfare of the consumers. This regulator is responsible for the adherence of telecommunications companies to

  16. Oleic Acid Induces Lung Injury in Mice through Activation of the ERK Pathway

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves-de-Albuquerque

    2012-01-01

    Full Text Available Oleic acid (OA can induce acute lung injury in experimental models. In the present work, we used intratracheal OA injection to show augmented oedema formation, cell migration and activation, lipid mediator, and cytokine productions in the bronchoalveolar fluids of Swiss Webster mice. We also demonstrated that OA-induced pulmonary injury is dependent on ERK1/2 activation, since U0126, an inhibitor of ERK1/2 phosphorylation, blocked neutrophil migration, oedema, and lipid body formation as well as IL-6, but not IL-1β production. Using a mice strain carrying a null mutation for the TLR4 receptor, we proved that increased inflammatory parameters after OA challenges were not due to the activation of the TLR4 receptor. With OA being a Na/K-ATPase inhibitor, we suggest the possible involvement of this enzyme as an OA target triggering lung inflammation.

  17. The European Energy Regulators Group. A panacea for good governance?

    International Nuclear Information System (INIS)

    Lavrijssen, S.A.C.M.

    2004-01-01

    This article analyses how the European Energy Regulators Group (ERGEG) may promote good governance in the EU. It is concluded that the ERGEG to some extent can stimulate national regulatory authorities into implementing European law more consistently, effectively and proportionally. Since the European Commission has a special responsibility as regards the functioning of the ERGEG, the future role of the ERGEG will depend on whether or not the Commission will leave it some autonomy to develop its advisory-, benchmarking- and coordinating role. Since the European legal framework does not include clear procedural good governance norms, there is a danger that the interests of the market parties are inadequately represented and protected at the European level. Although the ERGEG cannot take legally binding decisions, it is argued that its decisions or common standards may have legal effects. Therefore, it is of the utmost importance that the European legal framework regulates the right of access to ERGEG documents, the exchange and use of information within the ERGEG, the protection of confidential information, the right of participation and the involvement of the European Parliament [nl

  18. ERK2 suppresses self-renewal capacity of embryonic stem cells, but is not required for multi-lineage commitment.

    Directory of Open Access Journals (Sweden)

    William B Hamilton

    Full Text Available Activation of the FGF-ERK pathway is necessary for naïve mouse embryonic stem (ES cells to exit self-renewal and commit to early differentiated lineages. Here we show that genetic ablation of Erk2, the predominant ERK isozyme expressed in ES cells, results in hyper-phosphorylation of ERK1, but an overall decrease in total ERK activity as judged by substrate phosphorylation and immediate-early gene (IEG induction. Normal induction of this subset of canonical ERK targets, as well as p90RSK phosphorylation, was rescued by transgenic expression of either ERK1 or ERK2 indicating a degree of functional redundancy. In contrast to previously published work, Erk2-null ES cells exhibited no detectable defect in lineage specification to any of the three germ layers when induced to differentiate in either embryoid bodies or in defined neural induction conditions. However, under self-renewing conditions Erk2-null ES cells express increased levels of the pluripotency-associated transcripts, Nanog and Tbx3, a decrease in Nanog-GFP heterogeneity, and exhibit enhanced self-renewal in colony forming assays. Transgenic add-back of ERK2 is capable of restoring normal pluripotent gene expression and self-renewal capacity. We show that ERK2 contributes to the destabilization of ES cell self-renewal by reducing expression of pluripotency genes, such as Nanog, but is not specifically required for the early stages of germ layer specification.

  19. Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway

    Directory of Open Access Journals (Sweden)

    Edvinsson Lars

    2008-09-01

    Full Text Available Abstract Background MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2. Cerebral ischemia results in enhanced expression of cerebrovascular contractile receptors in the middle cerebral artery (MCA leading to the ischemic region. Here we explored the role of the MEK/ERK pathway in receptor expression following ischemic brain injury using the specific MEK1 inhibitor U0126. Methods and result Rats were subjected to a 2-h middle cerebral artery occlusion (MCAO followed by reperfusion for 48-h and the ischemic area was calculated. The expression of phosphorylated ERK1/2 and Elk-1, and of endothelin ETA and ETB, angiotensin AT1, and 5-hydroxytryptamine 5-HT1B receptors were analyzed with immunohistochemistry using confocal microscopy in cerebral arteries, microvessels and in brain tissue. The expression of endothelin ETB receptor was analyzed by quantitative Western blot. We demonstrate that there is an increase in the number of contractile smooth muscle receptors in the MCA and in micro- vessels within the ischemic region. The enhanced expression occurs in the smooth muscle cells as verified by co-localization studies. This receptor upregulation is furthermore associated with enhanced expression of pERK1/2 and of transcription factor pElk-1 in the vascular smooth muscle cells. Blockade of transcription with the MEK1 inhibitor U0126, given at the onset of reperfusion or as late as 6 hours after the insult, reduced transcription (pERK1/2 and pElk-1, the enhanced vascular receptor expression, and attenuated the cerebral infarct and improved neurology score. Conclusion Our results show that MCAO results in upregulation of cerebrovascular ETB, AT1 and 5-HT1B receptors. Blockade of this event with a MEK1 inhibitor as late as 6 h after the insult reduced the enhanced vascular receptor expression and the associated cerebral infarction.

  20. Alcohol and drugs in seriously injured drivers in 6 European countries

    DEFF Research Database (Denmark)

    Legrand, Sara-Ann; Isalberti, Cristina; Linden, Trudy Van der

    2012-01-01

    Objective: To determine the presence of alcohol and drugs in drivers severely injured in traffic crashes in 6 European countries. Methods: Data were collected from 2492 seriously injured drivers of cars and vans in Belgium, Denmark, Finland, Italy, Lithuania and The Netherlands, between 2007...

  1. Annual Report 1999

    International Nuclear Information System (INIS)

    2001-01-01

    applicant countries is developed. SKI has also participated in the European Commission's evaluation of forms of co-operation within the EU within reactor safety and has actively worked for more effective co-operation. In April 1999, the first review meeting was held under the international nuclear safety convention, under the chairmanship of SKI's Director General. The evaluation was a major success. All of the countries expressed their commitment to the continued improvement of safety, in accordance with the purpose of the convention. Actual measures implemented will be followed up at the next review meeting in three years' time and this will be a means of putting international pressure on further safety work. This pressure is also reflected in the resolutions following the review meeting which were adopted by the General Congresses of the IAEA and the UN. SKI has actively participated in work to tighten requirements on export control within EU and in work to improve the international rules for physical protection. SKI has also participated in the international discussions that have been initiated concerning a possible review of the convention on physical protection. SKI chairs central task groups working within the nuclear waste area in the EU and OECD/NEA. During the year, Sweden ratified the international nuclear waste convention, which SKI was instrumental in bringing about. SKI's extensive and important work on reinforcing nuclear safety in Eastern Europe, through the Swedish International Project and the safeguards project is reported separately

  2. Large aperture Fizeau interferometer commissioning and preliminary measurements of a long x-ray mirror at European X-ray Free Electron Laser

    Energy Technology Data Exchange (ETDEWEB)

    Vannoni, M., E-mail: maurizio.vannoni@xfel.eu; Freijo Martín, I. [European XFEL GmbH, Albert-Einstein-Ring 19, 22761 Hamburg (Germany)

    2016-05-15

    The European XFEL (X-ray Free Electron Laser) is a large facility under construction in Hamburg, Germany. It will provide a transversally fully coherent x-ray radiation with outstanding characteristics: high repetition rate (up to 2700 pulses with a 0.6 ms long pulse train at 10 Hz), short wavelength (down to 0.05 nm), short pulse (in the femtoseconds scale), and high average brilliance (1.6 ⋅ 10{sup 25} (photons s{sup −1} mm{sup −2} mrad{sup −2})/0.1% bandwidth). The beam has very high pulse energy; therefore, it has to be spread out on a relatively long mirror (about 1 m). Due to the very short wavelength, the mirrors need to have a high quality surface on their entire length, and this is considered very challenging even with the most advanced polishing methods. In order to measure the mirrors and to characterize their interaction with the mechanical mount, we equipped a metrology laboratory with a large aperture Fizeau interferometer. The system is a classical 100 mm diameter commercial Fizeau, with an additional expander providing a 300 mm diameter beam. Despite the commercial nature of the system, special care has been taken in the polishing of the reference flats and in the expander quality. We report the first commissioning of the instrument, its calibration, and performance characterization, together with some preliminary results with the measurement of a 950 mm silicon substrate. The intended application is to characterize the final XFEL mirrors with nanometer accuracy.

  3. Nuclear Regulatory Commission issuances: Volume 46, Number 6

    International Nuclear Information System (INIS)

    1997-12-01

    This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judges (ALJ), the Directors' Decision (DD), and the Decision on Petitions for Rulemaking (DPRM). The summaries and headnotes preceding the opinions reported herein are not to be deemed a part of those opinions or have any independent legal significance

  4. Nuclear Regulatory Commission issuances: Volume 46, Number 6

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-01

    This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judges (ALJ), the Directors` Decision (DD), and the Decision on Petitions for Rulemaking (DPRM). The summaries and headnotes preceding the opinions reported herein are not to be deemed a part of those opinions or have any independent legal significance.

  5. AND THE EUROPEAN UNION

    African Journals Online (AJOL)

    Regulations governing the production and use of genetically modified organisms have been developed in the United Kingdom since 1976. Regulations covering the release of transgenic organisms into the environment were initially voluntary. Since 1990, the European Economic Commission (EEC) Directive. 90/219 and ...

  6. MANAGEMENT BOARD MEETING OF 21 JUNE 1999

    CERN Multimedia

    1999-01-01

    For informationIn closed session the Management Board discussed the1999 advancement exercise. In open session the Director-General reported on the following highlights of the June meetings of the Scientific Policy Committee, Finance Committee, Committee of Council and Council:Member and Non-Member State MattersFollowing Bulgaria's accession to CERN as its twentieth Member State on 11 June 1999, a Bulgarian delegation headed by the deputy Prime Minister and Minister of Education and Science, Mr Vesselin Metodiev, had attended the Council for the first time. Welcoming the new members, the President of Council had expressed the hope that the new co-operation between CERN and Bulgaria would constitute a firmer basis for the Organisation's long-standing scientific collaboration with Bulgarian physicists and play a valuable role in widening its European network of partners.The Council had also approved a resolution providing for a redefinition of Greece's annual contributions to the CERN Budget for the period 1998-...

  7. Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

    Science.gov (United States)

    Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

    2013-06-15

    Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1

  8. ERK pathway activation bidirectionally affects visual recognition memory and synaptic plasticity in the perirhinal cortex

    Directory of Open Access Journals (Sweden)

    Davide eSilingardi

    2011-12-01

    Full Text Available ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies have identified its pivotal role in experience-dependent synaptic plasticity and in forms of long term memory involving hippocampus, amygdala or striatum. The perirhinal cortex (PRHC plays an essential role in familiarity-based object recognition memory. It is still unknown whether ERK activation in PRHC is necessary for recognition memory consolidation. Most important, it is unknown whether by modulating the gain of the ERK pathway it is possible to bidirectionally affect visual recognition memory and PRHC synaptic plasticity.We have first pharmacologically blocked ERK activation in the PRHC of adult mice and found that this was sufficient to impair long term recognition memory in a familiarity-based task, the Object Recognition Task (ORT. We have then tested performance in the ORT in Ras-GRF1 knock-out (KO mice, which exhibit a reduced activation of ERK by neuronal activity, and in ERK1 KO mice, which have an increased activation of ERK2 and exhibit enhanced striatal plasticity and striatal mediated memory. We found that Ras-GRF1 KO mice have normal short-term memory but display a long term memory deficit; memory reconsolidation is also impaired. On the contrary, ERK1 KO mice exhibit a better performance than WT mice at 72 hour retention interval, suggesting a longer lasting recognition memory. In parallel with behavioural data, LTD was strongly reduced and LTP was significantly smaller in PRHC slices from Ras-GRF1 KO than in WT mice while enhanced LTP and LTD were found in PRHC slices from ERK1 KO mice.

  9. HARMONISATION OF EUROPEAN CONTRACT LAW: SLOWLY BUT SURELY?

    Directory of Open Access Journals (Sweden)

    GEMA TOMÁS

    2013-05-01

    Full Text Available This paper deals with the harmonisation of European Contract Law from a gradual point of view. The main objective is to show the different academic and official steps carried out in this field. The so called Commission on European Contract Law under the leadership of Professor Ole Lando was the starting point in 1982. Some international research teams set up by European scholars and lawyers have been devoted to this aim for two decades. Time and effort have been made in the academic level to get a serious advance on bringing closer contractual national rules. This bottom-up approach met a stronger support in the last years although the European Parliament had “requested” the creation of a European Civil Code already in 1989. The momentous time comes in 2010 with a Green Paper from the European Commission on policy options for progress towards a European Contract Law for consumers and businesses. This Green Paper opened a public consultation period in 2011 and afterwards an expert group was appointed to draft a feasibility study for a future Instrument in European Contract Law. After all, a Proposal for a Regulation of the European Parliament and of the Council on a Common European Sales Law was adopted in October 2011 arising not few doubts, worries and misgivings from different points of view. This will be not the last step in this process.

  10. EURO-CARES as Roadmap for a European Sample Curation Facility

    Science.gov (United States)

    Brucato, J. R.; Russell, S.; Smith, C.; Hutzler, A.; Meneghin, A.; Aléon, J.; Bennett, A.; Berthoud, L.; Bridges, J.; Debaille, V.; Ferrière, L.; Folco, L.; Foucher, F.; Franchi, I.; Gounelle, M.; Grady, M.; Leuko, S.; Longobardo, A.; Palomba, E.; Pottage, T.; Rettberg, P.; Vrublevskis, J.; Westall, F.; Zipfel, J.; Euro-Cares Team

    2018-04-01

    EURO-CARES is a three-year multinational project funded under the European Commission Horizon2020 research program to develop a roadmap for a European Extraterrestrial Sample Curation Facility for samples returned from solar system missions.

  11. Politics and Policies of Promoting Multilingualism in the European Union

    Science.gov (United States)

    Romaine, Suzanne

    2013-01-01

    This article examines the politics of policies promoting multilingualism in the European Union (EU), specifically in light of the recently released European Union Civil Society Platform on Multilingualism. As the most far-reaching and ambitious policy document issued by the European Commission, the Platform warrants close scrutiny at a significant…

  12. Energy perspectives of the France by 2020-2050. European orientations

    International Nuclear Information System (INIS)

    2007-09-01

    The authors recall the absence in 2007 of a real european energy policy and present the new energy Plan of the european commission, fight against the climatic change, reinforce the security of the energy supply, maintain the competitiveness of the european economy. This plan is then discussed. (A.L.B.)

  13. PENANAMAN MODAL ASING DAN PERTUMBUHAN INDUSTRI DI ASEAN(6), CHINA, INDIA, DAN KOREA SELATAN 1999-20041

    OpenAIRE

    Kusumastuti, Sri Yani

    2015-01-01

    The objective of this study is to shed light on the determinants of foreign direct investment (FDI) in Asian developing countries and their impact on industrial growth. In order to undertake it, we perform an econometric model based in panel data analysis for 9 countries (such as ASEAN 6, China, India, and Korea) for the 1999-2004 periods. Weestimate the simultaneous equation using panel data estimation with fixed effect and random effect. Among the major conclusions we have that the FDI is d...

  14. Innovation Policy in European Union

    Directory of Open Access Journals (Sweden)

    Marta-Christina Suciu

    2006-11-01

    Full Text Available The innovation policies aim to analyze priority factors shaping innovative performance and to reflect the increasing appreciation of the economic and social importance of innovation. This paper is commissioned to examine topics of current interest or concern to innovation policy-makers in Europe. Based on literature and the framework of the European Action Plan for Innovation, this paper investigates different levels and fields of European innovational systems and practices.

  15. Tuberculosis en la Ciudad de la Habana, 1995-1999 Tuberculosis in Havana City, 1995-1999

    Directory of Open Access Journals (Sweden)

    José I Sevy Court

    2003-06-01

    Full Text Available OBJETIVO: La tuberculosis es un importante problema mundial de salud que recibe una atención priorizada del Sistema de Salud Cubano. Lo objetivo del trabajo es describir el comportamiento de los indicadores del Programa de Control de Tuberculosis cubano. MÉTODOS: A partir de una revisión de los documentos de la vigilancia de la tuberculosis en los registros del Centro Provincial de Higiene y Epidemiología se expone la infraestructura sanitaria, las estrategias del Programa de Control en la ciudad, se describen las tasas de incidencia, indicadores de localización, diagnóstico y manejo de casos. RESULTADOS: Se hallaron 8 sintomáticos respiratorios por cada mil consultantes de medicina general; la tasa de incidencia de tunerculosis en todas sus formas descendió de 16,4 (1995 a 12,0x105 habitantes (1999; la tuberculosis pulmonar descendió de 15,1 a 10,45 habitantes mientras la tuberculosis extrapulmonar ascendió de 1,3 a 1,6 x 105 habitantes, en igual período. Del total de los casos nuevos, el 40-50% fueron identificados en los policlínicos, el 67% fueron diagnosticados por baciloscopías, el 15,2% por cultivos, el 13.8% sólo por evidencias clínicas y radiológicas; el 0,9% y el 1,5%, respectivamente, fueron diagnosticados por biopsia o hallazgos de necropsia. Los grupos de 15-64 años incrementaron su incidencia en 1996-1997 y disminuyeron en 1998-1999; los casos >64 años de edad disminuyeron progresivamente de 1995 a 1999; en general, la tasa de incidencia de casos disminuyó. La demora promedio entre primeros síntomas y diagnóstico mejoró de 42 días en 1995 a 28,6 en 1999. CONCLUSIONES: La reversión de la tendencia de la notificación de casos nuevos parece haberse detenido en 1996. La situación de los indicadores de tuberculosis revelan cambios satisfactorios en el período analizado.OBJECTIVE: Tuberculosis is a worldwide health problem getting a prioritized attention by the Cuban National Health System. To describe the main

  16. Confirmation of hormones in animal serum by liquid chromatography/tandem mass spectrometry according to European Commission Decision 2002/657.

    Science.gov (United States)

    McDonald, Mark; Malone, Edward; McBride, John

    2010-01-01

    A novel and rapid method was developed and validated for the confirmation of endogenous and synthetic hormones in animal serum using LC/MS/MS. Detection of 17 beta-estradiol and beta-testosterone below the respective European Union-recommended levels of 0.1 and 0.5 microg/L was achieved, as was a required performance level of 0.1 microg/L for 17 alpha-estradiol and 0.5 microg/L for 17 alpha-testosterone, medroxyprogesterone-17-acetate, and progesterone. The method was established with dilution of serum followed by ion-exchange SPE, LC separation and MS detection with electrospray ionization, selected reaction monitoring, and positivelnegative switching. Two characteristic transitions were monitored for each analyte. The method was applied to bovine, ovine, porcine, equine, and avian samples and validated according to European Commission Decision 2002/657/EC and accepted for ISO/IEC 17025:2005 accreditation. An extended calibration curve allows naturally occurring levels of endogenous hormones to be quantified. Recoveries ranged from 97.3% for 17 alpha-testosterone to 102.0% for 17 alpha-estradiol. The decision limit CCalpha ranged from 0.02 microg/L for 17 alpha- and beta-estradiol to 0.12 microg/L for progesterone. Detection capability CCbeta ranged from 0.03 microg/L for 17 a-estradiol to 0.20 microg/L for progesterone.

  17. Behind the Scenes of Public Construction Clients – Collecting Data on Commissioning Activities and Organisational Approach

    NARCIS (Netherlands)

    Hermans, M.H.; Eisma, P.R.

    2015-01-01

    The understanding of public commissioning activity is fairly limited, with national and European research primarily focusing on large scale projects, European procurement procedures and new construction. However, most construction activities involve small scale projects and assignments performed by

  18. Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Sara Badodi

    2017-12-01

    Full Text Available Summary: We describe molecular convergence between BMI1 and CHD7 in the initiation of medulloblastoma. Identified in a functional genomic screen in mouse models, a BMI1High;CHD7Low expression signature within medulloblastoma characterizes patients with poor overall survival. We show that BMI1-mediated repression of the ERK1/2 pathway leads to increased proliferation and tumor burden in primary human MB cells and in a xenograft model, respectively. We provide evidence that repression of the ERK inhibitor DUSP4 by BMI1 is dependent on a more accessible chromatin configuration in G4 MB cells with low CHD7 expression. These findings extend current knowledge of the role of BMI1 and CHD7 in medulloblastoma pathogenesis, and they raise the possibility that pharmacological targeting of BMI1 or ERK may be particularly indicated in a subgroup of MB with low expression levels of CHD7. : Badodi et al. find convergence of the chromatin modifiers BMI1 and CHD7 in medulloblastoma pathogenesis, and they show that this pathway regulates tumor proliferation and growth via ERK signaling. Keywords: BMI1, CHD7, DUSP4, ERK, medulloblastoma, PcG genes, mouse models, epigenetics, chromatin

  19. H.R. 3532: This act may be cited as the Nuclear Regulatory Commission Authorization Act for Fiscal Year 1999. Introduced in the House of Representatives, One Hundred Fifth Congress, Second Session, March 24, 1998

    International Nuclear Information System (INIS)

    1998-01-01

    This bill authorizes appropriations for the Nuclear Regulatory Commission for fiscal year 1999. It is divided into the following sections: Section 1. Short title; Section 102. Allocation of amounts authorized; Section 103. Retention of funds; Section 104. Transfer of certain funds; Section 105. Limitation; Section 106. License fee exemption; Section 107. NRC user fees and actual charges. Section 201. Office location; Section 202. Period of a combined license; Section 203. Gift acceptance authority; Section 204. Carrying of firearms by licensee employees; Section 205. Sabotage of production, utilization or waste storage facilities under construction; Section 206. Unauthorized introduction of dangerous weapons; and Section 207. Continuation of Commissioner service

  20. Theoretical study of the guanine → 6-thioguanine substitution in duplexes, triplexes, and tetraplexes

    Czech Academy of Sciences Publication Activity Database

    Špačková, Naďa; Cubero, E.; Šponer, Jiří; Orozco, M.

    2004-01-01

    Roč. 126, č. 44 (2004), s. 14642-14650 ISSN 0002-7863 R&D Projects: GA MŠk LN00A016 Grant - others:European Training Mobility Program(XE) HPRI-CT-1999-00071; Ministry of Science and Technology (ES) BIO2003-06848; Wellcome Trust(GB) GR067507MF Institutional research plan: CEZ:AV0Z5004920 Keywords : 6-thioguanine * molecular dynamics simulations * thermodynamic integration Subject RIV: BO - Biophysics Impact factor: 6.903, year: 2004

  1. The role of national ethics commissions in Finland.

    Science.gov (United States)

    Halila, Ritva

    2003-08-01

    There are six national ethics commissions in Finland. The National Advisory Board on Research Ethics was first established in 1991, followed by the National Advisory Board on Biotechnology and the Board on Gene Technology in 1995. The National Advisory Board on Health Care Ethics was established in 1998, followed by its Sub-Committee on Medical Research Ethics in 1999. The Co-operation Group for Laboratory Animal Sciences was established in 2001. Only the Board on Gene Technology works as a national authority and gives binding opinions and recommendations about the use of genetically modified organisms. The Sub-Committee on Medical Research Ethics acts a national research ethics committee and gives opinions about research projects. Other advisory boards do not make legally binding decisions, but their expertise gives a lot of power to their opinions and statements. The commissions work in close collaboration with each other, having regular meetings. They arrange seminars and conferences, and share information with each other. The commissions also share duties and information in international collaboration. How the voice and opinions of these commissions is heard in society lies in the wide, multi-professional expertise of their members. Large commissions and wide expertise may make it difficult to find consensus in their opinions and statements, although wide expertise may, more than discussion in a small expert group, help to further process difficult ethical issues. Collaboration between different bodies is important in order to share duties, and also to add more emphasis to the statements and opinions where different bodies share interests. In our country, the interest that national commissions share is research ethics, where the advisory boards and their members have discharged collaborative activities for years.

  2. An advanced UV optical cavity for the European FEL project

    CERN Document Server

    Poole, M W; Chesworth, A A; Clarke, J A; Fell, B; Hill, C; Marl, R; Mullacrane, I D; Reid, R J

    2000-01-01

    A European collaboration is constructing a short wavelength FEL for the ELETTRA storage ring. The optical cavity has been designed and constructed at Daresbury Laboratory for delivery to Sincrotrone Trieste in Autumn 1999, following commissioning tests over the Summer. Initial FEL operation will be at 350 nm but subsequently down to 200 nm or less and mirrors will be 40 mm diameter. The 32 m optical cavity is controllable to 0.01 mu rad in mirror pitch and yaw using digital piezo translators. A novel feature is the simultaneous presence of three remotely interchangeable mirrors to extend the tuning range and also to interchange damaged mirrors immediately. In addition, a transfer arm and load-lock arrangement will permit a mirror to be withdrawn from the chamber and replaced without disruption to the UHV system. The FEL is designed to operate at high power (1-10 W) and multi-watt spontaneous emission is also present: power loading has been investigated by FEA analysis and has necessitated specification of a w...

  3. The atypical mitogen-activated protein kinase ERK3 is essential for establishment of epithelial architecture.

    Science.gov (United States)

    Takahashi, Chika; Miyatake, Koichi; Kusakabe, Morioh; Nishida, Eisuke

    2018-06-01

    Epithelia contribute to physical barriers that protect internal tissues from the external environment and also support organ structure. Accordingly, establishment and maintenance of epithelial architecture are essential for both embryonic development and adult physiology. Here, using gene knockout and knockdown techniques along with gene profiling, we show that extracellular signal-regulated kinase 3 (ERK3), a poorly characterized atypical mitogen-activated protein kinase (MAPK), regulates the epithelial architecture in vertebrates. We found that in Xenopus embryonic epidermal epithelia, ERK3 knockdown impairs adherens and tight-junction protein distribution, as well as tight-junction barrier function, resulting in epidermal breakdown. Moreover, in human epithelial breast cancer cells, inhibition of ERK3 expression induced thickened epithelia with aberrant adherens and tight junctions. Results from microarray analyses suggested that transcription factor AP-2α (TFAP2A), a transcriptional regulator important for epithelial gene expression, is involved in ERK3-dependent changes in gene expression. Of note, TFAP2A knockdown phenocopied ERK3 knockdown in both Xenopus embryos and human cells, and ERK3 was required for full activation of TFAP2A-dependent transcription. Our findings reveal that ERK3 regulates epithelial architecture, possibly together with TFAP2A. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. The EU commission and national governments as partners: EC regulatory expansion in telecommunications 1979-2000

    OpenAIRE

    Mark Thatcher

    2001-01-01

    Explicitly or implicitly, general models of European integration claim that EC regulatory expansion involves a struggle for power between Commission and national governments. The Commission is seen as a policy entrepreneur, taking the initiative to drive forward integration (Sandholtz and Zysman 1989). It seeks regulatory expansion due to constraints on its expenditure (Majone 1996, ch4). Neo-functionalists emphasise the Commission's ability to expand its role against the wishes of government...

  5. ARCHITECTURE OF EUROPEAN SYSTEM OF FINANCIAL SUPERVISION AFTER THE GLOBAL ECONOMIC CRISIS

    Directory of Open Access Journals (Sweden)

    Mateusz Muszyński

    2015-12-01

    Full Text Available This paper indicates how the last global financial crisis has affected the european financial system. As the depression evolved it brought all the weaknesses in the system of financial supervision to the surface. Then it became clear that deeper integration of the banking system was strongly needed. To mitigate systemic stability risk and improve the coordination process with international organizations, the European Commission decided to establish the European System of Financial Supervision. However, it seemed that it was not sufficient to prevent from further fragmentation of the financial market in Europe. As a result, in 2012 the European Commission initiated the banking union, a new form of political and economic integration.

  6. The position of the French coal industry on the European Commission strategy against acidification; Position de charbonnages de France sur la strategie de lutte contre l`acidification de la commission europeenne

    Energy Technology Data Exchange (ETDEWEB)

    Dejean, M. [CDF Energie, 92 - Rueil-Malmaison (France)

    1997-12-31

    The Charbonnages de France group (French coal industry) presents several objections to the projected European Commission program concerning the reduction of air pollution emission and acidification: reaching so rapidly the projected reduction level means a drastic improvement to the large burning plants, regardless of the low operating duration of the coal plants in France, which are used for electric power production only at peak or semi-base periods or in industries (principally food industry) with low energy duration requirements, and regardless of the important emission reductions already achieved in France. The coal industry proposes to simply apply the present IPPC directive; already, turning to circulating fluidized bed units has allowed important SO{sub 2} and NO{sub x} emission reductions. The evolution of sulfur and nitrogen oxide emissions in France between 1990 and 1995 is detailed

  7. Genotypic and allelic variability in CYP19A1 among populations of African and European ancestry.

    Directory of Open Access Journals (Sweden)

    Athena Starlard-Davenport

    Full Text Available CYP19A1 facilitates the bioconversion of estrogens from androgens. CYP19A1 intron single nucleotide polymorphisms (SNPs may alter mRNA splicing, resulting in altered CYP19A1 activity, and potentially influencing disease susceptibility. Genetic studies of CYP19A1 SNPs have been well documented in populations of European ancestry; however, studies in populations of African ancestry are limited. In the present study, ten 'candidate' intronic SNPs in CYP19A1 from 125 African Americans (AA and 277 European Americans (EA were genotyped and their frequencies compared. Allele frequencies were also compared with HapMap and ASW 1000 Genomes populations. We observed significant differences in the minor allele frequencies between AA and EA in six of the ten SNPs including rs10459592 (p<0.0001, rs12908960 (p<0.0001, rs1902584 (p = 0.016, rs2470144 (p<0.0001, rs1961177 (p<0.0001, and rs6493497 (p = 0.003. While there were no significant differences in allele frequencies between EA and CEU in the HapMap population, a 1.2- to 19-fold difference in allele frequency for rs10459592 (p = 0.004, rs12908960 (p = 0.0006, rs1902584 (p<0.0001, rs2470144 (p = 0.0006, rs1961177 (p<0.0001, and rs6493497 (p = 0.0092 was observed between AA and the Yoruba (YRI population. Linkage disequilibrium (LD blocks and haplotype clusters that is unique to the EA population but not AA was also observed. In summary, we demonstrate that differences in the allele frequencies of CYP19A1 intron SNPs are not consistent between populations of African and European ancestry. Thus, investigations into whether CYP19A1 intron SNPs contribute to variations in cancer incidence, outcomes and pharmacological response seen in populations of different ancestry may prove beneficial.

  8. A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activation.

    Science.gov (United States)

    Liu, Yan; Wang, Yubin; Zhu, Guoqi; Sun, Jiandong; Bi, Xiaoning; Baudry, Michel

    2016-06-01

    While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. European Community.

    Science.gov (United States)

    1987-05-01

    The European Community was established in 1951 to reconcile France and Germany after World War II and to make possible the eventual federation of Europe. By 1986, there were 12 member countries: France, Italy, Belgium, the Federal Republic of Germany, Luxembourg, the Netherlands, Denmark, Ireland, the United Kingdom, Greece, Spain, and Portugal. Principal areas of concern are internal and external trade, agriculture, monetary coordination, fisheries, common industrial and commercial policies, assistance, science and research, and common social and regional policies. The European Community has a budget of US$34.035 billion/year, funded by customs duties and 1.4% of each member's value-added tax. The treaties establishing the European Community call for members to form a common market, a common customs tariff, and common agricultural, transport, economic, and nuclear policies. Major European Community institutions include the Commission, Council of Ministers, European Parliament, Court of Justice, and Economic and Social Committee. The Community is the world's largest trading unit, accounting for 15% of world trade. The 2 main goals of the Community's industrial policy are to create an open internal market and to promote technological innovation in order to improve international competitiveness. The European Community aims to contribute to the economic and social development of Third World countries as well.

  10. Radiation regulations - a UK/European perspective

    International Nuclear Information System (INIS)

    Shrimpton, P.C.

    2000-01-01

    Full text: Basic standards for radiation protection in the European Union are laid down in Directives made under the EURATOM Treaty that must be implemented by Member States in national legislation. These Directives are presently based on the 1990 recommendations of the International Commission on Radiological Protection and include Basic Safety Standards (1996) for the protection of workers and the public, and the Medical Exposure Directive (1997) for the protection of patients. UK legislation has recently been revised to meet these new standards, principally through the Ionising Radiations Regulations 1999 and the Ionising Radiation (Medical Exposure) Regulations (IR(ME)R) 2000. A framework of formal and informal guidance supports these regulations. IR(ME)R 2000 clarifies and strengthens the roles and responsibilities of Employers, Practitioners, Operators and Referrers in relation to the justification and optimisation of protection for individual medical exposures. In particular, there is now a formal requirement for the adoption of diagnostic reference levels (DRLs) by employers as a practical tool for promoting patient protection during diagnostic exposures. The recent revision of regulations concerned with medical exposures in the UK is seen as an evolutionary rather than revolutionary process to strengthen the safe and effective use of radiation in medicine. Copyright (2000) Australasian College of Physical Scientists and Engineers in Medicine

  11. EU rural policy reform (1997-1999): between politics and policy learning

    DEFF Research Database (Denmark)

    Steffensen, Jonny Trapp

    2006-01-01

    EU rural development policy is gaining in relative significance as the "second pillar" of the Common Agricultural Policy (CAP). Its substance - objectives and instruments - is still under development. This article explores the contribution of so-called "policy learning" by the European Commission...

  12. THE DETAILS OF CONSTRUCTION AND APPLICATION OF EUROPEAN COMMISSION MACROMODEL QUEST III WITH EXTENDED FISCAL BLOCK

    Directory of Open Access Journals (Sweden)

    I. Lukianenko

    2015-10-01

    Full Text Available In this paper we provide detailed derivation of dynamic stochastic general equilibrium model QUEST III that was developed under European Commission project. The principal feature of the model is the presence of both monetary and extended fiscal blocks. In particular, Central Bank sets interest rate using monetary policy rule, while fiscal sector is represented by taxes and transfers. It allows analyzing the effect of complex shocks on the key macroeconomic variables. Our results show that parallel application of monetary and fiscal instruments is an effective way to combat stagflation, i.e. drastic decrease in production and acceleration of inflation. Due to the presence of extended fiscal block, the model can fit Ukrainian economic and policy structure quick good. The next steps of the research may be calibration and estimation of QUEST III prototype on the Ukrainian data with potentially some modification and inclusion of banking and other sectors that play critical role in the local conditions. Monetary policy instruments should be extended with the level of Central Bank reserves which have large influence on macro stability. In addition, dollarization is an important peculiarity that should be addressed in the future versions of the model.

  13. Low-level shear stress promotes migration of liver cancer stem cells via the FAK-ERK1/2 signalling pathway.

    Science.gov (United States)

    Sun, Jinghui; Luo, Qing; Liu, Lingling; Song, Guanbin

    2018-07-28

    Cancer stem cells (CSCs) are a small subpopulation of tumour cells that have been proposed to be responsible for cancer initiation, chemotherapy resistance and cancer recurrence. Shear stress activated cellular signalling is involved in cellular migration, proliferation and differentiation. However, little is known about the effects of shear stress on the migration of liver cancer stem cells (LCSCs). Here, we studied the effects of shear stress that are generated from a parallel plated flow chamber system, on LCSC migration and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2), using transwell assay and western blot, respectively. We found that 2 dyne/cm 2 shear stress loading for 6 h promotes LCSC migration and activation of the FAK and ERK1/2 signalling pathways, whereas treatment with the FAK phosphorylation inhibitor PF573228 or the ERK1/2 phosphorylation inhibitor PD98059 suppressed the shear stress-promoted migration, indicating the involvement of FAK and ERK1/2 activation in shear stress-induced LCSC migration. Additionally, atomic force microscopy (AFM) analysis showed that shear stress lowers LCSC stiffness via the FAK and ERK1/2 pathways, suggesting that the mechanism by which shear stress promotes LCSC migration might partially be responsible for the decrease in cell stiffness. Further experiments focused on the role of the actin cytoskeleton, demonstrating that the F-actin filaments in LCSCs are less well-defined after shear stress treatment, providing an explanation for the reduction in cell stiffness and the promotion of cell migration. Overall, our study demonstrates that shear stress promotes LCSC migration through the activation of the FAK-ERK1/2 signalling pathways, which further results in a reduction of organized actin and softer cell bodies. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. The European climate change program. An evaluation of stakeholder involvement and policy achievements

    International Nuclear Information System (INIS)

    Maxian Rusche, Tim

    2010-01-01

    In order to step up its efforts in reducing climate change, the European Commission (hereafter: the Commission) has launched in June 2000 its European climate change program (hereafter: ECCP). This wide-ranging stakeholder consultation aimed at identifying and developing all elements necessary for a European climate change strategy. The ECCP formally came to a close in April 2003. This paper analyses the inner workings of ECCP, and how ECCP has delivered with regard to its objectives. Special attention is paid to ECCP's Working Group 1, 'Flexible Mechanisms', which developed the foundations for the European emission trading scheme (hereafter: EU ETS). The paper draws on documents published on the Commission's ECCP web-site, on academic literature, on press releases from stakeholders and on interviews with four participants in the ECCP process. Using this method, the paper offers important insights as to how the consensus-building for establishing the world's biggest carbon-trading scheme has started long time before the formal legislative process. (author)

  15. Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif.

    Directory of Open Access Journals (Sweden)

    Mei Ying Ng

    Full Text Available Cycle inhibiting factors (Cifs are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL and consequently induction of cell cycle arrest. Here we show that Cif can function as a potent activator of MAPK/ERK signaling without significant activation of other signaling pathways downstream of receptor tyrosine kinases. Importantly, we found that the ability of Cif to activate ERK is dependent on its deamidase activity, but independent of Cullin E3 ligase inhibition. This suggests that apart from Nedd8, other cellular targets of Cif-dependent deamidation exist. We provide evidence that the mechanism involved in Cif-mediated ERK activation is dependent on recruitment of the Grb2-SOS1 complex to the plasma membrane. Further investigation revealed that Cif appears to modify the phosphorylation status of SOS1 in a region containing the CDC25-H and proline-rich domains. It is known that prolonged Cullin E3 ligase inhibition leads to cellular apoptosis. Therefore, we hypothesize that ERK activation is an important mechanism to counter the pro-apoptotic effects of Cif. Indeed, we show that Cif dependent ERK activation promotes phosphorylation of the proapoptotic protein Bim, thereby potentially conferring a pro-survival signal. In summary, we identified a novel deamidation-dependent mechanism of action of the B. pseudomallei virulence factor Cif/CHBP to activate MAPK/ERK signaling. Our study demonstrates that bacterial proteins such as Cif can serve as useful molecular tools to uncover novel aspects of mammalian signaling pathways.

  16. Potential Impact of Latest Proposals for New European Vehicle Noise Limits

    NARCIS (Netherlands)

    Dittrich, M.G.; Roo, F. de

    2013-01-01

    Noise emission of new road vehicles is regulated by European Directives [1] and subsequent amendments. Proposals for tighter noise emission limits for road vehicles made by the European Commission in 2011 [2] have been adopted in modified form by the European Parliament in 2013 [3]. In the VENOLIVA

  17. Commission de regulation de l'energie. Activity report june 2007

    International Nuclear Information System (INIS)

    2007-06-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets

  18. Technical memory 1999; Memoria tecnica 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    The technical memory 1999 of the Nuclear Regulatory Authority (NRA) of the Argentine Republic, compile the papers published in the subject on radiation protection and nuclear safety, safeguards and physical protection, and presented in congress or meetings of these specialities by personnel of the mentioned institution during 1999.

  19. Trends in cannabis use prior to first presentation with schizophrenia, in South-East London between 1965 and 1999.

    Science.gov (United States)

    Boydell, J; van Os, J; Caspi, A; Kennedy, N; Giouroukou, E; Fearon, P; Farrell, M; Murray, R M

    2006-10-01

    There is evidence that cannabis use might be relevant to the aetiology of schizophrenia. We aimed to measure any change in cannabis use over time in those first presenting with schizophrenia in South-East London from 1965 to 1999, and compare this with change in use in those presenting with non-psychotic psychiatric disorders. The rate of cannabis use in the year prior to first ever presentation was measured over seven time periods. Logistic regression modelling was used to determine (a) whether cannabis use changed over time, after controlling for age, sex and ethnicity, and (b) whether there was an interaction between diagnosis and time. Cannabis use increased over time in both the schizophrenia group [odds ratio per time period (OR) 2.03, 95% confidence interval (CI) 1.74-2.38, p<0.0001] and the non-psychotic disorders group (OR 1.24, 95% CI 1.05-1.47, p=0.012), after controlling for age, sex and ethnicity. However, the effect of time was significantly greater in the schizophrenia group than in the non-schizophrenia group (chi2=17, p<0.0001). Cannabis use in the year prior to presentation with schizophrenia increased markedly between 1965 and 1999, and disproportionately so compared to increase in cannabis use in other psychiatric disorders.

  20. Corporate strategies for European gas markets

    International Nuclear Information System (INIS)

    Chevalier, J.M.

    1992-01-01

    In January 1992, the Commission of the European Economic Community issued a proposal for accelerating the process of building up a single market for natural gas. After the first step, already taken, to introduce price transparency, the Commission is willing to introduce progressively Third Party Access (T.P.A.) and the freedom of establishment in all segments of the natural gas industry: L.N.G. terminals, storage facilities, transmission lines and public distribution. 1 tab

  1. Turkish-Greek relations within the European Union framework

    OpenAIRE

    Kılıç, Özlem; Kilic, Ozlem

    2009-01-01

    Turko-Greek relations have been strained by a number of conflicting issues such as Cyprus, Continental Shelf, Territorial Waters, the Öcalan affair, and the S-300 Missiles crisis on Cyprus. Until the December 1999 Helsinki Summit, Greece was one of the strong opponents of Turkey's membership in the European Union (EU). However, at the Helsinki Summit of 1999, Greece dropped her negative position permitting Turkey to be declared by the EU as a candidate country. This shift in foreign policy ha...

  2. Lahkunud 1999

    Index Scriptorium Estoniae

    2000-01-01

    Ilmar Torn (10. I), Leopold Ennosaar (21. I), Voldemar Vaga (23. II), Ilmar Laasi (15. VIII), Voldemar Peil (17. X), Ludvig Kruusmaa (7. XII), Aksel Vallaste (13. XII), Aldo van Eyck (1919-14. I 1999), Bernard Buffet (1928-4. X 1999), Tibor Kalman (1950-5. V 1999).

  3. Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.

    Science.gov (United States)

    Sun, Wei-Lun; Quizon, Pamela M; Zhu, Jun

    2016-01-01

    Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. Copyright © 2016. Published by Elsevier Inc.

  4. SMEs Financial Reporting in European Union: Steps towards a More Harmonized Reporting

    OpenAIRE

    Buculescu (Costicã) Maria Mãdãlina; Stoica Anamaria

    2014-01-01

    Recognizing the increasingly importance of SMEs in the economy, European Commission attempts to develop an “economic friendly” environment for SMEs business and further to create a harmonized accounting framework for SMEs financial reporting. Therefore, in 2013, European Commission issued a new Accounting Directive 2013/34/EU, to which the member states have to comply until July 2015, representing an important effort undertaken to reduce the administrative burden of SMEs financial reporting, ...

  5. Effect of mitomycin combined with Nd-YAG laser on cell proliferation and invasion as well as MEK/ERK signaling pathway in obstructive lacrimal duct model

    Directory of Open Access Journals (Sweden)

    Yu Yan

    2017-11-01

    Full Text Available Objective: To study the effect of mitomycin (MMC combined with Nd-YAG laser on cell proliferation and invasion as well as MEK/ERK signaling pathway in obstructive lacrimal duct model. Methods: New Zealand rabbits were selected as experimental animals and divided into model group, laser group and MMC + laser group; obstructive lacrimal duct model was established, then laser group were given Nd-YAG laser intervention, and MMC + laser group were given Nd-YAG laser combined with mitomycin intervention. 2 months after intervention, the expression of proliferation molecules, invasion molecules and MEK-ERK signaling molecules in lacrimal duct tissue were measured. Results: TGF-β, CTGF, PCNA, Ki-67, Col-I, Col-III, MEK, ERK1/2, MMP2 and MMP9 protein levels in lacrimal duct tissue of laser group were significantly higher than those of model group while TSG-6, Cthrc1 and TIMP1 protein levels were significantly lower than those of model group; TGF-β, CTGF, PCNA, Ki- 67, Col-I, Col-III, MEK, ERK1/2, MMP2 and MMP9 protein levels in lacrimal duct tissue of MMC + laser group were significantly lower than those of laser group while TSG-6, Cthrc1 and TIMP1 protein levels were significantly higher than those of laser group. Conclusion: Mitomycin can inhibit cell proliferation and invasion as well as MEK/ERK signaling pathway activation in obstructive lacrimal duct model after Nd-YAG laser treatment.

  6. Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells.

    Science.gov (United States)

    Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

    2018-04-01

    Exposure to specific electromagnetic field (EMF) patterns can affect a variety of biological systems. We have shown that exposure to Thomas-EMF, a low-intensity, frequency-modulated (25-6 Hz) EMF pattern, inhibited growth and altered cell signaling in malignant cells. Exposure to Thomas-EMF for 1 h/day inhibited the growth of malignant cells including B16-BL6 mouse melanoma cells, MDA-MB-231, MDA-MB-468, BT-20, and MCF-7 human breast cancer and HeLa cervical cancer cells but did not affect non-malignant cells. The Thomas-EMF-dependent changes in cell proliferation were mediated by adenosine 3',5'-cyclic monophosphate (cAMP) and extracellular-signal-regulated kinase (ERK) signaling pathways. Exposure of malignant cells to Thomas-EMF transiently changed the level of cellular cAMP and promoted ERK phosphorylation. Pharmacologic inhibitors (SQ22536) and activators (forskolin) of cAMP production both blocked the ability of Thomas-EMF to inhibit cell proliferation, and an inhibitor of the MAP kinase pathway (PD98059) was able to partially block Thomas-EMF-dependent inhibition of cell proliferation. Genetic modulation of protein kinase A (PKA) in B16-BL6 cells also altered the effect of Thomas-EMF on cell proliferation. Cells transfected with the constitutively active form of PKA (PKA-CA), which interfered with ERK phosphorylation, also interfered with the Thomas-EMF effect on cell proliferation. The non-malignant cells did not show any EMF-dependent changes in cAMP levels, ERK phosphorylation, or cell growth. These data indicate that exposure to the specific Thomas-EMF pattern can inhibit the growth of malignant cells in a manner dependent on contributions from the cAMP and MAP kinase pathways. Bioelectromagnetics. 39;217-230, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. ACER: demystifying the European energy supervisor from a consumer perspective

    NARCIS (Netherlands)

    Lavrijssen, S.A.C.M.; Bordei, I.

    2012-01-01

    The European energy regulatory triangle, consisting of National Regulatory Authorities (NRAs), the European Commission and the newly established Agency for the Cooperation of Energy Regulators (ACER), has an important role in enhancing cross border trade and wholesale market competition and

  8. Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations.

    Science.gov (United States)

    Arkun, Yaman; Yasemi, Mohammadreza

    2018-01-01

    Cell signaling is the process by which extracellular information is transmitted into the cell to perform useful biological functions. The ERK (extracellular-signal-regulated kinase) signaling controls several cellular processes such as cell growth, proliferation, differentiation and apoptosis. The ERK signaling pathway considered in this work starts with an extracellular stimulus and ends with activated (double phosphorylated) ERK which gets translocated into the nucleus. We model and analyze this complex pathway by decomposing it into three functional subsystems. The first subsystem spans the initial part of the pathway from the extracellular growth factor to the formation of the SOS complex, ShC-Grb2-SOS. The second subsystem includes the activation of Ras which is mediated by the SOS complex. This is followed by the MAPK subsystem (or the Raf-MEK-ERK pathway) which produces the double phosphorylated ERK upon being activated by Ras. Although separate models exist in the literature at the subsystems level, a comprehensive model for the complete system including the important regulatory feedback loops is missing. Our dynamic model combines the existing subsystem models and studies their steady-state and dynamic interactions under feedback. We establish conditions under which bistability and oscillations exist for this important pathway. In particular, we show how the negative and positive feedback loops affect the dynamic characteristics that determine the cellular outcome.

  9. Natalidad y riesgo reproductivo en adolescentes de Chile, 1990­1999

    Directory of Open Access Journals (Sweden)

    Enrique Donoso Siña

    2003-07-01

    Full Text Available OBJETIVOS: Evaluar en madres adolescentes chilenas menores de 15 años y de 15 a 19 años las tendencias de la natalidad y del riesgo reproductivo en el período de 1990­1999. MÉTODOS: Sobre la base de datos extraídos de los Anuarios de demografía publicados por el Instituto Nacional de Estadísticas de Chile para 1990­1999, se calcularon las tendencias mostradas por el número de nacidos vivos y las tasas de mortalidad materna, fetal tardía, neonatal e infantil entre madres adolescentes menores de 15 años y de 15 a 19 años de edad. Se calculó el riesgo (razón de posibilidades, RP de ambos grupos en comparación con el de mujeres de 20 a 34 años de edad. La comparación entre grupos se efectuó mediante la prueba de Fisher o de ji2, según el caso, y el análisis de tendencias en el período estudiado se realizó mediante la correlación de Pearson con un nivel alfa de 0,05. RESULTADOS: En el período estudiado, las tasas de mortalidad materna, fetal tardía, neonatal e infantil en madres adolescentes menores de 15 años fueron, respectivamente, de 41,9 (por 100 000 nacidos vivos [NV], 5,1 (por 1 000 NV, 15,2 (por 1 000 NV y 27,4 (por 1 000 NV; en adolescentes de 15 a 19 años, de 19,3, 4,1, 8,1 por 1 000 y 16,6, respectivamente, mientras que en adultas de 20 a 34 años dichas tasas fueron de 26,8, 5,0, 6,7 y 12,1, respectivamente. En las adolescentes menores de 15 años el mayor riesgo de muerte materna (RP = 1,56; IC95%: 0,50 a 4,31; P = 0,372 y de muerte fetal (RP = 1,02; IC95%: 0,76 a 1,36; P = 0,890 no fue estadísticamente significativo; en cambio, sí se detectó un riesgo significativamente mayor de muerte neonatal (RP = 2,27; IC95%: 1,92 a 2,68; P <0,0001 y el de muerte infantil (RP = 2,39; IC95%: 2,04 a 2,62; P <0,0001. Entre las madres adolescentes de 15 a 19 años, el riesgo de muerte materna (RP = 0,72; IC95%: 0,56 a 0,92; P <0,008 y el de muerte fetal (RP = 0,81; IC95%: 0,77 a 0,86; P <0,0001 fueron inferiores en grado

  10. LULI 1999 activity report

    International Nuclear Information System (INIS)

    1999-01-01

    This document gathers the main results obtained by scientists from the LULI (laboratory for the use of intense lasers) unit in 1999. It is made up of 55 short articles and is organized into 6 topics: 1) laser-matter interaction, 2) hydrodynamics, shocks, equations of state, 3) atom physics, X-ray lasers, 4) material treatment, 5) progress in optics for power lasers, and 6) instrumentation and other advances

  11. The Politics of the Economics of Education in the European Union

    Science.gov (United States)

    Jones, Peter

    2010-01-01

    This article critically examines the work of the European Commission-sponsored network, the European Expert Network on Economics of Education (EENEE). The aim is to develop understanding of the context and significance of the mobilization of the economics of education research and policy paradigm within the European Union's Education and Training…

  12. Commission of energy regulation. 2004 activity report

    International Nuclear Information System (INIS)

    2004-01-01

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  13. BMP suppresses PTEN expression via RAS/ERK signaling.

    Science.gov (United States)

    Beck, Stayce E; Carethers, John M

    2007-08-01

    Bone morphogenetic protein (BMP), a member of the transforming growth factor beta family, classically utilizes the SMAD signaling pathway for its growth suppressive effects,and loss of this signaling cascade may accelerate cell growth. In the colon cancer predisposition syndrome Juvenile Polyposis, as well as in the late progression stages of nonsyndromic colorectal cancers, SMAD4 function is typically abrogated. Here, we utilized the SMAD4-null SW480 colon cancer cell line to examine BMPs effect on a potential target gene, PTEN, and how its expression might be regulated. Initial treatment of the SMAD4-null cells with BMP resulted in mild growth suppression, but with prolonged exposure to BMP, the cells become growth stimulatory, which coincided with observed decreases in transcription and translation of PTEN, and with corresponding increases in phospho-AKT protein levels. BMP-induced PTEN suppression was mediated via the RAS/ERK pathway, as pharmacologic inhibition of RAS/ERK, or interference with protein function in the cytosol by DN-RAS prevented BMP-induced growth promotion and changes in PTEN levels, as did treatment with noggin, a BMP ligand inhibitor. Thus, BMP downregulates PTEN via RAS/ERK in a SMAD4-null environment that contributes to cell growth, and constitutes a SMAD4-independent but BMP-responsive signaling pathway.

  14. The euro and the European Central Bank

    OpenAIRE

    Jeffrey M. Wrase

    1999-01-01

    The formation of a monetary union by 11 European countries has received a lot of notice from the press since January 1, 1999, when the union's common currency, the euro, was officially introduced. To facilitate adoption of a single currency, these same countries have established a central bank that sets a common monetary policy for the members of the monetary union. In this article, Jeff Wrase gives some background on the European monetary union, outlines the procedure for introduction of the...

  15. RHIC BEAM ABORT KICKER POWER SUPPLY SYSTEM COMMISSIONING EXPERIENCE AND REMAINING ISSUES

    International Nuclear Information System (INIS)

    ZHANG, W.; AHRENS, L.A.; MI, J.; OERTER, B.; SANDERS, R.; SANDBERG, J.

    2001-01-01

    The RHIC Beam Abort Kicker Power Supply Systems commissioning experience and the remaining issues will be reported in this paper. The RHIC Blue Ring Beam Abort Kicker Power Supply System initial commissioning took place in June 1999. Its identical system in Yellow Ring was brought on line during Spring 2000. Each of the RHIC Beam Abort Kicker Power Supply Systems consists of five high voltage modulators and subsystems. These systems are critical devices for RHIC machine protection and environmental protection. They are required to be effective, reliable and operating with sufficient redundancy to safely abort the beam to its beam dump at the end of accumulation or at any time when they are commanded. To deflect 66 GeV ion beam to the beam absorbers, the RHIC Beam Abort Kicker Power Supply Systems were operated at 22 kV level. The RHIC 2000 commissioning run was very successful

  16. T4 report. An expert consortium review of the EC-commissioned report "Alternative (non-animal) methods for cosmetics testing: Current status and future prospects - 2010"

    NARCIS (Netherlands)

    Hartung, T.; Blaauboer, B.J.; Bosgra, S.; Carney, E.; Coenen, J.; Conolly, R.B.; Corsini, E.; Green, S.; Faustman, E.M.; Gaspari, A.; Hayashi, M.; Hayes, A.W.; Hengstler, J.G.; Knudsen, L.E.; Knudsen, T.B.; McKim, J.M.; Pfaller, W.; Roggen, E.L.

    2011-01-01

    The European cosmetics legislation foresees a review in 2011 and possible postponement of the 2013 marketing ban to enforce the testing ban for systemic and repeated-dose animal tests. For this purpose, a 119-page report commissioned by the European Commission was published recently. Here, a group

  17. EU Commission participation in the Troika mission: is there a European Union price to pay?

    Directory of Open Access Journals (Sweden)

    Antonio Goucha Soares

    2015-06-01

    Full Text Available The article is intended to debate two questions regarding the involvement of the Commission in the Troika's action: firstly, considering the nature of financial assistance programs, it aims to discuss the effect of the Commission's participation in Troika negotiations on the balance of power of the EU institutions; and secondly, the article raises the issue of the Commission's liability for the results achieved by the financial assistance program, taking into account the extent of the conditions imposed, as well as the intensity of scrutiny by the Troika.

  18. Requirements for BNCT at a nuclear research reactor. Results from a BNCT workshop organized by the European Commission in Prague, November 2005

    International Nuclear Information System (INIS)

    Moss, Ray; Sauerwein, Wolfgang; Wittig, Andrea; Burian, Jiri

    2006-01-01

    As part of the European Commission's Enlargement and Integration Action (E and IA), which is intended to improve exchange and relationship within the extended European Union (EU), a Workshop was organized in Prague in November 2005. The purpose of the workshop was to present and discuss technical and organisational requirements in setting up a BNCT facility at a research reactor. Topics included: treatment of a patient by BNCT; organisational aspects and regulatory affairs; BNCT from the nuclear perspective and BNCT from the clinician's perspective. Presentations were given by BNCT experts in their particular field, whilst eleven different national nuclear research centres from the New Member States and Accession Countries, interested in developing a BNCT programme, presented the status of their preparations. The conclusions of the Workshop were that an early and close collaboration between nuclear and medical groups is the basis for BNCT, that a local effort to build a BNCT facility should be supported by a national research programme including basic and clinical science and that the JRC and its partners are ready to support national initiatives within the EU and candidate countries. (author)

  19. Commission de regulation de l'electricite. Activity Report 30 June 2000

    International Nuclear Information System (INIS)

    2000-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity market for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity sector, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the June 2000 activity report of CRE. Content: A - Opening of the European electricity market: transposition into French law of the European Directive, access to the European power transportation network, obstacles to market deregulation, segmentation of the European market, deregulation impact on electricity market: the German example, state of the French market openness; B - The first regulation projects: network access, account un-bundling, production opening to competition modalities, studies relative to the creation of an electricity stock-exchange in France; C - The Commission: means, operation. D - Appendixes: Glossary; Units; Council of European Energy Regulators

  20. Efficient inhibition of the formation of joint adhesions by ERK2 small interfering RNAs

    International Nuclear Information System (INIS)

    Li, Fengfeng; Ruan, Hongjiang; Fan, Cunyi; Zeng, Bingfang; Wang, Chunyang; Wang, Xiang

    2010-01-01

    Transforming growth factor-β1 and fibroblast growth factor-2 play very important roles in fibroblast proliferation and collagen expression. These processes lead to the formation of joint adhesions through the SMAD and MAPK pathways, in which extracellular signal-regulated kinase (ERK)2 is considered to be crucial. Based on these theories, we examined the effects of a lentivirus-mediated small interfering RNA (siRNA) targeting ERK2 on the suppression of joint adhesion formation in vivo. The effects were assessed in vivo from different aspects including the adhesion score, histology and joint contracture angle. We found that the adhesions in the ERK2 siRNA group became soft and weak, and were easily stretched. Accordingly, the flexion contracture angles in the ERK2 siRNA group were also reduced (P < 0.05 compared with the control group). The animals appeared healthy, with no signs of impaired wound healing. In conclusion, local delivery of a lentivirus-mediated siRNA targeting ERK2 can ameliorate joint adhesion formation effectively and safely.

  1. ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo.

    Science.gov (United States)

    Yin, Gang; Fan, Jin; Zhou, Wei; Ding, Qingfeng; Zhang, Jun; Wu, Xuan; Tang, Pengyu; Zhou, Hao; Wan, Bowen; Yin, Guoyong

    2017-10-10

    mTOR is a valuable oncotarget for osteosarcoma. The anti-osteosarcoma activity by a novel mTOR kinase inhibitor, CZ415, was evaluated. We demonstrated that CZ415 potently inhibited survival and proliferation of known osteosarcoma cell lines (U2OS, MG-63 and SaOs2), and primary human osteosarcoma cells. Further, CZ415 provoked apoptosis and disrupted cell cycle progression in osteosarcoma cells. CZ415 treatment in osteosarcoma cells concurrently blocked mTORC1 and mTORC2 activation. Intriguingly, ERK-MAPK activation could be a major resistance factor of CZ415. ERK inhibition (by MEK162/U0126) or knockdown (by targeted ERK1/2 shRNAs) dramatically sensitized CZ415-induced osteosarcoma cell apoptosis. In vivo , CZ415 oral administration efficiently inhibited U2OS tumor growth in mice. Its activity was further potentiated with co-administration of MEK162. Collectively, we demonstrate that ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo . CZ415 could be further tested as a promising anti-osteosarcoma agent, alone or in combination of ERK inhibition.

  2. Commission of energy regulation. 2004 activity report; Commission de regulation de l'energie. Rapport d'activite 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  3. Experiences and challenges in developing European soil hydrological databases

    NARCIS (Netherlands)

    Lilly, A.; Nemes, A.; Wösten, J.H.M.; Hiederer, R.

    2014-01-01

    Development of the Hydraulic Properties of European Soils (HYPRES) database began in 1995 and was funded by the European Commission. The main aims of the project were to collate existing soil hydrological data held by Universities and Research Institutes into a single database and to use these data

  4. Institutional Aspects of European Commission Guidance in the Area of Antitrust Law

    OpenAIRE

    Ben Smulders

    2009-01-01

    From an institutional law perspective, the question arises how to qualify the more than thirty existing communications, notices and guidelines which the Commission has issued in the area of antitrust law.

  5. Region- or state-related differences in expression and activation of extracellular signal-regulated kinases (ERKs in naïve and pain-experiencing rats

    Directory of Open Access Journals (Sweden)

    Cui Xiu-Yu

    2007-07-01

    Full Text Available Abstract Background Extracellular signal-regulated kinase (ERK, one member of the mitogen-activated protein kinase (MAPK family, has been suggested to regulate a diverse array of cellular functions, including cell growth, differentiation, survival, as well as neuronal plasticity. Recent evidence indicates a role for ERKs in nociceptive processing in both dorsal root ganglion and spinal cord. However, little literature has been reported to examine the differential distribution and activation of ERK isoforms, ERK1 and ERK2, at different levels of pain-related pathways under both normal and pain states. In the present study, quantitative blot immunolabeling technique was used to determine the spatial and temporal expression of ERK1 and ERK2, as well as their activated forms, in the spinal cord, primary somatosensory cortex (SI area of cortex, and hippocampus under normal, transient pain and persistent pain states. Results In naïve rats, we detected regional differences in total expression of ERK1 and ERK2 across different areas. In the spinal cord, ERK1 was expressed more abundantly than ERK2, while in the SI area of cortex and hippocampus, there was a larger amount of ERK2 than ERK1. Moreover, phosphorylated ERK2 (pERK2, not phosphorylated ERK1 (pERK1, was normally expressed with a high level in the SI area and hippocampus, but both pERK1 and pERK2 were barely detectable in normal spinal cord. Intraplantar saline or bee venom injection, mimicking transient or persistent pain respectively, can equally initiate an intense and long-lasting activation of ERKs in all three areas examined. However, isoform-dependent differences existed among these areas, that is, pERK2 exhibited stronger response than pERK1 in the spinal cord, whereas ERK1 was more remarkably activated than ERK2 in the S1 area and hippocampus. Conclusion Taken these results together, we conclude that: (1 under normal state, while ERK immunoreactivity is broadly distributed in the rat

  6. The Provision of Services, Interest Margins and Loan Pricing in European Banking

    OpenAIRE

    Lepetit , Laetitia; Nys , Emmanuelle; Rous , Philippe; Tarazi , Amine

    2006-01-01

    This paper assesses the implications on bank interest margins of the expansion into non- traditional fee-based activities in European banking. We use a sample of 602 European commercial and cooperative banks from 1996 to 2002 and consider the total income shares of trading income and commission and fee income as measures of product diversification to explore loan pricing. Our results show that a higher income share from commission and fee activities is associated with lower margins and lower ...

  7. Role of a cysteine residue in the active site of ERK and the MAPKK family

    International Nuclear Information System (INIS)

    Ohori, Makoto; Kinoshita, Takayoshi; Yoshimura, Seiji; Warizaya, Masaichi; Nakajima, Hidenori; Miyake, Hiroshi

    2007-01-01

    Kinases of mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated protein kinase (ERK), represent likely targets for pharmacological intervention in proliferative diseases. Here, we report that FR148083 inhibits ERK2 enzyme activity and TGFβ-induced AP-1-dependent luciferase expression with respective IC 50 values of 0.08 and 0.05 μM. FR265083 (1'-2' dihydro form) and FR263574 (1'-2' and 7'-8' tetrahydro form) exhibited 5.5-fold less and no activity, respectively, indicating that both the α,β-unsaturated ketone and the conformation of the lactone ring contribute to this inhibitory activity. The X-ray crystal structure of the ERK2/FR148083 complex revealed that the compound binds to the ATP binding site of ERK2, involving a covalent bond to Sγ of ERK2 Cys166, hydrogen bonds with the backbone NH of Met108, Nζ of Lys114, backbone C=O of Ser153, Nδ2 of Asn154, and hydrophobic interactions with the side chains of Ile31, Val39, Ala52, and Leu156. The covalent bond motif in the ERK2/FR148083 complex assures that the inhibitor has high activity for ERK2 and no activity for other MAPKs such as JNK1 and p38MAPKα/β/γ/δ which have leucine residues at the site corresponding to Cys166 in ERK2. On the other hand, MEK1 and MKK7, kinases of the MAPKK family which also can be inhibited by FR148083, contain a cysteine residue corresponding to Cys166 of ERK2. The covalent binding to the common cysteine residue in the ATP-binding site is therefore likely to play a crucial role in the inhibitory activity for these MAP kinases. These findings on the molecular recognition mechanisms of FR148083 for kinases with Cys166 should provide a novel strategy for the pharmacological intervention of MAPK cascades

  8. Ferulic acid suppresses activation of hepatic stellate cells through ERK1/2 and Smad signaling pathways in vitro.

    Science.gov (United States)

    Xu, Tianjiao; Pan, Zhi; Dong, Miaoxian; Yu, Chunlei; Niu, Yingcai

    2015-01-01

    Hepatic stellate cells (HSCs) are the primary source of matrix components in hepatic fibrosis. Ferulic acid (FA) has antifibrotic potential in renal and cardiac disease. However, whether FA comprises inhibitive effects of HSCs activation remains to be clarified. This study aims at evaluating the hypothesis that FA inhibits extracellular matrix (ECM)-related gene expression by the interruption of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) or/and Smad signaling pathways in HSC-T6. Our results indicated that FA significantly inhibited both viability and activation of HSC-T6 cells in vitro. In addition, we demonstrated, for the first time, that FA dramatically inhibited the expression of α1(I) collagen (Col-I) and fibronectin at levels of transcription and translation. Moreover, FA treatment inhibited Smad transcriptional activity, as evaluated by transient transfection with a plasmid construction containing SMAD response element and the luciferase reporter gene. Furthermore, FA inhibition of HSCs activation involved in both focal adhesion kinase (FAK)-dependent ERK1/2 and Smad signaling pathways with independent manner. Blocking transforming growth factor-β by a neutralizing antibody caused a marked reduction in both ERK1/2 and Smad signaling. These results support FA as an effective therapeutic agent for the prevention and treatment of hepatic fibrosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Scientific report 1999

    International Nuclear Information System (INIS)

    1999-01-01

    The aim of this report is to outline the main developments of the 'Departement des Reacteurs Nucleaires' (DRN) during the year 1999. DRN is one of the CEA Institutions. This report is divided in three main parts: the DRN scientific programs, the scientific and technical publications (with abstracts in English) and economic data on staff, budget and communication. Main results of the Department for the year 1999 are presented giving information on the simulation of low mach number compressible flow, experimental irradiation of multi-materials, progress in the dry route conversion process of UF 6 to UO 2 , the neutronics, the CASCADE installation, the corium, the BWR type reactor cores technology, the reactor safety, the transmutation of americium and fuel cell flow studies, the crack propagation, the hybrid systems and the CEA sites improvement. (A.L.B.)

  10. Activation of ERK mitogen-activated protein kinase in human cells by the mycotoxin patulin

    International Nuclear Information System (INIS)

    Wu, T.-S.; Yu, F.-Y.; Su, C.-C.; Kan, J.-C.; Chung, C.-P.; Liu, B.-H.

    2005-01-01

    Patulin (PAT), a mycotoxin produced by certain species of Penicillium and Aspergillus, is often detectable in moldy fruits and their derivative products. PAT led to a concentration-dependent and time-dependent increase in phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure of HEK293 cells to concentrations above 5 μM PAT for 30 min induced ERK1/2 phosphorylation; activation of ERK1/2 was also observed after 24 h incubation with 0.05 μM of PAT. Treatment of human PBMCs for 30 min with 30 μM PAT dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors, U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells. In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation resulted in a significant decrease in levels of DNA damage, expressed as tail moment values, in the single cell gel electrophoresis assay. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, and the DNA synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15 μM PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells, PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway plays an important role in mediating PAT-induced DNA damage and egr-1 gene expression

  11. CityDelta: A model intercomparison study to explore the impact of emission reductions in European cities in 2010

    International Nuclear Information System (INIS)

    Cuvelier, C.; Thunis, P.; Vignati, E.; Vautard, R.; Hodzic, A.; Vautard, R.; Hodzic, A.; Amann, M.; Bessagnet, B.; Honore, C.; Rouil, L.; Bedogni, M.; Berkowicz, R.; Brandt, J.; Brocheton, F.; Peuch, V.H.; Builtjes, P.; Schaap, M.; Carnavale, C.; Volta, M.; Coppalle, A.; Denby, B.; Douros, J.; Moussiopoulos, N.; Graf, A.; Hellmuth, O.; Jonson, J.; Tarrason, L.; Wind, P.; Kerschbaumer, A.; Stern, R.; De Leeuw, F.; Minguzzi, E.; Pertot, C.; Pirovano, G.; Sauter, F.; White, L.; Zuber, A.

    2007-01-01

    This paper gives an overview of the set up, methodology and the obtained results of the CityDelta (phase 1 and 2) project. In the context of the Clean Air For Europe programme of the European Commission, the CityDelta project was designed to evaluate the impact of emission-reduction strategies on air quality at the European continental scale and in European cities. Ozone and particulate matter (PM) are the main components that have been studied. To achieve this goal, a model intercomparison study was organized with the participation of more than 20 modelling groups with a large number of modelling configurations. Two following main topics can be identified in the project. First, in order to evaluate their strengths and weaknesses, the participating models were evaluated against observations in a control year (1999). An accompanying paper will discuss in detail this evaluation aspect for four European cities. The second topic is the actual evaluation of the impact of emission reductions on levels of ozone and PM, with particular attention to the differences between large-scale and fine-scale models. An accompanying paper will discuss this point in detail. In this overview paper the main input to the intercomparison is described as well as the use of the ensemble approach. Finally, attention is given to the policy relevant issue on how to implement the urban air quality signal into large-scale air quality models through the use of functional relationships. (authors)

  12. Combined MEK and ERK inhibition overcomes therapy-mediated pathway reactivation in RAS mutant tumors.

    Directory of Open Access Journals (Sweden)

    Mark Merchant

    Full Text Available Mitogen-activated protein kinase (MAPK pathway dysregulation is implicated in >30% of all cancers, rationalizing the development of RAF, MEK and ERK inhibitors. While BRAF and MEK inhibitors improve BRAF mutant melanoma patient outcomes, these inhibitors had limited success in other MAPK dysregulated tumors, with insufficient pathway suppression and likely pathway reactivation. In this study we show that inhibition of either MEK or ERK alone only transiently inhibits the MAPK pathway due to feedback reactivation. Simultaneous targeting of both MEK and ERK nodes results in deeper and more durable suppression of MAPK signaling that is not achievable with any dose of single agent, in tumors where feedback reactivation occurs. Strikingly, combined MEK and ERK inhibition is synergistic in RAS mutant models but only additive in BRAF mutant models where the RAF complex is dissociated from RAS and thus feedback productivity is disabled. We discovered that pathway reactivation in RAS mutant models occurs at the level of CRAF with combination treatment resulting in a markedly more active pool of CRAF. However, distinct from single node targeting, combining MEK and ERK inhibitor treatment effectively blocks the downstream signaling as assessed by transcriptional signatures and phospho-p90RSK. Importantly, these data reveal that MAPK pathway inhibitors whose activity is attenuated due to feedback reactivation can be rescued with sufficient inhibition by using a combination of MEK and ERK inhibitors. The MEK and ERK combination significantly suppresses MAPK pathway output and tumor growth in vivo to a greater extent than the maximum tolerated doses of single agents, and results in improved anti-tumor activity in multiple xenografts as well as in two Kras mutant genetically engineered mouse (GEM models. Collectively, these data demonstrate that combined MEK and ERK inhibition is functionally unique, yielding greater than additive anti-tumor effects and

  13. European consumers and nutrition labelling

    DEFF Research Database (Denmark)

    Wills, Josephine M.; Grunert, Klaus G.; Celemín, Laura Fernández

    2009-01-01

    Nutrition labelling of food in Europe is not compulsory, unless a nutrition or health claim is made for the product. The European Commission is proposing mandatory nutrition labelling, even front of pack labelling with nutrition information. Yet, how widespread is nutrition labelling in the EU...

  14. The Role of ERK1/2 in the Development of Diabetic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Zheng Xu

    2016-12-01

    Full Text Available Diabetes mellitus is a chronic metabolic condition that affects carbohydrate, lipid and protein metabolism and may impair numerous organs and functions of the organism. Cardiac dysfunction afflicts many patients who experience the oxidative stress of the heart. Diabetic cardiomyopathy (DCM is one of the major complications that accounts for more than half of diabetes-related morbidity and mortality cases. Chronic hyperglycemia and hyperlipidemia from diabetes mellitus cause cardiac oxidative stress, endothelial dysfunction, impaired cellular calcium handling, mitochondrial dysfunction, metabolic disturbances, and remodeling of the extracellular matrix, which ultimately lead to DCM. Although many studies have explored the mechanisms leading to DCM, the pathophysiology of DCM has not yet been fully clarified. In fact, as a potential mechanism, the associations between DCM development and mitogen-activated protein kinase (MAPK activation have been the subjects of tremendous interest. Nonetheless, much remains to be investigated, such as tissue- and cell-specific processes of selection of MAPK activation between pro-apoptotic vs. pro-survival fate, as well as their relation with the pathogenesis of diabetes and associated complications. In general, it turns out that MAPK signaling pathways, such as extracellular signal-regulated kinase 1/2 (ERK1/2, c-Jun N-terminal protein kinase (JNK and p38 MAP kinase, are demonstrated to be actively involved in myocardial dysfunction, hypertrophy, fibrosis and heart failure. As one of MAPK family members, the activation of ERK1/2 has also been known to be involved in cardiac hypertrophy and dysfunction. However, many recent studies have demonstrated that ERK1/2 signaling activation also plays a crucial role in FGF21 signaling and exerts a protective environment of glucose and lipid metabolism, therefore preventing abnormal healing and cardiac dysfunction. The duration, extent, and subcellular compartment of ERK1

  15. Differential induction of c-Fos and phosphorylated ERK by a noxious stimulus after peripheral nerve injury.

    Science.gov (United States)

    Tabata, Mitsuyasu; Terayama, Ryuji; Maruhama, Kotaro; Iida, Seiji; Sugimoto, Tomosada

    2018-03-01

    In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury. We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury. A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury. ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.

  16. Fiscal policy surveillance in the enlarged European Union: Procedural checks or simple arithmetic?

    NARCIS (Netherlands)

    Groenendijk, Nico; Batten, Jonathan A.; Kearney, Colm

    2006-01-01

    In its recommendation on the 2004 update of the Broad Economic Policy Guidelines (BEPGs), the European Commission (2004) issued country-specific recommendations for fiscal policy in the Central and Eastern European (CEE) countries that have recently joined the European Union (EU) (henceforth the

  17. Blockade of the ERK pathway markedly sensitizes tumor cells to HDAC inhibitor-induced cell death

    International Nuclear Information System (INIS)

    Ozaki, Kei-ichi; Minoda, Ai; Kishikawa, Futaba; Kohno, Michiaki

    2006-01-01

    Constitutive activation of the extracellular signal-regulated kinase (ERK) pathway is associated with the neoplastic phenotype of a large number of human tumor cells. Although specific blockade of the ERK pathway by treating such tumor cells with potent mitogen-activated protein kinase/ERK kinase (MEK) inhibitors completely suppresses their proliferation, it by itself shows only a modest effect on the induction of apoptotic cell death. However, these MEK inhibitors markedly enhance the efficacy of histone deacetylase (HDAC) inhibitors to induce apoptotic cell death: such an enhanced cell death is observed only in tumor cells in which the ERK pathway is constitutively activated. Co-administration of MEK inhibitor markedly sensitizes tumor cells to HDAC inhibitor-induced generation of reactive oxygen species, which appears to mediate the enhanced cell death induced by the combination of these agents. These results suggest that the combination of MEK inhibitors and HDAC inhibitors provides an efficient chemotherapeutic strategy for the treatment of tumor cells in which the ERK pathway is constitutively activated

  18. The Rise of the Information Society amongst European Academics

    Science.gov (United States)

    Salajan, Florin D.

    2008-01-01

    This study investigates the information society discourse in the European Union in relation to the European Commission's eLearning programmes, based on selected academics' conceptualisation of the term. It reveals a mixed picture of the perceptions that academics have of the information society in their respective countries. The findings indicate…

  19. Contribution to the european discussion on the energy strategy

    International Nuclear Information System (INIS)

    Revol, H.; Valade, J.

    2001-01-01

    If no change occurs, the European Union will cover in 2020, 70% of its energy need by importation, for 50% today. This situation leads to a discussion on the energy dependence. In this context the European Commission provoked a discussion by publishing a ''green book'' on the european strategy concerning the energy supply. This document presents the point of view of the Senate Energy Study Group. (A.L.B.)

  20. European wind turbine procedure development blade test methods and techniques

    Energy Technology Data Exchange (ETDEWEB)

    Bulder, B H; Dam, J J.D. van; Delft, D R.V. van [and others

    1999-03-01

    In this paper the preliminary results obtained by performing the second task of the `European Wind Turbine Testing Procedure Development` project are presented. This project is performed within and with financial support of the Standards, Measurements and Testing programme of the European Commission. (au)

  1. The democratic accountability of the European Central Bank : A comment on two fairy-tales

    NARCIS (Netherlands)

    De Haan, J; Eijffinger, SCW

    The European Central Bank (ECB) is widely considered to be (legally) independent. Buiter (1999) critizes the ECB for its lack of democratic accountability, which he does not define in a very precise way. Issing (1999) replies to some of the points raised by Buiter and argues that the ECB is both

  2. Efficient inhibition of fibroblast proliferation and collagen expression by ERK2 siRNAs

    International Nuclear Information System (INIS)

    Li, Fengfeng; Fan, Cunyi; Cheng, Tao; Jiang, Chaoyin; Zeng, Bingfang

    2009-01-01

    Transforming growth factor-β1 and fibroblast growth factor-2 play very important roles in fibroblast proliferation and collagen expression. These processes lead to the formation of joint adhesions through the SMAD and MAPK pathways, in which ERK2 is supposed to be crucial. Based on these assumptions, lentivirus (LV)-mediated small interfering RNAs (siRNAs) targeting ERK2 were used to suppress the proliferation and collagen expression of rat joint adhesion tissue fibroblasts (RJATFs). Among four siRNAs examined, siRNA1 caused an 84% reduction in ERK2 expression (p < 0.01) and was selected as the most efficient siRNA for use in this study. In subsequent experiments, significant downregulation of types I and III collagen were observed by quantitative RT-PCR and Western blot analyses. MTT assays and flow cytometry revealed marked inhibition of RJATF proliferation, but no apoptosis. In conclusion, LV-mediated ERK2 siRNAs may represent novel therapies or drug targets for preventing joint adhesion formation.

  3. The three α1-adrenoceptor subtypes show different spatio-temporal mechanisms of internalization and ERK1/2 phosphorylation.

    Science.gov (United States)

    Perez-Aso, M; Segura, V; Montó, F; Barettino, D; Noguera, M A; Milligan, G; D'Ocon, P

    2013-10-01

    We analyzed the kinetic and spatial patterns characterizing activation of the MAP kinases ERK 1 and 2 (ERK1/2) by the three α1-adrenoceptor (α1-AR) subtypes in HEK293 cells and the contribution of two different pathways to ERK1/2 phosphorylation: protein kinase C (PKC)-dependent ERK1/2 activation and internalization-dependent ERK1/2 activation. The different pathways of phenylephrine induced ERK phosphorylation were determined by western blot, using the PKC inhibitor Ro 31-8425, the receptor internalization inhibitor concanavalin A and the siRNA targeting β-arrestin 2. Receptor internalization properties were studied using CypHer5 technology and VSV-G epitope-tagged receptors. Activation of α1A- and α1B-ARs by phenylephrine elicited rapid ERK1/2 phosphorylation that was directed to the nucleus and inhibited by Ro 31-8425. Concomitant with phenylephrine induced receptor internalization α1A-AR, but not α1B-AR, produced a maintained and PKC-independent ERK phosphorylation, which was restricted to the cytosol and inhibited by β-arrestin 2 knockdown or concanavalin A treatment. α1D-AR displayed constitutive ERK phosphorylation, which was reduced by incubation with prazosin or the selective α1D antagonist BMY7378. Following activation by phenylephrine, α1D-AR elicited rapid, transient ERK1/2 phosphorylation that was restricted to the cytosol and not inhibited by Ro 31-8425. Internalization of the α1D-AR subtype was not observed via CypHer5 technology. The three α1-AR subtypes present different spatio-temporal patterns of receptor internalization, and only α1A-AR stimulation translates to a late, sustained ERK1/2 phosphorylation that is restricted to the cytosol and dependent on β-arrestin 2 mediated internalization. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Annual report 1999; Rapport annuel 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    This report presents the activities of the Cogema group, its reports on management and its financial situation for the year 1999: boards of directors, executive committee and steering committee, main consolidated data, year 1999 highlights, group activities (mining-chemistry, enrichment, reprocessing-recycling and associated transport operations, engineering, services to industry), organization chart of the consolidated Cogema group, financial statements, directory. (J.S.)

  5. ERF is a Potential ERK-Modulated Tumor Suppressor in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0277 TITLE: ERF is a Potential ERK-Modulated Tumor Suppressor in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr...Rohit Bose CONTRACTING ORGANIZATION: Sloan Kettering Institute for Cancer Research New York NY 10065 REPORT DATE: October 2017 TYPE OF REPORT...4. TITLE AND SUBTITLE ERF is a Potential ERK-Modulated Tumor Suppressor in Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0277 5c

  6. THE ORIGIN OF ASTEROID 162173 (1999 JU3)

    International Nuclear Information System (INIS)

    Campins, Humberto; De León, Julia; Morbidelli, Alessandro; Gayon-Markt, Julie; Delbo, Marco; Michel, Patrick; Licandro, Javier

    2013-01-01

    Near-Earth asteroid (162173) 1999 JU 3 (henceforth JU 3 ) is a potentially hazardous asteroid and the target of the Japanese Aerospace Exploration Agency's Hayabusa-2 sample return mission. JU 3 is also a backup target for two other sample return missions: NASA's OSIRIS-REx and the European Space Agency's Marco Polo-R. We use dynamical information to identify an inner-belt, low-inclination origin through the ν 6 resonance, more specifically, the region with 2.15 AU 3 is 0.07 ± 0.01, and this inner-belt region contains four well-defined low-albedo asteroid families (Clarissa, Erigone, Polana, and Sulamitis), plus a recently identified background population of low-albedo asteroids outside these families. Only two of these five groups, the background and the Polana family, deliver JU 3 -sized asteroids to the ν 6 resonance, and the background delivers significantly more JU 3 -sized asteroids. The available spectral evidence is also diagnostic; the visible and near-infrared spectra of JU 3 indicate it is a C-type asteroid, which is compatible with members of the background, but not with the Polana family because it contains primarily B-type asteroids. Hence, this background population of low-albedo asteroids is the most likely source of JU 3

  7. Altered ERK1/2 Signaling in the Brain of Learned Helpless Rats: Relevance in Vulnerability to Developing Stress-Induced Depression

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2016-01-01

    Full Text Available Extracellular signal-regulated kinase 1/2- (ERK1/2- mediated cellular signaling plays a major role in synaptic and structural plasticity. Although ERK1/2 signaling has been shown to be involved in stress and depression, whether vulnerability to develop depression is associated with abnormalities in ERK1/2 signaling is not clearly known. The present study examined ERK1/2 signaling in frontal cortex and hippocampus of rats that showed vulnerability (learned helplessness, (LH or resiliency (non-learned helplessness, (non-LH to developing stress-induced depression. In frontal cortex and hippocampus of LH rats, we found that mRNA and protein expressions of ERK1 and ERK2 were significantly reduced, which was associated with their reduced activation and phosphorylation in cytosolic and nuclear fractions, where ERK1 and ERK2 target their substrates. In addition, ERK1/2-mediated catalytic activities and phosphorylation of downstream substrates RSK1 (cytosolic and nuclear and MSK1 (nuclear were also lower in the frontal cortex and hippocampus of LH rats without any change in their mRNA or protein expression. None of these changes were evident in non-LH rats. Our study indicates that ERK1/2 signaling is differentially regulated in LH and non-LH rats and suggests that abnormalities in ERK1/2 signaling may be crucial in the vulnerability to developing depression.

  8. N.6 report realized for the economical Affairs Commission on the law project, adopted by the National Assembly after urgency declaration, relative to the energy sector; N.6 rapport fait au nom de la commission des Affaires economiques sur le projet de loi, adopte par l'Assemblee Nationale apres declaration d'urgence, relatif au secteur de l'energie

    Energy Technology Data Exchange (ETDEWEB)

    Poniatowski, L

    2006-10-15

    This law project concerns the organization of the french energy sector and the definition of the public utilities. After a presentation of the juridical environment of the european energy sector, the author shows, in the framework of the world energy situation, that the evolution of the juridical aspects of Gaz de France answers a real necessity. He then presents the initial law project dispositions, the modifications of the National Assembly and the amendment of the commission. (A.L.B.)

  9. 26 CFR 1.985-8 - Special rules applicable to the European Monetary Union (conversion to euro).

    Science.gov (United States)

    2010-04-01

    ...-8 Special rules applicable to the European Monetary Union (conversion to euro). (a) Definitions—(1... euro is substituted for that legacy currency (in accordance with the Treaty on European Union); and (B... pursuant to the Treaty on European Union signed February 7, 1992. Assume that on January 1, 1999, X changes...

  10. Public health ethical perspectives on the values of the European Commission's White Paper "Together for Health".

    Science.gov (United States)

    Schröder-Bäck, Peter; Clemens, Timo; Michelsen, Kai; Schulte in den Bäumen, Tobias; Sørensen, Kristine; Borrett, Glenn; Brand, Helmut

    2012-06-01

    In 2007 the European Commission issued the White Paper: "Together for Health". Considered the EU Health Strategy for the years 2008-2013, it offers the cornerstones for setting priorities in EU health actions. The public health framework offered in this strategy is explicitly built on shared values--including the overarching values of universality, access to good quality care, equity and solidarity that reacted to certain health care challenges within the EU. This article analyses the Health Strategy via its ethical scope and considers implications for future health policy making. The Health Strategy and related documents are scrutinised to explore how the mentioned values are defined and enfolded. Additionally, scientific databases are searched for critical discussions of the value base of the Health Strategy. The results are discussed and reasoned from a public health ethical perspective. The Health Strategy is barely documented and discussed in the scientific literature. Furthermore, no attention was given to the value base of the Health Strategy. Our analysis shows that the mentioned values are particularly focussed on health care in general rather than on public health in particular. Besides this, the given values of the Health Strategy are redundant. An additional consideration of consequentialist public health ethics values would normatively strengthen a population-based health approach of EU health policy making.

  11. Multiple Sources of Pressure for Change: The Barroso Commission and Energy Policy for an Enlarged EU

    Directory of Open Access Journals (Sweden)

    Jan Frederik Braun

    2009-11-01

    Full Text Available This article presents a preliminary analysis of how and why the role, work and status of the European Commission are changing in an enlarged European Union. It does so by focusing on multiple sources of pressure for change. These include: enlargement, new modes of governance, administrative reforms and changed leadership under Barroso. Combined, though not interlinked, these multiple sources of pressure are evidence of the increasing difficulty for the Commission to design and propose Community-wide answers to complex challenges in a more diverse Union. For this reason, the Commission under Barroso relies less on its traditional monopoly power to propose formal legislation and more on non-traditional modes of policy-making. Energy policy, especially its external dimension, constitutes a policy field that has been affected by enlargement, i.e. characterised by an increasing heterogeneity of needs and preferences among the member states. Not only does it resists Community-wide answers, it also allows the Commission, as an agent, to make use of bureaucratic drifts, i.e. exploit its strategic position in the EU’s governance system and use of a range of formal and informal resources of expertise. To deliver sustainable European added value to this complex policy area, however, the Commission must focus more on pragmatic policy results by making smart use of the EU’s increasing asymmetry, diversity and subsidiarity in a bottom-up approach. A non-legislative approach can serve as a modus vivendi to keep the momentum going in the Union’s difficult struggle to establish a workable energy regime.

  12. Professional Burnout in European Young Oncologists

    DEFF Research Database (Denmark)

    Banerjee, Sutanuka; Califano, R; Corral, Javier

    2017-01-01

    ≤40 (YOs). Methods: A survey was conducted using the validated Maslach Burnout Inventory (MBI) and additional questions exploring work/lifestyle factors. Statistical analyses were performed to identify factors associated with burnout. Results: 737 surveys (all ages) were collected from 41 European......Background: Burnout in health care professionals could have serious negative consequences on quality of patient care, professional satisfaction and personal life. Our aim was to investigate the burnout prevalence, work and lifestyle factors potentially affecting burnout amongst European oncologists...... = 0.0001 ) and low accomplishment was highest in the 26-30 age group ( p work/life balance, access to support services, living alone and inadequate vacation time remained independent burnout factors ( p 

  13. Report made on behalf of the commission of economic affairs, of environment and territory, about the resolution proposal (n.1656) of Mr Andre Schneider and Mr Philippe Tourtelier, referees of the commission in charge of European affairs, about the second strategic analysis of the energy policy (E 4140, E 4106, E 4107, E 4108, E 4143 and E 4222); Rapport fait au nom de la commission des affaires economiques, de l'environnement et du territoire sur la proposition de resolution (n.1656) de MM. Andre Schneider et Philippe Tourtelier, rapporteurs de la commission chargee des affaires europeennes, sur la deuxieme analyse strategique de la politique energetique (E 4140, E 4106, E 4107, E 4108, E 4143 et E 4222)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-05-15

    This report aims at examining a resolution proposal explained by the commission in charge of European affairs and concerning the second strategic analysis of the energy policy which finds a consistency through the European action plan for the energy security and solidarity. The resolution proposal takes cognizance of the strategic trends proposed by the European Commission for the energy policy of the European Union at the 2020 and 2050 vistas, and invites the European Union and its member states to implement these trends. It stresses on the necessity to learn the lessons of the gas crisis of January 2009 and to diversify the gas supply sources of the member states. It recalls that a re-balancing of Europe's energy consumption in favour of low-carbon and renewable energies together with an improvement of energy efficiency is an urgent necessity and requires a coordination between the different national R and D programs and a communication effort, in particular in France. It encourages the proposal of implementation of a European nuclear safety framework and approves the priority given by the European Union to the development of power and gas interconnected networks in the respect of populations and territories. (J.S.)

  14. Legal contamination of food products in case of nuclear accident. The CRIIRAD criticizes the outrageous work performed by Euratom experts, and calls for a massive mobilisation against the project of the European Commission

    International Nuclear Information System (INIS)

    Castanier, Corinne

    2015-01-01

    After having recalled the content of the project of the European Commission on the definition of maximum permissible levels of radioactive contamination of food products which will be applied in case of nuclear accident, this report first outlines that the associated risk levels are unacceptable (the maximum dose limit would not be respected by far). The authors outline numerous extremely severe anomalies and errors which occurred in the process of elaboration of the project. They try to identify responsibilities for these errors, and wander whether they are due to incompetence, or made on purpose as they always go in the same direction. The CRIIRAD therefore calls for a European mobilisation to sign a petition for a complete review of the applicable regulation. Letters written to or by members of European institutions are provided

  15. The European Photovoltaic Technology Platform

    International Nuclear Information System (INIS)

    Nowak, S.; Aulich, H.; Bal, J.L.; Dimmler, B.; Garnier, A.; Jongerden, G.; Luther, J.; Luque, A.; Milner, A.; Nelson, D.; Pataki, I.; Pearsall, N.; Perezagua, E.; Pietruszko, S.; Rehak, J.; Schellekens, E.; Shanker, A.; Silvestrini, G.; Sinke, W.; Willemsen, H.

    2006-05-01

    The European Photovoltaic Technology Platform is one of the European Technology Platforms, a new instrument proposed by the European Commission. European Technology Platforms (ETPs) are a mechanism to bring together all interested stakeholders to develop a long-term vision to address a specific challenge, create a coherent, dynamic strategy to achieve that vision and steer the implementation of an action plan to deliver agreed programmes of activities and optimise the benefits for all parties. The European Photovoltaic Technology Platform has recently been established to define, support and accompany the implementation of a coherent and comprehensive strategic plan for photovoltaics. The platform will mobilise all stakeholders sharing a long-term European vision for PV, helping to ensure that Europe maintains and improves its industrial position. The platform will realise a European Strategic Research Agenda for PV for the next decade(s). Guided by a Steering Committee of 20 high level decision-makers representing all relevant European PV Stakeholders, the European PV Technology Platform comprises 4 Working Groups dealing with the subjects policy and instruments; market deployment; science, technology and applications as well as developing countries and is supported by a secretariat

  16. Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine.

    Science.gov (United States)

    Nagarajah, James; Le, Mina; Knauf, Jeffrey A; Ferrandino, Giuseppe; Montero-Conde, Cristina; Pillarsetty, Nagavarakishore; Bolaender, Alexander; Irwin, Christopher; Krishnamoorthy, Gnana Prakasam; Saqcena, Mahesh; Larson, Steven M; Ho, Alan L; Seshan, Venkatraman; Ishii, Nobuya; Carrasco, Nancy; Rosen, Neal; Weber, Wolfgang A; Fagin, James A

    2016-11-01

    Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer.

  17. IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK

    Directory of Open Access Journals (Sweden)

    Karsten Schmidt

    2017-01-01

    Full Text Available The pathology of inclusion body myositis (IBM involves an inflammatory response and β-amyloid deposits in muscle fibres. It is believed that MAP kinases such as the ERK signalling pathway mediate the inflammatory signalling in cells. Further, there is evidence that autophagic activity plays a crucial role in the pathogenesis of IBM. Using a well established in vitro model of IBM, the autophagic pathway, MAP kinases, and accumulation of β-amyloid were examined. We demonstrate that stimulation of muscle cells with IL-1β and IFN-γ led to an increased phosphorylation of ERK. The ERK inhibitor PD98059 diminished the expression of proinflammatory markers as well as the accumulation of β-amyloid. In addition, IL-1β and IFN-γ led to an increase of autophagic activity, upregulation of APP, and subsequent accumulation of β-sheet aggregates. Taken together, the data demonstrate that the ERK pathway contributes to formation of β-amyloid and regulation of autophagic activity in muscle cells exposed to proinflammatory cell stress. This suggests that ERK serves as an important mediator between inflammatory mechanisms and protein deposition in skeletal muscle and is a crucial element of the pathology of IBM.

  18. European energy policy: A new debate and an opportunity to help shape Europe's energy choices

    International Nuclear Information System (INIS)

    Daifuku, Karen

    2001-01-01

    On 28 November 2000, the European Commission adopted a Green Paper on a strategy for the security of energy supply. A consultation and debate will follow and interested parties have the right to submit comments relating to issues within the document. When the debate is brought to a close, a White Paper will be issued by the European Commission, which will then be sent to the European Parliament and Council. The White Paper will represent an official proposal reflecting all changes to the Green Paper already issued. The European Parliament will then adopt an opinion on the White Paper, which will then be communicated to the European Commission who in turn will adopt a draft directive or legislation. It will again be submitted to the European Parliament and Council for approval. Let us make no mistake. What might appear as a cumbersome process far from the grassroots preoccupations, will in fact affect all European citizens in the end. So in this democratic consultation, it is crucial that policies be established in an informed, educated manner. It is therefore the duty of the industry to communicate in a transparent fashion about its benefits and drawbacks so that in the end, the best decisions will be based on facts and not on fear

  19. How to Enforce European Law

    DEFF Research Database (Denmark)

    Rasmussen, Morten

    2017-01-01

    This article explores the well known saga of the European Court of Justice’s introduction of direct effect of Council directives on basis of new comprehensive archival research. The expansion of the doctrine of direct effect to include directives was part of a drive of the Legal Service of the Eu......This article explores the well known saga of the European Court of Justice’s introduction of direct effect of Council directives on basis of new comprehensive archival research. The expansion of the doctrine of direct effect to include directives was part of a drive of the Legal Service...... of the European Commission and the ECJ to strengthen the enforcement of European law. This threatened the deeper balance of competences between the European Community and its member states and consequently led to a sharp response from the national parliaments and courts. The force of these responses and the deep...

  20. European integration in education of the EQF and National Qualifications Frameworks : challenges and achievements by Malta

    OpenAIRE

    Gatt, Suzanne; Cippitani, Roberto;

    2012-01-01

    Europe, through the European Commission and the EU Member States have long recognised education as the key to strengthening the European economy and for promoting social cohesion in society (Green et al, 2003). It was with the Maastricht Treaty, back in the beginning of the 90s that the EU expanded its remit beyond being only an economic agreement. It is for this reason that the White Paper on Growth, Competitiveness and employment (European Commission, 1993) recognised education and training...