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

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.

Women's experiences of developing musculoskeletal diseases: employment challenges and policy recommendations.

Science.gov (United States)

Crooks, Valorie A

2007-07-30

To answer three specific questions: (i) How do women experience the workplace after the onset of a musculoskeletal disease; (ii) What employment policy and programme suggestions can they offer for ways to better support chronically ill women in their abilities to maintain workforce participation; and (iii) How are these women's employment policy and programme recommendations informed by their own lived experiences and desires? In-depth interviews were conducted with 18 women who had developed musculoskeletal diseases while involved in the labour market. Data were coded and analysed thematically. Participants identified three common workplace barriers experienced and three types of workplace accommodations commonly requested. They offered four specific employment policy and programme recommendations for ways to better support women who develop musculoskeletal diseases in maintaining labour market participation. It is found that their employment policy and programme recommendations are informed by their own experiences in the workplace and desires for being supported in maintaining involvement in paid labour. Creating employment programmes and policies that support chronically ill women in their attempts to remain involved in the workforce based on how much paid labour they are able to perform and where they are best able to work is of the utmost importance.

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...

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.

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

Expression Analysis of CB2-GFP BAC Transgenic Mice.

Science.gov (United States)

Schmöle, Anne-Caroline; Lundt, Ramona; Gennequin, Benjamin; Schrage, Hanna; Beins, Eva; Krämer, Alexandra; Zimmer, Till; Limmer, Andreas; Zimmer, Andreas; Otte, David-Marian

2015-01-01

The endocannabinoid system (ECS) is a retrograde messenger system, consisting of lipid signaling molecules that bind to at least two G-protein-coupled receptors, Cannabinoid receptor 1 and 2 (CB1 and 2). As CB2 is primarily expressed on immune cells such as B cells, T cells, macrophages, dendritic cells, and microglia, it is of great interest how CB2 contributes to immune cell development and function in health and disease. Here, understanding the mechanisms of CB2 involvement in immune-cell function as well as the trafficking and regulation of CB2 expressing cells are crucial issues. Up to now, CB2 antibodies produce unclear results, especially those targeting the murine protein. Therefore, we have generated BAC transgenic GFP reporter mice (CB2-GFPTg) to trace CB2 expression in vitro and in situ. Those mice express GFP under the CB2 promoter and display GFP expression paralleling CB2 expression on the transcript level in spleen, thymus and brain tissue. Furthermore, by using fluorescence techniques we show that the major sources for GFP-CB2 expression are B cells in spleen and blood and microglia in the brain. This novel CB2-GFP transgenic reporter mouse line represents a powerful resource to study CB2 expression in different cell types. Furthermore, it could be used for analyzing CB2-mediated mobilization and trafficking of immune cells as well as studying the fate of recruited immune cells in models of acute and chronic inflammation.

Expression Analysis of CB2-GFP BAC Transgenic Mice.

Directory of Open Access Journals (Sweden)

Anne-Caroline Schmöle

Full Text Available The endocannabinoid system (ECS is a retrograde messenger system, consisting of lipid signaling molecules that bind to at least two G-protein-coupled receptors, Cannabinoid receptor 1 and 2 (CB1 and 2. As CB2 is primarily expressed on immune cells such as B cells, T cells, macrophages, dendritic cells, and microglia, it is of great interest how CB2 contributes to immune cell development and function in health and disease. Here, understanding the mechanisms of CB2 involvement in immune-cell function as well as the trafficking and regulation of CB2 expressing cells are crucial issues. Up to now, CB2 antibodies produce unclear results, especially those targeting the murine protein. Therefore, we have generated BAC transgenic GFP reporter mice (CB2-GFPTg to trace CB2 expression in vitro and in situ. Those mice express GFP under the CB2 promoter and display GFP expression paralleling CB2 expression on the transcript level in spleen, thymus and brain tissue. Furthermore, by using fluorescence techniques we show that the major sources for GFP-CB2 expression are B cells in spleen and blood and microglia in the brain. This novel CB2-GFP transgenic reporter mouse line represents a powerful resource to study CB2 expression in different cell types. Furthermore, it could be used for analyzing CB2-mediated mobilization and trafficking of immune cells as well as studying the fate of recruited immune cells in models of acute and chronic inflammation.

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...

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

DEVELOPMENT OF FRANCHISING IN CROATIA OBSTACLES AND POLICY RECOMMENDATIONS

Directory of Open Access Journals (Sweden)

Mirela Alpeza

2015-11-01

Full Text Available 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 first phase of which was conducted in 2006, and second in 2014. The overall results of this research were presented in a form of PEST analysis and compared with the results of the 2006 research aiming to detect changes (improvements/ deterioration in individual areas of the research political, economic, legal and technologic factors of influence on the development of franchising in Croatia. Based on the detected changes, conclusions and policy recommendations were identified.The obstacles can be divided in two categories: franchising specific barriers and general business related obstacles for doing business in Croatia. Without removing most of these obstacles, it is unrealistic to expect high growth of franchising activities in Croatia in near future.

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.

Canadian solar export market study. Export policy recommendations

Energy Technology Data Exchange (ETDEWEB)

1983-11-01

This report outlines policies and recommendations on the export of Canadian solar equipment and technology, with a view toward stimulating the domestic solar industry. The current picture is of an industry which is relatively small, operates in a competitive domestic market with low profit margins, and needs assistance in order to break into the world market. A number of recommendations are therefore made on the main thrust of industry and government solar export development activities. An export development program is described which includes a strategy of concentrating on a limited number of product lines, namely: low-temperature solar heating systems for recreational applications, integrated residential water heating systems, prepackaged commercial water heating systems, and industrial pre-heat systems. It is also recommended that this strategy be directed only at a limited number of target countries where the market justifies such activity. Market research, international cooperation agreements, promotional services, and proper export organization are also needed.

Receptor-heteromer mediated regulation of endocannabinoid signaling in activated microglia. Role of CB1 and CB2 receptors 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

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.

IEA policies-G8 recommendations and an afterwards

International Nuclear Information System (INIS)

Onoda, Takao

2009-01-01

In response to threats posed to the future supply of energy and to the environment, the G8 leaders, in Gleneagles, UK in 2005, agreed to an initiative called the Gleneagles Plan of Action (GPOA) which addresses climate change, clean energy and sustainable development. In the GPOA, G8 leaders pledged to encourage the development of cleaner, more efficient and lower-emitting vehicles, and to promote their deployment by, among other means, asking the IEA to review existing standards and codes for vehicle efficiency and to identify best practices. In order to properly response to the above-mentioned requests from G8 leaders, the IEA has launched, among other activities, study on policies for 'transforming the way we use energy' focusing on end-use efficiency including the one in transport sector and made a comprehensive response to the GPOA at the 2008 G8 Summit Meeting in Japan with 25 recommendations on energy efficiency. Regarding these recommendations, the G8 leaders have proclaimed, in the G8 Hokkaido Toyako Summit Leaders Declaration, that they would maximize implementation of the IEA's 25 recommendations. This paper summarizes the IEA activities in transport sector regarding the GPOA and their findings and recommendations.

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.

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

Science.gov (United States)

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

2018-01-01

Abstract 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. PMID:29323862

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.

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

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

International Nuclear Information System (INIS)

Ten Donkelaar, M.; Van Oostvoorn, F.

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

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

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

Postnatal Development of CB1 Receptor Expression in Rodent Somatosensory Cortex

Science.gov (United States)

Deshmukh, Suvarna; Onozuka, Kaori; Bender, Kevin J.; Bender, Vanessa A.; Lutz, Beat; Mackie, Ken; Feldman, Daniel E.

2007-01-01

Endocannabinoids are powerful modulators of synaptic transmission that act on presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the dominant receptor in the CNS, and is present in many brain regions, including sensory cortex. To investigate the potential role of CB1 receptors in cortical development, we examined the developmental expression of CB1 in rodent primary somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific antibody. We found that before postnatal day (P) 6, CB1 receptor staining was present exclusively in the cortical white matter, and that CB1 staining appeared in the grey matter between P6 and P20 in a specific laminar pattern. CB1 staining was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6. CB1 null (−/−) mice showed altered anatomical barrel maps in layer 4, with enlarged inter-barrel septa, but normal barrel size. These results indicate that CB1 receptors are present in early postnatal development and influence development of sensory maps. PMID:17210229

Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

Directory of Open Access Journals (Sweden)

Ken Soderstrom

2017-10-01

Full Text Available Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

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.

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…

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.

Association of American Universities Policy Recommendations for President-Elect Obama

Science.gov (United States)

Association of American Universities, 2008

2008-01-01

In this document, the Association of American Universities offers a series of research and technology policy recommendations that would help our nation to continue its global pre-eminence in science and high technology, improve the quality of life and national security of our citizens, and speed our nation's economic recovery. After policy…

Health policy and systems research training: global status and recommendations for action

Science.gov (United States)

Tancred, Tara M; Schleiff, Meike; Peters, David H

2016-01-01

Abstract Objective To investigate the characteristics of health policy and systems research training globally and to identify recommendations for improvement and expansion. Methods We identified institutions offering health policy and systems research training worldwide. In 2014, we recruited participants from identified institutions for an online survey on the characteristics of the institutions and the courses given. Survey findings were explored during in-depth interviews with selected key informants. Findings The study identified several important gaps in health policy and systems research training. There were few courses in central and eastern Europe, the Middle East, North Africa or Latin America. Most (116/152) courses were instructed in English. Institutional support for courses was often lacking and many institutions lacked the critical mass of trained individuals needed to support doctoral and postdoctoral students. There was little consistency between institutions in definitions of the competencies required for health policy and systems research. Collaboration across disciplines to provide the range of methodological perspectives the subject requires was insufficient. Moreover, the lack of alternatives to on-site teaching may preclude certain student audiences such as policy-makers. Conclusion Training in health policy and systems research is important to improve local capacity to conduct quality research in this field. We provide six recommendations to improve the content, accessibility and reach of training. First, create a repository of information on courses. Second, establish networks to support training. Third, define competencies in health policy and systems research. Fourth, encourage multidisciplinary collaboration. Fifth, expand the geographical and language coverage of courses. Finally, consider alternative teaching formats. PMID:27429488

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.

Establishing global policy recommendations: the role of the Strategic Advisory Group of Experts on immunization.

Science.gov (United States)

Duclos, Philippe; Okwo-Bele, Jean-Marie; Salisbury, David

2011-02-01

The vaccine landscape has changed considerably over the last decade with many new vaccines and technological developments, unprecedented progress in reaching out to children and the development of new financing mechanisms. At the same time, there are more demands and additional expectations of national policy makers, donors and other interested parties for increased protection through immunization. The Global Immunization Vision and Strategy (GIVS), which broadens the previous scope of immunization efforts, sets a number of goals to be met by countries. The WHO has recently reviewed and adjusted both its policy making structure and processes for vaccines and immunization to include an enlarged consultation process to generate evidence-based recommendations, thereby ensuring the transparency of the decision making process and improving communications. This article describes the process of development of immunization policy recommendations at the global level and some of their impacts. It focuses on the roles and modes of operating of the Strategic Advisory Group of Experts on immunization, which is the overarching advisory group involved with the issuance of policy recommendations, monitoring and facilitating the achievement of the GIVS goals. The article also describes the process leading to the publication of WHO vaccine position papers, which provide WHO recommendations on vaccine use. WHO vaccine-related recommendations have become a necessary step in the pathway to the introduction and use of vaccines, especially in developing countries and, consequently, have a clear and significant impact.

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

Nuclear safety policy working group recommendations on nuclear propulsion safety for the space exploration initiative

Science.gov (United States)

Marshall, Albert C.; Lee, James H.; Mcculloch, William H.; Sawyer, J. Charles, Jr.; Bari, Robert A.; Cullingford, Hatice S.; Hardy, Alva C.; Niederauer, George F.; Remp, Kerry; Rice, John W.

1993-01-01

An interagency Nuclear Safety Working Group (NSPWG) was chartered to recommend nuclear safety policy, requirements, and guidelines for the Space Exploration Initiative (SEI) nuclear propulsion program. These recommendations, which are contained in this report, should facilitate the implementation of mission planning and conceptual design studies. The NSPWG has recommended a top-level policy to provide the guiding principles for the development and implementation of the SEI nuclear propulsion safety program. In addition, the NSPWG has reviewed safety issues for nuclear propulsion and recommended top-level safety requirements and guidelines to address these issues. These recommendations should be useful for the development of the program's top-level requirements for safety functions (referred to as Safety Functional Requirements). The safety requirements and guidelines address the following topics: reactor start-up, inadvertent criticality, radiological release and exposure, disposal, entry, safeguards, risk/reliability, operational safety, ground testing, and other considerations.

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.

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.

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.

77 FR 23250 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Science.gov (United States)

2012-04-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

76 FR 25355 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Science.gov (United States)

2011-05-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

78 FR 29134 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Science.gov (United States)

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

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.

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

Consequence of dopamine D2 receptor blockade on the hyperphagic effect induced by cannabinoid CB1 and CB2 receptors in layers.

Science.gov (United States)

Khodadadi, M; Zendehdel, M; Baghbanzadeh, A; Babapour, V

2017-10-01

1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed-intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor-induced hyperphagia in 3-h feed-deprived neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, l-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB 1 receptor agonist; 2 µg) and co-administration of l-DOPA (125 nmol) plus 2-AG (2 µg). Experiments 2-4 were similar to Experiment 1 except birds were injected with either 6-OHDA (6-hydroxydopamine as dopamine synthesis inhibitor; 150 nmol), SCH23390 (D1 receptor antagonist; 5 nmol) and AMI-193 (D2 receptor antagonist; 5 nmol) instead of l-DOPA, respectively. Additionally, Experiments 5-8 followed the previous ones using the same dose of l-DOPA, 6-OHDA and dopamine antagonists except that birds were injected with CB65 (CB2 receptor agonist; 5 µg) instead of 2-AG. Coadministrations were at the same dose for each experiment. Cumulative feed intakes were measured until 120 min after each injection. 3. ICV administration of 6-OHDA and AMI-193 significantly attenuated 2-AG-induced hyperphagia. Interestingly, the hyperphagic effect of CB65 was significantly attenuated by administration of l-DOPA, whereas the administration of 6-OHDA and AMI-193 together amplified the hyperphagic effect of CB65. 4. It was concluded that cannabinoid-induced feeding behaviour is probably modulated by dopamine receptors in neonatal layer-type chickens. It seems that their interaction may be mediated by the D2-dopamine receptor.

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

Final study summary and policy recommendations: participatory citizenship in the European Union

OpenAIRE

Hoskins, Bryony; Kerr, David

2012-01-01

The findings from the Participatory Citizenship in the European Union study suggest a number of key recommendations concerning policies, practices and effective approaches towards overcoming barriers to Participatory Citizenship in Europe. These keyrecommendations are summarised below and are explained in more detail in this report

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

Sensitivity study applied to the CB4 VVER-440 benchmark on burnup credit

International Nuclear Information System (INIS)

Markova, Ludmila

2003-01-01

A brief overview of four completed portions (CB1, CB2, CB3, CB3+, CB4) of the international VVER-440 benchmark focused on burnup credit and a sensitivity study as one of the final views of the benchmark results are presented in the paper. Finally, the influence of real and conservative VVER-440 fuel assembly models taken for the isotopics calculation by SCALE sas2 on the system k eff is shown in the paper. (author)

Nuclear power and the opting-out policy of the German Government. A matter of responsibility and controversy

International Nuclear Information System (INIS)

Grawe, J.; Voss, A.

2000-01-01

The article critically reviews the energy policy of the German Government and the plans for winding down nuclear power generation and instead pursue a policy for a ''green reshufflement'' of generation technologies, providing for incentives to switch to options for decentralized power generation with enhanced use of renewable energy sources. The article explains arguments against the Government's opting-out policy which were laid down in a memorandum presented to the Government by a group of five university professors, among them the authors of this article who, as experts in this domain, are aware of their responsibility as scientists and members of society and therefore explain their view of the policy issues, also referring to a recent expert opinion of the German Wissenschaftsrat (science council), which recommended to continue nuclear energy research programmes and nuclear power generation. (orig./CB) [de

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.

LEP measurements of $V_{cb}$ and $V_{ub}$

CERN Document Server

Hawkings, R

2001-01-01

The measurements of the magnitudes of the CKM matrix elements V/sub cb/ and V/sub ub/ from LEP are reviewed. V/sub cb/ is measured using the decay B/sup 0/ to D*/sup +/l/sup -/ nu , whilst V/sub ub/ is measured using inclusive charmless semileptonic b decays. Particular attention is paid to the limiting systematic errors in each case. (20 refs).

Stimulation of cannabinoid receptor 2 (CB2 suppresses microglial activation

Directory of Open Access Journals (Sweden)

Fernandez Francisco

2005-12-01

Full Text Available Abstract Background Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD, multiple sclerosis (MS, and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO, cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB2. Methods In this study, we investigated the effects of a cannabinoid agonist on CD40 expression and function by cultured microglial cells activated by IFN-γ using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB2 small interfering RNA (siRNA analyses. Furthermore, we examined if the stimulation of CB2 could modulate the capacity of microglial cells to phagocytise Aβ1–42 peptide using a phagocytosis assay. Results We found that the selective stimulation of cannabinoid receptor CB2 by JWH-015 suppressed IFN-γ-induced CD40 expression. In addition, this CB2 agonist markedly inhibited IFN-γ-induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-α and nitric oxide production induced either by IFN-γ or Aβ peptide challenge in the presence of CD40 ligation. Finally, we showed that CB2 activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Aβ1–42 peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB2 modulation in neurodegenerative diseases, particularly AD.

Prioritizing Sleep Health: Public Health Policy Recommendations.

Science.gov (United States)

Barnes, Christopher M; Drake, Christopher L

2015-11-01

The schedules that Americans live by are not consistent with healthy sleep patterns. In addition, poor access to educational and treatment aids for sleep leaves people engaging in behavior that is harmful to sleep and forgoing treatment for sleep disorders. This has created a sleep crisis that is a public health issue with broad implications for cognitive outcomes, mental health, physical health, work performance, and safety. New public policies should be formulated to address these issues. We draw from the scientific literature to recommend the following: establishing national standards for middle and high school start times that are later in the day, stronger regulation of work hours and schedules, eliminating daylight saving time, educating the public regarding the impact of electronic media on sleep, and improving access to ambulatory in-home diagnostic testing for sleep disorders. © The Author(s) 2015.

Sonographic demonstration of Cruveilhier-Baumgarten (CB) syndrome

Energy Technology Data Exchange (ETDEWEB)

Schulze, P J; Vogel, H M

1982-02-01

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.

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.)

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...

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)

Shift scheduling limits for the nuclear industry NRC policy and recommendations

International Nuclear Information System (INIS)

Koontz, J.; Morisseau, D.; Lewis, P.

1985-01-01

A study on shift scheduling and use of overtime and their effects on human performance in nuclear and non-nuclear industries was conducted. An analysis of the literature, current practices, and federal policy on shift scheduling resulted in human factors recommendations for limiting hours of work in the nuclear industry for nuclear power plant personnel conducting safety related functions. Recommended limits on total hours of work were developed by a panel of experts for both 8-hour and 12-hour daily shift schedules for weekly, biweekly, monthly, and annual work periods. The study results are particularly applicable to control room operators but should also be considered for other personnel where performance degradation due to fatigue could directly affect safe plant operations

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-.

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

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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.

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

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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.

CB1 cannabinoid receptor expression in the striatum: Association with corticostriatal circuits and developmental regulation

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Vincent eVan Waes

2012-03-01

Full Text Available Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains. We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25 and then progressively decreases towards adolescent (P40 and adult (P70 levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors receive inputs from cortical regions with higher expression (medial prefrontal cortex. In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.

Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader–Willi syndrome

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Ibrahim Knani

2016-12-01

Full Text Available Objective: Extreme obesity is a core phenotypic feature of Prader–Willi syndrome (PWS. Among numerous metabolic regulators, the endocannabinoid (eCB system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects. Methods: We studied eCB ‘tone’ in individuals with PWS and in the Magel2-null mouse model that recapitulates the major metabolic phenotypes of PWS and determined the efficacy of a peripherally restricted CB1R antagonist, JD5037 in treating obesity in these mice. Results: Individuals with PWS had elevated circulating levels of 2-arachidonoylglycerol and its endogenous precursor and breakdown ligand, arachidonic acid. Increased hypothalamic eCB ‘tone’, manifested by increased eCBs and upregulated CB1R, was associated with increased fat mass, reduced energy expenditure, and decreased voluntary activity in Magel2-null mice. Daily chronic treatment of obese Magel2-null mice and their littermate wild-type controls with JD5037 (3 mg/kg/d for 28 days reduced body weight, reversed hyperphagia, and improved metabolic parameters related to their obese phenotype. Conclusions: Dysregulation of the eCB/CB1R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB1R antagonists may be an effective strategy for the management of severe obesity in PWS. Author Video: Author Video Watch what authors say about their articles Keywords: Endocannabinoids, PWS, Magel2, Peripheral CB1 blockade, Metabolic syndrome

Policy recommendations to promote shale gas development in China based on a technical and economic evaluation

International Nuclear Information System (INIS)

Yuan, Jiehui; Luo, Dongkun; Xia, Liangyu; Feng, Lianyong

2015-01-01

Because of its resource potential and clean burning advantages, the development of shale gas can significantly increase the supply of cleaner energy while offering the associated benefits. To foster shale gas development, many policy incentives have been introduced in China. However, the current incentives have not been sufficiently aggressive, and the shale gas industry has been slow to develop. Existing policies thus need to be further improved. To provide effective support for decision makers in China, a technical and economic evaluation is performed in this study to explore the profitability of shale gas production in pilot zones. The results show that shale gas production is subeconomic under the current technical and economic conditions. Based on this evaluation, a policy analysis is conducted to investigate the profitability improvement offered by the major policies available in China to elucidate a path toward improving incentive policies. The results indicate that policy instruments related to gas prices, financial subsidies, corporate income taxes or combinations thereof could be used as priority options to improve policy incentives. Based on these results, recommendations are presented to improve the current incentive polices aimed at accelerating shale gas development. -- Highlights: •We explore the economic feasibility of shale gas development in China. •Current incentive policies cannot render shale gas development economically viable. •These incentives must be improved to effectively promote shale gas development. •We investigate the effect of the major policies available in China to light a path. •Recommendations are proposed to continually improve the incentive polices in China

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

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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.

From micronutrient recommendations to policy

DEFF Research Database (Denmark)

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

2010-01-01

towards achieving a greater link between micronutrient recommendations and behaviour. This study aims to examine the rationale and processes associated with consumer and stakeholder involvement in setting micronutrient recommendations across Europe. Subjects/Methods: Using the contacts established through......Background/Objectives: To achieve the nutritional goals stipulated by micronutrient recommendations, greater attention must be paid to the behavioural routes to such nutritional outcomes. Coopting stakeholders and consumers into decisions regarding micronutrient recommendations is an important step...... countries and its effect on final decisions. Stakeholders were not involved at the outset of the process ('framing' of the problem) in any of the countries, and there was no evidence of consumer involvement and open public fora. Conclusions: Some of the key explanatory factors for diversity in the degree...

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

The Caulobacter crescentus phage phiCbK: genomics of a canonical phage

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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

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions.

Science.gov (United States)

Ogbogu, Ubaka; Burningham, Sarah; Ollenberger, Adam; Calder, Kathryn; Du, Li; El Emam, Khaled; Hyde-Lay, Robyn; Isasi, Rosario; Joly, Yann; Kerr, Ian; Malin, Bradley; McDonald, Michael; Penney, Steven; Piat, Gayle; Roy, Denis-Claude; Sugarman, Jeremy; Vercauteren, Suzanne; Verhenneman, Griet; West, Lori; Caulfield, Timothy

2014-02-03

The increased use of human biological material for cell-based research and clinical interventions poses risks to the privacy of patients and donors, including the possibility of re-identification of individuals from anonymized cell lines and associated genetic data. These risks will increase as technologies and databases used for re-identification become affordable and more sophisticated. Policies that require ongoing linkage of cell lines to donors' clinical information for research and regulatory purposes, and existing practices that limit research participants' ability to control what is done with their genetic data, amplify the privacy concerns. To date, the privacy issues associated with cell-based research and interventions have not received much attention in the academic and policymaking contexts. This paper, arising out of a multi-disciplinary workshop, aims to rectify this by outlining the issues, proposing novel governance strategies and policy recommendations, and identifying areas where further evidence is required to make sound policy decisions. The authors of this paper take the position that existing rules and norms can be reasonably extended to address privacy risks in this context without compromising emerging developments in the research environment, and that exceptions from such rules should be justified using a case-by-case approach. In developing new policies, the broader framework of regulations governing cell-based research and related areas must be taken into account, as well as the views of impacted groups, including scientists, research participants and the general public. This paper outlines deliberations at a policy development workshop focusing on privacy challenges associated with cell-based research and interventions. The paper provides an overview of these challenges, followed by a discussion of key themes and recommendations that emerged from discussions at the workshop. The paper concludes that privacy risks associated with cell

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

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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.

Developmental and visual input-dependent regulation of the CB1 cannabinoid receptor in the mouse visual cortex.

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Taisuke Yoneda

Full Text Available The mammalian visual system exhibits significant experience-induced plasticity in the early postnatal period. While physiological studies have revealed the contribution of the CB1 cannabinoid receptor (CB1 to developmental plasticity in the primary visual cortex (V1, it remains unknown whether the expression and localization of CB1 is regulated during development or by visual experience. To explore a possible role of the endocannabinoid system in visual cortical plasticity, we examined the expression of CB1 in the visual cortex of mice. We found intense CB1 immunoreactivity in layers II/III and VI. CB1 mainly localized at vesicular GABA transporter-positive inhibitory nerve terminals. The amount of CB1 protein increased throughout development, and the specific laminar pattern of CB1 appeared at P20 and remained until adulthood. Dark rearing from birth to P30 decreased the amount of CB1 protein in V1 and altered the synaptic localization of CB1 in the deep layer. Dark rearing until P50, however, did not influence the expression of CB1. Brief monocular deprivation for 2 days upregulated the localization of CB1 at inhibitory nerve terminals in the deep layer. Taken together, the expression and the localization of CB1 are developmentally regulated, and both parameters are influenced by visual experience.

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

-induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest...... 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...... a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo....

Molecular basis of cannabinoid CB1 receptor coupling to the G protein heterotrimer Gαiβγ: identification of key CB1 contacts with the C-terminal helix α5 of Gαi.

Science.gov (United States)

Shim, Joong-Youn; Ahn, Kwang H; Kendall, Debra A

2013-11-08

The cannabinoid (CB1) receptor is a member of the rhodopsin-like G protein-coupled receptor superfamily. The human CB1 receptor, which is among the most expressed receptors in the brain, has been implicated in several disease states, including drug addiction, anxiety, depression, obesity, and chronic pain. Different classes of CB1 agonists evoke signaling pathways through the activation of specific subtypes of G proteins. The molecular basis of CB1 receptor coupling to its cognate G protein is unknown. As a first step toward understanding CB1 receptor-mediated G protein signaling, we have constructed a ternary complex structural model of the CB1 receptor and Gi heterotrimer (CB1-Gi), guided by the x-ray structure of β2-adrenergic receptor (β2AR) in complex with Gs (β2AR-Gs), through 824-ns duration molecular dynamics simulations in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer environment. We identified a group of residues at the juxtamembrane regions of the intracellular loops 2 and 3 (IC2 and IC3) of the CB1 receptor, including Ile-218(3.54), Tyr-224(IC2), Asp-338(6.30), Arg-340(6.32), Leu-341(6.33), and Thr-344(6.36), as potential key contacts with the extreme C-terminal helix α5 of Gαi. Ala mutations of these residues at the receptor-Gi interface resulted in little G protein coupling activity, consistent with the present model of the CB1-Gi complex, which suggests tight interactions between CB1 and the extreme C-terminal helix α5 of Gαi. The model also suggests that unique conformational changes in the extreme C-terminal helix α5 of Gα play a crucial role in the receptor-mediated G protein activation.

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...

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

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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.

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

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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.

Cannabinoid CB1 /CB2 receptor 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.

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

Review of $V_{cb}$ and $V_{td}/V_{ts}$

OpenAIRE

Forty, Roger W

1997-01-01

The current experimental status of the CKM matrix element V_cb and the ratio V_td/V_ts is reviewed. Knowledge of these elements has a strong impact on the unitarity triangle, of interest for studies of CP violation in the B system. The measurements of V_cb from both inclusive semileptonic b decays and the exclusive channel B -> D* l nu are reaching high precision. For V_td/V_ts the strongest upper limit is derived from studies of B-Bbar mixing.

Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis.

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Vanessa Deveaux

Full Text Available BACKGROUND: Obesity-associated inflammation is of critical importance in the development of insulin resistance and non-alcoholic fatty liver disease. Since the cannabinoid receptor CB2 regulates innate immunity, the aim of the present study was to investigate its role in obesity-induced inflammation, insulin resistance and fatty liver. METHODOLOGY: Murine obesity models included genetically leptin-deficient ob/ob mice and wild type (WT mice fed a high fat diet (HFD, that were compared to their lean counterparts. Animals were treated with pharmacological modulators of CB2 receptors. Experiments were also performed in mice knock-out for CB2 receptors (Cnr2 -/-. PRINCIPAL FINDINGS: In both HFD-fed WT mice and ob/ob mice, Cnr2 expression underwent a marked induction in the stromal vascular fraction of epididymal adipose tissue that correlated with increased fat inflammation. Treatment with the CB2 agonist JWH-133 potentiated adipose tissue inflammation in HFD-fed WT mice. Moreover, cultured fat pads isolated from ob/ob mice displayed increased Tnf and Ccl2 expression upon exposure to JWH-133. In keeping, genetic or pharmacological inactivation of CB2 receptors decreased adipose tissue macrophage infiltration associated with obesity, and reduced inductions of Tnf and Ccl2 expressions. In the liver of obese mice, Cnr2 mRNA was only weakly induced, and CB2 receptors moderately contributed to liver inflammation. HFD-induced insulin resistance increased in response to JWH-133 and reduced in Cnr2 -/- mice. Finally, HFD-induced hepatic steatosis was enhanced in WT mice treated with JWH-133 and blunted in Cnr2 -/- mice. CONCLUSION/SIGNIFICANCE: These data unravel a previously unrecognized contribution of CB2 receptors to obesity-associated inflammation, insulin resistance and non-alcoholic fatty liver disease, and suggest that CB2 receptor antagonists may open a new therapeutic approach for the management of obesity-associated metabolic disorders.

Fiscal policy to improve diets and prevent noncommunicable diseases: from recommendations to action.

Science.gov (United States)

Thow, Anne Marie; Downs, Shauna M; Mayes, Christopher; Trevena, Helen; Waqanivalu, Temo; Cawley, John

2018-03-01

The World Health Organization has recommended that Member States consider taxing energy-dense beverages and foods and/or subsidizing nutrient-rich foods to improve diets and prevent noncommunicable diseases. Numerous countries have either implemented taxes on energy-dense beverages and foods or are considering the implementation of such taxes. However, several major challenges to the implementation of fiscal policies to improve diets and prevent noncommunicable diseases remain. Some of these challenges relate to the cross-sectoral nature of the relevant interventions. For example, as health and economic policy-makers have different administrative concerns, performance indicators and priorities, they often consider different forms of evidence in their decision-making. In this paper, we describe the evidence base for diet-related interventions based on fiscal policies and consider the key questions that need to be asked by both health and economic policy-makers. From the health sector's perspective, there is most evidence for the impact of taxes and subsidies on diets, with less evidence on their impacts on body weight or health. We highlight the importance of scope, the role of industry, the use of revenue and regressive taxes in informing policy decisions.

GABAergic and cortical and subcortical glutamatergic axon terminals contain CB1 cannabinoid receptors in the ventromedial nucleus of the hypothalamus.

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Leire Reguero

Full Text Available BACKGROUND: Type-1 cannabinoid receptors (CB(1R are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH that participates in homeostatic and behavioral functions including food intake. Although CB(1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB(1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB(1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. METHODOLOGY/PRINCIPAL FINDINGS: Light and electron microscopy techniques were used to analyze CB(1R distribution in the VMH of CB(1R-WT, CB(1R-KO and conditional mutant mice bearing a selective deletion of CB(1R in cortical glutamatergic (Glu-CB(1R-KO or GABAergic neurons (GABA-CB(1R-KO. At light microscopy, CB(1R immunolabeling was observed in the VMH of CB(1R-WT and Glu-CB(1R-KO animals, being remarkably reduced in GABA-CB(1R-KO mice. In the electron microscope, CB(1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB(1R immunopositive profiles and CB(1R density in terminals making asymmetric or symmetric synapses in CB(1R-WT mice. Furthermore, the proportion of CB(1R immunopositive terminals/preterminals in CB(1R-WT and Glu-CB(1R-KO mice was reduced in GABA-CB(1R-KO mutants. CB(1R density was similar in all animal conditions. Finally, the percentage of CB(1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB(1R-KO mutants relative to CB(1R-WT mice, indicating that CB(1R was distributed in cortical and subcortical excitatory synaptic terminals. CONCLUSIONS/SIGNIFICANCE: Our anatomical results support the idea that the VMH is a relevant hub candidate in

Motor, visual and emotional deficits in mice after closed-head mild traumatic brain injury are alleviated by the novel CB2 inverse agonist SMM-189.

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Reiner, Anton; Heldt, Scott A; Presley, Chaela S; Guley, Natalie H; Elberger, Andrea J; Deng, Yunping; D'Surney, Lauren; Rogers, Joshua T; Ferrell, Jessica; Bu, Wei; Del Mar, Nobel; Honig, Marcia G; Gurley, Steven N; Moore, Bob M

2014-12-31

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.

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

What Determines Lean Manufacturing Implementation? A CB-SEM Model

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Tan Ching Ng

2018-02-01

Full Text Available This research aims to ascertain the determinants of effective Lean Manufacturing (LM. In this research, Covariance-based Structural Equation Modeling (CB-SEM analysis will be used in order to analyze the determinants. Through CB-SEM analysis, the significant key determinants can be determined and the direct relationships among determinants can be analyzed. Thus, the findings of this research can act as guidelines for achievement of LM effectiveness, not only providing necessary steps for successful implementation of lean, but also helping lean companies to achieve higher level of lean cost and time savings.

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

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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.

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

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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

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

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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.

SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor.

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Rinaldi-Carmona, M; Barth, F; Millan, J; Derocq, J M; Casellas, P; Congy, C; Oustric, D; Sarran, M; Bouaboula, M; Calandra, B; Portier, M; Shire, D; Brelière, J C; Le Fur, G L

1998-02-01

Based on both binding and functional data, this study introduces SR 144528 as the first, highly potent, selective and orally active antagonist for the CB2 receptor. This compound which displays subnanomolar affinity (Ki = 0.6 nM) for both the rat spleen and cloned human CB2 receptors has a 700-fold lower affinity (Ki = 400 nM) for both the rat brain and cloned human CB1 receptors. Furthermore it shows no affinity for any of the more than 70 receptors, ion channels or enzymes investigated (IC50 > 10 microM). In vitro, SR 144528 antagonizes the inhibitory effects of the cannabinoid receptor agonist CP 55,940 on forskolin-stimulated adenylyl cyclase activity in cell lines permanently expressing the h CB2 receptor (EC50 = 10 nM) but not in cells expressing the h CB1 (no effect at 10 microM). Furthermore, SR 144528 is able to selectively block the mitogen-activated protein kinase activity induced by CP 55,940 in cell lines expressing h CB2 (IC50 = 39 nM) whereas in cells expressing h CB1 an IC50 value of more than 1 microM is found. In addition, SR 144528 is shown to antagonize the stimulating effects of CP 55,940 on human tonsillar B-cell activation evoked by cross-linking of surface Igs (IC50 = 20 nM). In vivo, after oral administration SR 144528 totally displaced the ex vivo [3H]-CP 55,940 binding to mouse spleen membranes (ED50 = 0.35 mg/kg) with a long duration of action. In contrast, after the oral route it does not interact with the cannabinoid receptor expressed in the mouse brain (CB1). It is expected that SR 144528 will provide a powerful tool to investigate the in vivo functions of the cannabinoid system in the immune response.

The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

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Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

2012-01-01

The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

SUBMILLIMETER ARRAY AND SPITZER OBSERVATIONS OF BOK GLOBULE CB 17: A CANDIDATE FIRST HYDROSTATIC CORE?

Energy Technology Data Exchange (ETDEWEB)

Chen Xuepeng; Arce, Hector G.; Dunham, Michael M. [Department of Astronomy, Yale University, Box 208101, New Haven, CT 06520-8101 (United States); Zhang Qizhou; Bourke, Tyler L. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Launhardt, Ralf; Schmalzl, Markus; Henning, Thomas, E-mail: xuepeng.chen@yale.edu [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany)

2012-06-01

We present high angular resolution Submillimeter Array (SMA) and Spitzer observations toward the Bok globule CB 17. SMA 1.3 mm dust continuum images reveal within CB 17 two sources with an angular separation of {approx}21'' ({approx}5250 AU at a distance of {approx}250 pc). The northwestern continuum source, referred to as CB 17 IRS, dominates the infrared emission in the Spitzer images, drives a bipolar outflow extending in the northwest-southeast direction, and is classified as a low-luminosity Class 0/I transition object (L{sub bol} {approx} 0.5 L{sub Sun }). The southeastern continuum source, referred to as CB 17 MMS, has faint dust continuum emission in the SMA 1.3 mm observations ({approx}6{sigma} detection; {approx}3.8 mJy), but is not detected in the deep Spitzer infrared images at wavelengths from 3.6 to 70 {mu}m. Its bolometric luminosity and temperature, estimated from its spectral energy distribution, are {<=}0.04 L{sub Sun} and {<=}16 K, respectively. The SMA CO (2-1) observations suggest that CB 17 MMS may drive a low-velocity molecular outflow ({approx}2.5 km s{sup -1}), extending in the east-west direction. Comparisons with prestellar cores and Class 0 protostars suggest that CB 17 MMS is more evolved than prestellar cores but less evolved than Class 0 protostars. The observed characteristics of CB 17 MMS are consistent with the theoretical predictions from radiative/magnetohydrodynamical simulations of a first hydrostatic core, but there is also the possibility that CB 17 MMS is an extremely low luminosity protostar deeply embedded in an edge-on circumstellar disk. Further observations are needed to study the properties of CB 17 MMS and to address more precisely its evolutionary stage.

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

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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

A Feedforward Inhibitory Circuit Mediated by CB1-Expressing Fast-Spiking Interneurons in the Nucleus Accumbens.

Science.gov (United States)

Wright, William J; Schlüter, Oliver M; Dong, Yan

2017-04-01

The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1). Using a combination of paired electrophysiological recordings and pharmacological approaches, we characterized and compared feedforward inhibition of NAc MSNs from CB1 + FSIs and lateral inhibition from recurrent MSN collaterals. We observed that CB1 + FSIs exerted robust inhibitory control over a large percentage of nearby MSNs in contrast to local MSN collaterals that provided only sparse and weak inhibitory input to their neighboring MSNs. Furthermore, CB1 + FSI-mediated feedforward inhibition was preferentially suppressed by endocannabinoid (eCB) signaling, whereas MSN-mediated lateral inhibition was unaffected. Finally, we demonstrated that CB1 + FSI synapses onto MSNs are capable of undergoing experience-dependent long-term depression in a voltage- and eCB-dependent manner. These findings demonstrated that CB1 + FSIs are a major source of local inhibitory control of MSNs and a critical component of the feedforward inhibitory circuits regulating the output of the NAc.

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

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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.

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...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

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

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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.

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

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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.

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

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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.

Simultaneous biodegradation of bifenthrin and chlorpyrifos by Pseudomonas sp. CB2.

Science.gov (United States)

Zhang, Qun; Li, Shuhuai; Ma, Chen; Wu, Nancun; Li, Chunli; Yang, Xinfeng

2018-05-04

The degradation of bifenthrin (BF) and chlorpyrifos (CP), either together or individually, by a bacterial strain (CB2) isolated from activated sludge was investigated. Strain CB2 was identified as belonging to genus Pseudomonas based on the morphological, physiological, and biochemical characteristics and a homological analysis of the 16S rDNA sequence. Strain CB2 has the potential to degrade BF and CP, either individually or in a mixture. The optimum conditions for mixture degradation were as follows: OD 600nm = 0.5; incubation temperature = 30°C; pH = 7.0; BF-CP mixture (10 mg L -1 of each). Under these optimal conditions, the degradation rate constants (and half-lives) were 0.4308 d -1 (1.61 d) and 0.3377 d -1 (2.05 d) for individual BF and CP samples, respectively, and 0.3463 d -1 (2.00 d) and 0.2931 d -1 (2.36 d) for the BF-CP mixture. Major metabolites of BF and CP were 2-methyl-3-biphenylyl methanol and 3,5,6-trichloro-2-pyridinol, respectively. No metabolite bioaccumulation was observed. The ability of CB2 to efficiently degrade BF and CP, particularly in a mixture, may be useful in bioremediation efforts.

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.

Data of evolutionary structure change: 1A5CB-2QUTC [Confc[Archive

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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.

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade

Science.gov (United States)

Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-01-01

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors. PMID:23487769

Studies on the effects of EPDM, SR on PTC- of HDPE/CB before and after γ-radiation

International Nuclear Information System (INIS)

Jia Shaojin; Jiang Pingkai; Xiu Qihui; Wang Zongguang; Zhang Zhicheng

2004-01-01

High-density-polyethylene (HDPE), Si rubber (SR) and ethylene-density-polyethylene (EPDM) were used as the polymer matrices. A kinds of carbon blacks was used as the conductive filler. The positive temperature coefficient (PTC) intensity of the HDPE/CB, HDPE/EPDM/CB composites flow during extrusion to produced was tested before and after irradiation. Compared to that of HDPE/CB composites, the electrical reproducibility of the irradiated HDPE/EPDM/CB composites of is better. The effects of γ-rays irradiation were also estimated. The results showed that the reproductive of the PTC effect was related to the adhesion between the interface of the polymer matrices and CB particles. These PTC phenomena and their distinctive aspects were described. The explanations were given from the structural characteristics of the blends, CB particles distribution and motion of polymer segments. (authors)

Data of evolutionary structure change: 1A5CB-2QUUC [Confc[Archive

Lifescience Database Archive (English)

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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.

Participation of hypothalamic CB1 receptors in reproductive axis disruption during immune challenge.

Science.gov (United States)

Surkin, P N; Di Rosso, M E; Correa, F; Elverdin, J C; Genaro, A M; De Laurentiis, A; Fernández-Solari, J

2017-08-01

Immune challenge inhibits reproductive function and endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the eCB system mediates the inhibition of hormones that control reproduction as a result of immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on the hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated i.c.v. administration with a CB1 antagonist/inverse agonist (AM251) (500 ng/5 μL), followed by an i.p. injection of lipopolysaccharide (LPS) (5 mg/kg) 15 minutes later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 minutes post-LPS. The plasma concentration of tumour necrosis factor α and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 180 minutes post i.p. administration of LPS. However, cytokine mRNA expression in the hypothalamus increased only 180 minutes post-LPS, suggesting an inflammatory delay in this organ. CB1 receptor blockade with AM251 increased LPS inflammatory effects, particularly in the hypothalamus. LPS also inhibited the HPG axis by decreasing gonadotrophin-releasing hormone hypothalamic content and plasma levels of luteinising hormone and testosterone. These disruptor effects were accompanied by decreased hypothalamic Kiss1 mRNA expression and prostaglandin E2 content, as well as by increased gonadotrophin-inhibitory hormone (Rfrp3) mRNA expression. All these disruptive effects were prevented by the presence of AM251. In summary, our results suggest that, in male rats, eCB mediate immune challenge-inhibitory effects on reproductive axis at least partially via hypothalamic CB1 activation. In addition, this receptor also participates in homeostasis recovery by modulating the inflammatory process taking place after LPS

Modulación del tono vascular por la sobre-expresión de receptores a canabinoides CB1 y CB2 en arterioesclerosis inducida en ratas

OpenAIRE

Espinoza P., María Rosa

2013-01-01

La arteriosclerosis, es un proceso degenerativo responsable de la mayor parte de las enfermedades cardiovasculares, es una enfermedad compleja que se produce a partir de múltiples factores de riesgo. Se ha observado que los compuestos derivados de la planta cannabis sativa provocan efectos vasorelajantes por medio de receptores específicos CB1 y CB2. ACPA y JWH 133 son potentes agonistas a estos receptores, se desconoce el papel que desempeñan en la arteriosclerosis provocando una relajación ...

The central cannabinoid CB1 receptor is required for diet-induced obesity and rimonabant's antiobesity effects in mice.

Science.gov (United States)

Pang, Zhen; Wu, Nancy N; Zhao, Weiguang; Chain, David C; Schaffer, Erica; Zhang, Xin; Yamdagni, Preeti; Palejwala, Vaseem A; Fan, Chunpeng; Favara, Sarah G; Dressler, Holly M; Economides, Kyriakos D; Weinstock, Daniel; Cavallo, Jean S; Naimi, Souad; Galzin, Anne-Marie; Guillot, Etienne; Pruniaux, Marie-Pierre; Tocci, Michael J; Polites, H Greg

2011-10-01

Cannabinoid receptor CB1 is expressed abundantly in the brain and presumably in the peripheral tissues responsible for energy metabolism. It is unclear if the antiobesity effects of rimonabant, a CB1 antagonist, are mediated through the central or the peripheral CB1 receptors. To address this question, we generated transgenic mice with central nervous system (CNS)-specific knockdown (KD) of CB1, by expressing an artificial microRNA (AMIR) under the control of the neuronal Thy1.2 promoter. In the mutant mice, CB1 expression was reduced in the brain and spinal cord, whereas no change was observed in the superior cervical ganglia (SCG), sympathetic trunk, enteric nervous system, and pancreatic ganglia. In contrast to the neuronal tissues, CB1 was undetectable in the brown adipose tissue (BAT) or the liver. Consistent with the selective loss of central CB1, agonist-induced hypothermia was attenuated in the mutant mice, but the agonist-induced delay of gastrointestinal transit (GIT), a primarily peripheral nervous system-mediated effect, was not. Compared to wild-type (WT) littermates, the mutant mice displayed reduced body weight (BW), adiposity, and feeding efficiency, and when fed a high-fat diet (HFD), showed decreased plasma insulin, leptin, cholesterol, and triglyceride levels, and elevated adiponectin levels. Furthermore, the therapeutic effects of rimonabant on food intake (FI), BW, and serum parameters were markedly reduced and correlated with the degree of CB1 KD. Thus, KD of CB1 in the CNS recapitulates the metabolic phenotype of CB1 knockout (KO) mice and diminishes rimonabant's efficacy, indicating that blockade of central CB1 is required for rimonabant's antiobesity actions.

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.

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

KAUST Repository

Seo, Jeongsuk; Anjum, Dalaver H.; Takanabe, Kazuhiro; Kubota, Jun; Domen, Kazunari

2014-01-01

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.

Data of evolutionary structure change: 1A5CB-2QUTA [Confc[Archive

Lifescience Database Archive (English)

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Participatory and evidence-based recommendations for urban redevelopment following natural disasters: older adults as policy advisers.

Science.gov (United States)

Annear, Michael; Keeling, Sally; Wilkinson, Tim

2014-03-01

To develop community-generated recommendations to inform urban environmental remediation following earthquakes in Christchurch, New Zealand, and share these with local decision-makers during a participatory action research process. This study employed three focus group discussions to critique mixed-methods and multiphase results and develop evidence-based recommendations. Participants included 30 volunteers and 8 knowledgeable advisers aged 65 years and older. Participant recommendations addressed the remediation of earthquake-affected suburbs, access to transportation, age-friendly design, safer communities, resilient support agencies, and restoration of resources for social and cultural activities. Older collaborators identified salient barriers to active ageing and options for post-earthquake redevelopment that had not previously been considered in research or policy. Independently living older adults are well placed to work with researchers to develop recommendations to improve the urban environment following natural disasters as well as in times of relative stability. © 2013 ACOTA.

Mice expressing a “hyper-sensitive” form of the CB1 cannabinoid receptor (CB1) show modestly enhanced alcohol preference and consumption

Science.gov (United States)

Gonek, Maciej; Zee, Michael L.; Farnsworth, Jill C.; Amin, Randa A.; Andrews, Mary-Jeanette; Davis, Brian J.; Mackie, Ken; Morgan, Daniel J.

2017-01-01

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. PMID:28426670

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 chondrit...... planetesimals. The inferred μMg* value of -3.87 ± 0.93 ppm for the CB parent body is significantly lower than the bulk solar system value of 4.5 ± 1.1 ppm inferred from CI chondrites, suggesting that CB chondrites accreted material comprising an early formed Al-free component.......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......, indicating substantial suppression of isotopic fractionation during evaporative loss of Mg, possibly due to evaporation at high Mg partial pressure. Thus, the Mg-isotope data of skeletal chondrules from HH237 are consistent with their origin as melts produced in the impact-generated plume of colliding...

Localization and function of the cannabinoid CB1 receptor in the anterolateral bed nucleus of the stria terminalis.

Directory of Open Access Journals (Sweden)

Nagore Puente

Full Text Available BACKGROUND: The bed nucleus of the stria terminalis (BNST is involved in behaviors related to natural reward, drug addiction and stress. In spite of the emerging role of the endogenous cannabinoid (eCB system in these behaviors, little is known about the anatomy and function of this system in the anterolateral BNST (alBNST. The aim of this study was to provide a detailed morphological characterization of the localization of the cannabinoid 1 (CB1 receptor a necessary step toward a better understanding of the physiological roles of the eCB system in this region of the brain. METHODOLOGY/PRINCIPAL FINDINGS: We have combined anatomical approaches at the confocal and electron microscopy level to ex-vivo electrophysiological techniques. Here, we report that CB1 is localized on presynaptic membranes of about 55% of immunopositive synaptic terminals for the vesicular glutamate transporter 1 (vGluT1, which contain abundant spherical, clear synaptic vesicles and make asymmetrical synapses with alBNST neurons. About 64% of vGluT1 immunonegative synaptic terminals show CB1 immunolabeling. Furthermore, 30% and 35% of presynaptic boutons localize CB1 in alBNST of conditional mutant mice lacking CB1 mainly from GABAergic neurons (GABA-CB1-KO mice and mainly from cortical glutamatergic neurons (Glu-CB1-KO mice, respectively. Extracellular field recordings and whole cell patch clamp in the alBNST rat brain slice preparation revealed that activation of CB1 strongly inhibits excitatory and inhibitory synaptic transmission. CONCLUSIONS/SIGNIFICANCE: This study supports the anterolateral BNST as a potential neuronal substrate of the effects of cannabinoids on stress-related behaviors.

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.

Preconception care policy, guidelines, recommendations and services across six European countries: Belgium (Flanders), Denmark, Italy, the Netherlands, Sweden and the United Kingdom.

Science.gov (United States)

Shawe, Jill; Delbaere, Ilse; Ekstrand, Maria; Hegaard, Hanne Kristine; Larsson, Margareta; Mastroiacovo, Pierpaolo; Stern, Jenny; Steegers, Eric; Stephenson, Judith; Tydén, Tanja

2015-04-01

Preconception care is important for the screening, prevention and management of risk factors that affect pregnancy outcomes. We aimed to investigate pre-pregnancy care policies, guidelines, recommendations and services in six European countries. In 2013, an electronic search and investigation was undertaken of preconception policy, guidelines, recommendations and services available to healthcare professionals and the general public in six European countries: Belgium (Flanders), Denmark, Italy, the Netherlands, Sweden and the United Kingdom. Findings were compared within five categories: Governmental policy and legislation; Professional bodies and organisations; Healthcare providers; Charitable organisations; Web-based public information and internet sites. All countries had preconception recommendations for women with chronic diseases, such as diabetes and epilepsy. Recommendations for healthy women and men were fragmented and inconsistent. Preconception guidance was often included in antenatal and pregnancy guidelines. Differences between countries were seen with regard to nutritional and lifestyle advice particularly in relation to fish, caffeine and alcohol consumption, and vitamin supplementation. 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 population.

Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging.

Science.gov (United States)

Albayram, Onder; Alferink, Judith; Pitsch, Julika; Piyanova, Anastasia; Neitzert, Kim; Poppensieker, Karola; Mauer, Daniela; Michel, Kerstin; Legler, Anne; Becker, Albert; Monory, Krisztina; Lutz, Beat; Zimmer, Andreas; Bilkei-Gorzo, Andras

2011-07-05

Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1(-/-) mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1(-/-) mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation.

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.

Controlled-Deactivation CB1 Receptor Ligands as a Novel Strategy to Lower Intraocular Pressure

Directory of Open Access Journals (Sweden)

Sally Miller

2018-05-01

Full Text Available Nearly half a century has passed since the demonstration that cannabis and its chief psychoactive component Δ9-THC lowers intraocular pressure (IOP. Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a condition that places millions at risk of blindness. It is likely that Δ9-THC exerts much of its IOP-lowering effects via the activation of CB1 cannabinoid receptors. However, the initial promise of CB1 as a target for treating glaucoma has not thus far translated into a credible therapeutic strategy. We have recently shown that blocking monoacylglycerol lipase (MAGL, an enzyme that breaks the endocannabinoid 2-arachidonoyl glycerol (2-AG, substantially lowers IOP. Another strategy is to develop cannabinoid CB1 receptor agonists that are optimized for topical application to the eye. Recently we have reported on a controlled-deactivation approach where the “soft” drug concept of enzymatic deactivation was combined with a “depot effect” that is commonly observed with Δ9-THC and other lipophilic cannabinoids. This approach allowed us to develop novel cannabinoids with a predictable duration of action and is particularly attractive for the design of CB1 activators for ophthalmic use with limited or no psychoactive effects. We have tested a novel class of compounds using a combination of electrophysiology in autaptic hippocampal neurons, a well-characterized model of endogenous cannabinoid signaling, and measurements of IOP in a mouse model. We now report that AM7410 is a reasonably potent and efficacious agonist at CB1 in neurons and that it substantially (30% lowers IOP for as long as 5 h after a single topical treatment. This effect is absent in CB1 knockout mice. Our results indicate that the direct targeting of CB1 receptors with controlled-deactivation ligands is a viable approach to lower IOP in a murine model and merits further study in other model systems.

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

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

International Nuclear Information System (INIS)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey

2011-01-01

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 μM) 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: ► C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. ► Wild type and cannabinoid CB1 receptor knockout littermates

Spatial distribution of cannabinoid receptor type 1 (CB1 in normal canine central and peripheral nervous system.

Directory of Open Access Journals (Sweden)

Jessica Freundt-Revilla

Full Text Available The endocannabinoid system is a regulatory pathway consisting of two main types of cannabinoid receptors (CB1 and CB2 and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and peripheral nervous systems (PNS in mammalians and is involved in neuromodulatory functions. Since endocannabinoids were shown to be elevated in cerebrospinal fluid of epileptic dogs, knowledge about the species specific CB receptor expression in the nervous system is required. Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS. Immunohistochemistry of several regions of the brain, spinal cord and peripheral nerves from a healthy four-week-old puppy, three six-month-old dogs, and one ten-year-old dog revealed strong dot-like immunoreactivity in the neuropil of the cerebral cortex, Cornu Ammonis (CA and dentate gyrus of the hippocampus, midbrain, cerebellum, medulla oblongata and grey matter of the spinal cord. Dense CB1 expression was found in fibres of the globus pallidus and substantia nigra surrounding immunonegative neurons. Astrocytes were constantly positive in all examined regions. CB1 labelled neurons and satellite cells of the dorsal root ganglia, and myelinating Schwann cells in the PNS. These results demonstrate for the first time the spatial distribution of CB1 receptors in the healthy canine CNS and PNS. These results can be used as a basis for further studies aiming to elucidate the physiological consequences of this particular anatomical and cellular distribution.

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.

Paranoid schizophrenia is characterized by increased CB1 receptor binding in the dorsolateral prefrontal cortex.

Science.gov (United States)

Dalton, Victoria S; Long, Leonora E; Weickert, Cyndi Shannon; Zavitsanou, Katerina

2011-07-01

A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB(1) receptor (CB(1)R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB(1)R ligand [(3)H] CP 55,940 and CB(1)R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB(1)R expression. There was a main effect of diagnosis on [(3)H] CP 55,940 binding quantified across all layers of the DLPFC (F(2,71) = 3.740, p = 0.029). Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB(1)R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67) = 6.048, p = 0.004) with paranoid SCZ patients differing significantly from the control (p = 0.004) and from the non-paranoid group (p = 0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB(1)R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ.

Endogenous vs Exogenous Allosteric Modulators in GPCRs: A dispute for shuttling CB1 among different membrane microenvironments

Science.gov (United States)

Stornaiuolo, Mariano; Bruno, Agostino; Botta, Lorenzo; Regina, Giuseppe La; Cosconati, Sandro; Silvestri, Romano; Marinelli, Luciana; Novellino, Ettore

2015-10-01

A Cannabinoid Receptor 1 (CB1) binding site for the selective allosteric modulator ORG27569 is here identified through an integrate approach of consensus pocket prediction, mutagenesis studies and Mass Spectrometry. This unprecedented ORG27569 pocket presents the structural features of a Cholesterol Consensus Motif, a cholesterol interacting region already found in other GPCRs. ORG27569 and cholesterol affects oppositely CB1 affinity for orthosteric ligands. Moreover, the rise in cholesterol intracellular level results in CB1 trafficking to the axonal region of neuronal cells, while, on the contrary, ORG27568 binding induces CB1 enrichment at the soma. This control of receptor migration among functionally different membrane regions of the cell further contributes to downstream signalling and adds a previously unknown mechanism underpinning CB1 modulation by ORG27569 , that goes beyond a mere control of receptor affinity for orthosteric ligands.

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

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

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

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...

Spitzer Observations of a 24 μm Shadow: Bok Globule CB 190

Science.gov (United States)

Stutz, Amelia M.; Bieging, John H.; Rieke, George H.; Shirley, Yancy L.; Balog, Zoltan; Gordon, Karl D.; Green, Elizabeth M.; Keene, Jocelyn; Kelly, Brandon C.; Rubin, Mark; Werner, Michael W.

2007-08-01

We present Spitzer observations of the dark globule CB 190 (LDN 771). We observe a roughly circular 24 μm shadow with a 70" radius. The extinction profile of this shadow matches the profile derived from 2MASS photometry at the outer edges of the globule and reaches a maximum of ~32 visual magnitudes at the center. The corresponding mass of CB 190 is ~10 Msolar. Our 12CO and 13CO J=2-1 data over a 10'×10' region centered on the shadow show a temperature ~10 K. The thermal continuum indicates a similar temperature for the dust. The molecular data also show evidence of freezeout onto dust grains. We estimate a distance to CB 190 of 400 pc using the spectroscopic parallax of a star associated with the globule. Bonnor-Ebert fits to the density profile, in conjunction with this distance, yield ξmax=7.2, indicating that CB 190 may be unstable. The high temperature (56 K) of the best-fit Bonnor-Ebert model is in contradiction with the CO and thermal continuum data, leading to the conclusion that the thermal pressure is not enough to prevent free-fall collapse. We also find that the turbulence in the cloud is inadequate to support it. However, the cloud may be supported by the magnetic field, if this field is at the average level for dark globules. Since the magnetic field will eventually leak out through ambipolar diffusion, it is likely that CB 190 is collapsing or in a late precollapse stage. This work is based in part on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under NASA contract 1407.

Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

Science.gov (United States)

Fernández-Trapero, María; Espejo-Porras, Francisco; Rodríguez-Cueto, Carmen; Coates, Joan R.; Pérez-Díaz, Carmen; de Lago, Eva; Fernández-Ruiz, Javier

2017-01-01

ABSTRACT Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM), caused by mutations in the superoxide dismutase 1 gene (SOD1). We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity). Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining) or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells. PMID:28069688

Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

María Fernández-Trapero

2017-05-01

Full Text Available Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS. The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM, caused by mutations in the superoxide dismutase 1 gene (SOD1. We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity. Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.

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

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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.

Health policy and exercise: a brief BRFSS study and recommendations.

Science.gov (United States)

Larson, James S; Winn, Mylon

2010-03-01

The Behavioral Risk Factor Surveillance Survey is used to compare three predictors of self-rated health, specifically exercise, tobacco smoking, and a diagnosis of diabetes (a proxy for obesity). Exercise is found to be the best predictor, and the remainder of the article discusses the role of exercise in disease prevention and the all-important concept of exercise adherence. Government policy in the future needs to promote exercise adherence in a more rigorous way, because it is a key to both individual and societal health. Exercise habits need to be instilled from youth, and physical education requirements in school need to be re-established at all levels through high school. Adults also need encouragement with better neighborhood planning of exercise trails for walking and biking, as well as planned community activities to encourage fitness through one's lifetime. The article concludes with six recommendations for formal government action to encourage exercise adherence.

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)

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

LEP measurements of $V_{cb}$ using $B^{0} \\to D^{*}^{+}l^{-}\

CERN Document Server

Tarem, S

2001-01-01

CKM elements are free parameters to be measured. V/sub cb/ is the main CKM element allowing b decay. Its smallness accounts for the long b lifetime and our ability to observe higher order effects such as B oscillations. V/sub cb/ can be measured from the inclusive semileptonic decay rate of B hadrons to charm states or from the study of the decay rate of B/sup 0/ to D*/sup +/l/sup -/ nu as a function of D*+ recoil kinematics. Inclusive and exclusive channels, a four-velocity product and errors are discussed. (8 refs).CER 1121756 BASE L 13

Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia

Science.gov (United States)

Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

2013-01-01

The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB1-dependent manner, whereas pharmacological blockade of CB1 receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB1 receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB1-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB1 receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission. PMID:23563893

Cannabinoid CB2 Receptors Contribute to Upregulation of β-endorphin in Inflamed Skin Tissues by Electroacupuncture

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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

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...

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

Science.gov (United States)

Hirvonen, J; Goodwin, R S; Li, C-T; Terry, G E; Zoghbi, S S; Morse, C; Pike, V W; Volkow, N D; Huestis, M A; Innis, R B

2012-06-01

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

Cardiovascular angiography system Infinix{sub TM} CB; Shinzoyo junkanki shindan system Infinix{sub TM} CB

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

A cardiovascular angiography system Infinix{sub TM} CB is developed, which is a dedicated system for cardiovascular catheter treatment (intervention), from PTCA (percutaneous transluminal coronary angioplasty) down, capable of two-way biplanar photography. It is designed to be thoroughly operator-friendly, and some of its features are stated below. It is capable of high-speed biplanar positioning at the maximum speed of 10 degrees/second (25% faster than in the conventional type). A side beam vertical motion mechanism is provided rendering biplanar framing faster and easier. Hyper-handling is embodied with ergonomics introduced into the system. (translated by NEDO)

Cardiovascular angiography system Infinix[sub TM] CB. Shinzoyo junkanki shindan system Infinix[sub TM] CB

Energy Technology Data Exchange (ETDEWEB)

1999-03-01

A cardiovascular angiography system Infinix[sub TM] CB is developed, which is a dedicated system for cardiovascular catheter treatment (intervention), from PTCA (percutaneous transluminal coronary angioplasty) down, capable of two-way biplanar photography. It is designed to be thoroughly operator-friendly, and some of its features are stated below. It is capable of high-speed biplanar positioning at the maximum speed of 10 degrees/second (25% faster than in the conventional type). A side beam vertical motion mechanism is provided rendering biplanar framing faster and easier. Hyper-handling is embodied with ergonomics introduced into the system. (translated by NEDO)

Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer's disease.

Science.gov (United States)

Köfalvi, Attila; Lemos, Cristina; Martín-Moreno, Ana M; Pinheiro, Bárbara S; García-García, Luis; Pozo, Miguel A; Valério-Fernandes, Ângela; Beleza, Rui O; Agostinho, Paula; Rodrigues, Ricardo J; Pasquaré, Susana J; Cunha, Rodrigo A; de Ceballos, María L

2016-11-01

Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain. To that aim, we have undertaken 1) measurement of (3)H-deoxyglucose uptake in cultured cortical astrocytes and neurons and in acute hippocampal slices; 2) real-time visualization of fluorescently labeled deoxyglucose uptake in superfused hippocampal slices; and 3) in vivo PET imaging of cerebral (18)F-fluorodeoxyglucose uptake. We now show that both selective (JWH133 and GP1a) as well as non-selective (WIN55212-2) CB2R agonists, but not the CB1R-selective agonist, ACEA, stimulate glucose uptake, in a manner that is sensitive to the CB2R-selective antagonist, AM630. Glucose uptake is stimulated in astrocytes and neurons in culture, in acute hippocampal slices, in different brain areas of young adult male C57Bl/6j and CD-1 mice, as well as in middle-aged C57Bl/6j mice. Among the endocannabinoid metabolizing enzymes, the selective inhibition of COX-2, rather than that of FAAH, MAGL or α,βDH6/12, also stimulates the uptake of glucose in hippocampal slices of middle-aged mice, an effect that was again prevented by AM630. However, we found the levels of the endocannabinoid, anandamide reduced in the hippocampus of TgAPP-2576 mice (a model of β-amyloidosis), and likely as a consequence, COX-2 inhibition failed to stimulate glucose uptake in these mice. Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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

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 NO_x 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 NO_x from major source areas to potentially NO_x-sensitive areas where additional ozone may be produced in areas remote from direct NO_x sources.

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

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

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.

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.

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.

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

Expression analysis and functional characterization of a novel cold-responsive gene CbCOR15a from Capsella bursa-pastoris.

Science.gov (United States)

Zhou, Mingqi; Wu, Lihua; Liang, Jing; Shen, Chen; Lin, Juan

2012-05-01

The cold-responsive (COR) genes involved in C-repeat binding factor signaling pathway function essentially in cold acclimation of higher plants. A novel COR gene CbCOR15a from shepherd's purse (Capsella bursa-pastoris) was predicted to be a homolog of COR15 in Arabidopsis. The analysis of tissue specific expression pattern as well as characterization of the CbCOR15a promoter revealed that the expression of CbCOR15a was induced by coldness not only in leaves and stem but also in roots. Sequence analysis showed that a 909 bp promoter region of CbCOR15a contained two CRT/DRE elements, two ABRE elements, one auxin-responsive TGA-element and one MeJA-responsive CGTCA-motif. In young seedlings the expression of CbCOR15a could be apparently increased by SA, ABA, MeJA and IAA, and transiently increased by GA(3) accompanied by obvious feedback suppression. According to the altered physiological index values in tobacco under cold treatments, the overexpression of CbCOR15a significantly increased the cold tolerance of transgenic tobacco plants. It can be suggested that CbCOR15a was involved in cold response of Capsella bursa-pastoris associated with SA, ABA, MeJA, IAA and GA(3) regulation and confers enhanced cold acclimation in transgenic plants.

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.

Growth Promotion and Disease Suppression Ability of a Streptomyces sp. CB-75 from Banana Rhizosphere Soil

Science.gov (United States)

Chen, Yufeng; Zhou, Dengbo; Qi, Dengfeng; Gao, Zhufen; Xie, Jianghui; Luo, Yanping

2018-01-01

An actinomycete strain, CB-75, was isolated from the soil of a diseased banana plantation in Hainan, China. Based on phenotypic and molecular characteristics, and 99.93% sequence similarity with Streptomyces spectabilis NBRC 13424 (AB184393), the strain was identified as Streptomyces sp. This strain exhibited broad-spectrum antifungal activity against 11 plant pathogenic fungi. Type I polyketide synthase (PKS-I) and non-ribosomal peptide synthetase (NRPS) were detected, which were indicative of the antifungal compounds that Streptomyces sp. CB-75 could produce. An ethyl acetate extract from the strain exhibited the lowest minimum inhibitory concentration (MIC) against Colletotrichum musae (ATCC 96167) (0.78 μg/ml) and yielded the highest antifungal activity against Colletotrichum gloeosporioides (ATCC 16330) (50.0 μg/ml). Also, spore germination was significantly inhibited by the crude extract. After treatment with the crude extract of Streptomyces sp. CB-75 at the concentration 2 × MIC, the pathogenic fungi showed deformation, shrinkage, collapse, and tortuosity when observed by scanning electron microscopy (SEM). By gas chromatography-mass spectrometry (GC-MS) of the crude extract, 18 chemical constituents were identified; (Z)-13-docosenamide was the major constituent. Pot experiments showed that the incidence of banana seedlings was reduced after using Streptomyces sp. CB-75 treatment. The disease index was 10.23, and the prevention and control effect was 83.12%. Furthermore, Streptomyces sp. CB-75 had a growth-promoting effect on banana plants. The chlorophyll content showed 88.24% improvement, the leaf area, root length, root diameter, plant height, and stem showed 88.24, 90.49, 136.17, 61.78, and 50.98% improvement, respectively, and the shoot fresh weight, root fresh weight, shoot dry weight, and root dry weight showed 82.38, 72.01, 195.33, and 113.33% improvement, respectively, compared with treatment of fermentation broth without Streptomyces sp. CB-75

Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking.

Directory of Open Access Journals (Sweden)

Islam Gamaleddin

Full Text Available Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2 have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg and CB2 agonist AM1241 (1 to 10 mg/kg on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.

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

release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1...

Investing in Youth: A Compilation of Recommended Policies and Practices. National Conference (New Orleans, Louisiana, December 9-11, 1992).

Science.gov (United States)

National Governors' Association, Washington, DC.

These proceedings include 13 "perspectives from the field" and 9 selected papers (with abstracts) from a national conference on recommended policies and practices for investing in youth. The 13 perspectives papers are as follows: "Saving the Next Generation" (Berlin); "Effective Strategies for Investing in Youth"…

Genome Sequence of the 1,4-Dioxane-Degrading Pseudonocardia dioxanivoransStrain CB1190▿

Science.gov (United States)

Sales, Christopher M.; Mahendra, Shaily; Grostern, Ariel; Parales, Rebecca E.; Goodwin, Lynne A.; Woyke, Tanja; Nolan, Matt; Lapidus, Alla; Chertkov, Olga; Ovchinnikova, Galina; Sczyrba, Alexander; Alvarez-Cohen, Lisa

2011-01-01

Pseudonocardia dioxanivoransCB1190 is the first bacterium reported to be capable of growth on the environmental contaminant 1,4-dioxane and the first member of the genus Pseudonocardiafor which there is an annotated genome sequence. Preliminary analysis of the genome (chromosome and three plasmids) indicates that strain CB1190 possesses several multicomponent monooxygenases that could be involved in the aerobic degradation of 1,4-dioxane and other environmental contaminants. PMID:21725009

The CB1 Receptor as an Important Mediator of Hedonic Reward Processing

Science.gov (United States)

Friemel, Chris M; Zimmer, Andreas; Schneider, Miriam

2014-01-01

The endocannabinoid (ECB) system has emerged recently as a key mediator for reward processing. It is well known that cannabinoids affect appetitive learning processes and can induce reinforcing and rewarding effects. However, the involvement of the ECB system in hedonic aspects of reward-related behavior is not completely understood. With the present study, we investigated the modulatory role of the ECB system on hedonic perception, measured by the pleasure attenuated startle (PAS) paradigm for a palatable food reward. Here, a conditioned odor is thought to induce a pleasant affective state that attenuates an aversive reflex—the acoustic startle response. Modulatory effects of the CB1 receptor antagonist/inverse agonist SR1411716 and the cannabinoid agonist WIN 55 212-2 on PAS were examined in rats. PAS was also measured in CB1 receptor knockout (KO) and wild-type (WT) mice. Pharmacological inhibition as well as the absence of CB1 receptors was found to reduce PAS, whereas WIN 55 212-2 administration increased PAS. Finally, presentation of a conditioned reward cue was found to induce striatal FosB/ΔFosB expression in WT mice, but not in KO mice, indicating a reduced stimulation of reward-related brain regions in conditioned KO mice by odor presentation. We here show that in addition to our previous studies in rats, PAS may also serve as a valuable and suitable measure to assess hedonic processing in mice. Our data further indicate that the ECB system, and in particular CB1 receptor signaling, appears to be highly important for the mediation of hedonic aspects of reward processing. PMID:24718372

A Novel Selective Inverse Agonist of the CB2 Receptor as a Radiolabeled Tool Compound for Kinetic Binding Studies.

Science.gov (United States)

Martella, Andrea; Sijben, Huub; Rufer, Arne C; Grether, Uwe; Fingerle, Juergen; Ullmer, Christoph; Hartung, Thomas; IJzerman, Adriaan P; van der Stelt, Mario; Heitman, Laura H

2017-10-01

The endocannabinoid system, and in particular the cannabinoid type 2 receptor (CB2R), raised the interest of many medicinal chemistry programs for its therapeutic relevance in several (patho)physiologic processes. However, the physico-chemical properties of tool compounds for CB2R (e.g., the radioligand [ 3 H]CP55,940) are not optimal, despite the research efforts in developing effective drugs to target this system. At the same time, the importance of drug-target binding kinetics is growing since the kinetic binding profile of a ligand may provide important insights for the resulting in vivo efficacy. In this context we synthesized and characterized [ 3 H]RO6957022, a highly selective CB2R inverse agonist, as a radiolabeled tool compound. In equilibrium and kinetic binding experiments [ 3 H]RO6957022 showed high affinity for human CB2R with fast association ( k on ) and moderate dissociation ( k off ) kinetics. To demonstrate the robustness of [ 3 H]RO6957022 binding, affinity studies were carried out for a wide range of CB2R reference ligands, spanning the range of full, partial, and inverse agonists. Finally, we used [ 3 H]RO6957022 to study the kinetic binding profiles (i.e., k on and k off values) of selected synthetic and endogenous (i.e., 2-arachidonoylglycerol, anandamide, and noladin ether) CB2R ligands by competition association experiments. All tested ligands, and in particular the endocannabinoids, displayed distinct kinetic profiles, shedding more light on their mechanism of action and the importance of association rates in the determination of CB2R affinity. Altogether, this study shows that the use of a novel tool compound, i.e., [ 3 H]RO6957022, can support the development of novel ligands with a repertoire of kinetic binding profiles for CB2R. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

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

Elevation of endogenous anandamide impairs LTP, learning, and memory through CB1 receptor signaling in mice.

Science.gov (United States)

Basavarajappa, Balapal S; Nagre, Nagaraja N; Xie, Shan; Subbanna, Shivakumar

2014-07-01

In rodents, many exogenous and endogenous cannabinoids, such as anandamide (AEA) and 2-arachidonyl glycerol (2-AG), have been shown to play an important role in certain hippocampal memory processes. However, the mechanisms by which endogenous AEA regulate this processes are not well understood. Here the effects of AEA on long-term potentiation (LTP), hippocampal-dependent learning and memory tasks, pERK1/2, pCaMKIV, and pCREB signaling events in both cannabinoid receptor type 1 (CB1R) wild-type (WT) and knockout (KO) mice were assessed following administration of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH). Acute administration of URB597 enhanced AEA levels without affecting the levels of 2-AG or CB1R in the hippocampus and neocortex as compared to vehicle. In hippocampal slices, URB597 impaired LTP in CB1R WT but not in KO littermates. URB597 impaired object recognition, spontaneous alternation and spatial memory in the Y-maze test in CB1R WT mice but not in KO mice. Furthermore, URB597 enhanced ERK phosphorylation in WT without affecting total ERK levels in WT or KO mice. URB597 impaired CaMKIV and CREB phosphorylation in WT but not in KO mice. CB1R KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio as compared to WT littermates. Our results indicate that pharmacologically elevated AEA impair LTP, learning and memory and inhibit CaMKIV and CREB phosphorylation, via the activation of CB1Rs. Collectively, these findings also suggest that pharmacological elevation of AEA beyond normal concentrations is also detrimental for the underlying physiological responses. © 2014 Wiley Periodicals, Inc.

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.

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

Status of the SPES-charge breeder (SPES-CB) and its beam line at INFN-LNL

International Nuclear Information System (INIS)

Galatá, Àlessio; Comunian, M.; Bellan, L.; Maggiore, M.; Patti, G.; Roncolato, C.; Bisoffi, G.; Russo, A.D.; Calabretta, L.; Angot, J.; Lamy, T.

2016-01-01

The Selective Production of Exotic Species (SPES) facility is under construction at INFN-LNL: aim of this project is the production, ionization and post-acceleration of radioactive ions to perform forefront research in nuclear physics. Radioactive species will be produced by fissions induced by a proton beam impinging on an UC_x target: the proton beam will be delivered by a room temperature cyclotron (built by the Best Company) with a maximum energy of 40 MeV and 0.25 mA of maximum current. The radioactive species produced in the Target-Ion-Source system, extracted as a 1+ beam, cooled in a RFQ-cooler and purified from the isobars contaminants through a High Resolution Mass Spectrometer (HRMS). In order to allow post acceleration with the superconducting linac ALPI at INFN-LNL (up to 10 MeV/A for A/q = 7), an ECR-based charge breeding technique (ECR-CB) was chosen: in particular the SPES-CB was developed by the LPSC Grenoble on the basis of the Phoenix booster. The SPES-CB will be equipped with a complete test bench, totally integrated with the SPES beam line: in particular, in order to avoid beam contaminations induced by the impurities present inside the SPES-CB, and to have high transmission for a beam of very low intensity, special attention was paid not only to the transport efficiency but also to the resolution of the spectrometer downstream the charge breeder, with the design of a Medium Resolution Mass Spectrometer (MRMS). In the following paper the technical aspects connected with SPES-CB, its beam line and the transport of highly charged radioactive ions will be described.

Status of the SPES-charge breeder (SPES-CB) and its beam line at INFN-LNL

Energy Technology Data Exchange (ETDEWEB)

Galatá, Àlessio; Comunian, M. [INFN-Laboratori Nazionali di Legnaro, Viale dell’Universitá 2, 35020 Legnaro, Padova (Italy); Bellan, L. [INFN-Laboratori Nazionali di Legnaro, Viale dell’Universitá 2, 35020 Legnaro, Padova (Italy); Dipartimento di Fisica e Astronomia, Universitá degli Studi di Padova e Sezione INFN, Padova (Padova) (Italy); Maggiore, M.; Patti, G.; Roncolato, C.; Bisoffi, G. [INFN-Laboratori Nazionali di Legnaro, Viale dell’Universitá 2, 35020 Legnaro, Padova (Italy); Russo, A.D.; Calabretta, L. [INFN-Laboratori Nazionali del Sud, via S. Sofia 62, 95123 Catania (Italy); Angot, J.; Lamy, T. [LPSC – Université Grenoble Alpes – CNRS/IN2P3, 53 rue des Martyrs, 38026 Grenoble Cedex (France)

2016-06-01

The Selective Production of Exotic Species (SPES) facility is under construction at INFN-LNL: aim of this project is the production, ionization and post-acceleration of radioactive ions to perform forefront research in nuclear physics. Radioactive species will be produced by fissions induced by a proton beam impinging on an UC{sub x} target: the proton beam will be delivered by a room temperature cyclotron (built by the Best Company) with a maximum energy of 40 MeV and 0.25 mA of maximum current. The radioactive species produced in the Target-Ion-Source system, extracted as a 1+ beam, cooled in a RFQ-cooler and purified from the isobars contaminants through a High Resolution Mass Spectrometer (HRMS). In order to allow post acceleration with the superconducting linac ALPI at INFN-LNL (up to 10 MeV/A for A/q = 7), an ECR-based charge breeding technique (ECR-CB) was chosen: in particular the SPES-CB was developed by the LPSC Grenoble on the basis of the Phoenix booster. The SPES-CB will be equipped with a complete test bench, totally integrated with the SPES beam line: in particular, in order to avoid beam contaminations induced by the impurities present inside the SPES-CB, and to have high transmission for a beam of very low intensity, special attention was paid not only to the transport efficiency but also to the resolution of the spectrometer downstream the charge breeder, with the design of a Medium Resolution Mass Spectrometer (MRMS). In the following paper the technical aspects connected with SPES-CB, its beam line and the transport of highly charged radioactive ions will be described.

Informal alcohol in Malawi: stakeholder perceptions and policy recommendations.

Science.gov (United States)

Limaye, Rupali J; Rutkow, Lainie; Rimal, Rajiv N; Jernigan, David H

2014-02-01

Through the eyes of those involved in the alcohol policy-making process in Malawi, we explored the role of informal (non-commercial) alcohol in rural communities, its harmful effects, and implications for appropriate national policy. Harms included early drinking initiation, violence, and sexual risk exposure. Informants suggested that policy should address informal alcohol's content, selling times, and easy access. Because most informal alcohol producers are women who rely upon sales for subsistence, policies must avoid limiting women's economic opportunities while protecting community health.

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

European food and nutrition policies in action. Finland's food and nutrition policy: progress, problems and recommendations.

Science.gov (United States)

Milio, N

1998-01-01

Some progress has clearly been made in several aspects of Finland's food and nutrition policy: access to nutrition information and education, improvements in mass catering, increased availability of healthier food products, and pricing and quality requirements favourable to a healthy diet. Finnish eating patterns have improved in relation to some recommended foods and macronutrients. The structural changes in farm and food production are largely the result of new political and economic realities both in Finland and internationally, resulting in the Government focusing on fiscal efficiency, decentralization and a more competitive, consumer-oriented market. This new environment is creating pressures to reduce surplus animal fat production and to expand markets in new foods for Finns and other Europeans who, for reasons of demography, health or working or living arrangements, demand new and sometimes healthier foods. Within this context, some health leaders have been able to make and work for proposals that are consistent both with political and economic imperatives and with health needs. Although the populations health status is improving and in some respects is exemplary, diet-related death and illness rates and risk factors (such as serum cholesterol and obesity) are high and their decline, along with some healthy changes in eating patterns, has slowed since the mid-1980s (ironically, since the adoption of the nutrition policy). The more slowly improvements occur, the higher will be the social and economic costs. Major problems in policy implementation exist. Although much has been done in research and demonstration and in the development of national guidelines (in public catering and labeling, for example) there is an apparent lag in translating such soft technology into action and monitoring its implementation in order to develop corrective measures at the operational level. This problem may increase with decentralized budget control and a less regulated market

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.

The low-temperature structural behavior of sodium 1-carba-closo-decaborate: NaCB{sub 9}H{sub 10}

Energy Technology Data Exchange (ETDEWEB)

Wu, Hui, E-mail: hui.wu@nist.gov [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); Tang, Wan Si [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742-2115 (United States); Zhou, Wei [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); Tarver, Jacob D. [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); National Renewable Energy Laboratory, Golden, CO 80401 (United States); Stavila, Vitalie [Energy Nanomaterials, Sandia National Laboratories, Livermore, CA 94551 (United States); Brown, Craig M. [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); Udovic, Terrence J., E-mail: udovic@nist.gov [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States)

2016-11-15

Two ordered phases of the novel solid superionic conductor sodium 1-carba-closo-decaborate (NaCB{sub 9}H{sub 10}) were identified via synchrotron x-ray powder diffraction in combination with first-principles calculations and neutron vibrational spectroscopy. A monoclinic packing of the large ellipsoidal CB{sub 9}H{sub 10}{sup −} anions prevails at the lowest temperatures, but a first-order transformation to a slightly modified orthorhombic packing is largely complete by 240 K. The CB{sub 9}H{sub 10}{sup −} anion orientational alignments and Na{sup +} cation interstitial sitings in both phases are arranged so as to minimize the cation proximities to the uniquely more positive C-bonded H atoms of the anions. These results provide valuable structural information pertinent to understanding the relatively low-temperature, entropy-driven, order-disorder phase transition for this compound. - Graphical abstract: Ordered monoclinic and orthorhombic NaCB{sub 9}H{sub 10} phases were determined by XRD and DFT computations and corroborated by neutron vibrational spectroscopy. - Highlights: • Two T-dependent ordered structures of Na(1-CB{sub 9}H{sub 10}) were determined by XRD. • The lower-T monoclinic to higher-T orthorhombic transition occurs from 210 to 240 K. • The main structural differences involve changes in the canting of the CB{sub 9}H{sub 10}{sup −} anions. • DFT and neutron vibrational spectroscopy corroborate the lower-T monoclinic structure. • The results are important for understanding the nature of this superionic conductor.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

OpenAIRE

Hirvonen, J; Goodwin, RS; Li, C-T; Terry, GE; Zoghbi, SS; Morse, C; Pike, VW; Volkow, ND; Huestis, MA; Innis, RB

2011-01-01

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke ca...

In vitro metabolism of 2,2',3,4',5,5',6-heptachlorobiphenyl(CB187) with liver microsomes of rats, hamsters and guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Koga, N.; Ohta, C.; Kanamaru, T. [Nakamura Gakuen Univ., Fukuoka (Japan); Haraguchi, K. [Daiichi Coll. of Pharmaceutical Sciences, Fukuoka (Japan); Kato, Y.; Yamada, S. [Univ. of Shizuoka, Shizuoka (Japan)

2004-09-15

PCB congeners possess extremely high lipophilicity and biological stability, and as a result they are not easily eliminated from the body once ingested. In particular, not only 2,4,5-trichlorosubstituted but also 6 or more chlorine-substituted PCBs such as 2,2',3',4,4',5-hexa-chlorobiphenyl (hexaCB) (CB138), 2,2',4,4',5,5'-hexaCB (CB153), 2,2',3,4,4',5,5'-heptachloro-biphenyl (heptaCB) (CB180) and 2,2',3,4',5,5',6-heptaCB (CB187) have been detected in blood and adipose tissues of mammals and human mother's milk at higher concentration. In addition, the 4-hydroxy (OH)-metabolite of CB187 has been reported to be present in human blood at the highest concentration of that derived from other PCB congeners. Although CB187, a tri-ortho-PCB, is one of the minor component in the commercial PCB preparations such as Clophen, Aroclor and Kanechlor, the toxic equivalency factor (TEF) which is used for dioxin-like PCB congeners including coplanar-PCBs and mono-ortho-PCBs to assess the potency of the toxicity has not been set up for di- and tri-ortho-PCB congeners. These facts indicate that 4-OH-PCB187 become more persistent and more important toxicologically than the parent CB187. However, there is little report about biotransformation in vivo or in vitro of CB187 in animals. Therefore, we examined CB187 metabolism by liver microsomes of rats, hamsters and guinea pigs.

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.

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.

Nuclear energy policy and atomic energy law. Issues and developmental aspects

International Nuclear Information System (INIS)

Schmidt-Preuss, M.

1998-01-01

Nuclear energy policy and the atomic energy law recurrently have been a focal point of interest and an issue of political debate in Germany. However, this time the political debate is gaining a new dimension in the wake of the general elections held in September 1998 and the resulting change of government. The contribution compares aspects of the history of atomic energy research and nuclear technology with the current political situation and assesses the impacts of announced changes in government policy and legislation. (orig./CB) [de

Do use the climate policy mechanisms of the Kyoto protocol.. An interview with Hartmut Grass, Hamburg

International Nuclear Information System (INIS)

Anon.

1999-01-01

The aspects discussed in this interview are of a global and national nature. The global aspects relate to the results of the UN conference in Kyoto in matters of the UN Framework Convention on Climate Change, and the national aspects relate to Germany's environmental and energy policy and the current situation in the context of global policy for greenhouse gas abatement. (orig./CB) [de

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.

CbRCI35, a cold responsive peroxidase from Capsella bursa-pastoris regulates reactive oxygen species homeostasis and enhances cold tolerance in tobacco

Directory of Open Access Journals (Sweden)

Juan Lin

2016-10-01

Full Text Available Low temperature affects gene regulatory networks and alters cellular metabolism to inhibit plant growth. Peroxidases are widely distributed in plants and play a large role in adjusting and controlling reactive oxygen species (ROS homeostasis in response to abiotic stresses such as low temperature. The Rare Cold-Inducible 35 gene from Capsella bursa-pastoris (CbRCI35 belongs to the type III peroxidase family and has been reported to be a cold responsive gene in plants. Here we performed an expressional characterization of CbRCI35 under cold and ionic liquid treatments. The promoter of CbRCI35 was also cloned and its activity was examined using the GUS reporter system. CbRCI35 protein was localized in the cytoplasm according to sequence prediction and GFP fusion assay. Heterologous expression tests revealed that CbRCI35 conferred enhanced resistance to low temperature and activated endogenous cold responsive signaling in tobacco. Furthermore, in the normal condition the ROS accumulation was moderately enhanced while after chilling exposure superoxide dismutase (SOD activity was increased in CbRCI53 transgenic plants. The ROS metabolism related genes expression was altered accordingly. We conclude that CbRCI35 modulates ROS homeostasis and contributes to cold tolerance in plants.

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.

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.

Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

Science.gov (United States)

Han, Jing; Kesner, Philip; Metna-Laurent, Mathilde; Duan, Tingting; Xu, Lin; Georges, Francois; Koehl, Muriel; Abrous, Djoher Nora; Mendizabal-Zubiaga, Juan; Grandes, Pedro; Liu, Qingsong; Bai, Guang; Wang, Wei; Xiong, Lize; Ren, Wei; Marsicano, Giovanni; Zhang, Xia

2012-03-02

Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

LTER network data access policy revision: report and recommendations.

Science.gov (United States)

James Brunt; Peter McCartney; Stuart Gage; Don. Henshaw

2004-01-01

This document is a report on work carried out to update the LTER Network Data Access Policy. The current LTER Network Data Access Policy, approved by the coordinating committee in 1997, has been in use since 1990. An analysis of the current policies related to the release, access, and use of LTER data has been undertaken by a sub-committee of the LTER Network...

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

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.

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.

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.

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.

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.

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

not significantly different. Conclusions: Although changes in CB1 receptor expression have been demonstrated in human suicide victims with depression and in animal models of depression, the present maps of [3H]OMAR binding revealed no difference between FSL and FRL rats. We used a single concentration of [3H......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...

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.

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.

A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569.

Science.gov (United States)

Fay, Jonathan F; Farrens, David L

2012-09-28

Allosteric ligands that modulate how G protein-coupled receptors respond to traditional orthosteric drugs are an exciting and rapidly expanding field of pharmacology. An allosteric ligand for the cannabinoid receptor CB1, Org 27569, exhibits an intriguing effect; it increases agonist binding, yet blocks agonist-induced CB1 signaling. Here we explored the mechanism behind this behavior, using a site-directed fluorescence labeling approach. Our results show that Org 27569 blocks conformational changes in CB1 that accompany G protein binding and/or activation, and thus inhibit formation of a fully active CB1 structure. The underlying mechanism behind this behavior is that simultaneous binding of Org 27569 produces a unique agonist-bound conformation, one that may resemble an intermediate structure formed on the pathway to full receptor activation.

Policy Recommendations for Developing Foreign-invested Enterprise in China

Institute of Scientific and Technical Information of China (English)

原磊

2008-01-01

China has undergone the three major stages in its development of foreign-invested enterprise: exploratory development, accelerated development and innovative development. This harnessing of foreign investment has resulted in tremendous success for China, including making up for the funds shortage for economic construction, promoting corporate technological progress and management expertise, easing employment pressure, increasing fiscal revenue and boosting trade. At the same time, there have been problems, including questions of economic security, environment and energy issues, unequal competition and problems with the management of foreign-invested enterprises. To promote the development of foreign-invested enterprises in both a healthy and rapid fashion, China should look toward "maintaining policy continuity, promoting the forward-looking nature of policy, strengthening policy guidance and highlighting policy innovativeness."

Integrated cannabinoid CB1 receptor transmission within the amygdala-prefrontal cortical pathway modulates neuronal plasticity and emotional memory encoding.

Science.gov (United States)

Tan, Huibing; Lauzon, Nicole M; Bishop, Stephanie F; Bechard, Melanie A; Laviolette, Steven R

2010-06-01

The cannabinoid CB1 receptor system is functionally involved in the processing and encoding of emotionally salient sensory information, learning and memory. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC). In addition, synaptic plasticity in the form of long-term potentiation (LTP) within the BLA > mPFC pathway is an established correlate of exposure to emotionally salient events. We performed a series of in vivo LTP studies by applying tetanic stimulation to the BLA combined with recordings of local field potentials within prelimbic cortical (PLC) region of the rat mPFC. Systemic pretreatment with AM-251 dose dependently blocked LTP along the BLA-PLC pathway and also the behavioral acquisition of conditioned fear memories. We next performed a series of microinfusion experiments wherein CB1 receptor transmission within the BLA > PLC circuit was pharmacologically blocked. Asymmetrical, interhemispheric blockade of CB1 receptor transmission along the BLA > PLC pathway prevented the acquisition of emotionally salient associative memory. Our results indicate that coordinated CB1 receptor transmission within the BLA > PLC pathway is critically involved in the encoding of emotional fear memories and modulates neural plasticity related to the encoding of emotionally salient associative learning.

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

Evaluation of [11C]CB184 for imaging and quantification of TSPO overexpression in a rat model of herpes encephalitis

International Nuclear Information System (INIS)

Vallez Garcia, David; Vries, Erik F.J. de; Dierckx, Rudi A.J.O.; Doorduin, Janine; Toyohara, Jun; Ishiwata, Kiichi; Hatano, Kentaro

2015-01-01

Evaluation of translocator protein (TSPO) overexpression is considered an attractive research tool for monitoring neuroinflammation in several neurological and psychiatric disorders. [ 11 C]PK11195 PET imaging has been widely used for this purpose. However, it has a low sensitivity and a poor signal-to-noise ratio. For these reasons, [ 11 C]CB184 was evaluated as a potentially more sensitive PET tracer. A model of herpes simplex encephalitis (HSE) was induced in male Wistar rats. On day 6 or 7 after virus inoculation, [ 11 C]CB184 PET scans were acquired followed by ex vivo evaluation of biodistribution. In addition, [ 11 C]CB184 and [ 11 C]PK11195 PET scans with arterial blood sampling were acquired to generate input for pharmacokinetic modelling. Differences between the saline-treated control group and the virus-treated HSE group were explored using volumes of interest and voxel-based analysis. The biodistribution study showed significantly higher [ 11 C]CB184 uptake in the amygdala, olfactory bulb, medulla, pons and striatum (p < 0.05) in HSE rats than in control rats, and the voxel-based analysis showed higher bilateral uptake in the pons and medulla (p < 0.05, corrected at the cluster level). A high correlation was found between tracer uptake in the biodistribution study and on the PET scans (p < 0.001, r 2 = 0.71). Pretreatment with 5 mg/kg of unlabelled PK11195 effectively reduced (p < 0.001) [ 11 C]CB184 uptake in the whole brain. Both, [ 11 C]CB184 and [ 11 C]PK11195, showed similar amounts of metabolites in plasma, and the binding potential (BP ND ) was not significantly different between the HSE rats and the control rats. In HSE rats BP ND for [ 11 C]CB184 was significantly higher (p < 0.05) in the amygdala, hypothalamus, medulla, pons and septum than in control rats, whereas higher uptake of [ 11 C]PK11195 was only detected in the medulla. [ 11 C]CB184 showed nonspecific binding to healthy tissue comparable to that observed for [ 11 C]PK11195, but it

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

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...

Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice

Directory of Open Access Journals (Sweden)

Diego C. Mascarenhas

2017-10-01

Full Text Available Divergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1 and Cannabinoid type 1 (CB1 receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG of mice exposed to the tail-flick test. Accordingly, male Swiss mice received intra-dPAG injection of AEA (CB1/TRPV1 agonist, capsaicin (TRPV1 agonist, WIN (CB1 agonist, AM251 (CB1 antagonist, and 6-iodonordihydrocapsaicin (6-IODO (TRPV1 selective antagonist and their nociceptive response was assessed with the tail-flick test. In order to assess AEA effects on nociception specifically at vanilloid or cannabinoid (CB substrates into the dPAG, mice underwent an intrinsically inactive dose of AM251 or 6-IODO followed by local AEA injections and were subjected to the same test. While intra-dPAG AEA did not change acute pain, local injections of capsaicin or WIN induced a marked TRPV1- and CB1-dependent antinociceptive effect, respectively. Regarding the role of AEA specifically at CB/vanilloid substrates, while the blockade of TRPV1 did not change the lack of effects of intra-dPAG AEA on nociception, local pre-treatment of AM251, a CB1 antagonist, led to a clear AEA-induced antinociception. It seems that the exogenous AEA-induced antinociception is unmasked when it selectively binds to vanilloid substrates, which might be useful to address acute pain in basic and perhaps clinical trials.

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

Immunohistochemical characterisation and localisation of cannabinoid CB1 receptor protein in the rat vestibular nucleus complex and the effects of unilateral vestibular deafferentation.

Science.gov (United States)

Ashton, John C; Zheng, Yiwen; Liu, Ping; Darlington, Cynthia L; Smith, Paul F

2004-09-24

CB1 receptor expression has been reported to be low in the brainstem compared with the forebrain, and low in the vestibular nucleus complex (VNC) compared with other regions in the brainstem. However, a frequent effect of cannabis is dizziness and loss of balance. This may be due to the activation of cannabinoid receptors in the central vestibular pathways. We used immunohistochemistry to study the distribution of CB1 receptor protein in the VNC, and Western blotting to measure CB1 receptor expression in the VNC following unilateral vestibular deafferentation (UVD); the hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were also analysed for comparison. This study confirms a previous electrophysiological demonstration that CB1 receptors exist in significant densities in the VNC and are likely to contribute to the neurochemical control of the vestibular reflexes. Nonetheless, CB1 receptor expression did not change significantly in the VNC during vestibular compensation. In addition, despite some small but significant changes in CB1 receptor expression in the CA2/3 and the DG following UVD, in no case were these differences statistically significant in comparison to both control groups.

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.

Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation.

Science.gov (United States)

Mouro, Francisco M; Batalha, Vânia L; Ferreira, Diana G; Coelho, Joana E; Baqi, Younis; Müller, Christa E; Lopes, Luísa V; Ribeiro, Joaquim A; Sebastião, Ana M

2017-05-01

Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB 1 receptor (CB 1 R)-induced memory deficits through an adenosine A 1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A 2A receptors (A 2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB 1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB 1 /CB 2 receptor agonist WIN 55,212-2 (1 mg/kg) immediately after the NOR training, being tested for novelty recognition 24 h later. Anxiety levels were assessed by the Elevated Plus Maze test, immediately after the NOR. Mice were also tested for exploratory behaviour at the Open Field. For chronic A 2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A 2A Rs was assessed by i.p. injection of SCH 58261 (1 mg/kg) administered either together with WIN 55,212-2 or only 30 min before the NOR test phase. The involvement of CB 1 Rs was assessed by using the CB 1 R antagonist, AM251 (3 mg/kg, i.p.). WIN 55,212-2 caused a disruption in NOR, an action absent in mice also receiving AM251, KW-6002 or SCH 58261 during the encoding/consolidation phase; SCH 58251 was ineffective if present during retrieval only. No effects were detected in the Elevated Plus maze or Open Field Test. The finding that CB 1 R-mediated memory disruption is prevented by antagonism of adenosine A 2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB 1 R drugs is desired. Copyright © 2017 Elsevier Ltd. All rights reserved.

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor 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.

47 CFR 95.413 - (CB Rule 13) What communications are prohibited?

Science.gov (United States)

2010-10-01

..., traveler assistance, brief tests (radio checks), or voice paging; (5) To advertise or solicit the sale of any goods or services; (6) To transmit music, whistling, sound effects or any material to amuse or... (155.3 miles) away; (10) To advertise a political candidate or political campaign; (you may use your CB...

Evaluation of [{sup 11}C]CB184 for imaging and quantification of TSPO overexpression in a rat model of herpes encephalitis

Energy Technology Data Exchange (ETDEWEB)

Vallez Garcia, David; Vries, Erik F.J. de; Dierckx, Rudi A.J.O.; Doorduin, Janine [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, PO Box 30.001, Groningen (Netherlands); Toyohara, Jun; Ishiwata, Kiichi [Tokyo Metropolitan Institute of Gerontology, Research Team for Neuroimaging, Tokyo (Japan); Hatano, Kentaro [National Center for Geriatrics and Gerontology, Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, Obu, Aichi (Japan)

2015-03-13

Evaluation of translocator protein (TSPO) overexpression is considered an attractive research tool for monitoring neuroinflammation in several neurological and psychiatric disorders. [{sup 11}C]PK11195 PET imaging has been widely used for this purpose. However, it has a low sensitivity and a poor signal-to-noise ratio. For these reasons, [{sup 11}C]CB184 was evaluated as a potentially more sensitive PET tracer. A model of herpes simplex encephalitis (HSE) was induced in male Wistar rats. On day 6 or 7 after virus inoculation, [{sup 11}C]CB184 PET scans were acquired followed by ex vivo evaluation of biodistribution. In addition, [{sup 11}C]CB184 and [{sup 11}C]PK11195 PET scans with arterial blood sampling were acquired to generate input for pharmacokinetic modelling. Differences between the saline-treated control group and the virus-treated HSE group were explored using volumes of interest and voxel-based analysis. The biodistribution study showed significantly higher [{sup 11}C]CB184 uptake in the amygdala, olfactory bulb, medulla, pons and striatum (p < 0.05) in HSE rats than in control rats, and the voxel-based analysis showed higher bilateral uptake in the pons and medulla (p < 0.05, corrected at the cluster level). A high correlation was found between tracer uptake in the biodistribution study and on the PET scans (p < 0.001, r {sup 2} = 0.71). Pretreatment with 5 mg/kg of unlabelled PK11195 effectively reduced (p < 0.001) [{sup 11}C]CB184 uptake in the whole brain. Both, [{sup 11}C]CB184 and [{sup 11}C]PK11195, showed similar amounts of metabolites in plasma, and the binding potential (BP{sub ND}) was not significantly different between the HSE rats and the control rats. In HSE rats BP{sub ND} for [{sup 11}C]CB184 was significantly higher (p < 0.05) in the amygdala, hypothalamus, medulla, pons and septum than in control rats, whereas higher uptake of [{sup 11}C]PK11195 was only detected in the medulla. [{sup 11}C]CB184 showed nonspecific binding to healthy

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

Science.gov (United States)

Ronca, Richard D; Myers, Alyssa M; Ganea, Doina; Tuma, Ronald F; Walker, Ellen A; Ward, Sara Jane

2015-10-01

We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size. Mice received three injections of the CB2 selective agonist O-1966 or vehicle 1h prior to and 2 and 5days following induction of stroke. Infarct size was assessed at 1, 3, or 7days post-injury and learning and memory effects of injury and O-1966 treatment were assessed on days 6 and 7 using a novel object recognition task and an operant acquisition and retention procedure. O-1966 treated mice had significantly smaller infarct volumes compared with vehicle treated mice. Photoinjury was also associated with a significant memory impairment on day 7 post-injury, and this deficit was reversed with O-1966 treatment. Surprisingly, sham-operated mice receiving O-1966 treatment showed a significant learning deficit in both the recognition and operant tasks compared with vehicle treated sham mice. We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia, but may dysregulate glial or neuronal function of learning and memory circuits in the absence of injury and/or inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Best practices and recommendations on policy packaging

DEFF Research Database (Denmark)

Fearnley, Nils; Longva, Frode; Ramjerdi, Farideh

2011-01-01

. This report gives practical and general advice for each of these stages: 1. Define objectives and targets 2. Create an inventory of measures, identify potential primary measures and detect causal relationships 3. Assess policy package 4. Modify package 5. Package implementation 6. Evaluate effects, introduce...

A three-dimensional-weighted cone beam filtered backprojection (CB-FBP) algorithm for image reconstruction in volumetric CT-helical scanning

International Nuclear Information System (INIS)

Tang Xiangyang; Hsieh Jiang; Nilsen, Roy A; Dutta, Sandeep; Samsonov, Dmitry; Hagiwara, Akira

2006-01-01

Based on the structure of the original helical FDK algorithm, a three-dimensional (3D)-weighted cone beam filtered backprojection (CB-FBP) algorithm is proposed for image reconstruction in volumetric CT under helical source trajectory. In addition to its dependence on view and fan angles, the 3D weighting utilizes the cone angle dependency of a ray to improve reconstruction accuracy. The 3D weighting is ray-dependent and the underlying mechanism is to give a favourable weight to the ray with the smaller cone angle out of a pair of conjugate rays but an unfavourable weight to the ray with the larger cone angle out of the conjugate ray pair. The proposed 3D-weighted helical CB-FBP reconstruction algorithm is implemented in the cone-parallel geometry that can improve noise uniformity and image generation speed significantly. Under the cone-parallel geometry, the filtering is naturally carried out along the tangential direction of the helical source trajectory. By exploring the 3D weighting's dependence on cone angle, the proposed helical 3D-weighted CB-FBP reconstruction algorithm can provide significantly improved reconstruction accuracy at moderate cone angle and high helical pitches. The 3D-weighted CB-FBP algorithm is experimentally evaluated by computer-simulated phantoms and phantoms scanned by a diagnostic volumetric CT system with a detector dimension of 64 x 0.625 mm over various helical pitches. The computer simulation study shows that the 3D weighting enables the proposed algorithm to reach reconstruction accuracy comparable to that of exact CB reconstruction algorithms, such as the Katsevich algorithm, under a moderate cone angle (4 deg.) and various helical pitches. Meanwhile, the experimental evaluation using the phantoms scanned by a volumetric CT system shows that the spatial resolution along the z-direction and noise characteristics of the proposed 3D-weighted helical CB-FBP reconstruction algorithm are maintained very well in comparison to the FDK

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.

AAV-mediated overexpression of the CB1 receptor in the mPFC of adult rats alters cognitive flexibility, social behavior and emotional reactivity

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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.

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

Science.gov (United States)

Navarro, Gemma; Carriba, Paulina; Gandí, Jorge; Ciruela, Francisco; Casadó, Vicent; Cortés, Antoni; Mallol, Josefa; Canela, Enric I.; Lluis, Carmen; Franco, Rafael

2008-01-01

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. PMID:18956124

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.

Chronic alcohol exposure disrupts CB₁ regulation of GABAergic transmission in the rat basolateral amygdala

DEFF Research Database (Denmark)

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

2017-01-01

in BLA pyramidal neurons of rats exposed to 2–3 weeks intermittent ethanol. In the naïve rat BLA, the CB1 agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent......1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state....

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.

CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model.

Science.gov (United States)

Kossatz, Elk; Maldonado, Rafael; Robledo, Patricia

2016-12-01

The role of CB2 cannabinoid receptors (CB 2 R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB 2 R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. CB 2 R knockout (KO) mice and wild-type littermates (WT) underwent permanent ligation of the left common carotid artery and hypoxia. Behavioural measurements in the rotarod, beam walking, object recognition, open field, and Irwin tests were carried out 24h, 72h and 7 days. In KO mice, more extensive brain injury was observed. Behavioural deficits in the Irwin test were observed in both genotypes; while WT mice showed progressive recovery by day 7, KO mice did not. Only KO mice showed alterations in motor learning, coordination and balance, and did not recover over time. A higher expression of microglia and astrocytes was observed in several brain areas of lesioned WT and KO mice. The possible alteration of the inflammatory-related factors HIF-1α and TIM-3 was evaluated in these animals. In both genotypes, HIF-1α and TIM-3 expression was observed in lesioned areas associated with activated microglia. However, the expression levels of these proteins were exacerbated in KO mice in several lesioned and non-lesioned brain structures. Our results indicate that CB 2 R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor 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.

Perspectives of CB1 Antagonist in Treatment of Obesity: Experience of RIO-Asia

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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.

Climate protection policy and new jobs - a contradiction in itself?; Klimaschutz und neue Arbeitsplaetze - ein Gegensatz?

Energy Technology Data Exchange (ETDEWEB)

Scheelhaase, J. [Prognos AG, Koeln (Germany)

2002-04-01

The article summarizes the results of an expert opinion submitted by the Prognos AG to the German Federal Environmental Agency. The expert opinion was to examine in various scenarios whether implementation of additional, ambitious climate protection policies and programmes may indeed have an adverse effect on the employment situation in Germany. The experts found that under certain framework conditions, positive synergy effects will develop. (orig./CB) [German] Ob zusaetzliche klimaschuetzende Massnahmen tatsaechlich zu Lasten der Beschaeftigung gehen wuerden, ist Gegenstand eines Gutachtens der Prognos AG, Koeln, das im Auftrag des Umweltbundesamtes erarbeitet wurde. Der Artikel fasst die wesentlichen Ergebnisse des Gutachtens zusammen, das u.a. positive Synergieeffekte zwischen oekologischen und beschaeftigungspolitischen Zielen darlegt. (orig./CB)

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...

Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death

International Nuclear Information System (INIS)

Tomiyama, Ken-ichi; Funada, Masahiko

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB 1 receptor antagonist AM251, but not with the selective CB 2 receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB 1 receptor, but not by the CB 2 receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB 1 receptor, but not by the CB 2 receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB 1 receptors

High-resolution gamma spectroscopy with whole-body and partial-body counters. Experience, recommendations. Report

International Nuclear Information System (INIS)

Sahre, P.

1997-12-01

The application of high-resolution gamma spectroscopy with whole-body and partial-body counters shows a steadily rising upward trend over the last few years. This induced the ''Arbeitskreis Inkorporationsueberwachung'' of the association ''Fachverband fuer Strahlenschutz e.V.'' to organise a meeting for joint elaboration of a guide on recommended applications of this measuring technique, based on a review of existing experience and results. A key item on the agenda of the meeting was the comparative evaluation of the Ge semiconductor detector and the NaI solid scintillation detector. (orig./CB) [de

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

International Nuclear Information System (INIS)

Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

2014-01-01

Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

Modulation of Network Oscillatory Activity and GABAergic Synaptic Transmission by CB1 Cannabinoid Receptors in the Rat Medial Entorhinal Cortex

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Nicola H. Morgan

2008-01-01

Full Text Available Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide (ACPA; 10 M, an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500 nM, increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

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.

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.

Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration.

Science.gov (United States)

Scarlett, Kisha A; White, El-Shaddai Z; Coke, Christopher J; Carter, Jada R; Bryant, Latoya K; Hinton, Cimona V

2018-04-01

G-protein-coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential in vitro However, the reduced signaling entities responsible for the observed functional outputs remain elusive. This study now delineates the signaling mechanism whereby heterodimeric association between CXCR4 and CB2, induced by simultaneous agonist treatment, results in decreased CXCR4-mediated cell migration, invasion, and adhesion through inhibition of the Gα13/RhoA signaling axis. Activation of CXCR4 by its cognate ligand, CXCL12, stimulates Gα13 (GNA13), and subsequently, the small GTPase RhoA, which is required for directional cell migration and the metastatic potential of cancer cells. These studies in prostate cancer cells demonstrate decreased protein expression levels of Gα13 and RhoA upon simultaneous CXCR4/CB2 agonist stimulation. Furthermore, the agonist-induced heterodimer abrogated RhoA-mediated cytoskeletal rearrangement resulting in the attenuation of cell migration and invasion of an endothelial cell barrier. Finally, a reduction was observed in the expression of integrin α5 (ITGA5) upon heterodimerization, supported by decreased cell adhesion to extracellular matrices in vitro Taken together, the data identify a novel pharmacologic mechanism for the modulation of tumor cell migration and invasion in the context of metastatic disease. Implications: This study investigates a signaling mechanism by which GPCR heterodimerization inhibits cancer cell migration. Mol Cancer Res; 16(4); 728-39. ©2018 AACR . ©2018 American Association for Cancer Research.

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 ...

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.

BRICS Investment Policies from PFI Perspective

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Andrei Sakharov 

2017-12-01

Full Text Available The Organisation for Economic Co-operation and Development (OECD Policy Framework for Investment (PFI contains recommendations and best practices in 12 investment-related policy areas, and is widely regarded as the world’s most comprehensive and authoritative instrument on international investment regulation. The topicality of PFI recommendations for OECD members and other countries, including Russia, is dictated by competition in international investment markets. The instrument’s implementation can significantly boost a national jurisdiction’s attractiveness to investors and thus increase its economic competitiveness. The experience of the BRICS countries as large developing economies involved in collaboration with the OECD could be of great value from the standpoint of PFI implementation in Russia. This article examines investment policies of Brazil, India, China and South Africa from the perspective of PFI recommendations. The analysis is organized around four major themes: the general characteristics of investment regimes and investment stimuli, national investment regulation regimes, trade policies and overcoming structural limitations. The analysis forms the basis for recommendations to improve the investment policy regime in Russia

CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations.

Science.gov (United States)

Basavarajappa, Balapal S; Subbanna, Shivakumar

2014-02-01

Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as "Spice" or "K2" to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of "Spice/K2", including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of JWH-081 on pCaMKIV, pCREB, and pERK1/2 signaling events followed by long-term potentiation (LTP), hippocampal-dependent learning and memory tasks using CB1 receptor wild-type (WT) and knockout (KO) mice. Acute administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose impaired CaMKIV and CREB phosphorylation in a time-dependent manner in CB1 receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation. In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio compared with vehicle or WT littermates. In hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO littermates. Furthermore, JWH-081 at higher dose impaired object recognition, spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice but not in KO mice. Collectively our findings suggest that deleterious effects of JWH-081 on hippocampal function involves CB1 receptor mediated impairments in CaMKIV and CREB phosphorylation, LTP, learning and memory in mice. © 2013 Wiley Periodicals, Inc.

Candidate PET radioligands for cannabinoid CB1 receptors: [18F]AM5144 and related pyrazole compounds

International Nuclear Information System (INIS)

Li Zizhong; Gifford, Andrew; Liu Qian; Thotapally, Rajesh; Ding Yushin; Makriyannis, Alexandros; Gatley, S. John

2005-01-01

Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB 1 receptors that respond to Δ 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 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-[ 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-[ 18 F]fluoroaniline. The labeled precursor was synthesized from 1-[ 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/μmol 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 1 receptors, absolute uptake at 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 1 receptor that may require very lipophilic ligands

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.

Involvement of Gaba and Cannabinoid Receptors in Central Food Intake Regulation in Neonatal Layer Chicks: Role of CB1 and Gabaa Receptors

Directory of Open Access Journals (Sweden)

M Zendehdel

Full Text Available ABSTRACT Feeding behavior is regulated via a complex network which interacts via diverse signals from central and peripheral tissues. Endocannabinoids modulate release of GABA in a variety of regions of the central nervous system. Endocannabinoids and GABAergic system have an important role in the central regulation of appetite. Thus, the present study examines the possible interaction of central canabinoidergic and GABAergic systems on food intake in 3-h food-deprived (FD3 neonatal layer-type chicks. The results of this study showed that intracerebroventricular (ICV injection of 2-AG (2-Arachidonoylglycerol, selective CB1 receptors agonist, 2µg significantly increased food intake and this effect of 2-AG was attenuated by Picrotoxin (GABAA antagonist, 0.5µg (P0.05. Also, hyperphagic effect of CB65 (CB2 receptors agonist, 1.25µg was not affected by Picrotoxin or CGP54626 (p>0.05. Moreover, the food intake of chicks was significantly increased by ICV injection of GABAA agonist (Gaboxadol, 0.2 µg and SR141716A (CB1 receptors antagonist, 6.25µg significantly decreased Gaboxadol-induced hyperphagia (P0.05. These data showed there might be an interaction between central cannabinoidergic and GABAergic systems via CB1 and GABAA receptors in control of food intake in neonatal layer chicks.

Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB{sub 1} receptors and apoptotic cell death

Energy Technology Data Exchange (ETDEWEB)

Tomiyama, Ken-ichi; Funada, Masahiko, E-mail: mfunada@ncnp.go.jp

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB{sub 1} receptor antagonist AM251, but not with the selective CB{sub 2} receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB{sub 1} receptors.

Effects of perfusion pressure and insulin on (3H) cytochalasin B (CB) binding to control and diabetic rat hearts

International Nuclear Information System (INIS)

Pleta, M.; Chan, T.

1987-01-01

Using ( 3 H) CB, they attempted to quantitate the changes in the amount of glucose transporters in the plasma membrane (PM) and intracellular membranes (HSP) prepared from rat hearts perfused with insulin, under low and high pressure. Membranes isolated from non-perfused hearts showed a PM/HSP ratio of (0.593). Hearts perfused with low pressure showed a lower ratio of (0.474). Perfusion with insulin increased the ratio to (1.8), almost a 3-4 fold increase from low perfusion pressure. These data correlate with insulin effects in glucose transport and CB binding in the fat cells. High pressure perfusion increased the PM/HSP ratio by 1-2 fold. ( 3 H) 2-DG transport indicates a comparable increase in glucose uptake with high pressure, but with insulin only a 1.5 fold increase was observed. Initial data obtained from streptozotocin (STZ) injected diabetic rats indicate low CB binding in the PM fraction. Only insulin, but not high perfusion pressure increased PM/HSP ratio in the STZ-diabetic hearts. Their data imply that while both caused apparent translocation of glucose transporters, influences on cardiac glucose metabolism by work load are different. Furthermore, STZ induced diabetes affected only the high perfusion pressure-induced and not the insulin-stimulated change in CB binding

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.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

Directory of Open Access Journals (Sweden)

Xavier Viñals

2015-07-01

Full Text Available Activation of cannabinoid CB1 receptors (CB1R by delta9-tetrahydrocannabinol (THC produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

Science.gov (United States)

Viñals, Xavier; Moreno, Estefanía; Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I; McCormick, Peter J; Maldonado, Rafael; Robledo, Patricia

2015-07-01

Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Het endocannabinoïdsysteem, overgewicht en de CB1-endocannabinoïdreceptorblokker rimonabant

NARCIS (Netherlands)

Boekholdt, S. M.; Jukema, J. W.; Peters, R. J. G.

2007-01-01

--Obesity is an important healthcare issue. --Recent research has led to insights into the role of the endocannabinoid system in the regulation of body weight. --Rimonabant is a CB1-endocannabinoid-receptor antagonist. --Four trials were published recently on the efficacy and safety of rimonabant in

APPRAISING THE EUROPEAN NEIGHBOURHOOD POLICY: BACKGROUND, IMPLEMENTATION AND RECOMMENDATIONS

Directory of Open Access Journals (Sweden)

Kerry Longhurst

2011-09-01

Full Text Available The present article tackles the European Neighbourhood Policy (ENP in the context of the European Union’s Eastern neighbours – Ukraine, Moldova and Belarus. Reflected on the May 2011 Communication drafted by the European Commission and High Representative ‘A New Response to a Changing Neighbourhood’, the article focuses on the main steps of ENP’s evolution, looking at the political and economic offer made to the partner countries, the state of the neighbourhood, the progress made in the ENP Eastern countries, the regional component of the policy.

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

An analysis of the thermodynamic efficiency for exhaust gas recirculation-condensed water recirculation-waste heat recovery condensing boilers (EGR-CWR-WHR CB)

International Nuclear Information System (INIS)

Lee, Chang-Eon; Yu, Byeonghun; Lee, Seungro

2015-01-01

This study presents fundamental research on the development of a new boiler that is expected to have a higher efficiency and lower emissions than existing boilers. The thermodynamic efficiency of exhaust gas recirculation-condensed water recirculation-waste heat recovery condensing boilers (EGR-CWR-WHR CB) was calculated using thermodynamic analysis and was compared with other boilers. The results show the possibility of obtaining a high efficiency when the temperature of the exhaust gas is controlled within 50–60 °C because water in the exhaust gas is condensed within this temperature range. In addition, the enthalpy emitted by the exhaust gas for the new boiler is smaller because the amount of condensed water is increased by the high dew-point temperature and the low exhaust gas temperature. Thus, the new boiler can obtain a higher efficiency than can older boilers. The efficiency of the EGR-CWR-WHR CB proposed in this study is 93.91%, which is 7.04% higher than that of existing CB that is currently used frequently. - Highlights: • The study presents the development of a new boiler expected to have a high efficiency. • Thermodynamic efficiency of EGR-CWR-WHR condensing boiler was calculated. • Efficiency of EGR-CWR-WHR CB is 93.91%, which is 7.04% higher than existing CB

NSPWG-recommended safety requirements and guidelines for SEI nuclear propulsion

International Nuclear Information System (INIS)

Marshall, A.C.; Lee, J.H.; McCulloch, W.H.; Sawyer, J.C. Jr.; Bari, R.A.; Brown, N.W.; Cullingford, H.S.; Hardy, A.C.; Remp, K.; Sholtis, J.A.

1992-01-01

An Interagency Nuclear Safety Policy Working Group (NSPWG) was chartered to recommend nuclear safety policy, requirements, and guidelines for the Space Exploration Initiative (SEI) nuclear propulsion program to facilitate the implementation of mission planning and conceptual design studies. The NSPWG developed a top- level policy to provide the guiding principles for the development and implementation of the nuclear propulsion safety program and the development of Safety Functional Requirements. In addition the NSPWG reviewed safety issues for nuclear propulsion and recommended top-level safety requirements and guidelines to address these issues. Safety requirements were developed for reactor start-up, inadvertent criticality, radiological release and exposure, disposal, entry, and safeguards. Guidelines were recommended for risk/reliability, operational safety, flight trajectory and mission abort, space debris and meteoroids, and ground test safety. In this paper the specific requirements and guidelines will be discussed

Candidate PET radioligands for cannabinoid CB{sub 1} receptors: [{sup 18}F]AM5144 and related pyrazole compounds

Energy Technology Data Exchange (ETDEWEB)

Zizhong, Li [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); Qian, Liu [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Thotapally, Rajesh [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Yushin, Ding [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)

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.

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

Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory.

Science.gov (United States)

Sousa, Vasco C; Assaife-Lopes, Natália; Ribeiro, Joaquim A; Pratt, Judith A; Brett, Ros R; Sebastião, Ana M

2011-01-01

The cannabinoid CB(1) receptor-mediated modulation of γ-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A(1) receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A(1) receptors localized in GABAergic cells do not directly influence GABA release. CB(1) and A(1) receptors are the main targets for the effects of two of the most heavily consumed psychoactive substances worldwide: Δ(9)-tetrahydrocannabinol (THC, a CB(1) receptor agonist) and caffeine (an adenosine receptor antagonist). We first tested the hypothesis that an A(1)-CB(1) interaction influences GABA and glutamate release in the hippocampus. We found that A(1) receptor activation attenuated the CB(1)-mediated inhibition of GABA and glutamate release and this interaction was manifested at the level of G-protein activation. Using in vivo and in vitro approaches, we then investigated the functional implications of the adenosine-cannabinoid interplay that may arise following chronic caffeine consumption. Chronic administration of caffeine in mice (intraperitoneally, 3 mg/kg/day, for 15 days, >12 h before trials) led to an A(1)-mediated enhancement of the CB(1)-dependent acute disruptive effects of THC on a short-term spatial memory task, despite inducing a reduction in cortical and hippocampal CB(1) receptor number and an attenuation of CB(1) coupling with G protein. A(1) receptor levels were increased following chronic caffeine administration. This study shows that A(1) receptors exert a negative modulatory effect on CB(1)-mediated inhibition of GABA and glutamate release, and provides the first evidence of chronic caffeine-induced alterations on the cannabinoid system in the cortex and hippocampus, with functional implications in spatial memory.

Annual report 2000 of the German Commission on Radiological Protection (SSK). With explanations on the objectives, functions, and history of the SSK, complete lists of recommendations, statements, and publications. With a CD ROM containing full texts of recommendations and statements of the SSK on the Internet

International Nuclear Information System (INIS)

2001-01-01

The report begins with an introduction explaining the objectives, functions and composition of the SSK. Then the main areas and aspects of work in 2000 are addressed and the reports, recommendations or statements prepared by the six committees of the SSK are presented. The areas of work of the six committees are: radiation protection and health physics, radiological protection in health care, radioecology, radiological engineering, emergency preparedness, and non-ionizing radiation. (orig./CB) [de

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

Multimodel inference and adaptive management

Science.gov (United States)

Rehme, S.E.; Powell, L.A.; Allen, Craig R.

2011-01-01

Ecology is an inherently complex science coping with correlated variables, nonlinear interactions and multiple scales of pattern and process, making it difficult for experiments to result in clear, strong inference. Natural resource managers, policy makers, and stakeholders rely on science to provide timely and accurate management recommendations. However, the time necessary to untangle the complexities of interactions within ecosystems is often far greater than the time available to make management decisions. One method of coping with this problem is multimodel inference. Multimodel inference assesses uncertainty by calculating likelihoods among multiple competing hypotheses, but multimodel inference results are often equivocal. Despite this, there may be pressure for ecologists to provide management recommendations regardless of the strength of their study’s inference. We reviewed papers in the Journal of Wildlife Management (JWM) and the journal Conservation Biology (CB) to quantify the prevalence of multimodel inference approaches, the resulting inference (weak versus strong), and how authors dealt with the uncertainty. Thirty-eight percent and 14%, respectively, of articles in the JWM and CB used multimodel inference approaches. Strong inference was rarely observed, with only 7% of JWM and 20% of CB articles resulting in strong inference. We found the majority of weak inference papers in both journals (59%) gave specific management recommendations. Model selection uncertainty was ignored in most recommendations for management. We suggest that adaptive management is an ideal method to resolve uncertainty when research results in weak inference.

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB{sub 1} cannabinoid receptors

Energy Technology Data Exchange (ETDEWEB)

Jäntti, Maria H., E-mail: maria.jantti@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland); Mandrika, Ilona, E-mail: ilona@biomed.lu.lv [Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, Riga LV 1067 (Latvia); Kukkonen, Jyrki P., E-mail: jyrki.kukkonen@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland)

2014-03-07

Highlights: • OX{sub 1} and OX{sub 2} orexin and CB{sub 1} cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX{sub 1} orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB{sub 1} cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX{sub 1}, OX{sub 2} and CB{sub 1} receptors, C-terminally fused with either Renilla luciferase or GFP{sup 2} green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB{sub 1} receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP{sup 2} to CB{sub 1} produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX{sub 1}–OX{sub 2} interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB{sub 1} receptors, dimerization could be an effective way

Youth injury prevention in Canada: use of the Delphi method to develop recommendations.

Science.gov (United States)

Pike, Ian; Piedt, Shannon; Davison, Colleen M; Russell, Kelly; Macpherson, Alison K; Pickett, William

2015-12-22

The Health Behaviour in School-aged Children Survey is one of very few cross-national health surveys that includes information on injury occurrence and prevention within adolescent populations. A collaboration to develop a Canadian youth injury report using these data resulted in, Injury among Young Canadians: A national study of contextual determinants. The objective of this study was to develop specific evidence-based, policy-oriented recommendations arising from the national report, using a modified-Delphi process with a panel of expert stakeholders. Eight injury prevention experts and a 3-person youth advisory team associated with a Canadian injury prevention organization (Parachute Canada) reviewed, edited and commented on report recommendations through a three-stage iterative modified-Delphi process. From an initial list of 27 draft recommendations, the modified-Delphi process resulted in a final list of 19 specific recommendations, worded to resonate with the group(s) responsible to lead or take the recommended action. Two recommendations were rated as "extremely important" or "very important" by 100 % of the expert panel, two were deleted, a further two recommendations were deleted but the content included as text in the report, and four were merged with other existing recommendations. The modified-Delphi process was an appropriate method to achieve agreement on 19 specific evidence-based, policy-oriented recommendations to complement the national youth injury report. In providing their input, it is noted that the injury stakeholders each acted as individual experts, unattached to any organizational position or policy. These recommendations will require multidisciplinary collaborations in order to support the proposed policy development, additional research, programming and clear decision-making for youth injury prevention.

Recommendations for Institutional Prematriculation Immunizations

Science.gov (United States)

Journal of American College Health, 2011

2011-01-01

The recommendations presented in this article are provided to colleges and universities to facilitate the implementation of a comprehensive institutional prematriculation immunization policy. Vaccine-preventable diseases continue to occur on American campuses. In response to changing epidemiology and the introduction of new vaccines, the ACHA…

CB5C affects the glucosinolate profile in Arabidopsis thaliana

DEFF Research Database (Denmark)

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

2016-01-01

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...

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.

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

Prior stimulation of the endocannabinoid system prevents methamphetamine-induced dopaminergic neurotoxicity in the striatum through activation of CB2 receptors

Science.gov (United States)

Nader, Joëlle; Rapino, Cinzia; Gennequin, Benjamin; Chavant, Francois; Francheteau, Maureen; Makriyannis, Alexandros; Duranti, Andrea; Maccarrone, Mauro; Solinas, Marcello; Thiriet, Nathalie

2016-01-01

Methamphetamine toxicity is associated with cell death and loss of dopamine neuron terminals in the striatum similar to what is found in some neurodegenerative diseases. Conversely, the endocannabinoid system (ECS) has been suggested to be neuroprotective in the brain, and new pharmacological tools have been developed to increase their endogenous tone. In this study, we evaluated whether ECS stimulation could reduce the neurotoxicity of high doses of methamphetamine on the dopamine system. We found that methamphetamine alters the levels of the major endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in the striatum, suggesting that the ECS participates in the brain responses to methamphetamine. Δ9-tetrahydrocannabinol (THC), a cannabis-derived agonist of both CB1 and CB2 cannabinoid receptors, or inhibitors of the main enzymes responsible for the degradation of AEA and 2-AG (URB597 and JZL184, respectively), blunted the decrease in striatal protein levels of tyrosine hydroxylase induced by methamphetamine. In addition, antagonists of CB2, but not of CB1, blocked the preventive effects of URB597 and JZL184, suggesting that only the former receptor subtype is engaged in neuroprotection exerted by ECS stimulation. Finally, we found that methamphetamine increases striatal levels of the cytokine tumor necrosis factor alpha, an effect that was blocked by ECS stimulation. Altogether, our results indicate that stimulation of ECS prior to the administration of an overdose of meth-amphetamine considerably reduces the neurotoxicity of the drug through CB2 receptor activation and highlight a protective function for the ECS against the toxicity induced by drugs and other external insults to the brain. This article is part of the Special Issue entitled ‘CNS Stimulants’. PMID:24709540

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)

Electro-optically responsive composites of gold nanospheres in 5CB liquid crystal under direct current and alternating current joint action

International Nuclear Information System (INIS)

Hadjichristov, Georgi B.; Marinov, Yordan G.; Petrov, Alexander G.; Bruno, Emanuela; Marino, Lucia; Scaramuzza, Nicola

2014-01-01

Direct current (DC) electro-optical (EO) control of transmitted laser beam intensity based on EO controlled coherent light scattering and diffraction by stationary longitudinal texture pattern (LTP) is achieved in planar-oriented cells with a composite mixture of polymer-coated gold spherical nanoparticles (Au-NPs) with a mean diameter of about 12 nm and the room-temperature nematic pentylcyanobiphenyl (5CB). At relatively low DC voltage of about 5 V, the effective scattering/diffraction by Au-NPs/5CB composites leads to a spatial spreading of transmitted coherent light from a low-power continuous wave laser beam, resulting in a drastic reduction of its local intensity. The effect is polarization dependent and is strongest when the polarization of the input laser beam is along the LTP. The EO response of Au-NPs/5CB mixtures is studied under DC and alternating current (AC) joint action with the aim of the potential use of these composite materials as EO controlled diffusers. The specific V-shaped sharp dip in the DC voltage-dependent coherent light transmittance of Au-NPs/5CB planar films, as well as the possibility for erasing the scattering/diffractive LTP in the films by joint low AC voltage, can be useful for EO applications in the field of process control and for detection of weak dynamic electric fields

Electro-optically responsive composites of gold nanospheres in 5CB liquid crystal under direct current and alternating current joint action

Energy Technology Data Exchange (ETDEWEB)

Hadjichristov, Georgi B.; Marinov, Yordan G.; Petrov, Alexander G. [Institute of Solid State Physics, Bulgarian Academy of Sciences, Sofia 1784 (Bulgaria); Bruno, Emanuela [Dipartimento di Fisica, Università della Calabria, Via Pietro Bucci, Cubo 31C, 87036 Rende (CS) (Italy); Marino, Lucia, E-mail: lucia.marino@fis.unical.it [CNR-IPCF UoS di Cosenza, Licryl Laboratory, and Centro di Eccellenza CEMIF.CAL, Università della Calabria, 87036 Rende (CS) (Italy); Scaramuzza, Nicola [Dipartimento di Fisica, Università della Calabria, Via Pietro Bucci, Cubo 31C, 87036 Rende (CS) (Italy); CNR-IPCF UoS di Cosenza, Licryl Laboratory, and Centro di Eccellenza CEMIF.CAL, Università della Calabria, 87036 Rende (CS) (Italy)

2014-02-28

Direct current (DC) electro-optical (EO) control of transmitted laser beam intensity based on EO controlled coherent light scattering and diffraction by stationary longitudinal texture pattern (LTP) is achieved in planar-oriented cells with a composite mixture of polymer-coated gold spherical nanoparticles (Au-NPs) with a mean diameter of about 12 nm and the room-temperature nematic pentylcyanobiphenyl (5CB). At relatively low DC voltage of about 5 V, the effective scattering/diffraction by Au-NPs/5CB composites leads to a spatial spreading of transmitted coherent light from a low-power continuous wave laser beam, resulting in a drastic reduction of its local intensity. The effect is polarization dependent and is strongest when the polarization of the input laser beam is along the LTP. The EO response of Au-NPs/5CB mixtures is studied under DC and alternating current (AC) joint action with the aim of the potential use of these composite materials as EO controlled diffusers. The specific V-shaped sharp dip in the DC voltage-dependent coherent light transmittance of Au-NPs/5CB planar films, as well as the possibility for erasing the scattering/diffractive LTP in the films by joint low AC voltage, can be useful for EO applications in the field of process control and for detection of weak dynamic electric fields.

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

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...

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.

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...

Effect of sintering temperature on structure of C-B4C-SiC composites with silicon additive

International Nuclear Information System (INIS)

Wu Lijun; Academia Sinica, Shenyang; Huang Qizhong; Yang Qiaoqin; Zhao Lihu; Xu Zhongyu

1996-01-01

Carbon materials possess good electric conductivity, heat conductivity, corrosion-resistance, self-lubrication and hot-shocking resistance, and are easily machined. However, they have low mechanical strength, and are easily oxidized in air at high temperature. On the contrary, ceramic materials have high mechanical strength and hardness, and have good wear-resistance and oxidation-resistance. However, they have the shortages of poor thermal-shock resistance lubrication, and are difficult to machine. Therefore, carbon/ceramic composites with the advantages of both carbon and ceramic materials have been widely studied in the recent years. Huang prepared C-B 4 C-SiC composites with the free sintering method and the hot pressing method, and studied the effects of Si, Al, Al 2 O 3 , Ni and Ti additives on the properties of the composites. The results showed that these additives could improve the properties of the composites. Zhao et al. studies the structure of C-B 4 C-SiC composites with Si additive sintered at 2,000 C and found two c-center monoclinic phases. In this paper, the authors discussed the effect of the sintering temperature on the structure of C-B 4 C-SiC composites with Si additive by means of transmission electron microscope (TEM) and x-ray diffractometer (XRD)

Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor in experimental autoimmune encephalomyelitis models of multiple sclerosis.

Directory of Open Access Journals (Sweden)

Sofia Sisay

Full Text Available Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1 receptor and the orphan G protein receptor fifty-five (GPR55. Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 (tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational

Liberalisation of the German electricity sector and the role of energy policy

International Nuclear Information System (INIS)

Schleich, J.; Betz, R.; Gagelmann, F.; Jochem, E.; Koewener, D.

2000-01-01

This paper gives an account of the impacts of the liberalisation of the German electricity market and describes the existing energy policy and recent responses to the liberalisation with respect to the electricity sector. In the first section, electricity supply, electricity consumption and the structure of the electricity market are described. In the second section, the legal framework for the liberalisation of the electricity market in Germany and the consequences for prices, market structure, legal form of utilities, investment, cogeneration and products offered are presented. The final section first provides an overview of the national and international climate policy targets as well as the agreed upon phase-out of nuclear energy. Finally, existing electricity policy instruments and policy responses to the liberalised electricity market are reported. These policy instruments include support for hard coal and lignite, the new ecological-tax reform, the promotion of renewable energy sources, support for cogeneration, voluntary agreements, and the flexible mechanisms for greenhouse gas emission reductions as introduced in the Kyoto protocol. (orig./CB)

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.

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…

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.

Stakeholder attitudes toward influenza vaccination policy in the United States.

Science.gov (United States)

Berman, Pamela Protzel; Orenstein, Walter A; Hinman, Alan R; Gazmararian, Julie

2010-11-01

There is growing interest in simplifying recommendations to vaccinate Americans against influenza. The article discusses interviews with 35 stakeholders from the medical, public health, educational, insurance, and vaccine industry sectors to assess the potential for policy change, and discusses questions posed to the interviewees on current and future influenza vaccination policy and barriers to policy change. About 97% of respondents support the expansion of vaccination for all school-age children, and about 95% support universal vaccination, but there are reservations expressed by the respondents, despite the support for this policy change. Barriers to influenza vaccination recommendations include access, supply, confusing recommendations, and public perceptions. Barriers to universal vaccination include lack of infrastructure, cost, need for education, and vaccine supply. Issues concerning resources and education are challenges that impede policy change. The study findings can be useful to policy makers and practitioners for reviewing U.S. vaccination policy and changes to the policy.

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...

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.

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

and exemplary case studies from three European countries (D3.3). The overall aim of the report is to highlight priorities in ECEC professional development, based on WP3’s findings and develop recommendations regarding high-quality provisions for common EU-policies. This led to the identification of six policy...... development; and vi) addressing the vulnerable through professional development. The good practices highlighted in the report have been chosen as examples, given their success. However, these must be regarded as practices that may inspire changes, which must nevertheless be adopted to cultural and systemic...

Environmental policy and environment-saving technologies. Economic aspects of policy making under uncertainty

Energy Technology Data Exchange (ETDEWEB)

Ossokina, I.

2003-07-01

It is generally known that natural environment is profoundly influenced by technological change. The direction and the size of this influence are, however, surrounded by uncertainties, which substantially complicate environmental policy making. This dissertation uses game-theoretical models to study policy making under uncertainty about (a) the costs of technological advances in pollution control, (b) the preferences of the policy maker and the voters, and (c) the consequences of policy measures. From a positive point of view the analysis provides explanations for environmental policies in modern democracies. From a normative point of view it gives a number of recommendations to improve environmental policies.

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

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

Energy Technology Data Exchange (ETDEWEB)

Haurie, A. [ORDECSYS, Geneva (Switzerland); Tavoni, M. [Princeton University, Princeton, NJ (United States); Van der Zwaan, B.C.C. [Policy Studies Department, Energy research Centre of the Netherlands ECN, Amsterdam (Netherlands)

2011-07-15

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

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)

Can control banding be useful for the safe handling of nanomaterials? A systematic review

Science.gov (United States)

Eastlake, Adrienne; Zumwalde, Ralph; Geraci, Charles

2016-06-01

Control banding (CB) is a risk management strategy that has been used to identify and recommend exposure control measures to potentially hazardous substances for which toxicological information is limited. The application of CB and level of expertise required for implementation and management can differ depending on knowledge of the hazard potential, the likelihood of exposure, and the ability to verify the effectiveness of exposure control measures. A number of different strategies have been proposed for using CB in workplaces where exposure to engineered nanomaterials (ENMs) can occur. However, it is unclear if the use of CB can effectively reduce worker exposure to nanomaterials. A systematic review of studies was conducted to answer the question "can control banding be useful to ensure adequate controls for the safe handling of nanomaterials." A variety of databases were searched to identify relevant studies pertaining to CB. Database search terms included `control,' `hazard,' `exposure,' and `risk' banding as well as the use of these terms in the context of nanotechnology or nanomaterials. Other potentially relevant studies were identified during the review of articles obtained in the systematic review process. Identification of studies and the extraction of data were independently conducted by the reviewers. Quality of the studies was assessed using the methodological index for nonrandomized studies. The quality of the evidence was evaluated using grading of recommendations assessment, development and evaluation (GRADE). A total of 235 records were identified in the database search in which 70 records were determined to be eligible for full-text review. Only two studies were identified that met the inclusion criteria. These studies evaluated the application of the CB Nanotool in workplaces where ENMs were being handled. A total of 32 different nanomaterial handling activities were evaluated in these studies by comparing the recommended exposure controls using

Evidence for CB2 receptor involvement in LPS-induced reduction of cAMP intracellular levels in uterine explants from pregnant mice: pathophysiological implications.

Science.gov (United States)

Salazar, Ana Inés; Carozzo, Alejandro; Correa, Fernando; Davio, Carlos; Franchi, Ana María

2017-07-01

What is the role of the endocannabinoid system (eCS) on the lipopolysaccharide (LPS) effects on uterine explants from 7-day pregnant mice in a murine model of endotoxin-induced miscarriage? We found evidence for cannabinoid receptor type2 (CB2) involvement in LPS-induced increased prostaglandin-F2α (PGF2α) synthesis and diminished cyclic adenosine monophosphate (cAMP) intracellular content in uterine explants from early pregnant mice. Genital tract infections by Gram-negative bacteria are a common complication of human pregnancy that results in an increased risk of pregnancy loss. LPS, the main component of the Gram-negative bacterial wall, elicits a strong maternal inflammatory response that results in embryotoxicity and embryo resorption in a murine model endotoxin-induced early pregnancy loss. We have previously shown that the eCS mediates the embryotoxic effects of LPS, mainly via CB1 receptor activation. An in vitro study of mice uterine explants was performed to investigate the eCS in mediating the effects of LPS on PGF2α production and cAMP intracellular content. Eight to 12-week-old virgin female BALB/c or CD1 (wild-type [WT] or CB1-knockout [CB1-KO]) mice were paired with 8- to 12-week-old BALB/c or CD1 (WT or CB1-KO) males, respectively. On day 7 of pregnancy, BALB/c, CD1 WT or CD1 CB1-KO mice were euthanized, the uteri were excised, implantation sites were removed and the uterine tissues were separated from decidual and embryo tissues. Uterine explants were cultured and exposed for an appropriate amount of time to different pharmacological treatments. The tissues were then collected for cAMP assay and PGF2α content determination by radioimmunoassay. In vitro treatment of uteri explants from 7-day pregnant BALB/c or CD1 (WT or CB1-KO) mice with LPS induced an increased production of PGF2α (P Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Carlos Davio was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013

Identification of the C-Terminal GH5 Domain from CbCel9B/Man5A as the First Glycoside Hydrolase with Thermal Activation Property from a Multimodular Bifunctional Enzyme.

Directory of Open Access Journals (Sweden)

Rong Wang

Full Text Available Caldicellulosiruptor bescii encodes at least six unique multimodular glycoside hydrolases crucial for plant cell wall polysaccharides degradation, with each having two catalytic domains separated by two to three carbohydrate binding modules. Among the six enzymes, three have one N- or C-terminal GH5 domain with identical amino acid sequences. Despite a few reports on some of these multimodular enzymes, little is known about how the conserved GH5 domains behave, which are believed to be important due to the gene duplication. We thus cloned a representative GH5 domain from the C-terminus of a multimodular protein, i.e. the bifunctional cellulase/mannanase CbCel9B/Man5A which has been reported, and expressed it in Escherichia coli. Without any appending CBMs, the recombinant CbMan5A was still able to hydrolyze a variety of mannan substrates with different backbone linkages or side-chain decorations. While CbMan5A displayed the same pH optimum as CbCel9B/Man5A, it had an increased optimal temperature (90°C and moreover, was activated by heating at 70°C and 80°C, a property not ever reported for the full-length protein. The turnover numbers of CbMan5A on mannan substrates were, however, lower than those of CbCel9B/Man5A. These data suggested that evolution of CbMan5A and the other domains into a single polypeptide is not a simple assembly; rather, the behavior of one module may be affected by the other ones in the full-length enzyme. The differential scanning calorimetry analysis further indicated that heating CbMan5A was not a simple transition state process. To the best knowledge of the authors, CbMan5A is the first glycoside hydrolase with thermal activation property identified from a multimodular bifunctional enzyme.

Paradoxical effects of the cannabinoid CB2 receptor agonist GW405833 on rat osteoarthritic knee joint pain.

Science.gov (United States)

Schuelert, N; Zhang, C; Mogg, A J; Broad, L M; Hepburn, D L; Nisenbaum, E S; Johnson, M P; McDougall, J J

2010-11-01

The present study examined whether local administration of the cannabinoid-2 (CB(2)) receptor agonist GW405833 could modulate joint nociception in control rat knee joints and in an animal model of osteoarthritis (OA). OA was induced in male Wistar rats by intra-articular injection of sodium monoiodo-acetate with a recovery period of 14 days. Immunohistochemistry was used to evaluate the expression of CB(2) and transient receptor potential vanilloid channel-1 (TRPV1) receptors in the dorsal root ganglion (DRG) and synovial membrane of sham- and sodium mono-iodoacetate (MIA)-treated animals. Electrophysiological recordings were made from knee joint primary afferents in response to rotation of the joint both before and following close intra-arterial injection of different doses of GW405833. The effect of intra-articular GW405833 on joint pain perception was determined by hindlimb incapacitance. An in vitro neuronal release assay was used to see if GW405833 caused release of an inflammatory neuropeptide (calcitonin gene-related peptide - CGRP). CB(2) and TRPV1 receptors were co-localized in DRG neurons and synoviocytes in both sham- and MIA-treated animals. Local application of the GW405833 significantly reduced joint afferent firing rate by up to 31% in control knees. In OA knee joints, however, GW405833 had a pronounced sensitising effect on joint mechanoreceptors. Co-administration of GW405833 with the CB(2) receptor antagonist AM630 or pre-administration of the TRPV1 ion channel antagonist SB366791 attenuated the sensitising effect of GW405833. In the pain studies, intra-articular injection of GW405833 into OA knees augmented hindlimb incapacitance, but had no effect on pain behaviour in saline-injected control joints. GW405833 evoked increased CGRP release via a TRPV1 channel-dependent mechanism. These data indicate that GW405833 reduces the mechanosensitivity of afferent nerve fibres in control joints but causes nociceptive responses in OA joints. The observed

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

Obesity prevention advocacy in Australia: an analysis of policy impact on autonomy.

Science.gov (United States)

Haynes, Emily; Hughes, Roger; Reidlinger, Dianne P

2017-06-01

To explore obesity policy options recommended by stakeholders and identify their impact on individual autotomy. Qualitative and quantitative methods were used. A content analysis of submissions to the Australian Government's Inquiry into Obesity was conducted. Each recommendation was categorised by its impact on autonomy, according to existing frameworks. Chi-square test for independence was used to explore the association between autonomy and stakeholder support defined as frequency of recommendation. The extent of support for a policy option was significantly associated with impact on autonomy (pautonomy were least frequently recommended in every setting; but more likely in schools (27%) than other settings (autonomy were most widely recommended (46%). Stakeholders advocated policy options that enhance individual autonomy to a greater extent than those that diminish autonomy. Implications for public health: Targeting obesity policy options that enhance rather than diminish autonomy may be more politically acceptable across most settings, with the exception of schools where more restrictive policy options are appropriate. Re-framing options accordingly may improve leadership by government in obesity policy. © 2017 The Authors.

Cannabinoid Type 1 Receptor (CB1) Ligands with Therapeutic Potential for Withdrawal Syndrome in Chemical Dependents of Cannabis sativa.

Science.gov (United States)

Ferreira, Jaderson V; Chaves, Gisele A; Marino, Bianca L B; Sousa, Kessia P A; Souza, Lucilene R; Brito, Maiara F B; Teixeira, Hueldem R C; da Silva, Carlos H T P; Santos, Cleydson B R; Hage-Melim, Lorane I S

2017-08-22

Cannabis sativa withdrawal syndrome is characterized mainly by psychological symptoms. By using computational tools, the aim of this study was to propose drug candidates for treating withdrawal syndrome based on the natural ligands of the cannabinoid type 1 receptor (CB1). One compound in particular, 2-n-butyl-5-n-pentylbenzene-1,3-diol (ZINC1730183, also known as stemphol), showed positive predictions as a human CB1 ligand and for facile synthetic accessibility. Therefore, ZINC1730183 is a favorable candidate scaffold for further research into pharmacotherapeutic alternatives to treat C. sativa withdrawal syndrome. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optical transmission of nematic liquid crystal 5CB doped by single-walled and multi-walled carbon nanotubes.

Science.gov (United States)

Lisetski, L N; Fedoryako, A P; Samoilov, A N; Minenko, S S; Soskin, M S; Lebovka, N I

2014-08-01

Comparative studies of optical transmission of single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), dispersed in nematic liquid crystal matrix 5CB, were carried out. The data evidence violations of Beer-Lambert-Bouguer (BLB) law both in cell thickness and concentration dependencies. The most striking is the fact that optical transmission dependencies for SWCNTs and MWCNTs were quite different in the nematic phase, but they were practically indistinguishable in the isotropic phase. Monte Carlo simulations of the impact of aggregation on direct transmission and violation of BLB law were also done. The results were discussed accounting for the tortuous shape of CNTs, their physical properties and aggregation, as well as strong impact of perturbations of the nematic 5CB structure inside coils and in the vicinity of CNT aggregates.

Strength of recommendations in WHO guidelines using GRADE was associated with uptake in national policy.

Science.gov (United States)

Nasser, Syed Muhammad Umar; Cooke, Graham; Kranzer, Katharina; Norris, Susan L; Olliaro, Piero; Ford, Nathan

2015-06-01

This study assesses the extent to which the strength of a recommendation in a World Health Organization (WHO) guideline affects uptake of the recommendation in national guidelines. The uptake of recommendations included in HIV and TB guidelines issued by WHO from 2009 to 2013 was assessed across guidelines from 20 low- and middle-income countries in Africa and Southeast Asia. Associations between characteristics of recommendations (strength, quality of the evidence, type) and uptake were assessed using logistic regression. Eight WHO guidelines consisting of 109 strong recommendations and 49 conditional recommendations were included, and uptake assessed across 44 national guidelines (1,255 recommendations) from 20 countries. Uptake of WHO recommendations in national guidelines was 82% for strong recommendations and 61% for conditional recommendations. The odds of uptake comparing strong recommendations and conditional recommendations was 1.9 (95% confidence interval: 1.4, 2.7), after adjustment for quality of evidence. Higher levels of evidence quality were associated with greater uptake, independent of recommendation strength. Guideline developers should be confident that conditional recommendations are frequently adopted. The fact that strong recommendations are more frequently adopted than conditional recommendations underscores the importance of ensuring that such recommendations are justified. Copyright © 2015 Elsevier Inc. All rights reserved.

Measurement of |V{sub cb}| using {bar B}{sup 0} {yields} D*{sup +}{ell}{sup -}{bar {nu}}{sub {ell}} Decays

Energy Technology Data Exchange (ETDEWEB)

Della Ricca, Giuseppe

2003-08-12

A preliminary measurement of |V{sub cb}| and the branching fraction {Beta}({bar B}{sup 0} {yields} D*{sup +}{ell}{sup -}{bar {nu}}{sub {ell}}) has been performed based on a sample of about 55,700 {bar B}{sup 0} {yields} D*{sup +}{ell}{sup -}{bar {nu}}{sub {ell}} decays recorded with the BABAR detector. The decays are identified in the D*{sup +} {yields} D{sup 0}{pi}{sup +} final state, with the D{sup 0} reconstructed in three different decay modes. The differential decay rate is measured as a function of the relativistic boost of the D*{sup +} in the {bar B}{sup 0} rest frame. The value of the differential decay rate at ''zero recoil'', namely the point at which the D*{sup +} is at rest in the {bar B}{sup 0} frame, is predicted in Heavy Quark Effective Theory as a kinematic factor times F(1)|V{sub cb}|, where F is the unique form factor governing the decay. We extrapolate the measured differential decay rate to the zero recoil point and obtain F(1)|V{sub cb}| = (34.03 {+-} 0.24 {+-} 1.31) x 10{sup -3}. Using a theoretical calculation for F(1) we extract |V{sub cb}| = (37.27 {+-} 0.26(stat.) {+-} 1.43(syst.){sub -1.2}{sup +1.5}(theo.)) x 10{sup -3}. From the integrated decay rate we obtain {Beta}({bar B}{sup 0} {yields} D*{sup +}{ell}{sup -}{bar {nu}}{sub {ell}}) = (4.68 {+-} 0.03 {+-} 0.29)%.

Cannabinoid CB2 receptors are involved in the protection of RAW264.7 macrophages against the oxidative stress: an in vitro study

Directory of Open Access Journals (Sweden)

Sabrina Giacoppo

2017-01-01

Full Text Available Research in the last decades has widely investigated the anti-oxidant properties of natural products as a therapeutic approach for the prevention and the treatment of oxidative-stress related disorders. In this context, several studies were aimed to evaluate the therapeutic potential of phytocannabinoids, the bioactive compounds of Cannabis sativa. Here, we examined the anti-oxidant ability of Cannabigerol (CBG, a non-psychotropic cannabinoid, still little known, into counteracting the hydrogen peroxide (H2O2-induced oxidative stress in murine RAW264.7 macrophages. In addition, we tested selective receptor antagonists for cannabinoid receptors and specifically CB1R (SR141716A and CB2R (AM630 in order to investigate through which CBG may exert its action. Taken together, our in vitro results showed that CBG is able to counteract oxidative stress by activation of CB2 receptors. CB2 antagonist pre-treatment indeed blocked the protective effects of CBG in H2O2 stimulated macrophages, while CB1R was not involved. Specifically, CBG exhibited a potent action in inhibiting oxidative stress, by down-regulation of the main oxidative markers (iNOS, nitrotyrosine and PARP-1, by preventing IκB-α phosphorylation and translocation of the nuclear factor-κB (NF-κB and also via the modulation of MAP kinases pathway. On the other hand, CBG was found to increase anti-oxidant defense of cells by modulating superoxide dismutase-1 (SOD-1 expression and thus inhibiting cell death (results focused on balance between Bax and Bcl-2. Based on its antioxidant activities, CBG may hold great promise as an anti-oxidant agent and therefore used in clinical practice as a new approach in oxidative-stress related disorders.

International retrospective cohort study of neural tube defects in relation to folic acid recommendations : are the recommendations working?

NARCIS (Netherlands)

Botto, LD; Lisi, A; Robert-Gnansia, E; Erickson, JD; Vollset, SE; Mastroiacovo, P; Botting, B; Cocchi, G; de Vigan, C; de Walle, H; Feijoo, M; Irgens, LM; McDonnell, B; Merlob, P; Ritvanen, A; Scarano, G; Siffel, C; Metneki, J; Stoll, C; Smithells, R; Goujard, J

2005-01-01

Objective To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects. Design Retrospective cohort study of births monitored by birth defect registries. Setting 13 birth defects registries monitoring rates of neural tube defects

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.

Recommendations of ICRP for radiation protection in 2005

International Nuclear Information System (INIS)

Holm, L. E.

2004-01-01

The present recommendations of the International Commission on Radiological Protection (ICRP) were published in 1991, and since then, the ICRP has provided additional recommendations. The system of protection has become increasingly co plex with time, and the Commission has decided to adopt a new set of recommendations in 2005- These should be seen as a consolidation of earlier recommendations. The new recommendations will recognize where the responsibility for justifying the introduction of a new practice lies, maintain the existing dose limits for individuals, develop the concept of dose constraints, require optimisation of protection from any source to ensure that exposures are as law as reasonably achievable, include of a policy for protection of non-human species, and clarify the dramatics quantities. The Commission intends to adopt the new recommendations in 2005, and this will be 15 years after the current recommendations were adopted. (Author) 13 refs

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.

Illuminating the Decision Path: The Yucca Mountain Site Recommendation

International Nuclear Information System (INIS)

Knox, E.; Slothouber, L.

2003-01-01

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

National policies for the promotion of physical activity and healthy nutrition in the workplace context: a behaviour change wheel guided content analysis of policy papers in Finland.

Science.gov (United States)

Seppälä, Tuija; Hankonen, Nelli; Korkiakangas, Eveliina; Ruusuvuori, Johanna; Laitinen, Jaana

2017-08-02

Health policy papers disseminate recommendations and guidelines for the development and implementation of health promotion interventions. Such documents have rarely been investigated with regard to their assumed mechanisms of action for changing behaviour. The Theoretical Domains Framework (TDF) and Behaviour Change Techniques (BCT) Taxonomy have been used to code behaviour change intervention descriptions, but to our knowledge such "retrofitting" of policy papers has not previously been reported. This study aims first to identify targets, mediators, and change strategies for physical activity (PA) and nutrition behaviour change in Finnish policy papers on workplace health promotion, and second to assess the suitability of the Behaviour Change Wheel (BCW) approach for this purpose. We searched all national-level health policy papers effectual in Finland in August 2016 focusing on the promotion of PA and/or healthy nutrition in the workplace context (n = 6). Policy recommendations targeting employees' nutrition and PA including sedentary behaviour (SB) were coded using BCW, TDF, and BCT Taxonomy. A total of 125 recommendations were coded in the six policy papers, and in two additional documents referenced by them. Psychological capability, physical opportunity, and social opportunity were frequently identified (22%, 31%, and 24%, respectively), whereas physical capability was almost completely absent (1%). Three TDF domains (knowledge, skills, and social influence) were observed in all papers. Multiple intervention functions and BCTs were identified in all papers but several recommendations were too vague to be coded reliably. Influencing individuals (46%) and changing the physical environment (44%) were recommended more frequently than influencing the social environment (10%). The BCW approach appeared to be useful for analysing the content of health policy papers. Paying more attention to underlying assumptions regarding behavioural change processes may help to

NESS038C6, a novel selective CB1 antagonist agent with anti-obesity activity and improved molecular profile.

Science.gov (United States)

Mastinu, Andrea; Pira, Marilena; Pani, Luca; Pinna, Gérard Aimè; Lazzari, Paolo

2012-10-01

The present work aims to study the effects induced by a chronic treatment with a novel CB1 antagonist (NESS038C6) in C57BL/6N diet-induced obesity (DIO) mice. Mice treated with NESS038C6 and fed with a fat diet (NESS038C6 FD) were compared with the following three reference experimental groups: DIO mice fed with the same fat diet used for NESS038C6 and treated with vehicle or the reference CB1 antagonist/inverse agonist rimonabant, "VH FD" and "SR141716 FD", respectively; DIO mice treated with vehicle and switched to a normal diet (VH ND). NESS038C6 chronic treatment (30 mg/kg/day for 31 days) determined a significant reduction in DIO mice weight relative to that of VH FD. The entity of the effect was comparable to that detected in both SR141716 FD and VH ND groups. Moreover, if compared to VH FD, NESS038C6 FD evidenced: (i) improvement of cardiovascular risk factors; (ii) significant decrease in adipose tissue leptin expression; (iii) increase in mRNA expression of hypothalamic orexigenic peptides and a decrease of anorexigenic peptides; (iv) expression increase of metabolic enzymes and peroxisome proliferator-activated receptor-α in the liver; (v) normalization of monoaminergic transporters and neurotrophic expression in mesolimbic area. However, in contrast to the case of rimonabant, the novel CB1 antagonist improved the disrupted expression profile of genes linked to the hunger-satiety circuit, without altering monoaminergic transmission. In conclusion, the novel CB1 antagonist compound NESS038C6 may represent a useful candidate agent for the treatment of obesity and its metabolic complications, without or with reduced side effects relative to those instead observed with rimonabant. Copyright © 2012 Elsevier B.V. All rights reserved.

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.)

Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

OpenAIRE

Zlebnik, Natalie E.; Cheer, Joseph F.

2016-01-01

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 Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor t...

Can Control Banding be Useful for the Safe Handling of Nanomaterials? A Systematic Review

Science.gov (United States)

Eastlake, Adrienne; Zumwalde, Ralph; Geraci, Charles

2016-01-01

Objectives Control banding (CB) is a risk management strategy that has been used to identify and recommend exposure control measures to potentially hazardous substances for which toxicological information is limited. The application of CB and level of expertise required for implementation and management can differ depending on knowledge of the hazard potential, the likelihood of exposure, and the ability to verify the effectiveness of exposure control measures. A number of different strategies have been proposed for using CB in workplaces where exposure to engineered nanomaterials (ENMs) can occur. However, it is unclear if the use of CB can effectively reduce worker exposure to nanomaterials. A systematic review of studies was conducted to answer the question “can control banding be useful to ensure adequate controls for the safe handling of nanomaterials.” Methods A variety of databases were searched to identify relevant studies pertaining to CB. Database search terms included ‘control’, ‘hazard’, ‘exposure’ and ‘risk’ banding as well as the use of these terms in the context of nanotechnology or nanomaterials. Other potentially relevant studies were identified during the review of articles obtained in the systematic review process. Identification of studies and the extraction of data were independently conducted by the reviewers. Quality of the studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS). The quality of the evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results A total of 235 records were identified in the database search in which 70 records were determined to be eligible for full-text review. Only two studies were identified that met the inclusion criteria. These studies evaluated the application of the CB Nanotool in workplaces where ENMs were being handled. A total of 32 different nanomaterial handling activities were evaluated in these

Can control banding be useful for the safe handling of nanomaterials? A systematic review

International Nuclear Information System (INIS)

Eastlake, Adrienne; Zumwalde, Ralph; Geraci, Charles

2016-01-01

Control banding (CB) is a risk management strategy that has been used to identify and recommend exposure control measures to potentially hazardous substances for which toxicological information is limited. The application of CB and level of expertise required for implementation and management can differ depending on knowledge of the hazard potential, the likelihood of exposure, and the ability to verify the effectiveness of exposure control measures. A number of different strategies have been proposed for using CB in workplaces where exposure to engineered nanomaterials (ENMs) can occur. However, it is unclear if the use of CB can effectively reduce worker exposure to nanomaterials. A systematic review of studies was conducted to answer the question “can control banding be useful to ensure adequate controls for the safe handling of nanomaterials.” A variety of databases were searched to identify relevant studies pertaining to CB. Database search terms included ‘control,’ ‘hazard,’ ‘exposure,’ and ‘risk’ banding as well as the use of these terms in the context of nanotechnology or nanomaterials. Other potentially relevant studies were identified during the review of articles obtained in the systematic review process. Identification of studies and the extraction of data were independently conducted by the reviewers. Quality of the studies was assessed using the methodological index for nonrandomized studies. The quality of the evidence was evaluated using grading of recommendations assessment, development and evaluation (GRADE). A total of 235 records were identified in the database search in which 70 records were determined to be eligible for full-text review. Only two studies were identified that met the inclusion criteria. These studies evaluated the application of the CB Nanotool in workplaces where ENMs were being handled. A total of 32 different nanomaterial handling activities were evaluated in these studies by comparing the recommended

Can control banding be useful for the safe handling of nanomaterials? A systematic review

Energy Technology Data Exchange (ETDEWEB)

Eastlake, Adrienne, E-mail: aeastlake@cdc.gov [National Institute for Occupational Safety and Health, Nanotechnology Research Center (United States); Zumwalde, Ralph [RCS Corporation (United States); Geraci, Charles [National Institute for Occupational Safety and Health, Nanotechnology Research Center (United States)

2016-06-15

Control banding (CB) is a risk management strategy that has been used to identify and recommend exposure control measures to potentially hazardous substances for which toxicological information is limited. The application of CB and level of expertise required for implementation and management can differ depending on knowledge of the hazard potential, the likelihood of exposure, and the ability to verify the effectiveness of exposure control measures. A number of different strategies have been proposed for using CB in workplaces where exposure to engineered nanomaterials (ENMs) can occur. However, it is unclear if the use of CB can effectively reduce worker exposure to nanomaterials. A systematic review of studies was conducted to answer the question “can control banding be useful to ensure adequate controls for the safe handling of nanomaterials.” A variety of databases were searched to identify relevant studies pertaining to CB. Database search terms included ‘control,’ ‘hazard,’ ‘exposure,’ and ‘risk’ banding as well as the use of these terms in the context of nanotechnology or nanomaterials. Other potentially relevant studies were identified during the review of articles obtained in the systematic review process. Identification of studies and the extraction of data were independently conducted by the reviewers. Quality of the studies was assessed using the methodological index for nonrandomized studies. The quality of the evidence was evaluated using grading of recommendations assessment, development and evaluation (GRADE). A total of 235 records were identified in the database search in which 70 records were determined to be eligible for full-text review. Only two studies were identified that met the inclusion criteria. These studies evaluated the application of the CB Nanotool in workplaces where ENMs were being handled. A total of 32 different nanomaterial handling activities were evaluated in these studies by comparing the recommended

Energy policy perspectives from the angle of industry

International Nuclear Information System (INIS)

Stihl, H.P.

1998-01-01

Leave open the possibility to opt for nuclear power, monitor and eventually reduce the subsidies for coal, open up the electricity and natural gas markets to the competitive regime, and solve the conflicts of interest arising from utilization of energy and environmental protection on the national and international level by developing appropriate free market instruments. These requirements are the signposts along the road to comprehensive energy efficiency in generation and applications, which has to be achieved while keeping an eye on reliability and affordability of energy supplies, in order not to endanger economic growth or innovative impetus. The industry will continue to remind the policy makers of this interdependence of interests. (orig./CB) [de

Structural basis of G protein-coupled receptor-Gi protein interaction: formation of the cannabinoid CB2 receptor-Gi protein complex.

Science.gov (United States)

Mnpotra, Jagjeet S; Qiao, Zhuanhong; Cai, Jian; Lynch, Diane L; Grossfield, Alan; Leioatts, Nicholas; Hurst, Dow P; Pitman, Michael C; Song, Zhao-Hui; Reggio, Patricia H

2014-07-18

In this study, we applied a comprehensive G protein-coupled receptor-Gαi protein chemical cross-linking strategy to map the cannabinoid receptor subtype 2 (CB2)-Gαi interface and then used molecular dynamics simulations to explore the dynamics of complex formation. Three cross-link sites were identified using LC-MS/MS and electrospray ionization-MS/MS as follows: 1) a sulfhydryl cross-link between C3.53(134) in TMH3 and the Gαi C-terminal i-3 residue Cys-351; 2) a lysine cross-link between K6.35(245) in TMH6 and the Gαi C-terminal i-5 residue, Lys-349; and 3) a lysine cross-link between K5.64(215) in TMH5 and the Gαi α4β6 loop residue, Lys-317. To investigate the dynamics and nature of the conformational changes involved in CB2·Gi complex formation, we carried out microsecond-time scale molecular dynamics simulations of the CB2 R*·Gαi1β1γ2 complex embedded in a 1-palmitoyl-2-oleoyl-phosphatidylcholine bilayer, using cross-linking information as validation. Our results show that although molecular dynamics simulations started with the G protein orientation in the β2-AR*·Gαsβ1γ2 complex crystal structure, the Gαi1β1γ2 protein reoriented itself within 300 ns. Two major changes occurred as follows. 1) The Gαi1 α5 helix tilt changed due to the outward movement of TMH5 in CB2 R*. 2) A 25° clockwise rotation of Gαi1β1γ2 underneath CB2 R* occurred, with rotation ceasing when Pro-139 (IC-2 loop) anchors in a hydrophobic pocket on Gαi1 (Val-34, Leu-194, Phe-196, Phe-336, Thr-340, Ile-343, and Ile-344). In this complex, all three experimentally identified cross-links can occur. These findings should be relevant for other class A G protein-coupled receptors that couple to Gi proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Assessing Screening Policies for Childhood Obesity

Science.gov (United States)

Wein, Lawrence M.; Yang, Yan; Goldhaber-Fiebert, Jeremy D.

2014-01-01

To address growing concerns over childhood obesity, the United States Preventive Services Task Force (USPSTF) recently recommended that children undergo obesity screening beginning at age 6 [1]. An Expert Committee recommends starting at age 2 [2]. Analysis is needed to assess these recommendations and investigate whether there are better alternatives. We model the age- and sex-specific population-wide distribution of body mass index (BMI) through age 18 using National Longitudinal Survey of Youth data [3]. The impact of treatment on BMI is estimated using the targeted systematic review performed to aid the USPSTF [4]. The prevalence of hypertension and diabetes at age 40 are estimated from the Panel Study of Income Dynamics [5]. We fix the screening interval at 2 years, and derive the age- and sex-dependent BMI thresholds that minimize adult disease prevalence, subject to referring a specified percentage of children for treatment yearly. We compare this optimal biennial policy to biennial versions of the USPSTF and Expert Committee recommendations. Compared to the USPSTF recommendation, the optimal policy reduces adult disease prevalence by 3% in relative terms (the absolute reductions are disease prevalence at a 28% reduction in treatment referral rate. If compared to the Expert Committee recommendation, the reductions change to 6% and 40%, respectively. The optimal policy treats mostly 16 year olds and few children under age 14. Our results suggest that adult disease is minimized by focusing childhood obesity screening and treatment on older adolescents. PMID:22240724

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.

Treatment of severe psoriasis in children: recommendations of an Italian expert group.

Science.gov (United States)

Fortina, Anna Belloni; Bardazzi, Federico; Berti, Samantha; Carnevale, Claudia; Di Lernia, Vito; El Hachem, Maya; Neri, Iria; Gelmetti, Carlo Mario; Lora, Viviana; Mazzatenta, Carlo; Milioto, Mirella; Moretta, Gaia; Patrizi, Annalisa; Peris, Ketty; Villani, Alberto

2017-10-01

This article provides comprehensive recommendations for the systemic treatment of severe pediatric psoriasis based on evidence obtained from a systematic review of the literature and the consensus opinion of expert dermatologists and pediatricians. For each systemic treatment, the grade of recommendation (A, B, C) based on the treatment's approval by the European Medicines Agency for childhood psoriasis and the experts' opinions is discussed. The grade of recommendation for narrow-band-ultraviolet B phototherapy, cyclosporine, and retinoids is C, while that for methotrexate is C/B. The use of adalimumab, etanercept, and ustekinumab has a grade A recommendation. No conventional systemic treatments are approved for pediatric psoriasis. Adalimumab is approved by the European Medicines Agency as a first-line treatment for severe chronic plaque psoriasis in children (≥ 4 years old) and adolescents. Etanercept and ustekinumab are approved as second-line therapy in children ≥ 6 and ≥ 12 years, respectively. A treatment algorithm as well as practical tools (i.e., tabular summaries of differential diagnoses, treatment mechanism of actions, dosing regimens, control parameters) are provided to assist in therapeutic reasoning and decision-making for individual patients. These treatment recommendations are endorsed by major Italian Pediatric and Dermatology Societies. What is Known: • Guidelines for the treatment of severe pediatric psoriasis are lacking and most traditional systemic treatments are not approved for use in young patients. Although there has been decades of experience with some of the traditional agents such as phototherapy, acitretin, and cyclosporine in children, there are no RCTs on their pediatric use while RCTs investigating new biologic agents have been performed. What is New: • In this manuscript, an Italian multidisciplinary team of experts focused on treatment recommendations for severe forms of psoriasis in children based on an up

The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice

Directory of Open Access Journals (Sweden)

Francisco J. Bermudez-Silva

2016-01-01

Full Text Available The endocannabinoid system (ECS is an intercellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and expansion of the β-cell mass. The downstream signalling pathways mediating these effects are poorly understood. Mammalian target of rapamycin complex 1 (mTORC1 signalling is a key intracellular pathway involved in energy homeostasis and is known to importantly affect the physiology of pancreatic islets. We investigated the possible relationship between cannabinoid type 1 (CB1 receptor signalling and the mTORC1 pathway in the endocrine pancreas of mice by using pharmacological analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance tests were performed. The CB1 receptor antagonist rimonabant decreased glucose-stimulated insulin secretion (GSIS at 0.1 µM while increasing phosphorylation of p70S6K1 and ribosomal protein S6 (rpS6 within the islets. Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. In vivo experiments showed that 3 mg/kg body weight rimonabant decreased insulin levels and induced glucose intolerance in lean mice without altering peripheral insulin sensitivity; this effect was prevented by peripheral administration of low doses of rapamycin (0.1 mg/kg body weight, which increased insulin sensitivity. These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole-organism level, which could have implications for the development of new therapeutic approaches for pancreatic β-cell diseases.

Nuclear fuels policy. Report of the Atlantic Council's Nuclear Fuels Policy working group

International Nuclear Information System (INIS)

Anon.

1976-01-01

The purpose of the policy paper presented is to recommend the actions deemed necessary to assure that future US and other non-Communist countries' nuclear fuels supply will be adequate to meet future energy demand. Taken together, the recommended decisions and actions form a nuclear fuels supply policy for the United States Government and for the private sector, and new areas of responsibility for the appropriate international organizations in which the US participates. The principal conclusions and recommendations are that the US and the other industrialized non-Communist countries should strive for increased flexibility of primary energy fuel sources, and that a balanced energy strategy therefore depends upon the security of supply of energy resources and the ability to substitute one form of fuel for another. The substitutability and efficient use of energy resources are enhanced by accelerating the supply and use of electricity

The process of setting micronutrient recommendations

DEFF Research Database (Denmark)

Timotijevic, Lada; Barnett, Julie; Brown, Kerry

2011-01-01

in the field of micronutrient recommendations and a case study that focused on mandatory folic acid (FA) fortification. Setting: Questionnaire-based data were collected across thirty-five European countries. The FA fortification case study was conducted in the UK, Norway, Denmark, Germany, Spain, Czech...... Republic and Hungary. Results: Varied bodies are responsible for setting micronutrient recommendations, each with different statutory and legal models of operation. Transparency is highest where there are standing scientific advisory committees (SAC). Where the standing SAC is created, the range...... of expertise and the terms of reference for the SAC are determined by the government. Where there is no dedicated SAC, the impetus for the development of micronutrient recommendations and the associated policies comes from interested specialists in the area. This is typically linked with an ad hoc selection...

Energy efficiency and the liberalized market - new approaches in national climate protection policy

International Nuclear Information System (INIS)

Hennicke, P.

2000-01-01

The paper initially explains the rationale of energy policy-based governmental intervention in the liberalized electricity market ('the need for political governance'). It is shown why there is a 'demand for intelligent regulatory policy' in Germany's energy sector, despite, or rather as a consequence of the deregulation of the energy markets, and refers e.g. to a parliamentary paper of the Bundestag, (BTDrs. 14/2656, p. 9). The author continues with selecting and defining, from the stock of conceivable appropriate action and regulatory instruments, the corner stones of action plans and the range of instruments, specifically designed for the sector and the target groups, that will accelerate market penetration of the energy efficiency policies ('governance functions'). The author also shows that, due to the significance of regulatory and structurizing impacts, as well as resulting consequences to the leading paradigms of policy of this Government (opting out of nuclear power, global climate change), the electricity industry is just the right branch of industry to serve as a ''national demonstration project'' on the way towards sustainable development. (orig./CB) [de

Suitable exposure conditions for CB Throne? New model cone beam computed tomography unit for dental use

International Nuclear Information System (INIS)

Tanabe, Kouji; Nishikawa, Keiichi; Yajima, Aya; Mizuta, Shigeru; Sano, Tsukasa; Yajima, Yasutomo; Nakagawa, Kanichi; Kousuge, Yuuji

2008-01-01

The CB Throne is a cone beam computed tomography unit for dental use, and the smaller version of the CB MercuRay developed by Hitachi Medico Co. We investigated which exposure conditions were suitable in the clinical use. Suitable exposure conditions were determined by simple subjective comparisons. The right temporomandibular joint of the head phantom was scanned at all possible combinations of tube voltage (60, 80, 100, 120 kV) and tube current (10, 15 mA). Oblique-sagittal images of the same position were obtained using multiplanar reconstruction (MPR) function. Images obtained at 120 kV and 15 mA, which are the highest exposure conditions and certain to produce images of the best quality, were used to establish the standard. Eight oral radiologists observed each image and standard image on a LCD monitor. They compared subjectively spatial resolution and noise between each image and standard image using a 10 cm scale. Evaluation points were obtained from the check positions on the scales. The Steel method was used to determine significant differences. The images at 60 kV/10 mA and 80 kV/15 mA showed significantly lower evaluation points on spatial resolution. The images at 60 kV/10 mA, 60 kV/15 mA and 80 kV/10 mA showed significantly lower evaluation points on noise. In conclusion, even if exposure conditions are reduced to 100 kV/10 mA, 100 kV/15 mA or 120 kV/10 mA, the CB Throne will produce images of the best quality. (author)

Creating Adaptive Policies: A Guide for Policy-making in an ...

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

2009-01-01

Jan 1, 2009 ... This is an essential toolkit for those in the business of making, recommending, ... Policies that cannot perform effectively under today's complex, dynamic, and ... Suruchi Bhadwal is an Area Convener of the Centre for Global ...

Sustainable innovation policy advice using a policy watch approach to ‘policies’ mapping

OpenAIRE

Repo, Juha Petteri; Matschoss, Kaisa Johanna; Tregner-Mlinaric, Anita; Van Eynde, Sarah; Ramioul, Monique; Damianova, Zoya; Kozarev, Ventseslav

2017-01-01

This chapter illustrates via a piloted application how one of the five steps of the CASI Framework (CASI-F), which is designed for the management and assessment of sustainable innovation, can be applied to monitor policy developments. To this end, we reviewed 96 policy recommendations from CASI policy briefs concerning the Europe 2020 strategy, with a special focus on resource efficiency. The results show that CASI-F can provide a useful additional tool for analysing and reflecting on the out...

Recommendations for the Preparation of Environmental Assessments and Environmental Impact Statements, 2nd edition

Energy Technology Data Exchange (ETDEWEB)

None, None

2004-12-01

This document provides recommendations for the Department of Energy’s (DOE’s) preparation of environmental assessments and environmental impact statements under the National Environmental Policy Act of 1969 (NEPA). The Office of NEPA Policy and Compliance prepared these recommendations in consultation with the Office of the Assistant General Counsel for Environment and following coordination with the DOE NEPA Community. The recommendations should materially aid those responsible for preparing and reviewing NEPA documents to focus on significant environmental issues, adequately analyze environmental impacts, and effectively present the analysis to decisionmakers and the public. The recommendations are not all-encompassing, however; preparers must apply independent judgment to determine the appropriate scope and analytical requirements of NEPA for each proposal. These recommendations do not constitute legal requirements, but are intended to enhance compliance with existing NEPA regulations (40 CFR Parts 1500-1508, 10 CFR Part 1021).

Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB{sub 1} receptors using positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Terry, Garth E. [National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States); Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Hirvonen, Jussi; Liow, Jeih-San; Seneca, Nicholas; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B. [National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States); Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C. [Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN (United States); Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden)

2010-08-15

Cannabinoid subtype 1 (CB{sub 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{sub 1} receptors with two PET radioligands: {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 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 {sup 11}C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with {sup 18}F-FMPEP-d{sub 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 {sup 18}F-FMPEP-d{sub 2}. The effective doses of {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 2} are 4.6 and 19.7 {mu}Sv/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 {sup 11}C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from {sup 18}F-FMPEP-d{sub 2} showed both hepatobiliary and urinary excretion. {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 2} yield an effective dose similar to other PET radioligands labeled with either {sup 11}C or {sup 18}F. The high uptake in brain confirms the utility of these two radioligands to image CB{sub 1} receptors in brain, and both may also be useful to image CB{sub 1} receptors in the periphery. (orig.)

Energy policies of IEA countries: Australia 2005 review

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-11-16

The report reviews Australia's energy policies and makes recommendations to the government on future policy development. The IEA commends the efficiency and security of the Australian energy market but recommends that the country will have to substantially alter future energy supply and/or demand behaviour if it wants to moderate emission levels and work within any future global climate change mitigation programme. 23 figs., 27 tabs., 3 annexes.

Energy policies of IEA countries: Australia 2005 review

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-11-16

The report reviews Australia's energy policies and makes recommendations to the government on future policy development. The IEA commends the efficiency and security of the Australian energy market but recommends that the country will have to substantially alter future energy supply and/or demand behaviour if it wants to moderate emission levels and work within any future global climate change mitigation programme. 23 figs., 27 tabs., 3 annexes.

National policies for the promotion of physical activity and healthy nutrition in the workplace context: a behaviour change wheel guided content analysis of policy papers in Finland

Directory of Open Access Journals (Sweden)

Tuija Seppälä

2017-08-01

Full Text Available Abstract Background Health policy papers disseminate recommendations and guidelines for the development and implementation of health promotion interventions. Such documents have rarely been investigated with regard to their assumed mechanisms of action for changing behaviour. The Theoretical Domains Framework (TDF and Behaviour Change Techniques (BCT Taxonomy have been used to code behaviour change intervention descriptions, but to our knowledge such “retrofitting” of policy papers has not previously been reported. This study aims first to identify targets, mediators, and change strategies for physical activity (PA and nutrition behaviour change in Finnish policy papers on workplace health promotion, and second to assess the suitability of the Behaviour Change Wheel (BCW approach for this purpose. Method We searched all national-level health policy papers effectual in Finland in August 2016 focusing on the promotion of PA and/or healthy nutrition in the workplace context (n = 6. Policy recommendations targeting employees’ nutrition and PA including sedentary behaviour (SB were coded using BCW, TDF, and BCT Taxonomy. Results A total of 125 recommendations were coded in the six policy papers, and in two additional documents referenced by them. Psychological capability, physical opportunity, and social opportunity were frequently identified (22%, 31%, and 24%, respectively, whereas physical capability was almost completely absent (1%. Three TDF domains (knowledge, skills, and social influence were observed in all papers. Multiple intervention functions and BCTs were identified in all papers but several recommendations were too vague to be coded reliably. Influencing individuals (46% and changing the physical environment (44% were recommended more frequently than influencing the social environment (10%. Conclusions The BCW approach appeared to be useful for analysing the content of health policy papers. Paying more attention to underlying

Prevalence of Recommendations Made Within Dental Research Articles Using Uncontrolled Intervention or Observational Study Designs.

Science.gov (United States)

Wilson, M K; Chestnutt, I G

2016-03-01

Evidence to inform clinical practice is reliant on research carried out using appropriate study design. The objectives of this work were to (i) identify the prevalence of articles reporting on human studies using uncontrolled intervention or observational research designs published in peer-reviewed dental journals and (ii) determine the nature of recommendations made by these articles. Six peer-reviewed dental journals were selected. Issues published in January to June 2013 were examined and the types of articles published categorized. Following pre-defined inclusion/exclusion criteria, human studies classified as using uncontrolled intervention or observational research designs were subject to detailed review by two independent investigators, to examine if they presented clinical, policy or research recommendations and if these recommendations were supported by the data presented. 52.9% (n = 156) of studies published during the time period met the inclusion criteria. Studies with uncontrolled intervention or observational research designs comprised a larger proportion of the primary research studies published in the journals with lower impact factors (73.3%; n = 107) compared to the high impact journals (38.9%; n = 49). Analysis showed that 60.9% (n = 95) of the included studies made recommendations for clinical practice/dental policy. In 28.2% (n = 44) of studies, the clinical/policy recommendations made were judged to not be fully supported by the data presented. Many studies published in the current dental literature, which are not considered to produce strong evidence, make recommendations for clinical practice or policy. There were some cases when the recommendations were not fully supported by the data presented. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Localización de los Receptores Cannabinoides 1 (CB1) en Glándulas Salivales Submandibulares y Sublinguales de Ratones Durante el Desarrollo Postnatal

OpenAIRE

Hipkaeo, Wiphawi; Watanabe, Masahiko; Kondo, Hisatake

2015-01-01

In view of the fact that human marijuana users often show dry mouth symptom, the present study was attempted to examine the localization of CB1, which was originally identified in brain, in the submandibular and sublingual salivary glands of postnatal developing male mice by immunohistochemistry. In submandibular gland, CB1-immunoreactivity was positive in a majority of acinar cells in forms of granular appearance in their apical cytoplasm, while it was negative in the ducts at newborn stage....

7 CFR 925.50 - Marketing policy.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing policy. 925.50 Section 925.50 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... SOUTHEASTERN CALIFORNIA Regulations § 925.50 Marketing policy. Each season prior to making any recommendation...

Strong Public Health Recommendations from Weak Evidence? Lessons Learned in Developing Guidance on the Public Health Management of Meningococcal Disease

Directory of Open Access Journals (Sweden)

Germaine Hanquet

2015-01-01

Full Text Available The evidence underpinning public health policy is often of low quality, leading to inconsistencies in recommended interventions. One example is the divergence in national policies across Europe for managing contacts of invasive meningococcal disease. Aiming to develop consistent guidance at the European level, a group of experts reviewed the literature and formulated recommendations. The group defined eight priority research questions, searched the literature, and formulated recommendations using GRADE methodology. Five of the research questions are discussed in this paper. After taking into account quality of evidence, benefit, harm, value, preference, burden on patient of the intervention, and resource implications, we made four strong recommendations and five weak recommendations for intervention. Strong recommendations related not only to one question with very low quality of evidence as well as to two questions with moderate to high quality of evidence. The weak recommendations related to two questions with low and very low quality of evidence but also to one question with moderate quality of evidence. GRADE methodology ensures a transparent process and explicit recognition of additional factors that should be considered when making recommendations for policy. This approach can be usefully applied to many areas of public health policy where evidence quality is often low.

Nido-Carborane building-block reagents. 3. Cyclic and open-chain oligomers incorporating -CB4H6C - units. Crown carboranes

International Nuclear Information System (INIS)

Boyter, H.A. Jr.; Grimes, R.N.

1988-01-01

The open-chain dialkynes EtC≡C(CH 2 ) n C≡CEt (n = 4, 6), the trialkyne HC≡C(CH 2 ) 5 C≡CH, and the cyclic dialkynes CH 2 (CH 2 ) 4 C≡C(CH 2 ) n C≡C (n = 4-6) were treated with B 5 H 9 and (C 2 H 5 ) 3 to give the corresponding nido-carborane oligomers, in which the original -C≡C- units are converted to -CB 4 H 6 C- nido-carborane cages. In each case, all available -C≡C- groups were transformed to carborane moieties. No partially converted products (having both carborane and -C≡C- groups in the chain) were found; when the B 5 H 9 /-C≡C- ratio employed was 2+ and oxidative fusion, forming products incorporating C 4 B 8 cages. The cyclic bis(carborane) CH 2 (CH 2 ) 4 CB 4 H 6 C(CH 2 ) 5 CB 4 H 6 C is an air-stable oil that can be deprotonated but does not under metal-promoted oxidative fusion. All products were characterized by 11 B and 1 H NMR, infrared, visible-uv, and mass spectroscopy, and the 13 C NMR spectra of linear bis(carboranes) are reported. 9 references, 7 figures, 4 tables

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

Science.gov (United States)

De Luca, Maria Antonietta; Castelli, M Paola; Loi, Barbara; Porcu, Alessandra; Martorelli, Mariella; Miliano, Cristina; Kellett, Kathryn; Davidson, Colin; Stair, Jacqueline L; Schifano, Fabrizio; Di Chiara, Gaetano

2016-06-01

In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

The need for economic policy coordination between Europe, Japan, and the United States: Policy recommendations for the 1990s

NARCIS (Netherlands)

A. Knoester (Anthonie); A. Kolodziejak (André)

1994-01-01

textabstractBetter policy coordination between Europe, Japan, and the United States is urgently needed in order to restore economic growth and to diminish mutual trade imbalances. Using the EC Compact model it is shown how coordinated fiscal policies can contribute to reaching these goals in the

Determinations of vertical stroke V{sub cb} vertical stroke and vertical stroke V{sub ub} vertical stroke from baryonic Λ{sub b} decays

Energy Technology Data Exchange (ETDEWEB)

Hsiao, Y.K. [Shanxi Normal University, School of Physics and Information Engineering, Linfen (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Geng, C.Q. [Shanxi Normal University, School of Physics and Information Engineering, Linfen (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Hunan Normal University, Synergetic Innovation Center for Quantum Effects and Applications (SICQEA), Changsha (China)

2017-10-15

We present the first attempt to extract vertical stroke V{sub cb} vertical stroke from the Λ{sub b} → Λ{sub c}{sup +}l anti ν{sub l} decay without relying on vertical stroke V{sub ub} vertical stroke inputs from the B meson decays. Meanwhile, the hadronic Λ{sub b} → Λ{sub c}M{sub (c)} decays with M = (π{sup -},K{sup -}) and M{sub c} =(D{sup -},D{sup -}{sub s}) measured with high precisions are involved in the extraction. Explicitly, we find that vertical stroke V{sub cb} vertical stroke =(44.6 ± 3.2) x 10{sup -3}, agreeing with the value of (42.11 ± 0.74) x 10{sup -3} from the inclusive B → X{sub c}l anti ν{sub l} decays. Furthermore, based on the most recent ratio of vertical stroke V{sub ub} vertical stroke / vertical stroke V{sub cb} vertical stroke from the exclusive modes, we obtain vertical stroke V{sub ub} vertical stroke = (4.3 ± 0.4) x 10{sup -3}, which is close to the value of (4.49 ± 0.24) x 10{sup -3} from the inclusive B → X{sub u}l anti ν{sub l} decays. We conclude that our determinations of vertical stroke V{sub cb} vertical stroke and vertical stroke V{sub ub} vertical stroke favor the corresponding inclusive extractions in the B decays. (orig.)

Transfer Effect Ratio of Loosely Coupled Coils for Wireless Power through CB Wall under Station Blackout(SBO)

International Nuclear Information System (INIS)

Koo, Kil Mo; Hong, Seong Wan; Song, Jin Ho; Baek, Won Pil; Cheon, Sang Hoon

2016-01-01

Instrumentations have had the bad situation like a station blackout(SBO) as the severe accident in nuclear power plants. In recent years, there has been an increasing interest in wireless power transfer technology, In particular, significant processing has been charted for inductively coupled systems. In this paper, we introduce some new method as transfer effect ratio of loosely coupled coils for wireless power through the CB(Container Building) wall as an alternative method under a station blackout of severe accident conditions in nuclear power plants. As an equivalent circuit model that can describe wireless energy transfer systems via coupled magnetic resonances for the CB thickness wall. The solution shows that the transmission efficiency can be decreased simply by adjusting the spacing between the power and the sending coils or between the receiving and the load coils. The system design can be calculated the frequency characteristics, and then an equivalent circuit model was developed from the node equation and established in an electric design automation tool

Transfer Effect Ratio of Loosely Coupled Coils for Wireless Power through CB Wall under Station Blackout(SBO)

Energy Technology Data Exchange (ETDEWEB)

Koo, Kil Mo; Hong, Seong Wan; Song, Jin Ho; Baek, Won Pil [KAERI, Daejeon (Korea, Republic of); Cheon, Sang Hoon [ETRI, Daejeon (Korea, Republic of)

2016-05-15

Instrumentations have had the bad situation like a station blackout(SBO) as the severe accident in nuclear power plants. In recent years, there has been an increasing interest in wireless power transfer technology, In particular, significant processing has been charted for inductively coupled systems. In this paper, we introduce some new method as transfer effect ratio of loosely coupled coils for wireless power through the CB(Container Building) wall as an alternative method under a station blackout of severe accident conditions in nuclear power plants. As an equivalent circuit model that can describe wireless energy transfer systems via coupled magnetic resonances for the CB thickness wall. The solution shows that the transmission efficiency can be decreased simply by adjusting the spacing between the power and the sending coils or between the receiving and the load coils. The system design can be calculated the frequency characteristics, and then an equivalent circuit model was developed from the node equation and established in an electric design automation tool.

Policy Pathways: Energy Management Programmes for Industry

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-09-06

The IEA Policy Pathway publications provide details on how to implement specific recommendations drawn from the IEA 25 Energy Efficiency Policy Recommendations. This Policy Pathway, jointly produced by the International Energy Agency and the Institute for Industrial Productivity, develops the critical steps for policy makers implementing energy management programmes for industry. Optimising energy use in industry is essential to improve industrial competitiveness and achieve wider societal goals such as energy security, economic recovery and development, climate change mitigation and environmental protection.While there is significant potential to decrease energy consumption in this sector, opportunities to improve energy efficiency are still under-exploited. Energy management programmes have shown to be instrumental in addressing many of the barriers that inhibit wide-scale uptake of energy management in industry. The Policy Pathway builds on lessons learned from country experiences and provides actionable guidance on how to plan and design, implement, evaluate and monitor energy management programmes for industry.

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

Federal Government Electronic Bulletin Boards: An Assessment with Policy Recommendations.

Science.gov (United States)

Bertot, John Carlo; McClure, Charles R.

1993-01-01

Identifies and analyzes federal government electronic bulletin boards; assesses the types of information available to users, including costs and technological access issues; discusses federal information policy; and considers the role of federal bulletin boards in accessing and managing electronic government information. (Contains 29 references.)…

Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

OpenAIRE

Copley, Shelley D.; Crooks, Gwen P.

1992-01-01

4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed.

Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

Science.gov (United States)

Copley, Shelley D.; Crooks, Gwen P.

1992-01-01

4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed. PMID:16348702

7 CFR 945.50 - Marketing policy.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing policy. 945.50 Section 945.50 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Marketing policy. (a) Preparation. Prior to or at the same time as recommendations are made pursuant to...

7 CFR 924.50 - Marketing policy.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing policy. 924.50 Section 924.50 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Marketing policy. (a) Each season prior to making any recommendations pursuant to § 924.51, the committee...

CESM/CAM5 improvement and application: comparison and evaluation of updated CB05_GE and MOZART-4 gas-phase mechanisms and associated impacts on global air quality and climate

Science.gov (United States)

He, J.; Zhang, Y.; Tilmes, S.; Emmons, L.; Lamarque, J.-F.; Glotfelty, T.; Hodzic, A.; Vitt, F.

2015-12-01

Atmospheric chemistry plays a key role in determining the amounts and distributions of oxidants and gaseous precursors that control the formation of secondary gaseous and aerosol pollutants; all of those species can interact with the climate system. To understand the impacts of different gas-phase mechanisms on global air quality and climate predictions, in this work, a comprehensive comparative evaluation is performed using the Community Atmosphere Model (CAM) Version 5 with comprehensive tropospheric and stratospheric chemistry (CAM5-chem) within the Community Earth System Model (CESM) with the two most commonly used gas-phase chemical mechanisms: the 2005 Carbon Bond mechanism with Global Extension (CB05_GE) and the Model of OZone and Related chemical Tracers version 4 (MOZART-4) mechanism with additional updates (MOZART-4x). MOZART-4x and CB05_GE use different approaches to represent volatile organic compounds (VOCs) and different surrogates for secondary organic aerosol (SOA) precursors. MOZART-4x includes a more detailed representation of isoprene chemistry compared to CB05_GE. CB05_GE includes additional oxidation of SO2 by O3 over the surface of dust particles, which is not included in MOZART-4x. The results show that the two CAM5-chem simulations with CB05_GE and MOZART-4x predict similar chemical profiles for major gases (e.g., O3, CO, and NOx) compared to the aircraft measurements, with generally better agreement for NOy profiles by CB05_GE than MOZART-4x. The concentrations of SOA at four sites in the continental US (CONUS) and organic carbon (OC) over the IMPROVE sites are well predicted by MOZART-4x (with normalized mean biases (NMBs) of -1.9 and 2.1 %, respectively) but moderately underpredicted by CB05_GE (with NMBs of -23.1 and -20.7 %, respectively). This is mainly due to the higher biogenic emissions and OH levels simulated with MOZART-4x than with CB05_GE. The concentrations of OC over Europe are largely underpredicted by both MOZART-4x and CB05

CONSIDERATIONS REGARDING MONETARY POLICY IN ROMANIA

Directory of Open Access Journals (Sweden)

Pitorac Ruxandra

2015-07-01

Full Text Available The main objective of this paper is to study the Romania’s monetary policy, in the period 1996-2013. The research starts with a theoretical review of the monetary policy, whose main purpose is influencing the broad money supply and the lending requirements and the institution in charge of achieving this objective is the Central Bank, highlighting its impact upon the economic activity, through the Keynesian analysis model IS-LM and a correlation between the monetary policy measures and the phases of the economic cycle whose results indicate that during the recession periods it is recommended to reduce interest rates in order to stimulate investments, by raising the money supply, and during the expansion period it is recommended to increase the interest rate in order to cut back the money supply. Starting from this premises, the research takes into account the study of the monetary policy measures adopted by the governmental authority of Romania, making a quantitative analysis of the main macroeconomic indicators: the real interest rate, the lending interest rate, the deposit interest rate and the broad money supply and through a multifactorial regression, highlighting the impact of the interest rates upon the monetary aggregate M2. Moreover, a comparison between the monetary policy measures adopted in Romania and the monetary policies recommended by specialized literature has been done, and the results have indicated that during recession periods the attention of the governmental authorities is focused upon adopting the right measures, but during the expansion periods this doesn’t happen. The results of this research highlight the economic situation in Romania and the way in which the governmental authority intervened, through the monetary policy measures, in order to mitigate the negative effects of the cyclical fluctuations.

Energy policy and the scope of action of the EC; Die energiepolitischen Handlungsmoeglichkeiten der EG

Energy Technology Data Exchange (ETDEWEB)

Brand, E. [Universitaet Lueneburg, Lueneburg (Germany); Witthohn, A. [IHK Hannover (Germany)

2002-04-01

This contribution examines the legal basis of authorization and the scope of action of the European legislator with respect to legislation on the energy policy of the EC. The analysis starts with summarising the evolution of the primary law, looking inter alia at the constitutent treaties of the ECSC, EURATOM, and the EEC, and discusses further developments and treaties, as there is no specific, uniform basis of legislative power of the EC in the energy sector of EC. Subsequently, the basis for and secondary law making is discussed, the concluding part of the article giving an outlook on the future. (orig./CB) [German] Zentrale Frage des folgenden Beitrags ist, woraus der europaeische Gesetzgeber seine Kompetenz im Energiebereich ableitet und wie weit seine Regelungen in dem Bereich gehen duerfen. Um diese Fragen zu beantworten, wird zunaechst die Entwicklung des europaeischen Primaerrechts bzw. der Gruendungsvertraege im Energiebereich beleuchtet und werden die einschlaegigen Ermaechtigungsgrundlagen dargestellt. Im Anschluss daran stehen dann die wichtigsten sekundaerrechtlichen Regelungen im Mittelpunkt. Abschliessend wird ein Ausblick auf die weitere Entwicklung gegeben. (orig./CB)

Demand-Side Flexibility for Energy Transitions: Policy Recommendations for Developing Demand Response

OpenAIRE

Nursimulu, Anjali; Florin, Marie-Valentine; Vuille, François

2016-01-01

As a follow-up to IRGC's report on demand-side flexibility for energy transitions, this Policy Brief highlights that increasing flexibility in power systems is needed to accommodate higher shares of non-controllable and intermittent renewable generation, and that this requires changes to the market design and regulatory framework, to facilitate the development and deployment of appropriate technologies and market-based instruments (e.g. taxes and subsidies). The Policy Brief focuses on demand...

7 CFR 920.50 - Marketing policy.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing policy. 920.50 Section 920.50 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulations § 920.50 Marketing policy. (a) Each season prior to making any recommendations pursuant to § 920...

The Combined Inhibitory Effect of the Adenosine A1 and Cannabinoid CB1 Receptors on cAMP Accumulation in the Hippocampus Is Additive and Independent of A1 Receptor Desensitization

OpenAIRE

Serpa, Andr?; Correia, Sara; Ribeiro, Joaquim A.; Sebasti?o, Ana M.; Cascalheira, Jos? F.

2015-01-01

Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3?30??M) decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6 ? 2.7??M and an E max? of 31% ? 2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10?150?nM), an EC50 of 35 ? 19?nM, an...

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.

International Commission on Radiological Protection. History, policies, procedures

International Nuclear Information System (INIS)

Lindell, Bo; Dunster, H.J.; Valentin, Jack; )

2000-01-01

This report briefly reviews the history, mode of operation, concepts, and current policies of the International Commission on Radiological Protection (ICRP). It touches upon the objectives of the Commission's recommendations, the quantities used, the biological basis of the Commission's policy, the quantitative basis for its risk estimates, the structure of the system of protection, some problems of interpretation and application in that system, and the need for stability, consistency, and clarity in the Commission's recommendations. (author)

Influence of media composition on the production of alkaline α-amylase from Bacillus subtilis CB-18.

Science.gov (United States)

Ogbonnaya, Nwokoro; Odiase, Anthonia

2012-01-01

Starch, a homopolysaccharide is an important and an abundant food reserve and energy source. Starches are processed to yield different products which find many industrial applications. Alpha-amylases hydrolyze starch by cleaving α-1,4-glucosidic bonds and have been used in food, textile and pharmaceutical industries [Sun et al. 2010]. Enzymatic conversion of starch with amylase presents an economically superior alternative to the conventional method of starch gelatinization. Alkaline α-amylase has an important position in the global enzyme market as a constituent of detergent. In this paper, we screened soil bacteria and an isolate, alkalophilic Bacillus subtilis CB-18 was found to produce an alkaline α-amylase in different media. MATERIAL AND METHODS. Screening of the isolates for amylolytic activity was carried out by growing bacteria isolated from the soil in starch agar plates and subsequently staining the plates with iodine solution to reveal zones of hydrolysis of starch. The selected isolate, Bacillus subtlis CB-18 was grown in different media at alkaline pH to evaluate the influence of media composition on alkaline α-amylase production. Enzyme assay was carried out by growing the culture in a broth medium and obtaining cell - free culture supernatant after centrifugation at 2515 × g for 15 minutes Amylase activity was determined by incubating 0.5 ml of crude enzyme solution in 0.1M Tris/HCl buffer (pH 8.5) with 0.5 ml of 1% soluble starch solution. The reaction was terminated by the addition of DNS reagent and reducing sugar produced from the amylolytic reaction was determined. Bacillus subtilis CB-18 used for this work was selected because it produced 7 mm zone diameter on starch agar plate. This organism was cultured in different alkaline broth media containing 2% soluble starch as inducer carbohydrate for α-amylase production. Among the carbon sources used for enzyme production, sorbitol was the best to stimulate enzyme production with �

Role of Cannabinoid CB2 Receptor Gene (CNR2) Polymorphism in Children with Immune Thrombocytopenic Purpura in Beni-Suef Governorate in Egypt.

Science.gov (United States)

Ezzat, Dina A; Hammam, Amira A; El-Malah, Waleed M; Khattab, Rasha A; Mangoud, Eman M

2017-01-01

The cannabinoid system is involved in the immune regulation by modulation of Th cells type 1 and 2. It is composed of the CB2 receptor which is expressed at 10 to 100 folds greater levels on immune cells than the CB1 receptors. The CB2 is encoded by the cannabinoid CB receptor gene (CNR2) gene. This study aims to investigate the polymorphism in CNR2 gene variation rs 35761398 (Q63R) in Egyptian children with immune thrombocytopenic purpura and to investigate the relation between this gene polymorphism and either the susceptibility to or the chronicity of the disease. Forty children diagnosed as ITP were included in this study and 20 healthy children as normal control. CNR2 gene was investigated in those children by PCR RFLP technique (restriction fragment length polymorphism). CNR2 genotyping revealed that 45% of ITP patients had the QR heterotype, 50% had the RR homotype and 5% had QQ, the wild type with significantly higher frequency of homomutant genotype in comparison to controls. The relative odds ratio suggested a double risk for developing ITP in RR homotype (OR 2.152). A significant overpresentation of the RR genotype and of R allele was observed in the chronic patients (P=0.002 and 0.003, respectively). The associated risk to develop chronic ITP increased more than two folds for the RR homotype (OR=2.854). In conclusion, this study confirms the role of CNR2 Q63R polymorphism in the susceptibility to ITP in children and chronicity of the disease. Copyright© by the Egyptian Association of Immunologists.

Sexual Harassment Policies in Florida School Districts.

Science.gov (United States)

Rienzo, Barbara A.; Moore, Michele Johnson

1998-01-01

Investigated the extent to which Florida's school districts complied with the Florida Department of Education's (FDOE) recommendations for addressing sexual harassment in schools. Surveys of district equity coordinators and analysis of policies indicated that most districts approved sexual harassment policies incorporating many FDOE…

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

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

Building Scientific Data's list of recommended data repositories

Science.gov (United States)

Hufton, A. L.; Khodiyar, V.; Hrynaszkiewicz, I.

2016-12-01

When Scientific Data launched in 2014 we provided our authors with a list of recommended data repositories to help them identify data hosting options that were likely to meet the journal's requirements. This list has grown in size and scope, and is now a central resource for authors across the Nature-titled journals. It has also been used in the development of data deposition policies and recommended repository lists across Springer Nature and at other publishers. Each new addition to the list is assessed according to a series of criteria that emphasize the stability of the resource, its commitment to principles of open science and its implementation of relevant community standards and reporting guidelines. A preference is expressed for repositories that issue digital object identifiers (DOIs) through the DataCite system and that share data under the Creative Commons CC0 waiver. Scientific Data currently lists fourteen repositories that focus on specific areas within the Earth and environmental sciences, as well as the broad scope repositories, Dryad and figshare. Readers can browse and filter datasets published at the journal by the host repository using ISA-explorer, a demo tool built by the ISA-tools team at Oxford University1. We believe that well-maintained lists like this one help publishers build a network of trust with community data repositories and provide an important complement to more comprehensive data repository indices and more formal certification efforts. In parallel, Scientific Data has also improved its policies to better support submissions from authors using institutional and project-specific repositories, without requiring each to apply for listing individually. Online resources Journal homepage: http://www.nature.com/scientificdata Data repository criteria: http://www.nature.com/sdata/policies/data-policies#repo-criteria Recommended data repositories: http://www.nature.com/sdata/policies/repositories Archived copies of the list: https

Shaping Policy Change in Population Health: Policy Entrepreneurs, Ideas, and Institutions.

Science.gov (United States)

Béland, Daniel; Katapally, Tarun R

2018-01-14

Political realities and institutional structures are often ignored when gathering evidence to influence population health policies. If these policies are to be successful, social science literature on policy change should be integrated into the population health approach. In this contribution, drawing on the work of John W. Kingdon and related scholarship, we set out to examine how key components of the policy change literature could contribute towards the effective development of population health policies. Shaping policy change would require a realignment of the existing school of thought, where the contribution of population health seems to end at knowledge translation. Through our critical analysis of selected literature, we extend recommendations to advance a burgeoning discussion in adopting new approaches to successfully implement evidence-informed population health policies. © 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Monoclonal antibody 1.6.1 against human MPL receptor allows HSC enrichment of CB and BM CD34(+)CD38(-) populations.

Science.gov (United States)

Petit Cocault, Laurence; Fleury, Maud; Clay, Denis; Larghero, Jérôme; Vanneaux, Valérie; Souyri, Michèle

2016-04-01

Thrombopoietin (TPO) and its receptor Mpl (CD110) play a crucial role in the regulation of hematopoietic stem cells (HSCs). Functional study of Mpl-expressing HSCs has, however, been hampered by the lack of efficient monoclonal antibodies, explaining the very few data available on Mpl(+) HSCs during human embryonic development and after birth. Investigating the main monoclonal antibodies used so far to sort CD110(+) cells from cord blood (CB) and adult bone marrow (BM), we found that only the recent monoclonal antibody 1.6.1 engineered by Immunex Corporation was specific. Using in vitro functional assays, we found that this antibody can be used to sort a CD34(+)CD38(-)CD110(+) population enriched in hematopoietic progenitor stem cells, both in CB and in adult BM. In vivo injection into NSG mice further indicated that the CB CD34(+)CD38(-)CD110(+) population is highly enriched in HSCs compared with both CD34(+)CD38(-)CD110(-) and CD34(+)CD38(-) populations. Together our results validate MAb1.6.1 as an important tool, which has so far been lacking, in the HSC field. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

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, ...

National policies on the management of latent tuberculosis infection: review of 98 countries

Science.gov (United States)

Jagger, Ann; Reiter-karam, Silke; Getahun, Haileyesus

2018-01-01

Abstract Objective To review policies on management of latent tuberculosis infection in countries with low and high burdens of tuberculosis. Methods We divided countries reporting data to the World Health Organization (WHO) Global Tuberculosis Programme into low and high tuberculosis burden, based on WHO criteria. We identified national policy documents on management of latent tuberculosis through online searches, government websites, WHO country offices and personal communication with programme managers. We made a descriptive analysis with a focus on policy gaps and deviations from WHO policy recommendations. Findings We obtained documents from 68 of 113 low-burden countries and 30 of 35 countries with the highest burdens of tuberculosis or human immunodeficiency virus (HIV)-associated tuberculosis. Screening and treatment of latent tuberculosis infection in people living with HIV was recommended in guidelines of 29 (96.7%) high-burden and 54 (79.7%) low-burden countries. Screening for children aged countries. In most high-burden countries the recommendation was symptom screening alone before treatment, whereas in all low-burden countries it was testing before treatment. Some low-burden countries’ policies did not comply with WHO recommendations: nine (13.2%) recommended tuberculosis preventive treatment for travellers to high-burden countries and 10 (14.7%) for patients undergoing abdominal surgery. Conclusion Lack of solid evidence on certain aspects of management of latent tuberculosis infection results in national policies which vary considerably. This highlights a need to advance research and develop clear, implementable and evidence-based WHO policies. PMID:29531416

The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB2 receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy

Directory of Open Access Journals (Sweden)

Deng Liting

2012-09-01

Full Text Available Abstract Background Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone CB2 agonist, produces antinociception without producing central nervous system (CNS-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel. A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4 signaling to both chemotherapy-induced neuropathy and CB2 agonist efficacy. Results AM1710 (0.1, 1 or 5 mg/kg i.p. suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB2 antagonist AM630 (3 mg/kg i.p., but not the CB1 antagonist AM251 (3 mg/kg i.p., consistent with a CB2-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p. failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action. Conclusions Our results indicate that activation of cannabinoid CB2 receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB2 receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents.

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.

Capacity Building for Sustainable Marine Research in the Asia-Pacific Region

Science.gov (United States)

Hu, Liuming; Avril, Bernard; Zhang, Jing

2013-01-01

An international workshop on capacity building (CB) for marine research in the Asia-Pacific region (http://www.imber.info/index.php/Science/Working-Groups/Capacity-Building/2012-CB-Workshop) was held at the East China Normal University (ECNU), in Shanghai, China. The workshop brought together about 20 marine researchers and CB experts from 14 countries to discuss CB experiences, assess regional CB needs, and consider recommendations to improve regional CB, which would be of interest to other groups and other geographical regions.

Road safety policy of the European Union.

NARCIS (Netherlands)

2013-01-01

The European Union (EU) is important for national road safety policies. The EU has several policymaking instruments, such as binding regulations and directives, and non-binding recommendations. An important element in the EU policy plans on road safety are the non-binding European road safety

Fiscal policy surveillance in the enlarged European Union: Procedural checks or simple arithmetic?

NARCIS (Netherlands)

Groenendijk, Nico; Batten, Jonathan A.; Kearney, Colm

2006-01-01

In its recommendation on the 2004 update of the Broad Economic Policy Guidelines (BEPGs), the European Commission (2004) issued country-specific recommendations for fiscal policy in the Central and Eastern European (CEE) countries that have recently joined the European Union (EU) (henceforth the

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.

Improving tsunami resiliency: California's Tsunami Policy Working Group

Science.gov (United States)

Real, Charles R.; Johnson, Laurie; Jones, Lucile M.; Ross, Stephanie L.; Kontar, Y.A.; Santiago-Fandiño, V.; Takahashi, T.

2014-01-01

California has established a Tsunami Policy Working Group to facilitate development of policy recommendations for tsunami hazard mitigation. The Tsunami Policy Working Group brings together government and industry specialists from diverse fields including tsunami, seismic, and flood hazards, local and regional planning, structural engineering, natural hazard policy, and coastal engineering. The group is acting on findings from two parallel efforts: The USGS SAFRR Tsunami Scenario project, a comprehensive impact analysis of a large credible tsunami originating from an M 9.1 earthquake in the Aleutian Islands Subduction Zone striking California’s coastline, and the State’s Tsunami Preparedness and Hazard Mitigation Program. The unique dual-track approach provides a comprehensive assessment of vulnerability and risk within which the policy group can identify gaps and issues in current tsunami hazard mitigation and risk reduction, make recommendations that will help eliminate these impediments, and provide advice that will assist development and implementation of effective tsunami hazard risk communication products to improve community resiliency.

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

Transition from Spin Dewetting to continuous film in spin coating of Liquid Crystal 5CB.

Science.gov (United States)

Dhara, Palash; Bhandaru, Nandini; Das, Anuja; Mukherjee, Rabibrata

2018-05-08

Spin dewetting refers to spontaneous rupture of the dispensed solution layer during spin coating, resulting in isolated but periodic, regular sized domains of the solute and is pre-dominant when the solute concentration (C n ) is very low. In this article we report how the morphology of liquid crystal (LC) 5CB thin films coated on flat and patterned PMMA substrate transform from spin dewetted droplets to continuous films with increase in C n . We further show that within the spin dewetted regime, with gradual increase in the solute concentration, periodicity of the isotropic droplets (λ D ) as well as their mean diameter (d D ), gradually decreases, till the film becomes continuous at a critical concentration (C n *). Interestingly, the trend that λ D reduces with increase in C n is exact opposite to what is observed in thermal/solvent vapor induced dewetting of a thin film. The spin dewetted droplets exhibit transient Radial texture, in contrast to Schlieren texture observed in elongated threads and continuous films of 5CB, which remains in the Nematic phase at room temperature. Finally we show that by casting the film on a grating patterned substrate it becomes possible to align the spin dewetted droplets along the contours substrate patterns.

Rural Development Policy: Promises Made and Promises Denied.

Science.gov (United States)

Hyman, Drew

1991-01-01

Presents historical trends toward rural development policy. Describes the agrarian perspective and the industrial and urbanization perspective as current visions which guide policy. Recommends a new vision focusing on "livability for people" and "viability of community systems." (KS)

(Nuclear) energy policy in future

International Nuclear Information System (INIS)

1982-01-01

With this report the German Federal Diet submits the final results of the opinion-forming and decision-making process concerning the recommendations made by the investigation committee 'Future Nuclear Energy Policy' in June 1980. By means of this report it is intended to point out to an interested public the difficult and time-consuming process of parliamentary decision-making. This report is also to be seen as the final opinion delivered on the recommendations made by the investigation committee. The recommendations were to continue to pursue the peaceful use of nuclear energy, the necessity and technical justifiability of which had basically been approved by all parliamentary groups. In view of the import of the subject and in recognition of the work done by the investigation committee, the German Parliament has thoroughly discussed the report and has reviewed the analyses and recommendations in conjunction with other political fields to be considered. One part of the recommendations was taken up almost unanimously. As far as the safety of nuclear installations is concerned, the investigation committee could not submit any new findings which would give reasons for modifying the hitherto positive assessment of the safety of nuclear installations. The recommendations of the investigation committee mainly referred to the decision-making process in the field of energy policy which will effect the next decade. What fundamental decisions are to be made until when was pointed out as well as the findings and experience to be made until then. (orig./HP) [de

Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers.

Science.gov (United States)

Zuurman, Lineke; Passier, Paul C C M; de Kam, Marieke L; Kleijn, Huub J; Cohen, Adam F; van Gerven, Joop M A

2010-11-01

An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.

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

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...

Implementing evidence-based policy in a network setting: road safety policy in the Netherlands.

Science.gov (United States)

Bax, Charlotte; de Jong, Martin; Koppenjan, Joop

2010-01-01

In the early 1990s, in order to improve road safety in The Netherlands, the Institute for Road Safety Research (SWOV) developed an evidence-based "Sustainable Safety" concept. Based on this concept, Dutch road safety policy, was seen as successful and as a best practice in Europe. In The Netherlands, the policy context has now changed from a sectoral policy setting towards a fragmented network in which safety is a facet of other transport-related policies. In this contribution, it is argued that the implementation strategy underlying Sustainable Safety should be aligned with the changed context. In order to explore the adjustments needed, two perspectives of policy implementation are discussed: (1) national evidence-based policies with sectoral implementation; and (2) decentralized negotiation on transport policy in which road safety is but one aspect. We argue that the latter approach matches the characteristics of the newly evolved policy context best, and conclude with recommendations for reformulating the implementation strategy.

Special: Highlighting the past 50 years of the energy industry and energy policy in Germany. A retrospect on the occasion of the 50th anniversary of the journal ''et''

International Nuclear Information System (INIS)

Czaikainski, M.; Heck, H.; Lamprecht, F.

2000-01-01

The special contribution is a documentation (with many pictures) highlighting developments in energy policy and energy industry, from the postwar period in the young Federal Republic of Germany until today. The documentation focuses on the following aspects: 1. The postwar and reconstruction period. 2. Restructurization of the energy sector. 3. The energy economy in the wake of oil price explosions. 4. Growing awareness of environmental impacts and shattered public acceptance of technology in the focus of interest. 5. Globalisation, sustainable energy policy and greenhouse gas mitigation. (CB) [de

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.

Pb-Pb dating of individual chondrules from the CB_a 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....

European Policies to Promote Children's Rights and Combat Child Poverty.

Science.gov (United States)

Sandbæk, Mona

2017-07-26

The upbringing of children relies heavily on shared responsibilities between parents and society. The Council of Europe Recommendation (2006) 19 on Policy to Support Positive Parenting and the European Commission Recommendation (2013) Investing in Children: Breaking the Cycle of Disadvantage, both aim at supporting parents to care and provide for their children in accordance with the UN Convention on the Rights of the Child. By means of a document analysis this article examines what kind of parental practices and provision to parents the recommendations suggest to safeguard children's rights in the family. Three findings are highlighted: first, both recommendations reflect a commitment to respecting children's rights while at the same time acknowledging parents as children's primary caregivers. Second, both recognize parents' rights to work, while also recognizing the necessity of adequate income support if work is not available or income too low. Third, adequate resources are defined as a combination of universal policies and services, which guarantee a minimum level for all, and targeted measures reaching out to the most disadvantaged. The recommendations' emphasis on children and parents as partners and on the families' economic situations are valuable for future development of family and child policy and support programs.

Naturally occurring radioactivity in the Nordic countries. Recommendations

International Nuclear Information System (INIS)

2000-01-01

In the publication 'Naturally Occurring Radiation in the Nordic Countries - Recommendations' published in 1986 the radiation protection authorities in Denmark, Finland, Iceland, Norway and Sweden gave radiation protection recommendations for natural radiation in the Nordic countries. The exposure of the populations in the Nordic countries to natural radiation sources is among the highest in the world and much effort has been devoted during the last 10 to 20 years to characterising, assessing and, where feasible, to reduce these exposures. The exposure of workers to natural radiation sources has also been an important area of work in the same period. During this period the international recommendations on radiation protection policy have been further developed with ICRP Publication 60: '1990 Recommendations of the International Commission on Radiological Protection', and ICRP Publication 65: 'Protection Against Radon-222 at Home and at Work'. The European Basic Safety Standards Directive from 1996 (96/29/EURATOM), which is based on the ICRP recommendations, differs from the earlier versions in that special provisions have been laid down concerning exposure to natural radiation sources. As Denmark, Finland and Sweden are members of European Union and the EFTA-countries (Iceland and Norway) have close co-operation with the EU, the practical implementation of the EU-BSS will play an important role in all the Nordic countries. In November 1998, a new Drinking Water Directive, 98/83/EC, was adopted. The directive also includes radioactivity in drinking water, excluding potassium-40, radon, and radon decay products. Altogether this means that the Nordic recommendations from 1986 for natural radiation needed to be updated. The Nordic Radiation Protection Authorities therefore decided to set up a working group with the aim of revising the recommendations from 1986. The new revised recommendations will, as before, only deal with the components of the exposure to natural

A Conceptual Framework for Evolving, Recommender Online Learning Systems

Science.gov (United States)

Peiris, K. Dharini Amitha; Gallupe, R. Brent

2012-01-01

A comprehensive conceptual framework is developed and described for evolving recommender-driven online learning systems (ROLS). This framework describes how such systems can support students, course authors, course instructors, systems administrators, and policy makers in developing and using these ROLS. The design science information systems…

Targeting the Endocannabinoid/CB1 Receptor System For Treating Major Depression Through Antidepressant Activities of Curcumin and Dexanabinol-Loaded Solid Lipid Nanoparticles

Directory of Open Access Journals (Sweden)

Xiaolie He

2017-08-01

Full Text Available Background/Aims: This study investigated the underlying mechanisms of the antidepressant effects of curcumin and dexanabinol-loaded solid lipid nanoparticles in corticosterone-induced cell and mice depression models. Methods: Curcumin and dexanabinol-loaded solid lipid nanoparticles (Cur/SLNs-HU-211 were synthesized via an emulsifcation and low-temperature solidification method. Antidepressant activities of nanoparticles in a corticosterone-induced major depression model were investigated by MTT assay, cellular uptake by flow cytometry, behaviour by Forced Swimming Test and rotarod test, neurotransmitters by High Performance Liquid Chromatography, Western blotting, qPCR and immunofluorescence. Results: Treatment with Cur/SLNs-HU-211 induced greater dopamine (DA/5-hydroxytryptamine (5-HT release with reduced corticosterone-induced apoptotic cell death in PC12 cells. Additionally, in vivo Cur/SLNs-HU-211 significantly induced recovery from depressive behaviour with increased DA/5-HT levels, CB1 mRNA levels and CB1, p-MEK1 and p-ERK1/2 protein expression levels in the hippocampus and striatum. Cur/SLNs-HU-211 improved CB1 expression and inspired the proliferation of astrocytes in the hippocampus and striatum, exerted neuroprotective effects by preventing corticosterone -induced BDNF/NeuN expression reduction. Conclusion: Our study implies that Cur/SLNs-HU-211 may be a useful approach for treatment of major depression.

Some characteristics of two azoreductase systems in rat liver. Relevance to the activity of 2-[4'-di(2"-bromopropyl)-aminophenylazo]benzoic acid (CB10-252), a compound possessing latent cytotoxic activity

DEFF Research Database (Denmark)

Autrup, Herman; Warwick, Gerald P.

1975-01-01

-azoreductase was reduced by menadione (vitamin K3), cyanide and propylgallate. A diaphorase preparation from pig heart reduced both CB10-252 and methylred with both NADPH- and NADH-generating systems. The properties listed above and dependency of enzyme activity on both NADH and NADPH indicate a similarity of CB-10...

Staff immunisation: policy and practice in child care.

Science.gov (United States)

Spokes, Paula J; Ferson, Mark J; Ressler, Kelly-Anne

2011-08-01

The aims of this study were to determine the level of knowledge among child-care centre directors regarding the National Health and Medical Research Council (NHMRC) recommendations for the immunisation of child-care workers, the extent to which this knowledge was translated into practice and any organisational barriers to the development and implementation of staff immunisation policy. A cross-sectional survey, conducted in August 2006, in which a postal questionnaire was sent to a random sample of 784 NSW child-care centres. Centre directors were asked to complete the questionnaire on immunisation knowledge, policy and practice for the centre. A multivariate logistic-regression model was used to identify factors independently associated with centres with an immunisation policy for staff and centres that offered to pay all or part of the cost of vaccination of staff. Directors from 437 centres participated in the study for a response rate of 56%. Of these, 49% were aware of the NHMRC recommendations, and 57% had a staff immunisation policy in place. In the logistic regression model, centres with a written immunisation policy for staff were more likely to be aware of the NHMRC guidelines and offer long day care services. Centres that offered to pay all or part of the cost of immunisation for staff were more likely to be aware of the NHMRC guidelines, offer other child-care services and not operate for profit. Barriers to staff immunisation were related to the implementation of policy and included cost, time and access to information. The level of awareness of specific staff immunisation recommendations was relatively low. The transition of knowledge to policy was encouraging, although implementation of policies requires further commitment. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

An interagency space nuclear propulsion safety policy for SEI - Issues and discussion

Science.gov (United States)

Marshall, A. C.; Sawyer, J. C., Jr.

1991-01-01

An interagency Nuclear Safety Policy Working Group (NSPWG) was chartered to recommend nuclear safety policy, requirements, and guidelines for the Space Exploration Initiative nuclear propulsion program to facilitate the implementation of mission planning and conceptual design studies. The NSPWG developed a top level policy to provide the guiding principles for the development and implementation of the nuclear propulsion safety program and the development of Safety Functional Requirements. In addition, the NSPWG reviewed safety issues for nuclear propulsion and recommended top level safety requirements and guidelines to address these issues. Safety topics include reactor start-up, inadvertent criticality, radiological release and exposure, disposal, entry, safeguards, risk/reliability, operational safety, ground testing, and other considerations. In this paper the emphasis is placed on the safety policy and the issues and considerations that are addressed by the NSPWG recommendations.

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...

Recommendations from Inclusive Astronomy: Position Papers for The Decadal Survey

Science.gov (United States)

Coble, Kimberly A.; Inclusive Astronomy 2015 organizers

2018-06-01

In June 2015, 160 astronomers, sociologists, policy makers, and community leaders convened the first Inclusive Astronomy meeting at Vanderbilt University. The conference had a theme of intersectionality and was structured around four broad areas: (1) Eliminating Barriers to Access, (2) Creating Inclusive Environments, (3) Establishing a Community of Inclusive Practice, and (4) Policy, Power, and Leadership. From that meeting came the Nashville Recommendations, a road map for equity and inclusion in astronomy. At 41 pages long, the document is rich in topics for position papers relevant to the state of the profession section of the upcoming Decadal Survey. In this talk we will describe plans for position papers based on the recommendations relevant to various stake holders in the astronomical community, including funding agencies, professional societies, academic institutions, and other organizations. Feedback from Society members attending this session is encouraged.

Beyond Wishful Thinking: Integrating Consumer Preferences in the Assessment of Dietary Recommendations

Science.gov (United States)

2016-01-01

Convenience, taste, and prices are the main determinants of food choices. Complying with dietary recommendations therefore imposes a “taste cost” on consumers, potentially hindering adoption of those recommendations. The study presents and applies a new methodology, based on economic theory, to quantify this taste cost and assess the health and welfare effects of different dietary recommendations. Then, by comparison of those effects, we identify socially desirable recommendations that are most compatible with consumer preferences (i.e., that best balance health benefits against”taste cost”) and should be prioritized for promotion. The methodology proceeds in three-steps: first, an economic-behavioral model simulates how whole diets would change if consumers complied with dietary recommendations; second, an epidemiological model estimates the number of deaths avoided (DA) due to the dietary change; third, an efficiency analysis weighs the health benefits against the taste and policy costs of each recommendation. The empirical model is calibrated using French data. We find that recommendations to reduce consumption of red meat and soft-drinks, or raise consumption of milk products and fish/seafood impose relatively moderate taste costs. By comparison, recommendations related to F&V consumption and, to a lesser extent, butter/cream/cheese, snacks, and all meats impose larger taste costs on consumers. The F&V recommendation is the costliest for consumers to comply with, but it also reduces diet-related mortality the most, so that a large budget could be allocated to promoting F&V consumption while keeping this policy cost-beneficial. We conclude that promotion of most dietary recommendations improves social welfare. Our framework complements the programming models available in nutrition and public health: those models are best used to identify dietary targets, following which our framework identifies cost-beneficial ways of moving towards those targets. PMID

Beyond Wishful Thinking: Integrating Consumer Preferences in the Assessment of Dietary Recommendations.

Science.gov (United States)

Irz, Xavier; Leroy, Pascal; Réquillart, Vincent; Soler, Louis-Georges

2016-01-01

Convenience, taste, and prices are the main determinants of food choices. Complying with dietary recommendations therefore imposes a "taste cost" on consumers, potentially hindering adoption of those recommendations. The study presents and applies a new methodology, based on economic theory, to quantify this taste cost and assess the health and welfare effects of different dietary recommendations. Then, by comparison of those effects, we identify socially desirable recommendations that are most compatible with consumer preferences (i.e., that best balance health benefits against"taste cost") and should be prioritized for promotion. The methodology proceeds in three-steps: first, an economic-behavioral model simulates how whole diets would change if consumers complied with dietary recommendations; second, an epidemiological model estimates the number of deaths avoided (DA) due to the dietary change; third, an efficiency analysis weighs the health benefits against the taste and policy costs of each recommendation. The empirical model is calibrated using French data. We find that recommendations to reduce consumption of red meat and soft-drinks, or raise consumption of milk products and fish/seafood impose relatively moderate taste costs. By comparison, recommendations related to F&V consumption and, to a lesser extent, butter/cream/cheese, snacks, and all meats impose larger taste costs on consumers. The F&V recommendation is the costliest for consumers to comply with, but it also reduces diet-related mortality the most, so that a large budget could be allocated to promoting F&V consumption while keeping this policy cost-beneficial. We conclude that promotion of most dietary recommendations improves social welfare. Our framework complements the programming models available in nutrition and public health: those models are best used to identify dietary targets, following which our framework identifies cost-beneficial ways of moving towards those targets.

Beyond Wishful Thinking: Integrating Consumer Preferences in the Assessment of Dietary Recommendations.

Directory of Open Access Journals (Sweden)

Xavier Irz

Full Text Available Convenience, taste, and prices are the main determinants of food choices. Complying with dietary recommendations therefore imposes a "taste cost" on consumers, potentially hindering adoption of those recommendations. The study presents and applies a new methodology, based on economic theory, to quantify this taste cost and assess the health and welfare effects of different dietary recommendations. Then, by comparison of those effects, we identify socially desirable recommendations that are most compatible with consumer preferences (i.e., that best balance health benefits against"taste cost" and should be prioritized for promotion. The methodology proceeds in three-steps: first, an economic-behavioral model simulates how whole diets would change if consumers complied with dietary recommendations; second, an epidemiological model estimates the number of deaths avoided (DA due to the dietary change; third, an efficiency analysis weighs the health benefits against the taste and policy costs of each recommendation. The empirical model is calibrated using French data. We find that recommendations to reduce consumption of red meat and soft-drinks, or raise consumption of milk products and fish/seafood impose relatively moderate taste costs. By comparison, recommendations related to F&V consumption and, to a lesser extent, butter/cream/cheese, snacks, and all meats impose larger taste costs on consumers. The F&V recommendation is the costliest for consumers to comply with, but it also reduces diet-related mortality the most, so that a large budget could be allocated to promoting F&V consumption while keeping this policy cost-beneficial. We conclude that promotion of most dietary recommendations improves social welfare. Our framework complements the programming models available in nutrition and public health: those models are best used to identify dietary targets, following which our framework identifies cost-beneficial ways of moving towards those

Sugars and Dental Caries: Evidence for Setting a Recommended Threshold for Intake123

Science.gov (United States)

Moynihan, Paula

2016-01-01

Dental caries affects ≤80% of the world’s population with almost a quarter of US adults having untreated caries. Dental caries is costly to health care and negatively affects well-being. Dietary free sugars are the most important risk factor for dental caries. The WHO has issued guidelines that recommend intake of free sugars should provide ≤10% of energy intake and suggest further reductions to caries risk, which showed evidence of moderate quality from cohort studies that limiting free sugars to ≤10% of energy reduced, but did not eliminate, dental caries. Even low levels of dental caries in children are of concern because caries is a lifelong progressive and cumulative disease. The systematic review therefore explored if there were further benefits to dental health if the intake of free sugars was limited to caries when free sugar intake was 5% but ≤10% of energy. The WHO recommendations are intended for use by policy makers as a benchmark when assessing intake of sugars by populations and as a driving force for policy change. Multiple strategies encompassing both upstream and downstream preventive approaches are now required to translate the recommendations into policy and practice. PMID:26773022

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...

An integrated policy framework for the sustainable exploitation of biomass for bioenergy from marginal lands

Science.gov (United States)

Panoutsou, Calliope

2017-04-01

Currently, there are not sufficiently tailored policies focusing on biomass and bioenergy from marginal lands. This paper will provide an integrated policy framework and recommendations to facilitate understanding for the market sectors involved and the key principles which can be used to form future sustainable policies for this issue. The work will focus at EU level policy recommendations and discuss how these can interrelate with national and regional level policies to promote the usage of marginal lands for biomass and bioenergy. Recommended policy measures will be based on the findings of the Biomass Policies (www.biomasspolicies.eu) and S2Biom (www.s2biom.eu) projects and will be prepared taking into account the key influencing factors (technical, environmental, social and economic) on biomass and bioenergy from marginal lands: • across different types of marginality (biophysical such as: low temperature, dryness, excess soil moisture, poor chemical properties, steep slope, etc., and socio-economic resulting from lack of economic competitiveness in certain regions and crops, abandonment or rural areas, etc.) • across the different stages of the biomass value chain (supply, logistics, conversion, distribution and end-use). The aim of recommendations will be to inform policy makers on how to distinguish key policy related attributes across biomass and bioenergy from marginal lands, measure them and prioritise actions with a 'system' based approach.

Sugars and Dental Caries: Evidence for Setting a Recommended Threshold for Intake.

Science.gov (United States)

Moynihan, Paula

2016-01-01

Dental caries affects ≤80% of the world's population with almost a quarter of US adults having untreated caries. Dental caries is costly to health care and negatively affects well-being. Dietary free sugars are the most important risk factor for dental caries. The WHO has issued guidelines that recommend intake of free sugars should provide ≤10% of energy intake and suggest further reductions to caries risk, which showed evidence of moderate quality from cohort studies that limiting free sugars to ≤10% of energy reduced, but did not eliminate, dental caries. Even low levels of dental caries in children are of concern because caries is a lifelong progressive and cumulative disease. The systematic review therefore explored if there were further benefits to dental health if the intake of free sugars was limited to caries when free sugar intake was 5% but ≤10% of energy. The WHO recommendations are intended for use by policy makers as a benchmark when assessing intake of sugars by populations and as a driving force for policy change. Multiple strategies encompassing both upstream and downstream preventive approaches are now required to translate the recommendations into policy and practice. © 2016 American Society for Nutrition.

Early implementation of WHO recommendations for the retention of health workers in remote and rural areas.

Science.gov (United States)

Buchan, James; Couper, Ian D; Tangcharoensathien, Viroj; Thepannya, Khampasong; Jaskiewicz, Wanda; Perfilieva, Galina; Dolea, Carmen

2013-11-01

The maldistribution of health workers between urban and rural areas is a policy concern in virtually all countries. It prevents equitable access to health services, can contribute to increased health-care costs and underutilization of health professional skills in urban areas, and is a barrier to universal health coverage. To address this long-standing concern, the World Health Organization (WHO) has issued global recommendations to improve the rural recruitment and retention of the health workforce. This paper presents experiences with local and regional adaptation and adoption of WHO recommendations. It highlights challenges and lessons learnt in implementation in two countries - the Lao People's Democratic Republic and South Africa - and provides a broader perspective in two regions - Asia and Europe. At country level, the use of the recommendations facilitated a more structured and focused policy dialogue, which resulted in the development and adoption of more relevant and evidence-based policies. At regional level, the recommendations sparked a more sustained effort for cross-country policy assessment and joint learning. There is a need for impact assessment and evaluation that focus on the links between the rural availability of health workers and universal health coverage. The effects of any health-financing reforms on incentive structures for health workers will also have to be assessed if the central role of more equitably distributed health workers in achieving universal health coverage is to be supported.

CB1 Receptor-Mediated Signaling Underlies the Hippocampal Synaptic, Learning and Memory Deficits Following Treatment with JWH-081, a New Component of Spice/K2 Preparations

OpenAIRE

Basavarajappa, Balapal S.; Subbanna, Shivakumar

2014-01-01

Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as “Spice” or “K2” to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of “Spice/K2”, including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of...

The recurrent PPP1CB mutation p.Pro49Arg in an additional Noonan-like syndrome individual: Broadening the clinical phenotype.

Science.gov (United States)

Bertola, Débora; Yamamoto, Guilherme; Buscarilli, Michelle; Jorge, Alexander; Passos-Bueno, Maria Rita; Kim, Chong

2017-03-01

We report on a 12-year-old Brazilian boy with the p.Pro49Arg mutation in PPP1CB, a novel gene associated with RASopathies. This is the fifth individual described, and the fourth presenting the same variant, suggesting a mutational hotspot. Phenotypically, he also showed the same hair pattern-sparse, thin, and with slow growing-, similar to the typical ectodermal finding observed in Noonan syndrome-like disorder with loose anagen hair. Additionally, he presented craniosynostosis, a rare clinical finding in RASopathies. This report gives further support that this novel RASopathy-PPP1CB-related Noonan syndrome with loose anagen hair-shares great similarity to Noonan syndrome-like disorder with loose anagen hair, and expands the phenotypic spectrum by adding the cranial vault abnormality. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

What should be done about policy on alcohol pricing and promotions? Australian experts' views of policy priorities: a qualitative interview study.

Science.gov (United States)

Fogarty, Andrea S; Chapman, Simon

2013-06-25

Alcohol policy priorities in Australia have been set by the National Preventative Health Task Force, yet significant reform has not occurred. News media coverage of these priorities has not reported public health experts as in agreement and Government has not acted upon the legislative recommendations made. We investigate policy experts' views on alcohol policy priorities with a view to establishing levels of accord and providing suggestions for future advocates. We conducted semi-structured in depth interviews with alcohol policy experts and advocates around Australia. Open-ended questions examined participants' thoughts on existing policy recommendations, obvious policy priorities and specifically, the future of national reforms to price and promotions policies. All transcripts were analysed for major themes and points of agreement or disagreement. Twenty one alcohol policy experts agreed that pricing policies are a top national priority and most agreed that "something should be done" about alcohol advertising. Volumetric taxation and minimum pricing were regarded as the most important price policies, yet differences emerged in defining the exact form of a proposed volumetric tax. Important differences in perspective emerged regarding alcohol promotions, with lack of agreement about the preferred form regulations should take, where to start and who the policy should be directed at. Very few discussed online advertising and social networks. Despite existing policy collaborations, a clear 'cut through' message is yet to be endorsed by all alcohol control advocates. There is a need to articulate and promote in greater detail the specifics of policy reforms to minimum pricing, volumetric taxation and restrictions on alcohol advertising, particularly regarding sporting sponsorships and new media.

National neonatal weight policy survey.

LENUS (Irish Health Repository)

Walsh, B

2012-02-01

This survey was conducted to review the current practice regarding frequency of weight measurement in neonatal units in the Republic of Ireland, and whether these practices are in keeping with best practice as described in the literature. There was an 88.5% (23 of 26) response rate to this survey. 6 (26%) units had a written policy, and 16 (70%) had an unwritten agreed practice. In the Vermont Oxford Network\\'s potentially better practices daily weight measurements on newborn infants are recommended until the infant is stable and growing and then alternate day measurements The most common practices in this survey were to weigh infants on alternate days, this occurred in 9 (39%) units, and twice weekly in 6 (26%). Less than 31% of units had a separate policy for those less than 30 weeks, on assisted ventilation, or transitioning to enteral feeds. Most weigh infants on alternate days, and plot weights weekly, which is in keeping with best practice. Few units have separate policies for specific subgroups as is recommended in the limited literature. Consensus guidelines should be developed and promoted nationally.

National neonatal weight policy survey.

LENUS (Irish Health Repository)

Walsh, B

2009-06-01

This survey was conducted to review the current practice regarding frequency of weight measurement in neonatal units in the Republic of Ireland, and whether these practices are in keeping with best practice as described in the literature. There was an 88.5% (23 of 26) response rate to this survey. 6 (26%) units had a written policy, and 16 (70%) had an unwritten agreed practice. In the Vermont Oxford Network\\'s potentially better practices daily weight measurements on newborn infants are recommended until the infant is stable and growing and then alternate day measurements The most common practices in this survey were to weigh infants on alternate days, this occurred in 9 (39%) units, and twice weekly in 6 (26%). Less than 31% of units had a separate policy for those less than 30 weeks, on assisted ventilation, or transitioning to enteral feeds. Most weigh infants on alternate days, and plot weights weekly, which is in keeping with best practice. Few units have separate policies for specific subgroups as is recommended in the limited literature. Consensus guidelines should be developed and promoted nationally.

The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis

Directory of Open Access Journals (Sweden)

RICARDO N FELMER

2004-01-01

Full Text Available The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1 transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or loss

Improving Youth Employment Policies in Francophone Africa | IDRC ...

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

Africa's persistent job crisis calls for more effective employment policies, including training programs and support for job searches. This project will address the crisis through recommendations that will improve employment policies in francophone Africa. Youth employment initiatives in Africa Over the last two decades, ...

TogoDoc server/client system: smart recommendation and efficient management of life science literature.

Directory of Open Access Journals (Sweden)

Wataru Iwasaki

Full Text Available In this paper, we describe a server/client literature management system specialized for the life science domain, the TogoDoc system (Togo, pronounced Toe-Go, is a romanization of a Japanese word for integration. The server and the client program cooperate closely over the Internet to provide life scientists with an effective literature recommendation service and efficient literature management. The content-based and personalized literature recommendation helps researchers to isolate interesting papers from the "tsunami" of literature, in which, on average, more than one biomedical paper is added to MEDLINE every minute. Because researchers these days need to cover updates of much wider topics to generate hypotheses using massive datasets obtained from public databases or omics experiments, the importance of having an effective literature recommendation service is rising. The automatic recommendation is based on the content of personal literature libraries of electronic PDF papers. The client program automatically analyzes these files, which are sometimes deeply buried in storage disks of researchers' personal computers. Just saving PDF papers to the designated folders makes the client program automatically analyze and retrieve metadata, rename file names, synchronize the data to the server, and receive the recommendation lists of newly published papers, thus accomplishing effortless literature management. In addition, the tag suggestion and associative search functions are provided for easy classification of and access to past papers (researchers who read many papers sometimes only vaguely remember or completely forget what they read in the past. The TogoDoc system is available for both Windows and Mac OS X and is free. The TogoDoc Client software is available at http://tdc.cb.k.u-tokyo.ac.jp/, and the TogoDoc server is available at https://docman.dbcls.jp/pubmed_recom.

TogoDoc server/client system: smart recommendation and efficient management of life science literature.

Science.gov (United States)

Iwasaki, Wataru; Yamamoto, Yasunori; Takagi, Toshihisa

2010-12-13

In this paper, we describe a server/client literature management system specialized for the life science domain, the TogoDoc system (Togo, pronounced Toe-Go, is a romanization of a Japanese word for integration). The server and the client program cooperate closely over the Internet to provide life scientists with an effective literature recommendation service and efficient literature management. The content-based and personalized literature recommendation helps researchers to isolate interesting papers from the "tsunami" of literature, in which, on average, more than one biomedical paper is added to MEDLINE every minute. Because researchers these days need to cover updates of much wider topics to generate hypotheses using massive datasets obtained from public databases or omics experiments, the importance of having an effective literature recommendation service is rising. The automatic recommendation is based on the content of personal literature libraries of electronic PDF papers. The client program automatically analyzes these files, which are sometimes deeply buried in storage disks of researchers' personal computers. Just saving PDF papers to the designated folders makes the client program automatically analyze and retrieve metadata, rename file names, synchronize the data to the server, and receive the recommendation lists of newly published papers, thus accomplishing effortless literature management. In addition, the tag suggestion and associative search functions are provided for easy classification of and access to past papers (researchers who read many papers sometimes only vaguely remember or completely forget what they read in the past). The TogoDoc system is available for both Windows and Mac OS X and is free. The TogoDoc Client software is available at http://tdc.cb.k.u-tokyo.ac.jp/, and the TogoDoc server is available at https://docman.dbcls.jp/pubmed_recom.

Building sustainable policy framework for transport development: A review of national transport policy initiatives in Nigeria

Directory of Open Access Journals (Sweden)

Sumaila A.F.

2013-06-01

Full Text Available This paper is concerned with building a sustainable policy framework for transport development in Nigeria. Its objective is to review the country’s transport policy initiatives in order to understand the extent to which it addresses Nigeria’s mobility and transportation problems. From published materials and official government documents and files, the study identifies four national policy initiatives which are reviewed and analysed with regard to their context, contents, and consequences. The study reveals that while the policy initiatives could be said to be adequate and comprehensive in terms of their context and contents, the major challenge is implementation of recommended solutions. The study therefore provides a general checklist to guide policy direction, while advocating for policy-based researches and empirical studies in order to provide the data base for formulation of a sustainable national transport policy for Nigeria.

Energy policies of IEA Countries. The Netherlands 1996 review

International Nuclear Information System (INIS)

1996-01-01

As part of the IEA's on-going analysis of Member countries' energy policies, this review assess the Netherlands and offers recommendations taking account of major reforms announced by the Dutch Government in December 1995. The prominence of environmental objectives in Dutch energy policy and the widespread use of voluntary long-term agreements with industry provide constructive lessons for other countries. Targets for energy efficiency and renewability are especially ambitious. Moreover, the Dutch Government has made an important contribution to environmental policy by striving for a combination of market liberalization and a sustainable energy economy. The review recommends that market reforms be further developed, if necessary in the context of developments in European energy market policy. Gas pricing and a tendency for over-capacity to develop in the electricity sector are particular areas of discussion in the report. The review also draws attention to potentially high economic costs which may arise form energy-environment policies and affect the competitiveness of Dutch industry. (author). 18 figs., 13 tabs

Probiotics and prebiotics: prospects for public health and nutritional recommendations

NARCIS (Netherlands)

Sanders, Mary Ellen; Lenoir-Wijnkoop, Irene; Salminen, Seppo; Merenstein, Daniel J.; Gibson, Glenn R.; Petschow, Bryon W.; Nieuwdorp, Max; Tancredi, Daniel J.; Cifelli, Christopher J.; Jacques, Paul; Pot, Bruno

2014-01-01

Probiotics and prebiotics are useful interventions for improving human health through direct or indirect effects on the colonizing microbiota. However, translation of these research findings into nutritional recommendations and public health policy endorsements has not been achieved in a manner

Application of HTA research on policy decision-making.

Science.gov (United States)

Youngkong, Sitaporn

2014-05-01

This article provides an overview of the potential uses of health technology assessment (HTA) in health technology or health intervention-related policy decision-making. It summarises the role of HTA in policy planning, health system investment, price negotiation, development of clinical practice guidelines, and communication with health professionals. While the multifaceted nature of HTA means that some aspects of the data can result in conflicting conclusions, the comprehensive approach of HTA is still recommended. To help minimise the potential conflicts within HTA data, a multicriteria decision analysis (MCDA) approach is recommended as a way to assess a number of decision criteria simultaneously. A combination of HTA with MCDA allows policy decision-making to be undertaken in an empirically rigorous and rational way. This combination can be used to support policy decision-makers in Thailand and help them prioritise topics for assessment and make informed health benefit package coverage decisions. This approach enhances the legitimacy of policy decisions by increasing the transparency, systematic nature, and inclusiveness of the process.

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.

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.

HEALTH OCCUPATIONS SUPPORTIVE TO NURSING, A STATEMENT OF POLICIES AND RECOMMENDATIONS.

Science.gov (United States)

American Nurses' Association, New York, NY.

TO SOLVE THE NURSING PERSONNEL SHORTAGE, THE AMERICAN NURSES' ASSOCIATION RECOMMENDED--(1) THE FIRST PRIORITY FOR FEDERAL MONIES FOR TRAINING HEALTH WORKERS FOR NURSING SERVICES SHOULD BE TO PREPARE REGISTERED NURSES FOR TEACHING, SUPERVISION, AND ADMINISTRATION, (2) A CONCERTED EFFORT SHOULD BE MADE TO RECRUIT YOUNG PEOPLE AND TO ATTRACT INACTIVE…

Policy Pathways: Monitoring, Verification and Enforcement

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-07-01

The IEA estimates that, if implemented globally without delay, the 25 IEA Energy Efficiency recommendations could save 8.2 Gt CO2 per year by 2030. Yet many governments struggle with their implementation and thus miss a great part of the energy efficiency potential. The new IEA series Policy Pathways: Showing the way to energy efficiency implementation now aims to assist countries with improving energy efficiency policies. It features practical 'how-to' guides for designing, implementing and evaluating energy efficiency policies and achieving greater improvement.

Policy Pathways: Monitoring, Verification and Enforcement

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-07-01

The IEA estimates that, if implemented globally without delay, the 25 IEA Energy Efficiency recommendations could save 8.2 Gt CO2 per year by 2030. Yet many governments struggle with their implementation and thus miss a great part of the energy efficiency potential. The new IEA series Policy Pathways: Showing the way to energy efficiency implementation now aims to assist countries with improving energy efficiency policies. It features practical 'how-to' guides for designing, implementing and evaluating energy efficiency policies and achieving greater improvement.

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)

Positron emission tomography based analysis of long-circulating cross-linked triblock polymeric micelles in a U87MG mouse xenograft model and comparison of DOTA and CB-TE2A as chelators of copper-64.

Science.gov (United States)

Jensen, Andreas I; Binderup, Tina; Kumar EK, Pramod; Kjær, Andreas; Rasmussen, Palle H; Andresen, Thomas L

2014-05-12

Copolymers of ABC-type (PEG-PHEMA-PCMA) architecture were prepared by atom transfer radical polymerization and formulated as micelles with functionalizable primary alcohols in the shell-region (PHEMA-block) to which the metal-ion chelators DOTA or CB-TE2A were conjugated. Using this micelle system we compared the in vivo stabilities of DOTA and CB-TE2A as chelators of (64)Cu in micelle nanoparticles. The coumarin polymer (PCMA-block) micelle core was cross-linked by UV irradiation at 2 W/cm(2) for 30 min. The cross-linked micelles were labeled with (64)Cu at room temperature for 2 h (DOTA) or 80 °C for 3 h (CB-TE2A), giving labeling efficiencies of 60-76% (DOTA) and 40-47% (CB-TE2A). (64)Cu-micelles were injected into tumor-bearing mice (8 mg/kg) and PET/CT scans were carried out at 1, 22, and 46 h postinjection. The micelles showed good blood stability (T1/2: 20-26 h) and tumor uptake that was comparable with other nanoparticle systems. The DOTA micelles showed a biodistribution similar to the CB-TE2A micelles and the tumor uptake was comparable for both micelle types at 1 h (1.9% ID/g) and 22 h (3.9% ID/g) but diverged at 46 h with 3.6% ID/g (DOTA) and 4.9% ID/g (CB-TE2A). On the basis of our data, we conclude that cross-linked PEG-PHEMA-PCMA micelles have long circulating properties resulting in tumor accumulation and that DOTA and CB-TE2A (64)Cu-chelates show similar in vivo stability for the studied micelle system.

Political implications of US nuclear-export-policy development

International Nuclear Information System (INIS)

Johnson-Freese, J.S.

1981-01-01

There has been a great deal of international debate regarding how effective strict export controls on nuclear-energy supplies are toward a non-proliferation goal. With the Carter Administration, the debate was heightened by a new, more-vigorous US nuclear-export policy, much of which was codified by the Nuclear Non-Proliferation Act of 1978 (NNPA). Because of the US position in both the international non-proliferation regime and nuclear export market, the NNPA has had far-reaching consequences. The thesis of this paper is that a nuclear-export policy that fails to consider its short-term ramifications, as the NNPA has been accused of, will be self-defeating. If the US wants a viable worldwide nuclear non-proliferation policy, it must first direct its efforts toward building a domestic non-proliferation consensus, and then worldwide, rather than first setting a highly controversial policy and expecting other nations to fall into line. This work provides a comprehensive case study of US nuclear-export policy between the years 1976 to 1980 in support of the thesis. Further, the behavior and impact of the interest groups which seem to shape US nuclear-export policies is examined, and recommendations made regarding the role of groups in nuclear policy-making and implementation. Finally, recommendations are made regarding non-proliferation policy for the future, as it relates to nuclear exports

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

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.

2015 SUMMING-UP OF BANKING FINANCIAL SECTOR OF THE REPUBLIC OF MOLDOVA

Directory of Open Access Journals (Sweden)

Rodica PERCIUN

2016-01-01

Full Text Available Economic and political uncertainty in recent years has adversely affected the activity of Moldovan banks unfavoring the dynamics of the national economy. The 2015 year can be considered a "rigid" year for the Republic of Moldova, built by the liquidation of three financial institutions at the NBM decision (CB "Unibank" SA, CB "Banca Sociala" SA and BC "Banca de Economii" SA, and the tightening of the monetary policy. That has led to mistrust of the population in this sector, creating problems with bank loans and deteriorating of bank asset. However, commercial banks during 2015 remained sufficiently liquid and capitalized (exception is CB "Unibank" SA, CB "Banca Sociala" SA and BC "Banca de Economii" SA. This article aims to research the financial and banking sector from the Republic of Moldova in 2015 in terms of uncertainty. Therefore, the novelty of the article lies in the analysis of the banking sector from the Republic of Moldova under the main financial prudential indicators. The main research methods were: systemic analysis, synthesis, monographic, logic, etc. The main scientific results obtained in the article, as a conclusion of the research are the identification, analysis of the main activity of the banking sector and the proposed set of recommendations on strengthening the financial stability framework in the Republic of Moldova.

Evaluation of policies to promote physical activity in afterschool programs: are we meeting current benchmarks?

Science.gov (United States)

Beets, Michael W; Rooney, Laura; Tilley, Falon; Beighle, Aaron; Webster, Collin

2010-01-01

Policies now recommend afterschool programs (ASP, 3-6 pm) provide children a minimum amount of physical activity daily. We examined the extent to which children attending ASPs meet existing national and state-level policies that specify expected levels of physical activity (PA). Accelerometer-derived physical activity (light and moderate-to-vigorous, MVPA) of 253 children (5-13 years) was compared to policies that recommend varying amounts of PA children should achieve during an ASP. The proportion of children achieving a policy ranged from 0.0% (California 60 min MVPA and North Carolina 20% of daily program time devoted to MVPA), 1.2% (California 30 min MVPA), to 48.2% (National Afterschool Association 30 min light plus MVPA). Random effects logistic models indicated boys (odds ratio [OR] range 2.0 to 6.27) and children from a minority background (Black/Hispanic, OR range 1.87 to 3.98) were more likely to achieve a recommended level of physical activity, in comparison to girls and White children. Neither age nor BMI were related to achieving a policy. The PA of children attending ASP falls below policy recommended levels; however, these policies were developed in absence of data on expected PA levels during ASPs. Thus, concerted effort towards building a stronger ASP evidence-base for policy refinement is required. Copyright © 2010 Elsevier Inc. All rights reserved.

Regulation of Hippocampal Cannabinoid CB1 Receptor Actions by Adenosine A1 Receptors and Chronic Caffeine Administration: Implications for the Effects of Δ9-Tetrahydrocannabinol on Spatial Memory

OpenAIRE

Sousa, Vasco C; Assaife-Lopes, Natália; Ribeiro, Joaquim A; Pratt, Judith A; Brett, Ros R; Sebastião, Ana M

2010-01-01

Abstract The cannabinoid CB1 receptor-mediated modulation of ?-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A1 receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A1 receptors localized in GABAergic cells do not directly influence GABA release. CB1 and A1 receptors are the main targets for the effects of two of the most heavily consumed ps...

Energy policies of IEA countries: Belgium

International Nuclear Information System (INIS)

1997-01-01

The report contains a comprehensive in-depth assessment of the energy policies of Belgium, including recommendations on future policy. Belgium has been successful in phasing out the exploitation of its high-cost and uncompetitive coal, without major social problems. To enhance its energy supplies, it has developed a nuclear industry based on a high level of technology and promoted natural gas imports. The electricity and gas industries are highly concentrated and integrated, in many cases preventing competition from working to benefit consumers. Structural reforms in the electricity and gas markets are required to create competitive, efficient, and flexible markets. The report also recommends that responsibilities transferred from the federal government to the three governments need to be harmonized, especially those concerning climate change

What should be done about policy on alcohol pricing and promotions? Australian experts’ views of policy priorities: a qualitative interview study

Science.gov (United States)

2013-01-01

Background Alcohol policy priorities in Australia have been set by the National Preventative Health Task Force, yet significant reform has not occurred. News media coverage of these priorities has not reported public health experts as in agreement and Government has not acted upon the legislative recommendations made. We investigate policy experts’ views on alcohol policy priorities with a view to establishing levels of accord and providing suggestions for future advocates. Methods We conducted semi-structured in depth interviews with alcohol policy experts and advocates around Australia. Open-ended questions examined participants’ thoughts on existing policy recommendations, obvious policy priorities and specifically, the future of national reforms to price and promotions policies. All transcripts were analysed for major themes and points of agreement or disagreement. Results Twenty one alcohol policy experts agreed that pricing policies are a top national priority and most agreed that “something should be done” about alcohol advertising. Volumetric taxation and minimum pricing were regarded as the most important price policies, yet differences emerged in defining the exact form of a proposed volumetric tax. Important differences in perspective emerged regarding alcohol promotions, with lack of agreement about the preferred form regulations should take, where to start and who the policy should be directed at. Very few discussed online advertising and social networks. Conclusions Despite existing policy collaborations, a clear ‘cut through’ message is yet to be endorsed by all alcohol control advocates. There is a need to articulate and promote in greater detail the specifics of policy reforms to minimum pricing, volumetric taxation and restrictions on alcohol advertising, particularly regarding sporting sponsorships and new media. PMID:23800324

EURRECA: development of tools to improve the alignment of micronutrient recommendations

NARCIS (Netherlands)

Matthys, C.; Bucchini, L.; Busstra, M.C.; Cavelaars, A.J.E.M.; Eleftheriou, P.; Garcia-Alvarez, A.; Fairweather-Tait, S.; Gurinovic, M.; Ommen, van B.; Contor, L.

2010-01-01

Approaches through which reference values for micronutrients are derived, as well as the reference values themselves, vary considerably across countries. Harmonisation is needed to improve nutrition policy and public health strategies. The EURRECA (EURopean micronutrient RECommendations Aligned,

Mediation in matters of environmental policy and industrial project planning. Theory and case reports; Umweltmediation in Theorie und Anwendung