WorldWideScience

Sample records for policy recommendations cb

  1. From micronutrient recommendations to policy

    DEFF Research Database (Denmark)

    Timotijevic, Lada; Raats, Monique M.; Barnett, Julie

    2010-01-01

    the Eurreca network of excellence (commissioned by the European Commission), the research involved in-depth desk research of key documents and communication channels linked to the process of setting micronutrient recommendations across seven countries: the United Kingdom, Norway, Denmark, Germany, Spain......, the Czech Republic and Hungary. Results: Stakeholder engagement is recognized by most countries as an important aspect of the process of setting micronutrient recommendations and their translation into policy, although there is notable variation in the extent to which this has been achieved across the seven...... of involvement include historical sociopolitical context; the extent to which food and nutrition are key policy agenda; and the relative power of stakeholders in influencing food and nutrition policy....

  2. Policy Recommendations on Decentralization, Local Power and ...

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

    2010-12-22

    Policy Recommendations on Decentralization, Local Power and Women's Rights. December 22, 2010. Image. The present document comprises a set of policy recommendations that define a global agenda on gender and decentralization. It emerged from the analysis and experiences shared during the Conference and the ...

  3. Policy Recommendations on Decentralization, Local Power and ...

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

    Policy Recommendations on Decentralization, Local Power and Women's Rights. 22 décembre 2010. Image. The present document comprises a set of policy recommendations that define a global agenda on gender and decentralization. It emerged from the analysis and experiences shared during the Conference and the ...

  4. Recommendations for an energy policy for Australia

    International Nuclear Information System (INIS)

    1977-10-01

    Over the next few years, Australia must modify its dependence on natural oil and place greater reliance on other fossil fuels and renewable energy sources. The recommendations contained in this report are the result of two years of study, and the long term energy prospects for Australia and energy resource policies for coal, liquid fuels, nuclear energy, solar energy and natural gas are considered in detail. Energy conservation policies and the identification of areas where energy research, development and demonstration need to be undertaken are also covered. (J.R.)

  5. Policy analysis and recommendations for the DCM research data exchange.

    Science.gov (United States)

    2012-07-01

    This report is a policy analysis and set of recommendations regarding open data policies and policies for new, transformative data environments that are being developed as part of the Connected Vehicle research program. It is presented in three secti...

  6. Best practices and recommendations on policy packaging

    DEFF Research Database (Denmark)

    Fearnley, Nils; Longva, Frode; Ramjerdi, Farideh

    2011-01-01

    This report, which is the final deliverable of the Optic project (Optimal Policies for Transport In Combination), summarises two years of collaborative research into the policy process of combining individual measures into policy packages. Six stages of the policy process are identified. This rep...

  7. Nuclear Cyber Security Issues and Policy Recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Cheol-Kwon; Lee, Dong-Young [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, Na-Young; Hwang, Young-Soo [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2015-10-15

    The cyber-attack against computer systems causes the loss of function which brings about the big economic loss, and it becomes a national-wide issue. In recent days the cyber threat has occurred in the national critical infrastructure around the world. In the nuclear industry, while discussing responses to various threats against nuclear facilities since 2006, cyber-terrorism was also discussed. But at that time, cyber-attacks against control networks in nuclear facilities were not seriously considered because those networks were isolated from the Internet thoroughly and it was evaluated that cyber penetration would not be possible. However Stuxnet worm virus which attacked Iran's nuclear facilities confirmed that the cyber security problem could occur even in other nuclear facilities. The facilities were isolated from the Internet. After the cyber incident, we began to discuss the topic of NPP cyber security. It is very difficult to predict whether or when or how the cyber-attack will be occurred, which is a characteristic of cyber-attack. They could be always detected only after when an incident had occurred. This paper summarizes the report, 'Nuclear Cyber Security Issues and Policy Recommendations' by issue committee in the Korea Nuclear Society, which reviewed the cyber security framework for nuclear facilities in the Republic of Korea being established to prevent nuclear facilities from cyber-attacks and to respond systematically. As a result this paper proposes several comments to improve the security and furthermore safety of nuclear facilities Digital technology will be used more widely at the national critical infrastructure including nuclear facilities in the future, and moreover wireless technologies and mobile devices will be soon introduced to nuclear industry. It is therefore anticipated that the rapid advance in digital technology will accelerate the opportunity of hacking these facilities.

  8. Nuclear Cyber Security Issues and Policy Recommendations

    International Nuclear Information System (INIS)

    Lee, Cheol-Kwon; Lee, Dong-Young; Lee, Na-Young; Hwang, Young-Soo

    2015-01-01

    The cyber-attack against computer systems causes the loss of function which brings about the big economic loss, and it becomes a national-wide issue. In recent days the cyber threat has occurred in the national critical infrastructure around the world. In the nuclear industry, while discussing responses to various threats against nuclear facilities since 2006, cyber-terrorism was also discussed. But at that time, cyber-attacks against control networks in nuclear facilities were not seriously considered because those networks were isolated from the Internet thoroughly and it was evaluated that cyber penetration would not be possible. However Stuxnet worm virus which attacked Iran's nuclear facilities confirmed that the cyber security problem could occur even in other nuclear facilities. The facilities were isolated from the Internet. After the cyber incident, we began to discuss the topic of NPP cyber security. It is very difficult to predict whether or when or how the cyber-attack will be occurred, which is a characteristic of cyber-attack. They could be always detected only after when an incident had occurred. This paper summarizes the report, 'Nuclear Cyber Security Issues and Policy Recommendations' by issue committee in the Korea Nuclear Society, which reviewed the cyber security framework for nuclear facilities in the Republic of Korea being established to prevent nuclear facilities from cyber-attacks and to respond systematically. As a result this paper proposes several comments to improve the security and furthermore safety of nuclear facilities Digital technology will be used more widely at the national critical infrastructure including nuclear facilities in the future, and moreover wireless technologies and mobile devices will be soon introduced to nuclear industry. It is therefore anticipated that the rapid advance in digital technology will accelerate the opportunity of hacking these facilities

  9. 25 energy efficiency policy recommendations. 2011 update

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    The IEA recommends that G8 leaders adopt and urgently implement this package of measures to significantly enhance energy efficiency. This package was developed under the Gleneagles G8 Plan of Action, which mandates the pursuit of a clean, clever and competitive energy future.

  10. Problems and Recommendations over Tax Policies

    Directory of Open Access Journals (Sweden)

    Engin ONER

    2015-03-01

    Full Text Available Tax policy is a tool that state uses on economic, social and financial fields. Funding public expenditure is its financial goal, providing economic stability and development is its economic goal and contributing to fair distribution of income and wealth is its social goal. In result of high debt load, rupture between taxes and economic goals, being not established a document and registration order and lacking in management of administration and control functions, significantly increasing tax loss and evasion and factors such as unfair competition that it leads to show that our tax system is ineffective and have a negative influence in economic life. In order to succeed in tax policies, “taxes should be minimalistic, should consider the ability to pay with respect to income level, should prevent the luxurious consumption and waste, should decrease tax evasion and loss, should tax informal economy, should encourage export, employment and development, should be reformed in a permanent way and implementing tax consciousness into whole society” is inevitable.

  11. Patient dumping. Status, implications, and policy recommendations.

    Science.gov (United States)

    Ansell, D A; Schiff, R L

    1987-03-20

    Patient dumping, or the transfer of patients from private to public hospitals because of economic or social factors, is on the increase throughout the United States. Focusing on the dumping of patients by hospital emergency departments, the authors examine the economic, ethical, legal, and medical aspects of the problem. Although 22 states and the federal government have enacted statutes requiring hospitals to provide emergency care regardless of ability to pay and requiring that patients be stabilized before transfer to another hospital, Ansell and Schiff contend that even the best of these laws are deficient in defining such terms as "emergency" and "patient stability" and that monitoring and enforcement of existing laws and the guidelines of the American College of Emergency Physicians are inadequate. They propose a policy that no patient in need of emergency hospitalization should be denied admission or transferred for economic reasons.

  12. Progress Implementing the IEA 25 Energy Efficiency Policy Recommendations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    Significantly improving energy efficiency remains a priority for all countries. Meetings of G8 leaders and IEA ministers reaffirmed the critical role that improved energy efficiency can play in addressing energy security, environmental and economic challenges. Many IEA publications have also documented the essential role of energy efficiency. For example, the World Energy Outlook and the Energy Technology Perspectives reports identify energy efficiency as the most significant contributor to achieving energy security, economic and environmental goals. Energy efficiency is clearly the “first fuel” in the delivery of energy services in the coming low-carbon energy future. To support governments in their implementation of energy efficiency, the IEA recommended the adoption of specific energy efficiency policy measures to the G8 summits in 2006, 2007 and 2008. The consolidated set of recommendations to these summits is known as the ‘IEA 25 energy efficiency policy recommendations’ because it covers 25 fields of action across seven priority areas: cross-sectoral activity, buildings, appliances, lighting, transport, industry and energy utilities. The IEA estimates that if implemented globally without delay, the proposed actions could save as much as 7.6 giga tonnes (Gt) CO2/year by 2030 – almost 1.5 times the current annual carbon dioxide (CO2) emissions of the United States. The IEA 25 energy efficiency policy recommendations were developed to address policy gaps and priorities. This has two implications. First, the recommendations do not cover the full range of energy efficiency policy activity possible. Rather, they focus on priority energy efficiency policies identified by IEA analysis. Second, while IEA analysis, the energy efficiency professional literature and engagement with experts clearly demonstrate the broad benefits of these IEA priority measures, the recommendations are not weighted to reflect the different energy end-use make up of different

  13. DEVELOPMENT OF FRANCHISING IN CROATIA OBSTACLES AND POLICY RECOMMENDATIONS

    OpenAIRE

    Alpeza, Mirela; Erceg, Aleksandar; Oberman Peterka, Sunčica

    2015-01-01

    Franchising is very popular growth model but despite the wide application of franchising in the developed countries of the world, its impact on the Croatian economy is still marginal. The purpose of this research is to identify the obstacles and challenges to a wider application of franchising in Croatia and generate policy recommendations for removing the identified obstacles. Obstacles and recommendations are identified on the basis of a conducted longitudinal qualitative research, the firs...

  14. Recommendation 1074 on family policy, 3 May 1988.

    Science.gov (United States)

    1988-01-01

    This document contains a 1988 Recommendation of the Council of Europe on family policy in which the Council recognizes the profound changes which have occurred in family structure and the increased tensions within families caused by such factors as poverty and crime. The Council notes, however, that the family remains a popular institution for young people and that some changes, such as the replacement of the marriage-alliance with the marriage-partnership, have been positive. Also the family is the best place for nurturing human relationships and caring for children and the elderly. Both "legitimate" and "de facto" families must be recognized, and the emancipation of women requires a democratization of the family which implies equality and protects the exercise of free choice among its members. After drawing attention to earlier Recommendations, the Council recommends that the governments of member states base their preparation of family policy on specific proposals: 1) legislation should protect equality between the sexes and children's rights, pay attention to the problems encountered by spouses of different nationalities, contain policies on adoption and reproductive technologies, and be directed to eliminating domestic violence; 2) working life should have greater flexibility, including parental leave; 3) separate taxation should be enacted for spouses, a flat-rate child allowance should be introduced instead of tax reductions, and costs of caring for preschool-age children should be tax deductible; 4) social security should recognize the value of housework and child care, a minimum guaranteed income should be explored, individual rights should be established, people should be credited for time spent giving care to dependents, and the European Convention on Social Security should be ratified; 5) housing needs of families should be met and the infrastructures of towns should meet the needs of inhabitants, social infrastructure should help families care for

  15. A literature review of the market effects of federal biofuel policy and recommendations for future policy

    Science.gov (United States)

    Ayers, Alex Elgin

    The United States has had a federal biofuels policy since the 1970s. The purpose of this policy was to help the development of a biofuel industry during a time of high fuel prices in order to provide a domestic alternative to expensive foreign oil. Later the policy was changed to help lower the environmental impact caused by conventional fuels. Since that time the industry has grown and currently produces around 15 billion gallons of biofuels every year. The current federal biofuel policy is largely based on one program, the Renewable Fuel Standard (RFS), which mandates the production and blending of several different classes of biofuels and provides a form of subsidy to the biofuel industry. This paper examines the market effects of the federal biofuel policy and provides recommendations for improving the policy to counteract any negative effects. Federal biofuel policy has many far-reaching market effects. Some are easily calculable through expenditures and lost revenues, while others are harder to quantify because their full effects are not yet known. By evaluating these market effects, this paper will provide ample evidence that the federal biofuels policy needs to change, and will show what effects these changes could induce. The biofuels industry largely owes its existence to government policies, however as the research shows the industry can now stand on its own. This paper will examine what will happen if the federal policy is eliminated and what the future of the biofuels industry could hold. Based on these examinations, it is unlikely that the industry needs further government support and policies should be adjusted in light of this.

  16. Recommendations for responding to changes in reimbursement policy.

    Science.gov (United States)

    Byrnes, John; Fifer, Joe

    2010-01-01

    With profound changes in reimbursement policy on the horizon, organizations are preparing a variety of responses to ensure long-term success. Most are anticipating decreases in reimbursement rates from most payers. Whether due to nonpayment for hospital-acquired complications and infections, reductions due to high readmission rates, or a move toward value-based purchasing and bundled payment models, the impact is predicted to be substantial. Because of these sweeping changes, organizations must quickly prepare a thoughtful, effective response to ensure their financial stability. At the heart of these global changes in reimbursement, including those in the healthcare reform legislation, is a drive toward integration, the formation of integrated delivery systems in response to changing financial incentives. However, the new integrated systems must be not just an assemblage of the required components, but a true functional integration in which patients experience a seamless continuum of care that is highly coordinated, efficient, effective, and accessible. In this article, we'll address changes in reimbursement and recommended responses from three perspectives. First, we offer a three-pronged approach for managing general decreases in reimbursement. Second, we highlight strategies for managing nonpayment for readmissions, focusing on the demonstration project in the state of Michigan, MI STAAR. And finally, we review managing patient care in an environment of bundled payment, including the interventions at the center of the PROMETHEUS demonstration project.

  17. Biological invasions: recommendations for U.S. policy and management.

    Science.gov (United States)

    Lodge, David M; Williams, Susan; MacIsaac, Hugh J; Hayes, Keith R; Leung, Brian; Reichard, Sarah; Mack, Richard N; Moyle, Peter B; Smith, Maggie; Andow, David A; Carlton, James T; McMichael, Anthony

    2006-12-01

    The Ecological Society of America has evaluated current U.S. national policies and practices on biological invasions in light of current scientific knowledge. Invasions by harmful nonnative species are increasing in number and area affected; the damages to ecosystems, economic activity, and human welfare are accumulating. Without improved strategies based on recent scientific advances and increased investments to counter invasions, harm from invasive species is likely to accelerate. Federal leadership, with the cooperation of state and local governments, is required to increase the effectiveness of prevention of invasions, detect and respond quickly to new potentially harmful invasions, control and slow the spread of existing invasions, and provide a national center to ensure that these efforts are coordinated and cost effective. Specifically, the Ecological Society of America recommends that the federal government take the following six actions: (1) Use new information and practices to better manage commercial and other pathways to reduce the transport and release of potentially harmful species; (2) Adopt more quantitative procedures for risk analysis and apply them to every species proposed for importation into the country; (3) Use new cost-effective diagnostic technologies to increase active surveillance and sharing of information about invasive species so that responses to new invasions can be more rapid and effective; (4) Create new legal authority and provide emergency funding to support rapid responses to emerging invasions; (5) Provide funding and incentives for cost-effective programs to slow the spread of existing invasive species in order to protect still uninvaded ecosystems, social and industrial infrastructure, and human welfare; and (6) Establish a National Center for Invasive Species Management (under the existing National Invasive Species Council) to coordinate and lead improvements in federal, state, and international policies on invasive species

  18. NAACP Policy Recommendations for Economic Growth and Combating Inflation.

    Science.gov (United States)

    Crisis, 1981

    1981-01-01

    Reacts to the Reagan Administration's economic plans. Presents NAACP policy positions on combating inflation, tax relief, unemployment, and stimulating growth in inner cities to offset urban blight. (MK)

  19. Policy and science in children's health and environment : Recommendations from the PINCHE project

    NARCIS (Netherlands)

    Hazel, P.J. van den; Zuurbier, M.; Bistrup, M.L.; Busby, C.; Fucic, A.; Koppe, J.G.; Lundqvist, C.; Ronchetti, R.; Tusscher, G. Ten

    2006-01-01

    Background: Policy recommendations result from the discussions and analysis of the present situation in environment and health. Such analysis was performed in PINCHE. This led to recommendations based on the scientific literature. In the field of children's environmental health the policy process

  20. Using research evidence to reframe the policy debate around mental illness and guns: process and recommendations.

    Science.gov (United States)

    McGinty, Emma E; Frattaroli, Shannon; Appelbaum, Paul S; Bonnie, Richard J; Grilley, Anna; Horwitz, Joshua; Swanson, Jeffrey W; Webster, Daniel W

    2014-11-01

    Recent mass shootings have prompted a national dialogue around mental illness and gun policy. To advance an evidence-informed policy agenda on this controversial issue, we formed a consortium of national gun violence prevention and mental health experts. The consortium agreed on a guiding principle for future policy recommendations: restricting firearm access on the basis of certain dangerous behaviors is supported by the evidence; restricting access on the basis of mental illness diagnoses is not. We describe the group's process and recommendations.

  1. Resource Needs for English Learners: Getting Down to Policy Recommendations

    Science.gov (United States)

    Gandara, Patricia; Maxwell-Jolly, Julie; Rumberger, Russell W.

    2008-01-01

    This document is an extension of "Resource Needs for California's English Learners" and is the result of deliberations from several informal meetings and two formal meetings of major stakeholders in the area of English Learner (EL) education. Its intent is to suggest a series of policy options, based on data examined in the initial…

  2. Homeless and Special Education Administrative Collaboration: Recommendations. Policy Forum Proceedings

    Science.gov (United States)

    Bowman, Diana; Burdette, Paula; Julianelle, Patricia

    2008-01-01

    Project Forum at the National Association of State Directors of Special Education (NASDSE) and the National Center for Homeless Education (NCHE) worked together to collect information regarding the need for a policy forum on the topic of administrative collaboration between school personnel who support homeless education under the McKinney-Vento…

  3. Policy recommendations for Canadian municipal greenhouse gas trading

    International Nuclear Information System (INIS)

    Seskus, A.

    2002-01-01

    The municipal policies regarding greenhouse gas (GHG) emissions trading from municipalities in developed countries outside of Canada were examined in an effort to help establish a position on municipal carbon trading in Canada. The main uncertainty regarding this new concept of GHG emissions trading is the fate of the Kyoto Protocol, when or if it will be ratified. It is premature for municipalities to have well-established polices about emissions trading because the country in which a municipality is located determines the position towards GHG emissions trading. For this study, an extensive literature search of municipal policies was conducted for both GHG trading and domestic national GHG trading. This was followed by a survey on emissions trading which was distributed to more than 350 member cities (including the United States, Europe and Australia) of the International Council for Environmental Initiatives (ICLEI) Cities for Climate Protection (CCP) Campaign. The literature search revealed that municipalities outside of Canada have not yet formulated policies to address the issue of emissions trading. Only 7 per cent of the cities felt that they were informed about emissions trading, even in Europe and Australia where domestic emissions trading is closer to becoming a reality. This paper demonstrated that it is evident that more training is needed for municipalities regarding this issue. For the very few cities that had developed a GHG trading policy, each municipal policy supported municipal participation in emissions trading under conditions that included an environmental retirement, a do-no-harm clause, or an obligation to meet voluntary commitments before excess emissions can be traded. refs., tabs., figs

  4. Additive Manufacturing in Finland: Recommendations for a Renewed Innovation Policy

    Science.gov (United States)

    Ituarte, Iñigo Flores; Salmi, Mika; Ballardini, Rosa Maria; Tuomi, Jukka; Partanen, Jouni

    The objective of this research is to define an optimal innovation policy and funding strategy to improve Additive Manufacturing (AM) capabilities in Finnish companies. To do so, we present an international review of innovation programs in the area of AM. In addition, the study replied upon a survey prepared to evaluate factors for AM implementation. The ultimate goal is to help in the definition of a national policy strategy in the area of AM based on the characteristics of the Finnish industrial ecosystem. The methodology and data collection method involved defining the taxonomy of Finnish AM industry. The target group of the survey was a population of AM experts, and individuals with knowledge on AM and industrial processes. Overall, the survey revealed that research and innovation activities are well positioned in Finland. In order for future innovation policies to further support developments in the field, we estimated that policy strategies need to generate about 6-8 M€/year in national and EU- funding instruments for AM technology transfer, development, and innovation activities. Efforts should be targeted towards strengthening uses of AM in final production. In fact, only 36% of Finnish respondents declared to use AM for final production, while leading countries in AM use it in average more than 50%. Another area in need of development in Finland is the use of AM high performance materials. Moreover, outsourcing of AM services in Finland is 23 percentage point higher in national and 13 percentage point higher in international outsourcing to service bureaus and suppliers. In this regard, future policies and funding strategies should maintain the created momentum. However, there is a need to acquire high-end research and industrial equipment to stimulate AM integration to the existing production systems. This in the end can trigger the creation of new products, processes and intellectual property, enabling innovation and competitive advantage.

  5. Main Issues on Electronic Commerce and Policy Recommendations

    OpenAIRE

    Chongwha Lee; Seongbong Lee

    1998-01-01

    "Electronic Commerce" means that people sell and buy commodity, labor service and information through internet and now is mainly be used in commercial intercourse. The core of the international research related to Electronic Commerce is a tax-exemption, land tax, liberalization of encrypted technology and privacy protection policy, etc. Meanwhile, intellectual property, consumer protection and limitation of packing specification are also researched together with the business activeness. The r...

  6. OECD Policy Recommendations on Security for Biological Materials

    International Nuclear Information System (INIS)

    Radisch, J.

    2007-01-01

    Biomedical innovations derived from research on pathogenic micro-organisms promise astounding health and economic benefits. Some such biological resources employed in the RandD for diagnostic kits, vaccines and therapeutics, however, possess capacity for dual-use; they may be misused to develop biological weapons. Research facilities entrusted with possession of such dual-use materials have a responsibility to comply with biosecurity measures that are designed to prevent loss or theft and thereby reduce the probability of a bioterrorist attack. The OECD has provided a forum for its Member countries to engage in a dialogue of international co-operation with a view to produce policies that achieve a research environment fortified by biosecurity measures and capable of producing health innovations. In 2007, the OECD developed a risk assessment framework and risk management principles for Biological Resource Centres. Ongoing policy work at the OECD will look to design biosecurity guidelines appropriate to a broader range of facilities in possession of dual-use materials, such as university and industrial laboratories.(author)

  7. Supporting recommendations to policies for expanding the building of nuclear stations

    International Nuclear Information System (INIS)

    Nasr, Nahla

    2009-01-01

    This article speaks about the policy recommendations concerning the future of nuclear energy. It includes the findings and recommendations based upon the presentations and discussions at the meeting of nearly 40 scientists, policy makers, industry representatives, and non governmental experts from around the world. The Bulletin of the Atomic Scientists convened them. The meeting was cosponsored by the University of Chicago, Argonne National Laboratory, and the Chicago Council on Science and Technology

  8. Recommendations for a software quality assurance policy for the nuclear waste disposal risk assessment programme

    International Nuclear Information System (INIS)

    Hill, I.E.

    1985-05-01

    This study reviewed a number of published standards for software quality assurance, and included a series of interviews with software developers aimed at exploring their attitudes to software quality assurance. Recommendations for software quality assurance policy are made based on the above investigations. This document provides a summary of the recommendations made in the full report on project, reference MR-CDS-4. (author)

  9. ATS-6 and State Telecommunications Policy for Rural Alaska: An Analysis of Recommendations.

    Science.gov (United States)

    Pittman, Theda Sue; Orvik, James M.

    This paper analyzes thirteen recommendations for media policy making in rural Alaska which were formulated as a product of a study of the educational television aspect of the ATS-6 (Applications Technology Satellite) project in 1974-75. The recommendations, which emphasize local media control, were based on information provided by village…

  10. Main Issues on Electronic Commerce and Policy Recommendations

    Directory of Open Access Journals (Sweden)

    Chongwha Lee

    1998-03-01

    Full Text Available "Electronic Commerce" means that people sell and buy commodity, labor service and information through internet and now is mainly be used in commercial intercourse. The core of the international research related to Electronic Commerce is a tax-exemption, land tax, liberalization of encrypted technology and privacy protection policy, etc. Meanwhile, intellectual property, consumer protection and limitation of packing specification are also researched together with the business activeness. The reason why questions related to Electronic Commerce are in the back of the spotlight is that US and major countries in EU lead the international research to maximize their own benefits. These researches are related to rectify legal system framework for protecting development of Electronic Commerce and to work out international standards. Also, enlarging Electronic Commerce on online resources is also regarded as the core issue by OECD, APEC and other international organization and it is inevitable to have multilateral negotiation regarding this issue. Based on the opinion above mentioned, we collect all the problems brought by Electronic Commerce Activeness in each area in this paper and try to find out corresponding solutions to face these problems.

  11. Decarbonizing the international shipping industry: Solutions and policy recommendations.

    Science.gov (United States)

    Wan, Zheng; El Makhloufi, Abdel; Chen, Yang; Tang, Jiayuan

    2018-01-01

    Ship-source greenhouse gas (GHG) emissions could increase by up to 250% by 2050 from their 2012 levels, owing to increasing global freight volumes. Binding international legal agreements to regulate GHGs, however, are lacking as technical solutions remain expensive, and crucial industrial support is absent. In 2003, the International Maritime Organization adopted Resolution A.963 (23) to regulate shipping CO 2 emissions via technical, operational, and market-based routes. However, progress has been slow and uncertain; there is no concrete emission reduction target or definitive action plan. Yet, a full-fledged roadmap may not even emerge until 2023. In this policy analysis, we revisit the progress of technical, operational, and market-based routes and the associated controversies. We argue that 1) a performance-based index, though good-intentioned, has loopholes affecting meaningful CO 2 emission reductions driven by technical advancements; 2) using slow steaming to cut energy consumption stands out among all operational solutions thanks to its immediate and obvious results, but with the already slow speed in practice, this single source has limited emission reduction potential; 3) without a technology-savvy shipping industry, a market-based approach is essentially needed to address the environmental impact. To give shipping a 50:50 chance for contributing fairly and proportionately to keep global warming below 2°C, deep emission reductions should occur soon. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Leveraging Mindsets to Promote Academic Achievement: Policy Recommendations.

    Science.gov (United States)

    Rattan, Aneeta; Savani, Krishna; Chugh, Dolly; Dweck, Carol S

    2015-11-01

    The United States must improve its students' educational achievement. Race, gender, and social class gaps persist, and, overall, U.S. students rank poorly among peers globally. Scientific research shows that students' psychology-their "academic mindsets"-have a critical role in educational achievement. Yet policymakers have not taken full advantage of cost-effective and well-validated mindset interventions. In this article, we present two key academic mindsets. The first, a growth mindset, refers to the belief that intelligence can be developed over time. The second, a belonging mindset, refers to the belief that people like you belong in your school or in a given academic field. Extensive research shows that fostering these mindsets can improve students' motivation; raise grades; and reduce racial, gender, and social class gaps. Of course, mindsets are not a panacea, but with proper implementation they can be an excellent point of entry. We show how policy at all levels (federal, state, and local) can leverage mindsets to lift the nation's educational outcomes. © The Author(s) 2015.

  13. The Tax Wedge in Slovenia: International Comparison and Policy Recommendations

    Directory of Open Access Journals (Sweden)

    Primož Dolenc

    2005-09-01

    Full Text Available When taxes on labor are introduced, a “tax wedge” appears between the labor costs paid by the employer (gross wage and the net wage received by an employee. At a certain level of wage, a higher tax wedge increases unemployment and decreases employment, all other things being equal. The paper tackles three main questions: the characteristics of the tax wedge, unemployment and employment rates in OECD countries in the recent past, tax wedge policy in the EU15 and the new EU members and the tax system and its effects on the unemployment and employment rates in Slovenia. We found that the OECD countries can be classified into two groups of countries if the tax wedge, the unemployment rate and the employment rate are taken into consideration. The first group is the high tax wedge, high unemployment rate and low employment rate group of countries, whereas the other group has the opposite characteristics. European member states (old and new have on average a higher tax burden on labor than the OECD average, consequently suffering from higher unemployment rates. Slovenia has an unreasonably high tax wedge; in the EU only Belgium and Germany have a higher tax burden. According to previous and our empirical findings we suggest that Slovenia could benefit from a reduction in the tax wedge.

  14. Healthy food procurement and nutrition standards in public facilities: evidence synthesis and consensus policy recommendations.

    Science.gov (United States)

    Raine, Kim D; Atkey, Kayla; Olstad, Dana Lee; Ferdinands, Alexa R; Beaulieu, Dominique; Buhler, Susan; Campbell, Norm; Cook, Brian; L'Abbé, Mary; Lederer, Ashley; Mowat, David; Maharaj, Joshna; Nykiforuk, Candace; Shelley, Jacob; Street, Jacqueline

    2018-01-01

    Unhealthy foods are widely available in public settings across Canada, contributing to diet-related chronic diseases, such as obesity. This is a concern given that public facilities often provide a significant amount of food for consumption by vulnerable groups, including children and seniors. Healthy food procurement policies, which support procuring, distributing, selling, and/or serving healthier foods, have recently emerged as a promising strategy to counter this public health issue by increasing access to healthier foods. Although numerous Canadian health and scientific organizations have recommended such policies, they have not yet been broadly implemented in Canada. To inform further policy action on healthy food procurement in a Canadian context, we: (1) conducted an evidence synthesis to assess the impact of healthy food procurement policies on health outcomes and sales, intake, and availability of healthier food, and (2) hosted a consensus conference in September 2014. The consensus conference invited experts with public health/nutrition policy research expertise, as well as health services and food services practitioner experience, to review evidence, share experiences, and develop a consensus statement/recommendations on healthy food procurement in Canada. Findings from the evidence synthesis and consensus recommendations for healthy food procurement in Canada are described. Specifically, we outline recommendations for governments, publicly funded institutions, decision-makers and professionals, citizens, and researchers. Implementation of healthy food procurement policies can increase Canadians' access to healthier foods as part of a broader vision for food policy in Canada.

  15. Healthy food procurement and nutrition standards in public facilities: evidence synthesis and consensus policy recommendations

    Directory of Open Access Journals (Sweden)

    Kim D. Raine

    2018-01-01

    Full Text Available Introduction: Unhealthy foods are widely available in public settings across Canada, contributing to diet-related chronic diseases, such as obesity. This is a concern given that public facilities often provide a significant amount of food for consumption by vulnerable groups, including children and seniors. Healthy food procurement policies, which support procuring, distributing, selling, and/or serving healthier foods, have recently emerged as a promising strategy to counter this public health issue by increasing access to healthier foods. Although numerous Canadian health and scientific organizations have recommended such policies, they have not yet been broadly implemented in Canada. Methods: To inform further policy action on healthy food procurement in a Canadian context, we: (1 conducted an evidence synthesis to assess the impact of healthy food procurement policies on health outcomes and sales, intake, and availability of healthier food, and (2 hosted a consensus conference in September 2014. The consensus conference invited experts with public health/nutrition policy research expertise, as well as health services and food services practitioner experience, to review evidence, share experiences, and develop a consensus statement/recommendations on healthy food procurement in Canada. Results: Findings from the evidence synthesis and consensus recommendations for healthy food procurement in Canada are described. Specifically, we outline recommendations for governments, publicly funded institutions, decision-makers and professionals, citizens, and researchers. Conclusion: Implementation of healthy food procurement policies can increase Canadians’ access to healthier foods as part of a broader vision for food policy in Canada.

  16. Recommendations for NRC policy on shift scheduling and overtime at nuclear power plants

    International Nuclear Information System (INIS)

    Lewis, P.M.

    1985-07-01

    This report contains the Pacific Northwest Laboratory's (PNL's) recommendations to the US Nuclear Regulatory Commission (NRC) for an NRC policy on shift scheduling and hours of work (including overtime) for control room operators and other safety-related personnel in nuclear power plants. First, it is recommended that NRC make three additions to its present policy on overtime: (1) limit personnel to 112 hours of work in a 14-day period, 192 hours in 28 days, and 2260 hours in one year; exceeding these limits would require plant manager approval; (2) add a requirement that licensees obtain approval from NRC if plant personnel are expected to exceed 72 hours of work in a 7-day period, 132 hours in 14 days, 228 hours in 28 days, and 2300 hours in one year; and (3) make the policy a requirement, rather than a nonbinding recommendation. Second, it is recommended that licensees be required to obtain NRC approval to adopt a routine 12-hour/day shift schedule. Third, it is recommended that NRC add several nonbinding recommendations concerning routine 8-hour/day schedules. Finally, because additional data can strengthen the basis for future NRC policy on overtime, five methods are suggested for collecting data on overtime and its effects. 44 refs., 10 tabs

  17. Recommendations for NRC policy on shift scheduling and overtime at nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, P.M.

    1985-07-01

    This report contains the Pacific Northwest Laboratory's (PNL's) recommendations to the US Nuclear Regulatory Commission (NRC) for an NRC policy on shift scheduling and hours of work (including overtime) for control room operators and other safety-related personnel in nuclear power plants. First, it is recommended that NRC make three additions to its present policy on overtime: (1) limit personnel to 112 hours of work in a 14-day period, 192 hours in 28 days, and 2260 hours in one year; exceeding these limits would require plant manager approval; (2) add a requirement that licensees obtain approval from NRC if plant personnel are expected to exceed 72 hours of work in a 7-day period, 132 hours in 14 days, 228 hours in 28 days, and 2300 hours in one year; and (3) make the policy a requirement, rather than a nonbinding recommendation. Second, it is recommended that licensees be required to obtain NRC approval to adopt a routine 12-hour/day shift schedule. Third, it is recommended that NRC add several nonbinding recommendations concerning routine 8-hour/day schedules. Finally, because additional data can strengthen the basis for future NRC policy on overtime, five methods are suggested for collecting data on overtime and its effects. 44 refs., 10 tabs.

  18. A Community-Driven Approach to Generate Urban Policy Recommendations for Obesity Prevention

    Directory of Open Access Journals (Sweden)

    Julia Díez

    2018-03-01

    Full Text Available There is an increasing research interest in targeting interventions at the neighborhood level to prevent obesity. Healthy urban environments require including residents’ perspectives to help understanding how urban environments relate to residents’ food choices and physical activity levels. We describe an innovative community-driven process aimed to develop environmental recommendations for obesity prevention. We conducted this study in a low-income area in Madrid (Spain, using a collaborative citizen science approach. First, 36 participants of two previous Photovoice projects translated their findings into policy recommendations, using an adapted logical framework approach. Second, the research team grouped these recommendations into strategies for obesity prevention, using the deductive analytical strategy of successive approximation. Third, through a nominal group session including participants, researchers, public health practitioners and local policy-makers, we discussed and prioritized the obesity prevention recommendations. Participants identified 12 policy recommendations related to their food choices and 18 related to their physical activity. The research team grouped these into 11 concrete recommendations for obesity prevention. The ‘top-three’ ranked recommendations were: (1 to adequate and increase the number of public open spaces; (2 to improve the access and cost of existing sports facilities and (3 to reduce the cost of gluten-free and diabetic products.

  19. Micronutrient recommendations and policies in Spain: the cases of iodine, folic acid and vitamin D.

    Science.gov (United States)

    Brito Garcia, N; Serra Majem, L

    2012-01-01

    INTRODUCCIÓN: As part of the work carried out within the EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence in Spain, we conducted a series of semi-structured interviews with decision makers and relevant scientific institutions in the field of nutrition and public health. The information gathered was collated with national relevant official and unofficial documents and subsequently analysed. To describe the current situation about nutrition policy in Spain, with special focus on the process of setting micronutrient recommendations and the development of subsequent policies. 3 cases will be detailed: iodine, folic acid and vitamin D. Information from 9 interviews was contrasted with the available official and unofficial documents on micronutrients recommendations setting and subsequent policy applications to help the population to achieve their requirements. Common topics and themes were identified in the interviews and desk research. They describe a heterogenic picture of isolated initiatives and timid measures regarding micronutrients recommendations and subsequent policy instruments. Several recommendations coexist but none of them is the result of an official request by the government or competent authority. Iodine, folic acid and vitamin D represent the past, the present and the future of public health policy measures on micronutrients in Spain. Despite of some examples, there exist a need for action. Current nutrition strategies are focused on obesity, with little room for micronutrients national measures despite of the opinion of many experts. Regardless of the several nutrients recommendations coexisting nowadays in Spain, there exist the need for a coordinated action in the field of micronutrients recommendations, fostered by the health and nutrition official authorities with financial support and clear terms of reference.

  20. Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of seventh biannual meeting (March 2015).

    Science.gov (United States)

    2015-08-05

    The Malaria Policy Advisory Committee to the World Health Organization held its seventh meeting in Geneva, Switzerland from 5 to 7 March 2015. This article provides a summary of the discussions, conclusions and meeting recommendations. Meeting sessions included: an update on the Greater Mekong Subregion elimination strategy; an update on the RTS,S vaccine; G6PD testing to support the safe use of anti-relapse therapy for Plasmodium vivax; update from the Vector Control Advisory Group; newly proposed evidence reviews or consultations on malaria terminology, malaria in pregnancy, and the feasibility of eradication; as well as updates from the World Health Organization Global Malaria Programme regarding their strategy update and policy setting processes. Policy statements, position statements, and guidelines that arise from the Malaria Policy Advisory Committee meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

  1. Developing recommendations to improve the quality of diabetes care in Ireland: a policy analysis.

    LENUS (Irish Health Repository)

    Mc Hugh, Sheena M

    2014-09-01

    In 2006, the Health Service Executive (HSE) in Ireland established an Expert Advisory Group (EAG) for Diabetes, to act as its main source of operational policy and strategic advice for this chronic condition. The process was heralded as the starting point for the development of formal chronic disease management programmes. Although recommendations were published in 2008, implementation did not proceed as expected. Our aim was to examine the development of recommendations by the EAG as an instrumental case study of the policy formulation process, in the context of a health system undergoing organisational and financial upheaval.

  2. Preconception care policy, guidelines, recommendations and services across six European countries

    DEFF Research Database (Denmark)

    Shawe, Jill; Delbaere, Ilse; Ekstrand, Maria

    2015-01-01

    : Governmental policy and legislation; Professional bodies and organisations; Healthcare providers; Charitable organisations; Web-based public information and internet sites. Results All countries had preconception recommendations for women with chronic diseases, such as diabetes and epilepsy. Recommendations...... supplementation. Conclusions Current guidelines are heterogeneous. Collaborative research across Europe is required in order to develop evidence-based guidelines for preconception health and care. There is a need to establish a clear strategy for promoting advice and guidance within the European childbearing...

  3. Dismantling the Afghan Opiate Economy: A Cultural and Historical Policy Assessment, with Policy Recommendations

    National Research Council Canada - National Science Library

    Byrom, Christopher L

    2005-01-01

    .... Specific lessons are taken from a chapter dedicated to Afghan culture, history, and rural power structures, and applied in chapters analyzing the opiate economy and current counter-narcotics policies...

  4. Recommendations for international gambling harm-minimisation guidelines: comparison with effective public health policy.

    Science.gov (United States)

    Gainsbury, Sally M; Blankers, Matthijs; Wilkinson, Claire; Schelleman-Offermans, Karen; Cousijn, Janna

    2014-12-01

    Problem gambling represents a significant public health problem, however, research on effective gambling harm-minimisation measures lags behind other fields, including other addictive disorders. In recognition of the need for consistency between international jurisdictions and the importance of basing policy on empirical evidence, international conventions exist for policy on alcohol, tobacco, and illegal substances. This paper examines the evidence of best practice policies to provide recommendations for international guidelines for harm-minimisation policy for gambling, including specific consideration of the specific requirements for policies on Internet gambling. Evidence indicates that many of the public health policies implemented for addictive substances can be adapted to address gambling-related harms. Specifically, a minimum legal age of at least 18 for gambling participation, licensing of gambling venues and activities with responsible gambling and consumer protection strategies mandated, and brief interventions should be available for those at-risk for and experiencing gambling-related problems. However, there is mixed evidence on the effectiveness of limits on opening hours and gambling venue density and increased taxation to minimise harms. Given increases in trade globalisation and particularly the global nature of Internet gambling, it is recommended that jurisdictions take actions to harmonise gambling public health policies.

  5. Recommendations for institutional policy and network regulatory frameworks towards distributed generation in EU Member States

    Energy Technology Data Exchange (ETDEWEB)

    Ten Donkelaar, M.; Van Oostvoorn, F. [ECN Policy Studies, Petten (Netherlands)

    2005-01-01

    Recommendations regarding the development of regulatory frameworks and institutional policies towards an optimal integration of distributed generation (DG) into electricity networks are presented. These recommendations are based on findings from a benchmarking study conducted in the framework of the ENIRDG-net project. The aim of the benchmarking exercise was to identify examples of well-defined pro-DG policies, with clear targets and adequate implementation mechanisms. In this study an adequate pro-DG policy is defined on the basis of a level playing field, a situation where distributed and centralised generation receive equal incentives and have equal access to the liberalised markets for electricity. The benchmark study includes the results of a similar study conducted in the framework of the SUSTELNET project. When comparing the results a certain discrepancy can be noticed between the actual regulation and policy in a number of countries, the medium to long-term targets and the ideal situation described by the level playing field objective. To overcome this discrepancy, a number of recommendations have been drafted for future policy and regulation towards distributed generation.

  6. Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of fifth biannual meeting (March 2014).

    Science.gov (United States)

    2014-07-03

    The Malaria Policy Advisory Committee to the World Health Organization (WHO) held its fifth meeting in Geneva, Switzerland from 12 to 14 March 2014. This article provides a summary of the discussions, conclusions and recommendations from that meeting.Meeting sessions covered: maintaining universal coverage of long-lasting insecticidal nets; combining indoor residual spraying with long-lasting insecticidal nets; the sound management of old long-lasting insecticidal nets; malaria diagnosis in low transmission settings; the Global Technical Strategy for Malaria (2016 -2025); and Technical Expert Group updates on vector control, the RTS,S vaccine, the Malaria Treatment Guidelines, anti-malarial drug resistance and containment, and surveillance, monitoring and evaluation.Policy statements, position statements, and guidelines that arise from the Malaria Policy Advisory Committee meeting conclusions and recommendations will be formally issued and disseminated to WHO Member States by the WHO Global Malaria Programme.

  7. Supporting Evidence-Based Policy on Biodiversity and Ecosystem Services: Recommendations for Effective Policy Briefs

    Science.gov (United States)

    Balian, Estelle V.; Drius, Liza; Eggermont, Hilde; Livoreil, Barbara; Vandewalle, Marie; Vandewoestjine, Sofie; Wittmer, Heidi; Young, Juliette

    2016-01-01

    Knowledge brokerage on biodiversity and ecosystem services can apply communication tools such as policy briefs to facilitate the dialogue between scientists and policymakers. There is currently considerable debate on how to go beyond the linear communication model, outdated in theoretical debate but still often implicitly leading interaction with…

  8. Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of September 2012 meeting

    Directory of Open Access Journals (Sweden)

    2012-12-01

    Full Text Available Abstract The Malaria Policy Advisory Committee to the World Health Organization met in Geneva, Switzerland from 11 to 13 September, 2012. This article provides a summary of the discussions, conclusions and recommendations from that meeting. Meeting sessions included: updated policy recommendations on the use of sulphadoxine-pyrimethamine for Intermittent Preventive Treatment of malaria in pregnancy, as well as the use of single dose primaquine as a Plasmodium falciparum gametocytocide; the need to develop a Global Technical Strategy for Malaria Control and Elimination 2016– 2025 and a global strategy for control of Plasmodium vivax; the Affordable Medicines Facility for malaria independent evaluation and promoting malaria case management in the private sector; updates from the Technical Expert Group on drug resistance and containment and the Evidence Review Group on malaria burden estimation; update on the RTS,S/AS01 malaria vaccine; progress on the policy setting process for malaria vector control; and the process for updating the WHO Guidelines for the Treatment of Malaria. Policy statements, position statements, and guidelines that arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

  9. Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of September 2013 meeting.

    Science.gov (United States)

    2013-12-20

    The Malaria Policy Advisory Committee to the World Health Organization held its fourth meeting in Geneva, Switzerland from 11 to 13 September, 2013. This article provides a summary of the discussions, conclusions and recommendations from that meeting.Meeting sessions included: recommendations for achieving universal coverage of long-lasting insecticide-treated nets; guidance on estimating the longevity of insecticide-treated nets; improving capacity in entomology and vector control; a review of the latest evidence on intermittent preventive treatment in pregnancy; improving dissemination of Malaria Policy Advisory Committee guidance; updates on the development of the global technical strategy for malaria control and elimination (2016-2025) and the global strategy for control and elimination of Plasmodium vivax; updates from the drug resistance and containment technical expert group, the evidence review group on malaria burden estimation, a consultation on malaria case management indicators, and the constitution of the surveillance, monitoring and evaluation technical expert group; subnational elimination criteria; and consideration for future evidence review groups, including diagnosis in low transmission settings and testing for Glucose-6-Phosphate Dehydrogenase Deficiency.Policy statements, position statements and guidelines that arise from the Malaria Policy Advisory Committee meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

  10. Policy and science in children's health and environment: recommendations from the PINCHE project.

    Science.gov (United States)

    van den Hazel, Peter; Zuurbier, Moniek; Bistrup, Marie Louise; Busby, Chris; Fucic, Aleksandra; Koppe, Janna G; Lundqvist, Christofer; Ronchetti, Roberto; ten Tusscher, Gavin

    2006-10-01

    Policy recommendations result from the discussions and analysis of the present situation in environment and health. Such analysis was performed in PINCHE. This led to recommendations based on the scientific literature. In the field of children's environmental health the policy process will follow more or less fixed rules, but this process is still at an early level of development. The link between science and policy still faces many challenges. Scientific assessment of environmental risk must recognize and tackle the problems of data sets, variability of human and environmental systems, the range, spatial and temporal diffusion of potential health effects and many biases and confounding factors. The PINCHE network recommends a general improvement of the supporting scientific fields in environment and health. Assessments from epidemiology or toxicology should play a key role in influencing science-policy decisions in programmes that are intended to inform the public policy process. Scientific committees at a local level could play a role. The relation between health and environment needs to be better incorporated in training and education. There is a need for harmonization of data production and use. The priorities in PINCHE focus on the most important issues. A classification of low, medium or high priority for action was used to describe a range of different environmental stressors. PINCHE provided recommendations to reduce exposure for children. Exposure reduction is not always linked to improved health in the short term, but it will reduce the body burden of accumulating chemicals in children. A strategic choice is reduction of exposure of children to compounds by changing production techniques or by increasing the distance of child specific settings to sources. The contribution of all players in the production, distribution and use of scientific knowledge in the field of children's environmental health is necessary.

  11. A Review of Electric Vehicle Lifecycle Emissions and Policy Recommendations to Increase EV Penetration in India

    Directory of Open Access Journals (Sweden)

    Rachana Vidhi

    2018-02-01

    Full Text Available Electric vehicles reduce pollution only if a high percentage of the electricity mix comes from renewable sources and if the battery manufacturing takes place at a site far from the vehicle use region. Industries developed due to increased electric vehicle adoption may also cause additional air pollution. The Indian government has committed to solving New Delhi’s air pollution issues through an ambitious policy of switching 100% of the light duty consumer vehicles to electric vehicles by 2030. This policy is based on vehicle grid interaction and relies on shared mobility through the electric vehicle fleet. There are several human behavioral changes necessary to achieve 100% adoption of electric vehicles. This paper reviews different steps in the lifecycle of an electric vehicle (EV, their impact on environmental emissions, and recommends policies suitable for different socio-economic group that are relevant to the Indian market. To reduce air pollution through adoption of electric vehicles, the Indian government needs to adopt policies that increase sale of electric vehicles, increase percentage of renewable energy in the electricity mix, and prevent air pollution caused from battery manufacturing. The recommended policies can be customized for any market globally for reducing air pollution through increased adoption of electric vehicles.

  12. Developing recommendations to improve the quality of diabetes care in Ireland: a policy analysis.

    Science.gov (United States)

    Mc Hugh, Sheena M; Perry, Ivan J; Bradley, Colin; Brugha, Ruairí

    2014-09-18

    In 2006, the Health Service Executive (HSE) in Ireland established an Expert Advisory Group (EAG) for Diabetes, to act as its main source of operational policy and strategic advice for this chronic condition. The process was heralded as the starting point for the development of formal chronic disease management programmes. Although recommendations were published in 2008, implementation did not proceed as expected. Our aim was to examine the development of recommendations by the EAG as an instrumental case study of the policy formulation process, in the context of a health system undergoing organisational and financial upheaval. This study uses Kingdon's Multiple Streams Theory to examine the evolution of the EAG recommendations. Semi-structured interviews were conducted with a purposive sample of 15 stakeholders from the advisory group. Interview data were supplemented with documentary analysis of published and unpublished documents. Thematic analysis was guided by the propositions of the Kingdon model. In the problem stream, the prioritisation of diabetes within the policy arena was a gradual process resulting from an accumulation of evidence, international comparison, and experience. The policy stream was bolstered by group consensus rather than complete agreement on the best way to manage the condition. The EAG assumed the politics stream was also on course to converge with the other streams, as the group was established by the HSE, which had the remit for policy implementation. However, the politics stream did not converge due to waning support from health service management and changes to the organisational structure and financial capacity of the health system. These changes trumped the EAG process and the policy window remained closed, stalling implementation. Our results reflect the dynamic nature of the policy process and the importance of timing. The results highlight the limits of rational policy making in the face of organisational and fiscal upheaval

  13. Recommendations for policy development regarding sport-related concussion prevention and management in Canada.

    Science.gov (United States)

    Frémont, Pierre; Bradley, Lindsay; Tator, Charles H; Skinner, Jill; Fischer, Lisa K

    2015-01-01

    The Canadian Concussion Collaborative (CCC) is composed of health-related organisations concerned with the recognition, treatment and management of concussion. Its mission is to create synergy between organisations concerned with concussion to improve education and implementation of best practices for the prevention and management of concussions. Each of the organisations that constitute the CCC has endorsed two recommendations that address the need for relevant authorities to develop policies about concussion management in sports. The recommendations were developed to support advocacy for regulations, policies or legislation to improve concussion prevention and management at all levels of sport. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Radon in HUD assisted multifamily housing: Policy recommendations to the Congress

    International Nuclear Information System (INIS)

    1991-04-01

    The report complies with Section 1091 of the Stewart B. McKinney Homeless Assistance Amendments Act of 1988 which requires that the HUD Secretary report to the Congress on a recommended policy for addressing radon contamination in specified housing. The housing specified in the Act is virtually all rental housing predominantly for low-income and moderate-income households. Almost all of it is multifamily housing: row houses, walk-up apartment buildings, or high-rise buildings. There is inadequate information on the extent to which excessive concentrations of radon occur above the first floor of multistory buildings and on the variation in radon concentrations in attached houses in the same row. HUD's recommended policy is in the four topic areas specified in the Act: research, education, testing, and mitigation

  15. Practitioner-recommended policies and procedures for children exposed to domestic violence.

    Science.gov (United States)

    Black, Sally; Dempsey, Sandra H; Davis, Martha B

    2010-11-01

    Children exposed to domestic violence experience higher rates of psychosocial, behavioral, and physical problems. Current policy recommendations are that health care providers offer regular screening and treatment for childhood exposure to domestic violence (CEDV). However, screening recommendations have been slow to take hold. The purpose of this study was to identify recommended practices of CEDV, as reported by practitioners. Interviews were held with 24 experienced service providers from 14 agencies. Respondents provided practical suggestions for CEDV screening and intervention. Suggestions included refinement of screening tools for maximum validity and reliability, improved integration of DV education into medical training and practice, on-site DV resources in pediatric settings, and establishment of formal partnerships between human service organizations that promoted ongoing collaborative activities. Next steps are to evaluate outcomes for evidence-based practice.

  16. The 25 IEA energy efficiency policy recommendations to the G8 Gleneagles Plan of Action

    Energy Technology Data Exchange (ETDEWEB)

    Jollands, Nigel; Laustsen, Jens; Tanaka, Kanako; De T' Serclaes, Philippine; Barnsley, Ingrid; Bradley, Rick [International Energy Agency (France); Waide, Paul [Navigant (United States); Ellis, Mark [Mark Ellis and Associates (Australia); Onoda, Takao [Japan' s Ministry of Land, Infrastructure and Transport (Japan); Meier, Alan [The Lawrence Berkley Laboratory (United States)

    2010-11-15

    The imperative to pursue energy efficiency improvements is clearly on the political agenda at all levels of governments. This paper explores the lessons from past attempts at galvanising international efforts to expand energy efficiency activities through the use of international-level recommendations. Drawing on these lessons, the paper outlines the IEA response to the call for policy advice on energy efficiency through the G8 Gleneagles Plan of Action. Specifically, the paper outlines a 'necessary conditions' framework that was used to develop a set of energy efficiency policy priorities and describes the subsequent recommendations presented to the G8 in Hokkaido-Toyako Summit in 2008. The recommendations cover 25 fields of action in seven priority areas: buildings, appliances, lighting, transport, industry, energy utilities and cross-sectoral issues. Together, the suite of recommendations sets out an ambitious road map for global energy efficiency improvement. If implemented globally without delay, they could save around 8.2 GtCO{sub 2}/yr or 96 EJ/yr by 2030. This is equivalent to roughly twice the current total EU energy-related CO{sub 2} emissions. (author)

  17. Marine renewable energy policy in China and recommendations for improving implementation

    Science.gov (United States)

    Wang, Haifeng; Wang, Ji; Liu, Yuxin; Chen, Libo

    2018-02-01

    Renewable energy is the effective solution for the harmonious coexistence of human and environment as well as for the sustainable development. Marine renewable energy as one of the renewable energies, potentially offer fewer environmental risks and thus community acceptance than other renewable energy developments. Government support is the key and initial power for developing marine renewable energy. To promote the development and utilization of marine renewable energy, the Chinese government has established the special funding plan for marine renewable energy, and released “the 13th Five-years Plan (2016-2020) for marine renewable energy”. This paper describes the mechanisms established by the marine renewable Energy policy in China, and provides a comparative analysis of the Chinese marine renewable energy policy framework. We provides some policy recommendations for future development of marine renewable energy in China.

  18. Toward a national policy for managing low-level radioactive waste: key issues and recommendations

    International Nuclear Information System (INIS)

    Duerksen, C.J.; Mantell, M.; Thompson, G.P.

    1981-06-01

    The Conservation Foundation, a not-for-profit research and public education organization, asked individuals with diverse backgrounds and viewpoints to come together under Foundation leadership as a Dialogue Group on Low-Level Radioactive Waste Management. The group, including persons who represent waste generators, concerned citizens, state regulators, and environmentalists, met over an 18-month period to discuss issues crucial to the development of a national policy on low-level wastes. The Dialogue Group agreed that three principles, if accepted broadly, would form the basis of a sound national policy for managing low-level radioactive wastes: with proper implementation, technology exists to manage low-level waste safely; generators and their customers should pay disposal costs; and greater public involvement at all stages can improve the disposal system. These principles acted as polestars for the group as it worked toward a series of policy recommendations in four main areas: (1) cleaning up closed commercial sites; (2) remodeling a system for defining and classifying low-level radioactive waste; (3) siting new low-level waste disposal facilities; and (4) decommissioning, long-term care, and liability. This report presents an extensive discussion of these recommendations covering qualifications, limitations, and alternatives

  19. Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of sixth biannual meeting (September 2014).

    Science.gov (United States)

    2015-03-10

    The Malaria Policy Advisory Committee to the World Health Organization held its sixth meeting in Geneva, Switzerland from 10 to 12 September 2014. This article provides a summary of the discussions, conclusions and recommendations from that meeting.Meeting sessions covered the following: an update on drug resistance and containment including an assessment on the feasibility of elimination of Plasmodium falciparum malaria in the Greater Mekong Subregion; guidance on the control of residual malaria transmission by behaviourally resistant vectors; progress on the implementation of the Global Plan for Insecticide Resistance Management; updates on the Global Technical Strategy, Global Malaria Action Plan and the Plasmodium vivax technical brief; gaps in current World Health Organization Global Malaria Programme guidance for acceleration to elimination; surveillance, monitoring and evaluation; the updated World Health Organization Guidelines for the Prevention and Treatment of Malaria; Round 5 product testing for rapid diagnostic tests; and Intermittent Preventive Treatment for infants.Policy statements, position statements, and guidelines that arise from the Malaria Policy Advisory Committee meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

  20. Women Entrepreneurship in the Western Romania. Research Results and Policy Recommendations

    Directory of Open Access Journals (Sweden)

    Anca DODESCU

    2011-01-01

    Full Text Available Starting from the results of the empirical, quantitative, and qualitative research performed in the AntrES project, between 5.01.2009 - 4.01.2011, in the Western Romania, referring to the existence of obvious gender gaps regarding the start up of new businesses and the ownership of the businesses; the characteristics, the motivations, and the difficulties of the women entrepreneurs and potentially enterprising women; the successful women entrepreneurs' perceptions on the sex equality in the field of entrepreneurship - this paper presents arguments and recommendations of specific policies meant to support the potential women entrepreneurship in Romania, as an engine to overcome the economic crisis and to reconnect to the regional development mechanism facilitated by the European Union's regional policy.

  1. Short rotation plantations policy history in Europe: lessons from the past and recommendations for the future.

    Science.gov (United States)

    Lindegaard, Kevin N; Adams, Paul W R; Holley, Martin; Lamley, Annette; Henriksson, Annika; Larsson, Stig; von Engelbrechten, Hans-Georg; Esteban Lopez, Gonzalo; Pisarek, Marcin

    2016-08-01

    Short rotation plantations (SRPs) are fast-growing trees (such as willow ( Salix spp.), poplar ( Populus spp.) and Eucalyptus ) grown closely together and harvested in periods of 2-20 years. There are around 50,000 hectares of SRPs in Europe, a relatively small area considering that there have been supportive policy measures in many countries for 30 years. This paper looks at the effect that the policy measures used in different EU countries have had, and how other external factors have impacted on the development of the industry. Rokwood was a 3-year European funded project which attempted to understand the obstacles and barriers facing the woody energy crops sector using well established methods of SWOT and PESTLE analysis. Stakeholder groups were formed in six different European regions to analyze the market drivers and barriers for SRP and propose ways that the industry could make progress through targeted research and development and an improved policy framework. Based upon the outcomes of the SWOT and PESTLE analysis, each region produced a series of recommendations for policymakers, public authorities, and government agencies to support the development, production, and use of SRP-derived wood fuel in each of the partner countries. This study provides details of the SRP policy analysis and reveals that each region shared a number of similarities with broad themes emerging. There is a need to educate farmers and policymakers about the multifunctional benefits of SRPs. Greater financial support from regional and/or national government is required in order to grow the SRP market. Introducing targeted subsidies as an incentive for growers could address lack of local supply chains. Long-term policy initiatives should be developed while increasing clarity within Government departments. Research funding should enable closer working between universities and industry with positive research findings developed into supportive policy measures.

  2. The Status, Obstacles and Policy Recommendations of Shale Gas Development in China

    Directory of Open Access Journals (Sweden)

    Guanglin Pi

    2015-02-01

    Full Text Available The Chinese government has introduced numerous policies and development plans to boost its shale gas industry in recent years. However, China’s shale gas exploration and development is still in the initial stage and has been confronted with many challenges. This paper systematically analyzes the current status of China’s shale gas industry from five aspects for the first time—resource situation, exploration and development status, policy and planning situation, technology status and international cooperation—then respectively elaborates on the different obstacles of shale gas development in the short run and the medium and long term. We argue that short-term barriers to the Chinese shale gas industry mainly include objective factors, such as geological and surface conditions, shale gas proven reserves, technology innovation and environmental concerns, while some man-made obstacles (except for water scarcity may restrict shale gas development in the medium and long term. In order to better tackle the short-term challenges, this paper proposes policy recommendations from five perspectives: strengthening the investigation and evaluation of China’s shale gas resources; perfecting shale gas industry policy; establishing a national shale gas comprehensive experimental zone; enhancing scientific and technological research; and establishing a shale gas regulatory system with an emphasis on environmental protection and supervision.

  3. [Bad results obtained from the current public health policies and recommendations of hydration].

    Science.gov (United States)

    San Mauro Martín, Ismael; Romo Orozco, Denisse Aracely; Mendive Dubourdieu, Paula; Garicano Vilar, Elena; Valente, Ana; Betancor, Fabiana; Morales Hurtado, Alexis Daniel; Garagarza, Cristina

    2016-07-19

    Achieving an adequate intake of water is crucial within a balanced diet. For that purpose, dietary guidelines for healthy eating and drinking are an important consideration and need to be updated and disseminated to the population. We aimed to evaluate the liquid intake habits of a Mediterranean and Latin American population (Spain-Portugal and Mexico-Uruguay) and if they support the current recommendations of hydration by the EFSA. A record of fluid intake was obtained from 1168 participants from 4 countries above; and then compared with current consensus about hydration 1600 mL/day (female) and 2000 mL/day (male). The average fluid intake slightly surpassed the recommended: mean of 2049 mL/day (2,223 mL in males, 1,938 mL in females). Portugal stood out due to its lower intake (mean of 1,365 mL/day). Water contributed the largest part to total fluid intake (37%) in all countries (mean of 1365 mL/day). Hot beverages (18%) and milk and derivates (17%) follow water in highest consumption. The 20% of males and only 0.3% of females knew recommendations of hydration, while 63.3% of males and 62% of females followed them. Only 8.4% of people who follow the recommendations know them. The people studied surpassed the recommendation, although majority they didn´t know it. Future research should examine actual beverage consumption patterns and evaluate if the current consensuses are correctly adapted to the population needs. Hydration's policies should be transmitted to the population for their knowledge and adequate compliance.

  4. Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of March 2013 meeting

    Science.gov (United States)

    2013-01-01

    The Malaria Policy Advisory Committee to the World Health Organization met in Geneva, Switzerland from 13 to 15 March, 2013. This article provides a summary of the discussions, conclusions and recommendations from that meeting. Meeting sessions included: a review of the efficacy of artemisinin-based combination therapy in Guyana and Suriname; the outcomes from a consultation on non-malaria febrile illness; the outcomes from the second meeting of the Evidence Review Group on malaria burden estimation; an update on the review of the WHO Guidelines for the Treatment of Malaria; an update regarding progress on the constitution of the vector control Technical Expert Group; updates on the RTS, S/AS01 vaccine and the malaria vaccine technology roadmap; financing and resource allocation for malaria control; malaria surveillance and the need for a surveillance, monitoring and evaluation Technical Expert Group; criteria and classification related to malaria elimination; the next meeting of the Evidence Review Group on Intermittent Preventive Treatment in pregnancy; an update on the soon-to-be launched Elimination Scenario Planning Tool; and an update on the process for the Global Technical Strategy for Malaria Control and Elimination (2016–2025). Policy statements, position statements, and guidelines that arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme. PMID:23787092

  5. Climate change and mountain water resources: overview and recommendations for research, management and policy

    Directory of Open Access Journals (Sweden)

    D. Viviroli

    2011-02-01

    Full Text Available Mountains are essential sources of freshwater for our world, but their role in global water resources could well be significantly altered by climate change. How well do we understand these potential changes today, and what are implications for water resources management, climate change adaptation, and evolving water policy? To answer above questions, we have examined 11 case study regions with the goal of providing a global overview, identifying research gaps and formulating recommendations for research, management and policy.

    After setting the scene regarding water stress, water management capacity and scientific capacity in our case study regions, we examine the state of knowledge in water resources from a highland-lowland viewpoint, focusing on mountain areas on the one hand and the adjacent lowland areas on the other hand. Based on this review, research priorities are identified, including precipitation, snow water equivalent, soil parameters, evapotranspiration and sublimation, groundwater as well as enhanced warming and feedback mechanisms. In addition, the importance of environmental monitoring at high altitudes is highlighted. We then make recommendations how advancements in the management of mountain water resources under climate change could be achieved in the fields of research, water resources management and policy as well as through better interaction between these fields.

    We conclude that effective management of mountain water resources urgently requires more detailed regional studies and more reliable scenario projections, and that research on mountain water resources must become more integrative by linking relevant disciplines. In addition, the knowledge exchange between managers and researchers must be improved and oriented towards long-term continuous interaction.

  6. Decomposition of energy-related carbon emissions in Xinjiang and relative mitigation policy recommendations

    Science.gov (United States)

    Wang, Changjian; Zhang, Xiaolei; Wang, Fei; Lei, Jun; Zhang, Li

    2015-03-01

    Regional carbon emissions research is necessary and helpful for China in realizing reduction targets. The LMDI I (Logarithmic Mean Divisia Index I) technique based on an extended Kaya identity was conducted to uncover the main five driving forces for energy-related carbon emissions in Xinjiang, an important energy base in China. Decomposition results show that the affluence effect and the population effect are the two most important contributors to increased carbon emissions. The energy intensity effect had a positive influence on carbon emissions during the pre-reform period, and then became the dominant factor in curbing carbon emissions after 1978. The renewable energy penetration effect and the emission coefficient effect showed important negative but relatively minor effects on carbon emissions. Based on the local realities, a comprehensive suite of mitigation policies are raised by considering all of these influencing factors. Mitigation policies will need to significantly reduce energy intensity and pay more attention to the regional economic development path. Fossil fuel substitution should be considered seriously. Renewable energy should be increased in the energy mix. All of these policy recommendations, if implemented by the central and local government, should make great contributions to energy saving and emission reduction in Xinjiang.

  7. 47 CFR 95.417 - (CB Rule 17) Do I identify my CB communications?

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false (CB Rule 17) Do I identify my CB communications? 95.417 Section 95.417 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... Station § 95.417 (CB Rule 17) Do I identify my CB communications? (a) You need not identify your CB...

  8. Energy sector assistance in developing countries: Current trends and policy recommendations

    International Nuclear Information System (INIS)

    Tharakan, Pradeep J.; Castro, Julio de; Kroeger, Timm

    2007-01-01

    An estimated 2.5 billion people remain without access to modern energy supplies. This shortfall is expected to grow as the population in developing countries continues to grow rapidly and the existing infrastructure ages. The United Nations' goal of lowering poverty by half by 2015 will not be attained unless the poor in developing countries gain greater access to basic infrastructure and services, including energy services. The key objective of this paper is to analyze trends in overseas development assistance (ODA) to the energy sector in developing countries during the period 1990-2003, relative to realized private sector investments. This analysis then forms the basis for policy recommendations for consideration by decision makers within countries that are major contributors to ODA

  9. The Ethics of Virtual Reality Technology: Social Hazards and Public Policy Recommendations.

    Science.gov (United States)

    Spiegel, James S

    2017-09-23

    This article explores four major areas of moral concern regarding virtual reality (VR) technologies. First, VR poses potential mental health risks, including Depersonalization/Derealization Disorder. Second, VR technology raises serious concerns related to personal neglect of users' own actual bodies and real physical environments. Third, VR technologies may be used to record personal data which could be deployed in ways that threaten personal privacy and present a danger related to manipulation of users' beliefs, emotions, and behaviors. Finally, there are other moral and social risks associated with the way VR blurs the distinction between the real and illusory. These concerns regarding VR naturally raise questions about public policy. The article makes several recommendations for legal regulations of VR that together address each of the above concerns. It is argued that these regulations would not seriously threaten personal liberty but rather would protect and enhance the autonomy of VR consumers.

  10. The Belgian Health System Performance Report 2012: snapshot of results and recommendations to policy makers.

    Science.gov (United States)

    Vrijens, France; Renard, Françoise; Jonckheer, Pascale; Van den Heede, Koen; Desomer, Anja; Van de Voorde, Carine; Walckiers, Denise; Dubois, Cécile; Camberlin, Cécile; Vlayen, Joan; Van Oyen, Herman; Léonard, Christian; Meeus, Pascal

    2013-09-01

    Following the commitments of the Tallinn Charter, Belgium publishes the second report on the performance of its health system. A set of 74 measurable indicators is analysed, and results are interpreted following the five dimensions of the conceptual framework: accessibility, quality of care, efficiency, sustainability and equity. All domains of care are covered (preventive, curative, long-term and end-of-life care), as well as health status and health promotion. For all indicators, national/regional values are presented with their evolution over time. Benchmarking to results of other EU-15 countries is also systematic. The policy recommendations represent the most important output of the report. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. COLLABORATION BOARD (CB55)

    CERN Multimedia

    B. Cousins

    Open Access Publication Policy ATLAS had recently issued a short statement in support of open access publishing. The mood of the discussions in the December CMS Collaboration Board had appeared to be in favour and so it was being proposed that CMS issue the same statement as that made by ATLAS (the statement is attached to the agenda of this meeting). The Collaboration Board agreed. Election of the Chair of the Collaboration Board Following the agreement to shorten the terms of both the Spokesperson and the Collaboration Board Chair, and to introduce a longer overlap period between the election and the start of the term, the election for the next Collaboration Board Chair was due in December 2007. If the old standard schedule specified in the Constitution were adapted to this date, then the Board should be informed at the present meeting that the election was being prepared. However, it was felt that the experience of the previous year's election of the Spokesperson had shown that it would be desirable to...

  12. Ebola Virus Epidemic in West Africa: Global Health Economic Challenges, Lessons Learned, and Policy Recommendations.

    Science.gov (United States)

    Elmahdawy, Mahmoud; Elsisi, Gihan H; Carapinha, Joao; Lamorde, Mohamed; Habib, Abdulrazaq; Agyie-Baffour, Peter; Soualmi, Redouane; Ragab, Samah; Udezi, Anthony W; Usifoh, Cyril; Usifoh, Stella

    2017-09-01

    The Ebola virus has spread across several Western Africa countries, adding a significant financial burden to their health systems and economies. In this article the experience with Ebola is reviewed, and economic challenges and policy recommendations are discussed to help curb the impact of other diseases in the future. The West African Ebola virus disease epidemic started in resource-constrained settings and caused thousands of fatalities during the last epidemic. Nevertheless, given population mobility, international travel, and an increasingly globalized economy, it has the potential to re-occur and evolve into a global pandemic. Struggling health systems in West African countries hinder the ability to reduce the causes and effects of the Ebola epidemic. The lessons learned include the need for strengthening health systems, mainly primary care systems, expedited access to treatments and vaccines to treat the Ebola virus disease, guidance on safety, efficacy, and regulatory standards for such treatments, and ensuring that research and development efforts are directed toward existing needs. Other lessons include adopting policies that allow for better flow of relief, averting the adverse impact of strong quarantine policy that includes exaggerating the aversion behavior by alarming trade and business partners providing financial support to strengthen growth in the affected fragile economies by the Ebola outbreak. Curbing the impact of future Ebola epidemics, or comparable diseases, requires increased long-term investments in health system strengthening, better collaboration between different international organizations, more funding for research and development efforts aimed at developing vaccines and treatments, and tools to detect, treat, and prevent future epidemics. Copyright © 2017. Published by Elsevier Inc.

  13. Seasonal influenza vaccine policies, recommendations and use in the World Health Organization’s Western Pacific Region Original Research

    Directory of Open Access Journals (Sweden)

    Members of the Western Pacific Region Global Influenza Surveillance and Response System

    2013-09-01

    Full Text Available Objective: Vaccination is the most effective way to prevent seasonal influenza and its severe outcomes. The objective of our study was to synthesize information on seasonal influenza vaccination policies, recommendations and practices in place in 2011 for all countries and areas in the Western Pacific Region of the World Health Organization (WHO. Methods: Data were collected via a questionnaire on seasonal influenza vaccination policies, recommendations and practices in place in 2011. Results: Thirty-six of the 37 countries and areas (97% responded to the survey. Eighteen (50% reported having established seasonal influenza vaccination policies, an additional seven (19% reported having recommendations for risk groups for seasonal influenza vaccination only and 11 (30% reported having no policies or recommendations in place. Of the 25 countries and areas with policies or recommendations, health-care workers and the elderly were most frequently recommended for vaccination; 24 (96% countries and areas recommended vaccinating these groups, followed by pregnant women (19 [76%], people with chronic illness (18 [72%] and children (15 [60%]. Twenty-six (72% countries and areas reported having seasonal influenza vaccines available through public funding, private market purchase or both. Most of these countries and areas purchased only enough vaccine to cover 25% or less of their populations. Discussion: In light of the new WHO position paper on influenza vaccines published in 2012 and the increasing availability of country-specific data, countries and areas should consider reviewing or developing their seasonal influenza vaccination policies to reduce morbidity and mortality associated with annual epidemics and as part of ongoing efforts for pandemic preparedness.

  14. Variation in adult vaccination policies across Europe: an overview from VENICE network on vaccine recommendations, funding and coverage.

    Science.gov (United States)

    Kanitz, Elisabeth E; Wu, Lauren A; Giambi, Cristina; Strikas, Raymond A; Levy-Bruhl, Daniel; Stefanoff, Pawel; Mereckiene, Jolita; Appelgren, Eva; D'Ancona, Fortunato

    2012-07-27

    In 2010-2011, in the framework of the VENICE project, we surveyed European Union (EU) and Economic Area (EEA) countries to fill the gap of information regarding vaccination policies in adults. This project was carried out in collaboration with the United States National Vaccine Program Office, who conducted a similar survey in all developed countries. VENICE representatives of all 29 EU/EEA-countries received an online questionnaire including vaccination schedule, recommendations, funding and coverage in adults for 17 vaccine-preventable diseases. The response rate was 100%. The definition of age threshold for adulthood for the purpose of vaccination ranged from 15 to 19 years (median=18 years). EU/EEA-countries recommend between 4 and 16 vaccines for adults (median=11 vaccines). Tetanus and diphtheria vaccines are recommended to all adults in 22 and 21 countries respectively. The other vaccines are mostly recommended to specific risk groups; recommendations for seasonal influenza and hepatitis B exist in all surveyed countries. Six countries have a comprehensive summary document or schedule describing all vaccines which are recommended for adults. None of the surveyed countries was able to provide coverage estimates for all the recommended adult vaccines. Vaccination policies for adults are not consistent across Europe, including the meaning of "recommended vaccine" which is not comparable among countries. Coverage data for adults should be collected routinely like for children vaccination. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Cannabinoid Receptors CB1 and CB2 Form Functional Heteromers in Brain*

    Science.gov (United States)

    Callén, Lucía; Moreno, Estefanía; Barroso-Chinea, Pedro; Moreno-Delgado, David; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Lanciego, José Luis; Franco, Rafael; Lluis, Carmen; Canela, Enric I.; McCormick, Peter J.

    2012-01-01

    Exploring the role of cannabinoid CB2 receptors in the brain, we present evidence of CB2 receptor molecular and functional interaction with cannabinoid CB1 receptors. Using biophysical and biochemical approaches, we discovered that CB2 receptors can form heteromers with CB1 receptors in transfected neuronal cells and in rat brain pineal gland, nucleus accumbens, and globus pallidus. Within CB1-CB2 receptor heteromers expressed in a neuronal cell model, agonist co-activation of CB1 and CB2 receptors resulted in a negative cross-talk in Akt phosphorylation and neurite outgrowth. Moreover, one specific characteristic of CB1-CB2 receptor heteromers consists of both the ability of CB1 receptor antagonists to block the effect of CB2 receptor agonists and, conversely, the ability of CB2 receptor antagonists to block the effect of CB1 receptor agonists, showing a bidirectional cross-antagonism phenomenon. Taken together, these data illuminate the mechanism by which CB2 receptors can negatively modulate CB1 receptor function. PMID:22532560

  16. Emission trade in climate policy. Follow-up recommendation with regard to the Memorandum on Climate Policy, part 1. National measures

    International Nuclear Information System (INIS)

    2000-01-01

    In this recommendation the option to introduce tradable emission permits for greenhouse gases in the Netherlands and Europe is discussed, as well as the conditions for a national experiment with this market tool. In it's advice on the 'Memorandum on Climate Policy, part 1' the Social and Economic Council (SER) declared itself in favor of the options that are offered by emission trade for a cost-effective climate policy. In this follow-up advice on the same Memorandum the SER discusses this new, market tool for climate policy in more detail

  17. Tobacco Policies in Louisiana: Recommendations for Future Tobacco Control Investment from SimSmoke, a Policy Simulation Model.

    Science.gov (United States)

    Levy, David; Fergus, Cristin; Rudov, Lindsey; McCormick-Ricket, Iben; Carton, Thomas

    2016-02-01

    Despite the presence of tobacco control policies, Louisiana continues to experience a high smoking burden and elevated smoking-attributable deaths. The SimSmoke model provides projections of these health outcomes in the face of existing and expanded (simulated) tobacco control polices. The SimSmoke model utilizes population data, smoking rates, and various tobacco control policy measures from Louisiana to predict smoking prevalence and smoking-attributable deaths. The model begins in 1993 and estimates are projected through 2054. The model is validated against existing Louisiana smoking prevalence data. The most powerful individual policy measure for reducing smoking prevalence is cigarette excise tax. However, a comprehensive cessation treatment policy is predicted to save the most lives. A combination of tobacco control policies provides the greatest reduction in smoking prevalence and smoking-attributable deaths. The existing Louisiana excise tax ranks as one of the lowest in the country and the legislature is against further increases. Alternative policy measures aimed at lowering prevalence and attributable deaths are: cessation treatments, comprehensive smoke-free policies, and limiting youth access. These three policies have a substantial effect on smoking prevalence and attributable deaths and are likely to encounter more favor in the Louisiana legislature than increasing the state excise tax.

  18. Energy policies in the European Union. Germany's ecological tax reform

    International Nuclear Information System (INIS)

    Welfens, P.J.J.; Jungmittag, A.; Meyer, B.; Jasinski, P.

    2001-01-01

    The chapters discuss the following aspects: 1. Energy policy as a strategic element of economic policy in dynamic open economies. 2. Phasing out nuclear energy and core elements of sustainable energy strategy. 3. Ecological tax reform: Theory, modified double dividend and international aspects. 4. The policy framework in Europe and Germany. 5. Optimal ecological tax reform: Options and recommendations for an EU-action plan. 6. Conclusions. (orig./CB)

  19. Modeling Uncertainty and the Economics of Climate Change. Recommendations for Robust Energy Policy

    International Nuclear Information System (INIS)

    Haurie, A.; Tavoni, M.; Van der Zwaan, B.C.C.

    2011-01-01

    This special issue is meant to gather front-edge research and innovative analysis in the modeling of uncertainty related to the economics of climate change. The focus is notably on advancements in probabilistic integrated assessment modeling and stochastic analysis of climate futures. The possibility to use non-probabilistic economic methods to treat uncertainty in global or regional dynamic climate change models is explored as well. Given the intimate link between climate change and the nature of mankind's energy production and consumption system, this special issue also proffers direct practical recommendations for energy decision making at the global, regional, and national levels. The special issue originated from a series of research tasks carried out under the PLANETS project, funded by the European Commission under its 7th Framework Programme and co-coordinated by the Fondazione Eni Enrico Mattei (FEEM) and the Energy research Centre of the Netherlands (ECN). This project, accomplished in 2010, had, as main focus, how to incorporate uncertainty when carrying out numerical analysis of climate and energy policies. A special PLANETS session was organized during the 2010 edition of the International Energy Workshop (IEW 2010, Royal Institute of Technology, Stockholm), which generated broad expert discussion on both methodology and policy-related issues. The recognition of the importance of these topics and the diversity of approaches undertaken, plus a concern over them becoming fragmented in the literature, constituted the motivation to edit this special issue gathering the generated material in one orchestrated publication. Several contributions, in the form of 12 papers, have been brought together with the aim of providing a comprehensive overview of some of the main recent developments in the modeling of uncertainty in the economics of climate change. We categorize these 12 articles in five distinct domains in hybrid integrated assessment EEE (Energy

  20. Conflict between Supermarkets and Wet-Markets in Ghana: Early Warning Signals and Preventive Policy Recommendations

    Directory of Open Access Journals (Sweden)

    Etornam Kosi Anku

    2017-10-01

    Full Text Available The source of conflict between Supermarkets and Wet-markets arise from the use of market power and economies of scale by one group against the other. This study explores the tensions that exist between modern retailers and their traditional counterparts as a result of the influx of supermarkets in Ghana. The main objective of the study is to compare attributes related to the control of access to consumers by the Supermarket and the Wet-market. In this study, the dot-survey approach of Rapid Market Assessment Technique was used to elicit information from 438 respondents at the Madina market (wet-market and Melcom (supermarket over a period of two weeks and Wilcoxon-Mann-Whitney (WMW comparison test and descriptive statistics were employed for the analysis. The results revealed that consumers patronise the supermarkets for convenience and the wet-market for freshness of product. Their purchasing decisions were affected by their level of education and product selections of the retailer. The highly educated preferred to shop at the Supermarket instead of the Wet-market; however, over 50% of respondents preferred the wet-market for fresh food products and the supermarket for non-food items. Each retailer receives its fair share of purchases from its loyal customers, therefore the revolution arising from the supermarket influx in Ghana has not yet resulted into conflict between supermarkets and their traditional counterparts, though it is inevitable if nothing is done to prevent it from happening. To avoid the conflict, it is recommended that policies should be instituted to (i improve the market infrastructures and shopping environment in the Wet-markets, (ii give tax concession to modern retailers who source products from local farmers and small-scale processors, (iii enable traditional retailers position themselves on the fringe and co-exist with modern retailers and (iv enforce public standards with regards to food safety laws in the traditional

  1. Environmental components of OCS policy committee recommendations regarding national oil spill prevention and response program

    International Nuclear Information System (INIS)

    Groat, C.G.; Thorman, J.

    1991-01-01

    The Exxon Valdez oil spill of March 24, 1989 resulted in thousands of pages of analytical reports assessing the environmental, organizational, legal, procedural, social, economic, and political aspects of the event. Even though the accident was a transportation incident, it had a major impact on the public and political perception of offshore oil operations. This caused the OCS Policy Committee, which advises the Secretary of the Interior and the Minerals Management Service on Outer Continental Shelf resource development and environmental matters, to undertake a review of the reports for the purpose of developing recommendations to the secretary for improvements in OCS operations that would insure maximum efforts to prevent spills and optimal ability to deal with any that occur. The Committee felt strongly that 'a credible national spill prevention and response program from both OCS and non-OCS oil spills in the marine environment is needed to create the political climate for a viable OCS program.' The report of the Committee described eight essential elements of this program; four of these focused on the environmental aspects of oil spills, calling for (1) adequate characterization of the marine and coastal environment, including both information and analysis, accessible to decision makers, (2) the capacity to restore economic and environmental resources as quickly as possible if damage occurs, (3) a mechanism for research on oil spill impacts, and (4) a meaningful role for all interested and responsible parties, including the public, in as many of these activities as possible, from spill prevention and contingency planning to environmental oversight of ongoing operations and participation in clean-up and restoration activities

  2. A lexicographic approach to language policy and recommendations for future dictionaries

    DEFF Research Database (Denmark)

    Tarp, Sven; Gouws, Rufus H.

    2008-01-01

    Language policy prevails at different levels and its formulation typically results in a prescriptive presentation of data. In their dictionaries, lexicographers have to respond to the deci­sions of language policy makers. In this regard dictionaries can adhere to a strict prescriptive policy by i...

  3. A Policy Analysis of the Coast Guard's Existing Patient Satisfaction System and Recommendations for Improvement

    National Research Council Canada - National Science Library

    Coughlin, Kelly A

    2007-01-01

    .... This paper evaluates CG organizational demands, describes CG practice landscape, presents standards, reviews initial clinic process analysis, and evaluates the cost and criteria of proposed policy alternatives...

  4. Social Media Policy in Social Work Education: A Review and Recommendations

    Science.gov (United States)

    Karpman, Hannah E.; Drisko, James

    2016-01-01

    Although social media use has grown dramatically, program policies have not kept pace. Some programs now state that student social media activities have led to professional conduct reviews and may violate ethical standards. This article reviews current social media policies and conceptualizes their key elements. A review of current social media…

  5. Reducing the Impact of Immigration Enforcement Policies to Ensure the Health of North Carolinians: Statewide Community-Level Recommendations.

    Science.gov (United States)

    Mann, Lilli; Simán, Florence M; Downs, Mario; Sun, Christina J; de Hernandez, Brisa Urquieta; García, Manuel; Alonzo, Jorge; Lawlor, Emma; Rhodes, Scott D

    2016-01-01

    Research indicates that fear of immigration enforcement among Latinos in North Carolina results in limited access to and utilization of health services and negative health consequences. This project developed recommendations to mitigate the public health impact of immigration enforcement policies in North Carolina. Our community-based participatory research partnership conducted 6 Spanish-language report-backs (an approach to sharing, validating, and interpreting data) and 3 bilingual forums with community members and public health leaders throughout North Carolina. The goals of these events were to discuss the impact of immigration enforcement on Latino health and develop recommendations to increase health services access and utilization. Findings from the report-backs and forums were analyzed using grounded theory to identify and refine common recommendations. A total of 344 people participated in the report-backs and forums. Eight recommendations emerged: increase knowledge among Latinos about local health services; build capacity to promote policy changes; implement system-level changes among organizations providing health services; train lay health advisors to help community members navigate systems; share Latinos' experiences with policy makers; reduce transportation barriers; increase schools' support of Latino families; and increase collaboration among community members, organizations, health care providers, and academic researchers. Representatives from 16 of 100 North Carolina counties participated. These 16 counties represent geographically diverse regions, and many of these counties have large Latino populations. Immigration enforcement is a public health issue. Participants proposed developing new partnerships, identifying strategies, and implementing action steps for carrying out recommendations to reduce negative health outcomes among Latinos in North Carolina. ©2016 by the North Carolina Institute of Medicine and The Duke Endowment. All rights

  6. Cannabinoid Receptors CB1 and CB2 Modulate the Electroretinographic Waves in Vervet Monkeys

    DEFF Research Database (Denmark)

    Bouskila, Joseph; Harrar, Vanessa; Javadi, Pasha

    2016-01-01

    ) and CB2R is exclusively found in the retinal glia (Müller cells). However, the role of these cannabinoid receptors in normal primate retinal function remains elusive. Using full-field electroretinography in adult vervet monkeys, we recorded changes in neural activity following the blockade of CB1R and CB......The expression patterns of the cannabinoid receptor type 1 (CB1R) and the cannabinoid receptor type 2 (CB2R) are well documented in rodents and primates. In vervet monkeys, CB1R is present in the retinal neurons (photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells......-waves. In scotopic conditions, both blockers increased the b-wave amplitude but did not change the a-wave amplitude. These findings suggest an important role of CB1R and CB2R in primate retinal function....

  7. Policy analysis and recommendations for the open source application development portal (OSADP).

    Science.gov (United States)

    2012-06-01

    This white paper addresses the policy and institutional issues that are associated with the development of an open source applications development portal (OSADP), part of a larger research effort being conducted under the ITS Programs Dynamic Mobi...

  8. Advancing Health Marketing Research and Policy Recommendations by Incorporating Source Perspectives.

    Science.gov (United States)

    Mackert, Michael; Guadagno, Marie; Champlin, Sara

    2015-01-01

    Communication researchers, recognizing the message sent is not necessarily the same as the message received, have incorporated the perspective of advertising professionals into the study of advertising effects. Health marketing research could similarly benefit from incorporating this largely absent perspective into the academic and policy debate surrounding the impact of advertising on health issues ranging from obesity to alcohol use. This commentary serves as a call to action to stakeholders in this academic and policy debate: focus on the perspective of advertising professionals to enrich health marketing and public health research in which advertising is the delivery vehicle for health messages.

  9. Chancellors and Superintendents Employment Terms: Contracts, Policies, and Practices. Recommendations and Survey Results.

    Science.gov (United States)

    Smith, Cindra

    This document provides recommendations to Community College chancellors and superintendents based on survey responses from 11 multi-college district chancellors and 37 single college district superintendents and/or presidents of the Community College League of California. The report provides demographic information, such as gender, ethnicity,…

  10. Regulatory and Financial Reform of Federal Research Policy: Recommendations to the NRC Committee on Research Universities

    Science.gov (United States)

    Association of American Universities, 2011

    2011-01-01

    At the request of the National Research Council (NRC) Committee on Research Universities, the Council on Governmental Relations (COGR), the Association of American Universities (AAU), and the Association of Public and Land-grant Universities (APLU) have assembled a set of ten recommendations for regulatory reform that would improve research…

  11. Anonymous Communication Policies for the Internet: Results and Recommendations of the AAAS Conference.

    Science.gov (United States)

    Teich, Al; Frankel, Mark S.; Kling, Rob; Lee, Yaching

    1999-01-01

    Reports the results of a conference on the Internet and anonymous communication organized by the American Association for the Advancement of Science (AAAS). Discusses how anonymous communications can be shaped by the law, education, and public awareness, and highlights the importance of involving all affected interests in policy development.…

  12. Review of hookah tobacco smoking among college students: policy implications and research recommendations.

    Science.gov (United States)

    Gathuru, Irene M; Tarter, Ralph E; Klein-Fedyshin, Michele

    2015-01-01

    About 30% of college students have smoked hookah tobacco. Although most students perceive this product to be innocuous and non-addictive, hookah tobacco increases the risk for disease and nicotine dependence. Currently, the US Food and Drug Administration (FDA) does not regulate the manufacture, distribution, or sale of hookah tobacco. Empirical literature pertaining to hookah tobacco smoking is reviewed with a focus on the implications for regulatory policy. PubMed, PsycINFO, and Scopus databases were searched to locate articles published in English. The literature search combined several key words including "hookahs", "college", "advertising", "health effects", and "health policy". Smoking hookah tobacco may play a role in the initiation of smoking among tobacco-naïve college students and may portend persistent smoking among those who have smoked cigarettes. College students are typically nondaily, social smokers. They do not perceive that their heightened risk for tobacco diseases and nicotine dependence relates to their smoking behavior. However, few public health messages target college-age adults to counter media messages that endorse hookah tobacco smoking. Given that the FDA is not authorized to ban specific tobacco products, policy actions should focus on the development of effective risk communication strategies that target college-age adults and on limiting the accessibility of hookah tobacco products to these adults. Accordingly, a research agenda that would inform these policy actions is proposed.

  13. Physical and Psychological Health Following Military Sexual Assault: Recommendations for Care, Research, and Policy

    Science.gov (United States)

    2013-01-01

    syndrome, infertility , chronic fatigue, and chronic pain (Ciccone et al., 2005; Frayne et al., 1999; Golding, 1994). Acute psychological distress in...medical, forensic, and psychological support services. These reports are kept strictly confidential and are not released to commanding officers, and...those for combat exposure, policies and programs that support psychological health and deliver mental health care are applicable for MSA victims

  14. Practical Recommendations on the Improvement of the Effectiveness of Anti-Corruption Policy in Universities

    OpenAIRE

    Zamaletdinov, Radif R.; Yudina, Nadezhda P.; Lavrentyeva, Elvira I.; Savva, Lubov I.; Pugacheva, Natalya B.

    2016-01-01

    The relevance of the study is conditioned by the expansion of the scale of corruption in higher education. The purpose of the article is to develop practical recommendations for improving of anti-corruption policy’s effectiveness at universities. The study involved 450 teachers, 1200 students from 140 Russian universities. The main results of the study are to identify the causes of bribery and popular tools of counteraction of corruption in universities, organizational and practical measure...

  15. Tackling U.S. energy challenges and opportunities: preliminary policy recommendations for enhancing energy innovation in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Anadon, Laura Diaz; Gallagher, Kelly Sims; Bunn, Matthew; Jones, Charles

    2009-02-18

    The report offers preliminary recommendations for near-term actions to strengthen the U.S. effort to develop and deploy advanced energy technologies. The report comes as the Obama Administration and the 111th U.S. Congress face enormous challenges and opportunities in tackling the pressing security, economic, and environmental problems posed by the energy sector. Improving the technologies of energy supply and end-use is a prerequisite for surmounting these challenges in a timely and cost-effective way, and this report elaborates on how policy can support develop of these important energy technologies.

  16. Hazing in the U.S. Armed Forces: Recommendations for Hazing Prevention Policy and Practice

    Science.gov (United States)

    2015-01-01

    life. 2. Bullying —United States. 3. Hazing— United States—Government policy. 4. Military offenses—United States. 5. Soldiers— United States—Social...for hazing prevention and swift enforcement of punishment for hazing. – Ensure that there are options for reporting anonymously and outside the chain...standalone category in the database P P P P The system tracks bullying separately P The system tracks anonymous reports P P The system tracks initial

  17. A Review of Electric Vehicle Lifecycle Emissions and Policy Recommendations to Increase EV Penetration in India

    OpenAIRE

    Rachana Vidhi; Prasanna Shrivastava

    2018-01-01

    Electric vehicles reduce pollution only if a high percentage of the electricity mix comes from renewable sources and if the battery manufacturing takes place at a site far from the vehicle use region. Industries developed due to increased electric vehicle adoption may also cause additional air pollution. The Indian government has committed to solving New Delhi’s air pollution issues through an ambitious policy of switching 100% of the light duty consumer vehicles to electric vehicles by 2030....

  18. Contextual Positive Psychology: Policy Recommendations for Implementing Positive Psychology into Schools

    OpenAIRE

    Ciarrochi, Joseph; Atkins, Paul W. B.; Hayes, Louise L.; Sahdra, Baljinder K.; Parker, Philip

    2016-01-01

    There has been a rapid growth in positive psychology, a research and intervention approach that focuses on promoting optimal functioning and well-being. Positive psychology interventions are now making their way into classrooms all over the world. However, positive psychology has been criticized for being decontextualized and coercive, and for putting an excessive emphasis on positive states, whilst failing to adequately consider negative experiences. Given this, how should policy be used to ...

  19. Toward the Target Model 2.0. Policy Recommendations for a Sustainable EU Power Market Design. Executive summary

    International Nuclear Information System (INIS)

    Roques, Fabien; Perekhodtsev, Dmitri; Verhaeghe, Charles

    2015-06-01

    One of the 10 key priorities of the new European Commission President Jean-Claude Juncker consists of 'reform(ing) and reorganis(ing) Europe's energy policy into a new European Energy Union'. The Energy Union work programme released on 25 February 2015 suggests that a new electricity market design is needed in order to tackle Europe's chosen policy objectives of de-carbonisation whilst maintaining security of supply. The current regulatory and market framework does not provide a sound basis for the investments needed to maintain security of supply and de-carbonise the power sector at an affordable cost. As policy priorities in favour of de-carbonisation and maintaining security of supply have taken centre stage on the policy agenda in the past decade, the design of liberalised electricity markets has failed to evolve and be reconciled with these new priorities. In addition, the issues of competitiveness and affordability of electricity in Europe remain central in the discussions about the market framework. The objective of this study is to assess the deficiencies and gaps in the current European Target Model and the wider regulatory framework for power generation and to propose a number of policy recommendations for improvement. Recognising the need for 'fresh thinking' on the issue, this study looks outside Europe to learn the lessons from experiences with a range of alternative market designs that exist around the globe. The study provides a comprehensive assessment of the issues with current European electricity markets. The study investigates the lessons from market reforms in North America and in Latin America in the past decade to identify 'out of the box' thinking to fill the gaps in the current European Target model. This report presents some of the research findings and concludes with a set of alternative potential directions for reform of European power markets models in the long term, as well as a number of

  20. Hepatic expression of cannabinoid receptors CB1 and CB2 correlate with fibrogenesis in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Erhei Dai

    2017-06-01

    Conclusions: The hepatic expression of CB1 and CB2 plays an important role during the progression of fibrosis induced by CHB. Endogenous activation of CB1 receptors in patients with CHB enhances fibrogenesis by direct effect on activated HSCs.

  1. State of the art conference on weight management in VA: Policy and research recommendations for advancing behavioral interventions.

    Science.gov (United States)

    Masheb, Robin M; Chan, Stephanie H; Raffa, Susan D; Ackermann, Ronald; Damschroder, Laura J; Estabrooks, Paul A; Evans-Hudnall, Gina; Evans, Neil C; Histon, Trina; Littman, Alyson J; Moin, Tannaz; Nelson, Karin M; Pagoto, Sherry; Pronk, Nico P; Tate, Deborah F; Goldstein, Michael G

    2017-04-01

    This article summarizes outcomes of the behavioral interventions work group for the Veterans Health Administration (VHA) State of the Art Conference (SOTA) for Weight Management. Sixteen VHA and non-VHA subject matter experts, representing clinical care delivery, research, and policy arenas, participated. The work group reviewed current evidence of efficacy, effectiveness, and implementation of behavioral interventions for weight management, participated in phone- and online-based consensus processes, generated key questions to address gaps, and attended an in-person conference in March 2016. The work group agreed that there is strong evidence for efficacy and effectiveness of core behavioral intervention components and processes, but insufficient evidence to determine the comparative effectiveness of multiple clinician-delivered weight management modalities, as well as technologies that may or may not supplement clinician-delivered treatments. Effective strategies for implementation of weight management services in VHA were identified. The SOTA work group's foremost policy recommendations are to establish a system-wide culture for weight management and to identify a population-level health metric to measure the impact of weight management interventions that can be tracked and clearly communicated throughout VHA. The work group's top research recommendation is to determine how to deploy and scale the most effective behavioral weight management interventions for Veterans.

  2. INDIA’S FOREIGN DIRECT INVESTMENT: CURRENT STATUS, ISSUES AND POLICY RECOMMENDATIONS

    Directory of Open Access Journals (Sweden)

    Mukesh Ranga

    2010-12-01

    Full Text Available Foreign Direct Investment (FDI as an important driver of growth. It is an important source of non debt financial resources for country for economic development. Besides it is a means of achieving technical know-how and employment generation of employment. However, many are of the view that FDI is a big threat to sovereignty of host and domestic business houses. Faster exploitation of natural resources for profit may deprive host from such resources in long run. Midst of debate on pros and cons of FDI, world economy has observed a phenomenal change in volume and pattern of FDI. There is clearly an intense global competition of FDI. India is not behind this global race of attracting foreign investment. India emerged as an attractive FDI destination in services but has failed to evolve a manufacturing hub which has greater economic benefit. FDI though one of the important sources of financing the economic development, but not is not a solution for poverty eradication, unemployment and other economic ills. India needs a massive investment to achieve the goals of vision 20-20. Policy makers need to ensure transparency and consistency in policy making along with comprehensive long term development strategy.

  3. The Determinants of won/dollar Exchange Rate Volatility and Policy Recommendations

    Directory of Open Access Journals (Sweden)

    Chae-Shick Chung

    1998-09-01

    Full Text Available This thesis analyzed the feature and different points of the changing of the exchange rate of Korea won against US dollar, then discussed the direction of the completion of Korea exchange rate system. The prediction result of the model GARCH which vividly shows the phenomenon of the auto-regression of the exchange rate has indicated the level of the exchange rate yesterday could explain the circumstance of the change of exchange rate today. Meanwhile, the policy of the US exchange rate will affect the exchange rate of Korea won against US dollar and the volatility of foreign exchange rate. In the present situation of Korean economy in which the liberalization of capital and the independence of the central bank has been established, the choosing range of the exchange system could only be completely changeable exchange rate system or exchange rate system of multilateral arrangement like Europe. However, in terms of the condition of the world economy, the introduction of the latter system is too early. There is an idea that under the changeable exchange rate system which is the only choice, it is the right time to activate the main body of private economy, the financial derivatives market in which the exchange risk could be trade-off. Government should work on and create a policy that would be able to satisfy the expectations of the market participants.

  4. Contextual positive psychology: Policy recommendations for implementing positive psychology into schools.

    Directory of Open Access Journals (Sweden)

    Joseph Ciarrochi

    2016-10-01

    Full Text Available There has been a rapid growth in positive psychology, a research and intervention approach that focuses on promoting optimal functioning and well-being. Positive psychology interventions are now making their way into classrooms all over the world. However, positive psychology has been criticized for being decontextualized and coercive, and for putting an excessive emphasis on positive states, whilst failing to adequately consider negative experiences. Given this, how should policy be used to regulate and evaluate these interventions? We review evidence that suggests these criticisms may be valid, but only for those interventions that focus almost exclusively on changing the content of people’s inner experience (e.g., make it more positive and personality (improving character strength, and overemphasize the idea that inner experience causes action. We describe a contextualized form of positive psychology that not only deals with the criticisms, but also has clear policy implications for how to best implement and evaluate positive education programs so that they do not do more harm than good.

  5. Policy Implications and Research Recommendations: A Review of Hookah Use Among US College Students.

    Science.gov (United States)

    Fevrier, Bradley; Vidourek, Rebecca A; Privitera, Pauline

    2018-03-30

    The rate of Hookah use among college students during the last decade is about 30%. Although college students perceive hookah use as a safer alternative to conventional cigarettes, hookah use increases the risk of disease and nicotine dependence, and therefore remains an area of concern. Presently, the US Food and Drug Administration (FDA) has little regulation for the manufacture, distribution, or sale of hookah. This review attempts to assess empirical literature relating to hookah use while focusing on the consequences for regulatory policy. PubMed (including MEDLINE 2010-2017), PsycINFO, EBSCO, Scopus (Elsevier) databases were examined to pinpoint articles published in English. The following terms were used in the searches: Hookah or Waterpipe or nargile or "arghile" or "shisha" or "hubble bubble" or "alternative tobacco product" or "flavored tobacco". Hookah use may initiate smoking among tobacconaïve college students. College students who use hookah are generally not aware of the increased risks for tobacco related diseases as it relates to their behavior. In addition, few public health messages target college-age adults with anti-hookah messages. A lack of information regarding the dangers and potential harms of hookah use may be misinterpreted as a sign of "safety" which inadvertently may imply a suggestion of no need for safety measures. Hence, a research agenda that would inform about health policy actions has been proposed.

  6. Captive power generation in Saudi Arabia—Overview and recommendations on policies

    International Nuclear Information System (INIS)

    Abdul-Majeed, Mohammed Arif; Al-Hadhrami, Luai M.; Al-Soufi, Khaled Y.; Ahmad, Firoz; Rehman, Shafiqur

    2013-01-01

    The power sector in the Kingdom of Saudi Arabia is undergoing the restructuring process. Moreover, during the last decade the Kingdom has witnessed a phenomenal growth in the load demand, consequently a huge amount of generation is added to the electric utilities to meet the load. Up to now only the electric utility generation was taken in the planning of the electrical sector. The data regarding the captive power generation was not readily available. A survey is conducted regarding the captive power generation in Saudi Arabia based on its utilization pattern, fuel used and amount of excess energy available to the grid. The existing regulatory framework and institutional structure of the Saudi power industry was also reviewed. Based on the information collected in the survey of captive power, key guidelines that may be considered in developing the policy for the captive power generators are presented. Furthermore, these guidelines and later the policies will help promote the investors to come forward in developing the captive power generation in Saudi Arabia. -- Highlights: •Database of captive power generation in the Kingdom of Saudi Arabia. •Historical perspective of electrical power industry in the Kingdom. •Saudi Arabia′s power requirements. •Regulatory framework and key guidelines regarding captive power generation. •It is first of its kind study in the region

  7. Contextual Positive Psychology: Policy Recommendations for Implementing Positive Psychology into Schools.

    Science.gov (United States)

    Ciarrochi, Joseph; Atkins, Paul W B; Hayes, Louise L; Sahdra, Baljinder K; Parker, Philip

    2016-01-01

    There has been a rapid growth in positive psychology, a research and intervention approach that focuses on promoting optimal functioning and well-being. Positive psychology interventions are now making their way into classrooms all over the world. However, positive psychology has been criticized for being decontextualized and coercive, and for putting an excessive emphasis on positive states, whilst failing to adequately consider negative experiences. Given this, how should policy be used to regulate and evaluate these interventions? We review evidence that suggests these criticisms may be valid, but only for those interventions that focus almost exclusively on changing the content of people's inner experience (e.g., make it more positive) and personality (improving character strength), and overemphasize the idea that inner experience causes action. We describe a contextualized form of positive psychology that not only deals with the criticisms, but also has clear policy implications for how to best implement and evaluate positive education programs so that they do not do more harm than good.

  8. Policy Recommendations for the Argentinean Water Resources National Plan Related to Extreme Events in Forested Mountain Basins.

    Science.gov (United States)

    Urciuolo, A. B.; Iturraspe, R. J.; Lofiego, R.

    2007-05-01

    In the framework of activities developed by COHIFE (Federal Water Resource Council), Argentina is preparing the Water Resources National Plan. To achieve an integrating project and considering that Argentina is a federal country, each province is working on the basis of its own Water Resources Provincial Plan. The first step of the plan consists in the identification of problems, with the purpose of further defining solutions based on structural and non structural actions. The general perception of the stakeholders involved in the plan development is the necessity of the analysis of strategies for the integrated water resource management Although a first document for water policy, named "Principios Rectores de Política Hídrica" is available, there are not specific strategies for integrated management of water and land use oriented to extreme events. In other way, there are a lack of policies oriented to Mountain basin with forest coverage, may be because of most of the population and the economical structure of the country is located on plain regions. This article proposes recommendations for policy to be integrated to the Water Resources National Plan, based on studies developed in a pilot basin representative of the Andean-Patagonia eco-region, in the framework of the EPIC FORCE proyect, financed by the European Union. Project methodology includes basin instrumentation, reconstruction and analysis of extreme events and land-water management practices revision. Climate, flow and sediment Data are available for simulation using the Shetran model on different land use scenarios, including changes in the basin forest coverage. On the basis of the first results of the project, policy guides oriented to fill mentioned policy lacks were defined.

  9. Assessing the sustainability of African lion trophy hunting, with recommendations for policy.

    Science.gov (United States)

    Creel, Scott; M'soka, Jassiel; Dröge, Egil; Rosenblatt, Eli; Becker, Matthew S; Matandiko, Wigganson; Simpamba, Twakundine

    2016-10-01

    While trophy hunting provides revenue for conservation, it must be carefully managed to avoid negative population impacts, particularly for long-lived species with low natural mortality rates. Trophy hunting has had negative effects on lion populations throughout Africa, and the species serves as an important case study to consider the balance of costs and benefits, and to consider the effectiveness of alternative strategies to conserve exploited species. Age-restricted harvesting is widely recommended to mitigate negative effects of lion hunting, but this recommendation was based on a population model parameterized with data from a well-protected and growing lion population. Here, we used demographic data from lions subject to more typical conditions, including source-sink dynamics between a protected National Park and adjacent hunting areas in Zambia's Luangwa Valley, to develop a stochastic population projection model and evaluate alternative harvest scenarios. Hunting resulted in population declines over a 25-yr period for all continuous harvest strategies, with large declines for quotas >1 lion/concession (~0.5 lion/1,000 km 2 ) and hunting of males younger than seven years. A strategy that combined periods of recovery, an age limit of ≥7 yr, and a maximum quota of ~0.5 lions shot/1,000 km 2 yielded a risk of extirpation lion trophy hunting with a combination of regulations. To implement sustainable trophy hunting while maintaining revenue for conservation of hunting areas, our results suggest that hunting fees must increase as a consequence of diminished supply. These findings are broadly applicable to hunted lion populations throughout Africa and to inform global efforts to conserve exploited carnivore populations. © 2016 by the Ecological Society of America.

  10. An Investigation of the Vietnamese Shipping Industry and Policy Recommendations for Profound Participation into ASEAN Integration

    Directory of Open Access Journals (Sweden)

    Thanh Thuy Nguyen

    2016-06-01

    Full Text Available Vietnam is a coastal country of a long history of maritime trade, which includes a shipping fleet of 1.840 ships with a total deadweight of 7.3 million DWT. This shipping fleet has been transporting about 90% of domestic sea cargo volume. Taking advantage of participating in the ASEAN community presents the shipping industry with a number of key challenges. These include unbalanced fleet proportions, which makes maximizing the shipping space available problematic; limited financial and managerial competences as well as outdated and inadequate infrastructure. The aim of this paper is to examine the Vietnam shipping industry and consider possible changes in policy led factors to facilitate the country's full participation in the ASEAN integration.

  11. Predictors of physical inactivity among elderly malaysians: recommendations for policy planning.

    Science.gov (United States)

    Kaur, Jasvindar; Kaur, Gurpreet; Ho, Bee Kiau; Yao, Weng Keong; Salleh, Mohmad; Lim, Kuang Hock

    2015-04-01

    Physical inactivity is the fourth leading risk factor for global mortality. Regular moderate-intensity physical activity has significant benefits for health. To determine the socioeconomic predictors of physical inactivity among elderly Malaysian population. A nationwide community-based survey was conducted among 4831 respondents aged ≥60 years with a face-to-face questionnaire. The prevalence of physical inactivity among the elderly was 88.0%, highest in respondents aged older than 80 years (95.4%), females (90.1%), other Bumiputra (92.2%), earning household income less than RM1000 (87.9%), and residing in urban locality (88.4%). In the multivariate model, the predictors of physical inactivity were only sex, ethnicity, locality, and age group (adjusted odds ratio = 1.3-3.6). The predictors of physical inactivity can identify the risk factors to develop policies that will reduce the public health burden of noncommunicable diseases. © 2014 APJPH.

  12. Recommendations for Adopting the International Code of Marketing of Breast-milk Substitutes Into U.S. Policy.

    Science.gov (United States)

    Soldavini, Jessica; Taillie, Lindsey Smith

    2017-08-01

    In 1981, the World Health Organization adopted the International Code of Marketing of Breast-milk Substitutes ( International Code), with subsequent resolutions adopted since then. The International Code contributes to the safe and adequate provision of nutrition for infants by protecting and promoting breastfeeding and ensuring that human milk substitutes, when necessary, are used properly through adequate information and appropriate marketing and distribution. Despite the World Health Organization recommendations for all member nations to implement the International Code in its entirety, the United States has yet to take action to translate it into any national measures. In 2012, only 22.3% of infants in the United States met the American Academy of Pediatrics recommendation of at least 6 months of exclusive breastfeeding. Countries adopting legislation reflecting the provisions of the International Code have seen increases in breastfeeding rates. This article discusses recommendations for translating the International Code into U.S. policy. Adopting legislation that implements, monitors, and enforces the International Code in its entirety has the potential to contribute to increased rates of breastfeeding in the United States, which can lead to improved health outcomes in both infants and breastfeeding mothers.

  13. Professional Veterinary Programs' Perceptions and Experiences Pertaining to Emotional Support Animals and Service Animals, and Recommendations for Policy Development.

    Science.gov (United States)

    Schoenfeld-Tacher, Regina M; Kogan, Lori R

    Given the unique nature of programs in professional veterinary medicine (PVM), the increasing numbers of students requesting accommodations for emotional support animals (ESAs) in higher education settings is of growing interest to student affairs and administrative staff in PVM settings. Since the legislation pertaining to this type of support animal differs from the laws governing disability service animals, colleges and universities now need to develop new policies and guidelines. Representatives from a sample of 28 PVM programs completed a survey about the prevalence of student requests for ESAs and service animals. PVM associate deans for academic affairs also reported their perceptions of this issue and the challenges these requests might pose within veterinary teaching laboratories and patient treatment areas. Responses indicated that approximately one third of PVM programs have received requests for ESAs (32.1%) in the last 2 years, 17.9% have had requests for psychiatric service animals, and 17.9% for other types of service animals. Despite this, most associate deans reported not having or not being aware of university or college policies pertaining to these issues. Most associate deans are interested in learning more about this topic. This paper provides general recommendations for establishing university or PVM program policies.

  14. EFL Speaking Anxiety among Senior High School Students and Policy Recommendations

    Directory of Open Access Journals (Sweden)

    Amirul Mukminin

    2015-08-01

    Full Text Available This report drew on a larger study which was to describe and understand the sources of senior high school students’ English language speaking anxiety at senior high schools in Jambi, Indonesia. The purpose of this paper was to report some of findings from the qualitative interview data on the sources of senior high school students’ English language speaking anxiety at one senior high school in Jambi, Indonesia. Data were collected through demographic profiles and semi-structured interview with senior high school students. The demographic data were analysed descriptively while the interview data were transcribed and analysed line by line to generate and develop codes and themes. An analysis of the interview data revealed that five major themes were related to students’ English language speaking anxiety, including (1 low speaking skill due to lack of vocabulary and grammar, (2 fear of negative responses from others, (3 low self-esteem to speak in English, (4 fear of being evaluated by teachers, and (5 cultural influences to speak English due to a more teacher-centred style. Suggestions and policy implications are also discussed.

  15. Policy Recommendation from Stakeholders to Improve Forest Products Transportation: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Anil Koirala

    2017-11-01

    Full Text Available With recently announced federal funding and subsidies to redevelop vacant mills and the communities they were in, the forest products industry in Maine is poised to gain its momentum once again. One of the important components influencing the cost of delivered forest products is transportation. A recent study in the region has shown that the location and availability of markets along with lack of skilled labor force are the major challenges faced by the forest products transportation sector in Maine. This study was focused on developing a management guideline which included various field level options for improving trucking enterprises in Maine. For this, a qualitative research approach utilizing a case study research tradition was employed, with in-depth semi-structured interviews with professionals directly related to the forest products transportation sector used for data generation. Thirteen semi-structured interviews were conducted, with each being audio recorded and later transcribed verbatim. Interview transcriptions were analyzed using NVivo 11. Suggestions, like increasing benefits to drivers and providing training, were proposed for challenges related to manpower shortage, while the marketing of new forest products and adjustment in some state-level policies were proposed for challenges related to the forest products market condition of the state.

  16. Policies to Avoid Cost Overruns in Infrastructure Projects: Critical Evaluation and Recommendations

    Directory of Open Access Journals (Sweden)

    Hans Lind

    2014-09-01

    Full Text Available Many infrastructure projects have cost overruns and there has been a lot of research both on why these cost overruns occur and what can be done to reduce hem. Bent Flyvbjerg is the leading researcher in the area and in this article his proposals are used as the starting point. Besides a literature review, a questionnaire was sent out to experienced Swedish project managers to find out what they thought could reduce cost overruns. The literature review and the questionnaire were the foundation for the proposals formulated in this article. Proposals concerned three areas: (1. Organisational macro-structure, e.g. using more PPP projects but also decentralisation of budgets where cost overruns in one project in a region lead to less alternative projects in the specific region. (2. Organisational quality: It should be easy to see when and where cost overruns occur and who was responsible. There should be a well-developed knowledge management system in the organisation and an organisation culture of openness with a focus on improvements. (3. Organisational processes, e.g. a systematic use of external reviewers in different stages of a project.   Keywords: Cost overruns, Infrastructure projects, Policy measures

  17. Policies to Avoid Cost Overruns in Infrastructure Projects: Critical Evaluation and Recommendations

    Directory of Open Access Journals (Sweden)

    Hans Lind

    2014-09-01

    Full Text Available Many infrastructure projects have cost overruns and there has been a lot of research both on why these cost overruns occur and what can be done to reduce hem. Bent Flyvbjerg is the leading researcher in the area and in this article his proposals are used as the starting point. Besides a literature review, a questionnaire was sent out to experienced Swedish project managers to find out what they thought could reduce cost overruns. The literature review and the questionnaire were the foundation for the proposals formulated in this article. Proposals concerned three areas: (1. Organisational macro-structure, e.g. using more PPP projects but also decentralisation of budgets where cost overruns in one project in a region lead to less alternative projects in the specific region. (2. Organisational quality: It should be easy to see when and where cost overruns occur and who was responsible. There should be a well-developed knowledge management system in the organisation and an organisation culture of openness with a focus on improvements. (3. Organisational processes, e.g. a systematic use of external reviewers in different stages of a project. Keywords: Cost overruns, Infrastructure projects, Policy measures

  18. Contraceptive practices in Nigeria: Literature review and recommendation for future policy decisions

    Directory of Open Access Journals (Sweden)

    Emmanuel Monjok

    2010-05-01

    Full Text Available Emmanuel Monjok1, Andrea Smesny1, John E Ekabua2, E James Essien11Institute of Community Health, University of Houston, Texas, USA; 2Department of Obstetrics and Gynecology, University of Calabar, NigeriaAbstract: The current prevalence rate for contraceptive use in Nigeria is approximately 11%–13%. This rate is very low in spite of the high rate of sexual activity and widespread awareness of the various contraceptive methods among Nigerian adolescence and youths. As a result there are many unintended pregnancies and illegal abortions contributing to a high maternal mortality ratio, which seems to indicate a large unmet need for contraceptive use. There is ample research evidence identifying the various factors that contribute to the low prevalence of modern contraceptive use in Nigeria, with the most common factor being the myth about the side effects of modern contraceptives. However, what is lacking is a political will in Nigeria to provide family planning programs on a much larger scale, using community-oriented approaches and communication programs, to help change the myth about the side effects of modern contraceptives. This review highlights current methods and concepts in contraception, reasons for low contraceptive use and practice in Nigeria, and the need for Nigeria to generate a political priority and a will to make a change in maternal health indicators, with the ultimate goal of providing direction to guide changes in the Nigerian Population Policy as it affects contraceptive use and family planning.Keywords: contraceptive practice, literature review, research, Nigeria

  19. Family/children cash benefits in Serbia: The analysis and policy recommendations

    Directory of Open Access Journals (Sweden)

    Matković Gordana

    2014-01-01

    Full Text Available Around 400 thousand children in Serbia are covered with cash-benefits targeting poor children representing 31.7% of the total number of children in 2011. Additionally, around 60 thousand families receive birth grants that is more than 90% of the newly born. When it comes to child-birth related leaves, there were around 37 thousand beneficiaries in 2012. This means that around 50% of the newly born children’s parents are covered with maternity/parental leave, while the coverage of employed mothers is almost full. Coverage of the poor children, particularly by the financial social assistance (FSA, can be considered inadequate. When it comes to targeting (vertical efficiency, FSA is targeted quite well, while there is scope for improvement of the inclusion error within the child-allowance program. When the adequacy of cash benefits targeting poor children is analyzed from the perspective of meeting the basic needs, then the amount is at the verge of being acceptable and differs for different kinds of families - single parent and families with very young children (0-2 being better off. However, when compared to the minimum wage, the cumulative amount of FSA and child allowance is lower only for one- child families. Total expenditures for cash-benefits connected to children amount to 1.4%of GDP - 1.21% being related to ESSPROS family/children function and 0.18% for the FSA for families with children. When compared to the EU, the total expenditure is below the EU average, with the birth related expenditures being higher and child allowance lower than the EU average. The first group of recommendations for cash benefits aimed at families with children relate to the improvement of adequacy and coverage of benefits aiming at poverty reduction, while respecting budget constraints. The increase of benefits for children above 14 years old - increase of child allowance or/and assigning higher weights (0.5 instead of 0.3 for the FSA’s equivalence scale

  20. Passenger transport in Nigeria: Environmental and economic analysis with policy recommendations

    International Nuclear Information System (INIS)

    Gujba, H.; Mulugetta, Y.; Azapagic, A.

    2013-01-01

    This paper presents the life cycle environmental impacts and economic costs of the passenger transport sector in Nigeria for 2003–2030. Four scenarios are considered: business as usual (BAU); increased use of public transport (buses) at the expense of cars (LOWCAR) and motorcycles (LOWMC), respectively; and high economic growth with increased car ownership and decline of public transport (HICAR). The findings show that for the BAU scenario the life cycle environmental impacts double over the period, despite the assumption of increased fuel and vehicle efficiency of 35% over time. The total fuel costs at the sectoral level increase three times, from US$3.4 billion/yr in 2003 to US$9.7 billion in 2030. Increasing the use of buses would reduce the environmental impacts on average by 15–20% compared to BAU; at the same time, the total fuel costs would be 25–30% lower. If the use of cars grows much faster due to a high economic growth as in HICAR, the environmental impacts and fuel costs would increase by 16% and 26%, respectively. These results demonstrate clearly that future transport policy in Nigeria should promote and incentivise public (bus) transport as a much more environmentally and economically sustainable option than transport by cars and motorcycles. - Highlights: ► The life cycle environmental impacts of passenger transport in Nigeria estimated for 2003–2030. ► The tradeoffs between economic costs and environmental impacts discussed. ► Scenarios considered: business as usual; sustainable transport; high economic growth. ► Public transport is more sustainable than transport by cars and motorcycles. ► Ending gas flaring would improve substantially environmental, economic and social impacts

  1. Cannabinoid Receptors CB1 and CB2 Modulate the Electroretinographic Waves in Vervet Monkeys

    Directory of Open Access Journals (Sweden)

    Joseph Bouskila

    2016-01-01

    Full Text Available The expression patterns of the cannabinoid receptor type 1 (CB1R and the cannabinoid receptor type 2 (CB2R are well documented in rodents and primates. In vervet monkeys, CB1R is present in the retinal neurons (photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells and CB2R is exclusively found in the retinal glia (Müller cells. However, the role of these cannabinoid receptors in normal primate retinal function remains elusive. Using full-field electroretinography in adult vervet monkeys, we recorded changes in neural activity following the blockade of CB1R and CB2R by the intravitreal administration of their antagonists (AM251 and AM630, resp. in photopic and scotopic conditions. Our results show that AM251 increases the photopic a-wave amplitude at high flash intensities, whereas AM630 increases the amplitude of both the photopic a- and b-waves. In scotopic conditions, both blockers increased the b-wave amplitude but did not change the a-wave amplitude. These findings suggest an important role of CB1R and CB2R in primate retinal function.

  2. Reference centres for adults with rare and complex cancers - Policy recommendations to improve the organisation of care in Belgium.

    Science.gov (United States)

    Stordeur, S; Vrijens, F; Leroy, R

    2016-02-01

    Rare and/or complex cancers call for a very specific expertise and adequate infrastructure. In Belgium, every hospital with a programme in oncology can deliver care for adults with rare and/or complex cancer types, without having demonstrated a specific know-how to adequately manage these patients. Therefore, the Minister of Health ordered a scenario for the organisation of care for adults with rare and/or complex cancers, taking into account the current Belgian situation and relevant foreign experience. Combined methods were used in this study: a literature review, the consultation of stakeholders, in depth discussions in 14 multidisciplinary groups leading to concrete proposals for several rare/complex cancers and the consultation of a panel of expert pathologists. The core recommendation is the set-up of shared care networks around reference centres, with multidisciplinary teams of recognised expertise in specific rare/complex cancers. The definition of minimum caseloads for hospitals and medical specialists, the evaluation of the quality of care, a model of diagnostic confirmation and the set-up of a national portal website which provides information on rare and/or complex cancers and reference centres are highly recommended. It is no longer practicable, efficient or ethical that every hospital or every practitioner continues to offer care for every rare/complex cancer. Improving the quality of rare/complex cancer care requires to concentrate expertise and sophisticated infrastructure in reference centres. Furthermore, the formation of networks between reference centres and peripheral centres will allow a delivery of care combining expertise and proximity. The next step is the translation of the recommendations into policy decisions. It is very well realised that this will take some courage and that a certain degree of resistance will have to be surmounted, but eventually, the best interest of the patient should prevail. Copyright © 2015 Elsevier Masson SAS

  3. D3.4: Recommendations for common policy across the EU regarding professional development as an element of quality in ECEC and child wellbeing for all. Final report

    DEFF Research Database (Denmark)

    Jensen, Bente; Iannone, Rosa Lisa

    Executive summary This report’s discussion and recommendations build on Workpackage 3’s (WP3) work within CARE, including: 1) a review of the systems of professional development, pre-service and in-service across 10 European countries and the impact that structural and processual shifts have...... contexts. In an attempt to overcome the dualisms of structured-interactive systems and structural-processual approaches to quality enhancement, we acknowledge that the recommendations herein can be applied to ECEC settings across Europe, though actors and methods may vary. The strive is to strengthen...... European ECEC without suggesting radical system changes that disregard historical legacies. In light of this, WP3’s findings and recommendations address implications for policy, practice and research for each of the six policy priorities identified. Since ECEC’s policies, systems and professionals’ work...

  4. Cannabinoid receptor CB2 modulates axon guidance

    DEFF Research Database (Denmark)

    Duff, Gabriel; Argaw, Anteneh; Cecyre, Bruno

    2013-01-01

    Navigation of retinal projections towards their targets is regulated by guidance molecules and growth cone transduction mechanisms. Here, we present in vitro and in vivo evidences that the cannabinoid receptor 2 (CB2R) is expressed along the retino-thalamic pathway and exerts a modulatory action ...

  5. Economic evaluation on tight sandstone gas development projects in China and recommendation on fiscal and taxation support policies

    Directory of Open Access Journals (Sweden)

    Zhen Yang

    2016-11-01

    Full Text Available China is rich in tight sandstone gas resources (“tight gas” for short. For example, the Sulige Gasfield in the Ordos Basin and the Upper Triassic Xujiahe Fm gas reservoir in the Sichuan Basin are typical tight gas reservoirs. In the past decade, tight gas reserve and production both have increased rapidly in China, but tight gas reservoirs are always managed as conventional gas reservoirs without effective fiscal, taxation and policy supports. The potential of sustainable tight gas production increase is obviously restricted. The tight gas development projects represented by the Sulige Gasfield have failed to make profit for a long period, and especially tight gas production has presented a slight decline since 2015. In this paper, a new economic evaluation method was proposed for tight gas development projects. The new method was designed to verify the key parameters (e.g. production decline rate and single-well economic service life depending on tight gas development and production characteristics, and perform the depreciation by using the production method. Furthermore, the possibility that the operation cost may rise due to pressure-boosting production and intermittent opening of gas wells is considered. The method was used for the tight gas development project of Sulige Gasfield, showing that its profit level is much lower than the enterprise's cost level of capital. In order to support a sustainable development of tight gas industry in China, it is recommended that relevant authorities issue value-added tax (VAT refund policy as soon as possible. It is necessary to restore the non-resident gas gate price of the provinces where tight gas is produced to the fair and reasonable level in addition to the fiscal subsidy of CNY0.24/m3, or offer the fiscal subsidy of CNY0.32/m3 directly based on the on-going gate price. With these support policies, tax income is expected to rise directly, fiscal expenditure will not increase, and gas

  6. Nuclear Waste Policy Act of 1982; proposed general guidelines for recommendation of sites for nuclear waste repositories

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    In accordance with the requirements of the Nuclear Waste Policy Act of 1982 (Pub. L. 97-425), hereinafter referred to as the Act, the Department of Energy is proposing general guidelines for the recommendation of sites for repositories for disposal of high-level radioactive waste and spent nuclear fuel in geologic formations. These guidelines are based on the criteria that the Department has used in its National Waste Terminal Storage program, the criteria proposed by the Nuclear Regulatory Commission (NRC), and the environmental standards proposed by the Environmental Protection Agency. These guidelines establish the performance requirements for a geologic repository system, specify how the Department will implement its site-selection program, and define the technical qualifications that candidate sites must meet in the various steps of the site-selection process mandated by the Act. After considering comments from the public; consulting with the Council on Environmental Quality, the Administrator of the Environmental Protection Agency, the Director of the Geological Survey, and interested Governors; and obtaining NRC concurrence, the Department will issue these guidelines in final form as a new Part 960 to Title 10 of the Code of Federal Regulations (10 CFR Part 960)

  7. Recommendations concerning Tennessee's hazardous waste management policies by a task force representing generators, environmentalists, and other key constituencies

    International Nuclear Information System (INIS)

    Colglazier, E.W.; English, M.R.

    1987-01-01

    Four recommendations are proposed. 1) A Governor's Roundtable on Hazardous and Solid Wastes should be established to ensure that Tennessee have sound policies and plans for waste management, adequate waste treatment and disposal capacity, and the means to meet the October, 1989 deadline for certification of hazardous waste capacity. 2) Opportunities for early public information and participation in Tennessee's RCRA permitting process should be improved. 3) A Superfund Public Involvement Task Force should be appointed by the Commissioner of Health and Environment to find ways to ensure that a community affected by a Tennessee Superfund site has early and adequate opportunities for information and involvement. 4) Communications about hazardous waste issues should be improved by the appointment of a hazardous waste information officer, the establishment of a Speakers Bureau, the funding of the UT Center for Industrial Services' Hazardous Waste Extension Program, establishment of a crisis situation network of consultants for communities, and exploration of the possibility of Amnesty Days for household hazardous waste and for small-quantity generators waste

  8. Communicating human biomonitoring results to ensure policy coherence with public health recommendations: analysing breastmilk whilst protecting, promoting and supporting breastfeeding

    Directory of Open Access Journals (Sweden)

    Arendt Maryse

    2008-06-01

    Full Text Available Abstract This article addresses the problem of how to ensure consistency in messages communicating public health recommendations on environmental health and on child health. The World Health Organization states that the protection, promotion and support of breastfeeding rank among the most effective interventions to improve child survival. International public health policy recommends exclusive breastfeeding for six months, followed by continued breastfeeding with the addition of safe and adequate complementary foods for two years and beyond. Biomonitoring of breastmilk is used as an indicator of environmental pollution ending up in mankind. This article will therefore present the biomonitoring results of concentrations of residues in breastmilk in a wider context. These results are the mirror that reflects the chemical substances accumulated in the bodies of both men and women in the course of a lifetime. The accumulated substances in our bodies may have an effect on male or female reproductive cells; they are present in the womb, directly affecting the environment of the fragile developing foetus; they are also present in breastmilk. Evidence of man-made chemical residues in breastmilk can provide a shock tactic to push for stronger laws to protect the environment. However, messages about chemicals detected in breastmilk can become dramatized by the media and cause a backlash against breastfeeding, thus contradicting the public health messages issued by the World Health Organization. Analyses of breastmilk show the presence of important nutritional components and live protective factors active in building up the immune system, in gastro intestinal maturation, in immune defence and in providing antiviral, antiparasitic and antibacterial activity. Through cohort studies researchers in environmental health have concluded that long-term breastfeeding counterbalances the effect of prenatal exposure to chemicals causing delay in mental and

  9. Communicating human biomonitoring results to ensure policy coherence with public health recommendations: analysing breastmilk whilst protecting, promoting and supporting breastfeeding

    Directory of Open Access Journals (Sweden)

    Arendt Maryse

    2008-01-01

    Full Text Available Abstract This article addresses the problem of how to ensure consistency in messages communicating public health recommendations on environmental health and on child health. The World Health Organization states that the protection, promotion and support of breastfeeding rank among the most effective interventions to improve child survival. International public health policy recommends exclusive breastfeeding for six months, followed by continued breastfeeding with the addition of safe and adequate complementary foods for two years and beyond. Biomonitoring of breastmilk is used as an indicator of environmental pollution ending up in mankind. This article will therefore present the biomonitoring results of concentrations of residues in breastmilk in a wider context. These results are the mirror that reflects the chemical substances accumulated in the bodies of both men and women in the course of a lifetime. The accumulated substances in our bodies may have an effect on male or female reproductive cells; they are present in the womb, directly affecting the environment of the fragile developing foetus; they are also present in breastmilk. Evidence of man-made chemical residues in breastmilk can provide a shock tactic to push for stronger laws to protect the environment. However, messages about chemicals detected in breastmilk can become dramatized by the media and cause a backlash against breastfeeding, thus contradicting the public health messages issued by the World Health Organization. Analyses of breastmilk show the presence of important nutritional components and live protective factors active in building up the immune system, in gastro intestinal maturation, in immune defence and in providing antiviral, antiparasitic and antibacterial activity. Through cohort studies researchers in environmental health have concluded that long-term breastfeeding counterbalances the effect of prenatal exposure to chemicals causing delay in mental and

  10. A new condensed toluene mechanism for Carbon Bond: CB05-TU

    Science.gov (United States)

    Whitten, Gary Z.; Heo, Gookyoung; Kimura, Yosuke; McDonald-Buller, Elena; Allen, David T.; Carter, William P. L.; Yarwood, Greg

    2010-12-01

    Toluene is ubiquitous in urban atmospheres and is a precursor to tropospheric ozone and aerosol (smog). An important characteristic of toluene chemistry is the tendency of some degradation products (e.g., cresols and methyl-catechols) to form organic nitro and nitrate compounds that sequester NOx (NO and NO 2) from active participation in smog formation. Explaining the NOx sinks in toluene degradation has made mechanism development more difficult for toluene than for many other organic compounds. Another challenge for toluene is explaining sources of radicals early in the degradation process. This paper describes the development of a new condensed toluene mechanism consisting of 26 reactions, and evaluates the performance of CB05 with this new toluene scheme (Toluene Update, TU) against 38 chamber experiments at 7 different environmental chambers, and provides recommendations for future developments. CB05 with the current toluene mechanism (CB05-Base) under-predicted the maximum O 3 and O 3 production rate for many of these toluene-NOx chamber experiments, especially under low-NOx conditions ([NOx] t=0 toluene mechanism (CB05-TU) includes changes to the yields and reactions of cresols and ring-opening products, and showed better performance than CB05-Base in predicting the maximum O 3, O 3 formation rate, NOx removal rate and cresol concentration. Additional environmental chamber simulations with xylene-NOx experiments showed that the TU mechanism updates tended to improve mechanism performance for xylene.

  11. The role of CB1 receptors in psychostimulant addiction

    NARCIS (Netherlands)

    Wiskerke, J.; Pattij, T.; Schoffelmeer, A.N.M.; de Vries, T.J.

    2008-01-01

    Recent studies have implicated the endocannabinoid (eCB) system in the neuronal mechanisms underlying substance dependence. Here, we review results of studies using cannabinoid receptor subtype 1 (CB1) knockout mice as well as CB1 antagonists to elucidate the role of this neurotransmitter system in

  12. Δ9-tetrahydrocannabinol suppresses cytotoxic T lymphocyte function independent of CB1 and CB 2, disrupting early activation events.

    Science.gov (United States)

    Karmaus, Peer W F; Chen, Weimin; Kaplan, Barbara L F; Kaminski, Norbert E

    2012-12-01

    Previously, CD8(+) T cells were found to be a sensitive target for suppression by Δ(9)-tetrahydrocannabinol (Δ(9)-THC) in a murine model of influenza infection. To study the effect of Δ(9)-THC on CD8(+) cytotoxic T lymphocytes (CTL), an allogeneic model of MHC I mismatch was used to elicit CTL. In addition, to determine the requirement for the cannabinoid receptors 1 (CB(1)) and 2 (CB(2)) in Δ(9)-THC-mediated CTL response modulation, mice null for both receptors were used (CB(1) (-/-)CB(2) (-/-)). Δ(9)-THC suppressed CTL function independent of CB(1) and CB(2) as evidenced by reduction of (51)Cr release by CTL generated from CB(1) (-/-)CB(2) (-/-) mice. Furthermore, viability in CD4(+) and CD8(+) cells was reduced in a concentration-dependent manner with Δ(9)-THC, independent of CB(1) and CB(2), but no effect of Δ(9)-THC on proliferation was observed, suggesting that Δ(9)-THC decreases the number of T cells initially activated. Δ(9)-THC increased expression of the activation markers, CD69 in CD8(+) cells and CD25 in CD4(+) cells in a concentration-dependent manner in cells derived from WT and CB(1) (-/-)CB(2) (-/-) mice. Furthermore, Δ(9)-THC synergized with the calcium ionophore, ionomycin, to increase CD69 expression on both CD4(+) and CD8(+) cells. In addition, without stimulation, Δ(9)-THC increased CD69 expression in CD8(+) cells from CB(1) (-/-)CB(2) (-/-) and WT mice. Overall, these results suggest that CB(1) and CB(2) are dispensable for Δ(9)-THC-mediated suppression and that perturbation of Ca(2+) signals during T cell activation plays an important role in the mechanism by which Δ(9)-THC suppresses CTL function.

  13. Analysis on Green Agriculture Policy during the Development of Eco-city in European Countries and United States and Policy Recommendations

    OpenAIRE

    QIN, Li; QI, Yang

    2014-01-01

    Ecological agriculture is the important industrial foundation for building eco-cities, while green agriculture policy plays an essential role in promoting sustainable development of ecological agriculture. This paper analyzed the relationship between green agriculture policy and developing eco-cities and characteristics of green agriculture policies in European countries and the United States developing ecological cities. Besides, it summarized experience, in hope of providing beneficial refe...

  14. Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

    Directory of Open Access Journals (Sweden)

    Eleftheria Lakiotaki

    2015-01-01

    Full Text Available The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2, their endogenous ligands (endocannabinoids, and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n=43 and malignant (n=44 lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p=0.0010 and p=0.0005, resp.. Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p=0.0097 and p=0.0110, resp.. In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p=0.0301. Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p=0.1165, lymphatic (p=0.1989, and vascular invasion (p=0.0555, as well as in those with increased risk of recurrence rate (p=0.1165, at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.

  15. Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions.

    Science.gov (United States)

    Lakiotaki, Eleftheria; Giaginis, Constantinos; Tolia, Maria; Alexandrou, Paraskevi; Delladetsima, Ioanna; Giannopoulou, Ioanna; Kyrgias, George; Patsouris, Efstratios; Theocharis, Stamatios

    2015-01-01

    The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins' expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n = 43) and malignant (n = 44) lesions and was statistically analyzed with clinicopathological parameters, follicular cells' proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA) staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p = 0.0010 and p = 0.0005, resp.). Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p = 0.0097 and p = 0.0110, resp.). In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p = 0.0301). Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p = 0.1165), lymphatic (p = 0.1989), and vascular invasion (p = 0.0555), as well as in those with increased risk of recurrence rate (p = 0.1165), at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.

  16. 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.

  17. The level of perceived quality and safety of health services by recipients. Recommendations and inter- ventions for health care policies

    Directory of Open Access Journals (Sweden)

    Foteini Koulouri

    2017-06-01

    Full Text Available In recent years, the importance of the quality in health sector is more and more acknowledged. In broader terms the literature on quality in health care contributed to this, and stressed the importance of meeting the needs of the service recipient. Safety and quality in health care constitute a multi-dimensional parameter and involve many factors and various resources. Safety is positively associated to the quality, as the existence of the one ensures the improvement of the other. Thus, there is a great effort to create a framework, through guidelines and instructions that could contribute to the protection and development of quality and safety. It is important that this framework includes many features that have been expressed as requests by the patients themselves and which can contribute to the development of realistic and effective recommendations for improvement. Greek reality reveals certain gaps in safety and quality of services delivered, so the main attention has to be focused on developing an integral national health policy; the development of guidelines and the appropriate evaluation of their implementation could be a first effective approach. Formulating an institutional framework about safety and quality in health sector should be incorporated in the culture of all health organizations. To this end, the involvement of health professionals is a vital and strategic point. Health care practitioners should incorporate safety and quality culture in their daily routine and health managers should enact efficient ways of evaluation and control mechanisms in order to achieve better outcomes. Motivation to this direction and active participation should be encouraged with positive approaches, away from any kind of sanction. Any mistakes, adverse effects and deviations should be identified, reported, analyzed and formulate the base of the corrective action. In conclusion, safety and quality in health sector are essential and strongly associated

  18. Policy Document on Earth Observation for Urban Planning and Management: State of the Art and Recommendations for Application of Earth Observation in Urban Planning

    Science.gov (United States)

    Nichol, Janet; King, Bruce; Xiaoli, Ding; Dowman, Ian; Quattrochi, Dale; Ehlers, Manfred

    2007-01-01

    A policy document on earth observation for urban planning and management resulting from a workshop held in Hong Kong in November 2006 is presented. The aim of the workshop was to provide a forum for researchers and scientists specializing in earth observation to interact with practitioners working in different aspects of city planning, in a complex and dynamic city, Hong Kong. A summary of the current state of the art, limitations, and recommendations for the use of earth observation in urban areas is presented here as a policy document.

  19. The Policy Recommendations of the Association of American Geographers as Reflected In the Ventura County Community College.

    Science.gov (United States)

    McDannold, Thomas A.

    A survey was conducted to identify the degree to which the Association of American Geographers (AAG) 1970 recommendations on geography programs in two-year colleges were reflected in geography programs offered in the Ventura County Community College District (California). Results indicated that the recommendations were followed to a great extent,…

  20. Medium of Instruction Policies in Ghanaian and Indian Primary Schools: An Overview of Key Issues and Recommendations

    Science.gov (United States)

    Erling, Elizabeth J.; Adinolfi, Lina; Hultgren, Anna Kristina; Buckler, Alison; Mukorera, Mark

    2016-01-01

    This paper reports on a rigorous literature review of research into medium of instruction in Ghana and India, whose language-in-education policies represent two contrasting models of use of local languages and the development of competence in English. The paper begins by briefly overviewing the language-in-education policy in these two countries…

  1. Sexual Assault Prevention and Reporting on College Campuses in the US: A Review of Policies and Recommendations

    Science.gov (United States)

    Streng, Tara K.; Kamimura, Akiko

    2015-01-01

    Objective: Sexual violence within the collegiate environment is a pressing issue within American society. One way to address sexual violence is through the adaptation and implementation of a sexual assault policy by colleges and universities. The purpose of this study is to review sexual misconduct and assault policies of ten public universities…

  2. CB1 receptor signaling regulates social anxiety and memory.

    Science.gov (United States)

    Litvin, Y; Phan, A; Hill, M N; Pfaff, D W; McEwen, B S

    2013-07-01

    The endocannabinoid (eCB) system regulates emotion, stress, memory and cognition through the cannabinoid type 1 (CB1 ) receptor. To test the role of CB1 signaling in social anxiety and memory, we utilized a genetic knockout (KO) and a pharmacological approach. Specifically, we assessed the effects of a constitutive KO of CB1 receptors (CB1 KOs) and systemic administration of a CB1 antagonist (AM251; 5 mg/kg) on social anxiety in a social investigation paradigm and social memory in a social discrimination test. Results showed that when compared with wild-type (WT) and vehicle-treated animals, CB1 KOs and WT animals that received an acute dose of AM251 displayed anxiety-like behaviors toward a novel male conspecific. When compared with WT animals, KOs showed both active and passive defensive coping behaviors, i.e. elevated avoidance, freezing and risk-assessment behaviors, all consistent with an anxiety-like profile. Animals that received acute doses of AM251 also showed an anxiety-like profile when compared with vehicle-treated animals, yet did not show an active coping strategy, i.e. changes in risk-assessment behaviors. In the social discrimination test, CB1 KOs and animals that received the CB1 antagonist showed enhanced levels of social memory relative to their respective controls. These results clearly implicate CB1 receptors in the regulation of social anxiety, memory and arousal. The elevated arousal/anxiety resulting from either total CB1 deletion or an acute CB1 blockade may promote enhanced social discrimination/memory. These findings may emphasize the role of the eCB system in anxiety and memory to affect social behavior. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  3. 47 CFR 95.405 - (CB Rule 5) Where may I operate my CB station?

    Science.gov (United States)

    2010-10-01

    ... SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Citizens Band (CB) Radio Service General Provisions § 95... threat to the Arecibo Observatory shall notify the Interference Office, Arecibo Observatory, HC3 Box... notification to the Interference Office, Arecibo Observatory shall be made 45 days prior to commencing...

  4. Male circumcision for HIV prevention in Papua New Guinea: a summary of research evidence and recommendations for public health following a national policy forum.

    Science.gov (United States)

    Vallely, A; MacLaren, D J; Kaleva, W; Millan, J; Tommbe, R; Marape, W; Manineng, C; Buchanan, H; Amos, A; Frank, R; Kelly, A; Kupul, M; Aeno, H; Trowalle, E; John, L N; Redman-Maclaren, M L; Ryan, C; Browne, K; Tynan, A; Hill, P S; Gray, R T; Murray, J; Wilson, D P; Law, G; Siba, P; McBride, W J H; Farley, T; Kaldor, J M

    2011-01-01

    In 2005, a clinical trial in South Africa found that circumcision of young men could reduce their risk of acquiring HIV (human immunodeficiency virus) infection by over 60%. In the following year, two more trials in Africa confirmed this finding, leading the World Health Organization to recommend male circumcision as a public health strategy for HIV prevention in high-incidence countries. In order to inform public health policy in Papua New Guinea (PNG), two major research projects were initiated with the goals of investigating the status of penile cutting practices and assessing understandings, acceptability, feasibility and cost-effectiveness of male circumcision for HIV prevention. In addition, behavioural surveillance surveys systematically asked questions on penile cutting practices and an ethnographic literature review informed historical perspectives of penile cutting in PNG. Key findings from these research activities were presented at a National Policy Forum on Male Circumcision for HIV Prevention held in Port Moresby in November 2011. The Forum made three key recommendations: (1) the formation of a joint National Department of HealthlNational AIDS Council Secretariat Policy Committee on male circumcision; (2) the establishment of an integrated harm reduction program; and (3) that future policy on wide-scale roll-out of male circumcision for HIV prevention in PNG be informed by a combination of data from (a) male circumcision intervention pilot programs and (b) research on the potential protective effect of other forms of penile cutting.

  5. Low-Carbon City Policy Databook: 72 Policy Recommendations for Chinese Cities from the Benchmarking and Energy Savings Tool for Low Carbon Cities

    Energy Technology Data Exchange (ETDEWEB)

    Price, Lynn [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; Zhou, Nan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; Fridley, David [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; Ohshita, Stephanie [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; Khanna, Nina [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; Lu, Hongyou [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; Hong, Lixuan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; He, Gang [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; Romankiewicz, John [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Technologies Area. Energy Analysis and Environmental Impacts Division. China Energy Group; Min, Hu [Energy Foundation China, Beijing (China)

    2016-07-01

    This report is designed to help city authorities evaluate and prioritize more than 70 different policy strategies that can reduce their city’s energy use and carbon-based greenhouse gas emissions of carbon dioxide (CO2) and methane (CH4). Local government officials, researchers, and planners can utilize the report to identify policies most relevant to local circumstances and to develop a low carbon city action plan that can be implemented in phases, over a multi-year timeframe. The policies cover nine city sectors: industry, public and commercial buildings, residential buildings, transportation, power and heat, street lighting, water & wastewater, solid waste, and urban green space. See Table 1 for a listing of the policies. Recognizing the prominence of urban industry in the energy and carbon inventories of Chinese cities, this report includes low carbon city policies for the industrial sector. The policies gathered here have proven effective in multiple locations around the world and have the potential to achieve future energy and carbon savings in Chinese cities.

  6. How is the process of setting micronutrients recommendations reflected in nutrition policies in Poland? The case study of folate

    Directory of Open Access Journals (Sweden)

    Ewa Sicińska

    2018-03-01

    The current Polish nutrition recommendations for folate are consistent with the levels set by most other countries. The constant improvement of nutritional knowledge on folate among consumers, especially young women, is necessary.

  7. Induction of CB1 cannabinoid receptor by inflammation in primary afferent neurons facilitates antihyperalgesic effect of peripheral CB1 agonist.

    Science.gov (United States)

    Amaya, Fumimasa; Shimosato, Goshun; Kawasaki, Yasuhiko; Hashimoto, Satoru; Tanaka, Yoshifumi; Ji, Ru-Rong; Tanaka, Masaki

    2006-09-01

    Cannabinoids act on various regions in the nervous system to modulate neuronal activity including nociception. Here, we investigated CB1 receptor expression in primary afferent neurons in the dorsal root ganglion (DRG) and the efficacy of a local (intraplantar) application of the selective CB1 agonist, 2-arachidonyl-2-chloroethylamide (ACEA), on inflammatory thermal hyperalgesia. In situ hybridization showed normal CB1 mRNA expression in 28% of DRG neurons. Peripheral inflammation by CFA (complete Freund's adjuvant) significantly increased the ratio of CB1 mRNA-positive neurons to 43%, primarily with increase in NF200-negative C-fiber nociceptors. Furthermore, CB1 and TRPV1 (transient potential receptor vanilloid subtype-1) co-localization was increased from 41% before inflammation to 67% two days after inflammation. Inflammation also increased CB1 immunoreactivity in DRG neurons and in nerve fibers of the hindpaw dermis, indicating increased CB1 transport from the cell body to the peripheral nerve. The intraplantar application of ACEA attenuated CFA-induced thermal hyperalgesia. The antinociceptive properties of ACEA became more prominent at 2 days after inflammation, compared with those in non-inflamed and inflamed animals at 8 h. These results suggest that CB1 expression in primary afferent neurons is increased by inflammation and that the subsequent increase in CB1 transport to peripheral axons contributes to the increased antihyperalgesic efficacy of locally administered CB1 agonist.

  8. Loss of cannabinoid receptor CB1 induces preterm birth.

    Directory of Open Access Journals (Sweden)

    Haibin Wang

    2008-10-01

    Full Text Available Preterm birth accounting approximate 10% of pregnancies in women is a tremendous social, clinical and economic burden. However, its underlying causes remain largely unknown. Emerging evidence suggests that endocannabinoid signaling via cannabinoid receptor CB1 play critical roles in multiple early pregnancy events in both animals and humans. Since our previous studies demonstrated that loss of CB1 defers the normal implantation window in mice, we surmised that CB1 deficiency would influence parturition events.Exploiting mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing on the onset of parturition. We observed that genetic or pharmacological inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay analysis of circulating levels of ovarian steroid hormones revealed that premature birth resulting from CB1 inactivation is correlated with altered progesterone/estrogen ratios prior to parturition. More strikingly, the phenotypic defects of prolonged pregnancy length and parturition failure in mice missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice. In addition, loss of CB1 resulted in aberrant secretions of corticotrophin-releasing hormone and corticosterone during late gestation. The pathophysiological significance of this altered corticotrophin-releasing hormone-driven endocrine activity in the absence of CB1 was evident from our subsequent findings that a selective corticotrophin-releasing hormone antagonist was able to restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild-type females receiving excessive levels of corticosterone induced preterm birth.CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice. This defect is independent of prostaglandins produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in

  9. Dielectrical properties of composites LDPE+CB

    Directory of Open Access Journals (Sweden)

    Škipina Blanka

    2010-01-01

    Full Text Available There is currently great interest in the technological properties of conductive polymer composites because their cost-performance balance. They have a wide range of industrial applications -in anti-static materials, self regulating heaters, current overload and overheating protection devices, and materials for electromagnetic radiation shielding. Measurements of the electrical properties of polymer composites are one of the most convenient and sensitive methods for studying polymer structure. A polymer composite differs substantially from a free polymer in a wide range of properties. The presence of filler affects both the electrical, as well as mechanical properties. One of the most important characteristics of conductive polymer composites is that their electrical conductivity increases nonlinearly with the increase of the concentration of filler particles. When the concentration of filler particles reaches a certain critical value, a drastic transition from an electrical insulator to a conductor is exhibited. This conductivity behavior resulting in a sudden insulator-conductor transition is ascribed to a percolation process, and the critical filler concentration at which the conductivity jump occurs is called ‘percolation threshold’. In the past few years, a lot of studies have been carried out to analyze the percolation phenomenon and mechanisms of the conductive behavior in conductive polymer composites. It has been established that the electrical conductivity of conductive polymer composites uncommonly depends on the temperature. Some of such composites show a sharp increase and/or decrease in electrical conductivity at specific temperatures. The conductive temperature coefficient (CTC of conductive polymer composites has been widely investigated. In these work we investigated how concentration of the CB affects the dielectrical properties of the composite LDPE+CB. The ac electrical conductivity, σac, for such composites was measured

  10. Working Paper 78: Policy recommendations to the EU Commission, Changing families and sustainable societies: Policy contexts and diversity over the life course and across generations (2017) : Collaborative research project financed by the European Union’s Seventh Framework Programme 2013-2017 (Grant no. 320116, FP7-SSH-2012-1)

    OpenAIRE

    Carlson, Laura; Oláh, Livia; Hobson, Barbara

    2017-01-01

    These policy recommendations are based on main findings of the largescale EU Seventh Framework project, Changing families and sustainable societies: Policy contexts and diversity over the life course and across generations (FamiliesAndSocieties). This executive summary highlights a few of the key policy recommendations: • Policy makers ought to be aware of the remarkable diversity of family forms and relationships in contemporary Europe, and aim for a better understanding of the nature and me...

  11. No Child Left Behind in Art Education Policy: A Review of Key Recommendations for Arts Language Revisions

    Science.gov (United States)

    Grey, Anne C.

    2010-01-01

    From bipartisan origins and a laudable intent, the No Child Left Behind (Act) of 2001 has profoundly altered the condition of art education. A historical vantage point and review of literature reveals the current status of pending arts language revisions to the NCLB Act, as well as a pressing need to examine the key recommendations and to consider…

  12. Alternative fuel buses currently in use in China: Life-cycle fossil energy use, GHG emissions and policy recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Ou Xunmin, E-mail: oxm07@mails.tsinghua.edu.c [School of Public Policy and Management (SPPM), Tsinghua University, Beijing 100084 (China); China Automotive Energy Research Center (CAERC), Tsinghua University, Beijing 100084 (China); Institute of Energy, Environment and Economy (3E), Tsinghua University, Beijing 100084 (China); Zhang Xiliang, E-mail: zhang_xl@tsinghua.edu.c [China Automotive Energy Research Center (CAERC), Tsinghua University, Beijing 100084 (China); Institute of Energy, Environment and Economy (3E), Tsinghua University, Beijing 100084 (China); Chang Shiyan [China Automotive Energy Research Center (CAERC), Tsinghua University, Beijing 100084 (China); Institute of Energy, Environment and Economy (3E), Tsinghua University, Beijing 100084 (China)

    2010-01-15

    The Chinese government has enacted policies to promote alternative vehicle fuels (AVFs) and alternative fuel vehicles (AFVs), including city bus fleets. The life cycle (LC), energy savings (ES) and GHG reduction (GR) profiles of AVFs/AFVs are critical to those policy decisions. The well-to-wheels module of the Tsinghua-CA3EM model is employed to investigate actual performance data. Compared with conventional buses, AFVs offer differences in performance in terms of both ES and GR. Only half of the AFVs analyzed demonstrate dual benefits. However, all non-oil/gas pathways can substitute oil/gas with coal. Current policies seek to promote technology improvements and market creation initiatives within the guiding framework of national-level diversification and district-level uniformity. Combined with their actual LC behavior and in keeping with near- and long-term strategies, integrated policies should seek to (1) apply hybrid electric technology to diesel buses; (2) encourage NG/LPG buses in gas-abundant cities; (3) promote commercialize electric buses or plug-in capable vehicles through battery technology innovation; (4) support fuel cell buses and hydrogen technology R and D for future potential applications; and (5) conduct further research on boosting vehicle fuel efficiency, applying low-carbon transportation technologies, and addressing all resultant implications of coal-based transportation solutions to human health and natural resources.

  13. Alternative fuel buses currently in use in China. Life-cycle fossil energy use, GHG emissions and policy recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Ou, Xunmin [School of Public Policy and Management (SPPM), Tsinghua University, Beijing 100084 (China); China Automotive Energy Research Center (CAERC), Tsinghua University, Beijing 100084 (China); Institute of Energy, Environment and Economy (3E), Tsinghua University, Beijing 100084 (China); Zhang, Xiliang; Chang, Shiyan [China Automotive Energy Research Center (CAERC), Tsinghua University, Beijing 100084 (China); Institute of Energy, Environment and Economy (3E), Tsinghua University, Beijing 100084 (China)

    2010-01-15

    The Chinese government has enacted policies to promote alternative vehicle fuels (AVFs) and alternative fuel vehicles (AFVs), including city bus fleets. The life cycle (LC), energy savings (ES) and GHG reduction (GR) profiles of AVFs/AFVs are critical to those policy decisions. The well-to-wheels module of the Tsinghua-CA3EM model is employed to investigate actual performance data. Compared with conventional buses, AFVs offer differences in performance in terms of both ES and GR. Only half of the AFVs analyzed demonstrate dual benefits. However, all non-oil/gas pathways can substitute oil/gas with coal. Current policies seek to promote technology improvements and market creation initiatives within the guiding framework of national-level diversification and district-level uniformity. Combined with their actual LC behavior and in keeping with near- and long-term strategies, integrated policies should seek to (1) apply hybrid electric technology to diesel buses; (2) encourage NG/LPG buses in gas-abundant cities; (3) promote commercialize electric buses or plug-in capable vehicles through battery technology innovation; (4) support fuel cell buses and hydrogen technology R and D for future potential applications; and (5) conduct further research on boosting vehicle fuel efficiency, applying low-carbon transportation technologies, and addressing all resultant implications of coal-based transportation solutions to human health and natural resources. (author)

  14. IT Policies for Development: Analysis and Recommendations of Free Libre Open Source Software Initiatives of the Bolivarian Republic of Venezuela

    Science.gov (United States)

    Maldonado Rangel, Edgar A.

    2009-01-01

    In recent years the two concepts of economic development and technological advancement have become entwined so that they have, in many cases, come to mean the same thing. For countries seeking economic development through engagement with the Information Economy, policies supporting technological development claim privileged positions in national…

  15. Alternative fuel buses currently in use in China: Life-cycle fossil energy use, GHG emissions and policy recommendations

    International Nuclear Information System (INIS)

    Ou Xunmin; Zhang Xiliang; Chang Shiyan

    2010-01-01

    The Chinese government has enacted policies to promote alternative vehicle fuels (AVFs) and alternative fuel vehicles (AFVs), including city bus fleets. The life cycle (LC), energy savings (ES) and GHG reduction (GR) profiles of AVFs/AFVs are critical to those policy decisions. The well-to-wheels module of the Tsinghua-CA3EM model is employed to investigate actual performance data. Compared with conventional buses, AFVs offer differences in performance in terms of both ES and GR. Only half of the AFVs analyzed demonstrate dual benefits. However, all non-oil/gas pathways can substitute oil/gas with coal. Current policies seek to promote technology improvements and market creation initiatives within the guiding framework of national-level diversification and district-level uniformity. Combined with their actual LC behavior and in keeping with near- and long-term strategies, integrated policies should seek to (1) apply hybrid electric technology to diesel buses; (2) encourage NG/LPG buses in gas-abundant cities; (3) promote commercialize electric buses or plug-in capable vehicles through battery technology innovation; (4) support fuel cell buses and hydrogen technology R and D for future potential applications; and (5) conduct further research on boosting vehicle fuel efficiency, applying low-carbon transportation technologies, and addressing all resultant implications of coal-based transportation solutions to human health and natural resources.

  16. Europe's energy transition. The big five recommendations to guide and inspire EU policy-makers

    International Nuclear Information System (INIS)

    2014-09-01

    The energy transition is more than a shift from one energy system (finite resources) to another (more renewable and low energy-based). Our century's challenge is to radically reduce our energy use. The local level is where the new energy paradigm is happening. Ambitious policies at European level are crucial to speed up the movement

  17. Shadows of Stuxnet: Recommendations for U.S. Policy on Critical Infrastructure Cyber Defense Derived from the Stuxnet Attack

    Science.gov (United States)

    2016-03-01

    Programmable Logic Controller (PLC), Supervisory Control and Data Acquisition ( SCADA ) 15. NUMBER OF PAGES 137 16. PRICE CODE 17. SECURITY...Management xiv PDD presidential decision directive PPD 21 Presidential Policy Directive 21 PLC programmable logic controller SCADA supervisory...also required an update to the National Infrastructure Protection Plan (NIPP). The resulting work product was the NIPP 2013. EO 13636 called for

  18. Elastic and viscous properties of the nematic dimer CB7CB

    Science.gov (United States)

    Babakhanova, Greta; Parsouzi, Zeinab; Paladugu, Sathyanarayana; Wang, Hao; Nastishin, Yu. A.; Shiyanovskii, Sergij V.; Sprunt, Samuel; Lavrentovich, Oleg D.

    2017-12-01

    We present a comprehensive set of measurements of optical, dielectric, diamagnetic, elastic, and viscous properties in the nematic (N) phase formed by a liquid crystalline dimer. The studied dimer, 1,7-bis-4-(4'-cyanobiphenyl) heptane (CB7CB), is composed of two rigid rodlike cyanobiphenyl segments connected by a flexible aliphatic link with seven methyl groups. CB7CB and other nematic dimers are of interest due to their tendency to adopt bent configurations and to form two states possessing a modulated nematic director structure, namely, the twist-bend nematic, NTB, and the oblique helicoidal cholesteric, C hOH , which occurs when the achiral dimer is doped with a chiral additive and exposed to an external electric or magnetic field. We characterize the material parameters as functions of temperature in the entire temperature range of the N phase, including the pretransitional regions near the N -NTB and N-to-isotropic (I) transitions. The splay constant K11 is determined by two direct and independent techniques, namely, detection of the Frederiks transition and measurement of director fluctuation amplitudes by dynamic light scattering (DLS). The bend K33 and twist K22 constants are measured by DLS. K33, being the smallest of the three constants, shows a strong nonmonotonous temperature dependence with a negative slope in both N-I and N -NTB pretransitional regions. The measured ratio K11/K22 is larger than 2 in the entire nematic temperature range. The orientational viscosities associated with splay, twist, and bend fluctuations in the N phase are comparable to those of nematics formed by rodlike molecules. All three show strong temperature dependence, increasing sharply near the N -NTB transition.

  19. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro

    Science.gov (United States)

    Thomas, A; Baillie, G L; Phillips, A M; Razdan, R K; Ross, R A; Pertwee, R G

    2007-01-01

    Background and purpose: A nonpsychoactive constituent of the cannabis plant, cannabidiol has been demonstrated to have low affinity for both cannabinoid CB1 and CB2 receptors. We have shown previously that cannabidiol can enhance electrically evoked contractions of the mouse vas deferens, suggestive of inverse agonism. We have also shown that cannabidiol can antagonize cannabinoid receptor agonists in this tissue with a greater potency than we would expect from its poor affinity for cannabinoid receptors. This study aimed to investigate whether these properties of cannabidiol extend to CB1 receptors expressed in mouse brain and to human CB2 receptors that have been transfected into CHO cells. Experimental approach: The [35S]GTPγS binding assay was used to determine both the efficacy of cannabidiol and the ability of cannabidiol to antagonize cannabinoid receptor agonists (CP55940 and R-(+)-WIN55212) at the mouse CB1 and the human CB2 receptor. Key results: This paper reports firstly that cannabidiol displays inverse agonism at the human CB2 receptor. Secondly, we demonstrate that cannabidiol is a high potency antagonist of cannabinoid receptor agonists in mouse brain and in membranes from CHO cells transfected with human CB2 receptors. Conclusions and implications: This study has provided the first evidence that cannabidiol can display CB2 receptor inverse agonism, an action that appears to be responsible for its antagonism of CP55940 at the human CB2 receptor. The ability of cannabidiol to behave as a CB2 receptor inverse agonist may contribute to its documented anti-inflammatory properties. PMID:17245363

  20. The East Asian Development Experience: Policy Lessons, Implications, and Recommendations for Sub-Saharan Africa (SSA) Global Competitiveness

    OpenAIRE

    Ashford C. Chea

    2012-01-01

    The paper looks at the development experience of East Asia and draws lessons for Sub-Saharan Africa in building global competitiveness. It starts with a historical perspective of both regions’ developmental trajectories. This is followed by an analysis of the causes of East Asia’s superior economic performance and development and SSA underdevelopment. The article also draws policy lessons from East Asia development strategies for SSA global competitiveness. The paper ends with a presentation ...

  1. Recommendations regarding problems of research policy relating to the establishment and operation of atomic power stations in Denmark

    International Nuclear Information System (INIS)

    1976-01-01

    This report, which was submitted by the Danish Planning Council for Research to the Parliamentary Committee on Scientific Research, is based on reports from the DANISH Atomic Energy Commission. and on a sub-committee appointed by the Planning Council, as well as on the comments of the Danish Research Council on these reports. The Planning Council submit that: 1) the question of the introduction and scope of Danish utilization of atomic energy should be considered as a link in setting up a total plan for energy policy elucidating the possibilities in the energy field from both aspects of supply and demand, 2) that there is a continuous interaction between energy policy and research policy in the subject field 3) that the total resources for energy research and development should be considerably increased, 4) that investigations into the economy of atomic power should be intensified, and 5) that investigations of possibilities for long-term storage of radioactive waste in Denmark should be speeded up. Further, the Planning Council points out the need for research in areas such as a) wind and solar energy, b) the environmental impact of utilizing atomic power in relation to that of utilizing other forms of power, c) economic and social effects of different forms of energy supply, as well as the problems of siting, decision taking and public information and participation and finally, d) the utilization of the energy raw materials found in Greenland. (B.P.)

  2. Hybrid employment recommendation algorithm based on Spark

    Science.gov (United States)

    Li, Zuoquan; Lin, Yubei; Zhang, Xingming

    2017-08-01

    Aiming at the real-time application of collaborative filtering employment recommendation algorithm (CF), a clustering collaborative filtering recommendation algorithm (CCF) is developed, which applies hierarchical clustering to CF and narrows the query range of neighbour items. In addition, to solve the cold-start problem of content-based recommendation algorithm (CB), a content-based algorithm with users’ information (CBUI) is introduced for job recommendation. Furthermore, a hybrid recommendation algorithm (HRA) which combines CCF and CBUI algorithms is proposed, and implemented on Spark platform. The experimental results show that HRA can overcome the problems of cold start and data sparsity, and achieve good recommendation accuracy and scalability for employment recommendation.

  3. CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

    Energy Technology Data Exchange (ETDEWEB)

    Prather, Paul L. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M. [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Ford, Benjamin M.; Franks, Lirit N. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Radominska-Pandya, Anna, E-mail: RadominskaAnna@uams.edu [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States)

    2013-11-15

    Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

  4. CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

    International Nuclear Information System (INIS)

    Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

    2013-01-01

    Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

  5. Recommendations concerning the scientific foundation of radiohygienic policy based on the UNSCEAR-77, -82 and BEIR reports

    International Nuclear Information System (INIS)

    1985-01-01

    This report studies to what extent the UNSCEAR-77 report and other more recent scientific literature (in particular the BEIR-80 and UNSCEAR-82 reports) support the risk factors mentioned in ICRP-26, which formed the basis of the weighting factors per organ, recommended by the International Commission on Radiological Protection. It discusses the nature and size of the different contributions to the exposure to ionizing radiation both on a global level and with respect to the Dutch situation. An estimate is given of the average total annual dose equivalent for the world population, for the population of the Netherlands and for radiological workers in the Netherlands. An extensive discussion is presented of the dose-effect relationships of stochastic radiation effects in the female breast, the thyroid, red bone marrow, bone tissue, the lungs, other organs and the whole body. Furthermore consideration is given to nonstochastic effects in the lens of the eye and in the skin and to the late effects of radiotherapy. Finally the effects of prenatal irradiation and the genetic effects of ionizing radiation are discussed. Subsequently the risk factors used by ICRP in formulating its recommendations in publication ICRP-26, are compared with the risk factors mentioned in the scientific literature. (Auth.)

  6. European Federation of Organisations for Medical Physics (EFOMP) policy statement 12.1: Recommendations on medical physics education and training in Europe 2014.

    Science.gov (United States)

    Caruana, C J; Christofides, S; Hartmann, G H

    2014-09-01

    In 2010, EFOMP issued Policy Statement No. 12: "The present status of Medical Physics Education and Training in Europe. New perspectives and EFOMP recommendations" to be applied to education and training in Medical Physics within the context of the developments in the European Higher Education Area arising from the Bologna Declaration and with a view to facilitate the free movement of Medical Physics professionals within Europe. Concurrently, new recommendations regarding qualifications frameworks were published by the European Parliament and Council which introduced new terminology and a new qualifications framework - the European Qualifications Framework (EQF) for lifelong learning. In addition, a new European directive involving the medical use of ionizing radiations and set to replace previous directives in this area was in the process of development. This has now been realized as Council Directive 2013/59/Euratom of 5 December 2013 which has repealed directive 97/43/Euratom. In this regard, a new document was developed in the context of the EC financed project "European Guidelines on the Medical Physics Expert" and published as RP174. Among other items, these guidelines refer to the mission statement, key activities, qualification framework and curricula for the specialty areas of Medical Physics relating to radiological devices and protection from ionizing radiation. These developments have made necessary an update of PS12; this policy statement provides the necessary update. Copyright © 2014. Published by Elsevier Ltd.

  7. [Are nail polish, artificial nails and piercings allowed outside the surgical area?Recommendations for the perioperative policy].

    Science.gov (United States)

    Bucx, M J L; Krijtenburg, P; Scheffer, G J

    2017-01-01

    - An increasing number of patients wear nail polish, artificial nails or have piercings.- There is uncertainty about the perioperative management of these items, especially when located outside the surgical area.- In the majority of hospitals, patients are urged to remove these items preoperatively, under the assumption that they might cause problems.- Frequently, however, these items cannot be removed straightforwardly.- Nail polish and artificial nails only very rarely cause perioperative problems and therefore do not need to be removed pre-operatively.- The same applies to most piercings, except when located in or near the respiratory tract, if they have sharp endings or if they might cause problems as a result of the perioperative positioning of the patient.- Providing adequate information to the patient, knowledge about removal of these items and documentation of agreed arrangements are all important.- A national guideline concerning perioperative policy is urgently required.

  8. Recommendations on chemicals management policy and legislation in the framework of the Egyptian-German twinning project on hazardous substances and waste management.

    Science.gov (United States)

    Wagner, Burkhard O; Aziz, Elham Refaat Abdel; Schwetje, Anja; Shouk, Fatma Abou; Koch-Jugl, Juliane; Braedt, Michael; Choudhury, Keya; Weber, Roland

    2013-04-01

    The sustainable management of chemicals and their associated wastes-especially legacy stockpiles-is always challenging. Developing countries face particular difficulties as they often have insufficient treatment and disposal capacity, have limited resources and many lack an appropriate and effective regulatory framework. This paper describes the objectives and the approach of the Egyptian-German Twinning Project under the European Neighbourhood Policy to improve the strategy of managing hazardous substances in the Egyptian Environmental Affairs Agency (EEAA) between November 2008 and May 2011. It also provides an introduction to the Republic of Egypt's legal and administrative system regarding chemical controls. Subsequently, options for a new chemical management strategy consistent with the recommendations of the United Nations Chemicals Conventions are proposed. The Egyptian legal and administrative system is discussed in relation to the United Nations' recommendations and current European Union legislation for the sound management of chemicals. We also discuss a strategy for the EEAA to use the existing Egyptian legal system to implement the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals, the Stockholm Convention and other proposed regulatory frameworks. The analysis, the results, and the recommendations presented may be useful for other developing countries in a comparable position to Egypt aspiring to update their legislation and administration to the international standards of sound management of chemicals.

  9. The CMS Collaboration Board (CB) chairperson, deputy and secretary, with the CMS Spokesperson and deputies

    CERN Multimedia

    Lapka, M

    2012-01-01

    From left to right: Jorgen D'Hondt (CB Secretary), Claudia Wulz (CB Deputy Chair), Tiziano Camporesi (Deputy Spokesperson), Ian Shipsey (new CB Chair 2013-2014), Joe Incandela (CMS Spokesperson), Joao Varela (Deputy Spokesperson)

  10. CB5C affects the glucosinolate profile in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Vik, Daniel; Crocoll, Christoph; Andersen, Tonni Grube

    2016-01-01

    proteins support the cytochrome P450 enzymes of plant specialized metabolism and found CB5C from Arabidopsis thaliana to co-express with glucosinolate biosynthetic genes. We characterized the glucosinolate profiles of two T-DNA insertion mutants of CB5C, and found that long-chained aliphatic glucosinolates...... were reduced in one of the mutant lines - a phenotype that was exaggerated upon methyl-jasmonate treatment. These results support the hypothesis, that CB5C influences glucosinolate biosynthesis, however, the mode of action remains unknown. Furthermore, the mutants differed in their biomass response...

  11. Extensively Drug-resistant Tuberculosis (XDR-TB): A daunting challenge to the current End TB Strategy and policy recommendations.

    Science.gov (United States)

    Rahman, Md Arifur; Sarkar, Atanu

    2017-07-01

    Extensively Drug-resistant Tuberculosis (XDR-TB) has emerged as one of the most formidable challenges to the End TB Strategy that has targeted a 95% reduction in TB deaths and 90% reduction in cases by 2035. Globally, there were an estimated 55,100 new XDR-TB cases in 2015 in 117 countries. However, only one in 30 XDR-TB cases had been reported so far. Drug susceptibility test (DST) is the mainstay for diagnosing XDR-TB, but the lack of laboratory facilities in the resource-limited endemic countries limit its uses. A few new drugs including bedaquiline and delamanid, have the potential to improve the efficiency of XDR-TB treatment, but the drugs have been included in 39 countries only. The costs of XDR-TB treatment are several folds higher than that of the MDR-TB. Despite the financing from the donors, there is an urgent need to fill the current funding gap of US$ 2 billion to ensure effective treatment and robust surveillance. In the review article we have addressed current update on XDR-TB, including surveillance, diagnosis and the interventions needed to treat and limit its spread, emphasis on extensive financial support for implementing of current recommendations to meet the goals of End TB Strategy. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  12. The health of homeless people in high-income countries: descriptive epidemiology, health consequences, and clinical and policy recommendations.

    Science.gov (United States)

    Fazel, Seena; Geddes, John R; Kushel, Margot

    2014-10-25

    In the European Union, more than 400,000 individuals are homeless on any one night and more than 600,000 are homeless in the USA. The causes of homelessness are an interaction between individual and structural factors. Individual factors include poverty, family problems, and mental health and substance misuse problems. The availability of low-cost housing is thought to be the most important structural determinant for homelessness. Homeless people have higher rates of premature mortality than the rest of the population, especially from suicide and unintentional injuries, and an increased prevalence of a range of infectious diseases, mental disorders, and substance misuse. High rates of non-communicable diseases have also been described with evidence of accelerated ageing. Although engagement with health services and adherence to treatments is often compromised, homeless people typically attend the emergency department more often than non-homeless people. We discuss several recommendations to improve the surveillance of morbidity and mortality in homeless people. Programmes focused on high-risk groups, such as individuals leaving prisons, psychiatric hospitals, and the child welfare system, and the introduction of national and state-wide plans that target homeless people are likely to improve outcomes.

  13. The health of homeless people in high-income countries: descriptive epidemiology, health consequences, and clinical and policy recommendations

    Science.gov (United States)

    Fazel, Seena; Geddes, John R; Kushel, Margot

    2015-01-01

    In the European Union, more than 400 000 individuals are homeless on any one night and more than 600 000 are homeless in the USA. The causes of homelessness are an interaction between individual and structural factors. Individual factors include poverty, family problems, and mental health and substance misuse problems. The availability of low-cost housing is thought to be the most important structural determinant for homelessness. Homeless people have higher rates of premature mortality than the rest of the population, especially from suicide and unintentional injuries, and an increased prevalence of a range of infectious diseases, mental disorders, and substance misuse. High rates of non-communicable diseases have also been described with evidence of accelerated ageing. Although engagement with health services and adherence to treatments is often compromised, homeless people typically attend the emergency department more often than non-homeless people. We discuss several recommendations to improve the surveillance of morbidity and mortality in homeless people. Programmes focused on high-risk groups, such as individuals leaving prisons, psychiatric hospitals, and the child welfare system, and the introduction of national and state-wide plans that target homeless people are likely to improve outcomes. PMID:25390578

  14. Recommendations for Infant Feeding Policy and Programs in Dzimauli Region, South Africa: Results From the MAL-ED Birth Cohort.

    Science.gov (United States)

    Mushaphi, Lindelani Fhumudzani; Mahopo, Tjale Cloupas; Nesamvuni, Cebisa Noxolo; Baloyi, Brenda; Mashau, Ellen; Richardson, Jeniata; Dillingham, Rebecca; Guerrant, Richard; Ambikapathi, Ramya; Bessong, Pascal

    2017-09-01

    There is strong evidence that exclusive breastfeeding (EBF) in the first 6 months of life reduces the risk of diseases in infancy and in later life. To understand the maternal reasoning that influences optimum infant feeding practices of caregivers in semirural communities of Limpopo province. Nested qualitative study among mothers in an ongoing birth cohort study was conducted; structured and semi-structured interviews were used to collect data. Data from 234 infants after 6 months of follow-up was included for quantitative analysis. Four focus discussion groups comprising 7 to 10 caregivers were used to obtain perception of mothers on breastfeeding. A semi-structured interview guide was used to stimulate discussions. Thematic content analyses were conducted to identify the main themes that influence breastfeeding practices of caregivers. Over 90% of the caregivers initiated breastfeeding after delivery. However, less than 1% of mothers practiced EBF by 3 months, and none of the children were exclusively breastfed for up to 6 months. All caregivers introduced non-breast milk liquids and solids by the second month of child's life. Common reasons for introducing non-breast milk foods included insufficiency of breast milk production, going back to work or school, and influence by elderly women (mothers/mothers-in-law) and church members. Exclusive breastfeeding was not practiced in this community due to cultural and religious beliefs and misinformation. The involvement of elderly women and church members in infant feeding education and promotion programs and the dissemination of breastfeeding information through mobile phones to younger mothers are recommended.

  15. Sustainable prevention of resource conflicts. Policy and research recommendations (report 5); Rohstoffkonflikte nachhaltig vermeiden. Forschungs- und Handlungsempfehlungen (Teilbericht 5)

    Energy Technology Data Exchange (ETDEWEB)

    Taenzler, Dennis; Westerkamp, Meike [Adelphi Research, Berlin (Germany); Supersberger, Nikolaus; Ritthoff, Michael; Bleischwitz, Raimund [Wuppertal Institut (Germany)

    2011-04-15

    Raw material conflict occurs in various forms: in the form of supply bottlenecks and crises, violent disputes, or even war; as well as due to the effects of environmental destruction, whereby the sources of people's livelihood are lost. Raw material conflict is a reality in many instances, but in others is merely postulated. On the one hand, the nature, strategic importance and price of raw materials influence potential conflict constellations. On the other hand, much depends on the management and governance of raw material resources and production, material flows, value creation chains and sources of financing, across a variety of levels. Existing research into raw material conflict in the field of oil, gas and valuable minerals reveals the multi-layered complexity of the issue as well as the necessity and possibilities of avoiding such conflict in a sustainable manner over the long term. This research landscape was the starting point for the study by adelphi and the Wuppertal Institute titled ''Sustainable Prevention of Resource Conflicts: Identifying and reducing international conflict risk relating to access to and use of raw materials''. The project has added to existing research and delivered new perspectives in relation to lithium and rare earths - resources which are of special relevance for future energy supply and planning - with a view to developing renewable energy sources and meeting ambitious climate protection goals. This report summarises the results of the research project and sets out recommendations. The project was sponsored by the German Federal Environmental Agency, and was conducted in the period between July 2008 and September 2010. The results are published in a total of eight reports which are briefly summarised here. (orig.)

  16. Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies.

    Science.gov (United States)

    Kerlin, Roy; Bolon, Brad; Burkhardt, John; Francke, Sabine; Greaves, Peter; Meador, Vince; Popp, James

    2016-02-01

    Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and

  17. Next Generation LWIR Spectrum Projector (CB-2) Design Study

    National Research Council Canada - National Science Library

    Thomas, M

    2004-01-01

    ...) and the two best ways to meet those requirements. Based upon the success of the CB-1 Spectrum Projector built and tested by MRC, Dugway Proving Ground, Block Engineering and Edgewood Research Development and Engineering Center (now U.S...

  18. The European Federation of Organisations for Medical Physics Policy Statement No. 10.1: Recommended Guidelines on National Schemes for Continuing Professional Development of Medical Physicists.

    Science.gov (United States)

    Christofides, Stelios; Isidoro, Jorge; Pesznyak, Csilla; Cremers, Florian; Figueira, Rita; van Swol, Christiaan; Evans, Stephen; Torresin, Alberto

    2016-01-01

    Continuing Professional Development (CPD) is vital to the medical physics profession if it is to embrace the pace of change occurring in medical practice. As CPD is the planned acquisition of knowledge, experience and skills required for professional practice throughout one's working life it promotes excellence and protects the profession and public against incompetence. Furthermore, CPD is a recommended prerequisite of registration schemes (Caruana et al. 2014) and is implied in the Council Directive 2013/59/EURATOM (EU BSS) and the International Basic Safety Standards (BSS). It is to be noted that currently not all national registration schemes require CPD to maintain the registration status necessary to practise medical physics. Such schemes should consider adopting CPD as a prerequisite for renewing registration after a set period of time. This EFOMP Policy Statement, which is an amalgamation and an update of the EFOMP Policy Statements No. 8 and No. 10, presents guidelines for the establishment of national schemes for CPD and activities that should be considered for CPD. Copyright © 2016. Published by Elsevier Ltd.

  19. Magnesium isotopic constraints on the origin of CB b chondrites

    Science.gov (United States)

    Gounelle, Matthieu; Young, Edward D.; Shahar, Anat; Tonui, Eric; Kearsley, Anton

    2007-04-01

    The magnesium isotopic composition of Calcium-, Aluminium-rich Inclusions (CAIs) and chondrules from the CB b chondrites HH237 and QUE94411 was measured using MC-ICPMS coupled with a laser ablation system. CAIs from CB b chondrites exhibit limited mass-dependent fractionation ( δ25Mg' (DSM3) impulsive flares in the case of an irradiation origin of 26Al. In both cases, it implies that a protoplanetary disk was present ˜ 4563 Ma ago, when CB b chondrites agglomerated. Chondrules have δ25Mg' (DSM3) varying from - 0.80 to 0.95‰. A rough negative correlation is observed between the δ25Mg' of chondrules and their 24Mg/ 27Al ratio. This correlation is attributed to evaporation rather than mixing. Contrary to CAIs, chondrules from CB b chondrites have a magnesium isotopic composition similar to that of CV3 chondrules. This last result is surprising as CB b chondrules are significantly different from CV3 chondrules in mineralogy and chemistry. If chondrules from CB b chondrites formed in an impact-related vapour plume as proposed by Krot et al. [A.N. Krot, Y. Amelin, P. Cassen and A. Meibom, Young chondrules in CB chondrites formed by a giant impact in the early Solar System, Nature 436 (2005) 989-992], our data show that physical conditions in the vapour plume were similar to those of the solar accretion disk at the time and location of the formation of CV chondrules. We note that the oxygen isotopic composition of CAIs is incompatible with their remelting in the putative impact vapour plume. Alternatively, it is possible that CB b chondrules formed in a protoplanetary disk as the differences between these and "normal" CV3 chondrules can also be explained in term of spatial and temporal variations of the protoplanetary disk. We show that their young Pb-Pb age is not an argument in favour of an impact origin as protoplanetary disks can last as long as 10 Myr around protostars. If CB b chondrites formed in the solar accretion disk, we speculate they might be the last

  20. Clinical Policy Recommendations from the VHA State-of-the-Art Conference on Non-Pharmacological Approaches to Chronic Musculoskeletal Pain.

    Science.gov (United States)

    Kligler, Benjamin; Bair, Matthew J; Banerjea, Ranjana; DeBar, Lynn; Ezeji-Okoye, Stephen; Lisi, Anthony; Murphy, Jennifer L; Sandbrink, Friedhelm; Cherkin, Daniel C

    2018-05-01

    As a large national healthcare system, Veterans Health Administration (VHA) is ideally suited to build on its work to date and develop a safe, evidence-based, and comprehensive approach to the care of chronic musculoskeletal pain conditions that de-emphasizes opioid use and emphasizes non-pharmacological strategies. The VHA Office of Health Services Research and Development (HSR&D) held a state-of-the-art (SOTA) conference titled "Non-pharmacological Approaches to Chronic Musculoskeletal Pain Management" in November 2016. Goals of the conference were (1) to establish consensus on the current state of evidence regarding non-pharmacological approaches to chronic musculoskeletal pain to inform VHA policy in this area and (2) to begin to identify priorities for the future VHA research agenda. Workgroups were established and asked to reach consensus recommendations on clinical and research priorities for the following treatment strategies: psychological/behavioral therapies, exercise/movement therapies, manual therapies, and models for delivering multimodal pain care. Participants in the SOTA identified nine non-pharmacological therapies with sufficient evidence to be implemented across the VHA system as part of pain care. Participants further recommended that effective integration of these non-pharmacological approaches across the VHA and especially into VHA primary care, pain care, and mental health settings should be a priority, and that these treatments should be offered early in the course of pain treatment and delivered in a team-based, multimodal treatment setting concurrently with active self-care and self-management approaches. In addition, we recommend that VHA leadership and policy makers systematically address the barriers to implementation of these approaches by expanding opportunities for clinician and veteran education on the effectiveness of these strategies; supporting and funding further research to determine optimal dosage, duration, sequencing

  1. Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy Through Science – Addressing the ODWAC New Recommendation

    Science.gov (United States)

    Dingwall, S.; Mills, C.E.; Phan, N.; Taylor, K.; Boreham, D.R.

    2011-01-01

    Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered. The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from

  2. Müller cells express the cannabinoid CB2 receptor in the vervet monkey retina

    DEFF Research Database (Denmark)

    Bouskila, Joseph; Javadi, Pasha; Casanova, Christian

    2013-01-01

    The presence of the cannabinoid receptor type 1 (CB1R) has been largely documented in the rodent and primate retinae in recent years. There is, however, some controversy concerning the presence of the CB2 receptor (CB2R) within the central nervous system. Only recently, CB2R has been found...... in the rodent retina, but its presence in the primate retina has not yet been demonstrated. The aim of this study was twofold: 1) to characterize the distribution patterns of CB2R in the monkey retina and compare this distribution with that previously reported for CB1R and 2) to resolve the controversy...... on the presence of CB2R in the neural component of the retina. We therefore thoroughly examined the cellular localization of CB2R in the vervet monkey (Chlorocebus sabeus) retina, using confocal microscopy. Our results demonstrate that CB2R, like CB1R, is present throughout the retinal layers, but with striking...

  3. I. NIH TOOLBOX COGNITION BATTERY (CB): INTRODUCTION AND PEDIATRIC DATA*

    Science.gov (United States)

    Weintraub, Sandra; Bauer, Patricia J.; Zelazo, Philip David; Wallner-Allen, Kathleen; Dikmen, Sureyya S.; Heaton, Robert K.; Tulsky, David S.; Slotkin, Jerry; Blitz, David L.; Carlozzi, Noelle E.; Havlik, Richard J.; Beaumont, Jennifer L.; Mungas, Dan; Manly, Jennifer J.; Borosh, Beth G.; Nowinski, Cindy J.; Gershon, Richard C.

    2014-01-01

    This monograph presents the pediatric portion of the National Institutes of Health (NIH) Toolbox Cognition Battery (CB) of the NIH Toolbox for the Assessment of Neurological and Behavioral Function. The NIH Toolbox is an initiative of the Neuroscience Blueprint, a collaborative framework through which 16 NIH Institutes, Centers, and Offices jointly support neuroscience-related research, to accelerate discoveries and reduce the burden of nervous system disorders. The CB is one of four modules that measure cognitive, emotional, sensory, and motor health across the lifespan. The CB is unique in its continuity across childhood, adolescence, early adulthood, and old age, and in order to help create a common currency among disparate studies, it is also available at low cost to researchers for use in large-scale longitudinal and epidemiologic studies. This chapter describes the evolution of the CB; methods for selecting cognitive subdomains and instruments; the rationale for test design; and a validation study in children and adolescents, ages 3–15 years. Subsequent chapters feature detailed discussions of each test measure and its psychometric properties (Chapters 2–6), the factor structure of the test battery (Chapter 7), the effects of age and education on composite test scores (Chapter 8), and a final summary and discussion (Chapter 9). As the chapters in this monograph demonstrate, the CB has excellent psychometric properties, and the validation study provided evidence for the increasing differentiation of cognitive abilities with age. PMID:23952199

  4. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin

    Science.gov (United States)

    Pertwee, R G

    2007-01-01

    Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), (−)-cannabidiol (CBD) and (−)-trans-Δ9-tetrahydrocannabivarin (Δ9-THCV), interact with cannabinoid CB1 and CB2 receptors. Δ9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1- and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Δ9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Δ9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by Δ9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which Δ9-THC, CBD and Δ9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids. PMID:17828291

  5. Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB1and CB2Cannabinoid Receptors.

    Science.gov (United States)

    Simkins, Tyrell J; Fried, David; Parikh, Kevin; Galligan, James J; Goudreau, John L; Lookingland, Keith J; Kaplan, Barbara L F

    2016-12-01

    The spleen is a visceral organ that contracts during hypoxia to expel erythrocytes and immune cells into the circulation. Spleen contraction is under the control of noradrenergic sympathetic innervation. The activity of noradrenergic neurons terminating in the spleen capsule is regulated by α2-adrenergic receptors (AR). Interactions between endogenous cannabinoid signaling and noradrenergic signaling in other organ systems suggest endocannabinoids might also regulate spleen contraction. Spleens from mice congenitally lacking both CB 1 and CB 2 cannabinoid receptors (Cnr1 -/- /Cnr2 -/- mice) were used to explore the role of endocannabinoids in spleen contraction. Spleen contraction in response to exogenous norepinephrine (NE) was found to be significantly lower in Cnr1 -/- /Cnr2 -/- mouse spleens, likely due to decreased expression of capsular α1AR. The majority of splenic Cnr1 mRNA expression is by cells of the spleen capsule, suggestive of post-synaptic CB 1 receptor signaling. Thus, these studies demonstrate a role for CB 1 and/or CB 2 in noradrenergic splenic contraction.

  6. Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival.

    Science.gov (United States)

    Theocharis, Stamatios; Giaginis, Constantinos; Alexandrou, Paraskevi; Rodriguez, Jose; Tasoulas, Jason; Danas, Eugene; Patsouris, Efstratios; Klijanienko, Jerzy

    2016-03-01

    Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). CB1R and CB2R expression was assessed immunohistochemically on 28 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics and overall and disease-free patients' survival. CB1R, CB2R, and concomitant CB1R/CB2R expression was significantly increased in older compared to younger mobile tongue SCC patients (p = 0.0243, p = 0.0079, and p = 0.0366, respectively). Enhanced CB2R and concomitant CB1R/CB2R expression was significantly more frequently observed in female compared to male mobile tongue SCC patients (p = 0.0025 and p = 0.0016, respectively). Elevated CB2R expression was significantly more frequently observed in mobile tongue SCC patients presenting well-defined tumor shape compared to those with diffuse (p = 0.0430). Mobile tongue SCC patients presenting enhanced CB1R, CB2R, or concomitant CB1R/CB2R expression showed significantly longer overall (log-rank test, p = 0.004, p = 0.011, p = 0.018, respectively) and disease-free (log-rank test, p = 0.003, p = 0.007, p = 0.027, respectively) survival times compared to those with low expression. In multivariate analysis, CB1R was identified as an independent prognostic factor for disease-free patients' survival (Cox-regression analysis, p = 0.032). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.

  7. CB-SMoT+: UNA EXTENSIÓN AL ALGORITMO CB-SMoT

    Directory of Open Access Journals (Sweden)

    FRANCISCO MORENO

    2012-12-01

    Full Text Available Una trayectoria es un registro de la evoluciónde la posición de un objeto móvil. Por ejemplo,un vehículo que se mueve en el espacio durante unintervalo de tiempo. Una trayectoria se representamediante una secuencia de observaciones que indicanla posición y el tiempo en el que fue tomada cadaobservación. CB-SMoT es un algoritmo que identificalas partes de una trayectoria durante las cuales elobjeto mantuvo una velocidad promedio por debajode un límite dado. En este artículo se propone unaextensión para dicho algoritmo que permite identificarlas partes de una trayectoria durante las cualesel objeto mantuvo una velocidad promedio entre observacionespor debajo de un límite dado. Esto posibilitala identificación, por ejemplo, de violacionesa un límite de velocidad que no son advertidas porel algoritmo original. Para el estudio se usó el sistemade gestión de bases de datos PostgreSQL y losalgoritmos se implementaron en su lenguaje de programación,llamado PL/pgSQL. Además, se hicieronexperimentos con 100 trayectorias de vehículos conel propósito de mostrar la utilidad y la viabilidad de lapropuesta.

  8. Sonographic demonstration of Cruveilhier-Baumgarten (CB) syndrome

    International Nuclear Information System (INIS)

    Schulze, P.J.; Vogel, H.M.

    1982-01-01

    The term 'CB syndrome' comprises the presence of umbilical vein collateral circulation due to portal hypertension associated with cirrhosis or other recognizable structural anomalies of the liver. Usually the dilated remnant of the umbilical vein is the main collateral pathway. Demonstration of this structure not only indicates the presence of portal hypertension but also that the underlying obstruction is intra- or posthepatic rather than prehepatic. This paper reports sonographic visualization of CB syndrome in 23 patients with cirrhosis of the liver. Questions of differential diagnosis and nomenclature are discussed with respect to developmental and anatomical preconditions. (orig.)

  9. Green energy - the road to a Danish energy system without fossil fuels. Summary of the work, results and recommendations of the Danish Commission on Climate Change Policy

    Energy Technology Data Exchange (ETDEWEB)

    2010-09-15

    This summary report describes the main outcomes of the deliberations of the Danish Commission on Climate Change Policy. It includes a proposal for how Denmark can become independent of fossil fuels and, at the same time, meet the target of reducing greenhouse gases by 80%-95% compared with 1990. In addition, 40 specific recommendations for initiatives which will contribute to the realisation of the vision are presented. The documentation section of the overall report, which is only available in Danish, presents the Climate Commission's work in more detail, as well as a description of the comprehensive analyses on which the Climate Commission has based its recommendations. Finally, the background documents, which have been prepared at the request of the Climate Commission are available (in Danish) at the Commission's website, www.klimakommissionen.dk. We can both reduce Danish emissions of greenhouse gasses significantly, and make Denmark independent of fossil fuels. This will require a total conversion of the Danish energy system; conversion away from oil, coal and gas, which today account for more than 80% of our energy consumption, and to green energy with wind turbines and bioenergy as the most important elements. The cost of conversion may seem surprisingly low. The low cost means that not only can we maintain our present living standards, we can also have considerable economic growth, so that energy expenditures will constitute less of our budgets in the future than today. The reason the cost is not higher is primarily because we will not have to pay for overpriced fossil fuels and CO{sub 2} reductions, and we will be able to limit our energy consumption through efficiency improvements in all areas in the future. It is difficult to make predictions about the exact design of the green energy system of the future. However, in overall terms it could look like this: 1) Energy will be used far more efficiently, so that we can, for example, heat our houses

  10. The numerical benchmark CB2-S, final evaluation

    International Nuclear Information System (INIS)

    Chrapciak, V.

    2002-01-01

    In this paper are final results of numerical benchmark CB2-S compared (activity, gamma and neutron sources, concentration of important nuclides and decay heat). The participants are: Vladimir Chrapciak (SCALE), Ludmila Markova (SCALE), Svetlana Zabrodskaja (SCALA), Pavel Mikolas (WIMS). Eva Tinkova (HELIOS) and Maria Manolova (SCALE) (Authors)

  11. CB1 receptor-mediated respiratory depression by endocannabinoids.

    Science.gov (United States)

    Iring, András; Hricisák, László; Benyó, Zoltán

    2017-06-01

    Endocannabinoids (ECs) are bioactive lipid mediators acting on two distinct cannabinoid receptors (CB1 and CB2), which are ubiquitously expressed in many tissues including the respiratory system. Despite numerous experimental data showing that cannabinomimetics influence respiration, the role of endogenously produced ECs in respiratory control has not been verified yet. Pulse oximetry was used in the present study to directly measure changes in respiratory parameters during elevation of EC levels. The cannabinoid reuptake inhibitor AM-404 (10mgkg -1 , i.v.), but not its vehicle, induced a transient reduction of respiratory rate with a concomitant depression of arterial oxygen saturation and increase in breath distension in wild-type mice. In contrast, CB1 knock-out mice showed no alteration in any of these parameters upon administration of AM-404. Our results imply that the EC system has an important role in the physiological control of respiration by modulating the respiratory rate and consequently influencing arterial oxygen saturation. Furthermore, this mechanism is entirely dependent on CB1 receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Greek health professionals’ perceptions of the HPV vaccine, state policy recommendations and their own role with regards to communication of relevant health information

    Directory of Open Access Journals (Sweden)

    Christina Karamanidou

    2016-06-01

    Full Text Available Abstract Background Every year in Europe 60,000 women develop cervical cancer and 30,000 die from the disease. HPV vaccines are currently believed to constitute an important element of cervical cancer control strategy. Currently in Greece, the HPV vaccine is given on demand after prescription by a healthcare professional. Health care professionals’ role is key as they are in a position to discuss HPV vaccination with parents, adolescents and young women. This study is aiming to explore health care professionals’ perceptions of the HPV vaccine, state policy recommendations and their own role with regards to communication of relevant health information. Methods This was an in-depth, qualitative study, employing a stratified, purposeful sampling. Fifteen face-to-face, semi-structured interviews were conducted with health care professionals from a variety of disciplines: pediatrics, obstetrics and gynecology, infectious diseases, pharmacy, dermatology, general practice. Thematic qualitative analysis was used to analyze participants’ accounts. Results Five major themes were identified: health care professionals’ perceptions towards the HPV vaccine (recognition of importance, concerns about safety, effectiveness and impact of long-term use, animosity between medical specialties (territorial disputes among professional bodies, role advocacy, role limitations, health care professionals’ perceptions of the public’s attitudes (effects of cultural beliefs, health professionals’ attitudes, media and family, the role of the state (health policy issues, lack of guidance, unmet expectations and their own role (provision of health information, sex education. Conclusions Health professionals’ concerns, lack of role definition and uniform information provision have led to territorial disputes among professional bodies and distrust among different medical specialties. Positive and negative judgements deriving from a multitude of sources have

  13. Greek health professionals' perceptions of the HPV vaccine, state policy recommendations and their own role with regards to communication of relevant health information.

    Science.gov (United States)

    Karamanidou, Christina; Dimopoulos, Kostas

    2016-06-03

    Every year in Europe 60,000 women develop cervical cancer and 30,000 die from the disease. HPV vaccines are currently believed to constitute an important element of cervical cancer control strategy. Currently in Greece, the HPV vaccine is given on demand after prescription by a healthcare professional. Health care professionals' role is key as they are in a position to discuss HPV vaccination with parents, adolescents and young women. This study is aiming to explore health care professionals' perceptions of the HPV vaccine, state policy recommendations and their own role with regards to communication of relevant health information. This was an in-depth, qualitative study, employing a stratified, purposeful sampling. Fifteen face-to-face, semi-structured interviews were conducted with health care professionals from a variety of disciplines: pediatrics, obstetrics and gynecology, infectious diseases, pharmacy, dermatology, general practice. Thematic qualitative analysis was used to analyze participants' accounts. Five major themes were identified: health care professionals' perceptions towards the HPV vaccine (recognition of importance, concerns about safety, effectiveness and impact of long-term use), animosity between medical specialties (territorial disputes among professional bodies, role advocacy, role limitations), health care professionals' perceptions of the public's attitudes (effects of cultural beliefs, health professionals' attitudes, media and family), the role of the state (health policy issues, lack of guidance, unmet expectations) and their own role (provision of health information, sex education). Health professionals' concerns, lack of role definition and uniform information provision have led to territorial disputes among professional bodies and distrust among different medical specialties. Positive and negative judgements deriving from a multitude of sources have resulted in the confusion of the general public, as manifested by low vaccination

  14. Risperidone treatment increases CB1 receptor binding in rat brain

    DEFF Research Database (Denmark)

    Secher, Anna; Husum, Henriette; Holst, Birgitte

    2010-01-01

    , the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. METHODS: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20......% hydroxypropyl beta-cyclodextrin) for 28 days. Expression of the aforementioned factors were examined together with plasma prolactin and ghrelin levels. RESULTS: No difference in body weight gained during treatment was observed between risperidone and vehicle treated rats, but plasma risperidone levels...... positively correlated with visceral fat mass. Risperidone treatment increased CB(1) receptor binding in the arcuate nucleus (40%), hippocampus (25-30%) and amygdala (35%) without concurrent alterations in the CB(1) receptor mRNA. Risperidone treatment increased adiponectin mRNA. CONCLUSION: The present study...

  15. 47 CFR 95.415 - (CB Rule 15) Who is responsible for communications I make?

    Science.gov (United States)

    2010-10-01

    ... communications I make? 95.415 Section 95.415 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... A Cb Station § 95.415 (CB Rule 15) Who is responsible for communications I make? You are responsible for all communications which are made by you from a CB station. ...

  16. Marketingový mix firmy ALU KOLA CB

    OpenAIRE

    URBAN, Karel

    2011-01-01

    This bachelor thesis is focused on a marketing mix practical application in my own company ALU KOLA CB. My company sells alloy wheels and tyres for personal cars. In a literary review are introduced and explained terms marketing, marketing mix and its parts - product, price, place and promotion. In a practical part of this thesis are these terms applied on my company. The end of this part contains results and improvement suggestions.

  17. YUCCA MOUNTAIN PROJECT RECOMMENDATION BY THE SECRETARY OF ENERGY REGARDING THE SUITABILITY OF THE YUCCA MOUNTAIN SITE FOR A REPOSITORY UNDER THE NUCLEAR WASTE POLICY ACT OF 1982

    Energy Technology Data Exchange (ETDEWEB)

    NA

    2002-03-26

    For more than half a century, since nuclear science helped us win World War II and ring in the Atomic Age, scientists have known that !he Nation would need a secure, permanent facility in which to dispose of radioactive wastes. Twenty years ago, when Congress adopted the Nuclear Waste Policy Act of 1982 (NWPA or ''the Act''), it recognized the overwhelming consensus in the scientific community that the best option for such a facility would be a deep underground repository. Fifteen years ago, Congress directed the Secretary of Energy to investigate and recommend to the President whether such a repository could be located safely at Yucca Mountain, Nevada. Since then, our country has spent billions of dollars and millions of hours of research endeavoring to answer this question. I have carefully reviewed the product of this study. In my judgment, it constitutes sound science and shows that a safe repository can be sited there. I also believe that compelling national interests counsel in favor of proceeding with this project. Accordingly, consistent with my responsibilities under the NWPA, today I am recommending that Yucca Mountain be developed as the site for an underground repository for spent fuel and other radioactive wastes. The first consideration in my decision was whether the Yucca Mountain site will safeguard the health and safety of the people, in Nevada and across the country, and will be effective in containing at minimum risk the material it is designed to hold. Substantial evidence shows that it will. Yucca Mountain is far and away the most thoroughly researched site of its kind in the world. It is a geologically stable site, in a closed groundwater basin, isolated on thousands of acres of Federal land, and farther from any metropolitan area than the great majority of less secure, temporary nuclear waste storage sites that exist in the country today. This point bears emphasis. We are not confronting a hypothetical problem. We have a

  18. YUCCA MOUNTAIN PROJECT RECOMMENDATION BY THE SECRETARY OF ENERGY REGARDING THE SUITABILITY OF THE YUCCA MOUNTAIN SITE FOR A REPOSITORY UNDER THE NUCLEAR WASTE POLICY ACT OF 1982

    International Nuclear Information System (INIS)

    2002-01-01

    For more than half a century, since nuclear science helped us win World War II and ring in the Atomic Age, scientists have known that the Nation would need a secure, permanent facility in which to dispose of radioactive wastes. Twenty years ago, when Congress adopted the Nuclear Waste Policy Act of 1982 (NWPA or ''the Act''), it recognized the overwhelming consensus in the scientific community that the best option for such a facility would be a deep underground repository. Fifteen years ago, Congress directed the Secretary of Energy to investigate and recommend to the President whether such a repository could be located safely at Yucca Mountain, Nevada. Since then, our country has spent billions of dollars and millions of hours of research endeavoring to answer this question. I have carefully reviewed the product of this study. In my judgment, it constitutes sound science and shows that a safe repository can be sited there. I also believe that compelling national interests counsel in favor of proceeding with this project. Accordingly, consistent with my responsibilities under the NWPA, today I am recommending that Yucca Mountain be developed as the site for an underground repository for spent fuel and other radioactive wastes. The first consideration in my decision was whether the Yucca Mountain site will safeguard the health and safety of the people, in Nevada and across the country, and will be effective in containing at minimum risk the material it is designed to hold. Substantial evidence shows that it will. Yucca Mountain is far and away the most thoroughly researched site of its kind in the world. It is a geologically stable site, in a closed groundwater basin, isolated on thousands of acres of Federal land, and farther from any metropolitan area than the great majority of less secure, temporary nuclear waste storage sites that exist in the country today. This point bears emphasis. We are not confronting a hypothetical problem. We have a staggering amount of

  19. Searching for circumbinary planets with CB-BLS

    Science.gov (United States)

    Ofir, Aviv

    2015-08-01

    Transiting circumbinary planets (CBP) produce transit signals that are neither periodic not constant in duration or depth. These complications contribute to the low number of detected transiting CBP (nine in total so far), and limited detection to systems that exhibit transits that are relatively deep, i.e. individually-significant transit events. Planets around single stars taught us that small planets far outnumber larger ones, consequently the ability to detect small CBP is of the essence in order to correctly describe CBP demographics. Unfortunately, all currently known transiting CBP were detected either by eye or by some ad-hoc technique that has nothing to do with the 3-body dynamics of CBP (e.g. QATS, Carter & Agol 2013) -- limiting their detection power. CB-BLS (Ofir 2008) is an algorithm for the detection of transiting CBP that was proposed well before the first transiting CBP was detected (Doyle et al 2011). CB-BLS is tailored for CBP dynamics and is optimally sensitive and general. Here we present further evolution and the Matlab source code of CB-BLS that allows it to detect all currently known transiting CBP, including in eccentric and/or inclined orbits. We then describe our preliminary results on searching for transiting CBP in a small subset of the Kepler eclipsing binaries.

  20. The European Federation of Organisations for Medical Physics Policy Statement No 14: the role of the Medical Physicist in the management of safety within the magnetic resonance imaging environment: EFOMP recommendations.

    Science.gov (United States)

    Hand, J; Bosmans, H; Caruana, C; Keevil, S; Norris, D G; Padovani, R; Speck, O

    2013-03-01

    This European Federation of Organisations for Medical Physics (EFOMP) Policy Statement outlines the way in which a Safety Management System can be developed for MRI units. The Policy Statement can help eliminate or at least minimize accidents or incidents in the magnetic resonance environment and is recommended as a step towards harmonisation of safety of workers, patients, and the general public regarding the use of magnetic resonance imaging systems in diagnostic and interventional procedures. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  1. Vibrational spectra and structure of icosahedral anion of monocarba-closo-dodecaborane [CB11H12]- and its nido-derivative: [CB10H13]-

    International Nuclear Information System (INIS)

    Kononova, E.G.; Bukalov, S.S.; Lejtes, L.A.; Lysenko, K.A.; Ol'shevskaya, V.A.

    2003-01-01

    Raman and IR spectra of cesium salts of monocarborane anions [closo-CB 11 H 12 ] - and [nido-CB 10 H 13 ] - were recorded, assignment of frequencies being provided. Quantum-chemical calculation of geometry of the closo-polyhedrons [B 12 H 12 ] 2- and [CB 11 H 12 ] - along with that of frequencies and forms of normal vibrations of the latter was made. Comparison of structural and spectral characteristics in the series of isoelectronic closo-polyhedrons [B 12 H 12 ] 2- , [CB 11 H 12 ] - and p-C 2 B 10 H 12 , as well as those of the closo- and nido structures, was made [ru

  2. Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    2007-07-01

    Full Text Available Characterization of intrinsic and extrinsic factors regulating the self-renewal/division and differentiation of stem cells is crucial in determining embryonic stem (ES cell fate. ES cells differentiate into multiple hematopoietic lineages during embryoid body (EB formation in vitro, which provides an experimental platform to define the molecular mechanisms controlling germ layer fate determination and tissue formation.The cannabinoid receptor type 1 (CB1 and cannabinoid receptor type 2 (CB2 are members of the G-protein coupled receptor (GPCR family, that are activated by endogenous ligands, the endocannabinoids. CB1 receptor expression is abundant in brain while CB2 receptors are mostly expressed in hematopoietic cells. However, the expression and the precise roles of CB1 and CB2 and their cognate ligands in ES cells are not known. We observed significant induction of CB1 and CB2 cannabinoid receptors during the hematopoietic differentiation of murine ES (mES-derived embryoid bodies. Furthermore, mES cells as well as ES-derived embryoid bodies at days 7 and 14, expressed endocannabinoids, the ligands for both CB1 and CB2. The CB1 and CB2 antagonists (AM251 and AM630, respectively induced mES cell death, strongly suggesting that endocannabinoids are involved in the survival of mES cells. Treatment of mES cells with the exogenous cannabinoid ligand Delta(9-THC resulted in the increased hematopoietic differentiation of mES cells, while addition of AM251 or AM630 blocked embryoid body formation derived from the mES cells. In addition, cannabinoid agonists induced the chemotaxis of ES-derived embryoid bodies, which was specifically inhibited by the CB1 and CB2 antagonists.This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine ES cell differentiation. This study provides insights into cannabinoid system involvement in ES cell

  3. Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration

    Directory of Open Access Journals (Sweden)

    Juan Mendizabal-Zubiaga

    2016-10-01

    Full Text Available The cannabinoid type 1 (CB1 receptor is widely distributed in the brain and peripheral organs where it regulates cellular functions and metabolism. In the brain, CB1 is mainly localized on presynaptic axon terminals but is also found on mitochondria (mtCB1, where it regulates cellular respiration and energy production. Likewise, CB1 is localized on muscle mitochondria, but very little is known about it. The aim of this study was to further investigate in detail the distribution and functional role of mtCB1 in three different striated muscles. Immunoelectron microscopy for CB1 was used in skeletal muscles (gastrocnemius and rectus abdominis and myocardium from wild-type and CB1-KO mice. Functional assessments were performed in mitochondria purified from the heart of the mice and the mitochondrial oxygen consumption upon application of different acute delta-9-tetrahidrocannabinol (Δ9-THC concentrations (100 nM or 200 nM was monitored. About 26% of the mitochondrial profiles in gastrocnemius, 22% in the rectus abdominis and 17% in the myocardium expressed CB1. Furthermore, the proportion of mtCB1 versus total CB1 immunoparticles was about 60% in the gastrocnemius, 55% in the rectus abdominis and 78% in the myocardium. Importantly, the CB1 immunolabeling pattern disappeared in muscles of CB1-KO mice. Functionally, acute 100 nM or 200 nM THC treatment specifically decreased mitochondria coupled respiration between 12% and 15% in wild-type isolated mitochondria of myocardial muscles but no significant difference was noticed between THC treated and vehicle in mitochondria isolated from CB1-KO heart. Furthermore, gene expression of key enzymes involved in pyruvate synthesis, tricarboxylic acid (TCA cycle and mitochondrial respiratory chain was evaluated in the striated muscle of CB1-WT and CB1-KO. CB1-KO showed an increase in the gene expression of Eno3, Pkm2, and Pdha1, suggesting an increased production of pyruvate. In contrast, no significant

  4. Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats

    Science.gov (United States)

    Delis, Foteini; Polissidis, Alexia; Poulia, Nafsika; Justinova, Zuzana; Nomikos, George G.; Goldberg, Steven R.

    2017-01-01

    Abstract Background: Studies have shown the involvement of cannabinoid (CB) receptors in the behavioral and neurobiological effects of psychostimulants. Most of these studies have focused on the role of CB1 receptors in the psychostimulant effects of cocaine, while very few have investigated the respective role of CB2 receptors. Further studies are warranted to elucidate the extent of CB receptor involvement in the expression of cocaine-induced effects. Methods: The role of CB1 and CB2 receptors in the rewarding and motor properties of cocaine was assessed in conditioned place preference, conditioned motor activity, and open field activity in rats. Results: The CB1 receptor antagonist rimonabant (3 mg/kg) decreased the acquisition and the expression of conditioned place preference induced by cocaine (20 mg/kg). Rimonabant inhibited cocaine-elicited conditioned motor activity when administered during the expression of cocaine-induced conditioned place preference. Rimonabant decreased ambulatory and vertical activity induced by cocaine. The CB2 receptor agonist JWH-133 (10 mg/kg) decreased the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 inhibited cocaine-elicited conditioned motor activity when administered during the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 decreased ambulatory activity and abolished vertical activity induced by cocaine. The effects of JWH-133 on cocaine conditioned and stimulated responses were abolished when the CB2 receptor antagonist/inverse agonist AM630 (5 mg/kg) was preadministered. Conclusions: Cannabinoid CB1 and CB2 receptors modulate cocaine-induced rewarding behavior and appear to have opposite roles in the regulation of cocaine’s reinforcing and psychomotor effects. PMID:27994006

  5. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor.

    Science.gov (United States)

    Laprairie, R B; Bagher, A M; Kelly, M E M; Denovan-Wright, E M

    2015-10-01

    Cannabidiol has been reported to act as an antagonist at cannabinoid CB1 receptors. We hypothesized that cannabidiol would inhibit cannabinoid agonist activity through negative allosteric modulation of CB1 receptors. Internalization of CB1 receptors, arrestin2 recruitment, and PLCβ3 and ERK1/2 phosphorylation, were quantified in HEK 293A cells heterologously expressing CB1 receptors and in the STHdh(Q7/Q7) cell model of striatal neurons endogenously expressing CB1 receptors. Cells were treated with 2-arachidonylglycerol or Δ(9)-tetrahydrocannabinol alone and in combination with different concentrations of cannabidiol. Cannabidiol reduced the efficacy and potency of 2-arachidonylglycerol and Δ(9)-tetrahydrocannabinol on PLCβ3- and ERK1/2-dependent signalling in cells heterologously (HEK 293A) or endogenously (STHdh(Q7/Q7)) expressing CB1 receptors. By reducing arrestin2 recruitment to CB1 receptors, cannabidiol treatment prevented internalization of these receptors. The allosteric activity of cannabidiol depended upon polar residues being present at positions 98 and 107 in the extracellular amino terminus of the CB1 receptor. Cannabidiol behaved as a non-competitive negative allosteric modulator of CB1 receptors. Allosteric modulation, in conjunction with effects not mediated by CB1 receptors, may explain the in vivo effects of cannabidiol. Allosteric modulators of CB1 receptors have the potential to treat CNS and peripheral disorders while avoiding the adverse effects associated with orthosteric agonism or antagonism of these receptors. © 2015 The British Pharmacological Society.

  6. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

    Directory of Open Access Journals (Sweden)

    Emmanuel S Onaivi

    Full Text Available BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R but not (H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

  7. Designing strategies to implement research-based policies and procedures: a set of recommendations for nurse leaders based on the PARiHS framework.

    Science.gov (United States)

    Squires, Janet E; Reay, Trish; Moralejo, Donna; Lefort, Sandra M; Hutchinson, Alison M; Estabrooks, Carole A

    2012-05-01

    Organizational policies and procedures are one vehicle for translating research into nursing practice and improving quality and patient and organizational outcomes. However, their existence alone is not sufficient to ensure use. In this article, we describe the Promoting Action on Research Implementation in Health Services framework and how nurse leaders can use the framework to support the implementation of research-based policies and procedures.

  8. Availability Perception And Constraints Of Final Year Students To The Use Of Computer-Based Information Communication Technologies Cb-Icts.

    Directory of Open Access Journals (Sweden)

    Nto

    2015-08-01

    Full Text Available There is no doubt that ICTs are the major focus for the day to day running of every society. ICTs create a room for a quicker faster easier access and exchange of information in the world today. The study investigated the availability attitude and constraints of final year students in the use of computer-based ICTs CB-ICTs in Abia State. Data were collected with the use of a well structured questionnaire. Data collected were analysed with descriptive statistics. Results from analysis revealed that the mean age of the respondents was 23 years 7 CB-ICTs were available to the respondents at varying degrees. The respondents had a positive attitude x amp773 3.11 to the use of CB-ICTs and the major constraint to their use of CB-ICTs was poor resource centre where they can access CB-ICTs. Based on the findings we recommended that resource centres should be built in the institution and if it exists should be well equipped and running. Equally awareness to the fact that there is or there will be a resource centre in the institution should be widely spread so that students can utilize the opportunity of its existence and make maximum use of the facilities there in. On the other hand internet service provider should scale up their services in the area so as to provide a more stable internet connection in the institution as this will enable the students to use more effectively CB-ICTs in the institution and for their academic work.

  9. Activation of Both CB1 and CB2 Endocannabinoid Receptors Is Critical for Masculinization of the Developing Medial Amygdala and Juvenile Social Play Behavior.

    Science.gov (United States)

    Argue, Kathryn J; VanRyzin, Jonathan W; Falvo, David J; Whitaker, Allison R; Yu, Stacey J; McCarthy, Margaret M

    2017-01-01

    Juvenile social play behavior is a shared trait across a wide variety of mammalian species. When play is characterized by the frequency or duration of physical contact, males usually display more play relative to females. The endocannabinoid system contributes to the development of the sex difference in social play behavior in rats. Treating newborn pups with a nonspecific endocannabinoid agonist, WIN55,212-2, masculinizes subsequent juvenile rough-and-tumble play behavior by females. Here we use specific drugs to target signaling through either the CB1 or CB2 endocannabinoid receptor (CB1R or CB2R) to determine which modulates the development of sex differences in play. Our data reveal that signaling through both CB1R and CB2R must be altered neonatally to modify development of neural circuitry regulating sex differences in play. Neonatal co-agonism of CB1R and CB2R masculinized play by females, whereas co-antagonism of these receptors feminized rates of male play. Because of a known role for the medial amygdala in the sexual differentiation of play, we reconstructed Golgi-impregnated neurons in the juvenile medial amygdala and used factor analysis to identify morphological parameters that were sexually differentiated and responsive to dual agonism of CB1R and CB2R during the early postnatal period. Our results suggest that sex differences in the medial amygdala are modulated by the endocannabinoid system during early development. Sex differences in play behavior are loosely correlated with differences in neuronal morphology.

  10. The European Federation of Organisations for Medical Physics Policy Statement no. 15: recommended guidelines on the role of the Medical Physicist within the hospital governance board.

    Science.gov (United States)

    Christofides, Stelios; Sharp, Peter

    2015-05-01

    This EFOMP Policy Statement presents an outline on hospital governance and encourages the participation of the Medical Physicist in the hospital governance. It also emphasises how essential it is for Medical Physicists to engage in their hospital's governing board's committees for the overall good of the patient. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  11. Practical Recommendations for the Development and Implementation of Youth Policy in the University as a Tool for Development of Student Public Associations

    Science.gov (United States)

    Ezhov, Sergey G.; Komarova, Nataliya M.; Khairullina, Elmira R.; Rapatskaia, Liudmila, A.; Miftakhov, Radik R.; Khusainova, Liana R.

    2016-01-01

    The research urgency is caused by the increase of social responsibility of universities for improvement of the quality of higher education and development of students' socio-professional values. In terms of the conflicting realities of modern society the youth policy at the University is the most important tool to form students' commitment to…

  12. Recommender systems

    CERN Document Server

    Kembellec, Gérald; Saleh, Imad

    2014-01-01

    Acclaimed by various content platforms (books, music, movies) and auction sites online, recommendation systems are key elements of digital strategies. If development was originally intended for the performance of information systems, the issues are now massively moved on logical optimization of the customer relationship, with the main objective to maximize potential sales. On the transdisciplinary approach, engines and recommender systems brings together contributions linking information science and communications, marketing, sociology, mathematics and computing. It deals with the understan

  13. Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

    Science.gov (United States)

    Gaffal, E; Cron, M; Glodde, N; Tüting, T

    2013-08-01

    ∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors. We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro. Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner. Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Evaluation of selective cannabinoid CB(1) and CB(2) receptor agonists in a mouse model of lipopolysaccharide-induced interstitial cystitis.

    Science.gov (United States)

    Tambaro, Simone; Casu, Maria Antonietta; Mastinu, Andrea; Lazzari, Paolo

    2014-04-15

    Interstitial cystitis is a debilitating bladder inflammation disorder. To date, the understanding of the causes of interstitial cystitis remains largely fragmentary and there is no effective treatment available. Recent experimental results have shown a functional role of the endocannabinoid system in urinary bladder. In this study, we evaluated the anti-inflammatory effect of selective cannabinoid CB1 and CB2 receptor agonists in a mouse model of interstitial cystitis. Bladder inflammation was induced in mice by lipopolysaccharide (LPS) and whole bladders were removed 24h later. LPS induced a significant increase of the contractile amplitude in spontaneous activity and a hypersensitivity to exogenous acetylcholine-induced contraction of whole-isolated bladder. Next, we evaluated the anti-inflammatory activity of cannabinoidergic compounds by pretreating mice with CB1 or CB2 selective agonist compounds, respectively ACEA and JWH015. Interestingly, JWH015, but not ACEA, antagonized LPS-induced bladder inflammation. Additionally, anti-inflammatory activity was studied by evaluation, leukocytes mucosa infiltration, myeloperoxidase activity, and mRNA expression of pro-inflammatory interleukin (IL-1α and IL-1β), tumor necrosis factor-alpha (TNF-α) and cannabinoid CB1 and CB2 receptors. JWH015 significantly decreased leukocytes infiltration in both submucosa and mucosa, as well as the myeloperoxydase activity, in LPS treated mice. JWH015 reduced mRNA expression of IL-1α, IL-1β, and TNF-α. LPS treatment increased expression of bladder CB2 but not CB1 mRNA. Taken together, these findings strongly suggest that modulation of the cannabinoid CB2 receptors might be a promising therapeutic strategy for the treatment of bladder diseases and conditions characterized by inflammation, such as interstitial cystitis. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Computational analysis of the CB1 carboxyl-terminus in the receptor-G protein complex.

    Science.gov (United States)

    Shim, Joong-Youn; Khurana, Leepakshi; Kendall, Debra A

    2016-04-01

    Despite the important role of the carboxyl-terminus (Ct) of the activated brain cannabinoid receptor one (CB1) in the regulation of G protein signaling, a structural understanding of interactions with G proteins is lacking. This is largely due to the highly flexible nature of the CB1 Ct that dynamically adapts its conformation to the presence of G proteins. In the present study, we explored how the CB1 Ct can interact with the G protein by building on our prior modeling of the CB1-Gi complex (Shim, Ahn, and Kendall, The Journal of Biological Chemistry 2013;288:32449-32465) to incorporate a complete CB1 Ct (Glu416(Ct)-Leu472(Ct)). Based on the structural constraints from NMR studies, we employed ROSETTA to predict tertiary folds, ZDOCK to predict docking orientation, and molecular dynamics (MD) simulations to obtain two distinct plausible models of CB1 Ct in the CB1-Gi complex. The resulting models were consistent with the NMR-determined helical structure (H9) in the middle region of the CB1 Ct. The CB1 Ct directly interacted with both Gα and Gβ and stabilized the receptor at the Gi interface. The results of site-directed mutagenesis studies of Glu416(Ct), Asp423(Ct), Asp428(Ct), and Arg444(Ct) of CB1 Ct suggested that the CB1 Ct can influence receptor-G protein coupling by stabilizing the receptor at the Gi interface. This research provided, for the first time, models of the CB1 Ct in contact with the G protein. © 2016 Wiley Periodicals, Inc.

  16. Cannabinoid CB1 receptor-interacting proteins: novel targets for central nervous system drug discovery?

    OpenAIRE

    Smith, Tricia H; Sim-Selley, Laura J; Selley, Dana E

    2010-01-01

    The main pharmacological effects of marijuana, as well as synthetic and endogenous cannabinoids, are mediated through G-protein-coupled receptors (GPCRs), including CB1 and CB2 receptors. The CB1 receptor is the major cannabinoid receptor in the central nervous system and has gained increasing interest as a target for drug discovery for treatment of nausea, cachexia, obesity, pain, spasticity, neurodegenerative diseases and mood and substance abuse disorders. Evidence has accumulated to sugge...

  17. Motor, Visual and Emotional Deficits in Mice after Closed-Head Mild Traumatic Brain Injury Are Alleviated by the Novel CB2 Inverse Agonist SMM-189

    Directory of Open Access Journals (Sweden)

    Anton Reiner

    2014-12-01

    Full Text Available We have developed a focal blast model of closed-head mild traumatic brain injury (TBI in mice. As true for individuals that have experienced mild TBI, mice subjected to 50–60 psi blast show motor, visual and emotional deficits, diffuse axonal injury and microglial activation, but no overt neuron loss. Because microglial activation can worsen brain damage after a concussive event and because microglia can be modulated by their cannabinoid type 2 receptors (CB2, we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189 in altering microglial activation and mitigating deficits after mild TBI. In vitro analysis indicated that SMM-189 converted human microglia from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed that daily administration of SMM-189 for two weeks beginning shortly after blast greatly reduced the motor, visual, and emotional deficits otherwise evident after 50–60 psi blasts, and prevented brain injury that may contribute to these deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189 after a mild TBI event can reduce its adverse consequences by beneficially modulating microglial activation. These findings recommend further evaluation of CB2 inverse agonists as a novel therapeutic approach for treating mild TBI.

  18. The European Federation of Organisations for Medical Physics. Policy Statement No. 12: The present status of Medical Physics Education and Training in Europe. New perspectives and EFOMP recommendations

    DEFF Research Database (Denmark)

    Eudaldo, T.; Olsen, Kjeld

    2010-01-01

    A recently published EFOMP's survey on the status of Education and Training in Europe, has showed the important role played by the NMOs in the organisation of the Medical Physics education and training in most countries and their efforts to fulfil EFOMP recommendations. However, despite of this...... of the architecture of the European Higher Education System, arising from the "Botogna Declaration", for 2010, 2. the recently issued European directive: "Directive 2005/36/EC of the European Parliament and of the Council of 7 September 2005 on the recognition of professional qualifications". EFOMP is now challenged...... to make recommendations for education and training in Medical Physics, within the context of the current developments in the European Higher Education Area arising from "The Bologna Declaration", and with a view to facilitate the free movement of professionals within Europe, according to the new Directive...

  19. CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    János Haskó

    2014-05-01

    Full Text Available During parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB. The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesis of leukocytes. Extravasation of leukocytes through the BBB is decreased by the activation of type 2 cannabinoid receptors (CB2; therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. First, we identified the presence of CB1, CB2(A, GPR18 (transcriptional variant 1 and GPR55 receptors in brain endothelial cells, while melanoma cells expressed CB1, CB2(A, GPR18 (transcriptional variants 1 and 2, GPR55 and GPR119. We observed that activation of CB2 receptors with JWH-133 reduced the adhesion of melanoma cells to the layer of brain endothelial cells. JWH-133 decreased the transendothelial migration rate of melanoma cells as well. Our results suggest that changes induced in endothelial cells are critical in the mediation of the effect of CB2 agonists. Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.

  20. CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Balázs Csóka

    2009-07-01

    Full Text Available Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB(2 receptors on immune cells. Here we examined the role of CB(2 receptors in regulating the host's response to sepsis.The role of CB(2 receptors was studied by subjecting CB(2 receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB(2 receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB(2 receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF-kappaB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB(2 receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b(+ and CD19(+ cells during CLP.Taken together, our results establish for the first time that CB(2 receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2 receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.

  1. A peripherally selective diphenyl purine antagonist of the CB1 receptor

    Science.gov (United States)

    Fulp, Alan; Bortoff, Katherine; Zhang, Yanan; Mathews, James; Snyder, Rodney; Fennell, Tim; Marusich, Julie A.; Wiley, Jenny L.; Seltzman, Herbert; Maitra, Rangan

    2014-01-01

    Antagonists of the CB1 receptor can be useful in the treatment of several diseases including obesity, diabetes, and liver disease. However, to date, the only clinically approved CB1 receptor antagonist, rimonabant, was withdrawn due to adverse CNS related side effects such as depression and suicidal ideation. Since rimonabant’s withdrawal, several groups have begun pursuing peripherally selective CB1 antagonists. These compounds are expected to be devoid of undesirable CNS related effects but maintain efficacy through antagonism of peripherally expressed CB1 receptors within target tissues. Reported here are our latest results toward development of a peripherally selective analog of the diphenyl purine CB1 antagonist otenabant 1. Compound 9 (N-{1-[8-(2-Chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]piperidin-4-yl}pentanamide) is a potent, orally absorbed antagonist of the CB1 receptor that is >50-fold selective for CB1 over CB2, highly selective for the periphery in a rodent model, and without efficacy in a series of in vivo assays designed to evaluate its ability to mitigate the central effects of Δ9-THC through the CB1 receptor. PMID:24041123

  2. Accurate market price formation model with both supply-demand and trend-following for global food prices providing policy recommendations.

    Science.gov (United States)

    Lagi, Marco; Bar-Yam, Yavni; Bertrand, Karla Z; Bar-Yam, Yaneer

    2015-11-10

    Recent increases in basic food prices are severely affecting vulnerable populations worldwide. Proposed causes such as shortages of grain due to adverse weather, increasing meat consumption in China and India, conversion of corn to ethanol in the United States, and investor speculation on commodity markets lead to widely differing implications for policy. A lack of clarity about which factors are responsible reinforces policy inaction. Here, for the first time to our knowledge, we construct a dynamic model that quantitatively agrees with food prices. The results show that the dominant causes of price increases are investor speculation and ethanol conversion. Models that just treat supply and demand are not consistent with the actual price dynamics. The two sharp peaks in 2007/2008 and 2010/2011 are specifically due to investor speculation, whereas an underlying upward trend is due to increasing demand from ethanol conversion. The model includes investor trend following as well as shifting between commodities, equities, and bonds to take advantage of increased expected returns. Claims that speculators cannot influence grain prices are shown to be invalid by direct analysis of price-setting practices of granaries. Both causes of price increase, speculative investment and ethanol conversion, are promoted by recent regulatory changes-deregulation of the commodity markets, and policies promoting the conversion of corn to ethanol. Rapid action is needed to reduce the impacts of the price increases on global hunger.

  3. Finnish contribution to the CB4 burnup credit benchmark

    International Nuclear Information System (INIS)

    Wasastjerna, F.

    2001-01-01

    The CB4 phase of the WWER burnup credit benchmark series studies the effect of flat and realistic axial burnup profiles on the multiplication factor of a conceptual WWER cask loaded with spent fuel. The benchmark was calculated at VTT Energy with MCNP4C, using mainly ENDF/B-V1 cross sections. According to the calculation results the effect of the axial homogenization on the k eff estimate is complex. At low burnups the use of a axial profile overestimates k eff but at high burnups the reverse is the case. Ignoring fission products leads to conservative k eff and the effect of axial homogenization on the multiplication factor is similar to a reduction of the burnup (Authors)

  4. VVER-1000 burnup credit benchmark (CB5). New results evaluation

    International Nuclear Information System (INIS)

    Manolova, M.; Mihaylov, N.; Prodanova, R.

    2008-01-01

    The validation of depletion codes is an important task in spent fuel management, especially for burnup credit application in criticality safety analysis of spent fuel facilities. Because of lack of well documented experimental data for VVER-1000, the validation could be made on the basis of code intercomparison based on the numerical benchmark problems. Some years ago a VVER-1000 burnup credit benchmark (CB5) was proposed to the AER research community and the preliminary results from three depletion codes were compared. In the paper some new results for the isotopic concentrations of twelve actinides and fifteen fission products calculated by the depletion codes SCALE5.1, WIMS9, SCALE4.4 and NESSEL-NUKO are compared and evaluated. (authors)

  5. Reversible disruption of pre-pulse inhibition in hypomorphic-inducible and reversible CB1-/- mice.

    Directory of Open Access Journals (Sweden)

    Maria Franca Marongiu

    Full Text Available Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes. Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout ((-/- mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1(-/- mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1(-/- only in absence of doxycycline (Dox. In such mice, under Dox(+ or vehicle, as well as in wild-type (WT and CB1(-/-, two endophenotypes motor activity (increased in animal models of schizophrenia and pre-pulse inhibition (PPI of startle reflex (disrupted in schizophrenia were analyzed. Both CB1(-/- and IRh-CB1(-/- showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1(-/- animals, was on the contrary highly and significantly disrupted only in Dox(+ IRh-CB1(-/- mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1(-/- mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1(-/- mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in

  6. Research for health policy

    National Research Council Canada - National Science Library

    Bell, Erica

    2010-01-01

    ... Explicit, implicit, and pragmatic dimensions of policy-maker's needs and context 31 Constraints on policy-makers 32 Deciphering trade-offs 33 The policy-problem: deciphering uncertainty and the problem of innovation 34 A tool for deciphering policy problems 35 The different components of the policy problem 37 Recommended reading 38 Case studies in...

  7. Cannabinoid-1 receptor (CB1R) blockers as medicines: beyond obesity and cardiometabolic disorders to substance abuse/drug addiction with CB1R neutral antagonists.

    Science.gov (United States)

    Janero, David R

    2012-03-01

    Addiction to chemical substances with abuse potential presents medical needs largely unsolved by extant therapeutic strategies. Signal transmission through the cannabinoid-1 receptor (CB1R) in the central nervous system (CNS) modulates neurotransmitters/neuronal pathways contributing to the rewarding properties and hedonic effects of certain nondrug stimuli (e.g., food) and many prototypical addictive drugs, promoting excessive intake and its pathological consequences. Typical CB1R antagonists/inverse agonists reduce the rewarding effects and normalize behavioral phenotypes associated with food and abused drugs, but carry an unacceptable adverse-event profile that may reflect, at least partly, their intrinsic ability to alter basal homeostatic CB1R signaling in the CNS and elicit a negative efficacy response. Alternatively, peripherally biased CB1R inverse agonists with limited CNS permeability and putative CB1R neutral antagonists expressing modest (if any) inverse-agonist efficacy are garnering attention for treating obesity and related cardiometabolic complications with a potentially enhanced benefit-to-risk profile. This mini-review calls attention to the proposition that CB1R neutral antagonists offer attractive opportunities for pharmacotherapeutic exploitation in the substance abuse/drug addiction space, whereas the restricted CNS accessibility of peripherally biased CB1R inverse agonists circumscribes their therapeutic utility for this indication. The unique preclinical pharmacology, efficacy profiles, and reduced adverse-event risk of CB1R neutral antagonists make them worthy of translational study for their potential therapeutic application beyond obesity/cardiometabolic disease to include substance-abuse/drug-addiction disorders.

  8. The European Federation of Organisations for Medical Physics. Policy Statement No. 12: The present status of Medical Physics Education and Training in Europe. New perspectives and EFOMP recommendations.

    Science.gov (United States)

    Eudaldo, Teresa; Olsen, Kjeld

    2010-01-01

    A recently published EFOMP's survey on the status of Education and Training in Europe, has showed the important role played by the NMOs in the organisation of the Medical Physics education and training in most countries and their efforts to fulfil EFOMP recommendations. However, despite of this, there is still a wide variety of approaches within Europe, not only in the education and training programmes but also in professional practice. There is right now some European issues that can affect not only education and training but also the future of Medical Physics as a profession: 1. the harmonisation of the architecture of the European Higher Education System, arising from the "Bologna Declaration", for 2010, 2. the recently issued European directive: "Directive 2005/36/EC of the European Parliament and of the Council of 7 September 2005 on the recognition of professional qualifications". EFOMP is now challenged to make recommendations for education and training in Medical Physics, within the context of the current developments in the European Higher Education Area arising from "The Bologna Declaration", and with a view to facilitate the free movement of professionals within Europe, according to the new Directive. Copyright 2009 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  9. Official Position of the American Academy of Clinical Neuropsychology Social Security Administration Policy on Validity Testing: Guidance and Recommendations for Change.

    Science.gov (United States)

    Chafetz, M D; Williams, M A; Ben-Porath, Y S; Bianchini, K J; Boone, K B; Kirkwood, M W; Larrabee, G J; Ord, J S

    2015-01-01

    The milestone publication by Slick, Sherman, and Iverson (1999) of criteria for determining malingered neurocognitive dysfunction led to extensive research on validity testing. Position statements by the National Academy of Neuropsychology and the American Academy of Clinical Neuropsychology (AACN) recommended routine validity testing in neuropsychological evaluations. Despite this widespread scientific and professional support, the Social Security Administration (SSA) continued to discourage validity testing, a stance that led to a congressional initiative for SSA to reevaluate their position. In response, SSA commissioned the Institute of Medicine (IOM) to evaluate the science concerning the validation of psychological testing. The IOM concluded that validity assessment was necessary in psychological and neuropsychological examinations (IOM, 2015 ). The AACN sought to provide independent expert guidance and recommendations concerning the use of validity testing in disability determinations. A panel of contributors to the science of validity testing and its application to the disability process was charged with describing why the disability process for SSA needs improvement, and indicating the necessity for validity testing in disability exams. This work showed how the determination of malingering is a probability proposition, described how different types of validity tests are appropriate, provided evidence concerning non-credible findings in children and low-functioning individuals, and discussed the appropriate evaluation of pain disorders typically seen outside of mental consultations. A scientific plan for validity assessment that additionally protects test security is needed in disability determinations and in research on classification accuracy of disability decisions.

  10. 40 CFR Table 1 to Subpart Cb of... - Nitrogen Oxides Guidelines for Designated Facilities

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Nitrogen Oxides Guidelines for... September 20, 1994 Pt. 60, Subpt. Cb, Table 1 Table 1 to Subpart Cb of part 60—Nitrogen Oxides Guidelines for Designated Facilities Municipal waste combustor technology Before April 28, 2009,nitrogen oxides...

  11. Prototypic implementations of the building block for component based open Hypermedia systems (BB/CB-OHSs)

    DEFF Research Database (Denmark)

    Mohamed, Omer I. Eldai

    2005-01-01

    In this paper we describe the prototypic implementations of the BuildingBlock (BB/CB-OHSs) that proposed to address some of the Component-based Open Hypermedia Systems (CB-OHSs) issues, including distribution and interoperability [4, 11, 12]. Four service implementations were described below. The...

  12. A restricted population of CB1 cannabinoid receptors with neuroprotective activity

    Science.gov (United States)

    Chiarlone, Anna; Bellocchio, Luigi; Blázquez, Cristina; Resel, Eva; Soria-Gómez, Edgar; Cannich, Astrid; Ferrero, José J.; Sagredo, Onintza; Benito, Cristina; Romero, Julián; Sánchez-Prieto, José; Lutz, Beat; Fernández-Ruiz, Javier; Galve-Roperh, Ismael; Guzmán, Manuel

    2014-01-01

    The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown. Here, we first induced excitotoxic damage in the mouse brain by (i) administering quinolinic acid to conditional mutant animals lacking CB1 receptors selectively in GABAergic or glutamatergic neurons, and (ii) manipulating corticostriatal glutamatergic projections remotely with a designer receptor exclusively activated by designer drug pharmacogenetic approach. We next examined the alterations that occur in the R6/2 mouse, a well-established model of Huntington disease, upon (i) fully knocking out CB1 receptors, and (ii) deleting CB1 receptors selectively in corticostriatal glutamatergic or striatal GABAergic neurons. The data unequivocally identify the restricted population of CB1 receptors located on glutamatergic terminals as an indispensable player in the neuroprotective activity of (endo)cannabinoids, therefore suggesting that this precise receptor pool constitutes a promising target for neuroprotective therapeutic strategies. PMID:24843137

  13. Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1receptor ligand antagonists.

    Science.gov (United States)

    Murineddu, Gabriele; Deligia, Francesco; Ragusa, Giulio; García-Toscano, Laura; Gómez-Cañas, María; Asproni, Battistina; Satta, Valentina; Cichero, Elena; Pazos, Ruth; Fossa, Paola; Loriga, Giovanni; Fernández-Ruiz, Javier; Pinna, Gerard A

    2018-01-01

    A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB 1 and CB 2 receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB 1 receptors (K i values of 44.6 nM for CB 1 receptors and >40 μM for CB 2 receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB 1 receptors with K i values of 75.5 and 73.2 nM, respectively. These novel compounds behave as antagonists/inverse agonists at CB 1 receptor in the [ 35 S]-GTPγS binding assays, and none showed adequate predictive blood-brain barrier permeation, exhibiting low estimated LD 50 . However, testing compound 12 in a supraspinal analgesic test (hot-plate) revealed that it was as effective as the classic CB 1 receptor antagonist rimonabant, in reversing the analgesic effect of a cannabinoid agonist. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Deficits in Sensory-Specific Devaluation Task Performance Following Genetic Deletions of Cannabinoid (CB1) Receptor

    Science.gov (United States)

    Crombag, Hans S.; Johnson, Alexander W.; Zimmer, Anne M.; Zimmer, Andreas; Holland, Peter C.

    2010-01-01

    Cannabinoid CB1 receptor is abundantly expressed throughout the CNS and is implicated in numerous physiological and behavioral functions, including appetite and feeding. In the present study, wild-type and CB1 heterozygous and homozygous knockout mice were tested on an instrumental outcome-selective devaluation task to assess changes in acquired…

  15. 47 CFR 95.408 - (CB Rule 8) How high may I put my antenna?

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false (CB Rule 8) How high may I put my antenna? 95....408 (CB Rule 8) How high may I put my antenna? (a) Antenna means the radiating system (for... everything else attached to the radiating system and the structure. (b) If your antenna is mounted on a hand...

  16. Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

    DEFF Research Database (Denmark)

    Hansen, H.H.; Ramos, J.A.; Fernández-Ruiz, J.

    2002-01-01

    The ability of cannabinoid CB, receptors to influence glutamatergic excitatory neurotransmission has fueled interest in how these receptors and their endogenous ligands may interact in conditions of excitotoxic insults. The present study characterized the impact of stimulated and inhibited CB...... receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA...

  17. Appraisal of literature reviews on end-of-life care for minority ethnic groups in the UK and a critical comparison with policy recommendations from the UK end-of-life care strategy

    Directory of Open Access Journals (Sweden)

    Pool Robert

    2011-06-01

    Full Text Available Abstract Background Evidence of low end-of-life (EoL care service use by minority ethnic groups in the UK has given rise to a body of research and a number of reviews of the literature. This article aims to review and evaluate literature reviews on minority ethnic groups and EoL care in the UK and assess their suitability as an evidence base for policy. Methods Systematic review. Searches were carried out in thirteen electronic databases, eight journals, reference lists, and grey literature. Reviews were included if they concerned minority ethnic groups and EoL care in the UK. Reviews were graded for quality and key themes identified. Results Thirteen reviews (2001-2009 met inclusion criteria. Seven took a systematic approach, of which four scored highly for methodological quality (a mean score of six, median seven. The majority of systematic reviews were therefore of a reasonable methodological quality. Most reviews were restricted by ethnic group, aspect of EoL care, or were broader reviews which reported relevant findings. Six key themes were identified. Conclusions A number of reviews were systematic and scored highly for methodological quality. These reviews provide a good reflection of the primary evidence and could be used to inform policy. The complexity and inter-relatedness of factors leading to low service use was recognised and reflected in reviews' recommendations for service improvement. Recommendations made in the UK End-of-Life Care Strategy were limited in comparison, and the Strategy's evidence base concerning minority ethnic groups was found to be narrow. Future policy should be embedded strongly in the evidence base to reflect the current literature and minimise bias.

  18. Appraisal of literature reviews on end-of-life care for minority ethnic groups in the UK and a critical comparison with policy recommendations from the UK end-of-life care strategy.

    Science.gov (United States)

    Evans, Natalie; Meñaca, Arantza; Andrew, Erin Vw; Koffman, Jonathan; Harding, Richard; Higginson, Irene J; Pool, Robert; Gysels, Marjolein

    2011-06-02

    Evidence of low end-of-life (EoL) care service use by minority ethnic groups in the UK has given rise to a body of research and a number of reviews of the literature. This article aims to review and evaluate literature reviews on minority ethnic groups and EoL care in the UK and assess their suitability as an evidence base for policy. Systematic review. Searches were carried out in thirteen electronic databases, eight journals, reference lists, and grey literature. Reviews were included if they concerned minority ethnic groups and EoL care in the UK. Reviews were graded for quality and key themes identified. Thirteen reviews (2001-2009) met inclusion criteria. Seven took a systematic approach, of which four scored highly for methodological quality (a mean score of six, median seven). The majority of systematic reviews were therefore of a reasonable methodological quality. Most reviews were restricted by ethnic group, aspect of EoL care, or were broader reviews which reported relevant findings. Six key themes were identified. A number of reviews were systematic and scored highly for methodological quality. These reviews provide a good reflection of the primary evidence and could be used to inform policy. The complexity and inter-relatedness of factors leading to low service use was recognised and reflected in reviews' recommendations for service improvement. Recommendations made in the UK End-of-Life Care Strategy were limited in comparison, and the Strategy's evidence base concerning minority ethnic groups was found to be narrow. Future policy should be embedded strongly in the evidence base to reflect the current literature and minimise bias.

  19. CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action.

    Science.gov (United States)

    Degroot, Aldemar; Köfalvi, Attila; Wade, Mark R; Davis, Richard J; Rodrigues, Ricardo J; Rebola, Nelson; Cunha, Rodrigo A; Nomikos, George G

    2006-10-01

    Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct

  20. RTD and D to increase the share of renewables in emerging and developing countries with European technologies. Policy Assessment, Stakeholders opinions, Best-practices and Recommendations

    International Nuclear Information System (INIS)

    Hanekamp, E.

    2008-11-01

    The future energy demand worldwide will increase by 45% in 2030. To be able to meet this demand, respond to the threats of Climate Change and also improve access to energy for the very poor in emerging and developing countries (especially in rural areas) renewable energy technologies play a crucial role. The European Union envisions a thriving and sustainable future economy, with world leadership in a diverse portfolio of clean, efficient and low-carbon energy technologies as a motor for prosperity and a key contributor to growth and jobs. Strengthening of the international dimension in European Technology Platforms and in Joint Technology Initiatives is a priority in the EU. The demographic trends in Europe coupled with an ambitious strategy of growth based on the Lisbon agenda provide a new context for considering international co-operation in Science and Technology. No fortress Europe, but an open Europe - building open 'win-win' S and T relations with EDCs. The RTD4EDC project is focussed on the role of research, technological development and demonstration (RTD and D) in the implementation of renewable energy technologies in Emerging and Developing Countries (EDCs). The project is executed by a consortium of four partners based in Europe (Belgium/The Netherlands), and in Emerging and Developing Countries (Paraguay, South- Africa and India). The project consisted of desk research on relevant policies and developments, interviews with policymakers, representatives from EU RE industries and development cooperation agencies, a survey amongst EU RE industry representatives and analysis of 74 cases of RE implementations in EDCs. In this report the overall results are presented. Other deliverables are three reports with background material (policies, case studies and market potential for EU RE industry) and a website (www.developingrenewables.org) containing all information as reported and with a database containing the 74 cases of RE implementations in EDCs.

  1. Association of cannabis use during adolescence, prefrontal CB1 receptor signaling and schizophrenia

    Directory of Open Access Journals (Sweden)

    Adriana eCaballero

    2012-05-01

    Full Text Available The cannabinoid receptor 1 (CB1R is the G-protein coupled receptor responsible for the majority of the endocannabinoid signaling in the human brain. It is widely distributed in the limbic system, basal ganglia, and cerebellum, which are areas responsible for cognition, memory, and motor control. Because of this widespread distribution, it is not surprising that drugs that co-opt CB1R have expected behavioral outcomes consistent with dysregulated signaling from these areas (e.g. memory loss, cognitive deficits, etc. In the context of this review, we present evidence for the role of CB1R signaling in the prefrontal cortex (PFC, an area involved in executive functions, with emphasis on the developmental regulation of CB1R signaling in the acquisition of mature PFC function. We further hypothesize how alterations of CB1R signaling specifically during adolescent maturation might confer liability to psychiatric disorders.

  2. Lessons Learned from the Niger Delta Conflict: A Policy Recommendation for a New Framework for Relations Between Extractive Companies and Host Communities

    Science.gov (United States)

    Gilman, Alison

    The tumultuous experience of the Shell Petroleum Development Company of Nigeria Ltd (SPDC) in the Niger Delta region of Nigeria has contributed to the debates surrounding the role of transnational companies in their host communities and the impact that resource extraction has on the economic development of emerging countries. The case study demonstrates that methods used by extraction companies for interacting with their host communities are ineffective and superficial. Using the lessons learned from the Niger Delta conflict, this thesis proposes a new strategy, entitled community- corporate diplomacy, and a protocol for companies to implement before opening production sites in Africa. The proposed strategy and an accompanying protocol offer a break from the status quo in that they are built upon an understanding of the specificities of the African continent, that host communities need to be respected as key stakeholders, and that extraction activities have a higher risk of negatively impacting neighboring communities. The recommendation could be applied to other countries and industries, but the increasing importance of African natural resources, the particularities of African political and social structures and the effects of extraction activities make this proposal especially important for extractive companies beginning production in Africa. Keywords: Nigeria, Niger Delta, Shell, corporate social responsibility, transnational advocacy networks, multi-stakeholder initiatives, community relations, corporate diplomacy, Africa, extractive industries.

  3. Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast cancer.

    Science.gov (United States)

    Pérez-Gómez, Eduardo; Andradas, Clara; Blasco-Benito, Sandra; Caffarel, María M; García-Taboada, Elena; Villa-Morales, María; Moreno, Estefanía; Hamann, Sigrid; Martín-Villar, Ester; Flores, Juana M; Wenners, Antonia; Alkatout, Ibrahim; Klapper, Wolfram; Röcken, Christoph; Bronsert, Peter; Stickeler, Elmar; Staebler, Annette; Bauer, Maret; Arnold, Norbert; Soriano, Joaquim; Pérez-Martínez, Manuel; Megías, Diego; Moreno-Bueno, Gema; Ortega-Gutiérrez, Silvia; Artola, Marta; Vázquez-Villa, Henar; Quintanilla, Miguel; Fernández-Piqueras, José; Canela, Enric I; McCormick, Peter J; Guzmán, Manuel; Sánchez, Cristina

    2015-06-01

    Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen, and Freiburg between 1997 and 2010 and CB2 mRNA expression in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2) rat ortholog (neu) and lacks CB2 and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by colocalization, coimmunoprecipitation, and proximity ligation assays. Statistical tests were two-sided. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis (decreased overall survival, hazard ratio [HR] = 0.29, 95% confidence interval [CI] = 0.09 to 0.71, P = .009) and higher probability to suffer local recurrence (HR = 0.09, 95% CI = 0.049 to 0.54, P = .003) and to develop distant metastases (HR = 0.33, 95% CI = 0.13 to 0.75, P = .009). We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade and that an increased CB2 expression activates the HER2 pro-oncogenic signaling at the level of the tyrosine kinase c-SRC. Finally, we show HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and they suggest that CB2 may be a biomarker with

  4. International recommendations

    International Nuclear Information System (INIS)

    Lindell, Bo

    1986-01-01

    Full text: This short presentation will indicate the general radiation protection background to protective measures against foodstuffs contaminated with radioactive substances. A number of international organizations are involved in various aspects of radiation protection, for example, the International Atomic Energy Agency (IAEA), the United Nations Food and Agriculture Organization (FAO), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO). Two international organizations, however, provide the basic background. These are the International Commission on Radiological Protection (ICRP) and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). UNSCEAR provides the scientific information on radiation levels and effects. It consists of 21 member countries, with truly international coverage. It issues reports to the UN General Assembly, including comprehensive scientific annexes. Its latest comprehensive report was issued in 1982, the next is expected to be published in 1988. That report will include an assessment of the radiological consequences of the Chernobyl accident. The ICRP is a non-governmental organization. It has issued recommendations on radiation protection since 1928. The postulated biological basis for radiation protection recommendations involves two types of biological effects. The so-called non-stochastic effects, mainly due to cell death, appear only when the radiation doses exceed a certain threshold value. These effects, therefore, can only appear after high accidental exposures. After the Chernobyl accident, they only affected about 200 individuals involved in fire extinction and rescue work at the damaged nuclear power plant. Stochastic effects, with some simplification, may be seen as the result of initial changes in the genetic code of some surviving cells. If these cells are germ cells, this may lead to hereditary harm. If they are somatic cells, the result could be cancer

  5. Carbon Incorporation and Anion Dynamics as Synergistic Drivers for Ultrafast Diffusion in Superionic LiCB11H12 and NaCB11H12

    Energy Technology Data Exchange (ETDEWEB)

    Dimitrievska, Mirjana [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Shea, Patrick [Lawrence Livermore National Laboratory; Kweon, Kyoung E. [Lawrence Livermore National Laboratory; Bercx, Marnik [University of Antwerp; Varley, Joel B. [Lawrence Livermore National Laboratory; Tang, Wan Si [National Institute of Standards and Technology; University of Maryland; Skripov, Alexander V. [Ural Division of the Russian Academy of Sciences; Stavila, Vitalie [Sandia National Laboratories; Udovic, Terrence J. [National Institute of Standards and Technology; Wood, Brandon C. [Lawrence Livermore National Laboratory

    2018-02-02

    The disordered phases of LiCB11H12 and NaCB11H12 possess superb superionic conductivities that make them suitable as solid electrolytes. In these materials, cation diffusion correlates with high orientational mobilities of the CB11H12- anions; however, the precise relationship has yet to be demonstrated. In this work, ab initio molecular dynamics and quasielastic neutron scattering are combined to probe anion reorientations and their mechanistic connection to cation mobility over a range of timescales and temperatures. It is found that anions do not rotate freely, but rather transition rapidly between orientations defined by the cation sublattice symmetry. The symmetry-breaking carbon atom in CB11H12- also plays a critical role by perturbing the energy landscape along the instantaneous orientation of the anion dipole, which couples fluctuations in the cation probability density directly to the anion motion. Anion reorientation rates exceed 3 x 1010 s-1, suggesting the underlying energy landscape fluctuates dynamically on diffusion-relevant timescales. Furthermore, carbon is found to modify the orientational preferences of the anions and aid rotational mobility, creating additional symmetry incompatibilities that inhibit ordering. The results suggest that synergy between the anion reorientational dynamics and the carbon-modified cation-anion interaction accounts for the higher ionic conductivity in CB11H12- salts compared with B12H122-.

  6. Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2Receptors.

    Science.gov (United States)

    Martínez-Pinilla, Eva; Varani, Katia; Reyes-Resina, Irene; Angelats, Edgar; Vincenzi, Fabrizio; Ferreiro-Vera, Carlos; Oyarzabal, Julen; Canela, Enric I; Lanciego, José L; Nadal, Xavier; Navarro, Gemma; Borea, Pier Andrea; Franco, Rafael

    2017-01-01

    The mechanism of action of cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa L., is not completely understood. First assumed that the compound was acting via cannabinoid CB 2 receptors (CB 2 Rs) it is now suggested that it interacts with non-cannabinoid G-protein-coupled receptors (GPCRs); however, CBD does not bind with high affinity to the orthosteric site of any GPCR. To search for alternative explanations, we tested CBD as a potential allosteric ligand of CB 2 R. Radioligand and non-radioactive homogeneous binding, intracellular cAMP determination and ERK1/2 phosphorylation assays were undertaken in heterologous systems expressing the human version of CB 2 R. Using membrane preparations from CB 2 R-expressing HEK-293T (human embryonic kidney 293T) cells, we confirmed that CBD does not bind with high affinity to the orthosteric site of the human CB 2 R where the synthetic cannabinoid, [ 3 H]-WIN 55,212-2, binds. CBD was, however, able to produce minor but consistent reduction in the homogeneous binding assays in living cells using the fluorophore-conjugated CB 2 R-selective compound, CM-157. The effect on binding to CB 2 R-expressing living cells was different to that exerted by the orthosteric antagonist, SR144528, which decreased the maximum binding without changing the K D . CBD at nanomolar concentrations was also able to significantly reduce the effect of the selective CB 2 R agonist, JWH133, on forskolin-induced intracellular cAMP levels and on activation of the MAP kinase pathway. These results may help to understand CBD mode of action and may serve to revisit its therapeutic possibilities.

  7. CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus.

    Science.gov (United States)

    Scerif, Miski; Füzesi, Tamás; Thomas, Julia D; Kola, Blerina; Grossman, Ashley B; Fekete, Csaba; Korbonits, Márta

    2013-10-01

    AMP-activated protein kinase (AMPK), a regulator of cellular and systemic energy homeostasis, can be influenced by several hormones. Tissue-specific alteration of AMPK activity by glucocorticoids may explain the increase in appetite, the accumulation of lipids in adipose tissues, and the detrimental cardiac effects of Cushing's syndrome. Endocannabinoids are known to mediate the effects of various hormones and to influence AMPK activity. Cannabinoids have central orexigenic and direct peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). In our preliminary experiments, WT mice received implants of a corticosterone-containing pellet to establish a mouse model of Cushing's syndrome. Subsequently, WT and Cb1 (Cnr1)-knockout (CB1-KO) littermates were treated with corticosterone and AMPK activity in the hypothalamus, various adipose tissues, liver and cardiac tissue was measured. Corticosterone-treated CB1-KO mice showed a lack of weight gain and of increase in hypothalamic and hepatic AMPK activity. In adipose tissues, baseline AMPK activity was higher in CB1-KO mice, but a glucocorticoid-induced drop was observed, similar to that observed in WT mice. Cardiac AMPK levels were reduced in CB1-KO mice, but while WT mice showed significantly reduced AMPK activity following glucocorticoid treatment, CB1-KO mice showed a paradoxical increase. Our findings indicate the importance of the CB1 receptor in the central orexigenic effect of glucocorticoid-induced activation of hypothalamic AMPK activity. In the periphery adipose tissues, changes may occur independently of the CB1 receptor, but the receptor appears to alter the responsiveness of the liver and myocardial tissues to glucocorticoids. In conclusion, our data suggest that an intact cannabinoid pathway is required for the full metabolic effects of chronic glucocorticoid excess.

  8. Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors

    Directory of Open Access Journals (Sweden)

    Eva Martínez-Pinilla

    2017-10-01

    Full Text Available The mechanism of action of cannabidiol (CBD, the main non-psychotropic component of Cannabis sativa L., is not completely understood. First assumed that the compound was acting via cannabinoid CB2 receptors (CB2Rs it is now suggested that it interacts with non-cannabinoid G-protein-coupled receptors (GPCRs; however, CBD does not bind with high affinity to the orthosteric site of any GPCR. To search for alternative explanations, we tested CBD as a potential allosteric ligand of CB2R. Radioligand and non-radioactive homogeneous binding, intracellular cAMP determination and ERK1/2 phosphorylation assays were undertaken in heterologous systems expressing the human version of CB2R. Using membrane preparations from CB2R-expressing HEK-293T (human embryonic kidney 293T cells, we confirmed that CBD does not bind with high affinity to the orthosteric site of the human CB2R where the synthetic cannabinoid, [3H]-WIN 55,212-2, binds. CBD was, however, able to produce minor but consistent reduction in the homogeneous binding assays in living cells using the fluorophore-conjugated CB2R-selective compound, CM-157. The effect on binding to CB2R-expressing living cells was different to that exerted by the orthosteric antagonist, SR144528, which decreased the maximum binding without changing the KD. CBD at nanomolar concentrations was also able to significantly reduce the effect of the selective CB2R agonist, JWH133, on forskolin-induced intracellular cAMP levels and on activation of the MAP kinase pathway. These results may help to understand CBD mode of action and may serve to revisit its therapeutic possibilities.

  9. Behavioral effects of the novel potent cannabinoid CB1 agonist AM 4054.

    Science.gov (United States)

    McLaughlin, Peter J; Thakur, Ganesh A; Vemuri, V Kiran; McClure, Evan D; Brown, Cara M; Winston, Keisha M; Wood, Jodianne T; Makriyannis, Alexandros; Salamone, John D

    2013-08-01

    Due to the ubiquity of the CB1 cannabinoid receptor throughout the nervous system, as well as the many potential therapeutic uses of CB1 agonist-based interventions, it is desirable to synthesize novel probes of the CB1 receptor. Here, the acute behavioral effects of systemic (i.p.) administration of the putative novel CB1 full agonist AM 4054 were tested in rats. In Experiment 1, a dose range (0.15625-1.25 mg/kg) of AM 4054 produced effects consistent with CB1 agonism in the cannabinoid tetrad of tasks in rats, including induction of analgesia, catalepsy, hypothermia, and locomotor suppression. These effects were reversed with the CB1-selective inverse agonist AM 251 in Experiment 2, indicating that AM 4054 produced CB1 receptor-mediated effects. Analysis of open-field activity indicated that the reduction in locomotion is more consistent with general motor slowing than anxiogenesis. AM 4054 (0.0625-0.5 mg/kg) also dose-dependently reduced fixed-ratio 5 (FR5) operant responding for food in Experiment 3, and microanalysis of the timing and rate of lever pressing indicated a pattern of suppression similar to other CB1 agonists. Minimum doses of AM 4054 (0.125-0.3125 mg/kg) required to produce significant effects in these behavioral assays were lower than those of many CB1 agonists. It is likely that AM 4054 is a potent pharmacological tool for assessment of cannabinoid receptor function. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala

    DEFF Research Database (Denmark)

    Varodayan, Florence P.; Soni, Neeraj; Bajo, Michal

    2016-01-01

    The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and Type 1 cannabinoid receptor (CB1) expression and function in brain regions associated with addiction. CB1 inhibits GABA...

  11. 47 CFR 95.416 - (CB Rule 16) Do I have to limit the length of my communications?

    Science.gov (United States)

    2010-10-01

    ... Operate A Cb Station § 95.416 (CB Rule 16) Do I have to limit the length of my communications? (a) You must limit your CB communications to the minimum practical time. (b) If you are communicating with... my communications? 95.416 Section 95.416 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

  12. Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling*

    Science.gov (United States)

    Moreno, Estefanía; Andradas, Clara; Medrano, Mireia; Caffarel, María M.; Pérez-Gómez, Eduardo; Blasco-Benito, Sandra; Gómez-Cañas, María; Pazos, M. Ruth; Irving, Andrew J.; Lluís, Carme; Canela, Enric I.; Fernández-Ruiz, Javier; Guzmán, Manuel; McCormick, Peter J.; Sánchez, Cristina

    2014-01-01

    The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology. PMID:24942731

  13. Anandamide and Δ9-Tetrahydrocannabinol Directly Inhibit Cells of the Immune System via CB2 Receptors

    Science.gov (United States)

    Eisenstein, Toby K.; Meissler, Joseph J.; Wilson, Qiana; Gaughan, John P.; Adler, Martin W.

    2007-01-01

    This study shows that two cannabinoids, Δ9-tetrahydrocannabinol (THC) and anandamide, induce dose related immunosuppression in both the primary and secondary in vitro plaque-forming cell assays of antibody formation. The immunosuppression induced by both compounds could be blocked by SR144528, an antagonist specific for the CB2 receptor, but not by SR141716, a CB1 antagonist. These studies are novel in that they show that both anadamide and THC are active in the nanomolar to picomolar (for anandamide) range in these assays of immune function, and that both mediate their effects directly on cells of the immune system through the CB2 receptor. PMID:17640739

  14. Decreased Cocaine Motor Sensitization and Self-Administration in Mice Overexpressing Cannabinoid CB2 Receptors

    Science.gov (United States)

    Aracil-Fernández, Auxiliadora; Trigo, José M; García-Gutiérrez, María S; Ortega-Álvaro, Antonio; Ternianov, Alexander; Navarro, Daniela; Robledo, Patricia; Berbel, Pere; Maldonado, Rafael; Manzanares, Jorge

    2012-01-01

    The potential involvement of the cannabinoid CB2 receptors (CB2r) in the adaptive responses induced by cocaine was studied in transgenic mice overexpressing the CB2r (CB2xP) and in wild-type (WT) littermates. For this purpose, the acute and sensitized locomotor responses to cocaine, conditioned place preference, and cocaine intravenous self-administration were evaluated. In addition, we assessed whether CB2r were localized in neurons and/or astrocytes, and whether they colocalized with dopamine D1 and D2 receptors (D1Dr and D2Dr). Dopamine (DA) extracellular levels in the nucleus accumbens (NAcc), and gene expression of tyrosine hydroxylase (TH) and DA transporter (DAT) in the ventral tegmental area (VTA), and μ-opioid and cannabinoid CB1 receptors in the NAcc were also studied in both genotypes. CB2xP mice showed decreased motor response to acute administration of cocaine (10–20 mg/kg) and cocaine-induced motor sensitization compared with WT mice. CB2xP mice presented cocaine-induced conditioned place aversion and self-administered less cocaine than WT mice. CB2r were found in neurons and astrocytes and colocalized with D2Dr in the VTA and NAcc. No significant differences in extracellular DA levels in the NAcc were observed between genotypes after cocaine administration. Under baseline conditions, TH and DAT gene expression was higher and μ-opioid receptor gene expression was lower in CB2xP than in WT mice. However, both genotypes showed similar changes in TH and μ-opioid receptor gene expression after cocaine challenge independently of the pretreatment received. Importantly, the cocaine challenge decreased DAT gene expression to a lesser extent in cocaine-pretreated CB2xP than in cocaine-pretreated WT mice. These results revealed that CB2r are involved in cocaine motor responses and cocaine self-administration, suggesting that this receptor could represent a promising target to develop novel treatments for cocaine addiction. PMID:22414816

  15. Neurophysiological evidence for the presence of cannabinoid CB1 receptors in the laterodorsal tegmental nucleus

    DEFF Research Database (Denmark)

    Soni, Neeraj; Satpathy, Shankha; Kohlmeier, Kristi Anne

    2014-01-01

    Marijuana, which acts within the endocannabinoid (eCB) system as an agonist of the cannabinoid type 1 receptor (CB1R), exhibits addictive properties and has powerful actions on the state of arousal of an organism. The laterodorsal tegmental nucleus (LDT), as a component of the reticular activating...... the firing frequency and synaptic activity of neurons in this nucleus. Therefore, endogenous eCB transmission could play a role in processes involving the LDT, such as cortical activation and motivated behaviours and, further, behavioural actions of marijuana are probably mediated, in part, via cellular...

  16. The Effect of Nonnormality on CB-SEM and PLS-SEM Path Estimates

    OpenAIRE

    Z. Jannoo; B. W. Yap; N. Auchoybur; M. A. Lazim

    2014-01-01

    The two common approaches to Structural Equation Modeling (SEM) are the Covariance-Based SEM (CB-SEM) and Partial Least Squares SEM (PLS-SEM). There is much debate on the performance of CB-SEM and PLS-SEM for small sample size and when distributions are nonnormal. This study evaluates the performance of CB-SEM and PLS-SEM under normality and nonnormality conditions via a simulation. Monte Carlo Simulation in R programming language was employed to generate data based on the theoretical model w...

  17. Reproductive biology of Tinantia anomala (Torr. C.B. Clarke

    Directory of Open Access Journals (Sweden)

    Joanna Gębura

    2014-04-01

    Full Text Available Tinantia anomala (Torr. C.B. Clarke (Commelinaceae is an annual plant endemic to central Texas in the United States and Durango in northern Mexico. T. anomala has zygomorphic flowers with three different petals, androecium consists of six various stamens and gynoecium consists of three carpels. Furthermore in T. anomala’s flowers there are many staminal hairs (Faden 2006. Its semi-succulent, grass-like leaves emerge in late fall and remain green throughout the cold months. It grows rapidly in early spring and blooms mid-spring (from March to May. A few weeks later the fruits (capsules with four seeds usually appear. This entire cycle is usually completed by summer, when the plant has often turned yellow and limp. We studied T. anomala due to the occurrence of two types of strikingly different stamens occur in one flower. According to available literature, one type of the stamens (the upper one with smaller anthers produces sterile pollen grains which do not participate in fertilization but only attract insects. The other type, i.e. the lower stamens with bigger anthers can form abundant pollen grains used for pollination (Simpson et al. 1986. Our aim was to investigate type of pollination of T. anomala. Using many microscopic methods we were able to analyze and compare the morphology of two types of anthers and staminal hairs in T. anomala’s flowers. We also investigated this species in terms of development of its gametophytes. An embryo sac develops according to the type of Polygonum. Pollen grains develop during different ways depending on the chemical composition of each anther. We identified that the insects of Thysanoptera which preys on the withered flowers T. anomala could be responsible for pollination of this species under greenhouse condition.

  18. Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.

    Directory of Open Access Journals (Sweden)

    Angel Arevalo-Martin

    Full Text Available Spinal cord injury (SCI induces a cascade of processes that may further expand the damage (secondary injury or, alternatively, may be part of a safeguard response. Here we show that after a moderate-severe contusive SCI in rats there is a significant and very early increase in the spinal cord content of the endocannabinoids 2-arachidonoylglycerol (2-AG and arachidonoyl ethanolamide (anandamide, AEA. Since 2-AG and AEA act through CB1 and CB2 cannabinoid receptors, we administered at 20 minutes after lesion a single injection of their respective antagonists AM281 and AM630 alone or in combination to block the effects of this early endocannabinoid accumulation. We observed that AM281, AM630 or AM281 plus AM630 administration impairs the spontaneous motor recovery of rats according to the Basso-Beattie-Bresnahan (BBB locomotor scale. However, blockade of CB1, CB2 or both receptors produced different effects at the histopathological level. Thus, AM630 administration results at 90 days after lesion in increased MHC-II expression by spinal cord microglia/monocytes and reduced number of serotoninergic fibres in lumbar spinal cord (below the lesion. AM281 exerted the same effects but also increased oedema volume estimated by MRI. Co-administration of AM281 and AM630 produced the effects observed with the administration of either AM281 or AM630 and also reduced white matter and myelin preservation and enhanced microgliosis in the epicentre. Overall, our results suggest that the endocannabinoids acting through CB1 and CB2 receptors are part of an early neuroprotective response triggered after SCI that is involved in the spontaneous recovery after an incomplete lesion.

  19. Acute Pharmacological Effects of 2C-B in Humans: An Observational Study

    Directory of Open Access Journals (Sweden)

    Esther Papaseit

    2018-03-01

    Full Text Available 2,5-dimethoxy-4-bromophenethylamine (2C-B is a psychedelic phenylethylamine derivative, structurally similar to mescaline. It is a serotonin 5-hydroxytryptamine-2A (5-HT2A, 5-hydroxytryptamine-2B (5-HT2B, and 5-hydroxytryptamine-2C (5-HT2C receptor partial agonist used recreationally as a new psychoactive substance. It has been reported that 2C-B induces mild psychedelic effects, although its acute pharmacological effects and pharmacokinetics have not yet been fully studied in humans. An observational study was conducted to assess the acute subjective and physiological effects, as well as pharmacokinetics of 2C-B. Sixteen healthy, experienced drug users self-administered an oral dose of 2C-B (10, 15, or 20 mg. Vital signs (blood pressure and heart rate were measured at baseline 1, 2, 3, 4, and 6 hours (h. Each participant completed subjective effects using three rating scales: the visual analog scale (VAS, the Addiction Research Centre Inventory (ARCI, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE at baseline, 2–3 and 6 h after self-administration (maximum effects along 6 h, and the Hallucinogenic Rating Scale (maximum effects along 6 h. Oral fluid (saliva was collected to assess 2C-B and cortisol concentrations during 24 h. Acute administration of 2C-B increased blood pressure and heart rate. Scores of scales related to euphoria increased (high, liking, and stimulated, and changes in perceptions (distances, colors, shapes, and lights and different body feelings/surrounding were produced. Mild hallucinating effects were described in five subjects. Maximum concentrations of 2C-B and cortisol were reached at 1 and 3 h after self-administration, respectively. Oral 2C-B at recreational doses induces a constellation of psychedelic/psychostimulant-like effects similar to those associated with serotonin-acting drugs.

  20. Prototypic implementations of the building block for component based open Hypermedia systems (BB/CB-OHSs)

    DEFF Research Database (Denmark)

    Mohamed, Omer I. Eldai

    2005-01-01

    In this paper we describe the prototypic implementations of the BuildingBlock (BB/CB-OHSs) that proposed to address some of the Component-based Open Hypermedia Systems (CB-OHSs) issues, including distribution and interoperability [4, 11, 12]. Four service implementations were described below....... These are the math service, navigational service, naming and location service and the storage service in addition to two communication protocols (TCP/IP and JAVA RMI)....

  1. Cannabinoid CB1Discrimination: Effects of Endocannabinoids and Catabolic Enzyme Inhibitors.

    Science.gov (United States)

    Leonard, Michael Z; Alapafuja, Shakiru O; Ji, Lipin; Shukla, Vidyanand G; Liu, Yingpeng; Nikas, Spyros P; Makriyannis, Alexandros; Bergman, Jack; Kangas, Brian D

    2017-12-01

    An improved understanding of the endocannabinoid system has provided new avenues of drug discovery and development toward the management of pain and other behavioral maladies. Exogenous cannabinoid type 1 (CB 1 ) receptor agonists such as Δ 9 -tetrahydrocannabinol are increasingly used for their medicinal actions; however, their utility is constrained by concern regarding abuse-related subjective effects. This has led to growing interest in the clinical benefit of indirectly enhancing the activity of the highly labile endocannabinoids N -arachidonoylethanolamine [AEA (or anandamide)] and/or 2-arachidonoylglycerol (2-AG) via catabolic enzyme inhibition. The present studies were conducted to determine whether such actions can lead to CB 1 agonist-like subjective effects, as reflected in CB 1 -related discriminative stimulus effects in laboratory subjects. Squirrel monkeys ( n = 8) that discriminated the CB 1 full agonist AM4054 (0.01 mg/kg) from vehicle were used to study, first, the inhibitors of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MGL) alone or in combination [FAAH (URB597, AM4303); MGL (AM4301); FAAH/MGL (JZL195, AM4302)] and, second, the ability of the endocannabinoids AEA and 2-AG to produce CB 1 agonist-like effects when administered alone or after enzyme inhibition. Results indicate that CB 1 -related discriminative stimulus effects were produced by combined, but not selective, inhibition of FAAH and MGL, and that these effects were nonsurmountably antagonized by low doses of rimonabant. Additionally, FAAH or MGL inhibition revealed CB 1 -like subjective effects produced by AEA but not by 2-AG. Taken together, the present data suggest that therapeutic effects of combined, but not selective, enhancement of AEA or 2-AG activity via enzyme inhibition may be accompanied by CB 1 receptor-mediated subjective effects. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Cannabinoid CB1 receptor immunoreactivity in the prefrontal cortex: Comparison of schizophrenia and major depressive disorder.

    Science.gov (United States)

    Eggan, Stephen M; Stoyak, Samuel R; Verrico, Christopher D; Lewis, David A

    2010-09-01

    We recently showed that measures of cannabinoid 1 receptor (CB1R) mRNA and protein were significantly reduced in dorsolateral prefrontal cortex (DLPFC) area 9 in schizophrenia subjects relative to matched normal comparison subjects. However, other studies have reported unaltered or higher measures of CB1R levels in schizophrenia. To determine whether these discrepancies reflect differences across brain regions or across subject groups (eg, presence of depression, cannabis exposure, etc), we used immunocytochemical techniques to determine whether lower levels of CB1R immunoreactivity are (1) present in another DLPFC region, area 46, in the same subjects with schizophrenia, (2) present in area 46 in a new cohort of schizophrenia subjects, (3) present in major depressive disorder (MDD) subjects, or (4) attributable to factors other than a diagnosis of schizophrenia, including prior cannabis use. CB1R immunoreactivity levels in area 46 were significantly 19% lower in schizophrenia subjects relative to matched normal comparison subjects, a deficit similar to that observed in area 9 in the same subjects. In a new cohort of subjects, CB1R immunoreactivity levels were significantly 20 and 23% lower in schizophrenia subjects relative to matched comparison and MDD subjects, respectively. The lower levels of CB1R immunoreactivity in schizophrenia subjects were not explained by other factors such as cannabis use, suicide, or pharmacological treatment. In addition, CB1R immunoreactivity levels were not altered in monkeys chronically exposed to haloperidol. Thus, the lower levels of CB1R immunoreactivity may be common in schizophrenia, conserved across DLPFC regions, not present in MDD, and not attributable to other factors, and thus a reflection of the underlying disease process.

  3. Electrodeposited ultrafine TaOx/CB catalysts for PEFC cathode application: Their oxygen reduction reaction kinetics

    KAUST Repository

    Seo, Jeongsuk

    2014-12-01

    Ultrafine TaOx nanoparticles were electrodeposited on carbon black (CB) powder in a nonaqueous Ta complex solution at room temperature, and the resultant TaOx/CB catalysts were assessed as oxygen reduction reaction (ORR) electrocatalysts for polymer electrolyte fuel cell (PEFC) cathodes. The Ta electrodeposition process was scaled up using a newly designed working electrode containing a CB dense layer, without introducing any binder such as the ionomer Nafion in the electrode for electrodeposition. The electrodeposited TaOx/CB powders were removed from the deposition electrode and subsequent H2 treatment at varying temperatures between 523 and 1073 K was attempted to increase the ORR performance. The TaOx/CB samples were characterized by SEM, STEM, XPS, and EELS measurements. XPS and EELS results indicated the reduced nature of the Ta species caused by the high-temperature treatment in H2, while STEM images clearly revealed that the TaOx particles aggregated as the treatment temperature increased. When the TaOx/CB catalyst, which was treated at 873 K for 2 h, was deposited on a glassy carbon substrate with Nafion ionomer, it resulted in the highest activity among the samples investigated, giving an onset potential of 0.95 VRHE at -2 μA cm-2 in a 0.1 M H2SO4 solution. Moreover, the long-term stability test with 10,000 cycles of the voltammetry only led to a 6% loss in the ORR currents, demonstrating the high stability of the TaOx/CB catalysts. Kinetic analysis by R(R)DE indicated that the four-electron transfer pathway in the ORR process was dominant for this TaOx/CB catalyst, and Tafel plots showed a slope corresponding to a one-electron reaction for the rate-determining step.

  4. Receptor-heteromer mediated regulation of endocannabinoid signaling in activated microglia. Role of CB1and CB2receptors and relevance for Alzheimer's disease and levodopa-induced dyskinesia.

    Science.gov (United States)

    Navarro, Gemma; Borroto-Escuela, Dasiel; Angelats, Edgar; Etayo, Íñigo; Reyes-Resina, Irene; Pulido-Salgado, Marta; Rodríguez-Pérez, Ana I; Canela, Enric I; Saura, Josep; Lanciego, José Luis; Labandeira-García, José Luis; Saura, Carlos A; Fuxe, Kjell; Franco, Rafael

    2018-01-01

    Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB 1 and CB 2 receptors, which may form heteromeric complexes (CB 1 -CB 2 Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. In activated microglia mRNA transcripts increased (2 fold for CB 1 and circa 20 fold for CB 2 ), whereas receptor levels were similar for CB 1 and markedly upregulated for CB 2 ; CB 1 -CB 2 Hets were also upregulated. Unlike in resting cells, CB 2 receptors became robustly coupled to G i in activated cells, in which CB 1 -CB 2 Hets mediated a potentiation effect. Hence, resting cells were refractory while activated cells were highly responsive to cannabinoids. Interestingly, similar results were obtained in cultures treated with ß-amyloid (Aß 1-42 ). Microglial activation markers were detected in the striatum of a Parkinson's disease (PD) model and, remarkably, in primary microglia cultures from the hippocampus of mutant β-amyloid precursor protein (APP Sw,Ind ) mice, a transgenic Alzheimer's disease (AD) model. Also of note was the similar cannabinoid receptor signaling found in primary cultures of microglia from APP Sw,Ind and in cells from control animals activated using LPS plus IFN-γ. Expression of CB 1 -CB 2 Hets was increased in the striatum from rats rendered dyskinetic by chronic levodopa treatment. In summary, our results showed sensitivity of activated microglial cells to cannabinoids, increased CB 1 -CB 2 Het expression in activated microglia and in microglia from the hippocampus of an AD model, and a correlation between levodopa-induced dyskinesia and striatal microglial activation in a PD model. Cannabinoid receptors and the CB 1 -CB 2 heteroreceptor complex in activated microglia have potential as targets in the

  5. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

    Science.gov (United States)

    Kalia, Sarah S; Adelman, Kathy; Bale, Sherri J; Chung, Wendy K; Eng, Christine; Evans, James P; Herman, Gail E; Hufnagel, Sophia B; Klein, Teri E; Korf, Bruce R; McKelvey, Kent D; Ormond, Kelly E; Richards, C Sue; Vlangos, Christopher N; Watson, Michael; Martin, Christa L; Miller, David T

    2017-02-01

    the process was implemented. Applying the new process while upholding the core principles of the original policy statement resulted in the addition of four genes and removal of one gene; one gene did not meet criteria for inclusion. The updated secondary findings minimum list includes 59 medically actionable genes recommended for return in clinical genomic sequencing. We discuss future areas of focus, encourage continued input from the medical community, and call for research on the impact of returning genomic secondary findings.Genet Med 19 2, 249-255.

  6. Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

    Science.gov (United States)

    Busquets-Garcia, Arnau; Gomis-González, Maria; Srivastava, Raj Kamal; Cutando, Laura; Ortega-Alvaro, Antonio; Ruehle, Sabine; Remmers, Floortje; Bindila, Laura; Bellocchio, Luigi; Marsicano, Giovanni; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés

    2016-08-30

    Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.

  7. Pyrazole antagonists of the CB1 receptor with reduced brain penetration.

    Science.gov (United States)

    Fulp, Alan; Zhang, Yanan; Bortoff, Katherine; Seltzman, Herbert; Snyder, Rodney; Wiethe, Robert; Amato, George; Maitra, Rangan

    2016-03-01

    Type 1 cannabinoid receptor (CB1) antagonists might be useful for treating obesity, liver disease, metabolic syndrome, and dyslipidemias. Unfortunately, inhibition of CB1 in the central nervous system (CNS) produces adverse effects, including depression, anxiety and suicidal ideation in some patients, which led to withdrawal of the pyrazole inverse agonist rimonabant (SR141716A) from European markets. Efforts are underway to produce peripherally selective CB1 antagonists to circumvent CNS-associated adverse effects. In this study, novel analogs of rimonabant (1) were explored in which the 1-aminopiperidine group was switched to a 4-aminopiperidine, attached at the 4-amino position (5). The piperidine nitrogen was functionalized with carbamates, amides, and sulfonamides, providing compounds that are potent inverse agonists of hCB1 with good selectivity for hCB1 over hCB2. Select compounds were further studied using in vitro models of brain penetration, oral absorption and metabolic stability. Several compounds were identified with predicted minimal brain penetration and good metabolic stability. In vivo pharmacokinetic testing revealed that inverse agonist 8c is orally bioavailable and has vastly reduced brain penetration compared to rimonabant. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Cannabinoid CB1 receptor recognition of endocannabinoids via the lipid bilayer: molecular dynamics simulations of CB1 transmembrane helix 6 and anandamide in a phospholipid bilayer

    Science.gov (United States)

    Lynch, Diane L.; Reggio, Patricia H.

    2006-08-01

    The phospholipid bilayer plays a central role in the lifecycle of the endogenous cannabinoid, N-arachidonoylethanolamine (anandamide, AEA). Therefore, the orientation and location of AEA in the phospholipid bilayer with respect to key membrane associated proteins, is a central issue in understanding the mechanism of endocannabinoid signaling. In this paper, we report a test of the hypothesis that a βXX β motif (formed by beta branching amino acids, V6.43 and I6.46) on the lipid face of the cannabinoid CB1 receptor in its inactive state may serve as an initial CB1 interaction site for AEA. Eight 6 ns NAMD2 molecular dynamics simulations of AEA were conducted in a model system composed of CB1 transmembrane helix 6 (TMH6) in a 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) bilayer. In addition, eight 6 ns NAMD2 molecular dynamics simulations of a low CB1 affinity (20:2, n-6) analog of AEA were conducted in the same model system. AEA was found to exhibit a higher incidence of V6.43/I6.46 groove insertion than did the (20:2, n-6) analog. In certain cases, AEA established a high energy of interaction with TMH6 by first associating with the V6.43/I6.46 groove and then molding itself to the lipid face of TMH6 to establish a hydrogen bonding interaction with the exposed backbone carbonyl of P6.50. Based upon these results, we propose that the formation of this hydrogen bonded AEA/TMH6 complex may be the initial step in CB1 recognition of AEA in the lipid bilayer.

  9. The Caulobacter crescentus phage phiCbK: genomics of a canonical phage

    Directory of Open Access Journals (Sweden)

    Gill Jason J

    2012-10-01

    Full Text Available Abstract Background The bacterium Caulobacter crescentus is a popular model for the study of cell cycle regulation and senescence. The large prolate siphophage phiCbK has been an important tool in C. crescentus biology, and has been studied in its own right as a model for viral morphogenesis. Although a system of some interest, to date little genomic information is available on phiCbK or its relatives. Results Five novel phiCbK-like C. crescentus bacteriophages, CcrMagneto, CcrSwift, CcrKarma, CcrRogue and CcrColossus, were isolated from the environment. The genomes of phage phiCbK and these five environmental phage isolates were obtained by 454 pyrosequencing. The phiCbK-like phage genomes range in size from 205 kb encoding 318 proteins (phiCbK to 280 kb encoding 448 proteins (CcrColossus, and were found to contain nonpermuted terminal redundancies of 10 to 17 kb. A novel method of terminal ligation was developed to map genomic termini, which confirmed termini predicted by coverage analysis. This suggests that sequence coverage discontinuities may be useable as predictors of genomic termini in phage genomes. Genomic modules encoding virion morphogenesis, lysis and DNA replication proteins were identified. The phiCbK-like phages were also found to encode a number of intriguing proteins; all contain a clearly T7-like DNA polymerase, and five of the six encode a possible homolog of the C. crescentus cell cycle regulator GcrA, which may allow the phage to alter the host cell’s replicative state. The structural proteome of phage phiCbK was determined, identifying the portal, major and minor capsid proteins, the tail tape measure and possible tail fiber proteins. All six phage genomes are clearly related; phiCbK, CcrMagneto, CcrSwift, CcrKarma and CcrRogue form a group related at the DNA level, while CcrColossus is more diverged but retains significant similarity at the protein level. Conclusions Due to their lack of any apparent relationship to

  10. The Caulobacter crescentus phage phiCbK: genomics of a canonical phage

    Science.gov (United States)

    2012-01-01

    Background The bacterium Caulobacter crescentus is a popular model for the study of cell cycle regulation and senescence. The large prolate siphophage phiCbK has been an important tool in C. crescentus biology, and has been studied in its own right as a model for viral morphogenesis. Although a system of some interest, to date little genomic information is available on phiCbK or its relatives. Results Five novel phiCbK-like C. crescentus bacteriophages, CcrMagneto, CcrSwift, CcrKarma, CcrRogue and CcrColossus, were isolated from the environment. The genomes of phage phiCbK and these five environmental phage isolates were obtained by 454 pyrosequencing. The phiCbK-like phage genomes range in size from 205 kb encoding 318 proteins (phiCbK) to 280 kb encoding 448 proteins (CcrColossus), and were found to contain nonpermuted terminal redundancies of 10 to 17 kb. A novel method of terminal ligation was developed to map genomic termini, which confirmed termini predicted by coverage analysis. This suggests that sequence coverage discontinuities may be useable as predictors of genomic termini in phage genomes. Genomic modules encoding virion morphogenesis, lysis and DNA replication proteins were identified. The phiCbK-like phages were also found to encode a number of intriguing proteins; all contain a clearly T7-like DNA polymerase, and five of the six encode a possible homolog of the C. crescentus cell cycle regulator GcrA, which may allow the phage to alter the host cell’s replicative state. The structural proteome of phage phiCbK was determined, identifying the portal, major and minor capsid proteins, the tail tape measure and possible tail fiber proteins. All six phage genomes are clearly related; phiCbK, CcrMagneto, CcrSwift, CcrKarma and CcrRogue form a group related at the DNA level, while CcrColossus is more diverged but retains significant similarity at the protein level. Conclusions Due to their lack of any apparent relationship to other described phages, this

  11. Recommendations on national radioactive waste management policies

    International Nuclear Information System (INIS)

    1981-01-01

    As a nation, we have learned that sound technical solutions to the problems of waste disposal cannot be carried out without public acceptance. The key to gaining the public's confidence is a process of decision making which is open and accessible to elected officials from all levels of government. The Council believes that such a process can be put in place through a renewal of the traditional principles of our federal system of government. State, local, and tribal officials must become working partners with the federal government in making the crucial decisions about how radioactive wastes will be handled, transported, and ultimately disposed. A workable and effective partnership must include, first the full sharing of information and plans regarding waste disposal activities among all levels of government and, second, the opportunity for state, local, and tribal governments to participate effectively in waste management decisions which affect their jurisdictions. Finally, althougcome this difficulty

  12. CB1Cannabinoid Receptors Mediate Cognitive Deficits and Structural Plasticity Changes During Nicotine Withdrawal.

    Science.gov (United States)

    Saravia, Rocio; Flores, África; Plaza-Zabala, Ainhoa; Busquets-Garcia, Arnau; Pastor, Antoni; de la Torre, Rafael; Di Marzo, Vincenzo; Marsicano, Giovanni; Ozaita, Andrés; Maldonado, Rafael; Berrendero, Fernando

    2017-04-01

    Tobacco withdrawal is associated with deficits in cognitive function, including attention, working memory, and episodic memory. Understanding the neurobiological mechanisms involved in these effects is crucial because cognitive deficits during nicotine withdrawal may predict relapse in humans. We investigated in mice the role of CB 1 cannabinoid receptors (CB 1 Rs) in memory impairment and spine density changes induced by nicotine withdrawal precipitated by the nicotinic antagonist mecamylamine. Drugs acting on the endocannabinoid system and genetically modified mice were used. Memory impairment during nicotine withdrawal was blocked by the CB 1 R antagonist rimonabant or the genetic deletion of CB 1 R in forebrain gamma-aminobutyric acidergic (GABAergic) neurons (GABA-CB 1 R). An increase of 2-arachidonoylglycerol (2-AG), but not anandamide, was observed during nicotine withdrawal. The selective inhibitor of 2-AG biosynthesis O7460 abolished cognitive deficits of nicotine abstinence, whereas the inhibitor of 2-AG enzymatic degradation JZL184 did not produce any effect in cognitive impairment. Moreover, memory impairment was prevented by the selective mammalian target of rapamycin inhibitor temsirolimus and the protein synthesis inhibitor anisomycin. Mature dendritic spines on CA1 pyramidal hippocampal neurons decreased 4 days after the precipitation of nicotine withdrawal, when the cognitive deficits were still present. Indeed, a correlation between memory performance and mature spine density was found. Interestingly, these structural plasticity alterations were normalized in GABA-CB 1 R conditional knockout mice and after subchronic treatment with rimonabant. These findings underline the interest of CB 1 R as a target to improve cognitive performance during early nicotine withdrawal. Cognitive deficits in early abstinence are associated with increased relapse risk. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Identifying the causes of differences in ozone production from the CB05 and CBMIV chemical mechanisms

    Directory of Open Access Journals (Sweden)

    R. D. Saylor

    2012-02-01

    Full Text Available An investigation was conducted to identify the mechanistic differences between two versions of the carbon bond gas-phase chemical mechanism (CB05 and CBMIV which consistently lead to larger ground-level ozone concentrations being produced in the CB05 version of the National Air Quality Forecasting Capability (NAQFC modeling system even though the two parallel forecast systems utilize the same meteorology and base emissions and similar initial and boundary conditions. Box models of each of the mechanisms as they are implemented in the NAQFC were created and a set of 12 sensitivity simulations was designed. The sensitivity simulations independently probed the conceptual mechanistic differences between CB05 and CBMIV and were exercised over a 45-scenario simulation suite designed to emulate the wide range of chemical regimes encountered in a continental-scale atmospheric chemistry model. Results of the sensitivity simulations indicate that two sets of reactions that were included in the CB05 mechanism, but which were absent from the CBMIV mechanism, are the primary causes of the greater ozone production in the CB05 version of the NAQFC. One set of reactions recycles the higher organic peroxide species of CB05 (ROOH, resulting in additional photochemically reactive products that act to produce additional ozone in some chemical regimes. The other set of reactions recycles reactive nitrogen from less reactive forms back to NO2, increasing the effective NOx concentration of the system. In particular, the organic nitrate species (NTR, which was a terminal product for reactive nitrogen in the CBMIV mechanism, acts as a reservoir species in CB05 to redistribute NOx from major source areas to potentially NOx-sensitive areas where additional ozone may be produced in areas remote from direct NOx sources.

  14. Increased CB2 mRNA and anandamide in human blood after cessation of cannabis abuse.

    Science.gov (United States)

    Muhl, Daniela; Kathmann, Markus; Hoyer, Carolin; Kranaster, Laura; Hellmich, Martin; Gerth, Christoph W; Faulhaber, Johannes; Schlicker, Eberhard; Leweke, F Markus

    2014-07-01

    In previous studies, long-term cannabis use led to alterations of the endocannabinoid system including an increase in CB1 and/or CB2 receptor messenger RNA (mRNA) in blood cells and an increase in the serum level of the endocannabinoid 2-arachidonoyl glycerol. However, in those studies, cannabis use was stopped only few days before testing or not interrupted at all. Therefore, one cannot decide whether the alterations are due to long-term cannabis abuse or are confounded by acute effects of cannabis. Blood was sampled from donors that had smoked marijuana ≥20 times in their lives but had abstained from cannabis for ≥6 months (high-frequency users, HFU) and from controls (cannabis use ≤5 times lifetime). CB1 and CB2 mRNA was determined in peripheral mononuclear blood cells using the reverse transcriptase polymerase chain reaction. Serum anandamide level was assayed using electrospray tandem mass spectrometry. CB2 mRNA was increased by 45 % in HFU when compared to controls, whereas CB1 mRNA did not differ. The anandamide level in HFU exceeded that in controls by 90 %. Tobacco smoking could be excluded as a confounding factor. In conclusion, marijuana users that had smoked marijuana ≥20 times in their lives and stopped cannabis use at least 6 months before the study show an increase in CB2 receptor mRNA in the blood and in serum anandamide level. These alterations resemble those obtained for marijuana smokers that had stopped cannabis use only few days before testing and may be implicated in the pathogenesis of disorders associated with long-term cannabis use.

  15. High tumour cannabinoid CB1 receptor immunoreactivity negatively impacts disease-specific survival in stage II microsatellite stable colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Sofia B Gustafsson

    Full Text Available BACKGROUND: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1 receptor immunoreactive intensity (CB(1IR intensity is associated with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483 and invasive front (n = 486 CB(1IR was scored from 0 (absent to 3 (intense staining and the data was analysed as a median split i.e. CB(1IR <2 and ≥2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins, there was a significant positive association of the tumour grade with the CB(1IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1IR upon disease specific survival. The 5 year probabilities of event-free survival were: 85±5 and 66±8%; tumour interior, 86±4% and 63±8% for the CB(1IR<2 and CB(1IR≥2 groups, respectively. CONCLUSIONS/SIGNIFICANCE: The level of CB(1 receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients.

  16. Clarifying CB2 Receptor-Dependent and Independent Effects of THC on Human Lung Epithelial Cells

    Science.gov (United States)

    Sarafian, Theodore; Montes, Cindy; Harui, Airi; Beedanagari, Sudheer R.; Kiertscher, Sylvia; Stripecke, Renata; Hossepian, Derik; Kitchen, Christina; Kern, Rita; Belperio, John; Roth, Michael D.

    2008-01-01

    Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that Δ9-tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 (Sarafian et al., 2003; Sarafian et al., 2005). The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10 % serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p < 0.05) and were 80- to 100-fold more sensitive to the inhibitory effects of THC. Studies using SR144528, a selective CB2R antagonist, verified that these effects were mediated by the CB2R. Marijuana smoke extract, but not smoke extracts from tobacco or placebo marijuana cigarettes, reproduced these effects (p < 0.05). THC decreased ATP level and mitochondrial membrane potential (Ψm) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher Ψm than did control cells. Since both Ψm and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of IκB-α and JNK were regulated in a CB2R-and THC-dependent manner. We conclude that airway

  17. The endocannabinoid-CB receptor system: Importance for development and in pediatric disease.

    Science.gov (United States)

    Fride, Ester

    2004-01-01

    Endogenous cannabinoids (endocannabinoids) and their cannabinoid CB1 and CB2 receptors, are present from the early stages of gestation and play a number of vital roles for the developing organism. Although most of these data are collected from animal studies, a role for cannabinoid receptors in the developing human brain has been suggested, based on the detection of "atypically" distributed CB1 receptors in several neural pathways of the fetal brain. In addition, a role for the endocannabinoid system for the human infant is likely, since the endocannabinoid 2-arachidonoyl glycerol has been detected in human milk. Animal research indicates that the Endocannabinoid-CB1 Receptor ('ECBR') system fulfills a number of roles in the developing organism: 1. embryonal implantation (requires a temporary and localized reduction in anandamide); 2. in neural development (by the transient presence of CB1 receptors in white matter areas of the nervous system); 3. as a neuroprotectant (anandamide protects the developing brain from trauma-induced neuronal loss); 4. in the initiation of suckling in the newborn (where activation of the CB1 receptors in the neonatal brain is critical for survival). 5. In addition, subtle but definite deficiencies have been described in memory, motor and addictive behaviors and in higher cognitive ('executive') function in the human offspring as result of prenatal exposure to marihuana. Therefore, the endocanabinoid-CB1 receptor system may play a role in the development of structures which control these functions, including the nigrostriatal pathway and the prefrontal cortex. From the multitude of roles of the endocannabinoids and their receptors in the developing organism, there are two distinct stages of development, during which proper functioning of the endocannabinoid system seems to be critical for survival: embryonal implantation and neonatal milk sucking. We propose that a dysfunctional Endocannabinoid-CB1 Receptor system in infants with growth

  18. Eutectic superalloys strengthened by delta Ni3Cb lamellae, and gamma prime, Ni3Al precipitates.

    Science.gov (United States)

    Lemkey, F. D.; Thompson, E. R.

    1972-01-01

    Bivariant eutectic alloys, located on a liquidus surface within the Ni-Cb-Cr-Al quaternary, were identified which permitted the production of aligned delta Ni3Cb lamellae within a nichrome matrix containing the fcc precipitate gamma prime Ni3Al. The volume fraction of delta and gamma prime could be varied significantly by compositional changes. After directional solidification certain alloys possessed improved ductility and corrosion resistance with respect to the Ni3Al-Ni3Cb eutectic, while their values of tensile and creep strength approached or exceeded those for the Ni3Al-Ni3Cb pseudobinary system. The mechanical properties of the directionally solidified alloy, Ni-19.7 wt % Cb-6.0 wt % Cr-2.5 wt % Al, were evaluated. Its longitudinal strength in tension and creep was found to be superior to all advanced nickel base superalloys. It is thus demonstrated that useful properties for gas turbine airfoil applications can be achieved by reinforcing a strong and tough gamma nichrome matrix containing precipitated gamma prime by a strong lamellar intermetallic compound having greater strength at elevated temperature.

  19. Sensitization to green coffee bean (GCB) and castor bean (CB) allergens among dock workers.

    Science.gov (United States)

    De Zotti, R; Patussi, V; Fiorito, A; Larese, F

    1988-01-01

    Dock workers (n = 218) occupationally exposed to green coffee beans (GCB) were studied, using a specific questionnaire for allergic symptoms and skin tests for common and occupational allergens. Thirty-one workers (14.3%) complained of allergic symptoms of the eye, nose and bronchial system at the workplace. The prick tests, using both commercial allergens and specific extracts prepared from the most common types of coffee and their corresponding sacks, confirmed a sensitization in 21 workers (9.6%). A positive skin reaction to castor beans (CB) was found in nearly all these cases; in ten workers there was also a positive reaction to GCB allergens and in 14 cases prick tests were positive to extracts of sacks. There was a good concordance between prick tests and specific IgE for CB (95.0%) and also, but to a lesser extent, for GCB. The authors concluded that there is a significant risk of sensitization to CB and GCB allergens in dock workers occupied in handling green coffee bean, despite the fact that the exposure is not continuous. CB emerged as a common contaminant of GCB from various countries. For effective prevention, a modification of the methods of transport is required to avoid CB contamination to other products. Eliminating environmental dust during shipping operations is the most important preventive measure and it can be achieved by the use of containers, as some exporting countries are already doing.

  20. METHODS FOR RECOMBINANT EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF HUMAN CANNABINOID RECEPTOR CB2

    Directory of Open Access Journals (Sweden)

    Alexei A. Yeliseev

    2013-03-01

    Full Text Available Cannabinoid receptor CB2 is a seven transmembrane-domain integral membrane protein that belongs to a large superfamily of G protein-coupled receptors (GPCR. CB2 is a part of the endocannabinoid system that plays vital role in regulation of immune response, inflammation, pain sensitivity, obesity and other physiological responses. Information about the structure and mechanisms of functioning of this receptor in cell membranes is essential for the rational development of specific pharmaceuticals. Here we review the methodology for recombinant expression, purification, stabilization and biochemical characterization of CB2 suitable for preparation of multi-milligram quantities of functionally active receptor. The biotechnological protocols include expression of the recombinant CB2 in E. coli cells as a fusion with the maltose binding protein, stabilization with a high affinity ligand and a derivative of cholesterol in detergent micelles, efficient purification by tandem affinity chromatography, and reconstitution of the receptor into lipid bilayers. The purified recombinant CB2 receptor is amenable to functional and structural studies including nuclear magnetic resonance spectroscopy and a wide range of biochemical and biophysical techniques.

  1. Anandamide, Acting via CB2 Receptors, Alleviates LPS-Induced Neuroinflammation in Rat Primary Microglial Cultures

    Directory of Open Access Journals (Sweden)

    Natalia Malek

    2015-01-01

    Full Text Available Microglial activation is a polarized process divided into potentially neuroprotective phenotype M2 and neurotoxic phenotype M1, predominant during chronic neuroinflammation. Endocannabinoid system provides an attractive target to control the balance between microglial phenotypes. Anandamide as an immune modulator in the central nervous system acts via not only cannabinoid receptors (CB1 and CB2 but also other targets (e.g., GPR18/GPR55. We studied the effect of anandamide on lipopolysaccharide-induced changes in rat primary microglial cultures. Microglial activation was assessed based on nitric oxide (NO production. Analysis of mRNA was conducted for M1 and M2 phenotype markers possibly affected by the treatment. Our results showed that lipopolysaccharide-induced NO release in microglia was significantly attenuated, with concomitant downregulation of M1 phenotypic markers, after pretreatment with anandamide. This effect was not sensitive to CB1 or GPR18/GPR55 antagonism. Administration of CB2 antagonist partially abolished the effects of anandamide on microglia. Interestingly, administration of a GPR18/GPR55 antagonist by itself suppressed NO release. In summary, we showed that the endocannabinoid system plays a crucial role in the management of neuroinflammation by dampening the activation of an M1 phenotype. This effect was primarily controlled by the CB2 receptor, although functional cross talk with GPR18/GPR55 may occur.

  2. EURRECA—Framework for Aligning Micronutrient Recommendations

    NARCIS (Netherlands)

    Veer, van 't P.; Grammatikaki, E.; Matthys, C.; Raats, M.M.; Contor, L.

    2013-01-01

    There is currently no standard approach for deriving micronutrient recommendations, and large variations exist across Europe, causing confusion among consumers, food producers, and policy makers. More aligned information could influence dietary behaviors and potentially lead to a healthier

  3. Cannabinoid CB1/CB2receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia.

    Science.gov (United States)

    Scherma, Maria; Satta, Valentina; Collu, Roberto; Boi, Maria Francesca; Usai, Paolo; Fratta, Walter; Fadda, Paola

    2017-08-01

    Anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug-related therapy of this disease and this leads to high relapse rate. Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients. The activity-based anorexia (ABA) rodent model mimics the severe body weight loss and increased physical activity, as well as the neuroendocrine disturbances (i.e. hypoleptinaemia and hypercortisolaemia) in AN. This study investigated whether cannabinoid agonists can effectively modify anorexic-like behaviours and neuroendocrine changes in rats subjected to a repeated ABA regime that mimics the human condition in which patients repeatedly undergo a recovery and illness cycle. Our data show that subchronic treatment with both the natural CB 1 /CB 2 receptor agonist Δ 9 -tetrahydrocannabinol and the synthetic CB 1 /CB 2 receptor agonist CP-55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioural effects were accompanied by an increase in leptin signalling and a decrease in plasma levels of corticosterone. Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance. © 2017 The British Pharmacological Society.

  4. Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling.

    Science.gov (United States)

    Moreno, Estefanía; Andradas, Clara; Medrano, Mireia; Caffarel, María M; Pérez-Gómez, Eduardo; Blasco-Benito, Sandra; Gómez-Cañas, María; Pazos, M Ruth; Irving, Andrew J; Lluís, Carme; Canela, Enric I; Fernández-Ruiz, Javier; Guzmán, Manuel; McCormick, Peter J; Sánchez, Cristina

    2014-08-08

    The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1 show modestly enhanced alcohol preference and consumption.

    Directory of Open Access Journals (Sweden)

    David J Marcus

    Full Text Available We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6% but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg, morphine (10 mg/kg, and cocaine (10 mg/kg, demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.

  6. Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production.

    Science.gov (United States)

    Shmist, Yelena A; Goncharov, Igor; Eichler, Maor; Shneyvays, Vladimir; Isaac, Ahuva; Vogel, Zvi; Shainberg, Asher

    2006-02-01

    Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular system during stress conditions, but the defence mechanism is still unclear. The present study was designed to investigate the central (CB1) and the peripheral (CB2) cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia. Pre-treatment of cardiomyocytes that were grown in vitro with 0.1 - 10 microM THC for 24 h prevented hypoxia-induced lactate dehydrogenase (LDH) leakage and preserved the morphological distribution of alpha-sarcomeric actin. The antagonist for the CB2 (10 microM), but not CB1 receptor antagonist (10 microM) abolished the protective effect of THC. In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors. Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined. It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors. L-NAME (NOS inhibitor, 100 microM) prevented the cardioprotection provided by THC. Taken together, our findings suggest that THC protects cardiac cells against hypoxia via CB2 receptor activation by induction of NO production. An NO mechanism occurs also in the classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions.

  7. Extraterrestrial Amino Acids Identified in Metal-Rich CH and CB Carbonaceous Chondrites from Antarctica

    Science.gov (United States)

    Burton, Aaron S.; Elsila, Jamie E.; Hein, Jason E.; Glavin, Daniel P.; Dworkin, Jason P.

    2013-01-01

    Carbonaceous chondrites contain numerous indigenous organic compounds and could have been an important source of prebiotic compounds required for the origin of life on Earth or elsewhere. Extraterrestrial amino acids have been reported in five of the eight groups of carbonaceous chondrites and are most abundant in CI, CM, and CR chondritesbut are also present in the more thermally altered CV and CO chondrites. We report the abundance, distribution, and enantiomeric and isotopic compositions of simple primary amino acids in six metal-rich CH and CB carbonaceous chondrites that have not previously been investigated for amino acids: Allan Hills (ALH) 85085 (CH3), Pecora Escarpment(PCA) 91467 (CH3), Patuxent Range (PAT) 91546 (CH3), MacAlpine Hills (MAC) 02675(CBb), Miller Range (MIL) 05082 (CB), and Miller Range (MIL) 07411 (CB). Amino acid abundances and carbon isotopic values were obtained by using both liquid chromatography time-of-flight mass spectrometry and fluorescence, and gas chromatography isotope ratiomass spectrometry. The (delta D, delta C-13, delta N-15) ratios of multiple amino acids fall outside of the terrestrial range and support their extraterrestrial origin. Extracts of CH chondrites were found to be particularly rich in amino acids (1316 parts per million, ppm) while CB chondrite extracts had much lower abundances (0.22 ppm). The amino acid distributions of the CH and CB chondrites were distinct from the distributions observed in type 2 and 3 CM and CR chondrites and contained elevated levels of beta-, gamma-, and delta-amino acids compared to the corresponding alpha-amino acids, providing evidence that multiple amino acid formation mechanisms were important in CH and CB chondrites.

  8. Remarkably Divergent Regions Punctuate the Genome Assembly of the Caenorhabditis elegans Hawaiian Strain CB4856.

    Science.gov (United States)

    Thompson, Owen A; Snoek, L Basten; Nijveen, Harm; Sterken, Mark G; Volkers, Rita J M; Brenchley, Rachel; Van't Hof, Arjen; Bevers, Roel P J; Cossins, Andrew R; Yanai, Itai; Hajnal, Alex; Schmid, Tobias; Perkins, Jaryn D; Spencer, David; Kruglyak, Leonid; Andersen, Erik C; Moerman, Donald G; Hillier, LaDeana W; Kammenga, Jan E; Waterston, Robert H

    2015-07-01

    The Hawaiian strain (CB4856) of Caenorhabditis elegans is one of the most divergent from the canonical laboratory strain N2 and has been widely used in developmental, population, and evolutionary studies. To enhance the utility of the strain, we have generated a draft sequence of the CB4856 genome, exploiting a variety of resources and strategies. When compared against the N2 reference, the CB4856 genome has 327,050 single nucleotide variants (SNVs) and 79,529 insertion-deletion events that result in a total of 3.3 Mb of N2 sequence missing from CB4856 and 1.4 Mb of sequence present in CB4856 but not present in N2. As previously reported, the density of SNVs varies along the chromosomes, with the arms of chromosomes showing greater average variation than the centers. In addition, we find 61 regions totaling 2.8 Mb, distributed across all six chromosomes, which have a greatly elevated SNV density, ranging from 2 to 16% SNVs. A survey of other wild isolates show that the two alternative haplotypes for each region are widely distributed, suggesting they have been maintained by balancing selection over long evolutionary times. These divergent regions contain an abundance of genes from large rapidly evolving families encoding F-box, MATH, BATH, seven-transmembrane G-coupled receptors, and nuclear hormone receptors, suggesting that they provide selective advantages in natural environments. The draft sequence makes available a comprehensive catalog of sequence differences between the CB4856 and N2 strains that will facilitate the molecular dissection of their phenotypic differences. Our work also emphasizes the importance of going beyond simple alignment of reads to a reference genome when assessing differences between genomes. Copyright © 2015 by the Genetics Society of America.

  9. Artificial Intelligence in Prediction of Secondary Protein Structure Using CB513 Database

    Science.gov (United States)

    Avdagic, Zikrija; Purisevic, Elvir; Omanovic, Samir; Coralic, Zlatan

    2009-01-01

    In this paper we describe CB513 a non-redundant dataset, suitable for development of algorithms for prediction of secondary protein structure. A program was made in Borland Delphi for transforming data from our dataset to make it suitable for learning of neural network for prediction of secondary protein structure implemented in MATLAB Neural-Network Toolbox. Learning (training and testing) of neural network is researched with different sizes of windows, different number of neurons in the hidden layer and different number of training epochs, while using dataset CB513. PMID:21347158

  10. Artificial Intelligence in Prediction of Secondary Protein Structure Using CB513 Database.

    Science.gov (United States)

    Avdagic, Zikrija; Purisevic, Elvir; Omanovic, Samir; Coralic, Zlatan

    2009-03-01

    In this paper we describe CB513 a non-redundant dataset, suitable for development of algorithms for prediction of secondary protein structure. A program was made in Borland Delphi for transforming data from our dataset to make it suitable for learning of neural network for prediction of secondary protein structure implemented in MATLAB Neural-Network Toolbox. Learning (training and testing) of neural network is researched with different sizes of windows, different number of neurons in the hidden layer and different number of training epochs, while using dataset CB513.

  11. Characterization of structurally novel G protein biased CB1 agonists: Implications for drug development.

    Science.gov (United States)

    Ford, Benjamin M; Franks, Lirit N; Tai, Sherrica; Fantegrossi, William E; Stahl, Edward L; Berquist, Michael D; Cabanlong, Christian V; Wilson, Catheryn D; Penthala, Narsimha R; Crooks, Peter A; Prather, Paul L

    2017-11-01

    The human cannabinoid subtype 1 receptor (hCB 1 R) is highly expressed in the CNS and serves as a therapeutic target for endogenous ligands as well as plant-derived and synthetic cannabinoids. Unfortunately, acute use of hCB 1 R agonists produces unwanted psychotropic effects and chronic administration results in development of tolerance and dependence, limiting the potential clinical use of these ligands. Studies in β-arrestin knockout mice suggest that interaction of certain GPCRs, including μ-, δ-, κ-opioid and hCB 1 Rs, with β-arrestins might be responsible for several adverse effects produced by agonists acting at these receptors. Indeed, agonists that bias opioid receptor activation toward G-protein, relative to β-arrestin signaling, produce less severe adverse effects. These observations indicate that therapeutic utility of agonists acting at hCB 1 Rs might be improved by development of G-protein biased hCB 1 R agonists. Our laboratory recently reported a novel class of indole quinulidinone (IQD) compounds that bind cannabinoid receptors with relatively high affinity and act with varying efficacy. The purpose of this study was to determine whether agonists in this novel cannabinoid class exhibit ligand bias at hCB 1 receptors. Our studies found that a novel IQD-derived hCB 1 receptor agonist PNR-4-20 elicits robust G protein-dependent signaling, with transduction ratios similar to the non-biased hCB 1 R agonist CP-55,940. In marked contrast to CP-55,940, PNR-4-20 produces little to no β-arrestin 2 recruitment. Quantitative calculation of bias factors indicates that PNR-4-20 exhibits from 5.4-fold to 29.5-fold bias for G protein, relative to β-arrestin 2 signaling (when compared to G protein activation or inhibition of forskolin-stimulated cAMP accumulation, respectively). Importantly, as expected due to reduced β-arrestin 2 recruitment, chronic exposure of cells to PNR-4-20 results in significantly less desensitization and down-regulation of hCB 1

  12. The Universal Recommender

    OpenAIRE

    Kunegis, Jérôme; Said, Alan; Umbrath, Winfried

    2009-01-01

    We describe the Universal Recommender, a recommender system for semantic datasets that generalizes domain-specific recommenders such as content-based, collaborative, social, bibliographic, lexicographic, hybrid and other recommenders. In contrast to existing recommender systems, the Universal Recommender applies to any dataset that allows a semantic representation. We describe the scalable three-stage architecture of the Universal Recommender and its application to Internet Protocol Televisio...

  13. 47 CFR 95.412 - (CB Rule 12) What communications may be transmitted?

    Science.gov (United States)

    2010-10-01

    ... activities in connection with official tests or drills conducted by, or actual emergencies announced by, the civil defense agency with authority over the area in which your station is located. (b) You may use your CB station to transmit a tone signal only when the signal is used to make contact or to continue...

  14. Draft Genome Sequence of Synechococcus sp. Strain CB0101, Isolated From the Chesapeake Bay Estuary.

    Science.gov (United States)

    Marsan, David; Wommack, K Eric; Ravel, Jacques; Chen, Feng

    2014-01-09

    Here, we report the draft genome sequence of the estuarine Synechococcus sp. strain CB0101. The genomics information of this strain will facilitate the study of the poorly understood Synechococcus subcluster 5.2 and how this strain is capable of thriving in a dynamic estuarine system, such as the Chesapeake Bay.

  15. Highly Branched Polyisobutylene by Radical Polymerization under Li[CB11(CH3)(12)] Catalysis

    Czech Academy of Sciences Publication Activity Database

    Volkis, V.; Shoemaker, R. K.; Michl, Josef

    2012-01-01

    Roč. 45, č. 23 (2012), s. 9250-9257 ISSN 0024-9297 Institutional research plan: CEZ:AV0Z40550506 Keywords : Dodecamethylcarba-closo-dodecaborate(-)Anion * polymerization * LiCB11(CH3)(12) Subject RIV: CC - Organic Chemistry Impact factor: 5.521, year: 2012

  16. Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954.

    Science.gov (United States)

    Fu, Yue; Buryanovskyy, Leonid; Zhang, Zhongtao

    2005-10-14

    CB1954 is a cancer pro-drug that can be activated through reduction by Escherichia coli nitro-reductases and quinone reductases. Human quinone reductase 2 is very efficient in the activation of CB1954, approximately 3000 times more efficient than human QR1 in terms of k(cat)/K(m). We have solved the three-dimensional structure of QR2 in complex with CB1954 to a nominal resolution of 1.5A. The complex structure indicates the essentiality of the two nitro groups: one nitro group forms hydrogen bonds with the side-chain of Asn161 of QR2 to hold the other nitro group in position for the reduction. We further conclude that residue 161, an Asn in QR2 and a His in QR1, is critical in differentiating the substrate specificities of these two enzymes. Mutation of Asn161 to His161 in QR2 resulted in the total loss of the enzymatic activity towards activation of CB1954, whereas the rates of reduction towards menadione are not altered.

  17. Determination of |$V_{ub}$|/|$V_{cb}$| with DELPHI at LEP

    CERN Document Server

    Abreu, P.; Adye, T.; Adzic, P.; Albrecht, Z.; Alderweireld, T.; Alekseev, G.D.; Alemany, R.; Allmendinger, T.; Allport, P.P.; Almehed, S.; Amaldi, U.; Amapane, N.; Amato, S.; Anassontzis, E.G.; Andersson, P.; Andreazza, A.; Andringa, S.; Antilogus, P.; Apel, W.D.; Arnoud, Y.; Asman, B.; Augustin, J.E.; Augustinus, A.; Baillon, P.; Bambade, P.; Barao, F.; Barbiellini, G.; Barbier, R.; Bardin, D.Yu.; Barker, G.J.; Baroncelli, A.; Battaglia, M.; Baubillier, M.; Becks, K.H.; Begalli, M.; Behrmann, A.; Beilliere, P.; Belokopytov, Yu.; Belous, K.; Benekos, N.C.; Benvenuti, A.C.; Berat, C.; Berggren, M.; Bertrand, D.; Besancon, M.; Bigi, M.; Bilenky, Mikhail S.; Bizouard, M.A.; Bloch, D.; Blom, H.M.; Bonesini, M.; Boonekamp, M.; Booth, P.S.L.; Borgland, A.W.; Borisov, G.; Bosio, C.; Botner, O.; Boudinov, E.; Bouquet, B.; Bourdarios, C.; Bowcock, T.J.V.; Boyko, I.; Bozovic, I.; Bozzo, M.; Bracko, M.; Branchini, P.; Brenner, R.A.; Bruckman, P.; Brunet, J.M.; Bugge, L.; Buran, T.; Buschbeck, B.; Buschmann, P.; Cabrera, S.; Caccia, M.; Calvi, M.; Camporesi, T.; Canale, V.; Carena, F.; Carroll, L.; Caso, C.; Castillo Gimenez, M.V.; Cattai, A.; Cavallo, F.R.; Chabaud, V.; Chapkin, M.; Charpentier, P.; Checchia, P.; Chelkov, G.A.; Chierici, R.; Shlyapnikov, P.; Chochula, P.; Chorowicz, V.; Chudoba, J.; Cieslik, K.; Collins, P.; Contri, R.; Cortina, E.; Cosme, G.; Cossutti, F.; Crawley, H.B.; Crennell, D.; Crepe-Renaudin, Sabine; Crosetti, G.; Cuevas Maestro, J.; Czellar, S.; Davenport, M.; Da Silva, W.; Della Ricca, G.; Delpierre, P.A.; Demaria, N.; De Angelis, A.; de Boer, W.; De Clercq, C.; De Lotto, B.; De Min, A.; De Paula, L.; Dijkstra, H.; Di Ciaccio, L.; Dolbeau, J.; Doroba, K.; Dracos, M.; Drees, J.; Dris, M.; Duperrin, A.; Durand, J.D.; Eigen, G.; Ekelof, T.; Ekspong, G.; Ellert, M.; Elsing, M.; Engel, J.P.; Espirito Santo, M.C.; Fanourakis, G.; Fassouliotis, D.; Fayot, J.; Feindt, M.; Ferrer, A.; Ferrer-Ribas, E.; Ferro, F.; Fichet, S.; Firestone, A.; Flagmeyer, U.; Foeth, H.; Fokitis, E.; Fontanelli, F.; Franek, B.; Frodesen, A.G.; Fruhwirth, R.; Fulda-Quenzer, F.; Fuster, J.; Galloni, A.; Gamba, D.; Gamblin, S.; Gandelman, M.; Garcia, C.; Gaspar, C.; Gaspar, M.; Gasparini, U.; Gavillet, P.; Gazis, Evangelos; Gele, D.; Ghodbane, N.; Gil Botella, Ines; Glege, F.; Gokieli, R.; Golob, B.; Gomez-Ceballos, G.; Goncalves, P.; Gonzalez Caballero, I.; Gopal, G.; Gorn, L.; Guz, Yu.; Gracco, V.; Grahl, J.; Graziani, E.; Gris, P.; Grosdidier, G.; Grzelak, K.; Guy, J.; Haag, C.; Hahn, F.; Hahn, S.; Haider, S.; Hallgren, A.; Hamacher, K.; Hansen, J.; Harris, F.J.; Hedberg, V.; Heising, S.; Hernandez, J.J.; Herquet, P.; Herr, H.; Hessing, T.L.; Heuser, J.M.; Higon, E.; Holmgren, S.O.; Holt, P.J.; Hoorelbeke, S.; Houlden, M.; Hrubec, J.; Huber, M.; Huet, K.; Hughes, G.J.; Hultqvist, K.; Jackson, John Neil; Jacobsson, R.; Jalocha, P.; Janik, R.; Jarlskog, C.; Jarlskog, G.; Jarry, P.; Jean-Marie, B.; Jeans, D.; Johansson, Erik Karl; Jonsson, P.; Joram, C.; Juillot, P.; Jungermann, L.; Kapusta, Frederic; Karafasoulis, K.; Katsanevas, S.; Katsoufis, E.C.; Keranen, R.; Kernel, G.; Kersevan, B.P.; Khomenko, B.A.; Khovanskii, N.N.; Kiiskinen, A.; King, B.J.; Kinvig, A.; Kjaer, N.J.; Klapp, O.; Klein, Hansjorg; Kluit, P.; Kokkinias, P.; Kostyukhin, V.; Kourkoumelis, C.; Kuznetsov, O.; Krammer, M.; Kriznic, E.; Krumshtein, Z.; Kubinec, P.; Kurowska, J.; Kurvinen, K.; Lamsa, J.W.; Lane, D.W.; Lapin, V.; Laugier, J.P.; Lauhakangas, R.; Leder, G.; Ledroit, Fabienne; Lefebure, V.; Leinonen, L.; Leisos, A.; Leitner, R.; Lenzen, G.; Lepeltier, V.; Lesiak, T.; Lethuillier, M.; Libby, J.; Liebig, W.; Liko, D.; Lipniacka, A.; Lippi, I.; Loerstad, B.; Loken, J.G.; Lopes, J.H.; Lopez, J.M.; Lopez-Fernandez, R.; Loukas, D.; Lutz, P.; Lyons, L.; MacNaughton, J.; Mahon, J.R.; Maio, A.; Malek, A.; Malmgren, T.G.M.; Maltezos, S.; Malychev, V.; Mandl, F.; Marco, J.; Marco, R.; Marechal, B.; Margoni, M.; Marin, J.C.; Mariotti, C.; Markou, A.; Martinez-Rivero, C.; Martinez-Vidal, F.; Marti i Garcia, S.; Masik, J.; Mastroyiannopoulos, N.; Matorras, F.; Matteuzzi, C.; Matthiae, G.; Mazzucato, F.; Mazzucato, M.; McCubbin, M.; McKay, R.; McNulty, R.; McPherson, G.; Meroni, C.; Meyer, W.T.; Migliore, E.; Mirabito, L.; Mitaroff, W.A.; Mjornmark, U.; Moa, T.; Moch, M.; Moller, Rasmus; Monig, Klaus; Monge, M.R.; Moraes, D.; Moreau, X.; Morettini, P.; Morton, G.; Muller, U.; Muenich, K.; Mulders, M.; Mulet-Marquis, C.; Muresan, R.; Murray, W.J.; Muryn, B.; Myatt, G.; Myklebust, T.; Naraghi, F.; Nassiakou, M.; Navarria, F.L.; Navas, Sergio; Nawrocki, K.; Negri, P.; Neufeld, N.; Nicolaidou, R.; Nielsen, B.S.; Niezurawski, P.; Nikolenko, M.; Nomokonov, V.; Nygren, A.; Obraztsov, V.F.; Olshevskii, A.G.; Onofre, A.; Orava, R.; Orazi, G.; Osterberg, K.; Ouraou, A.; Paganoni, M.; Paiano, S.; Pain, R.; Paiva, R.; Palacios, J.; Palka, H.; Papadopoulou, T.D.; Papageorgiou, K.; Pape, L.; Parkes, C.; Parodi, F.; Parzefall, U.; Passeri, A.; Passon, O.; Pavel, T.; Pegoraro, M.; Peralta, L.; Pernicka, M.; Perrotta, A.; Petridou, C.; Petrolini, A.; Phillips, H.T.; Pierre, F.; Pimenta, M.; Piotto, E.; Podobnik, T.; Pol, M.E.; Polok, G.; Poropat, P.; Pozdnyakov, V.; Privitera, P.; Pukhaeva, N.; Pullia, A.; Radojicic, D.; Ragazzi, S.; Rahmani, H.; Rames, J.; Ratoff, P.N.; Read, Alexander L.; Rebecchi, P.; Redaelli, Nicola Giuseppe; Regler, M.; Rehn, J.; Reid, D.; Reinhardt, R.; Renton, P.B.; Resvanis, L.K.; Richard, F.; Ridky, J.; Rinaudo, G.; Ripp-Baudot, Isabelle; Rohne, O.; Romero, A.; Ronchese, P.; Rosenberg, E.I.; Rosinsky, P.; Roudeau, P.; Rovelli, T.; Royon, C.; Ruhlmann-Kleider, V.; Ruiz, A.; Saarikko, H.; Sacquin, Y.; Sadovskii, A.; Sajot, G.; Salt, J.; Sampsonidis, D.; Sannino, M.; Schwemling, P.; Schwering, B.; Schwickerath, U.; Scuri, Fabrizio; Seager, P.; Sedykh, Yu.; Segar, A.M.; Seibert, N.; Sekulin, R.; Shellard, R.C.; Siebel, M.; Simard, L.; Simonetto, F.; Sisakian, A.N.; Smadja, G.; Smirnova, O.; Smith, G.R.; Sokolov, A.; Solovianov, O.; Sopczak, A.; Sosnowski, R.; Spassoff, Tz.; Spiriti, E.; Squarcia, S.; Stanescu, C.; Stanic, S.; Stanitzki, M.; Stevenson, K.; Stocchi, A.; Strauss, J.; Strub, R.; Stugu, B.; Szczekowski, M.; Szeptycka, M.; Tabarelli de Fatis, T.; Taffard, A.; Tegenfeldt, F.; Terranova, F.; Thomas, J.; Timmermans, Jan; Tinti, N.; Tkatchev, L.G.; Tobin, M.; Todorova, S.; Tomaradze, A.G.; Tome, B.; Tonazzo, A.; Tortora, L.; Tortosa, P.; Transtromer, G.; Treille, D.; Tristram, G.; Trochimczuk, M.; Troncon, C.; Turluer, M.L.; Tyapkin, I.A.; Tzamarias, S.; Ullaland, O.; Uvarov, V.; Valenti, G.; Vallazza, E.; Vander Velde, C.; Van Dam, Piet; Vanden Boeck, W.; Van Doninck, Walter; Van Eldik, J.; Van Lysebetten, A.; van Remortel, N.; Van Vulpen, I.; Vegni, G.; Ventura, L.; Venus, W.; Verbeure, F.; Verdier, P.; Verlato, M.; Vertogradov, L.S.; Verzi, V.; Vilanova, D.; Vitale, L.; Vlasov, E.; Vodopianov, A.S.; Voulgaris, G.; Vrba, V.; Wahlen, H.; Walck, C.; Washbrook, A.J.; Weiser, C.; Wicke, D.; Wickens, J.H.; Wilkinson, G.R.; Winter, M.; Witek, M.; Wolf, G.; Yi, J.; Yushchenko, O.; Zaitsev, A.; Zalewska, A.; Zalewski, P.; Zavrtanik, D.; Zevgolatakos, E.; Zimine, N.I.; Zintchenko, A.; Zoller, P.; Zucchelli, G.C.; Zumerle, G.

    2000-01-01

    The ratio of the CKM quark-mixing matrix elements |V_{ub}|/|V_{cb}|has been measured using B hadron semileptonic decays.The analysis is based on a novel technique, recently proposed by theoreticians, that uses the reconstructed mass M_X ofthe secondary hadronic system produced in association with an identified lepton.Since B rightarrow X_u \\ell \\bar \

  18. 47 CFR 95.410 - (CB Rule 10) How much power may I use?

    Science.gov (United States)

    2010-10-01

    ... Rule 10) How much power may I use? (a) Your CB station transmitter power output must not exceed the following values under any conditions: AM (A3)—4 watts (carrier power) SSB—12 watts (peak envelope power) (b.... (c) Use of a transmitter which has carrier or peak envelope power in excess of that authorized voids...

  19. Dielectric relaxation studies in 5CB nematic liquid crystal at 9 GHz ...

    Indian Academy of Sciences (India)

    Resonance width, shift in resonance frequency, relaxation time and activation energy of 5CB nematic liquid crystal are measured using microwave cavity technique under the influence of an external magnetic field at 9 GHz and at different temperatures. The dielectric response in liquid crystal at different temperatures and ...

  20. Dielectric relaxation studies in 5CB nematic liquid crystal at 9 GHz ...

    Indian Academy of Sciences (India)

    Abstract. Resonance width, shift in resonance frequency, relaxation time and activation energy of. 5CB nematic liquid crystal are measured using microwave cavity technique under the influence of an external magnetic field at 9 GHz and at different temperatures. The dielectric response in liquid crystal at different ...

  1. CB1 - cannabinoid receptor antagonist effects on cortisol in cannabis-dependent men.

    Science.gov (United States)

    Goodwin, Robert S; Baumann, Michael H; Gorelick, David A; Schwilke, Eugene; Schwope, David M; Darwin, William D; Kelly, Deanna L; Schroeder, Jennifer R; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

    2012-01-01

    The endocannabinoid system modulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effect of cannabinoid type 1 (CB1) receptor antagonism following chronic CB1 receptor stimulation in humans is unknown. To evaluate effects of the CB1 receptor antagonist rimonabant on the HPA axis in cannabis-dependent individuals. Fourteen daily cannabis smokers received increasingly frequent 20 mg oral Δ9-tetrahydrocannabinol (THC) doses (60-120 mg/day) over 8 days to standardize cannabis tolerance. Concurrent with the last THC dose, double-blind placebo or rimonabant (20 or 40 mg) was administered. Cannabinoid, rimonabant, and cortisol plasma concentrations were measured 1.5 hours prior to rimonabant administration and 2.0, 5.5, and 12.5 hours post-dose. Ten participants completed before premature study termination due to rimonabant's withdrawal from development. Five participants received 20 mg, three received 40 mg, and two placebo. There was a significant positive association between rimonabant concentration and change in cortisol concentration from baseline (r = .53, p 40 mg might elicit cortisol changes, confirming a role for CB1 receptors in modulating the HPA axis in humans.

  2. Engineered regulation of lysozyme by the SH3-CB1 binding interaction.

    Science.gov (United States)

    Pham, Elizabeth; Truong, Kevin

    2012-06-01

    The ability to design proteins with desired properties by using protein structural information will allow us to create high-value therapeutic and diagnostic products. Using the protein structures of lambda lysozyme and the SH3 domain of human Crk, we designed a synthetic protein switch that controls the activity of lysozyme by sterically hindering its active cleft through the binding of SH3 to its CB1 peptide-binding partner. First, several fusion protein designs with lysozyme and CB1 were modeled to determine the one with greatest steric effect in the presence of SH3. Next, the selected fusion protein was created and tested in vitro. In the absence of SH3, the lysozyme-CB1 fusion protein functioned normally. In the presence of SH3, the lysozyme activity was inhibited and with the addition of excess CB1 peptides to compete for SH3 binding, the lysozyme activity was restored. Lastly, this structure-based strategy can be used to engineer synthetic regulation by peptide-domain-binding interfaces into a variety of proteins.

  3. Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

    Energy Technology Data Exchange (ETDEWEB)

    Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey, E-mail: carey.pope@okstate.edu

    2011-11-15

    Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

  4. Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

    International Nuclear Information System (INIS)

    Sarafian, Theodore; Montes, Cindy; Harui, Airi; Beedanagari, Sudheer R.; Kiertscher, Sylvia; Stripecke, Renata; Hossepian, Derik; Kitchen, Christina; Kern, Rita; Belperio, John; Roth, Michael D.

    2008-01-01

    Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that Δ 9 -tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 [Sarafian, T. A., Kouyoumjian, S., Khoshaghideh, F., Tashkin, D. P., and Roth, M. D. (2003). Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284, L298-306; Sarafian, T., Habib, N., Mao, J. T., Tsu, I. H., Yamamoto, M. L., Hsu, E., Tashkin, D. P., and Roth, M. D. (2005). Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett 158, 95-107]. The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10% serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p m ) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher Ψ m than did control cells. Since both Ψ m and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of IκB-α and JNK was regulated in a CB2R- and THC

  5. Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer progression and predicts patient survival

    Science.gov (United States)

    Martínez-Martínez, Esther; Gómez, Irene; Martín, Paloma; Sánchez, Antonio; Román, Laura; Tejerina, Eva; Bonilla, Félix; Merino, Antonio García; de Herreros, Antonio García; Provencio, Mariano; García, Jose M.

    2015-01-01

    Many studies have demonstrated that the endocannabinoid system (ECS) is altered in different tumor types, including colon cancer. However, little is known about the role of the ECS in tumor progression. Here we report the correlation between CB2 expression and pathological data in a series of 175 colorectal cancer patients, as well as the response of the HT29 colon cancer-derived cell line upon CB2 activation. CB2 mRNA was detected in 28.6% of samples tested. It was more frequent in N+ patients and predicts disease free survival and overall survival in colon cancer. In positive samples, CB2 was expressed with great intensity in tumor epithelial cells and correlated with tumor growth. Treatment of HT29 with CB2 agonist revealed membrane loss of E-cadherin and SNAIL1 overexpression. A direct correlation between CB2 and SNAIL1 expression was also found in human tumors. CB2 receptor expression is a poor prognostic marker for colon cancer and the activation of this receptor, with non-apoptotic doses of agonists, could be collaborating with disease progression. These results raise the question whether the activation of CB2 should be considered as anti-tumoral therapy. PMID:25859556

  6. Surface grafting of epoxy polymer on CB to improve its dispersion to be the filler of resistive ink for PCB

    Directory of Open Access Journals (Sweden)

    Guoyun Zhou

    Full Text Available In this paper, we report a novel and efficient method of promoting the dispersing uniformity of carbon black (CB in epoxy polymer substrate of PCB (printed circuit board by chemical grafting. The reported method shows the promising capability in the application of advanced printable resistor ink. By taking advantage of the functionalized CB surfaces, the grafting reaction of epoxy polymer on CB particles was investigated with Fourier-transform infrared spectroscopy (FT-IR, transmission electron microscope (TEM and thermo gravimetric analysis (TGA. FT-IR spectra evidenced the polymerization of epoxy resin with coupling agent and TEM investigation directly confirmed the polymerization occurred on CB surface. The polymerization occurred on the limited part of the CB surfaces to form a network-structure polymer to reside on the CB particles and hence greatly improved CB dispersion in ink as evidenced in ink-droplet spreading verification on glass and PCB resin substrates. On the other hand, the polymer grafting has limited effect on the increasing of the as-cured ink filled with the grafted CBs. Finally, the cross-section observation also confirmed the dispersion improvement and sheet resistance uniformity due to epoxy polymer grafting on PCB substrate, indicating the prospective candidate as embedded resistors for PCB. Keywords: Grafting, Carbon black (CB, Epoxy polymer, Resistive ink, Printed circuit board (PCB

  7. Cb-LIKE – Cumulonimbus Likelihood: Thunderstorm forecasting with fuzzy logic

    Directory of Open Access Journals (Sweden)

    Martin Köhler

    2017-04-01

    Full Text Available Aviation is heavily affected by thunderstorms. Approaching storm cells with accompanying effects such as heavy rain, hail or downdrafts cause delays and flight cancellations. Consequently, the airlines and airport operators have to bear high additional costs, with reduced flight safety and passenger comfort. A reliable thunderstorm forecast up to several hours ahead saves time for decision makers, as the airport authorities, air traffic control, airline operation centre, and the crew in the cockpit for an appropriate and harmonised reaction, and for mitigating the consequences of a thunderstorm. The algorithm Cb-LIKE (Cumulonimbus-Likelihood has been developed to provide such forecasts. Cb-LIKE is an automated system which designates areas with possible thunderstorm development by using output of the COSMO-DE numerical weather prediction model operated by the German Meteorological Service (DWD. The algorithm includes a newly developed “Best-Member-Selection” which allows the automatic selection of that member of a COSMO-DE ensemble that matches best with the current weather situation. An innovative fuzzy logic system combines selected model data and calculates a thunderstorm indicator for each grid point of the model domain for the following six hours in one hour intervals. Comparing thunderstorm observations by radar with Cb-LIKE forecasts in the summer period of 2012 verifies the algorithm and demonstrates the system's performance. The verification shows that Cb-LIKE gives better thunderstorm forecasts in comparison with the COSMO-DE radar reflectivity. Moreover, the verification results allow transformation of the Cb-LIKE indicator field into a field of thunderstorm probability. These probability forecasts are valid for thunderstorms within a certain spatial distance from the observed storms.

  8. Stabilization of functional recombinant cannabinoid receptor CB(2 in detergent micelles and lipid bilayers.

    Directory of Open Access Journals (Sweden)

    Krishna Vukoti

    Full Text Available Elucidation of the molecular mechanisms of activation of G protein-coupled receptors (GPCRs is among the most challenging tasks for modern membrane biology. For studies by high resolution analytical methods, these integral membrane receptors have to be expressed in large quantities, solubilized from cell membranes and purified in detergent micelles, which may result in a severe destabilization and a loss of function. Here, we report insights into differential effects of detergents, lipids and cannabinoid ligands on stability of the recombinant cannabinoid receptor CB(2, and provide guidelines for preparation and handling of the fully functional receptor suitable for a wide array of downstream applications. While we previously described the expression in Escherichia coli, purification and liposome-reconstitution of multi-milligram quantities of CB(2, here we report an efficient stabilization of the recombinant receptor in micelles - crucial for functional and structural characterization. The effects of detergents, lipids and specific ligands on structural stability of CB(2 were assessed by studying activation of G proteins by the purified receptor reconstituted into liposomes. Functional structure of the ligand binding pocket of the receptor was confirmed by binding of (2H-labeled ligand measured by solid-state NMR. We demonstrate that a concerted action of an anionic cholesterol derivative, cholesteryl hemisuccinate (CHS and high affinity cannabinoid ligands CP-55,940 or SR-144,528 are required for efficient stabilization of the functional fold of CB(2 in dodecyl maltoside (DDM/CHAPS detergent solutions. Similar to CHS, the negatively charged phospholipids with the serine headgroup (PS exerted significant stabilizing effects in micelles while uncharged phospholipids were not effective. The purified CB(2 reconstituted into lipid bilayers retained functionality for up to several weeks enabling high resolution structural studies of this GPCR at

  9. Stabilization of Functional Recombinant Cannabinoid Receptor CB2 in Detergent Micelles and Lipid Bilayers

    Science.gov (United States)

    Vukoti, Krishna; Kimura, Tomohiro; Macke, Laura; Gawrisch, Klaus; Yeliseev, Alexei

    2012-01-01

    Elucidation of the molecular mechanisms of activation of G protein-coupled receptors (GPCRs) is among the most challenging tasks for modern membrane biology. For studies by high resolution analytical methods, these integral membrane receptors have to be expressed in large quantities, solubilized from cell membranes and purified in detergent micelles, which may result in a severe destabilization and a loss of function. Here, we report insights into differential effects of detergents, lipids and cannabinoid ligands on stability of the recombinant cannabinoid receptor CB2, and provide guidelines for preparation and handling of the fully functional receptor suitable for a wide array of downstream applications. While we previously described the expression in Escherichia coli, purification and liposome-reconstitution of multi-milligram quantities of CB2, here we report an efficient stabilization of the recombinant receptor in micelles - crucial for functional and structural characterization. The effects of detergents, lipids and specific ligands on structural stability of CB2 were assessed by studying activation of G proteins by the purified receptor reconstituted into liposomes. Functional structure of the ligand binding pocket of the receptor was confirmed by binding of 2H-labeled ligand measured by solid-state NMR. We demonstrate that a concerted action of an anionic cholesterol derivative, cholesteryl hemisuccinate (CHS) and high affinity cannabinoid ligands CP-55,940 or SR-144,528 are required for efficient stabilization of the functional fold of CB2 in dodecyl maltoside (DDM)/CHAPS detergent solutions. Similar to CHS, the negatively charged phospholipids with the serine headgroup (PS) exerted significant stabilizing effects in micelles while uncharged phospholipids were not effective. The purified CB2 reconstituted into lipid bilayers retained functionality for up to several weeks enabling high resolution structural studies of this GPCR at physiologically relevant

  10. Elevated Brain Cannabinoid CB1 Receptor Availability in Posttraumatic Stress Disorder: A Positron Emission Tomography Study

    Science.gov (United States)

    Neumeister, Alexander; Normandin, Marc D.; Pietrzak, Robert H.; Piomelli, Daniele; Zheng, Ming-Qiang; Gujarro-Anton, Ana; Potenza, Marc N.; Bailey, Christopher R.; Lin, Shu-fei; Najafzadeh, Soheila; Ropchan, Jim; Henry, Shannan; Corsi-Travali, Stefani; Carson, Richard E.; Huang, Yiyun

    2013-01-01

    Endocannabinoids and their attending cannabinoid type 1 receptor (CB1) have been implicated in animal models of posttraumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [11C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma controls [TC]) and those without such histories (healthy controls [HC]). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance (MR) imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [11C]OMAR, which measures volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [11C]OMAR VT values (F(2,53)=7.96, p=.001; 19.5% and 14.5% higher, respectively) which were most pronounced in women (F(1,53)=5.52, p=.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively—OMAR VT, anandamide, and cortisol—correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder. PMID:23670490

  11. Energetic policy, society and environment

    International Nuclear Information System (INIS)

    Oliveira, George Gurgel de

    1999-01-01

    This paper sets out connections between emerging philosophies of economic development grouped together within the concept of sustainability, and future energy policies. The article discusses Brazilian energy policy recommendations formulated on the basis of present energy supply and demand levels

  12. Searching for transiting circumbinary planets in CoRoT and ground-based data using CB-BLS

    Science.gov (United States)

    Ofir, A.; Deeg, H. J.; Lacy, C. H. S.

    2009-10-01

    Aims: Already from the initial discoveries of extrasolar planets it was apparent that their population and environments are far more diverse than initially postulated. Discovering circumbinary (CB) planets will have many implications, and in this context it will again substantially diversify the environments that produce and sustain planets. We search for transiting CB planets around eclipsing binaries (EBs). Methods: CB-BLS is a recently-introduced algorithm for the detection of transiting CB planets around EBs. We describe progress in search sensitivity, generality and capability of CB-BLS, and detection tests of CB-BLS on simulated data. We also describe an analytical approach for the determination of CB-BLS detection limits, and a method for the correct detrending of intrinsically-variable stars. Results: We present some blind-tests with simulated planets injected to real CoRoT data. The presented upgrades to CB-BLS allowed it to detect all the blind tests successfully, and these detections were in line with the detection limits analysis. We also correctly detrend bright eclipsing binaries from observations by the TrES planet search, and present some of the first results of applying CB-BLS to multiple real light curves from a wide-field survey. Conclusions: CB-BLS is now mature enough for its application to real data, and the presented processing scheme will serve as the template for our future applications of CB-BLS to data from wide-field surveys such as CoRoT. Being able to put constraints even on non-detection will help to determine the correct frequency of CB planets, contributing to the understanding of planet formation in general. Still, searching for transiting CB planets is still a learning experience, similarly to the state of transiting planets around single stars only a few years ago. The recent rapid progress in this front, coupled with the exquisite quality of space-based photometry, allows to realistically expect that if transiting CB planets

  13. Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease

    Science.gov (United States)

    Sagredo, Onintza; González, Sara; Aroyo, Ilia; Pazos, María Ruth; Benito, Cristina; Lastres-Becker, Isabel; Romero, Juan P.; Tolón, Rosa M.; Mechoulam, Raphael; Brouillet, Emmanuel; Romero, Julián; Fernández-Ruiz, Javier

    2009-01-01

    Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington’s disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed by using the selective CB2 receptor antagonist, SR144528, and by the observation that mice deficient in CB2 receptor were more sensitive to malonate than wild-type animals. CB2 receptors are scarce in the striatum in healthy conditions but they are markedly up-regulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB2 receptors in cells labelled with the marker of reactive microglia OX-42, and also in cells labelled with GFAP (a marker of astrocytes). We further showed that the activation of CB2 receptors significantly reduced the levels of tumor necrosis factor-α (TNF-α) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be up-regulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-α. Altogether our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD. PMID:19115380

  14. The European Federation of Organisations for Medical Physics Policy Statement No 14, The role of the Medical Physicist in the management of safety within the magnetic resonance imaging environment, EFOMP recommendations

    NARCIS (Netherlands)

    Hand, J.; Bosmans, H.; Caruana, C.; Keevil, S.; Norris, David Gordon; Padovani, R.; Speck, O.

    2013-01-01

    This European Federation of Organisations for Medical Physics (EFOMP) Policy Statement outlines the way in which a Safety Management System can be developed for MRI units. The Policy Statement can help eliminate or at least minimize accidents or incidents in the magnetic resonance environment and is

  15. Ozone and NOx chemistry in the eastern US: evaluation of CMAQ/CB05 with satellite (OMI data

    Directory of Open Access Journals (Sweden)

    T. P. Canty

    2015-10-01

    Full Text Available Regulatory air quality models, such as the Community Multiscale Air Quality model (CMAQ, are used by federal and state agencies to guide policy decisions that determine how to best achieve adherence with National Ambient Air Quality Standards for surface ozone. We use observations of ozone and its important precursor NO2 to test the representation of the photochemistry and emission of ozone precursors within CMAQ. Observations of tropospheric column NO2 from the Ozone Monitoring Instrument (OMI, retrieved by two independent groups, show that the model overestimates urban NO2 and underestimates rural NO2 under all conditions examined for July and August 2011 in the US Northeast. The overestimate of the urban to rural ratio of tropospheric column NO2 for this baseline run of CMAQ (CB05 mechanism, mobile NOx emissions from the National Emissions Inventory; isoprene emissions from MEGAN v2.04 suggests this model may underestimate the importance of interstate transport of NOx. This CMAQ simulation leads to a considerable overestimate of the 2-month average of 8 h daily maximum surface ozone in the US Northeast, as well as an overestimate of 8 h ozone at AQS sites during days when the state of Maryland experienced NAAQS exceedances. We have implemented three changes within CMAQ motivated by OMI NO2 as well as aircraft observations obtained in July 2011 during the NASA DISCOVER-AQ campaign: (a the modeled lifetime of organic nitrates within CB05 has been reduced by a factor of 10, (b emissions of NOx from mobile sources has been reduced by a factor of 2, and (c isoprene emissions have been reduced by using MEGAN v2.10 rather than v2.04. Compared to the baseline simulation, the CMAQ run using all three of these changes leads to considerably better simulation of column NO2 in both urban and rural areas, better agreement with the 2-month average of daily 8 h maximum ozone in the US Northeast, fewer number of false positives of an ozone exceedance

  16. The Cannabinoid Delta-9-tetrahydrocannabinol Mediates Inhibition of Macrophage Chemotaxis to RANTES/CCL5 through the CB2 Receptor

    Science.gov (United States)

    Raborn, Erinn S.; Marciano-Cabral, Francine; Buckley, Nancy E.; Martin, Billy R.; Cabral, Guy A.

    2009-01-01

    The chemotactic response of murine peritoneal macrophages to RANTES/CCL5 was inhibited significantly following pretreatment with delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana. Significant inhibition of this chemokine directed migratory response was obtained also when the full cannabinoid agonist CP55940 was used. The CB2 receptor-selective ligand O-2137 exerted a robust inhibition of chemotaxis while the CB1 receptor-selective ligand ACEA had a minimal effect. The THC-mediated inhibition was reversed by the CB2 receptor-specific antagonist SR144528 but not by the CB1 receptor-specific antagonist SR141716A. In addition, THC treatment had a minimal effect on the chemotactic response of peritoneal macrophages from CB2 knockout mice. Collectively, these results suggest that cannabinoids act through the CB2 receptor to trans-deactivate migratory responsiveness to RANTES/CCL5. Furthermore, the results suggest that the CB2 receptor may be a constituent element of a network of G protein-coupled receptor signal transductional systems, inclusive of chemokine receptors, that act coordinately to modulate macrophage migration. PMID:18247131

  17. Cannabinoid Receptor CB2 Is Involved in Tetrahydrocannabinol-Induced Anti-Inflammation against Lipopolysaccharide in MG-63 Cells

    Directory of Open Access Journals (Sweden)

    Lei Yang

    2015-01-01

    Full Text Available Cannabinoid Δ9-tetrahydrocannabinol (THC is effective in treating osteoarthritis (OA, and the mechanism, however, is still elusive. Activation of cannabinoid receptor CB2 reduces inflammation; whether the activation CB2 is involved in THC-induced therapeutic action for OA is still unknown. Cofilin-1 is a cytoskeleton protein, participating in the inflammation of OA. In this study, MG-63 cells, an osteosarcoma cell-line, were exposed to lipopolysaccharide (LPS to mimic the inflammation of OA. We hypothesized that the activation of CB2 is involved in THC-induced anti-inflammation in the MG-63 cells exposed to LPS, and the anti-inflammation is mediated by cofilin-1. We found that THC suppressed the release of proinflammatory factors, including tumor necrosis factor α (TNF-α, interleukin- (IL- 1β, IL-6, and IL-8, decreased nuclear factor-κB (NF-κB expression, and inhibited the upregulation of cofilin-1 protein in the LPS-stimulated MG-63 cells. However, administration of CB2 receptor antagonist or the CB2-siRNA, not CB1 antagonist AM251, partially abolished the THC-induced anti-inflammatory effects above. In addition, overexpression of cofilin-1 significantly reversed the THC-induced anti-inflammatory effects in MG-63 cells. These results suggested that CB2 is involved in the THC-induced anti-inflammation in LPS-stimulated MG-63 cells, and the anti-inflammation may be mediated by cofilin-1.

  18. Surface grafting of epoxy polymer on CB to improve its dispersion to be the filler of resistive ink for PCB

    Science.gov (United States)

    Zhou, Guoyun; Xu, Xiaolan; Wang, Shouxu; He, Xuemei; He, Wei; Su, Xinhong; Wong, Ching Ping

    In this paper, we report a novel and efficient method of promoting the dispersing uniformity of carbon black (CB) in epoxy polymer substrate of PCB (printed circuit board) by chemical grafting. The reported method shows the promising capability in the application of advanced printable resistor ink. By taking advantage of the functionalized CB surfaces, the grafting reaction of epoxy polymer on CB particles was investigated with Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscope (TEM) and thermo gravimetric analysis (TGA). FT-IR spectra evidenced the polymerization of epoxy resin with coupling agent and TEM investigation directly confirmed the polymerization occurred on CB surface. The polymerization occurred on the limited part of the CB surfaces to form a network-structure polymer to reside on the CB particles and hence greatly improved CB dispersion in ink as evidenced in ink-droplet spreading verification on glass and PCB resin substrates. On the other hand, the polymer grafting has limited effect on the increasing of the as-cured ink filled with the grafted CBs. Finally, the cross-section observation also confirmed the dispersion improvement and sheet resistance uniformity due to epoxy polymer grafting on PCB substrate, indicating the prospective candidate as embedded resistors for PCB.

  19. CB 1/2 dual agonists with 3-carbamoyl 2-pyridone derivatives as antipruritics: reduction of CNS side effects by introducing polar functional groups.

    Science.gov (United States)

    Odan, Masahide; Ishizuka, Natsuki; Hiramatsu, Yoshiharu; Inagaki, Masanao; Hashizume, Hiroshi; Fujii, Yasuhiko; Mitsumori, Susumu; Morioka, Yasuhide; Soga, Masahiko; Deguchi, Masashi; Yasui, Kiyoshi; Arimura, Akinori

    2012-04-15

    Our lead compound 1 showed high affinity for both CB1 and CB2 receptors, suggesting the possibility of inducing psychoactive side effects through the CB1 receptor in the brain. To solve this issue, polar functional groups were introduced at the 3-position of the pyridone core of compound 1 to find CB1/2 dual agonists such as 17 and 20 which did not show any CNS side effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins

    OpenAIRE

    Lauckner, Jane E.; Hille, Bertil; Mackie, Ken

    2005-01-01

    Central nervous system responses to cannabis are primarily mediated by CB1 receptors, which couple preferentially to Gi/o G proteins. Here, we used calcium photometry to monitor the effect of CB1 activation on intracellular calcium concentration. Perfusion with 5 μM CB1 aminoalkylindole agonist, WIN55,212-2 (WIN), increased intracellular calcium by several hundred nanomolar in human embryonic kidney 293 cells stably expressing CB1 and in cultured hippocampal neurons. The increase was blocked ...

  1. Cannabinoid CB1 Receptor Activation Mediates the Opposing Effects of Amphetamine on Impulsive Action and Impulsive Choice

    Science.gov (United States)

    Wiskerke, Joost; Stoop, Nicky; Schetters, Dustin; Schoffelmeer, Anton N. M.; Pattij, Tommy

    2011-01-01

    It is well known that acute challenges with psychostimulants such as amphetamine affect impulsive behavior. We here studied the pharmacology underlying the effects of amphetamine in two rat models of impulsivity, the 5-choice serial reaction time task (5-CSRTT) and the delayed reward task (DRT), providing measures of inhibitory control, an aspect of impulsive action, and impulsive choice, respectively. We focused on the role of cannabinoid CB1 receptor activation in amphetamine-induced impulsivity as there is evidence that acute challenges with psychostimulants activate the endogenous cannabinoid system, and CB1 receptor activity modulates impulsivity in both rodents and humans. Results showed that pretreatment with either the CB1 receptor antagonist/inverse agonist SR141716A or the neutral CB1 receptor antagonist O-2050 dose-dependently improved baseline inhibitory control in the 5-CSRTT. Moreover, both compounds similarly attenuated amphetamine-induced inhibitory control deficits, suggesting that CB1 receptor activation by endogenously released cannabinoids mediates this aspect of impulsive action. Direct CB1 receptor activation by Δ9-Tetrahydrocannabinol (Δ9-THC) did, however, not affect inhibitory control. Although neither SR141716A nor O-2050 affected baseline impulsive choice in the DRT, both ligands completely prevented amphetamine-induced reductions in impulsive decision making, indicating that CB1 receptor activity may decrease this form of impulsivity. Indeed, acute Δ9-THC was found to reduce impulsive choice in a CB1 receptor-dependent way. Together, these results indicate an important, though complex role for cannabinoid CB1 receptor activity in the regulation of impulsive action and impulsive choice as well as the opposite effects amphetamine has on both forms of impulsive behavior. PMID:22016780

  2. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint.

    Science.gov (United States)

    Burston, James J; Sagar, Devi Rani; Shao, Pin; Bai, Mingfeng; King, Emma; Brailsford, Louis; Turner, Jenna M; Hathway, Gareth J; Bennett, Andrew J; Walsh, David A; Kendall, David A; Lichtman, Aron; Chapman, Victoria

    2013-01-01

    Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic OA

  3. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint.

    Directory of Open Access Journals (Sweden)

    James J Burston

    Full Text Available Osteoarthritis (OA of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2 receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation

  4. Magnesium isotope evidence for single stage formation of CB chondrules by colliding planetesimals

    DEFF Research Database (Denmark)

    Olsen, Mia Bjørg Stolberg; Schiller, Martin; Krot, Alexander N.

    2013-01-01

    Chondrules are igneous spherical objects preserved in chondritic meteorites and believed to have formed during transient heating events in the solar protoplanetary disk. Chondrules present in the metal-rich CB chondrites show unusual chemical and petrologic features not observed in other chondrite...... groups, implying a markedly distinct formation mechanism. Here, we report high-precision Mg-isotope data for 10 skeletal olivine chondrules from the Hammadah al Hamra 237 (HH237) chondrite to probe the formation history of CB chondrules. The Al/Mg ratios of individual chondrules are positively correlated...... to their stable Mg-isotope composition (μMg), indicating that the correlated variability was imparted by a volatility-controlled process (evaporation/condensation). The mass-independent Mg composition (μMg*) of chondrules is consistent with single stage formation from an initially homogeneous magnesium reservoir...

  5. Timing of the formation and migration of giant planets as constrained by CB chondrites.

    Science.gov (United States)

    Johnson, Brandon C; Walsh, Kevin J; Minton, David A; Krot, Alexander N; Levison, Harold F

    2016-12-01

    The presence, formation, and migration of giant planets fundamentally shape planetary systems. However, the timing of the formation and migration of giant planets in our solar system remains largely unconstrained. Simulating planetary accretion, we find that giant planet migration produces a relatively short-lived spike in impact velocities lasting ~0.5 My. These high-impact velocities are required to vaporize a significant fraction of Fe,Ni metal and silicates and produce the CB (Bencubbin-like) metal-rich carbonaceous chondrites, a unique class of meteorites that were created in an impact vapor-melt plume ~5 My after the first solar system solids. This indicates that the region where the CB chondrites formed was dynamically excited at this early time by the direct interference of the giant planets. Furthermore, this suggests that the formation of the giant planet cores was protracted and the solar nebula persisted until ~5 My.

  6. Design, synthesis and evaluation of fluorescent CB2 cannabinoid receptor ligands

    OpenAIRE

    Holt, Christopher James

    2009-01-01

    Cannabis has been used as a medicinal and natural product for thousands of years. Whether it has been used to make rope or paper, or been used to treat pain or depression, cannabis has always had a place in human civilisation. With the isolation of the psychoactive compounds responsible for cannabis’ effects, the discovery of two human cannabinoid receptors and an expanding knowledge of the therapeutic uses of cannabis, interest in the development of novel cannabinoids grew. The CB2 cann...

  7. Memory Encoding in Hippocampal Ensembles is Negatively Influenced by Cannabinoid CB1 Receptors

    OpenAIRE

    Hampson, Robert E.; Sweatt, Andrew J.; Goonawardena, Anushka V.; Song, Dong; Chan, Rosa H.M.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

    2011-01-01

    It has been previously demonstrated that the detrimental effect on performance of a delayed nonmatch to sample (DNMS) memory task by exogenously administered cannabinoid CB1 receptor agonist, WIN 55212-2 (WIN), is reversed by the receptor antagonist Rimonabant (Rmbt). In addition Rmbt administered alone elevates DNMS performance, presumably via suppression of negative modulation by released endocannabinoids during normal task performance. Other investigations have shown that Rmbt enhances enc...

  8. Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation.

    Science.gov (United States)

    Stanley, Christopher P; Hind, William H; Tufarelli, Cristina; O'Sullivan, Saoirse E

    2015-09-01

    The protective effects of cannabidiol (CBD) have been widely shown in preclinical models and have translated into medicines for the treatment of multiple sclerosis and epilepsy. However, the direct vascular effects of CBD in humans are unknown. Using wire myography, the vascular effects of CBD were assessed in human mesenteric arteries, and the mechanisms of action probed pharmacologically. CBD-induced intracellular signalling was characterized using human aortic endothelial cells (HAECs). CBD caused acute, non-recoverable vasorelaxation of human mesenteric arteries with an Rmax of ∼ 40%. This was inhibited by cannabinoid receptor 1 (CB1) receptor antagonists, desensitization of transient receptor potential channels using capsaicin, removal of the endothelium, and inhibition of potassium efflux. There was no role for cannabinoid receptor-2 (CB2) receptor, peroxisome proliferator activated receptor (PPAR)γ, the novel endothelial cannabinoid receptor (CBe), or cyclooxygenase. CBD-induced vasorelaxation was blunted in males, and in patients with type 2 diabetes or hypercholesterolemia. In HAECs, CBD significantly reduced phosphorylated JNK, NFκB, p70s6 K and STAT5, and significantly increased phosphorylated CREB, ERK1/2, and Akt levels. CBD also increased phosphorylated eNOS (ser1177), which was correlated with increased levels of ERK1/2 and Akt levels. CB1 receptor antagonism prevented the increase in eNOS phosphorylation. This study shows, for the first time, that CBD causes vasorelaxation of human mesenteric arteries via activation of CB1 and TRP channels, and is endothelium- and nitric oxide-dependent. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  9. Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward-associated memory in rats.

    Science.gov (United States)

    Fang, Qin; Li, Fang-Qiong; Li, Yan-Qin; Xue, Yan-Xue; He, Ying-Ying; Liu, Jian-Feng; Lu, Lin; Wang, Ji-Shi

    2011-10-01

    Exposure to cues previously associated with drug intake leads to relapse by activating previously acquired memories. Based on previous findings, in which cannabinoid CB(1) receptors were found to be critically involved in specific aspects of learning and memory, we investigated the role of CB(1) receptors in nicotine reward memory using a rat conditioned place preference (CPP) model. In Experiment 1, rats were trained for CPP with alternating injections of nicotine (0.5mg/kg, s.c.) and saline to acquire the nicotine-conditioned memory. To examine the effects of rimonabant on the reconsolidation of nicotine reward memory, rats were administered rimonabant (0, 0.3, and 3.0mg/kg, i.p.) immediately after reexposure to the drug-paired context. In Experiment 2, rats were trained for CPP similarly to Experiment 1. To examine the effects of rimonabant on the reinstatement of nicotine reward memory, rimonabant (0, 0.3, and 3.0mg/kg, i.p.) was administered before the test of nicotine-induced CPP reinstatement. In Experiment 3, to evaluate whether rimonabant itself produces a reward memory, rats were trained for CPP with alternating injections of different doses of rimonabant (0, 0.3, and 3.0mg/kg) and saline. Rimonabant at a dose of 3.0mg/kg significantly disrupted the reconsolidation of nicotine memory and significantly blocked the reinstatement of nicotine-induced CPP. However, rimonabant itself did not produce CPP. These findings provide clear evidence that CB(1) receptors play a role in nicotine reward memory, suggesting that CB(1) receptor antagonists may be a potential target for managing nicotine addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Effects of caffeine on striatal neurotransmission: focus on cannabinoid CB1 receptors.

    Science.gov (United States)

    Rossi, Silvia; De Chiara, Valentina; Musella, Alessandra; Mataluni, Giorgia; Sacchetti, Lucia; Siracusano, Alberto; Bernardi, Giorgio; Usiello, Alessandro; Centonze, Diego

    2010-04-01

    Caffeine is the most commonly self-administered psychoactive substance worldwide. At usual doses, the effects of caffeine on vigilance, attention, mood and arousal largely depend on the modulation of central adenosine receptors. The present review article describes the action of caffeine within the striatum, to provide a possible molecular mechanism at the basis of the psychomotor and reinforcing properties of this pharmacological agent. The striatum is in fact a subcortical area involved in sensorimotor, cognitive, and emotional processes, and recent experimental findings showed that chronic caffeine consumption enhances the sensitivity of striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors. The endocannabinoid system is involved in the psychoactive effects of many compounds, and adenosine A2A receptors (the main receptor target of caffeine) elicit a permissive effect towards CB1 receptors, thus suggesting that A2A-CB1 receptor interaction plays a major role in the generation and maintenance of caffeine reinforcing behavior. Aim of this review is to describe the effects of caffeine on striatal neurotransmission with special reference to the modulation of the endocannabinoid system.

  11. Memory Encoding in Hippocampal Ensembles is Negatively Influenced by Cannabinoid CB1 Receptors

    Science.gov (United States)

    Hampson, Robert E.; Sweatt, Andrew J.; Goonawardena, Anushka V.; Song, Dong; Chan, Rosa H.M.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

    2011-01-01

    It has been previously demonstrated that the detrimental effect on performance of a delayed nonmatch to sample (DNMS) memory task by exogenously administered cannabinoid CB1 receptor agonist, WIN 55212-2 (WIN), is reversed by the receptor antagonist Rimonabant (Rmbt). In addition Rmbt administered alone elevates DNMS performance, presumably via suppression of negative modulation by released endocannabinoids during normal task performance. Other investigations have shown that Rmbt enhances encoding of DNMS task-relevant information on a trial-by-trial, delay-dependent basis. In the current study these reciprocal pharmacological actions were fully characterized by long-term, chronic intrahippocampal infusion of both agents (WIN and Rmbt) in successive 2 week intervals. Such long-term exposure allowed extraction and confirmation of task-related firing patterns where Rmbt reversed effects of CB1 agonists. This information was then utilized to artificially impose the facilitatory effects of Rmbt and reverse the effects of WIN on DNMS performance, by delivering multichannel electrical stimulation in the same firing patterns to the same hippocampal regions. Direct comparison of normal and WIN injected animals, in which Rmbt injections and ensemble firing facilitated performance, verified reversal of the modulation of hippocampal memory processes by CB1 receptor agonists, including released endocannabinoids. PMID:21558844

  12. Staffing Policy for Solving the Information Security

    Directory of Open Access Journals (Sweden)

    A. I. Tolstoy

    2012-06-01

    Full Text Available Determining staffing policy implementation of information security tasks is given. The basic requirements that must be taken into account when developing policies are defined. The policy framework is determined and recommendations for the design of such policies are formulated. Requirements for the implementation of the policy are defined.

  13. Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Müller Anke

    2010-06-01

    Full Text Available Abstract Background Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC and Cannabidiol (CBD fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1 deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail. Results THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX-expressing intermediate progenitor cells. Conclusion CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.

  14. Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle.

    Directory of Open Access Journals (Sweden)

    Sergio Arrabal

    Full Text Available Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD, a flavoprotein component (E3 of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1, 14 days on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle--regulated by both diet and CB1 receptor activity--through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI, triosephosphate isomerase (TPI, enolase (Eno3, lactate dehydrogenase (LDHa, glyoxalase-1 (Glo1 and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD.

  15. Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle.

    Science.gov (United States)

    Arrabal, Sergio; Lucena, Miguel Angel; Canduela, Miren Josune; Ramos-Uriarte, Almudena; Rivera, Patricia; Serrano, Antonia; Pavón, Francisco Javier; Decara, Juan; Vargas, Antonio; Baixeras, Elena; Martín-Rufián, Mercedes; Márquez, Javier; Fernández-Llébrez, Pedro; De Roos, Baukje; Grandes, Pedro; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1), 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle--regulated by both diet and CB1 receptor activity--through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD.

  16. 12 CFR 368.4 - Recommendations to customers.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Recommendations to customers. 368.4 Section 368... POLICY GOVERNMENT SECURITIES SALES PRACTICES § 368.4 Recommendations to customers. In recommending to a customer the purchase, sale or exchange of a government security, a bank that is a government securities...

  17. Controlled downregulation of the cannabinoid CB1 receptor provides a promising approach for the treatment of obesity and obesity-derived type 2 diabetes.

    Science.gov (United States)

    Lu, Dai; Dopart, Rachel; Kendall, Debra A

    2016-01-01

    Increased activity of the endocannabinoid system has emerged as a pathogenic factor in visceral obesity, which is a risk factor for type 2 diabetes mellitus (T2DM). The endocannabinoid system is composed of at least two Gprotein-coupled receptors (GPCRs), the cannabinoid receptor type 1 (CB1), and the cannabinoid receptor type 2 (CB2). Downregulation of CB1 activity in rodents and humans has proven efficacious to reduce food intake, abdominal adiposity, fasting glucose levels, and cardiometabolic risk factors. Unfortunately, downregulation of CB1 activity by universally active CB1 inverse agonists has been found to elicit psychiatric side effects, which led to the termination of using globally active CB1 inverse agonists to treat diet-induced obesity. Interestingly, preclinical studies have shown that downregulation of CB1 activity by CB1 neutral antagonists or peripherally restricted CB1 inverse agonists provided similar anorectic effects and metabolic benefits without psychiatric side effects seen in globally active CB1 inverse agonists. Furthermore, downregulation of CB1 activity may ease endoplasmic reticulum and mitochondrial stress which are contributors to obesity-induced insulin resistance and type 2 diabetes. This suggests new approaches for cannabinoid-based therapy in the management of obesity and obesity-related metabolic disorders including type 2 diabetes.

  18. Comparison of Corner-Butt 45 (Cb-45 and Corner-Lap (Cl joints in friction stir welding

    Directory of Open Access Journals (Sweden)

    Setiawan Widia

    2018-01-01

    Full Text Available The 10 mm thick Aluminum 6061 plates have been corner joined using varied design and those were 45° Corner Butt and Corner Lap Joints (CB-45 & CL. Friction tool was hardened EMS 45. True experimental method was used with independent parameters is feed rate which varied at 10 mm/min, 15 mm/min and 30 mm/min respectively. Other parameter such as rotating speed was kept constant. Experiment results show that, CB-45 yields better properties than CL. The tensile strength of CB-45 reaches 163.7 MPa for 10 mm/min feed rate. Whilst CL produces joint with tensile strength equal 120 MPa for equal parameters. Microstructure observation showed that CB-45 produces fine and homogenous appearance of MgO compared to CL. This phenomenon is caused by the pin of CB-45 joint which fully penetrates the nugget zone which is not found in CL design. This microstructure in turn promotes higher tensile strength of CB-45.

  19. Is compulsive buying related to materialism, depression or temperament? Findings from a sample of treatment-seeking patients with CB.

    Science.gov (United States)

    Müller, Astrid; Claes, Laurence; Georgiadou, Ekaterini; Möllenkamp, Maike; Voth, Eva M; Faber, Ron J; Mitchell, James E; de Zwaan, Martina

    2014-04-30

    The aim of the present work was to examine the influence of reactive and regulatory temperament on compulsive buying (CB) in a sample of 102 patients (79 women, 23 men) with clinical CB. All participants answered the Compulsive Buying Scale (CBS), the Behavioral Inhibition System and Behavioral Activation System Scales (BIS/BAS), and the Effortful Control subscale (ATQ-EC) of the Adult Temperament Questionnaire-Short Form. Based on previous studies demonstrating that depression and materialism are linked with CB, in addition, the Patient Health Questionnaire depression scale (PHQ-9) and the Materialistic Values Scale (MVS) were administered. CBS scores were significantly correlated with the MVS, PHQ-9, and BAS scores. The findings of the hierarchical regression analysis, however, indicated that in the present sample of treatment-seeking patients the only significant association was found between CB and depression. The results highlight the prominent role of depression in CB. There is a need for longitudinal studies in order to answer the question whether depression is the cause or the consequence of CB. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Trust for intelligent recommendation

    CERN Document Server

    Bhuiyan, Touhid

    2013-01-01

    Recommender systems are one of the recent inventions to deal with the ever-growing information overload in relation to the selection of goods and services in a global economy. Collaborative Filtering (CF) is one of the most popular techniques in recommender systems. The CF recommends items to a target user based on the preferences of a set of similar users known as the neighbors, generated from a database made up of the preferences of past users. In the absence of these ratings, trust between the users could be used to choose the neighbor for recommendation making. Better recommendations can b

  1. [Policy recommendations based on SWOT analysis for agricultural industrialization of traditional Chinese medicinal materials--a case study of uncariae ramulus cum uncis from Jianhe county in Guizhou province].

    Science.gov (United States)

    Hu, Yong; Huo, Ke-Yi; Xiang, Hua

    2013-09-01

    This thesis reviews the historical background of agricultural industrialization, and analyzes the major theories of agricultural industrialization. It also utilizes SWOT analysis method to discuss the industrialization of traditional Chinese medicinal materials in Jianhe county, and finally it puts forward the recommendations for its further development.

  2. Leveraging position bias to improve peer recommendation.

    Directory of Open Access Journals (Sweden)

    Kristina Lerman

    Full Text Available With the advent of social media and peer production, the amount of new online content has grown dramatically. To identify interesting items in the vast stream of new content, providers must rely on peer recommendation to aggregate opinions of their many users. Due to human cognitive biases, the presentation order strongly affects how people allocate attention to the available content. Moreover, we can manipulate attention through the presentation order of items to change the way peer recommendation works. We experimentally evaluate this effect using Amazon Mechanical Turk. We find that different policies for ordering content can steer user attention so as to improve the outcomes of peer recommendation.

  3. Perspectives of CB1 Antagonist in Treatment of Obesity: Experience of RIO-Asia

    Directory of Open Access Journals (Sweden)

    Changyu Pan

    2011-01-01

    Full Text Available Rimonabant, a selective cannabinoid-1 (CB1 receptor antagonist, has been shown to reduce weight and enhance improvements in cardiometabolic risk parameters in Western populations. This study assessed these effects of rimonabant in Asian population. A total of 643 patients (BMI 25 kg/m2 or greater without diabetes from China, Republic of Korea, and Taiwan were prescribed a hypocaloric diet (600 kcal/day deficit and randomized to rimonabant 20 mg (n=318 or placebo (n=325 for 9months. The primary efficacy variable was weight change from baseline after 9 months of treatment. Results showed that rimonabant group lost more weight than placebo, (LSM ± SEM of −4.7 ± 0.3 kg vs. −1.7 ± 0.3 kg, P<.0001. The 5% and 10% responders were 2 or 3 folds more in the rimonabant group (53.0% vs. 20.0% and 21.5% vs. 5.7%, resp. (P<.0001. Rimonabant also significantly increased HDL-cholesterol, decreased triglycerides and waist circumference,by 7.1%, 10.6%, and 2.8 cm, respectively (P<.0001. This study confirmed the comparable efficacy and safety profile of rimonabant in Asian population to Caucasians. Owing to the recent suspension of all the CB1 antagonists off the pharmaceutical market for weight reduction in Europe and USA, a perspective in drug discovery for intervening peripheral CB1 receptor in the management of obesity is discussed.

  4. Pb-Pb dating of individual chondrules from the CBa chondrite Gujba

    DEFF Research Database (Denmark)

    Bollard, Jean Francois André; Connelly, James; Bizzarro, Martin

    2015-01-01

    -stage impact origin. Here, we report high-precision internal isochrons for four individual chondrules of the Gujba chondrite to probe the formation history of CB chondrites and evaluate the concordancy of relevant short-lived radionuclide chronometers. All four chondrules define a brief formation interval......-behaved Pb-Pb systematics of all four chondrules, a precise formation age and the concordancy of the Mn-Cr, Hf-W, and I-Xe short-lived radionuclide relative chronometers, we propose that Gujba may serve as a suitable time anchor for these systems....

  5. Cb-LIKE - Thunderstorm forecasts up to six hours with fuzzy logic

    Science.gov (United States)

    Köhler, Martin; Tafferner, Arnold

    2016-04-01

    Thunderstorms with their accompanying effects like heavy rain, hail, or downdrafts cause delays and flight cancellations and therefore high additional cost for airlines and airport operators. A reliable thunderstorm forecast up to several hours could provide more time for decision makers in air traffic for an appropriate reaction on possible storm cells and initiation of adequate counteractions. To provide the required forecasts Cb-LIKE (Cumulonimbus-LIKElihood) has been developed at the DLR (Deutsches Zentrum für Luft- und Raumfahrt) Institute of Atmospheric Physics. The new algorithm is an automated system which designates areas with possible thunderstorm development by using model data of the COSMO-DE weather model, which is driven by the German Meteorological Service (DWD). A newly developed "Best-Member- Selection" method allows the automatic selection of that particular model run of a time-lagged COSMO- DE model ensemble, which matches best the current thunderstorm situation. Thereby the application of the best available data basis for the calculation of the thunderstorm forecasts by Cb-LIKE is ensured. Altogether there are four different modes for the selection of the best member. Four atmospheric parameters (CAPE, vertical wind velocity, radar reflectivity and cloud top temperature) of the model output are used within the algorithm. A newly developed fuzzy logic system enables the subsequent combination of the model parameters and the calculation of a thunderstorm indicator within a value range of 12 up to 88 for each grid point of the model domain for the following six hours in one hour intervals. The higher the indicator value the more the model parameters imply the development of thunderstorms. The quality of the Cb-LIKE thunderstorm forecasts was evaluated by a substantial verification using a neighborhood verification approach and multi-event contingency tables. The verification was performed for the whole summer period of 2012. On the basis of a

  6. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    McAlindon, T. E.; Driban, J. B.; Henrotin, Y.

    2015-01-01

    The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct......, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After...... and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials...

  7. Activation of type 1 cannabinoid receptor (CB1R promotes neurogenesis in murine subventricular zone cell cultures.

    Directory of Open Access Journals (Sweden)

    Sara Xapelli

    Full Text Available The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive, neurons and astrocytes. Stimulation of the CB1R by (R-(+-Methanandamide (R-m-AEA increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation, at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca(2+]i in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.

  8. Interactions of CB1 and mGlu5 receptor antagonists in food intake, anxiety and memory models in rats.

    Science.gov (United States)

    Varga, Balázs; Kassai, Ferenc; Gyertyán, István

    2012-12-01

    CB(1) receptor antagonists proved to be effective anti-obesity drugs, however, their depressive and anxiogenic effects became also evident. Finding solution to overcome these psychiatric side effects is still in focus of research. Based on the available clinical and preclinical results we hypothesized that the combination of CB(1) and mGlu(5) receptor antagonisms may result in a pharmacological intervention, where the anxiolytic mGlu(5) receptor inhibition may counteract the anxiogenic psychiatric side effects of CB(1) antagonism, while CB(1) antagonism may ameliorate the memory impairing effect of mGlu(5) receptor antagonism. Further, the two components will synergistically interact in blocking food-intake and reducing obesity. For testing the interaction of mGlu(5) and CB(1) receptor antagonism MTEP [3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pridine; SIB-1757, 6-methyl-2-(phenylazo)-3-pyridinol)] (mGlu(5) antagonist) and rimonabant [(5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide)hydrochloride] (CB(1) antagonist) were used. All experiments were carried out in rats. Effects of the compounds on anxiety were tested in two foot shock induced ultrasonic vocalization paradigms, appetite suppression was assessed in the food intake test, while memory effects were tested in a context conditioned ultrasonic vocalization setup. MTEP abolished the anxiogenic effect of rimonabant, while there was an additive cooperation in suppressing appetite. However, rimonabant did not ameliorate the memory impairing effect of MTEP. By combination of CB(1) and mGluR5 antagonism, anxiety related side effects might be attenuated, appetite suppression maintained, nevertheless, the possible emergence of unwanted memory impairments can overshadow its therapeutic success. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Policies and procedures related to testing for weak D phenotypes and administration of Rh immune globulin: results and recommendations related to supplemental questions in the Comprehensive Transfusion Medicine survey of the College of American Pathologists.

    Science.gov (United States)

    Sandler, S Gerald; Roseff, Susan D; Domen, Ronald E; Shaz, Beth; Gottschall, Jerome L

    2014-05-01

    Advances in RHD genotyping offer an opportunity to update policies and practices for testing weak D phenotypes and administration of Rh immune globulin to postpartum women. To repeat questions from a 1999 College of American Pathologists proficiency test survey, to evaluate current practices for testing for weak D and administration of Rh immune globulin, and to determine whether there is an opportunity to begin integrating RHD genotyping in laboratory practice. The College of American Pathologists Transfusion Medicine Resource Committee sent questions from the 1999 survey to laboratories that participated in the 2012 proficiency test survey. The results of the 2012 survey were compared with those from 1999. Results from published RHD genotyping studies were analyzed to determine if RHD genotyping could improve current policies and practices for serological Rh typing. More than 3100 survey participants responded to the 2012 questions. The most significant finding was a decrease in the number of transfusion services performing a serological weak D test on patients as a strategy to manage those with a weak D as Rh negative (from 58.2% to 19.8%, P policies and practices could improve the accuracy of Rh typing results, reduce unnecessary administration of Rh immune globulin in women with a weak D, and decrease transfusion of Rh-negative red blood cells in most recipients with a serological weak D phenotype.

  10. Mental Health and Mental Disorder Recommendation Programs.

    Science.gov (United States)

    Ruchiwit, Manyat

    2017-12-01

    The characteristic differences among the Greater Mekong Subregion (GMS) countries in terms of trade and investment, society and cultural values, medical information and technology, and the living and working environment have become major health problems in terms of mental disorders. The purpose of this article is to identify the gaps in those aspects, to propose mental health and mental disorder recommendation programs, and to recommend policies for policy makers and research investors. A comparative analysis and literature review of existing policy, including overviews of previous research were used to generate a synthesis of the existing knowledge of the mental health and mental disorder recommendation programs. The review results recommend mental health and mental disorder programs for policy makers, research investors, and stakeholders in order to strengthen the directions for implementing these programs in the future. The healthcare provision in each country will not be limited only to its citizens; the healthcare markets and target groups are likely to expand to the neighboring countries in the context of changes in domestic and international factors, which have both positive and negative impacts according to the political, economic, and social situations of the influencing countries.

  11. Trust and Recommendations

    Science.gov (United States)

    Victor, Patricia; de Cock, Martine; Cornelis, Chris

    Recommendation technologies and trust metrics constitute the two pillars of trust-enhanced recommender systems. We discuss and illustrate the basic trust concepts such as trust and distrust modeling, propagation and aggregation. These concepts are needed to fully grasp the rationale behind the trust-enhanced recommender techniques that are discussed in the central part of the chapter, which focuses on the application of trust metrics and their operators in recommender systems. We explain the benefits of using trust in recommender algorithms and give an overview of state-of-the-art approaches for trust-enhanced recommender systems. Furthermore, we explain the details of three well-known trust-based systems and provide a comparative analysis of their performance. We conclude with a discussion of some recent developments and open challenges, such as visualizing trust relationships in a recommender system, alleviating the cold start problem in a trust network of a recommender system, studying the effect of involving distrust in the recommendation process, and investigating the potential of other types of social relationships.

  12. Resummation of running coupling effects in semileptonic B meson decays and extraction of |V$_{cb}$|

    CERN Document Server

    Ball, Patricia; Braun, Vladimir M.; Ball, Patricia; Beneke, M; Braun, V M

    1995-01-01

    We present a determination of |V_{cb}| from semileptonic B decays that includes resummation of supposedly large perturbative corrections originating from the running of the strong coupling. We argue that the low value of the BLM scale found previously for inclusive decays is a manifestation of the renormalon divergence of the perturbative series starting already in third order. A reliable etermination of |V_{cb}| from inclusive decays is possible if one either uses a short distance b quark mass or eliminates all unphysical mass parameters in terms of measured observables, such that all infra-red contributions of order 1/m_b cancel explicitly. We find that using the \\overline{\\rm MS} running mass significantly reduces the perturbative coefficients already in low orders. The resummation of running coupling effects is numerically important and increases the decay rate by (20-40)\\%, when calculated with the same input parameters as without resummation. The scheme- and scale-dependence of the results is reduced. F...

  13. Research recommendations [Chapter 10

    Science.gov (United States)

    Daniel G. Neary; Alvin L. Medina; John N. Rinne

    2012-01-01

    This chapter contains a number of research recommendations that have developed from the 15 years of research on the UVR conducted by the Southwest Watershed Science Team, as well as from insights from key cooperators and contacts. It is meant to be our best insight as to where efforts should go now. Achieving these recommendations will depend on a number of factors,...

  14. Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.

    Science.gov (United States)

    Bhattacharyya, Sagnik; Egerton, Alice; Kim, Euitae; Rosso, Lula; Riano Barros, Daniela; Hammers, Alexander; Brammer, Michael; Turkheimer, Federico E; Howes, Oliver D; McGuire, Philip

    2017-11-03

    Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [ 11 C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors.

  15. Differences in spontaneously avoiding or approaching mice reflect differences in CB1-mediated signaling of dorsal striatal transmission.

    Directory of Open Access Journals (Sweden)

    Daniela Laricchiuta

    Full Text Available Approach or avoidance behaviors are accompanied by perceptual vigilance for, affective reactivity to and behavioral predisposition towards rewarding or punitive stimuli, respectively. We detected three subpopulations of C57BL/6J mice that responded with avoiding, balancing or approaching behaviors not induced by any experimental manipulation but spontaneously displayed in an approach/avoidance conflict task. Although the detailed neuronal mechanisms underlying the balancing between approach and avoidance are not fully clarified, there is growing evidence that endocannabinoid system (ECS plays a critical role in the control of these balancing actions. The sensitivity of dorsal striatal synapses to the activation of cannabinoid CB1 receptors was investigated in the subpopulations of spontaneously avoiding, balancing or approaching mice. Avoiding animals displayed decreased control of CB1 receptors on GABAergic striatal transmission and in parallel increase of behavioral inhibition. Conversely, approaching animals exhibited increased control of CB1 receptors and in parallel increase of explorative behavior. Balancing animals reacted with balanced responses between approach and avoidance patterns. Treating avoiding animals with URB597 (fatty acid amide hydrolase inhibitor or approaching animals with AM251 (CB1 receptor inverse agonist reverted their respective behavioral and electrophysiological patterns. Therefore, enhanced or reduced CB1-mediated control on dorsal striatal transmission represents the synaptic hallmark of the approach or avoidance behavior, respectively. Thus, the opposite spontaneous responses to conflicting stimuli are modulated by a different involvement of endocannabinoid signaling of dorsal striatal neurons in the range of temperamental traits related to individual differences.

  16. The Staphylococcal Toxins γ-Hemolysin AB and CB Differentially Target Phagocytes by Employing Specific Chemokine Receptors

    Science.gov (United States)

    Spaan, András N.; Vrieling, Manouk; Wallet, Pierre; Badiou, Cédric; Reyes-Robles, Tamara; Ohneck, Elizabeth A.; Benito, Yvonne; de Haas, Carla J.C.; Day, Christopher J.; Jennings, Michael P.; Lina, Gérard; Vandenesch, François; van Kessel, Kok P.M.; Torres, Victor J.; van Strijp, Jos A.G.; Henry, Thomas

    2014-01-01

    Evasion of the host phagocyte response by Staphylococcus aureus is crucial to successful infection with the pathogen. γ-Hemolysin AB and CB (HlgAB, HlgCB) are bicomponent pore-forming toxins present in almost all human S. aureus isolates. Cellular tropism and contribution of the toxins to S. aureus pathophysiology are poorly understood. Here, we identify the chemokine receptors CXCR1, CXCR2 and CCR2 as targets for HlgAB, and the complement receptors C5aR and C5L2 as targets for HlgCB. The receptor expression patterns allow the toxins to efficiently and differentially target phagocytic cells. Murine neutrophils are resistant to HlgAB and HlgCB. CCR2 is the sole murine receptor orthologue compatible with γ-Hemolysin. In a murine peritonitis model, HlgAB contributes to S. aureus bacteremia in a CCR2-dependent manner. HlgAB-mediated targeting of CCR2+ cells highlights the involvement of inflammatory macrophages during S. aureus infection. Functional quantification identifies HlgAB and HlgCB as major secreted staphylococcal leukocidins. PMID:25384670

  17. Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice.

    Science.gov (United States)

    Yu, Lu-lu; Wang, Xue-yi; Zhao, Mei; Liu, Yu; Li, Yan-qin; Li, Fang-qiong; Wang, Xiaoyi; Xue, Yan-xue; Lu, Lin

    2009-06-01

    Previous studies have shown that cannabinoid CB1 receptors play an important role in specific aspects of learning and memory, yet there has been no systematic study focusing on the involvement of cannabinoid CB1 receptors in methamphetamine-related reward memory. The purpose of this study was to examine whether rimonabant, a cannabinoid CB1 receptor antagonist, would disrupt the consolidation and reconsolidation of methamphetamine-related reward memory, using conditioned place preference paradigm (CPP). Separate groups of male Kunming mice were trained to acquire methamphetamine CPP. Vehicle or rimonabant (1 mg/kg or 3 mg/kg, i.p.) was given at different time points: immediately after each CPP training session (consolidation), 30 min before the reactivation of CPP (retrieval), or immediately after the reactivation of CPP (reconsolidation). Methamphetamine CPP was retested 24 h and 1 and 2 weeks after rimonabant administration. Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the consolidation of methamphetamine CPP. Only high-dose rimonabant (3 mg/kg) disrupted the retrieval and reconsolidation of methamphetamine CPP. Rimonabant had no effect on methamphetamine CPP in the absence of methamphetamine CPP reactivation. Our findings suggest that cannabinoid CB1 receptors play a major role in methamphetamine reward memory, and cannabinoid CB1 receptor antagonists may be a potential pharmacotherapy to manage relapse associated with drug-reward-related memory.

  18. Classification of Recommender Expertise in the Wikipedia Recommender System

    DEFF Research Database (Denmark)

    Jensen, Christian D.; Pilkauskas, Povilas; Lefevre, Thomas

    2011-01-01

    The Wikipedia is a web-based encyclopedia, written and edited collaboratively by Internet users. The Wikipedia has an extremely open editorial policy that allows anybody, to create or modify articles. This has promoted a broad and detailed coverage of subjects, but also introduced problems relating...... to the quality of articles. The Wikipedia Recommender System (WRS) was developed to help users determine the credibility of articles based on feedback from other Wikipedia users. The WRS implements a collaborative filtering system with trust metrics, i.e., it provides a rating of articles "which emphasizes...... in the Wikipedia. In this paper, we examine different ways to classify the subject area of Wikipedia article according to well established knowledge classification schemes. We identify a number of requirements that a classification scheme must meet in order to be useful in the context of the WRS and present...

  19. Sustainability transition dynamics: Towards overcoming policy resistance

    NARCIS (Netherlands)

    Gooyert, V. de; Rouwette, E.A.J.A.; Kranenburg, H.L. van; Freeman, R.E.; Breen, H.J. van

    2016-01-01

    Sustainability transitions receive major scholarly attention, often explicitly with the intention to develop policy recommendations aimed towards progressing such transitions. Despite these efforts, many implemented transition policies have not been able to meet expectations. This tendency of

  20. Mapping CB1 cannabinoid receptors with [3H]OMAR in the Flinders rodent model of depression

    DEFF Research Database (Denmark)

    Nahimi, A.; Gjedde, A.; Wong, D. F.

    2012-01-01

    Background: The endocannabinoid system regulates cognitive and emotional processes and pathology of this system is implicated in psychiatric disorders, including depression and schizophrenia. The precise role of the endocannabinoid system in psychiatric disorders remains unclear, but changes...... in expression of CB1 receptors and subsequent altered modulation of monoamines is suggested in depression (Esteban & Garcia-Sevilla, 2011). CB1 receptor agonists, such as WIN55,212-2 and CP55,940 regulate synthesis and release of monoamines and are suggested as a novel therapy in the treatment of depression....... However, further studies are needed to identify the precise mechanisms of action and pathology of the endocannabinoid system in depression. The hypothesis that depressive-like traits are related to altered CB1 receptor expression were tested in in-vitro autoradiography experiments, measuring binding of [3...

  1. Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors.

    Science.gov (United States)

    Mollica, Adriano; Pelliccia, Sveva; Famiglini, Valeria; Stefanucci, Azzurra; Macedonio, Giorgia; Chiavaroli, Annalisa; Orlando, Giustino; Brunetti, Luigi; Ferrante, Claudio; Pieretti, Stefano; Novellino, Ettore; Benyhe, Sandor; Zador, Ferenc; Erdei, Anna; Szucs, Edina; Samavati, Reza; Dvrorasko, Szalbolch; Tomboly, Csaba; Ragno, Rino; Patsilinakos, Alexandros; Silvestri, Romano

    2017-12-01

    Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at sub-effective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH 2 . The bivalent compound (9) has been used for in vitro binding assays, for in vivo antinociception models and in vitro hypothalamic perfusion test, to evaluate the neurotransmitters release.

  2. Analysis of Cumulonimbus (Cb), Thunderstorm and Fog for Izmir Adnan Menderes Airport

    Science.gov (United States)

    Avsar, Ercument

    2016-07-01

    Demand for airline transport has been increasing day by day with the development of the aviation industry in Turkey. Meteorological conditions are among the most important factors that influence aviation facilities. Meteorological events cause delays and cancellation of flights which create economic and time losses, and they even lead to accidents and breakups. The most important meteorological events that affect the takeoff and landing of airplanes can be listed as wind, runway visual range, cloud, rain, icing, turbulence, and low level windshear. Meteorological events that affect the aviation facilities most often in Adnan Menderes Airport (LTBJ), the fourth largest airport in Turkey in terms of air traffic, are fog, Cumulonimbus (Cb) clouds and thunderstorms (TS-Thunderstorm). Therefore, it is important to identify the occurrence time of these events based on the analysis of data over many years and do the flight plans based on this meteorological information in order to make the aviation facilities safer and without delays. In this study, statistical analysis on the formation of Cb clouds, thunderstorm and foggy days is conducted using observations produced for aviation (METAR) and special observers (SPECI). It is found that there are two types of fog that are observed most often at LTBJ, namely radiation and advection fogs, accordingly to the results of statistical analysis based on data from 2004 to 2014. Fog events are found to occur most often in the months of December and January, during 04:00 - 07:00 UTC time interval, between pressure values over 1015-1020 hPa, in 130-190 degree light breeze (1-5KT) and in temperature levels between 5°C and 8°C. Thunderstorm events recorded at LTBJ between the years 2004 and 2014 are most often observed in the months of January and February, in 120-210 degree gentle breeze winds (6-10KT), and in temperature levels between 8 and 18 °C. Key Words: Adnan Menderes International Airport, LTBJ, Fog, Thunderstorm (TS), Cb

  3. Recommender Systems for Learning

    CERN Document Server

    Manouselis, Nikos; Verbert, Katrien; Duval, Erik

    2013-01-01

    Technology enhanced learning (TEL) aims to design, develop and test sociotechnical innovations that will support and enhance learning practices of both individuals and organisations. It is therefore an application domain that generally covers technologies that support all forms of teaching and learning activities. Since information retrieval (in terms of searching for relevant learning resources to support teachers or learners) is a pivotal activity in TEL, the deployment of recommender systems has attracted increased interest. This brief attempts to provide an introduction to recommender systems for TEL settings, as well as to highlight their particularities compared to recommender systems for other application domains.

  4. Collection Development Policies in Community College Libraries.

    Science.gov (United States)

    Mesling, Chris Fowler

    2003-01-01

    Emphasizes the need for collection development policy in community college academic libraries. Highlights areas of resource sharing, community analysis, and collection assessment. Also provides an overview of how to create a collection for development policy, and recommends books on writing such policy. Includes model policy statements. (NB)

  5. Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1Receptor Heteromers in the Dorsal Striatum.

    Science.gov (United States)

    Moreno, Estefanía; Chiarlone, Anna; Medrano, Mireia; Puigdellívol, Mar; Bibic, Lucka; Howell, Lesley A; Resel, Eva; Puente, Nagore; Casarejos, María J; Perucho, Juan; Botta, Joaquín; Suelves, Nuria; Ciruela, Francisco; Ginés, Silvia; Galve-Roperh, Ismael; Casadó, Vicent; Grandes, Pedro; Lutz, Beat; Monory, Krisztina; Canela, Enric I; Lluís, Carmen; McCormick, Peter J; Guzmán, Manuel

    2018-04-01

    The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A 2A receptor (A 2A R) and cannabinoid CB 1 receptor (CB 1 R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A 2A R and CB 1 R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A 2A R-CB 1 R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically modified animal models, together with biochemical and pharmacological approaches, we provide a high-resolution expression map and a detailed functional characterization of A 2A R-CB 1 R heteromers in the dorsal striatum. Specifically, our data unveil that the A 2A R-CB 1 R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington's disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases.

  6. Cannabinoid CB2 Receptors Contribute to Upregulation of β-endorphin in Inflamed Skin Tissues by Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Su Tang-feng

    2011-12-01

    Full Text Available Abstract Background Electroacupuncture (EA can produce analgesia by increasing the β-endorphin level and activation of peripheral μ-opioid receptors in inflamed tissues. Endogenous cannabinoids and peripheral cannabinoid CB2 receptors (CB2Rs are also involved in the antinociceptive effect of EA on inflammatory pain. However, little is known about how peripheral CB2Rs interact with the endogenous opioid system at the inflammatory site and how this interaction contributes to the antinociceptive effect of EA on inflammatory pain. In this study, we determined the role of peripheral CB2Rs in the effects of EA on the expression of β-endorphin in inflamed skin tissues and inflammatory pain. Results Inflammatory pain was induced by injection of complete Freund's adjuvant into the left hindpaw of rats. Thermal hyperalgesia was tested with a radiant heat stimulus, and mechanical allodynia was quantified using von Frey filaments. The mRNA level of POMC and protein level of β-endorphin were quantified by real-time PCR and Western blotting, respectively. The β-endorphin-containing keratinocytes and immune cells in the inflamed skin tissues were detected by double-immunofluorescence labeling. The CB2R agonist AM1241 or EA significantly reduced thermal hyperalgesia and mechanical allodynia, whereas the selective μ-opioid receptor antagonist β-funaltrexamine significantly attenuated the antinociceptive effect produced by them. AM1241 or EA significantly increased the mRNA level of POMC and the protein level of β-endorphin in inflamed skin tissues, and these effects were significantly attenuated by pretreatment with the CB2R antagonist AM630. AM1241 or EA also significantly increased the percentage of β-endorphin-immunoreactive keratinocytes, macrophages, and T-lymphocytes in inflamed skin tissues, and these effects were blocked by AM630. Conclusions EA and CB2R stimulation reduce inflammatory pain through activation of μ-opioid receptors. EA increases

  7. The cannabinoid receptor CB1 contributes to the development of ectopic lesions in a mouse model of endometriosis.

    Science.gov (United States)

    Sanchez, Ana-Maria; Quattrone, Federica; Pannese, Maria; Ulisse, Adele; Candiani, Massimo; Diaz-Alonso, Javier; Velasco, Guillermo; Panina-Bordignon, Paola

    2017-01-01

    Does signaling via the cannabinoid (CB 1 ) receptor play a role in the pathogenesis of endometriosis in a mouse model? Mice treated with a CB 1 agonist developed larger ectopic lesions, while less severe lesions developed in the absence of functional CB 1 expression. The expression of components of the endocannabinoid system has been demonstrated in both mouse and human uteri. CB 1 receptors are expressed in human epithelial and stromal cell lines derived from eutopic endometrium and deep infiltrating endometriosis nodules. This was a randomized study in a mouse model of endometriosis. In a first set of experiments, mice with endometriosis were treated with the CB 1 receptor agonist methanandamide (MET) (5 mg/kg, n = 20) on Days 1-5 and 8-12. In a second set of experiments, endometriosis development was evaluated in CB 1 -/- mice and in their wild-type (WT) littermates. Endometriosis-like lesions were induced in Balb/c and C57/Bl6 mice. Two weeks after disease induction, the lesions were counted, measured and either included for immunohistochemistry analysis or frozen for gene expression profiling by semi-quantitative real-time PCR. To limit the role of chance, the experiments were conducted under standardized laboratory conditions with appropriate controls. The lesion total volume was significantly higher in MET-treated compared with vehicle-treated mice (P endometriosis in a mouse model. However, the relative contribution of the CB 1 -mediated signaling pathways active in inflammatory, uterine and peritoneal cells remains to be ascertained. Since the study was performed in a mouse model, the significance of the findings in the human system warrants further investigation. Clarifying the function and regulation of CB 1 and its molecular interactions with endogenous ligands, and how endocannabinoids levels are regulated in women with endometriosis, represent critical areas of research for the potential development of a novel medical treatment of the disease. A

  8. Search and Recommendation

    DEFF Research Database (Denmark)

    Bogers, Toine

    2014-01-01

    In just a little over half a century, the field of information retrieval has experienced spectacular growth and success, with IR applications such as search engines becoming a billion-dollar industry in the past decades. Recommender systems have seen an even more meteoric rise to success with wide......-scale application by companies like Amazon, Facebook, and Netflix. But are search and recommendation really two different fields of research that address different problems with different sets of algorithms in papers published at distinct conferences? In my talk, I want to argue that search and recommendation...... are more similar than they have been treated in the past decade. By looking more closely at the tasks and problems that search and recommendation try to solve, at the algorithms used to solve these problems and at the way their performance is evaluated, I want to show that there is no clear black and white...

  9. Microgrid Policy Review of Selected Major Countries, Regions, and Organizations

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Min [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Marnay, Chris [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Zhou, Nan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2011-11-30

    This report collects and reviews policies and regulations related to microgrid development, and is intended as a reference. The material is divided into three parts under five dimensions: interconnection, RD&D, tariff policy, other policies, and recommendations.

  10. Probabilistic approaches to recommendations

    CERN Document Server

    Barbieri, Nicola; Ritacco, Ettore

    2014-01-01

    The importance of accurate recommender systems has been widely recognized by academia and industry, and recommendation is rapidly becoming one of the most successful applications of data mining and machine learning. Understanding and predicting the choices and preferences of users is a challenging task: real-world scenarios involve users behaving in complex situations, where prior beliefs, specific tendencies, and reciprocal influences jointly contribute to determining the preferences of users toward huge amounts of information, services, and products. Probabilistic modeling represents a robus

  11. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Emery, C. A.; Roos, Ewa M.; Verhagen, E.

    2015-01-01

    the design, conduct and analytical approaches to RCTs evaluating the preventative effect of joint injury prevention strategies. Recommendations regarding the design, conduct, and reporting of RCTs evaluating injury prevention interventions were established based on the consensus of nine researchers...... regarding the research question, research design, study participants, randomization, baseline characteristics, intervention, outcome measurement, analysis, implementation, cost evaluation, reporting and future considerations including the impact on development of PTOA. Methodological recommendations...

  12. The future of endocannabinoid-oriented clinical research after CB1 antagonists

    Science.gov (United States)

    Le Foll, Bernard; Gorelick, David A.; Goldberg, Steven R.

    2009-01-01

    Great interest has been shown by the medical community and the public in the cannabinoid CB1 receptor antagonists, such as rimonabant, for treatment of obesity, metabolic syndrome, and possibly drug addiction. This novel class of drug has therapeutic potential for other disorders, as the endocannabinoid system is involved in various health conditions. However, rimonabant, the first clinically available member of this class of drugs, has been linked to increased risk of anxiety, depression, and suicidality. Due to those risks, the European Medicines Agency (EMEA) called for its withdrawal from the market in October, 2008. Shortly after this decision, several pharmaceutical companies (Sanofi-aventis, Merck, Pfizer, Solvay) announced they would stop further clinical research on this class of drug. Here, we provide an overview of those events and make several suggestions for continuing such clinical research, while safeguarding the safety of patients and clinical trial subjects. PMID:19300982

  13. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

    Science.gov (United States)

    Zlebnik, Natalie E; Cheer, Joseph F

    2016-07-08

    The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia. Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders. Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD). Unlike Δ(9)-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders. Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression. Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.

  14. Three-dimensional single-photon emission computed tomography using cone beam collimation (CB-SPECT)

    International Nuclear Information System (INIS)

    Jaszczak, R.J.; Floyd, C.E. Jr.; Manglos, S.H.; Greer, K.L.; Coleman, R.E.

    1986-01-01

    A simple and economically practical method of improving the sensitivity of camera-based SPECT was developed using converging (cone-beam) collimation. This geometry is particularly advantageous for SPECT devices using large field-of-view cameras in imaging smaller, centrally located activity distributions. Geometric sensitivities, spatial resolutions, and fields-of-view of a cone-beam collimator having a focal length of 48 cm and a similarly designed parallel hole collimator were compared analytically. At 15 cm from the collimator surface the point-source sensitivity of the cone-beam collimator was 2.4 times the sensitivity of the parallel-hole collimator. SPECT projection data (simulated using Monte Carlo methodology) were reconstructed using a 3-D filtered backprojection algorithm. Cone-beam emission CT (CB-SPECT) seems potentially useful for animal investigations, pediatric studies, and for brain imaging

  15. Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

    Science.gov (United States)

    Jayant, Shalini; Sharma, Brij Mohan; Bansal, Rani; Sharma, Bhupesh

    2016-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aβ plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Identification of novel nitroreductases from Bacillus cereus and their interaction with the CB1954 prodrug.

    Science.gov (United States)

    Gwenin, Vanessa V; Poornima, Paramasivan; Halliwell, Jennifer; Ball, Patrick; Robinson, George; Gwenin, Chris D

    2015-12-01

    Directed enzyme prodrug therapy is a form of cancer chemotherapy in which bacterial prodrug-activating enzymes, or their encoding genes, are directed to the tumour before administration of a prodrug. The prodrug can then be activated into a toxic drug at the tumour site, reducing off-target effects. The bacterial nitroreductases are a class of enzymes used in this therapeutic approach and although very promising, the low turnover rate of prodrug by the most studied nitroreductase enzyme, NfnB from Escherichia coli (NfnB_Ec), is a major limit to this technology. There is a continual search for enzymes with greater efficiency, and as part of the search for more efficient bacterial nitroreductase enzymes, two novel enzymes from Bacillus cereus (strain ATCC 14579) have been identified and shown to reduce the CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) prodrug to its respective 2'-and 4'-hydroxylamine products. Both enzymes shared features characteristic of the nitro-FMN-reductase superfamily including non-covalently associated FMN, requirement for the NAD(P)H cofactor, homodimeric, could be inhibited by Dicoumarol (3,3'-methylenebis(4-hydroxy-2H-chromen-2-one)), and displayed ping pong bi bi kinetics. Based on the biochemical characteristics and nucleotide alignment with other nitroreductase enzymes, one enzyme was named YdgI_Bc and the other YfkO_Bc. Both B. cereus enzymes had greater turnover for the CB1954 prodrug compared with NfnB_Ec, and in the presence of added NADPH cofactor, YfkO_Bc had superior cell killing ability, and produced mainly the 4'-hydroxylamine product at low prodrug concentration. The YfkO_Bc was identified as a promising candidate for future enzyme prodrug therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Announcement of recommendations of the Reaktor-Sicherheitskommission. As of 24 July 1997. Joint recommendations of RSK and GPR for safety requirements of future nuclear PWR-type power plants. English versions published in the years 1995 through 1997

    International Nuclear Information System (INIS)

    1997-01-01

    The recommendations, most parts given in English, refer to the European Pressurized Water Reactor (EPR) and have been established by the German RSK (reactor safety commission), the corresponding French organization GPR and the German SSK (radiation protection commission). This publication continues earlier joint recommendations by the national bodies, last published by the German BMU (responsible German ministry) on 5 May 1995, in BAnz. page 7452. The safety recommendations establish the basis for further activities in the Franco-German project for development of the EPR, a PWR type reactor of the next generation. (CB) [de

  18. A Hybrid Recommender System Based on User-Recommender Interaction

    OpenAIRE

    Zhang, Heng-Ru; Min, Fan; He, Xu; Xu, Yuan-Yuan

    2015-01-01

    Recommender systems are used to make recommendations about products, information, or services for users. Most existing recommender systems implicitly assume one particular type of user behavior. However, they seldom consider user-recommender interactive scenarios in real-world environments. In this paper, we propose a hybrid recommender system based on user-recommender interaction and evaluate its performance with recall and diversity metrics. First, we define the user-recommender interaction...

  19. Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine

    Directory of Open Access Journals (Sweden)

    Rodríguez-Muñoz María

    2009-03-01

    Full Text Available Abstract Background Although the systemic administration of cannabinoids produces antinociception, their chronic use leads to analgesic tolerance as well as cross-tolerance to morphine. These effects are mediated by cannabinoids binding to peripheral, spinal and supraspinal CB1 and CB2 receptors, making it difficult to determine the relevance of each receptor type to these phenomena. However, in the brain, the CB1 receptors (CB1Rs are expressed at high levels in neurons, whereas the expression of CB2Rs is marginal. Thus, CB1Rs mediate the effects of smoked cannabis and are also implicated in emotional behaviors. We have analyzed the production of supraspinal analgesia and the development of tolerance at CB1Rs by the direct injection of a series of cannabinoids into the brain. The influence of the activation of CB1Rs on supraspinal analgesia evoked by morphine was also evaluated. Results Intracerebroventricular (icv administration of cannabinoid receptor agonists, WIN55,212-2, ACEA or methanandamide, generated a dose-dependent analgesia. Notably, a single administration of these compounds brought about profound analgesic tolerance that lasted for more than 14 days. This decrease in the effect of cannabinoid receptor agonists was not mediated by depletion of CB1Rs or the loss of regulated G proteins, but, nevertheless, it was accompanied by reduced morphine analgesia. On the other hand, acute morphine administration produced tolerance that lasted only 3 days and did not affect the CB1R. We found that both neural mu-opioid receptors (MORs and CB1Rs interact with the HINT1-RGSZ module, thereby regulating pertussis toxin-insensitive Gz proteins. In mice with reduced levels of these Gz proteins, the CB1R agonists produced no such desensitization or morphine cross-tolerance. On the other hand, experimental enhancement of Gz signaling enabled an acute icv administration of morphine to produce a long-lasting tolerance at MORs that persisted for more than

  20. Beneficial metabolic effects of CB1R anti-sense oligonucleotide treatment in diet-induced obese AKR/J mice.

    Directory of Open Access Journals (Sweden)

    Yuting Tang

    Full Text Available An increasing amount of evidence supports pleiotropic metabolic roles of the cannibinoid-1 receptor (CB1R in peripheral tissues such as adipose, liver, skeletal muscle and pancreas. To further understand the metabolic consequences of specific blockade of CB1R function in peripheral tissues, we performed a 10-week-study with an anti-sense oligonucleotide directed against the CB1R in diet-induced obese (DIO AKR/J mice. DIO AKR/J mice were treated with CB1R ASO Isis-414930 (6.25, 12.5 and 25 mg/kg/week or control ASO Isis-141923 (25 mg/kg/week via intraperitoneal injection for 10 weeks. At the end of the treatment, CB1R mRNA from the 25 mg/kg/week CB1R ASO group in the epididymal fat and kidney was decreased by 81% and 63%, respectively. Body weight gain was decreased in a dose-dependent fashion, significantly different in the 25 mg/kg/week CB1R ASO group (46.1±1.0 g vs veh, 51.2±0.9 g, p<0.05. Body fat mass was reduced in parallel with attenuated body weight gain. CB1R ASO treatment led to decreased fed glucose level (at week 8, 25 mg/kg/week group, 145±4 mg/dL vs veh, 195±10 mg/dL, p<0.05. Moreover, CB1R ASO treatment dose-dependently improved glucose excursion during an oral glucose tolerance test, whereas control ASO exerted no effect. Liver steatosis was also decreased upon CB1R ASO treatment. At the end of the study, plasma insulin and leptin levels were significantly reduced by 25 mg/kg/week CB1R ASO treatment. SREBP1 mRNA expression was decreased in both epididymal fat and liver. G6PC and fatty acid translocase/CD36 mRNA levels were also reduced in the liver. In summary, CB1R ASO treatment in DIO AKR/J mice led to improved insulin sensitivity and glucose homeostasis. The beneficial effects of CB1R ASO treatment strongly support the notion that selective inhibition of the peripheral CB1R, without blockade of central CB1R, may serve as an effective approach for treating type II diabetes, obesity and the metabolic syndrome.

  1. Nuclear power phaseout policy and the economic implications for Germany

    International Nuclear Information System (INIS)

    Pfaffenberger, W.

    1999-01-01

    Implementation of Germany's nuclear power phaseout policy and the expected consequences are discussed in this paper, referring to environmental aspects and Germany's international commitments under the UN Framework Convention on Climate Change, implications for the national economy, the required structural transformation of the energy industry, and changes in the general legal setting for the energy sector. Proposals are discussed for modifying the planned nuclear power phaseout policy so as to make the process of winding down nuclear generation more compatible with economic, social, and environmental policy conditions. (orig./CB) [de

  2. Distributed Deliberative Recommender Systems

    Science.gov (United States)

    Recio-García, Juan A.; Díaz-Agudo, Belén; González-Sanz, Sergio; Sanchez, Lara Quijano

    Case-Based Reasoning (CBR) is one of most successful applied AI technologies of recent years. Although many CBR systems reason locally on a previous experience base to solve new problems, in this paper we focus on distributed retrieval processes working on a network of collaborating CBR systems. In such systems, each node in a network of CBR agents collaborates, arguments and counterarguments its local results with other nodes to improve the performance of the system's global response. We describe D2ISCO: a framework to design and implement deliberative and collaborative CBR systems that is integrated as a part of jcolibritwo an established framework in the CBR community. We apply D2ISCO to one particular simplified type of CBR systems: recommender systems. We perform a first case study for a collaborative music recommender system and present the results of an experiment of the accuracy of the system results using a fuzzy version of the argumentation system AMAL and a network topology based on a social network. Besides individual recommendation we also discuss how D2ISCO can be used to improve recommendations to groups and we present a second case of study based on the movie recommendation domain with heterogeneous groups according to the group personality composition and a group topology based on a social network.

  3. A TEM study of morphological and structural degradation phenomena in LiFePO4-CB cathodes

    DEFF Research Database (Denmark)

    Ngo, Duc-The; Scipioni, Roberto; Simonsen, Søren Bredmose

    2016-01-01

    LiFePO4-based cathodes suffer from various degradation mechanisms, which influences the battery performance. In this paper, morphological and structural degradation phenomena in laboratory cathodes made of LiFePO4 mixed with carbon black (CB) in a 1 mol/L LiPF6 in EC : DMC (1:1 by weight...

  4. Summary (and) recommendations

    International Nuclear Information System (INIS)

    1992-01-01

    This report looks at the Health and Safety record at the Atomic Weapons Establishment at Aldermaston. The last outside report was by Pochin in 1978 which recommended that staffing for health physicists and maintenance staff should be increased and that some buildings where solid and liquid radioactive wastes were processed should be replaced. A new facility to process contaminated heavy equipment was also recommended. This report finds that none of the recommendations have been fully implemented. It also lists accidents, fires and worker contamination. It is concluded that some of the problems are that nuclear weapons production is inherently unsafe and cannot be made safe, that the secrecy surrounding the establishments' safety record is not good for improving it and finally the report calls for production at Aldermaston to be halted. (UK)

  5. Archetypal Game Recommender Systems

    DEFF Research Database (Denmark)

    Sifa, Rafet; Bauckhage, C.; Drachen, Anders

    2014-01-01

    Contemporary users (players, consumers) of digital games have thousands of products to choose from, which makes nding games that t their interests challenging. Towards addressing this challenge, in this paper two dierent formulations of Archetypal Analysis for Top-L recommender tasks using implicit...... feedback are presented: factor- and neighborhood-oriented models. These form the rst application of rec- ommender systems to digital games. Both models are tested on a dataset of 500,000 users of the game distribution platform Steam, covering game ownership and playtime data across more than 3000 games....... Compared to four other recommender models (nearest neighbor, two popularity mod- els, random baseline), the archetype based models provide the highest recall rates showing that Archetypal Analysis can be successfully applied for Top-L recommendation purposes...

  6. Recommending Multidimensional Queries

    Science.gov (United States)

    Giacometti, Arnaud; Marcel, Patrick; Negre, Elsa

    Interactive analysis of datacube, in which a user navigates a cube by launching a sequence of queries is often tedious since the user may have no idea of what the forthcoming query should be in his current analysis. To better support this process we propose in this paper to apply a Collaborative Work approach that leverages former explorations of the cube to recommend OLAP queries. The system that we have developed adapts Approximate String Matching, a technique popular in Information Retrieval, to match the current analysis with the former explorations and help suggesting a query to the user. Our approach has been implemented with the open source Mondrian OLAP server to recommend MDX queries and we have carried out some preliminary experiments that show its efficiency for generating effective query recommendations.

  7. New Insulin Delivery Recommendations.

    Science.gov (United States)

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  8. Anti-Obesity Effect of the CB2 Receptor Agonist JWH-015 in Diet-Induced Obese Mice.

    Science.gov (United States)

    Verty, A N A; Stefanidis, A; McAinch, A J; Hryciw, D H; Oldfield, Brian

    2015-01-01

    The cannabinoid receptor 2 (CB2) is well known for its immune modulatory role. However, recent localisation of CB2 receptors in metabolically active tissue suggests that the CB2 receptor plays a significant role in energy homeostasis. This study was designed to investigate the impact of chronic CB2 receptor stimulation on food intake, body weight and mood. Lean male C57BL/6 mice were injected i.p. with the selective CB2 receptor agonist, JWH-015 (0.0, 1.0, 5.0 and 10.0 mg kg-1) to establish dose response parameters. Mice made obese following exposure to a diet consisting of 19.4 MJ/kg (4641 Kcal/kg) of energy (19.0% protein, 21.0% total fat, 4.7% crude fiber, and 4.7% AD fiber were given either vehicle or 10 mg/kg JWH-015. Impact on mood, food intake, body weight, plasma metabolites, expression of key metabolic proteins in the brown adipose tissue (BAT) and white adipose tissue (WAT), and markers of inflammation were measured. High dose (10 mg/kg) JWH-015 reduced food intake after 1, 2, 4, and 24 h in lean mice. When given to diet induced obese (DIO) mice, a 10 mg/kg dose of JWH-015 significantly reduced body weight compared to vehicle. This dose led to a shift in markers of lipid metabolism and inflammation in WAT consistent with lipolysis and improved immune response. Furthermore, JWH-015 (10 mg/kg) produced a transient reduction in food intake and significant reduction in fat mass and adipocyte cell size. Importantly, JWH-015 produced an anxiolytic response in the elevated plus maze while having no effect on immobility time in the forced swim test. It should be noted that though the 10 mg/kg dose produced positive effects on the obese state, the possibility that these effects are mediated via non-CB2 receptor mechanisms cannot be ruled out. These results demonstrate a role for CB2 receptors in modulating energy homeostasis and obesity associated metabolic pathologies in the absence of any adverse impact on mood.

  9. Anti-Obesity Effect of the CB2 Receptor Agonist JWH-015 in Diet-Induced Obese Mice.

    Directory of Open Access Journals (Sweden)

    A N A Verty

    Full Text Available The cannabinoid receptor 2 (CB2 is well known for its immune modulatory role. However, recent localisation of CB2 receptors in metabolically active tissue suggests that the CB2 receptor plays a significant role in energy homeostasis. This study was designed to investigate the impact of chronic CB2 receptor stimulation on food intake, body weight and mood. Lean male C57BL/6 mice were injected i.p. with the selective CB2 receptor agonist, JWH-015 (0.0, 1.0, 5.0 and 10.0 mg kg-1 to establish dose response parameters. Mice made obese following exposure to a diet consisting of 19.4 MJ/kg (4641 Kcal/kg of energy (19.0% protein, 21.0% total fat, 4.7% crude fiber, and 4.7% AD fiber were given either vehicle or 10 mg/kg JWH-015. Impact on mood, food intake, body weight, plasma metabolites, expression of key metabolic proteins in the brown adipose tissue (BAT and white adipose tissue (WAT, and markers of inflammation were measured. High dose (10 mg/kg JWH-015 reduced food intake after 1, 2, 4, and 24 h in lean mice. When given to diet induced obese (DIO mice, a 10 mg/kg dose of JWH-015 significantly reduced body weight compared to vehicle. This dose led to a shift in markers of lipid metabolism and inflammation in WAT consistent with lipolysis and improved immune response. Furthermore, JWH-015 (10 mg/kg produced a transient reduction in food intake and significant reduction in fat mass and adipocyte cell size. Importantly, JWH-015 produced an anxiolytic response in the elevated plus maze while having no effect on immobility time in the forced swim test. It should be noted that though the 10 mg/kg dose produced positive effects on the obese state, the possibility that these effects are mediated via non-CB2 receptor mechanisms cannot be ruled out. These results demonstrate a role for CB2 receptors in modulating energy homeostasis and obesity associated metabolic pathologies in the absence of any adverse impact on mood.

  10. Latin America Regional Seminar 'Civil-Military Responses to Terrorism' Group Recommendations

    OpenAIRE

    Shemella, Paul

    2004-01-01

    Given the high degree of cultural continuity in the region, we recommend proposing a common definition of terrorism to guide national policy formulation for responding to terrorist activities. We further recommend...

  11. Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands

    Science.gov (United States)

    Kruk-Slomka, Marta; Boguszewska-Czubara, Anna; Slomka, Tomasz; Budzynska, Barbara; Biala, Grazyna

    2016-01-01

    The endocannabinoid system, through cannabinoid (CB) receptors, is involved in memory-related responses, as well as in processes that may affect cognition, like oxidative stress processes. The purpose of the experiments was to investigate the impact of CB1 and CB2 receptor ligands on the long-term memory stages in male Swiss mice, using the passive avoidance (PA) test, as well as the influence of these compounds on the level of oxidative stress biomarkers in the mice brain. A single injection of a selective CB1 receptor antagonist, AM 251, improved long-term memory acquisition and consolidation in the PA test in mice, while a mixed CB1/CB2 receptor agonist WIN 55,212-2 impaired both stages of cognition. Additionally, JWH 133, a selective CB2 receptor agonist, and AM 630, a competitive CB2 receptor antagonist, significantly improved memory. Additionally, an acute administration of the highest used doses of JWH 133, WIN 55,212-2, and AM 630, but not AM 251, increased total antioxidant capacity (TAC) in the brain. In turn, the processes of lipids peroxidation, expressed as the concentration of malondialdehyde (MDA), were more advanced in case of AM 251. Thus, some changes in the PA performance may be connected with the level of oxidative stress in the brain. PMID:26839719

  12. 40 CFR Table 2 to Subpart Cb of... - Nitrogen Oxides Limits for Existing Designated Facilities Included in an Emissions Averaging Plan...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Nitrogen Oxides Limits for Existing.... 60, Subpt. Cb, Table 2 Table 2 to Subpart Cb of Part 60—Nitrogen Oxides Limits for Existing... by volume) b On and after April 28, 2009, nitrogen oxides emission limit (parts permillion by volume...

  13. Endocannabinoid CB1 Receptor Mediated Rises in Ca2+ and Depolarization-Induced Suppression of Inhibition within the Laterodorsal Tegmental Nucleus

    DEFF Research Database (Denmark)

    Soni, Neeraj; Kohlmeier, Kristi Anne

    2016-01-01

    in this nucleus, we examined whether CB1R activation led to rises in intracellular Ca(2+) ([Ca(2+)]i) and whether processes shown in other regions to involve endocannabinoid (eCB) transmission were present in the LDT. Using a combination of Ca(2+) imaging in multiple cells loaded with Ca(2+) imaging dye via 'bulk...

  14. Differential interaction of the staphylococcal toxins panton-valentine leukocidin and γ-hemolysin CB with human C5a receptors

    NARCIS (Netherlands)

    Spaan, András N.|info:eu-repo/dai/nl/357396995; Schiepers, Ariën; De Haas, Carla J C; Van Hooijdonk, Davy D J J; Badiou, Cédric; Contamin, Hugues; Vandenesch, François; Lina, Gérard; Gerard, Norma P.; Gerard, Craig; Van Kessel, Kok P M; Henry, Thomas; Van Strijp, Jos A G|info:eu-repo/dai/nl/074307053

    2015-01-01

    Staphylococcus aureus is well adapted to the human host. Evasion of the host phagocyte response is critical for successful infection. The staphylococcal bicomponent pore-forming toxins Panton-Valentine leukocidin LukSF-PV (PVL) and γ-hemolysin CB (HlgCB) target human phagocytes through interaction

  15. Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro.

    Science.gov (United States)

    Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

    2016-12-01

    Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ‑rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ‑rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma.

  16. Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

    Science.gov (United States)

    Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

    2016-01-01

    Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ-rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ-rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ-rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ-ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma. PMID:27840931

  17. Detection of Heteromers Formed by Cannabinoid CB1, Dopamine D2, and Adenosine A2A G-Protein-Coupled Receptors by Combining Bimolecular Fluorescence Complementation and Bioluminescence Energy Transfer

    Directory of Open Access Journals (Sweden)

    Gemma Navarro

    2008-01-01

    Full Text Available Functional interactions in signaling occur between dopamine D2 (D2R and cannabinoid CB1 (CB1R receptors, between CB1R and adenosine A2A (A2AR receptors, and between D2R and A2AR. Furthermore, direct molecular interactions have been reported for the pairs CB1R-D2R, A2AR-D2R, and CB1R-A2AR. Here a combination of bimolecular fluorescence complementation and bioluminescence energy transfer techniques was used to identify the occurrence of D2R-CB1R-A2AR hetero-oligomers in living cells.

  18. Manpower Policy and Programmes in Canada. Reviews of Manpower and Social Policies No. 4.

    Science.gov (United States)

    Organisation for Economic Cooperation and Development, Paris (France).

    This report describes the Canadian labor force and economic climate, and the employment and manpower policies which comprise Canada's active manpower policy. Expanded programs for vocational and technical training are recommended, especially for unemployed youth. (BH)

  19. Cannabis Users Show Enhanced Expression of CB1-5HT2AReceptor Heteromers in Olfactory Neuroepithelium Cells.

    Science.gov (United States)

    Galindo, Liliana; Moreno, Estefanía; López-Armenta, Fernando; Guinart, Daniel; Cuenca-Royo, Aida; Izquierdo-Serra, Mercè; Xicota, Laura; Fernandez, Cristina; Menoyo, Esther; Fernández-Fernández, José M; Benítez-King, Gloria; Canela, Enric I; Casadó, Vicent; Pérez, Víctor; de la Torre, Rafael; Robledo, Patricia

    2018-01-02

    Cannabinoid CB1 receptors (CB 1 R) and serotonergic 2A receptors (5HT 2A R) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB 1 R-5HT 2A R heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na + currents in patch clamp recordings. Interestingly, CB 1 R-5HT 2A R heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB 1 R-5HT 2A R heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

  20. Candidate PET radioligands for cannabinoid CB{sub 1} receptors: [{sup 18}F]AM5144 and related pyrazole compounds

    Energy Technology Data Exchange (ETDEWEB)

    Li Zizhong [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Gifford, Andrew [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Liu Qian [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Thotapally, Rajesh [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Ding Yushin [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Makriyannis, Alexandros [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Gatley, S. John [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States)]. E-mail: s.gatley@neu.edu

    2005-05-01

    Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB{sub 1} receptors that respond to {delta}{sup 9}-tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB{sub 1} receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[{sup 18}F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[{sup 18}F]fluoroaniline. The labeled precursor was synthesized from 1-[{sup 18}F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/{mu}mol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB{sub 1} receptors, absolute uptake at <0.003% injected radioactivity per cubic centimeter was lower than the previously reported uptake of the radioiodinated pyrazole AM281. Conclusions: The relatively poor brain uptake of AM5144 and other pyrazole CB{sub 1} receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB{sub 1} receptor that may require very lipophilic ligands.

  1. CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice

    Directory of Open Access Journals (Sweden)

    Shivakumar Subbanna

    2018-02-01

    Full Text Available Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD. However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7 mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2 levels. The developmental expression of MeCP2 in mice is closely correlated with synaptogenesis and neuronal maturation. It was shown that ethanol treatment of P7 mice enhanced Mecp2 mRNA levels but reduced protein levels. The genetic deletion of CB1R prevented, and administration of a CB1R antagonist before ethanol treatment of P7 mice inhibited caspase-3 activation. Additionally, it reversed the loss of MeCP2 protein, cAMP response element binding protein (CREB activation, and activity-regulated cytoskeleton-associated protein (Arc expression. The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP, spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. This CB1R-mediated instability of MeCP2 during active synaptic maturation may disrupt synaptic circuit maturation and lead to neurobehavioral abnormalities, as observed in this animal model of FASD.

  2. Structure-kinetic relationship studies of cannabinoid CB2receptor agonists reveal substituent-specific lipophilic effects on residence time.

    Science.gov (United States)

    Soethoudt, Marjolein; Hoorens, Mark W H; Doelman, Ward; Martella, Andrea; van der Stelt, Mario; Heitman, Laura H

    2018-03-21

    A decade ago, the drug-target residence time model has been (re-)introduced, which describes the importance of binding kinetics of ligands on their protein targets. Since then, it has been applied successfully for multiple protein targets, including GPCRs, for the development of lead compounds with slow dissociation kinetics (i.e. long target residence time) to increase in vivo efficacy or with short residence time to prevent on-target associated side effects. To date, this model has not been applied in the design and pharmacological evaluation of novel selective ligands for the cannabinoid CB 2 receptor (CB 2 R), a GPCR with therapeutic potential in the treatment of tissue injury and inflammatory diseases. Here, we have investigated the relationships between physicochemical properties, binding kinetics and functional activity in two different signal transduction pathways, G protein activation and β-arrestin recruitment. We synthesized 24 analogues of 3-cyclopropyl-1-(4-(6-((1,1-dioxidothiomorpholino)methyl)-5-fluoropyridin-2-yl)benzyl)imidazoleidine-2,4-dione (LEI101), our previously reported in vivo active and CB 2 R-selective agonist, with varying basicity and lipophilicity. We identified a positive correlation between target residence time and functional potency due to an increase in lipophilicity on the alkyl substituents, which was not the case for the amine substituents. Basicity of the agonists did not show a relationship with affinity, residence time or functional activity. Our findings provide important insights about the effects of physicochemical properties of the specific substituents of this scaffold on the binding kinetics of agonists and their CB 2 R pharmacology. This work therefore shows how CB 2 R agonists can be designed to have optimal kinetic profiles, which could aid the lead optimization process in drug discovery for the study or treatment of inflammatory diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights

  3. SINTEZA ORIENTATĂ A POLIZAHARIDELOR ACIDE LA CIANOBACTERIA SPIRULINA PLATENSIS CNM CB-02

    Directory of Open Access Journals (Sweden)

    Valentina BULIMAGA

    2017-07-01

    Full Text Available  Cultivarea cianobacteriei Spirulina platensis CNM CB-02 în două etape cu adaos de NaCl (0,25 şi 0,50 M la a 2-a etapă de cultivare, fără a varia regimul de iluminare, sporeşte conţinutul de polizaharide sulfatate în biomasă cu 29 şi, respectiv, 31,3%, comparativ cu proba de referinţă (fără NaCl. În acest caz n-a fost observat un efect evident al acestei sări asupra conţinutului total de polizaharide acide. Majorarea intensităţii de iluminare (până la 5500 lx şi supli­men­tarea cu NaCl (0,25 M la a 2-a etapă de cultivare a asigurat un spor cu 23,45% al conţinutului total de polizaharide acide, com­parativ cu conţinutul acestora în proba de referinţă (cultivată la 3500 lx. Adăugarea CuSO4·5H2O (1-4 mg/l nu a exer­citat un efect semnificativ asupra conţinutului de polizaharide acide şi sulfatate în biomasa de spirulină, însă a stimulat considerabil producerea de exopolizaharide acide (până la 238,3 g/kg la 5500 lx.ACIDIC POLYSACCHARIDES DIRECTED SYNTHESIS AT CYANOBACTERIA SPIRULINA PLATENSIS CNM CB-02Two-stage cultivation of cyanobacterium Spirulina platensis CNM CB-02 with NaCl (0,25 and 0,50 M supple­men­tation on the second stage of cultivation, without varying of the lighting regime ensured an increasing of the content of sulfated polysaccharides in biomass by 29 and 31,3%, respectively, compared to the reference sample (without NaCl. It wasn’t found an evident effect of NaCl on the total content of acidic polysaccharides in this case. Light intensity increasing (up to 5500 lx with NaCl (0,25 M supplementation ensured the increasing of the acidic polysaccharides content with 23,45%, compared to the reference sample (cultivated at 3500lx. CuSO4·5H2O (1-4 mg/l hadn’t a significant effect on the content of acidic and sulfated polysaccharides in spirulina biomass, but considerably stimulated acidic exopoly­saccharides production (up to238,3 g / kg at 5500 lx.

  4. Recommendations for Alternative Credit.

    Science.gov (United States)

    Lenderman, Ed; And Others

    Following a review of the mathematics topics taught in accounting, electronics, auto, food and clothing, and metals courses at Linn-Benton Community College, Albany, Oregon, recommendations were made to grant one semester of mathematics credit for completing a two-year sequence of these courses. The other required semester of mathematics should be…

  5. Privacy in Recommender Systems

    NARCIS (Netherlands)

    Jeckmans, Arjan; Beye, Michael; Erkin, Zekeriya; Erkin, Zekeriya; Hartel, Pieter H.; Lagendijk, Reginald; Tang, Qiang; Ramzan, Naeem; van Zwol, Roelof; Lee, Jong-Seok; Clüver, Kai; Hua, Xian-Sheng

    In many online applications, the range of content that is offered to users is so wide that a need for automated recommender systems arises. Such systems can provide a personalized selection of relevant items to users. In practice, this can help people find entertaining movies, boost sales through

  6. Privacy enhanced recommender system

    NARCIS (Netherlands)

    Erkin, Zekeriya; Erkin, Zekeriya; Beye, Michael; Veugen, Thijs; Lagendijk, Reginald L.

    2010-01-01

    Recommender systems are widely used in online applications since they enable personalized service to the users. The underlying collaborative filtering techniques work on user’s data which are mostly privacy sensitive and can be misused by the service provider. To protect the privacy of the users, we

  7. Chapter 10: Management recommendations

    Science.gov (United States)

    Deborah M. Finch; Janie Agyagos; Tracy McCarthey; Robert M. Marshall; Scott H. Stoleson; Mary J. Whitfield

    2000-01-01

    This chapter was developed over a series of meetings using a group-consensus process. Our recommendations are based on published results, on information compiled in the previous chapters, on expert opinion, and on unpublished data of conservation team members. This chapter is available as temporary guidance until the Recovery Plan for the southwestern willow flycatcher...

  8. The In Vivo Effects of the CB1-Positive Allosteric Modulator GAT229 on Intraocular Pressure in Ocular Normotensive and Hypertensive Mice.

    Science.gov (United States)

    Cairns, Elizabeth A; Szczesniak, Anna-Maria; Straiker, Alex J; Kulkarni, Pushkar M; Pertwee, Roger G; Thakur, Ganesh A; Baldridge, William H; Kelly, Melanie E M

    2017-10-01

    Orthosteric cannabinoid receptor 1 (CB 1 ) activation leads to decreases in intraocular pressure (IOP). However, use of orthosteric CB 1 agonists chronically has several disadvantages, limiting their usefulness as clinically relevant drugs. Allosteric modulators interact with topographically distinct sites to orthosteric ligands and may be useful to circumvent some of these disadvantages. The purpose of this study was to investigate the effects of the novel CB 1 -positive allosteric modulator (PAM) GAT229 on IOP. IOP was measured using rebound tonometry in anesthetized normotensive C57Bl/6 mice and in a genetic model of ocular hypertension [nose, eyes, ears (nee) mice] before drug administration, and at 1, 6, and 12 h thereafter. In normotensive mice, topical administration of 5 μL GAT229 alone at either 0.2% or 2% did not reduce IOP. However, a subthreshold dose (0.25%) of the nonselective orthosteric CB 1 agonist WIN 55,212-2, when combined with 0.2% GAT229, significantly reduced IOP compared with vehicle at 6 and 12 h. Similarly, combination of subthreshold Δ 9 -tetrahydrocannabinol (a nonselective orthosteric CB 1 agonist; 1 mg/kg) with topical 0.2% GAT229 produced IOP lowering at 6 h. In nee mice, administration of topical 0.2% GAT229 or 10 mg/kg GAT229 alone was sufficient to lower IOP at 6 and 12 h, and 12 h, respectively. The CB 1 PAM GAT229 reduces IOP in ocular hypertensive mice and enhanced CB 1 -mediated IOP reduction when combined with subthreshold CB 1 orthosteric ligands in normotensive mice. Administration of CB 1 PAMs may provide a novel approach to reduce IOP with fewer of the disadvantages associated with orthosteric CB 1 activation.

  9. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

    Science.gov (United States)

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

  10. Biological characterization of PM226, a chromenoisoxazole, as a selective CB2 receptor agonist with neuroprotective profile.

    Science.gov (United States)

    Gómez-Cañas, M; Morales, P; García-Toscano, L; Navarrete, C; Muñoz, E; Jagerovic, N; Fernández-Ruiz, J; García-Arencibia, M; Pazos, M R

    2016-08-01

    Cannabinoids have emerged as promising neuroprotective agents due to their capability to activate specific targets, which are involved in the control of neuronal homeostasis and survival. Specifically, those ligands that selectively target and activate the CB2 receptor may be useful for their anti-inflammatory and neuroprotective properties in various neurological disorders, with the advantage of being devoid of psychotropic effects associated with the activation of CB1 receptors. The aim of this work has been to investigate the neuroprotective properties of 7-(1,1-dimethylheptyl)-4,4-dimethyl-9-methoxychromeno[3,4-d]isoxazole (PM226), a compound derived from a series of chromeno-isoxazoles and -pyrazoles, which seems to have a promising profile related to the CB2 receptor. The compound binds selectively to this receptor with an affinity in the nanomolar range (Ki=12.8±2.4nM). It has negligible affinity for the CB1 receptor (Ki>40000nM) and no activity at the GPR55. PM226 was also evaluated in GTPγS binding assays specific to the CB2 receptor showing agonist activity (EC50=38.67±6.70nM). In silico analysis of PM226 indicated that it has a good pharmacokinetic profile and a predicted ability to cross the blood-brain barrier. Next, PM226 was investigated in an in vitro model to explore its anti-inflammatory/neuroprotective properties. Conditioned media were collected from LPS-stimulated cultures of BV2 microglial cell line in the absence or presence of different doses of PM226, and then media were added to cultured M213-2O neuronal cells to record their influence on cell viability evaluated using MTT assays. As expected, cell viability was significantly reduced by the exposure to these conditioned media, while the addition of PM226 attenuated this reduction in a dose-dependent manner. This effect was reversed by co-incubating with the CB2 antagonist SR144528, thus confirming the involvement of CB2 receptors, whereas the addition of PM226 to neuronal cultures

  11. Innovation and the policy environment

    DEFF Research Database (Denmark)

    Baker, Derek; Hamann, Karen

    This report summarises discussions with a small number of meat industry firms about the effects of policy on their innovation activities, and their recommendations for future policy changes. Although firms, like researchers and policymakers, lack strong definitions and measurement procedures...... for innovation, they were able to list and describe their innovation processes and outcomes. Firms expressed some dissatisfaction with innovation policy, and were able to make a number of recommendations for change. Notably, this included its linkage to an overall strategy that emphasises international...

  12. IV. NIH Toolbox Cognition Battery (CB): measuring language (vocabulary comprehension and reading decoding).

    Science.gov (United States)

    Gershon, Richard C; Slotkin, Jerry; Manly, Jennifer J; Blitz, David L; Beaumont, Jennifer L; Schnipke, Deborah; Wallner-Allen, Kathleen; Golinkoff, Roberta Michnick; Gleason, Jean Berko; Hirsh-Pasek, Kathy; Adams, Marilyn Jager; Weintraub, Sandra

    2013-08-01

    Mastery of language skills is an important predictor of daily functioning and health. Vocabulary comprehension and reading decoding are relatively quick and easy to measure and correlate highly with overall cognitive functioning, as well as with success in school and work. New measures of vocabulary comprehension and reading decoding (in both English and Spanish) were developed for the NIH Toolbox Cognition Battery (CB). In the Toolbox Picture Vocabulary Test (TPVT), participants hear a spoken word while viewing four pictures, and then must choose the picture that best represents the word. This approach tests receptive vocabulary knowledge without the need to read or write, removing the literacy load for children who are developing literacy and for adults who struggle with reading and writing. In the Toolbox Oral Reading Recognition Test (TORRT), participants see a letter or word onscreen and must pronounce or identify it. The examiner determines whether it was pronounced correctly by comparing the response to the pronunciation guide on a separate computer screen. In this chapter, we discuss the importance of language during childhood and the relation of language and brain function. We also review the development of the TPVT and TORRT, including information about the item calibration process and results from a validation study. Finally, the strengths and weaknesses of the measures are discussed. © 2013 The Society for Research in Child Development, Inc.

  13. Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zarrindast

    2009-04-01

    Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

  14. Effect of Modified Alkaline Supplementation on Syngenic Melanoma Growth in CB57/BL Mice.

    Directory of Open Access Journals (Sweden)

    Tommaso Azzarito

    Full Text Available Tumor extracellular acidity is a hallmark of malignant cancers. Thus, in this study we evaluated the effects of the oral administration of a commercially available water alkalizer (Basenpulver® (BP on tumor growth in a syngenic melanoma mouse model. The alkalizer was administered daily by oral gavage starting one week after tumor implantation in CB57/BL mice. Tumors were calipered and their acidity measured by in vivo MRI guided 31P MRS. Furthermore, urine pH was monitored for potential metabolic alkalosis. BP administration significantly reduced melanoma growth in mice; the optimal dose in terms of tolerability and efficacy was 8 g/l (p< 0.05. The in vivo results were supported by in vitro experiments, wherein BP-treated human and murine melanoma cell cultures exhibited a dose-dependent inhibition of tumor cell growth. This investigation provides the first proof of concept that systemic buffering can improve tumor control by itself and that this approach may represent a new strategy in prevention and/or treatment of cancers.

  15. Backscatter measurements of aerosolized CB simulants with a frequency agile CO2 lidar

    Science.gov (United States)

    Vanderbeek, Richard; Gurton, Kristan

    2004-02-01

    A novel windowless chamber was developed to allow aerosol backscatter measurements with a frequency-agile CO2 lidar. The chamber utilizes curtains of air to contain the cloud, thus preventing the inevitable backscatter off of conventional windows from corrupting the desired measurements. This feature is critical because the CO2 lidar has a long (1 μs) pulse and the backscatter off the window cannot be temporally separated from the backscatter off the aerosol in the chamber. The chamber was designed for testing with a variety of CB simulants and interferents in both vapor and aerosol form and has been successfully shown to contain a cloud of known size, concentration, and particle size distribution for 10-15 minutes. This paper shows the results using Arizona road dust that was screened by the manufacturer into 0-3 μm and 5-10 μm particle size distributions. The measurements clearly show the effect of size distribution on the infrared backscatter coefficients as well as the dynamic nature of the size distribution for a population of aerosols. The test methodology and experimental results are presented.

  16. Electromagnetic Characterization of a Composite (RE-CB-MT by Time Domain Spectroscopy

    Directory of Open Access Journals (Sweden)

    Amina Bounar

    2017-01-01

    Full Text Available The aim of this article is to study the dielectric behavior (ε, σ in microwaves domain of composites made with Epoxy Resin (RE, Carbon Black (CB, and Magnesium Titanate (MT on a large band of frequency. This kind of composites is very solicited for applications and miniaturization of the components circuits (cavities, antennas, substrates, etc. in hyperfrequency electronics. In this study we have also highlighted the effect of the fillers nature and their concentrations on the behavior of these composites. The results obtained by time domain spectroscopy (TDS have revealed the strong dependence of complex permittivity of the composite materials on both the nature and the concentration of conductive environment. Low frequency analysis (500 MHz has been investigated to determine the conductivity of composites which is related to the percolation phenomenon. Moreover, the comparison between experimental results and theoretical models shows that the modeling Lichtenecker law is applicable to the ternary mixture in this frequency range and is in accordance with the approach postulated by Bottreau.

  17. Exposure to CB-153 and p,p'-DDE and human sperm chromatin integrity

    Energy Technology Data Exchange (ETDEWEB)

    Rignell-Hydbom, A.; Rylander, L.; Joensson, B.A.G.; Hagmar, L. [Dept. of Occupational and Environmental Medicine, Lund Univ. Hospital (Sweden); Giwercman, A. [Fertility Centre, Malmoe Univ. hospital (Sweden); Spano, M. [Section of Toxicology and Biomedical Sciences, ENEA Casaccia Research Centre, Rome (Italy)

    2004-09-15

    In Sweden, the consumption of fatty fish from the Baltic Sea (off the Swedish east coast) is the single most important source of exposure to persistent organochlorine pollutants (POPs). Fishermen from the east coast have averagely higher plasma levels of polychlorinated biphenyls (PCBs) and total POP derived TEQ in plasma than both west coast fishermen and men from the general population. Dichlorodiphenyl dichloroethene (p,p'-DDE), a relevant biomarker for POP is still present in relatively high serum concentrations in men consuming fish from the Baltic Sea. Several studies have shown that POPs are capable of interfering with reproductive and endocrine function in animals. Human studies have shown that exposure to PCBs and polychlorinated dibenzofurans (PCDFs) has a negative effect on male reproductive function, and especially sperm motility seems vulnerable. However, studies relating to human sperm genetic integrity are few. The aim of the study was to investigate whether exposure to POP using 2,2',4,4',5,5'- hexachlorobiphenyl (CB-153) and p,p'-DDE as biomarkers, are associated with sperm chromatin integrity. In order to ensure a sufficient variation in POP exposure fishermen from both the Swedish east (''more exposed'') and west coasts (''less exposed'') formed the study base.

  18. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Kraus, V B; Blanco, F J; Englund, M

    2015-01-01

    The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from...... both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials...... and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety...

  19. 16 CFR Appendix I to Part 1402 - Recommended Outline for Instruction Booklet on “How To Safely Install Your CB Base Station Antenna”

    Science.gov (United States)

    2010-01-01

    .... d. Raising the mast without an X-frame. 4. Guy Wires. B. How to Install a Tripod: 1. Preparation. 2... Mount: a. Preparation. b. Erecting the assembly. c. Securing the assembly. 2. Chimney Mount: a.... Preparation. 2. Erecting the assembly. 3. Securing the assembly. E. How to Install a Tower:* 1. Preparation. 2...

  20. Recommending audio mixing workflows

    OpenAIRE

    Sauer, Christian; Roth-Berghofer, Thomas; Auricchio, Nino; Proctor, Sam

    2013-01-01

    This paper describes our work on Audio Advisor, a workflow recommender for audio mixing. We examine the process of eliciting, formalising and modelling the domain knowledge and expert’s experience. We are also describing the effects and problems associated with the knowledge formalisation processes. We decided to employ structured case-based reasoning using the myCBR 3 to capture the vagueness encountered in the audio domain. We detail on how we used extensive similarity measure modelling to ...

  1. Badali recommends simplified bills

    International Nuclear Information System (INIS)

    Anon

    2003-01-01

    A report on the variety of retail electricity bills across the province, authored by Salvatore Badali of Deloitte Consulting, was recently released by the Ontario Government. The report was commissioned by the Government to examine the underlying reasons for the significant format differences and the wide variation of fixed and variable charges among the approximately 95 local electricity distribution companies across the province. Regarding the appropriateness of the charges the report recommends common definitions for local distribution company (LDC) fixed and variable costs, and consideration of options for reducing LDC charges, mainly by consolidating the sector and sharing such services as customer billing, accounting and out sourcing operations. Seven recommendations deal with bill simplification. These include bills that are clear and easy to read and provide sufficient information for consumers to verify charges; promote energy conservation, e.g. by including historical information; allow comparisons between retail suppliers and distributors; accommodate revenue collection, marketing needs and other billing services. The report also recommends clearly defined and consistently used terminology for standardized line items, suggests ways to provide consumer information in a form useful for making energy conservation decisions, development of an LDC scorecard to enable stake holders to compare their own LDCs with LDCs around the province, creation of a conservation and bill calculation website, consideration of further use of shared services, and solutions to address the removal of line losses from invoices

  2. Tough Policies, Incredible Policies?

    OpenAIRE

    Andres Velasco; Alejandro Neut

    2003-01-01

    We revisit the question of what determines the credibility of macroeconomic policies here, of promises to repay public debt. Almost all thinking on the issue has focused on governments' strategic decision to default (or erode the value of outstanding debt via inflation/devaluation). But sometimes governments default not because they want to, but because they cannot avoid it: adverse shocks leave them no option. We build a model in which default/devaluation can occur deliberately (for strategi...

  3. The 16 CB11(CH3)(n)(CD3)(12-n)(center dot) Radicals with 5-Fold Substitution Symmetry: Spin Density Distribution in CB11Me12 center dot

    Czech Academy of Sciences Publication Activity Database

    Kaleta, Jiří; Tarábek, Ján; Akdag, A.; Pohl, Radek; Michl, Josef

    2012-01-01

    Roč. 51, č. 20 (2012), s. 10819-10824 ISSN 0020-1669 R&D Projects: GA ČR GC203/09/J058 Grant - others:AV ČR(CZ) M200550906 Institutional support: RVO:61388963 Keywords : anion * oxidation * polymerization * isobutylene * carboranes * CB11Me12 Subject RIV: CC - Organic Chemistry Impact factor: 4.593, year: 2012

  4. Structural Volatility in Mexico: A Policy Report

    OpenAIRE

    Caballero, Ricardo J.

    2000-01-01

    This paper surveys Mexico`s economic weaknesses and provides related policy recommendations. Current problems include weak international financial links and external conditions, a recurrent credit crunch and financial underdevelopment problem, with particularly fragile banks, a weak fiscal situation, due to extreme vulnerability to internal and external shocks, and a latent monetary policy credibility problem. The paper`s policy recommendations include improving external financial links, redu...

  5. CB1 Receptor Activation on VgluT2-Expressing Glutamatergic Neurons Underlies Δ9-Tetrahydrocannabinol (Δ9-THC)-Induced Aversive Effects in Mice.

    Science.gov (United States)

    Han, Xiao; He, Yi; Bi, Guo-Hua; Zhang, Hai-Ying; Song, Rui; Liu, Qing-Rong; Egan, Josephine M; Gardner, Eliot L; Li, Jing; Xi, Zheng-Xiong

    2017-09-26

    Cannabis can be rewarding or aversive. Cannabis reward is believed to be mediated by activation of cannabinoid CB1 receptors (CB1Rs) on GABAergic neurons that disinhibit dopaminergic neurons in the ventral tegmental area (VTA). However, little is known about the mechanisms underlying cannabis aversion in rodents. In the present study, CB1Rs are found not only on VTA GABAergic neurons, but also on VTA glutamatergic neurons that express vesicular glutamate transporter 2 (VgluT2). We then used Cre-Loxp transgenic technology to selectively delete CB1Rs in VgluT2-expressing glutamatergic neurons (VgluT2-CB1 -/- ) and Cre-dependent viral vector to express light-sensitive channelrhodopsin-2 into VTA glutamatergic neurons. We found that photoactivation of VTA glutamatergic neurons produced robust intracranial self-stimulation (ICSS) behavior, which was dose-dependently blocked by DA receptor antagonists, but enhanced by cocaine. In contrast, Δ 9 -tetrahydrocannabinol (Δ 9 -THC), the major psychoactive component of cannabis, produced dose-dependent conditioned place aversion and a reduction in the above optical ICSS in VgluT2-cre control mice, but not in VgluT2-CB1 -/- mice. These findings suggest that activation of CB1Rs in VgluT2-expressing glutamate neurons produces aversive effects that might explain why cannabinoid is not rewarding in rodents and might also account for individual differences in the hedonic effects of cannabis in humans.

  6. A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands.

    Science.gov (United States)

    Ishiguro, H; Carpio, O; Horiuchi, Y; Shu, A; Higuchi, S; Schanz, N; Benno, R; Arinami, T; Onaivi, E S

    2010-01-01

    Marijuana use activates cannabinoid receptors (CB-Rs) producing several behavioral effects related to addiction, mood, and appetite. We investigated the association between CNR2 gene, which encodes cannabinoid CB2 receptor (CB2-R) and eating disorders in 204 subjects with eating disorders and 1876 healthy volunteers in Japanese population. The effect of treatment with CB2-R ligands on mouse food consumption was also determined. The CB2-R ligands used suppressed food intake in a time- and strain-dependent manner when food was available ad libitum and during the 12-h fast except, AM 630-the CB2-R antagonist that stimulated food consumption in food-deprived mice. There is an association between the R63Q polymorphism of the CNR2 gene and eating disorders (P = 0.04; Odds ratio 1.24, 95% CI, (1.01-1.53). These results suggest that cannabinoid CB2-R is involved in the endocannabinoid signaling mechanisms associated with the regulation of food intake and in eating disorders.

  7. Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sung-Yun Cho

    2013-01-01

    Full Text Available Here, antitumor mechanism of cinnamaldehyde derivative CB-PIC was elucidated in human SW620 colon cancer cells. CB-PIC significantly exerted cytotoxicity, increased sub-G1 accumulation, and cleaved PARP with apoptotic features, while it enhanced the phosphorylation of AMPK alpha and ACC as well as activated the ERK in hypoxic SW620 cells. Furthermore, CB-PIC suppressed the expression of HIF1 alpha, Akt, and mTOR and activated the AMPK phosphorylation in hypoxic SW620 cells. Conversely, silencing of AMPKα blocked PARP cleavage and ERK activation induced by CB-PIC, while ERK inhibitor PD 98059 attenuated the phosphorylation of AMPKα in hypoxic SW620 cells, implying cross-talk between ERK and AMPKα. Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1α and Akt/mTOR and the activation of AMPKα and pACC in hypoxic SW620 cells. In addition, CB-PIC suppressed the growth of SW620 cells inoculated in BALB/c athymic nude mice, and immunohistochemistry revealed that CB-PIC treatment attenuated the expression of Ki-67, CD34, and CAIX and increased the expression of pAMPKα in CB-PIC-treated group. Interestingly, CP-PIC showed better antitumor activity in SW620 colon cancer cells under hypoxia than under normoxia, since it may be applied to chemoresistance. Overall, our findings suggest that activation of AMPKα and ERK mediates CB-PIC-induced apoptosis in hypoxic SW620 colon cancer cells.

  8. CB1 receptors in the formation of the different phases of memory-related processes in the inhibitory avoidance test in mice.

    Science.gov (United States)

    Kruk-Slomka, Marta; Biala, Grażyna

    2016-03-15

    The endocannabinoid system, through the cannabinoid type 1 (CB1) and 2 (CB2) receptors modulates many physiological functions, including different aspects of memory-related processes. The aim of the present experiments was to explore the role of the endocannabinoid system, through CB1 receptors in the different stages of short-term (acquisition, retention and retrieval) and long-term (acquisition, consolidation and retrieval) memory-related responses, using the inhibitory avoidance (IA) test in mice. Our results revealed that an acute injection of oleamide (10 and 20mg/kg), a CB1 receptor agonist, impairs the short-term or/and long-term acquisition, retention/consolidation, retrieval memory and learning processes in the IA test in mice. In turn, in this test an acute injection of AM 251 (1 and 3mg/kg), a CB1 receptor antagonist, improves the short-term or/and long-term memory stages, described above. Moreover, this memory impairment induced by effective dose of oleamide (20mg/kg) is reversed by non-effective dose of AM 251 (0.25mg/kg) in the IA task, which proves the selectivity of oleamide to CB1 receptors and confirms that the CB1 receptor-related mechanism is one of the possible mechanisms, responsible for memory and learning responses. Obtained results provide clear evidence that the endocannabinoid system, through CB1 receptors, participates in the different stages of short- and long-term memory-related behavior. This knowledge may open in the future new possibilities for the development of CB-based therapies, especially for memory impairment human disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Comparison of Cell Regeneration Mechanisms Between Isolated Cb Clouds Moving Along A Valley and Over Flat Terrain

    Science.gov (United States)

    Curic, M.; Janc, D.; Vuckovic, V.; Vujovic, D.

    Cell regeneration mechanism within air-mass Cb cloud moving along the river valley is investigated by three-dimensional mesoscale ARPS model with improved micro- physics. Simulated cloud characteristics are then compared with those performed for the flat terrain conditions. The Western Morava valley area (Serbia) has selected as an important place for formation of such clouds in agreement with observations. Ana- lyzed results suggest that the river valley plays an important role for the cell regenera- tion mechanism in front of the mother cloud. Futher, it contributes to the fast Cb cloud propagation along the valley. In contrast, the front-side cell regeneration mechanism is absent for the flat terrain conditions since the cold air below cloud base deverges in all directions without any restrictions. This investigation gives us more complete insight in cell regeneration mechanisms than classic approach.

  10. Predicting the properties of a new class of host-guest complexes: C60 fullerene and CB[9] cucurbituril.

    Science.gov (United States)

    Fileti, Eudes; Colherinhas, Guilherme; Malaspina, Thaciana

    2014-11-07

    DFT, semi-empirical and classical molecular dynamics methods were used to describe the structure and stability of the inclusion complex formed by the fullerene C60 and the cucurbituril CB[9]. Our results indicate a high structural compatibility between the two monomers, which is evident from the potential energy curve for the inclusion process of the C60 into the CB[9] cavity. The interaction between the two monomers is mainly of the van der Waals type and leads to a highly stable complex. Thermal contributions and environmental interaction are taken into account by the free energy of binding of -224 kJ mol(-1), indicating that even in aqueous medium the complex remains very stable.

  11. The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala.

    Science.gov (United States)

    Ratano, Patrizia; Everitt, Barry J; Milton, Amy L

    2014-10-01

    We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.

  12. ICRS Recommendation Document

    DEFF Research Database (Denmark)

    Roos, Ewa M.; Engelhart, Luella; Ranstam, Jonas

    2011-01-01

    and function evaluated for validity and psychometric properties in patients with articular cartilage lesions. Results: The knee-specific instruments, titled the International Knee Documentation Committee Subjective Knee Form and the Knee injury and Osteoarthritis and Outcome Score, both fulfill the basic......, and confirmatory longitudinal studies are needed prior to recommending this scale for use in cartilage repair. Inclusion of a generic measure is feasible in cartilage repair studies and allows analysis of health-related quality of life and health economic outcomes. The Marx or Tegner Activity Rating Scales...

  13. Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography

    International Nuclear Information System (INIS)

    Terry, Garth E.; Hirvonen, Jussi; Liow, Jeih-San; Seneca, Nicholas; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B.; Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C.; Halldin, Christer

    2010-01-01

    Cannabinoid subtype 1 (CB 1 ) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB 1 receptors with two PET radioligands: 11 C-MePPEP and 18 F-FMPEP-d 2 . Here we describe the biodistribution and dosimetry estimates for these two radioligands. Seven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with 11 C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with 18 F-FMPEP-d 2 . Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for 18 F-FMPEP-d 2 . The effective doses of 11 C-MePPEP and 18 F-FMPEP-d 2 are 4.6 and 19.7 μSv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of 11 C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from 18 F-FMPEP-d 2 showed both hepatobiliary and urinary excretion. 11 C-MePPEP and 18 F-FMPEP-d 2 yield an effective dose similar to other PET radioligands labeled with either 11 C or 18 F. The high uptake in brain confirms the utility of these two radioligands to image CB 1 receptors in brain, and both may also be useful to image CB 1 receptors in the periphery. (orig.)

  14. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism

    Science.gov (United States)

    Hill, T D M; Cascio, M-G; Romano, B; Duncan, M; Pertwee, R G; Williams, C M; Whalley, B J; Hill, A J

    2013-01-01

    BACKGROUND AND PURPOSE Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors. EXPERIMENTAL APPROACH The anticonvulsant profiles of two CBDV BDSs (50–422 mg·kg−1) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays. KEY RESULTS CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg−1) and audiogenic seizure models (≥87 mg·kg−1), and suppressed pilocarpine-induced convulsions (≥100 mg·kg−1). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ9-tetrahydrocannabinol and Δ9-tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV. CONCLUSIONS AND IMPLICATIONS CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy. PMID:23902406

  15. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.

    Science.gov (United States)

    Hill, T D M; Cascio, M-G; Romano, B; Duncan, M; Pertwee, R G; Williams, C M; Whalley, B J; Hill, A J

    2013-10-01

    Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors. The anticonvulsant profiles of two CBDV BDSs (50-422 mg·kg(-1) ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays. CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg(-1) ) and audiogenic seizure models (≥87 mg·kg(-1) ), and suppressed pilocarpine-induced convulsions (≥100 mg·kg(-1) ). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ(9) -tetrahydrocannabinol and Δ(9) -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV. CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy. © 2013 The British Pharmacological Society.

  16. Endocannabinoid activation of CB1receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation.

    Science.gov (United States)

    Sun, L; Tai, L; Qiu, Q; Mitchell, R; Fleetwood-Walker, S; Joosten, E A; Cheung, C W

    2017-05-01

    Spinal cord stimulation (SCS) has been shown to be effective in the management of certain neuropathic pain conditions, however, the underlying mechanisms are incompletely understood. In this study, we investigated repetitive SCS in a rodent neuropathic pain model, revealing long-lasting and incremental attenuation of hyperalgesia and a mechanism of action involving endocannabinoids. Animals were implanted with monopolar electrodes at the time of partial sciatic nerve injury. Dorsal columns at spinal segments T12/13 were stimulated 3 days later (early SCS), and again at day 7 (late SCS) using low-frequency parameters. Hypersensitivity to cutaneous mechanical stimuli was assessed using von Frey filaments. Pharmacological agents, selected to identify endocannabinoid and opioid involvement, were administered intraperitoneally, 10 min before SCS. Early SCS caused partial reversal of mechanical hypersensitivity with corresponding changes in the biomarker of central sensitization, [phospho-Tyr 1472 ]-GluN2B. The partial reversal of hyperalgesia by early SCS was amplified by co-administration of LY 2183240, an inhibitor of endocannabinoid reuptake/breakdown. This amplification was inhibited by a CB 1 R antagonist, AM251, but not by a CB 2 R antagonist, AM630. Early SCS-induced reversal of hyperalgesia was attenuated by naloxone, indicating a role for opioids. Late SCS resulted in an incremental level of reversal of hyperalgesia, which was inhibited by AM251, but not by CB 2 or opioid receptor antagonists. The endocannabinoid system, and in particular the CB 1 R, plays a pivotal role in the long-lasting and incremental reversal of hyperalgesia induced by repetitive SCS in a neuropathic pain model. Alternative parameters for repetitive spinal cord stimulation (SCS) at 25/10 Hz elicit particularly long-lasting and incremental reversal of hyperalgesia in a neuropathic pain model through a mechanism involving endocannabinoids. © 2017 European Pain Federation - EFIC®.

  17. Trade policy and health: from conflicting interests to policy coherence.

    Science.gov (United States)

    Blouin, Chantal

    2007-03-01

    Policy incoherence at the interface between trade policy and health can take many forms, such as international trade commitments that strengthen protection of pharmaceutical patents, or promotion of health tourism that exacerbates the shortage of physicians in rural areas. Focusing on the national policy-making process, we make recommendations regarding five conditions that are necessary, but not sufficient, to ensure that international trade policies are coherent with national health objectives. These conditions are: space for dialogue and joint fact-finding; leadership by ministries of health; institutional mechanisms for coordination; meaningful engagement with stakeholders; and a strong evidence base.

  18. Toxin-Antitoxin Systems in Estuarine Synechococcus Strain CB0101 and Their Transcriptomic Responses to Environmental Stressors

    Directory of Open Access Journals (Sweden)

    David Marsan

    2017-07-01

    Full Text Available Bacterial toxin–antitoxin (TA systems are genetic elements composed of a toxin gene and its cognate antitoxin, with the ability to regulate growth. TA systems have not previously been reported in marine Synechococcus or Prochlorococcus. Here we report the finding of seven TA system pairs (Type II in the estuarine Synechococcus CB0101, and their responses of these TA genes to under different stress conditions, which include; nitrogen and phosphate starvation, phage infection, zinc toxicity, and photo-oxidation. Database searches discovered that eight other marine Synechococcus strains also contain at least one TA pair but none were found in Prochlorococcus. We demonstrate that the relB/relE TA pair was active and resulted in RNA degradation when CB0101 was under oxidative stress caused by either zinc toxicity or high light intensities, but the growth inhibition was released when the stress was removed. Having TA systems allows Synechococcus CB0101 to adapt to the low light and highly variable environments in the Chesapeake Bay. We propose that TA systems could be more important for picocyanobacteria living in the freshwater and estuarine environments compared to those living in the open ocean.

  19. Combined multi-spectrum and orthogonal Laplacianfaces for fast CB-XLCT imaging with single-view data

    Science.gov (United States)

    Zhang, Haibo; Geng, Guohua; Chen, Yanrong; Qu, Xuan; Zhao, Fengjun; Hou, Yuqing; Yi, Huangjian; He, Xiaowei

    2017-12-01

    Cone-beam X-ray luminescence computed tomography (CB-XLCT) is an attractive hybrid imaging modality, which has the potential of monitoring the metabolic processes of nanophosphors-based drugs in vivo. Single-view data reconstruction as a key issue of CB-XLCT imaging promotes the effective study of dynamic XLCT imaging. However, it suffers from serious ill-posedness in the inverse problem. In this paper, a multi-spectrum strategy is adopted to relieve the ill-posedness of reconstruction. The strategy is based on the third-order simplified spherical harmonic approximation model. Then, an orthogonal Laplacianfaces-based method is proposed to reduce the large computational burden without degrading the imaging quality. Both simulated data and in vivo experimental data were used to evaluate the efficiency and robustness of the proposed method. The results are satisfactory in terms of both location and quantitative recovering with computational efficiency, indicating that the proposed method is practical and promising for single-view CB-XLCT imaging.

  20. A cell population that strongly expresses the CB1 cannabinoid receptor in the ependyma of the rat spinal cord.

    Science.gov (United States)

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Sierra-Palomares, Yolanda; Molina-Holgado, Eduardo

    2013-01-01

    The cells surrounding the central canal of the spinal cord are a source of stem/precursor cells that may give rise to neurons, astrocytes, or oligodendrocytes. However, they are a heterogeneous population that remains poorly understood. Here we describe a subpopulation characterized by their strong expression of the CB(1) cannabinoid receptor, oval/round soma, apical nucleus, a variable number of cilia (0, 1, or 2), and the presence of a single short and occasionally ramified basal process. These cells are mainly located in the lateral and dorsal central canal throughout the spinal cord. These CB(1)(HIGH) cells are closely related to the basal lamina labyrinths or fractones derived from subependymal microglia. In addition, CB(1)(HIGH) cells express some stem/precursor cell markers, including vimentin, nestin, Sox2, Sox9, and GLAST, but not others such as CD15 or GFAP. In addition, this cell population does not proliferate in the intact adult spinal cord, although up to 50% of these cells express the proliferation marker Ki67 in newly born rats or after a spinal cord contusion. The present findings contribute to our understanding of the spinal cord central canal structure and reveal the targets for endocannabinoids inside this neurogenic niche. Copyright © 2012 Wiley Periodicals, Inc.

  1. Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK.

    Science.gov (United States)

    Hwang, Young Sun; Kim, Youn-Jung; Kim, Mi Ok; Kang, Mingyeong; Oh, Sae Woong; Nho, Youn Hwa; Park, See-Hyoung; Lee, Jongsung

    2017-08-01

    Melanogenesis plays a critical role in the protection of skin against external stresses such as ultraviolet irradiation and oxidative stressors. This study was aimed to investigate the effects of cannabidiol on melanogenesis and its mechanisms of action in human epidermal melanocytes. We found that cannabidiol increased both melanin content and tyrosinase activity. The mRNA levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP) 1, and TRP2 were increased following cannabidiol treatment. Likewise, cannabidiol increased the protein levels of MITF, TRP 1, TRP 2, and tyrosinase. Mechanistically, we found that cannabidiol regulated melanogenesis by upregulating MITF through phosphorylation of p38 mitogen-activated protein kinase (MAPK) and p42/44 MAPK, independent of cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling. In addition, the melanogenic effect of cannabidiol was found to be mediated by cannabinoid CB 1 receptor, not by CB 2 receptor. Taken together, these findings indicate that cannabidiol-induced melanogenesis is cannabinoid CB 1 receptor-dependent, and cannabidiol induces melanogenesis through increasing MITF gene expression which is mediated by activation of p38 MAPK and p42/44 MAPK. Our results suggest that cannabidiol might be useful as a protective agent against external stresses. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Involvement of cannabinoid CB1 receptors in drug addiction: effects of rimonabant on behavioral responses induced by cocaine.

    Science.gov (United States)

    Filip, Małgorzata; Gołda, Anna; Zaniewska, Magdalena; McCreary, Andrew C; Nowak, Ewa; Kolasiewicz, Wacław; Przegaliński, Edmund

    2006-01-01

    A lot of evidence indicate that endocannabinoids and cannabinoid CB(1) receptors are implicated in drug addiction. In the present study, we investigated the effect of the cannabinoid CB(1) receptor antagonist/partial agonist rimonabant on the cocaine-maintained reinforcement and relapse to cocaine seeking as well as on the cocaine challenge-induced hyperactivity in sensitized rats and on discriminative stimulus effects of cocaine in rats. We found that endocannabinoids were not involved in maintenance of cocaine reinforcement and its subjective effects since pharmacological blockade of cannabinoid CB(1) receptors altered neither self-administration nor discriminative stimulus effects of cocaine. On the other hand, withdrawal from repeated access or exposure to cocaine and then a reinstatement of cocaine-seeking behavior or a sensitized locomotor response to a single cocaine challenge, respectively, was potently reduced by pretreatment with rimonabant. The latter observations may show that repeated cocaine treatment and the drug withdrawal produce--apart from behavioral effects--also different neural consequences in the endocannabinoid systems in rats.

  3. DETECTION OF TWO CARBON-CHAIN-RICH CORES: CB130-3 AND L673-SMM4

    International Nuclear Information System (INIS)

    Hirota, Tomoya; Sakai, Takeshi; Sakai, Nami; Yamamoto, Satoshi

    2011-01-01

    We have found two dense cores, CB130-3 and L673-SMM4, where the carbon-chain molecules are extremely abundant relative to NH 3 , during a survey observation of radio emission lines of CCS, HC 3 N, HC 5 N, and NH 3 toward dark cloud cores. Judging from the low NH 3 /CCS ratios, they are possible candidates for 'Carbon-Chain-Producing Regions' (CCPRs) recognized as chemically young dark cloud cores. The deuterium fractionation ratios DNC/HN 13 C in CB130-3 and L673-SMM4 are found to be 1.28 +0.27 -0.05 and 1.96 +0.32 -0.01 , respectively, which are comparable to or slightly higher than those in CCPRs found previously. We suggest that the dense cores of CB130-3 and L673-SMM4 are analogous to CCPRs, but their chemical evolutionary phase would be slightly older than those of the dense cores in the Taurus region.

  4. Community-Based Coastal Resource Management (CB-CRM: a Case Study f Mariveles, Bataan, Philippines

    Directory of Open Access Journals (Sweden)

    Andrew Lou L. Mungcal

    2013-11-01

    Full Text Available This paper addressed the issue of sustainable coastal resource management through a successful Community-Based Coastal Resource Management (CB-CRM Program in the Municipality of Mariveles, province of Bataan in the Philippines. The paper investigated how governance and institutional and legislative framework, and the concept of sustainable development complemented each other to promote good local eco-governance in the management and protection of finite local marine resources. Specifically, it analyzed how the local fisherfolk community of Mariveles utilized efficiently their finite marine resources in the context of eco-governance. It also investigated how the cooperative efforts of various stakeholders: peoples’ organizations (POs, local government unit (LGU, and a non-government organization (NGO in Mariveles, Bataan affected their coastal resources against environmental degradation and exploitation. This paper would benefit POs, LGUs, and NGOs in their quest for sustainable management and conservation of their limited coastal resources. This paper yielded the following findings. First, POs and NGOs engage when NGOs can strengthen the POs’ capacity building through the transfer of skills and technology, when NGOs can enhance the POs’ indigenous knowledge, and when NGOs are more knowledgeable of formal venues of LGU participation. Second, LGUs, NGOs and POs engage when POs and NGOs can complement each other to strengthen their capacity building, and when NGOs can help implement environmental programs that are beneficial to the POs. Third, NGOs and POs engage when POs are threatened by elite power, and when NGOs want their environmental issues on LGU’s legislative agenda. Finally, NGOs and POs engage when they see possible LGU cooperation. Participant observation through focus group discussion (FGD and key informants’ interview of different stakeholders was a primary source of information in formulating the aforementioned conclusions

  5. Small quartz silica spheres induced disorder in octylcyanobiphenyl (8CB) liquid crystals: A thermal study

    International Nuclear Information System (INIS)

    Marinelli, M.; Ghosh, A. K.; Mercuri, F.

    2001-01-01

    A photopyroelectric technique has been applied to the study of specific heat and thermal conductivity of homeotropically aligned mixtures of small quartz spheres (aerosil) and octylcyanobiphenyl (8CB) with concentration 0≤ρ s ≤0.04g/cm 3 . Thermal conductivity data show that, even at these very low concentrations, an annealing of the disorder introduced by the aerosil takes place on cooling at the smectic-A - nematic (Sm-A - N) phase transition and not only at the nematic-isotropic (N-I) one. This means that there is some elastic strain in the nematic phase of the sample which is not quenched. Accordingly the suppression of the N-I transition temperature as a function of ρ s does not fit a random field with a random dilution model that accounts for random quenched disorder only. High resolution specific heat measurements at the A-N and N-I transition show the effect of the aerosil is not the same. While in the first case its peak is suppressed with increasing concentration, in the second case there are some indications that outside the two-phase coexistence region it is enhanced. The effect of surface-induced alignment is also discussed to explain some discrepancies between our data and the ones reported in literature. It is concluded that the amount of disorder in the sample does not depend on ρ s only, but also on other variables such as external fields. Finally, a relaxation phenomenon in the aerosil network that partially compensate the disordering effect of the particles is suggested to explain the concentration dependence of the transition temperatures

  6. Ebola virus: recommendations

    CERN Multimedia

    CERN Medical Service

    2014-01-01

    The CERN Medical Service has been closely following, in particular via the WHO, the development of the Ebola virus outbreak currently affecting some African countries. This infectious disease may be passed on through direct contact with the bodily fluids of a sick person.   Based on the recommendations of the WHO and the two Host States, Switzerland and France, as updated on their respective websites, so far there has been no ban on travel to the countries concerned. However, unless it is absolutely essential, you are advised not to visit any of the countries affected by Ebola (Guinea, Republic of Sierra Leone, Liberia, Nigeria). The two Host States have established an alert system, and a check is carried out on departure from the airports of those countries. It is strongly recommended that you contact the Medical Service if you are travelling to those countries. We remind you to observe the basic rules of hygiene such as frequent hand washing, whatever your destination. The Medical Service is...

  7. Infant and young child feeding in four departments in Haiti: mixed-method study on prevalence of recommended practices and related attitudes, beliefs, and other determinants

    Directory of Open Access Journals (Sweden)

    Anne Laterra

    2014-11-01

    Full Text Available OBJECTIVE: To determine and describe the prevalence and patterns of three recommended practices for infant and young child feeding-exclusive breastfeeding (EB, continued breastfeeding (CB, and achievement of minimum dietary diversity-in four regions in Haiti, and to identify the attitudes and beliefs that inform these practices and any other factors that may facilitate or impede their implementation. METHODS: This study utilized a mixed-methods approach consisting of 1 a cross-sectional survey (n = 310 and 2 12 focus group discussions among women ≥18 years old with children ≤ 2 years old. Multivariable logistic regression analyses were conducted to identify factors associated with 1 EB during the first six months of life, 2 CB for children ≥ 2 years old, and 3 receipt of a diverse variety of complementary foods. Qualitative data were recorded, transcribed verbatim, and analyzed for common themes. Data were collected in June and July 2013 in four departments in Haiti: Artibonite, Nippes, Ouest, and Sud-Est. RESULTS: Prevalence of EB, CB, and achievement of minimum dietary diversity was 57.0%, 11.9%, and 21.2% respectively. EB was statistically significantly associated with infant's age when controlling for annual household income, location of most recent birth, or receipt of CB counseling (odds ratio (OR = 0.67 (95% CI: 0.47-0.97. CB was not statistically significantly associated with rural place of residence, receipt of CB counseling, parity, or infant's age. Meeting minimum dietary diversity was not significantly associated with parity, receipt of postnatal care, rural place of residence, location of most recent birth, receipt of infant and young child feeding counseling, or level of schooling. Beliefs surrounding the relationship between the mother's health and her diet on the quality of breast milk may prohibit EB and CB. Qualitative data revealed that dietary diversity may be low because 1 mothers often struggle to introduce

  8. Mining and representing recommendations in actively evolving recommender systems

    DEFF Research Database (Denmark)

    Assent, Ira

    2010-01-01

    Recommender systems provide an automatic means of filtering out interesting items, usually based on past similarity of user ratings. In previous work, we have suggested a model that allows users to actively build a recommender network. Users express trust, obtain transparency, and grow (anonymous......) recommender connections. In this work, we propose mining such active systems to generate easily understandable representations of the recommender network. Users may review these representations to provide active feedback. This approach further enhances the quality of recommendations, especially as topics...... of interest change over time. Most notably, it extends the amount of control users have over the model that the recommender network builds of their interests....

  9. Wind farm policy 1995

    International Nuclear Information System (INIS)

    Anon.

    1995-03-01

    Argyll and Bute District Council, having received a number of planning applications for the erection of wind farms, seeks, in this document, to set out its environmental policy on these installations in line with national government guidelines and those from Strathclyde Regional Council. District Council policy on thirteen environmental issues connected with wind farm construction is set out, covering issues such as environmental impacts on wild-life, noise pollution, access for construction, maintenance and decommissioning vehicles as well as planning consent issues. Recommendations are made to four interested bodies, Strathclyde Regional Council, the Forestry Authority and Scottish Natural Heritage and the Royal Society for the Protection of Birds. (UK)

  10. Nutrition recommendations and science: next parallel steps.

    Science.gov (United States)

    Fogelholm, Mikael

    2016-03-15

    This article examines nutrition recommendations in relation to developments in nutrition science. Combining data on the genome, metabolome and microbiota is likely to open possibilities for personalized nutrition planning, but we are still far from practical applications. However, even these new steps are unlikely to challenge the role and importance of population-based nutrition recommendations as a tool to promote dietary patterns, policies and public health. Developments in science could help in deriving more benefits from nutrition recommendations. For instance, improved accuracy of dietary intake assessment is needed both for surveillance and for understanding the quantitative interplay between diet and health. Applying metabolomics together with food diaries or questionnaires, and also modern technologies such as digital photography, are potentially interesting methods in this respect. Research on consumer behaviour, attitudes and policy interventions, such as taxation of unhealthy foods and nutrition labelling, are needed to gain more insight into how to change eating behaviour for better health at the population level. © 2015 Society of Chemical Industry.

  11. Tobacco Free * Japan: Recommendations for Tobacco Control Policy

    OpenAIRE

    Mochizuki-Kobayashi, Y; Samet, JM; Yamaguchi, N

    2004-01-01

    Worldwide, tobacco use is a leading cause of preventable disease and premature death. For a century, large corporations have manufactured and sold cigarettes, a highly, addictive tobacco product. Today, over 1 billion people smoke. In recent decades, as smoking has declined in developed countries, the multinational tobacco companies have aggressively sought new markets in the developing countries. In Japan, tobacco smoking is one of the main avoidable causes of disease and death. The...

  12. Relieving Consumer Overindebtedness in South Africa: Policy Reviews and Recommendations

    Science.gov (United States)

    Ssebagala, Ralph Abbey

    2017-01-01

    A large fraction of South African consumers are highly leveraged, inadequately insured, and/or own little to no assets of value, which increases their exposure not only to idiosyncratic risk but also to severe indebtedness and/or default. This scenario can present negative ramifications that lead well beyond the confines of individual households.…

  13. Decarbonizing the international shipping industry : solutions and policy recommendations

    NARCIS (Netherlands)

    el Makhloufi, A.

    2017-01-01

    Ship-source greenhouse gas (GHG) emissions could increase by up to 250% from 2012 levels by 2050 owing to increasing global freight volumes. Binding international legal agreements to regulate GHGs, however, are lacking as technical solutions remain expensive and crucial industrial support is absent.

  14. Islamic Fundamentalism in Egypt: U.S. Policy Recommendations

    National Research Council Canada - National Science Library

    Liberatore, Carla

    1994-01-01

    Islamic fundamentalism is frightening to many Americans. It immediately draws reminders of the American hostages in Iran, the Ayatollah Khomeni, and the bombing of the World Trade Center in New York...

  15. Basolateral amygdala CB1 cannabinoid receptors are involved in cross state-dependent memory retrieval between morphine and ethanol.

    Science.gov (United States)

    Ofogh, Sattar Norouzi; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

    2016-09-01

    Ethanol and morphine are largely co-abused and affect memory formation. The present study intended to investigate the involvement of cannabinoid CB1 receptors of the basolateral amygdala (BLA) in cross state-dependent memory retrieval between morphine and ethanol. Adult male Wistar rats received bilateral cannulation of the BLA, and memory retrieval was measured in step-through type passive avoidance apparatus. Our results showed that post-training intraperitoneal (i.p.) administration of morphine (6mg/kg) induced amnesia. Pre-test administration of ethanol (0.5g/kg, i.p.) significantly improved morphine-induced memory impairment, suggesting that there is cross state-dependent memory retrieval between morphine and ethanol. It should be considered that pre-test administration of ethanol (0.1 and 0.5g/kg, i.p.) by itself had no effect on memory retrieval in the passive avoidance task. Interestingly, pre-test intra-BLA microinjection of different doses of WIN55,212-2 (0.1, 0.2 and 0.3μg/rat), a non-selective CB1/CB2 receptor agonist, plus an ineffective dose of ethanol (0.1g/kg, i.p.) improved morphine-induced memory impairment. Intra-BLA microinjection of AM251 (0.4-0.6ng/rat), a selective CB1 receptor antagonist, inhibited the improved effect of ethanol (0.5g/kg, i.p.) on morphine response. Pre-test intra-BLA microinjection of WIN55,212-2 or AM251 had no effect on memory retrieval or morphine-induced amnesia. Taken together, it can be concluded that morphine and ethanol can induce state-dependent memory retrieval. In addition, the BLA endocannabinoid system mediates via CB1 receptors the functional interaction of morphine and ethanol state-dependent memory retrieval which may depend on the rewarding effects of the drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Condensates from vapor made by impacts between metal-, silicate-rich bodies: Comparison with metal and chondrules in CB chondrites

    Science.gov (United States)

    Fedkin, Alexei V.; Grossman, Lawrence; Humayun, Munir; Simon, Steven B.; Campbell, Andrew J.

    2015-09-01

    The impact hypothesis for the origin of CB chondrites was tested by performing equilibrium condensation calculations in systems composed of vaporized mixtures of projectile and target materials. When one of the impacting bodies is composed of the metal from CR chondrites and the other is an H chondrite, good agreement can be found between calculated and observed compositions of unzoned metal grains in CB chondrites but the path of composition variation of the silicate condensate computed for the same conditions that reproduce the metal grain compositions does not pass through the measured compositions of barred olivine (BO) or cryptocrystalline (CC) chondrules in the CBs. The discrepancy between measured chondrule compositions and those of calculated silicates is not reduced when diogenite, eucrite or howardite compositions are substituted for H chondrite as the silicate-rich impacting body. If, however, a CR chondrite body is differentiated into core, a relatively CaO-, Al2O3-poor mantle and a CaO-, Al2O3-rich crust, and later accretes significant amounts of water, a collision between it and an identical body can produce the necessary chemical conditions for condensation of CB chondrules. If the resulting impact plume is spatially heterogeneous in its proportions of crust and mantle components, the composition paths calculated for silicate condensates at the same Ptot, Ni/H and Si/H ratios and water abundance that produce good matches to the unzoned metal grain compositions pass through the fields of BO and CC chondrules, especially if high-temperature condensates are fractionated in the case of the CCs. While equilibrium evaporation of an alloy containing solar proportions of siderophiles into a dense impact plume is an equally plausible hypothesis for explaining the compositions of the unzoned metal grains, equilibrium evaporation can explain CB chondrule compositions only if an implausibly large number of starting compositions is postulated. Kinetic models

  17. "Highly recommended introduction"

    DEFF Research Database (Denmark)

    Christiansen, Ask Vest

    2009-01-01

    by detachment, normatively and morally. Besides researching the actual abuse, individually and in aggregate, they also study structural circumstances that promote the use of drugs in sports; besides evaluations of the efficacy of the anti-doping efforts, they consider the effects of various anti-doping schemes...... on the integrity and privacy of the athletes. Ask Vest Christiansen, himself an internationally renowned scholar in the field, has read a recent, thus detached, introduction to drug use in sports, An Introduction to Drugs in Sport: Addicted to Winning by Ivan Waddington and Andy Smith (Routledge). Christiansen...... finds much to appreciate in the book, and a couple of disconcerting mistakes and misjudgments notwithstanding, he recommends the book as a solid introduction to the problem of doping – knowledgeable, well written and easy to read....

  18. Conclusions and recommendations

    International Nuclear Information System (INIS)

    1984-01-01

    The FAO/IAEA/GSF/SIDA Co-ordinated Research Programme on Cereal Grain Protein Improvement by Nuclear Techniques was a follow-up to the FAO/IAEA/GSF Co-ordinated Research Programme on the Use of Nuclear Techniques for Seed Protein Improvement. It was initiated in 1969 and ended in 1981. The objectives of the meeting were to review and evaluate the achievements of the current and previous programmes in order to draw conclusions on the possibility of genetic improvement of cereal grain protein using nuclear techniques, to identify unsolved problems and to discuss and propose possible approaches for their solution. Through reviews and discussions, conclusions and recommendations were made by the participants

  19. Urgent recommendation. Interim report

    International Nuclear Information System (INIS)

    Nakano, Masayuki

    2000-01-01

    The Investigation Committee for Critical Accident at Uranium Processing Plant was founded immediately after the accident to investigate the cause of the accident and to establish measures to prevent the similar accident. On September 30, 1999 around 10:35, the Japan's first criticality accident occurred at JCO Co. Ltd. Uranium processing plant (auxiliary conversion plant) located at Tokai-mura Ibaraki-ken. The criticality continued on and off for approximately 20 hours after the first instantaneous criticality. The accident led the recommendation of tentative evacuation and sheltering indoors for residents living in the neighborhood. The serious exposure to neutrons happened to three workers. The dominant effect is dose due to neutrons and gamma rays from the precipitation tank. When the accident took place, three workers dissolved sequentially about 2.4 kg uranium powder with 18.8 % enrichment in the 10-litter bucket with nitric acid. The procedure of homogenization of uranium nitrate was supposed to be controlled using the shape-limited narrow storage column. Actually, however, the thick and large precipitation tank was used. As a result, about 16.6 kg of uranium was fed into the tank, which presumably caused criticality. The first notification by JCO was delayed and the following communication was not smooth. This led to the delay of correct understanding of the situation and made the initial proper response difficult, then followed by insufficient communication between the nation, prefecture, and local authority. Urgent recommendations were made on the following items; (1) Safety measures to be taken at the accident site, (2) health cares for residents and others, (3) Comprehensive safety securing at nuclear operators such as Establishment of the effective audit system, Safety education for employees and Qualification and licensing system, Safety related documents, etc. (4) Reconstruction of the government's safety regulations such as How safety regulation

  20. Illuminating the Decision Path: The Yucca Mountain Site Recommendation

    Energy Technology Data Exchange (ETDEWEB)

    Knox, E.; Slothouber, L.

    2003-02-25

    On February 14, 2002, U.S. Secretary of Energy Spencer Abraham provided to the President the ''Recommendation by the Secretary of Energy Regarding the Suitability of the Yucca Mountain Site for a Repository Under the Nuclear Waste Policy Act of 1982.'' This Recommendation, along with supporting materials, complied with statutory requirements for communicating a site recommendation to the President, and it did more: in 49 pages, the Recommendation also spoke directly to the Nation, illuminating the methodology and considerations that led toward the decision to recommend the site. Addressing technical suitability, national interests, and public concerns, the Recommendation helped the public understand the potential risks and benefits of repository development and placed those risks and benefits in a meaningful national context.

  1. Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible structure-specific plasticity process in 6-OHDA lesioned rats.

    Directory of Open Access Journals (Sweden)

    Gabriela P Chaves-Kirsten

    Full Text Available The endocannabinoid system has been implicated in several neurobiological processes, including neurodegeneration, neuroprotection and neuronal plasticity. The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in Parkinson's Disease (PD. Some studies show variation of CB1 expression in basal ganglia in different animal models of PD, however the results are quite controversial, due to the differences in the procedures employed to induce the parkinsonism and the periods analyzed after the lesion. The present study evaluated the CB1 expression in four basal ganglia structures, namely striatum, external globus pallidus (EGP, internal globus pallidus (IGP and substantia nigra pars reticulata (SNpr of rats 1, 5, 10, 20, and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that causes retrograde dopaminergic degeneration. We also investigated tyrosine hydroxylase (TH, parvalbumin, calbindin and glutamic acid decarboxylase (GAD expression to verify the status of dopaminergic and GABAergic systems. We observed a structure-specific modulation of CB1 expression at different periods after lesions. In general, there were no changes in the striatum, decreased CB1 in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained over time. No changes in GAD and parvalbumin expression were observed in basal ganglia, whereas TH levels were decreased and the calbindin increased in striatum in short periods after lesion. We believe that the structure-specific variation of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a compensatory process involving the GABAergic transmission, which is impaired due to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and calbindin expression may represent a plasticity process in this PD model.

  2. Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xuqin [Department of Endocrinology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029 (China); Sun, Tao [Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province 210002 (China); Wang, Xiaodong, E-mail: xdwang666@hotmail.com [Department of Endocrinology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029 (China)

    2013-07-05

    Highlights: •TC, a CB2R specific agonist, stimulates SIRT1 activity by PKA/CREB pathway. •TC promotes PGC-1α transcriptional activity by increasing its deacetylation. •TC increases the expression of genes linked to FAO and promotes the rate of FAO. •The effects of TC in FAO are dependent on CB2R. •Suggesting CB2R as a target to treat diseases with lipid dysregulation. -- Abstract: Abnormal fatty acid oxidation has been associated with obesity and type 2 diabetes. At the transcriptional level, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) has been reported to strongly increase the ability of hormone nuclear receptors PPARα and ERRα to drive transcription of fatty acid oxidation enzymes. In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fatty acid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fatty acid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also drastically accelerates the rate of complete fatty acid oxidation in C2C12 myotubes, neither of which occur when CB2R mRNA is knocked down using siRNA. These results reveal that activation of CB2R by a selective agonist promotes lipid oxidation through a signaling/transcriptional pathway. Our findings imply that pharmacological manipulation of CB2R may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.

  3. Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

    Science.gov (United States)

    Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

    2015-08-01

    There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  4. AAV-mediated overexpression of the CB1 receptor in the mPFC of adult rats alters cognitive flexibility, social behavior and emotional reactivity

    Directory of Open Access Journals (Sweden)

    Matthias eKlugmann

    2011-07-01

    Full Text Available The endocannabinoid (ECB system is strongly involved in the regulation of cognitive processing and emotional behavior and evidence indicates that ECB signaling might affect these behavioral abilities by modulations of prefrontal cortical functions. The aim of the present study was to examine the role of the CB1 receptor in the medial prefrontal cortex (mPFC on cognitive flexibility and emotional behavior. Therefore, the CB1 receptor was overexpressed by adeno-associated virus (AAV vector-mediated gene transfer specifically in the mPFC of adult Wistar rats. Animals were then tested in different anxiety-related paradigms for emotional reactivity (e.g. elevated plus maze (EPM, light/dark emergence test (EMT, social interaction and the attentional set shift task (ASST - an adaptation of the human Wisconsin card sorting test - for cognitive abilities and behavioral flexibility. A subtle increase in exploratory behavior was found in CB1 receptor overexpressing animals (CB1-R compared to empty vector injected controls (Empty in the EMT and EPM, although general locomotor activity did not differ between the groups. During social interaction testing, social contact behavior towards the unknown conspecific was found to be decreased, whereas social withdrawal was increased in CB1-R animals and they showed an inadequate increase in exploratory behavior compared to control animals. In the ASST, impaired reversal learning abilities were detected in CB1-R animals compared to controls, indicating reduced behavioral flexibility. In conclusion, upregulation of the CB1 receptor specifically in the rat mPFC induces alterations in emotional reactivity, leads to inadequate social behavior and impairs cognitive flexibility. These findings might be relevant for neuropsychiatric disorders, since higher cortical CB1 receptor expression levels as well as similar behavioral impairments as observed in the present study have been described in schizophrenic patients.

  5. Recommendation in evolving online networks

    Science.gov (United States)

    Hu, Xiao; Zeng, An; Shang, Ming-Sheng

    2016-02-01

    Recommender system is an effective tool to find the most relevant information for online users. By analyzing the historical selection records of users, recommender system predicts the most likely future links in the user-item network and accordingly constructs a personalized recommendation list for each user. So far, the recommendation process is mostly investigated in static user-item networks. In this paper, we propose a model which allows us to examine the performance of the state-of-the-art recommendation algorithms in evolving networks. We find that the recommendation accuracy in general decreases with time if the evolution of the online network fully depends on the recommendation. Interestingly, some randomness in users' choice can significantly improve the long-term accuracy of the recommendation algorithm. When a hybrid recommendation algorithm is applied, we find that the optimal parameter gradually shifts towards the diversity-favoring recommendation algorithm, indicating that recommendation diversity is essential to keep a high long-term recommendation accuracy. Finally, we confirm our conclusions by studying the recommendation on networks with the real evolution data.

  6. The policies

    International Nuclear Information System (INIS)

    Laruelle, Ph.; Snegaroff, Th.; Moreau, S.; Tellenne, C.; Brunel, S.

    2005-01-01

    Fourth chapter of the book on the geo-policy of the sustainable development, this chapter deal with the different and international policies concerned by the problem. The authors analyze the american energy attitude and policy, the economical equilibrium facing the environmental equilibrium for the european policy, the sanctified and sacrificed nature and the japanese attitude, India and China, the great fear of the 21 century and the sustainable development in Africa. (A.L.B.)

  7. Urgent recommendation. Interim report

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Masayuki [International Affairs and Safeguards Division, Atomic Energy Bureau, Science and Technology Agency, Tokyo (Japan)

    2000-12-01

    The Investigation Committee for Critical Accident at Uranium Processing Plant was founded immediately after the accident to investigate the cause of the accident and to establish measures to prevent the similar accident. On September 30, 1999 around 10:35, the Japan's first criticality accident occurred at JCO Co. Ltd. Uranium processing plant (auxiliary conversion plant) located at Tokai-mura Ibaraki-ken. The criticality continued on and off for approximately 20 hours after the first instantaneous criticality. The accident led the recommendation of tentative evacuation and sheltering indoors for residents living in the neighborhood. The serious exposure to neutrons happened to three workers. The dominant effect is dose due to neutrons and gamma rays from the precipitation tank. When the accident took place, three workers dissolved sequentially about 2.4 kg uranium powder with 18.8 % enrichment in the 10-litter bucket with nitric acid. The procedure of homogenization of uranium nitrate was supposed to be controlled using the shape-limited narrow storage column. Actually, however, the thick and large precipitation tank was used. As a result, about 16.6 kg of uranium was fed into the tank, which presumably caused criticality. The first notification by JCO was delayed and the following communication was not smooth. This led to the delay of correct understanding of the situation and made the initial proper response difficult, then followed by insufficient communication between the nation, prefecture, and local authority. Urgent recommendations were made on the following items; (1) Safety measures to be taken at the accident site, (2) health cares for residents and others, (3) Comprehensive safety securing at nuclear operators such as Establishment of the effective audit system, Safety education for employees and Qualification and licensing system, Safety related documents, etc. (4) Reconstruction of the government's safety regulations such as How safety

  8. Evaluation of 4-oxo-quinoline-based CB2 PET radioligands in R6/2 chorea huntington mouse model and human ALS spinal cord tissue.

    Science.gov (United States)

    Haider, Ahmed; Spinelli, Francesco; Herde, Adrienne Müller; Mu, Boshuai; Keller, Claudia; Margelisch, Markus; Weber, Markus; Schibli, Roger; Mu, Linjing; Ametamey, Simon M

    2018-02-10

    The cannabinoid receptor 2 (CB2) has been implicated in a series of neurodegenerative disorders and has emerged as an interesting biological target for therapeutic as well as diagnostic purposes. In the present work, we describe an improved radiosynthetic approach to obtain the previously reported CB2-specific PET radioligand [ 18 F]RS-126 in higher radiochemical yields and molar activities. Additionally, the study revealed that prolongation of the [ 18 F]RS-126 fluoroalkyl side chain ultimately leads to an improved stability towards mouse liver enzymes but is accompanied by a reduction in selectivity over the cannabinoid receptor 1 (CB1). Huntington-related phenotypic changes as well as striatal D2R downregulation were confirmed for the transgenic R6/2 mouse model. CB2 upregulation in R6/2 Chorea Huntington mice was observed in hippocampus, cortex, striatum and cerebellum by qPCR, however, these results could not be confirmed at the protein level by PET imaging. Furthermore, we evaluated the utility of the newly developed [ 11 C]RS-028, a potent [ 18 F]RS-126 derivative with increased polarity and high selectivity over CB1 in post-mortem human ALS spinal cord and control tissue. Applying in vitro autoradiography, the translational relevance of CB2 imaging was demonstrated by the specific binding of [ 11 C]RS-028 to post-mortem human ALS spinal cord tissue. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  9. National Recommended Water Quality Criteria

    Data.gov (United States)

    U.S. Environmental Protection Agency — The National Recommended Water Quality Criteria is a compilation of national recommended water quality criteria for the protection of aquatic life and human health...

  10. Guidelines for a sustainable energy policy

    International Nuclear Information System (INIS)

    Maichel, G.; Klemmer, P.; Voss, A.; Grill, K.D.

    2000-01-01

    The publication contains four contributions of four different authors which elaborate the role, functions and capabilities of policymakers, the energy industry, and the population (consumers) in the process of designing, implementing, enforcing and accepting the paradigms and the framework conditions that will initiate and finally support in concrete terms a transition towards sustainable development in the context of energy demand and energy consumption in Europe. The titles of the four contributions (translated for the purpose of this abstract) are: 1. Regulatory policy and/or a free market system in the energy sector. 2. Self-commitments and self-regulatory approaches in the energy industry. 3. What does it take to establish a system of sustainable energy supply? 4. For an energy policy fit for the future in the 21. century. (orig./CB) [de

  11. Site Recommendation Subsurface Layout

    International Nuclear Information System (INIS)

    C.L. Linden

    2000-01-01

    The purpose of this analysis is to develop a Subsurface Facility layout that is capable of accommodating the statutory capacity of 70,000 metric tons of uranium (MTU), as well as an option to expand the inventory capacity, if authorized, to 97,000 MTU. The layout configuration also requires a degree of flexibility to accommodate potential changes in site conditions or program requirements. The objective of this analysis is to provide a conceptual design of the Subsurface Facility sufficient to support the development of the Subsurface Facility System Description Document (CRWMS M andO 2000e) and the ''Emplacement Drift System Description Document'' (CRWMS M andO 2000i). As well, this analysis provides input to the Site Recommendation Consideration Report. The scope of this analysis includes: (1) Evaluation of the existing facilities and their integration into the Subsurface Facility design. (2) Identification and incorporation of factors influencing Subsurface Facility design, such as geological constraints, thermal loading, constructibility, subsurface ventilation, drainage control, radiological considerations, and the Test and Evaluation Facilities. (3) Development of a layout showing an available area in the primary area sufficient to support both the waste inventories and individual layouts showing the emplacement area required for 70,000 MTU and, if authorized, 97,000 MTU

  12. CERN anti-fraud policy

    CERN Multimedia

    2013-01-01

    In 2011, a working group on improved fraud prevention and management was established. The group was composed of the Director of Administration and General Infrastructure, the Head of the Human Resources Department, and the Heads of the Legal Service and Internal Audit. It recommended the adoption of a global fraud prevention and management policy.   The global fraud prevention and management policy was implemented through the CERN Anti-Fraud Policy, which was endorsed by the Enlarged Directorate in May 2012 and approved by the Director-General for entry into force on 1 January 2013. The CERN Anti-Fraud Policy defines the Organization’s policy in matters of fraud.  CERN has a zero tolerance approach towards fraud, as it would compromise the accomplishment of its objectives and undermine its functioning, credibility and reputation. The policy also states CERN’s commitment to the prevention, identification and investigation of fraud. All CERN contributors have a key rol...

  13. New staff contract policy

    CERN Multimedia

    HR Department

    2006-01-01

    Following discussion at TREF and on the recommendation of the Finance Committee, Council approved a new staff contract policy, which became effective on 1 January 2006. Its application is covered by a new Administrative Circular No. 2 (Rev. 3) 'Recruitment, appointment and possible developments regarding the contractual position of staff members'. The revised circular replaces the previous Circulars No. 9 (Rev. 3) 'Staff contracts' and No. 2 (Rev. 2) 'Guidelines and procedures concerning recruitment and probation period for staff members'. The main features of the new contract policy are as follows: The new policy provides chances for long-term employment for all staff recruits staying for four years without distinguishing between those assigned to long-term or short-term activities when joining CERN. In addition, it presents a number of simplifications for the award of ICs. There are henceforth only 2 types of contract: Limited Duration (LD) contracts for all recruitment and Indefinite Contracts (IC) for...

  14. Improving health through policies that promote active travel

    DEFF Research Database (Denmark)

    de Nazelle, Audrey; Nieuwenhuijsen, Mark J; Antó, Josep M

    2011-01-01

    Substantial policy changes to control obesity, limit chronic disease, and reduce air pollution emissions, including greenhouse gasses, have been recommended. Transportation and planning policies that promote active travel by walking and cycling can contribute to these goals, potentially yielding ...

  15. 78 FR 24749 - Health Information Technology Policy Committee Appointment

    Science.gov (United States)

    2013-04-26

    ... GOVERNMENT ACCOUNTABILITY OFFICE Health Information Technology Policy Committee Appointment AGENCY... Recovery and Reinvestment Act of 2009 (ARRA) established the Health Information Technology Policy Committee to make recommendations on the implementation of a nationwide health information technology...

  16. Joint safety recommendations

    International Nuclear Information System (INIS)

    Birkhofer, A.; Cogne, F.X.

    1996-01-01

    In 1992, the French utility EdF, a consortium of German utilities, and the vendor NPI, a joint venture of Siemens and Framatome, joint the efforts in developing an advanced reactor concept called EPR (European Pressurized water Reactor). Therefore, the French and German safety authorities decided to work out a common safety approach which has been laid down in the form of recommendations firstly drawn up by GRS and IPSN and then reviewed by the French and German Nuclear Safety commissions GPR and RSK. The main objective of this approach is the strengthening of accident prevention through optimization of defense-in-depth. Particular objectives are the improvement of plant behavior during transients, especially by increasing thermal inertia and the grace periods for interventions by the control room personnel, the reduction of the possibility of common cause failures, a further improvement of the man-machine interface, the simplification of the systems configuration, and the use of advanced information technology. These objectives are similar to those of many other evolutionary rector concepts. Regarding severe accidents, the French-German approach surpasses current evolutionary developments. One of the fundamental aims is the practical elimination of accidents situations which would lead to large early releases such as containment bypass, shutdown states and open containment building, reactivity accidents, high pressure core melt, depressurization of the RPV or global hydrogen detonation. The dual concept of 'practical elimination' of scenarios or phenomena and of 'dealing with them' is essential for the consistency of the approach and the safety demonstration. This would be expressed by no permanent relocation, no need for emergency evacuation outside the immediate vicinity of the plant, limited sheltering and no long-term restriction in the consumption of food. Such a reduction of radioactive release implies a substantial improvement of the containment function

  17. [Recommendations for neonatal transport].

    Science.gov (United States)

    Moreno Hernando, J; Thió Lluch, M; Salguero García, E; Rite Gracia, S; Fernández Lorenzo, J R; Echaniz Urcelay, I; Botet Mussons, F; Herranz Carrillo, G; Sánchez Luna, M

    2013-08-01

    During pregnancy, it is not always possible to identify maternal or foetal risk factors. Infants requiring specialised medical care are not always born in centres providing intensive care and will need to be transferred to a referral centre where intensive care can be provided. Therefore Neonatal Transport needs to be considered as part of the organisation of perinatal health care. The aim of Neonatal Transport is to transfer a newborn infant requiring intensive care to a centre where specialised resources and experience can be provided for the appropriate assessment and continuing treatment of a sick newborn infant. Intrauterine transfer is the ideal mode of transport when the birth of an infant with risk factors is diagnosed. Unfortunately, not all problems can be detected in advance with enough time to safely transfer a pregnant woman. Around 30- 50% of risk factors will be diagnosed during labour or soon after birth. Therefore, it is important to have the knowledge and resources to resuscitate and stabilise a newborn infant, as well as a specialised neonatal transport system. With this specialised transport it is possible to transfer newly born infants with the same level of care that they would receive if they had been born in a referral hospital, without increasing their risks or affecting the wellbeing of the newborn. The Standards Committee of the Spanish Society of Neonatology reviewed and updated recommendations for intrauterine transport and indications for neonatal transfer. They also reviewed organisational and logistic factors involved with performing neonatal transport. The Committee review included the type of personnel who should be involved; communication between referral and receiving hospitals; documentation; mode of transport; equipment to stabilise newly born infants; management during transfer, and admission at the referral hospital. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  18. Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin on food reward and aversion in healthy volunteers.

    Science.gov (United States)

    Tudge, Luke; Williams, Clare; Cowen, Philip J; McCabe, Ciara

    2014-12-25

    Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders. We previously showed that the cannabis receptor subtype (CB1) inverse agonist rimonabant, an antiobesity drug withdrawn due to depressogenic side effects, diminished neural reward responses yet increased aversive responses (Horder et al., 2010). Unlike rimonabant, tetrahydrocannabivarin is a neutral CB1 receptor antagonist (Pertwee, 2005) and may therefore produce different modulations of the neural reward system. We hypothesized that tetrahydrocannabivarin would, unlike rimonabant, leave intact neural reward responses but augment aversive responses. We used a within-subject, double-blind design. Twenty healthy volunteers received a single dose of tetrahydrocannabivarin (10mg) and placebo in randomized order on 2 separate occasions. We measured the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (picture of moldy strawberries and/or a less pleasant strawberry taste) using functional magnetic resonance imaging. Volunteers rated pleasantness, intensity, and wanting for each stimulus. There were no significant differences between groups in subjective ratings. However, tetrahydrocannabivarin increased responses to chocolate stimuli in the midbrain, anterior cingulate cortex, caudate, and putamen. Tetrahydrocannabivarin also increased responses to aversive stimuli in the amygdala, insula, mid orbitofrontal cortex, caudate, and putamen. Our findings are the first to show that treatment with the CB1 neutral antagonist tetrahydrocannabivarin increases neural responding to rewarding and aversive stimuli. This effect profile suggests therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  19. The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

    Science.gov (United States)

    Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

    2017-01-01

    Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB 1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB 1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB 1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of

  20. CB1-Dependent Long-Term Depression in Ventral Tegmental Area GABA Neurons: A Novel Target for Marijuana.

    Science.gov (United States)

    Friend, Lindsey; Weed, Jared; Sandoval, Philip; Nufer, Teresa; Ostlund, Isaac; Edwards, Jeffrey G

    2017-11-08

    The VTA is necessary for reward behavior with dopamine cells critically involved in reward signaling. Dopamine cells in turn are innervated and regulated by neighboring inhibitory GABA cells. Using whole-cell electrophysiology in juvenile-adolescent GAD67-GFP male mice, we examined excitatory plasticity in fluorescent VTA GABA cells. A novel CB1-dependent LTD was induced in GABA cells that was dependent on metabotropic glutamate receptor 5, and cannabinoid receptor 1 (CB1). LTD was absent in CB1 knock-out mice but preserved in heterozygous littermates. Bath applied Δ 9 -tetrahydrocannabinol depressed GABA cell activity, therefore downstream dopamine cells will be disinhibited; and thus, this could potentially result in increased reward. Chronic injections of Δ 9 -tetrahydrocannabinol occluded LTD compared with vehicle injections; however, a single exposure was insufficient to do so. As synaptic modifications by drugs of abuse are often tied to addiction, these data suggest a possible mechanism for the addictive effects of Δ 9 -tetrahydrocannabinol in juvenile-adolescents, by potentially altering reward behavioral outcomes. SIGNIFICANCE STATEMENT The present study identifies a novel form of glutamatergic synaptic plasticity in VTA GABA neurons, a currently understudied cell type that is critical for the brain's reward circuit, and how Δ 9 -tetrahydrocannabinol occludes this plasticity. This study specifically addresses a potential unifying mechanism whereby marijuana could exert rewarding and addictive/withdrawal effects. Marijuana use and legalization are a pressing issue for many states in the United States. Although marijuana is the most commonly abused illicit drug, the implications of legalized, widespread, or continued usage are speculative. This study in juvenile-adolescent aged mice identifies a novel form of synaptic plasticity in VTA GABA cells, and the synaptic remodeling that can occur after Δ 9 -tetrahydrocannabinol use. Copyright © 2017 the

  1. Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling.

    Science.gov (United States)

    Rivas, Priscila M S; Vechiato, Fernanda M V; Borges, Beatriz C; Rorato, Rodrigo; Antunes-Rodrigues, Jose; Elias, Lucila L K

    2017-07-01

    Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100μg/kg body weight, ip) or repeated injections of LPS over 6days (6 LPS). Food intake was reduced in the 1 LPS, but not in the 6 LPS group. 6 LPS rats showed an increased serum concentration of acylated ghrelin and reduced ghrelin receptor mRNA expression in the hypothalamus. Ghrelin injection (40μg/kg body weight, ip) increased food intake, body weight gain, p-AMPK hypothalamic expression, neuropeptide Y (NPY) and Agouti related peptide (AgRP) mRNA expression in control animals (Saline). However, in 6 LPS rats, ghrelin did not alter these parameters. Central administration of a CB1R antagonist (AM251, 200ng/μl in 5μl/rat) induced hypophagia in 6 LPS animals, suggesting that the endocannabinoid system contributes to preserved food intake during LPS tolerance. In the presence of AM251, the ability of ghrelin to phosphorylate AMPK in the hypothalamus of 6 LPS group was restored, but not its orexigenic effect. Our data highlight that the orexigenic effects of ghrelin require CB1R signaling downstream of AMPK activation. Moreover, CB1R-mediated pathways contribute to the absence of hypophagia during repeated exposure to endotoxin. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Mice Expressing a "Hyper-Sensitive" Form of the Cannabinoid Receptor 1 (CB1 Are Neither Obese Nor Diabetic.

    Directory of Open Access Journals (Sweden)

    David J Marcus

    Full Text Available Multiple lines of evidence implicate the endocannabinoid signaling system in the modulation of metabolic disease. Genetic or pharmacological inactivation of CB1 in rodents leads to reduced body weight, resistance to diet-induced obesity, decreased intake of highly palatable food, and increased energy expenditure. Cannabinoid agonists stimulate feeding in rodents and increased levels of endocannabinoids can disrupt lipid metabolism. Therefore, the hypothesis that sustained endocannabinoid signaling can lead to obesity and diabetes was examined in this study using S426A/S430A mutant mice expressing a desensitization-resistant CB1 receptor. These mice display exaggerated and prolonged responses to acute administration of phytocannabinoids, synthetic cannabinoids, and endocannabinoids. As a consequence these mice represent a novel model for determining the effect of enhanced endocannabinoid signaling on metabolic disease. S426A/S430A mutants consumed equivalent amounts of both high fat (45% and low fat (10% chow control diet compared to wild-type littermate controls. S426A/S430A mutants and wild-type mice fed either high or low fat control diet displayed similar fasting blood glucose levels and normal glucose clearance following a 2 g/kg glucose challenge. Furthermore, S426A/S430A mutants and wild-type mice consumed similar amounts of chow following an overnight fast. While both THC and JZL195 significantly increased food intake two hours after injection, this increase was similar between the S426A/S430A mutant and wildtype control mice Our results indicate that S426A/S430A mutant mice expressing the desensitization-resistant form of CB1 do not exhibit differences in body weight, food intake, glucose homeostasis, or re-feeding following a fast.

  3. Land policy reform in Rwanda: A Catalyst for Land Information ...

    African Journals Online (AJOL)

    Step in geo-ICT application for data handling was achieved, despite a big gap in technical and skills capabilities. Since new land policy coincided with decentralization policy, we recommend research on parallel implementation of policies with some similar dimensions. Keywords: Land policy reform, organizational change, ...

  4. Multi-Criteria Recommender Systems

    Science.gov (United States)

    Adomavicius, Gediminas; Manouselis, Nikos; Kwon, Youngok

    This chapter aims to provide an overview of the class of multi-criteria recommender systems. First, it defines the recommendation problem as a multicriteria decision making (MCDM) problem, and reviews MCDM methods and techniques that can support the implementation of multi-criteria recommenders. Then, it focuses on the category of multi-criteria rating recommenders - techniques that provide recommendations by modelling a user's utility for an item as a vector of ratings along several criteria. A review of current algorithms that use multi-criteria ratings for calculating predictions and generating recommendations is provided. Finally, the chapter concludes with a discussion on open issues and future challenges for the class of multi-criteria rating recommenders.

  5. Targeting the cannabinoid CB2 receptor to attenuate the progression of motor deficits in LRRK2-transgenic mice.

    Science.gov (United States)

    Palomo-Garo, Cristina; Gómez-Gálvez, Yolanda; García, Concepción; Fernández-Ruiz, Javier

    2016-08-01

    Most of cases of Parkinson's disease (PD) have a sporadic origin, with their causes mostly unknown, although overexposure to some environmental factors has been found to occur in some cases. Other forms of parkinsonism are the consequence of dominant or recessive mutations in specific genes, e.g. α-synuclein, parkin and, more recently, leucine-rich repeat kinase 2 (LRRK2), whose G2019S mutation represents the most prevalent form of late-onset, autosomal dominant familial PD. A transgenic mouse model expressing the G2019S mutation of LRRK2 is already available and apparently may represent a valuable experimental model for investigating PD pathogenesis and novel treatments. We designed a long-term study with these animals aimed at: (i) elucidating the changes experienced by the endocannabinoid signaling system in the basal ganglia during the progression of the disease in these mice, paying emphasis in the CB2 receptor, which has emerged as a promising target in PD, and (ii) evaluating the potential of compounds selectively activating this CB2 receptor, as disease-modifying agents in these mice. Our results unequivocally demonstrate that LRRK2 transgenic mice develop motor impairment consisting of small anomalies in rotarod performance (presumably reflecting a deficit in motor coordination and dystonia) and a strong deficiency in the hanging-wire test (reflecting muscle weakness), rather than hypokinesia which was difficult to be demonstrated in the actimeter. These behavioral responses occurred in absence of any evidence of reactive gliosis and neuronal losses, as well as synaptic deterioration in the basal ganglia, except an apparent impairment in autophagy reflected by elevated LAMP-1 immunolabelling in the striatum and substantia nigra. Furthermore, there were no changes in the status of the CB2 receptor, as well as in other elements of the endocannabinoid signaling, in the basal ganglia, but, paradoxically, the selective activation of this receptor partially

  6. Recommendation Process in SR1 Web Document Recommender System

    Directory of Open Access Journals (Sweden)

    Dan MUNTEANU

    2008-12-01

    Full Text Available This paper presents a recommender system for web documents (given as bookmarks. The system uses for classification a combination of content, event and collaborative filters and for recommendation a modified Pearson-r algorithm. The algorithm for recommendation is using not only the correlation between users but also the similarity between classes. Some experimental results that support this approach are also presented.

  7. Differential Interaction of the Staphylococcal Toxins Panton-Valentine Leukocidin and γ-Hemolysin CB with Human C5a Receptors.

    Science.gov (United States)

    Spaan, András N; Schiepers, Ariën; de Haas, Carla J C; van Hooijdonk, Davy D J J; Badiou, Cédric; Contamin, Hugues; Vandenesch, François; Lina, Gérard; Gerard, Norma P; Gerard, Craig; van Kessel, Kok P M; Henry, Thomas; van Strijp, Jos A G

    2015-08-01

    Staphylococcus aureus is well adapted to the human host. Evasion of the host phag