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Sample records for partnering gluing contracts

  1. The Process of Partnering; Gluing Contracts, Organising and Financing together

    DEFF Research Database (Denmark)

    Koch, Christian; Thuesen, Christian; Gottlieb, Stefan

    2005-01-01

    This paper discusses management of partnering projects where construction companies and clients cooperate in developing buildings and services. Taking a practice based theory and political process approach, partnering is seen as an example of a complex project operation, characterised by processual...... level these elements is continuously mobilized, negotiated and stabilized in their intersection with the practices and skill basis for the project. It is thus shown how incentives becomes especially problematic for the architects due to tensions between new and old contractual forms, and that project...... management levels are more successful in one case in mediating between operations and governance frames than in the other The research imply that the governance frame and the operations of the projects are mutually interacting throughout the projects, in contrast to the traditional sequential phase breakdown...

  2. Partnering and contracting

    DEFF Research Database (Denmark)

    Bohnstedt, Kristian Ditlev

    2014-01-01

    Purpose - Partnering is often, by economists, and construction managerial literature related to more incomplete contracts. This can be explained by seeing partnering as something that neutralizes opportunism. The aim is to uncover whether partnering neutralizes opportunism when there is an incomp...

  3. Intercomparison campaign of Contracted Partner Institutes 1997

    International Nuclear Information System (INIS)

    Reinen, H.A.J.M.; Tijsmans, M.H.; Van Tuinen, S.T.; Overwater, R.M.W.; Aldenkamp, F.J.

    1998-01-01

    The Dutch National Plan for Nuclear Emergency Planning and Response (EPR) is trained frequently. Intercomparison campaigns and exercises are part of this training for the Contracted Partner Institutes (CPI). The results of an intercomparison campaign in 1997 for the CPI are reported. Two carbon cartridges, one contaminated homogeneously and one inhomogeneously with 131 I, and a water sample contaminated with 134 Cs and 137 Cs were analysed by means of gamma spectroscopy. The results had to be faxed to RIVM within the time limits prescribed in the emergency protocols for CPI, i.e. 2 hours for the cartridges and 24 hours for the water sample. Most CPI reported in time. The results for the inhomogeneously contaminated cartridge are within 25% from the accepted reference value (ARV). For the homogeneously contaminated cartridge the results are within 40% from the ARV. In reality, the contamination of the cartridge will have an exponential profile, with most of the activity in the first few millimeters. In this situation results can be expected to be within 20% from the true value. The results for the water sample are within 5% from the ARV. Although most CPI have applied corrections for coincidence summing for 134 Cs there is still a systematic error of 4% for this nuclide. In regard of the requirements for measurements during emergency situations, the results of this intercomparison campaign are satisfactory

  4. U.S., European ALMA Partners Award Prototype Antenna Contracts

    Science.gov (United States)

    2000-03-01

    The U.S. and European partners in the Atacama Large Millimeter Array (ALMA) project have awarded contracts to U.S. and Italian firms, respectively, for two prototype antennas. ALMA is a planned telescope array, expected to consist of 64 millimeter-wave antennas with 12-meter diameter dishes. The array will be built at a high-altitude, extremely dry mountain site in Chile's Atacama desert, and is scheduled to be completed sometime in this decade. On February 22, 2000, Associated Universities Inc. (AUI) signed an approximately $6.2 million contract with Vertex Antenna Systems, of Santa Clara, Calif., for construction of one prototype ALMA antenna. AUI operates the U.S. National Radio Astronomy Observatory (NRAO) for the National Science Foundation under a cooperative agreement. The European partners contracted with the consortium of European Industrial Engineering and Costamasnaga, of Mestre, Italy, on February 21, 2000, for the production of another prototype. (Mestre is located on the inland side of Venice.) The two antennas must meet identical specifications, but will inherently be of different designs. This will ensure that the best possible technologies are incorporated into the final production antennas. Only one of the designs will be selected for final production. Several technical challenges must be met for the antennas to perform to ALMA specifications. Each antenna must have extremely high surface accuracy (25 micrometers, or one-third the diameter of a human hair, over the entire 12-meter diameter). This means that, when completed, the surface accuracy of the ALMA dishes will be 20 times greater than that of the Very Large Array (VLA) antennas, and about 50 times greater than dish antennas for communications or radar. The ALMA antennas must also have extremely high pointing accuracy (0.6 arcseconds). An additional challenge is that the antennas, when installed at the ALMA site in Chile, will be exposed to the ravages of weather at 16,500 feet (5000 meters

  5. Best intentions: Lessons learned on international partnering and alliance contracts

    International Nuclear Information System (INIS)

    Farrell, S.; McDermott, J.R.; Ramsay, A.; Watzke, J.

    1996-01-01

    Although the energy industry is still in the early stages of partnering and alliancing, there is enough accumulated experience to be worth sharing information on what has worked and what has not. This paper explores the lessons learned in six agreements in the UK, the US, and the Middle East. It concludes that not all projects are potential candidates for partnering or alliances. Those likely to be successful will contain common characteristics of complexity, uncertainty, technology and duration. Management structure is moving towards integrated teams, although projects currently fall along a broad spectrum before becoming truly integrated. The risk/reward structure is becoming more complex over time, although it is unclear that tinkering with percentage sharing schemes will actually change the behavior of project participants and result in additional cost savings. The use of team building techniques and facilitators may well enhance the alliance implementation, but the choice of both company and individual members is fundamental to success. The overriding success factor, however, is the setting of fair and achievable targets. All of the managers surveyed stated that their projects benefited from the use of a partnering or alliance structure. Three of the projects were far enough along to cite significant cost savings. Although some in the industry are still doubtful that alliances can make a true difference to a project's outcome, those who have participated are convinced they have achieved results which would have been unattainable in a traditional structure. They would add, however, that partnering and alliancing is not easy, and not for all projects. The industry must share practical information if significant learning is to occur

  6. To tender, re-negotiate or partner: Strategies for contracting service companies

    International Nuclear Information System (INIS)

    Gouldie, T.A.

    1994-01-01

    The contracting of oilfield service companies by petroleum exploration and production operating companies is different than the contracting of civil engineering, construction or other project-oriented contractors. The relationship between operating companies and oilfield service companies has had a long and unique history which has evolved since the first oil wells were drilled over a century ago. The process of contracting service companies by operating companies for petroleum exploration and production work can be split into three distinct stages: (1) decide what it is that should be contracted out and what should be kept in house; (2) determine the method to use to select the contractor(s) to perform the work; and (3) agree to the contractual structure to best reflect the relationship the operating company and the service company with to initiate and maintain. As there are ongoing changes to the business structures and corporate thinking of both operating and service companies, there are also evolving changes to what are considered core businesses and the methods of selecting and contracting service companies by operating companies. Operating companies are recognizing the high costs of tendering for contractor services in terms of personnel time and administrative effort, and are relying more on negotiating and rolling-over existing contracts with their suitable, capable contractors. Partnering, in its many forms and levels, is increasingly being recognized as a useful method to get better work done at cheaper overall costs

  7. Managing Projects with the Public, -bringing Partnering, Contracts and Financing together in Building Public Services

    DEFF Research Database (Denmark)

    Koch, Christian

    2004-01-01

    of opportunity shows that on the operational level the contractual, financial and skill basis for the project has to be mobilized, negotiated, partly stabilized and renegotiated. The participating actors thus have to develop a new set of skills in dealing with municipalities and managing operations in PPPs....... of projects have had trouble to develop. The paper views PPP as an interaction between an emergent governance frame and operational activities in the project. PPP is an element of a networked public sector and the paper takes a network and political process approach to the shaping of PPP in Denmark....... It is analysed how the governance frame for these type of projects constituted a window of opportunity in the late nineties for “sale and lease back” arrangements, combined with partnering and more traditional design-build contracts. A case of a municipality renewing its school services, exploiting this window...

  8. Intercomparison Contracted Partner Institutes for Nuclear Emergency 2007; Ringonderzoek waakvlaminstituten kernongevallenbestrijding 2007

    Energy Technology Data Exchange (ETDEWEB)

    Overwater-van Buuren, R.M.W.; Glastra, P.; Tukker, K.

    2009-07-01

    The quality of the so-called Contracted Partner Institutes (CPI's) is amply complying with the objectives. Nonetheless, some desirable improvements remain, especially issues concerning the calibration of the measuring equipment. These issues emerged during an investigation performed by RIVM, in which the quality of the analysis of water and air samples was tested. In the Netherlands there are eight CPI's, evenly spread across the country, who can inform the government about radioactivity in air and water. The CPIs are part of the Dutch National Plan for Nuclear Emergency Planning and Response, which has been drawn up after the nuclear disaster in Chernobyl. RIVM is coordinating the activities of the CPI's. The Contracted Partner Institutes are tested on a two-yearly base by way of intercomparisons. In these intercomparisons, testing is done on both the timely reporting of the results and on the agreement with the reference value within pre-defined boundaries. Most CPI's were able to deliver the air results within two hours, and the water results within 24 hours. The results of the air samples for one institute were outside the pre-defined boundaries. Four samples were prepared for the intercomparison: an aerosol filter, a charcoal filter, a charcoal cartridge and a water sample. All four contained radionuclides characteristic for nuclear accidents. [Dutch] De kwaliteit van de zogeheten Waakvlaminstituten (WVI's) voldoet in 2007 ruimschoots aan de doelstellingen. Wel zijn enkele verbeteringen wenselijk, vooral op het gebied van kalibratie van de meetopstellingen. Dit blijkt uit onderzoek van het RIVM waarin de kwaliteit is getest van de analyse van water- en luchtmonsters. In Nederland bestaan er verspreid over het land acht WVI's die bij een kernongeval de overheid informeren over radioactiviteit in lucht en water. De WVI's zijn een onderdeel van het Nationaal Plan Kernongevallenbestrijding (NPK), dat is opgesteld enkele jaren na

  9. ALMA Partners Award Prototype Antenna Contracts in Europe and the USA

    Science.gov (United States)

    2000-03-01

    The European and U.S. partners in the Atacama Large Millimeter Array (ALMA) project have awarded contracts to firms in Italy and the USA, respectively, for two prototype antennas. ALMA is a planned telescope array, expected to consist of 64 millimeter-wave antennas with 12-meter diameter dishes, cf. ESO Press Release 09/99 and ESO PR Video Clip 08/99. The array will be built at a high-altitude, extremely dry mountain site in Chile's Atacama desert, and is scheduled to be completed sometime in this decade. The European partners contracted with the consortium of European Industrial Engineering and Costamasnaga (Mestre, Italy), on February 21, 2000, for the production of one prototype ALMA antenna. On February 22, 2000, Associated Universities Inc. signed a contract with Vertex Antenna Systems (Santa Clara, California), for construction of another prototype antenna. The two antennas must meet identical specifications, but will inherently be of different designs. This will ensure that the best possible technologies are incorporated into the final production antennas. Several technical challenges must be met for the antennas to perform to ALMA specifications. Each antenna must have extremely high surface accuracy (25 µm, or one-third the diameter of a human hair, over the entire 12-meter diameter). This means that, when completed, the surface accuracy of the ALMA dishes will be 20 times greater than that of the Very Large Array (VLA) antennas near Socorro (New Mexico, USA), and about 50 times greater than dish antennas for communications or radar. The ALMA antennas must also have extremely high pointing accuracy (0.6 arcseconds). An additional challenge is that the antennas, when installed at the ALMA site in Chile, will be exposed to the ravages of weather at 5000 m elevation. All previous millimeter-wavelength antennas that meet such exacting specifications for surface accuracy and pointing accuracy have been housed within telescope enclosures. The U.S. and European

  10. Glued structural members

    Science.gov (United States)

    Russell C. Moody; Jen Y. Liu

    1999-01-01

    Glued structural members are manufactured in a variety of configurations. Structural composite lumber (SCL) products consist of small pieces of wood glued together into sizes common for solid-sawn lumber. Glued-laminated timber (glulam) is an engineered stress-rated product that consists of two or more layers of lumber in which the grain of all layers is oriented...

  11. When do they care to share? : How manufacturers make contracted service partners share knowledge

    NARCIS (Netherlands)

    de Vries, J.; Schepers, J.; van Weele, A.; van der Valk, W.

    2014-01-01

    Manufacturing firms that outsource customer-facing services, risk losing touch with their customers and thereby forfeit valuable market and customer-related knowledge. To maintain informed and competitive, the manufacturer's customer-facing service partners should engage in knowledge sharing and

  12. When do they care to share? : how manufacturers make contracted service partners share knowledge

    NARCIS (Netherlands)

    Vries, de J.J.A.P.; Schepers, J.J.L.; Weele, van A.J.; Valk, van der W.

    2014-01-01

    Manufacturing firms that outsource customer-facing services, risk losing touch with their customers and thereby forfeit valuable market and customer-related knowledge. To maintain informed and competitive, the manufacturer's customer-facing service partners should engage in knowledge sharing and

  13. The autonomy of the contracting partner. An argument for heuristic contractarian business ethics

    NARCIS (Netherlands)

    de Graaf, G.

    2006-01-01

    Due to the domain characteristics of business ethics, a contractarian theory for business ethics will need to be essentially different from the contract model as it is applied to other domains. Much of the current criticism of contractarian business ethics (CBE) can be traced back to autonomy, one

  14. Skeletal muscle excitation-contraction coupling: who are the dancing partners?

    Science.gov (United States)

    Rebbeck, Robyn T; Karunasekara, Yamuna; Board, Philip G; Beard, Nicole A; Casarotto, Marco G; Dulhunty, Angela F

    2014-03-01

    There is an overwhelming body of work supporting the idea that excitation-contraction coupling in skeletal muscle depends on a physical interaction between the skeletal muscle isoform of the dihydropyridine receptor L-type Ca(2+) channel and the skeletal isoform of the ryanodine receptor Ca(2+) release channel. A general assumption is that this physical interaction is between "critical" residues that have been identified in the II-III loop of the dihydropyridine receptor alpha subunit and the ryanodine receptor. However, despite extensive searches, the complementary "critical" residues in the ryanodine receptor have not been identified. This raises the possibility that the coupling proceeds either through other subunits of the dihydropyridine receptor and/or other co-proteins within the large RyR1 protein complex. There have been some remarkable advances in recent years in identifying proteins in the RyR complex that impact on the coupling process, and these are considered in this review. A major candidate for a role in the coupling mechanism is the beta subunit of the dihydropyridine receptor, because specific residues in both the beta subunit and ryanodine receptor have been identified that facilitate an interaction between the two proteins and these also impact on excitation-contraction coupling. This role of beta subunit remains to be fully investigated as well as the degree to which it may complement any other direct or indirect voltage-dependent coupling interactions between the DHPR alpha II-III loop and the ryanodine receptor. Copyright © 2014. Published by Elsevier Ltd.

  15. Ionotropic glutamate receptors (iGluRs) of the delta family (GluD1 ...

    African Journals Online (AJOL)

    ... such as Neurexin1. This review presents current knowledge regarding the expression, structure and function of Glu delta receptors (GluD1, GluD2) in brain, focusing on synapse formation, function and dysfunction. Keywords: iGluRs; GluD1; GluD2; Synaptogenesis; Autism spectrum disorder (ASD); Schizophrenia (SCZ) ...

  16. mGluR5

    DEFF Research Database (Denmark)

    Mølck, Christina; Harpsøe, Kasper; Gloriam, David E

    2014-01-01

    Since its discovery in 1992, mGluR5 has attracted significant attention and been linked to several neurological and psychiatric diseases. Ligand development was initially focused on the orthosteric binding pocket, but lack of subtype selective ligands changed the focus to the transmembrane...... allosteric binding pocket. This strategy has resulted in several drug candidates in clinical testing. In the present article we explore the orthosteric and allosteric binding pockets in terms of structure and ligand recognition across the mGluR subtypes and groups, and discuss the clinical potential...... of ligands targeting these pockets. We have performed binding mode analyses of non- and group-selective orthosteric ligands based on molecular docking in mGluR crystal structures and models. For the analysis of the allosteric binding pocket we have combined data from all mGluR5-mutagenesis studies...

  17. Ionotropic glutamate receptors (iGluRs of the delta family (GluD1 and GluD2 and synaptogenesis

    Directory of Open Access Journals (Sweden)

    Muhammad Zahid Khan

    2017-08-01

    Full Text Available Glutamate delta-1 (GluD1 and glutamate delta-2 (GluD2 form the delta family of ionotropic glutamate receptors (iGluRs and are distinct from other (iGluRs in that they do not exhibit typical agonist-induced ion channel currents. Recent studies have demonstrated a crucial role of the delta receptors in synapse formation by interacting with presynaptic proteins such as Neurexin1. This review presents current knowledge regarding the expression, structure and function of Glu delta receptors (GluD1, GluD2 in brain, focusing on synapse formation, function and dysfunction.

  18. Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.

    Directory of Open Access Journals (Sweden)

    Lotta von Ossowski

    Full Text Available Recent studies indicate that glutamatergic signaling involves, and is regulated by, thiol modifying and redox-active compounds. In this study, we examined the role of a reactive cysteine residue, Cys-893, in the cytosolic C-terminal tail of GluA1 AMPA receptor as a potential regulatory target. Elimination of the thiol function by substitution of serine for Cys-893 led to increased steady-state expression level and strongly reduced interaction with SAP97, a major cytosolic interaction partner of GluA1 C-terminus. Moreover, we found that of the three cysteine residues in GluA1 C-terminal tail, Cys-893 is the predominant target for S-nitrosylation induced by exogenous nitric oxide donors in cultured cells and lysates. Co-precipitation experiments provided evidence for native association of SAP97 with neuronal nitric oxide synthase (nNOS and for the potential coupling of Ca2+-permeable GluA1 receptors with nNOS via SAP97. Our results show that Cys-893 can serve as a molecular target for regulatory thiol modifications of GluA1 receptors, including the effects of nitric oxide.

  19. Ionotropic glutamate receptors (iGluRs) of the delta family (GluD1 ...

    African Journals Online (AJOL)

    Muhammad Zahid Khan

    2016-10-20

    Oct 20, 2016 ... GluD1 knockout mice (GluD1 KO) have normal learning in the Morris water maze .... could bind and activate the receptor.5,6 D-Ser and glycine have now been identified as .... English editing of this manuscript. References. 1.

  20. Negotiating Efficient PPP Contracts

    DEFF Research Database (Denmark)

    Tvarnø, Christina D.

    . An opportunity the member states should consider using when procuring a PPP. This paper looks at the negotiation and contracting of a PPP in an economic theoretical and EU public procurement perspective and discusses how to establish an efficient PPP contract under a strong public law doctrine. Governments......This paper concerns Public Private Partnership (PPP) contracts in concern to the coming new 2014/24IEU public procurement directive. The new EU public procurement directive gives the public authority the opportunity to negotiate PPPs much more when they are implemented in national law...... procurement law. Furthermore, the paper seeks to establish a connection between public law, private law and the efficient PPP contract by drawing upon economic theory and empirical contract data from UK, US and Danish partnering contracts from the construction industry and the aim of contracting joint utility...

  1. An adventitious interaction of filamin A with RhoGDI2(Tyr153Glu)

    International Nuclear Information System (INIS)

    Song, Mia; He, Qianjing; Berk, Benjamin-Andreas; Hartwig, John H.; Stossel, Thomas P.; Nakamura, Fumihiko

    2016-01-01

    Filamin A (FLNA) is an actin filament crosslinking protein with multiple intracellular binding partners. Mechanical force exposes cryptic FLNA binding sites for some of these ligands. To identify new force-dependent binding interactions, we used a fusion construct composed of two FLNA domains, one of which was previously identified as containing a force-dependent binding site as a bait in a yeast two-hybrid system and identified the Rho dissociation inhibitor 2 (RhoGDI2) as a potential interacting partner. A RhoGDI2 truncate with 81 N-terminal amino acid residues and a phosphomimetic mutant, RhoGDI(Tyr153Glu) interacted with the FLNA construct. However, neither wild-type or full-length RhoGDI2 phosphorylated at Y153 interacted with FLNA. Our interpretation of these contradictions is that truncation and/or mutation of RhoGDI2 perturbs its conformation to expose a site that adventitiously binds FLNA and is not a bona–fide interaction. Therefore, previous studies reporting that a RhoGDI(Y153E) mutant suppresses the metastasis of human bladder cancer cells must be reinvestigated in light of artificial interaction of this point mutant with FLNA. - Highlights: • RhoGDI2 is identified as a potential filamin A (FLNA)-binding partner. • Phosphomimetic mutant, RhoGDI2(Tyr153Glu) interacts with FLNA. • RhoGDI2 phosphorylated (Tyr153) by src kinase does not interact with FLNA. • Mutation of Tyr-153 to Glu of RhoGDI2 does not mimic phosphorylation. • RhoGDI2(Tyr153Glu) provokes an adventitious interaction with FLNA.

  2. An adventitious interaction of filamin A with RhoGDI2(Tyr153Glu)

    Energy Technology Data Exchange (ETDEWEB)

    Song, Mia; He, Qianjing [Hematology Division, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston MA (United States); Berk, Benjamin-Andreas [Faculty of Veterinary Medicine and Faculty of Biosciences and Pharmacy, University of Leipzig, Leipzig (Germany); Hartwig, John H.; Stossel, Thomas P. [Hematology Division, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston MA (United States); Nakamura, Fumihiko, E-mail: fnakamura@partners.org [Hematology Division, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston MA (United States)

    2016-01-15

    Filamin A (FLNA) is an actin filament crosslinking protein with multiple intracellular binding partners. Mechanical force exposes cryptic FLNA binding sites for some of these ligands. To identify new force-dependent binding interactions, we used a fusion construct composed of two FLNA domains, one of which was previously identified as containing a force-dependent binding site as a bait in a yeast two-hybrid system and identified the Rho dissociation inhibitor 2 (RhoGDI2) as a potential interacting partner. A RhoGDI2 truncate with 81 N-terminal amino acid residues and a phosphomimetic mutant, RhoGDI(Tyr153Glu) interacted with the FLNA construct. However, neither wild-type or full-length RhoGDI2 phosphorylated at Y153 interacted with FLNA. Our interpretation of these contradictions is that truncation and/or mutation of RhoGDI2 perturbs its conformation to expose a site that adventitiously binds FLNA and is not a bona–fide interaction. Therefore, previous studies reporting that a RhoGDI(Y153E) mutant suppresses the metastasis of human bladder cancer cells must be reinvestigated in light of artificial interaction of this point mutant with FLNA. - Highlights: • RhoGDI2 is identified as a potential filamin A (FLNA)-binding partner. • Phosphomimetic mutant, RhoGDI2(Tyr153Glu) interacts with FLNA. • RhoGDI2 phosphorylated (Tyr153) by src kinase does not interact with FLNA. • Mutation of Tyr-153 to Glu of RhoGDI2 does not mimic phosphorylation. • RhoGDI2(Tyr153Glu) provokes an adventitious interaction with FLNA.

  3. Social Partners

    DEFF Research Database (Denmark)

    Tikkanen, Tarja; Hansen, Leif Emil; Guðmundsson, Bernharður

    2012-01-01

    based on a survey carried out in the Nordic countries in the regie of Nordic Council of Ministries the article deals with the role of social partners in senior and older workers policies and practises......based on a survey carried out in the Nordic countries in the regie of Nordic Council of Ministries the article deals with the role of social partners in senior and older workers policies and practises...

  4. Banking contracts

    OpenAIRE

    Durčáková, Klára

    2010-01-01

    Resumé - Bank Contracts Bank Contracts are an integral part of our everyday lives. Citizen and bussines entities used bank contracts very often. Despite this fact we can't find legal definition in the Czech law. Banking contracts understand contracts that are signed by banks in their business activities and obligations under these contracts arise. While the banking contracts have been widely used, in Czech law there is not too much literature and judgements abou this issue. Lack of legislatio...

  5. PARTNER Project

    CERN Multimedia

    Ballantine, A; Dixon-Altaber, H; Dosanjh, M; Kuchina, L

    2011-01-01

    Hadrontherapy uses particle beams to treat tumours located near critical organs and tumours that respond poorly to conventional radiation therapy. It has become evident that there is an emerging need for reinforcing research in hadrontherapy and it is essential to train professionals in this rapidly developing field. PARTNER is a 4-year Marie Curie Training project funded by the European Commission with 5.6 million Euros aimed at the creation of the next generation of experts. Ten academic institutes and research centres and two leading companies are participating in PARTNER, that is coordinated by CERN, forming a unique multidisciplinary and multinational European network. The project offers research and training opportunities to 25 young biologists, engineers, physicians and physicists and is allowing them to actively develop modern techniques for treating cancer in close collaboration with leading European Institutions. For this purpose PARTNER relies on cutting edge research and technology development, ef...

  6. Lateral testing of glued laminated timber tudor arch

    Science.gov (United States)

    Douglas R. Rammer; Philip Line

    2016-01-01

    Glued laminated timber Tudor arches have been in wide use in the United States since the 1930s, but detailed knowledge related to seismic design in modern U.S. building codes is lacking. FEMA P-695 (P-695) is a methodology to determine seismic performance factors for a seismic force resisting system. A limited P-695 study for glued laminated timber arch structures...

  7. Presynaptic mGlu1 and mGlu5 autoreceptors facilitate glutamate exocytosis from mouse cortical nerve endings.

    Science.gov (United States)

    Musante, Veronica; Neri, Elisa; Feligioni, Marco; Puliti, Aldamaria; Pedrazzi, Marco; Conti, Valerio; Usai, Cesare; Diaspro, Alberto; Ravazzolo, Roberto; Henley, Jeremy M; Battaglia, Giuseppe; Pittaluga, Anna

    2008-09-01

    The effects of mGlu1 and mGlu5 receptor activation on the depolarization-evoked release of [3H]d-aspartate ([3H]D-ASP) from mouse cortical synaptosomes were investigated. The mGlu1/5 receptor agonist 3,5-DHPG (0.1-100microM) potentiated the K+(12mM)-evoked [3H]D-ASP overflow. The potentiation occurred in a concentration-dependent manner showing a biphasic pattern. The agonist potentiated [3H]D-ASP exocytosis when applied at 0.3microM; the efficacy of 3,5-DHPG then rapidly declined and reappeared at 30-100microM. The fall of efficacy of agonist at intermediate concentration may be consistent with 3,5-DHPG-induced receptor desensitization. Facilitation of [3H]D-ASP exocytosis caused by 0.3microM 3,5-DHPG was prevented by the selective mGlu5 receptor antagonist MPEP, but was insensitive to the selective mGlu1 receptor antagonist CPCCOEt. In contrast, CPCCOEt prevented the potentiation by 50microM 3,5-DHPG, while MPEP had minimal effect. Unexpectedly, LY 367385 antagonized both the 3,5-DHPG-induced effects. A total of 0.3microM 3,5-DHPG failed to facilitate the K+-evoked [3H]D-ASP overflow from mGlu5 receptor knockout (mGlu5-/-) cortical synaptosomes, but not from nerve terminals prepared from the cortex of animals lacking the mGlu1 receptors, the crv4/crv4 mice. On the contrary, 50microM 3,5-DHPG failed to affect the [3H]D-ASP exocytosis from cortical synaptosomes obtained from crv4/crv4 and mGlu5-/-mice. Western blot analyses in subsynaptic fractions support the existence of both mGlu1 and mGlu5 autoreceptors located presynaptically, while immunocytochemistry revealed their presence at glutamatergic terminals. We propose that mGlu1 and mGlu5 autoreceptors exist on mouse glutamatergic cortical terminals; mGlu5 receptors may represent the "high affinity" binding sites for 3,5-DHPG, while mGlu1 autoreceptors represent the "low affinity" binding sites.

  8. The influence of Glu-1 and Glu-3 loci on dough rheology and bread-making properties in wheat (Triticum aestivum L.) doubled haploid lines.

    Science.gov (United States)

    Langner, Monika; Krystkowiak, Karolina; Salmanowicz, Bolesław P; Adamski, Tadeusz; Krajewski, Paweł; Kaczmarek, Zygmunt; Surma, Maria

    2017-12-01

    The major determinants of wheat quality are Glu-1 and Glu-3 glutenin loci and environmental factors. Additive effects of alleles at the Glu-1 and Glu-3 loci, as well as their interactions, were evaluated for dough rheology and baking properties in four groups of wheat doubled haploid lines differing in high- and low-molecular-weight glutenin composition. Flour quality, Reomixer (Reologica Instruments, Lund, Sweden), dough extension, Farinograph (Brabender GmbH, Duisburg, Germany) and baking parameters were determined. Groups of lines with the alleles Glu-A3b and Glu-B3d were characterized by higher values of dough and baking parameters compared to those with the Glu-A3e and Glu-B3a alleles. Effects of interactions between allelic variants at the Glu-1 and Glu-3 loci on Reomixer parameters, dough extension tests and baking parameters were significant, although additive effects of individual alleles were not always significant. The allelic variants at Glu-B3 had a much greater effect on dough rheological parameters than the variants at Glu-A3 or Glu-D3 loci. The effect of allelic variations at the Glu-D3 loci on rheological parameters and bread-making quality was non-significant, whereas their interactions with a majority of alleles at the other Glu-1 × Glu-3 loci were significant. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  9. Functional characterisation of homomeric ionotropic glutamate receptors GluR1-GluR6 in a fluorescence-based high throughput screening assay

    DEFF Research Database (Denmark)

    Strange, Mette; Bräuner-Osborne, Hans; Jensen, Anders A.

    2006-01-01

    We have constructed stable HEK293 cell lines expressing the rat ionotropic glutamate receptor subtypes GluR1(i), GluR2Q(i), GluR3(i), GluR4(i), GluR5Q and GluR6Q and characterised the pharmacological profiles of the six homomeric receptors in a fluorescence-based high throughput screening assay...... assay reported to date. We propose that high throughput screening of compound libraries at the six GluR-HEK293 cell lines could be helpful in the search for structurally and pharmacologically novel ligands acting at the receptors....

  10. Pharmacological properties of homomeric and heteromeric GluR1o and GluR3o receptors

    DEFF Research Database (Denmark)

    Nielsen, B S; Banke, T G; Schousboe, A

    1998-01-01

    Homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits GluR1o and GluR3o were expressed in Spodoptera frugiperda (Sf9) insect cells. Membranes containing the recombinant receptors showed a doublet of bands of the expected size (99-109 kDa) after...

  11. Partnering for Canada's nuclear future

    International Nuclear Information System (INIS)

    Koenderman, P.P.

    1997-01-01

    ''Partnering'' is an evolving relationship that could lead to a partnership or joint ownership. Babcock and Wilcox (BW) has used a variety of forms of contracting and partnering to develop global strategy for the supply of its products, both fossil and nuclear steam generating equipment. A strategic mix of consortia, strategic alliances and joint ventures has provided the impetus for BW to lead in worldwide market share in many categories, including the supply of nuclear replacement steam generators to the USA since 1992. The implication is that continuing cooperation with BW will benefit the Canadian nuclear industry. 6 refs., 12 figs

  12. Social Partners

    DEFF Research Database (Denmark)

    Hansen, Leif Emil

    2011-01-01

    The purpose of the paper is to present findings from a new Nordic survey on social partners’ policy and practice in regards older workers. The goal of the survey was to find out to what extent the social partners have developed policies and outlined strategies, which explicitly address the demogr...... lifelong learning and career development to their senior members during their last 15-20 years in working life. In this issue the social partners can and should play an active role – indeed, a leading role if needed – among the other key actors in society....... the demographic change and promote opportunities for lifelong learning and career development among their senior members (45+). Workforce in the Nordic countries tend to be highly organised – especially the older workers. The social partners’ involvement in the discussion of sustainable society...... and the contribution of lifelong learning to the needs and potential of older workers is crucial, as the demographic situation already today, and in particular the one to be expected within the next about 40 years, is historically without a precedent. The idea of continuous learning and the need for a meaningful work...

  13. Association between ALDH 2 Glu504Lys polymorphism and ...

    African Journals Online (AJOL)

    : a meta-analysis. Jiang Xinhua, Zhao Yanfei. Abstract. Background: The findings from studies on the relationship between aldehyde dehydrogenases(ALDH) gene Glu504Lys polymorphism and colorectal cancer(CRC) were inconsistent.

  14. Evidence of intralocus recombination at the Glu-3 loci in bread wheat (Triticum aestivum L.)

    Science.gov (United States)

    The low-molecular weight glutenin subunits (LMW-GSs) are a class of wheat seed storage proteins that play a critical role in the determination of wheat flour bread-making quality. These proteins are encoded by multigene families located at the orthologous Glu-3 loci (Glu-A3, Glu-B3 and Glu-D3), on t...

  15. Construction of a high affinity zinc binding site in the metabotropic glutamate receptor mGluR1

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Sheppard, P O; Jensen, L B

    2001-01-01

    a molecular model of the ATD of mGluR1 based on a weak amino acid sequence similarity with a bacterial periplasmic binding protein. The ATD consists of two globular lobes, which are speculated to contract from an "open" to a "closed" conformation following agonist binding. In the present study, we have...... created a Zn(2+) binding site in mGluR1b by mutating the residue Lys(260) to a histidine. Zinc acts as a noncompetitive antagonist of agonist-induced IP accumulation on the K260H mutant with an IC(50) value of 2 microm. Alanine mutations of three potential "zinc coligands" in proximity to the introduced...

  16. Polymorphic Contracts

    Science.gov (United States)

    Belo, João Filipe; Greenberg, Michael; Igarashi, Atsushi; Pierce, Benjamin C.

    Manifest contracts track precise properties by refining types with predicates - e.g., {x : Int |x > 0 } denotes the positive integers. Contracts and polymorphism make a natural combination: programmers can give strong contracts to abstract types, precisely stating pre- and post-conditions while hiding implementation details - for example, an abstract type of stacks might specify that the pop operation has input type {x :α Stack |not ( empty x )} . We formalize this combination by defining FH, a polymorphic calculus with manifest contracts, and establishing fundamental properties including type soundness and relational parametricity. Our development relies on a significant technical improvement over earlier presentations of contracts: instead of introducing a denotational model to break a problematic circularity between typing, subtyping, and evaluation, we develop the metatheory of contracts in a completely syntactic fashion, omitting subtyping from the core system and recovering it post facto as a derived property.

  17. Adhesion quality of glued joints from different commercial wood species

    Directory of Open Access Journals (Sweden)

    Alexandre Miguel do Nascimento

    2013-12-01

    Full Text Available The objective of this study was to determine the effect of wood density, adhesive type and gluing pressure on the shear strength of glued joints of fourteen commercial wood species. Wood pieces were classified in three density classes (Class 1: less than 0.55 g cm-3; Class 2: from 0.55 to 0.75 g cm-3; and Class 3: greater than 0.75 g cm-3 and joints bonded with two adhesives: polyvinyl acetate (PVA and urea-formaldehyde (UF, under two different pressures: 6 and 12 kgf cm-2. Glued joints bonded with PVA adhesive presented higher shear strength than those bonded with UF adhesive. For percentage of wood failure, the PVA adhesive had the best performance, however, only Classes 1 and 2 reached the values required by ASTM 3110 standard. Glued joints from Class 3, bonded with UF adhesive, did not reach the values of solid wood. The gluing pressure of 12 kgf cm-2 was more efficient for Class 3, for both shear strength and percentage of wood failure.

  18. Administrative contracts

    Directory of Open Access Journals (Sweden)

    Vukićević-Petković Milica

    2015-01-01

    Full Text Available Administrative contracts are a special type of contract where usually one of the contracting parties is a public law body and which is concluded for the performance of public service and the realization of a public interest. They go a long way since its inception to its eventual final acceptance of all the legal systems. One of the enduring characteristics of this type of contract is their disquised or unnoticed existence. This is why only monitoring their development may lead to a complete understanding of the importance and essence of this institution as well as the need for its complete legal regulation.

  19. Electrical contracting

    CERN Document Server

    Neidle, Michael

    2013-01-01

    Electrical Contracting, Second Edition is a nine-chapter text guide for the greater efficiency in planning and completing installations for the design, installation and control of electrical contracts. This book starts with a general overview of the efficient cabling and techniques that must be employed for safe wiring design, as well as the cost estimation of the complete electrical contract. The subsequent chapters are devoted to other electrical contracting requirements, including electronic motor control, lighting, and electricity tariffs. A chapter focuses on the IEE Wiring Regulations an

  20. Administrative contracts

    OpenAIRE

    Vukićević-Petković Milica

    2015-01-01

    Administrative contracts are a special type of contract where usually one of the contracting parties is a public law body and which is concluded for the performance of public service and the realization of a public interest. They go a long way since its inception to its eventual final acceptance of all the legal systems. One of the enduring characteristics of this type of contract is their disquised or unnoticed existence. This is why only monitoring their development may lead to a complete u...

  1. Managing Adaptation in Multi-Partner Collaboration: Role of Alliance Board

    OpenAIRE

    Barbic, Frano; Hidalgo Nuchera, Antonio

    2015-01-01

    Adaptation to changing circumstances is crucial for success of alliances. Using a longitudinal case study of the R&D non-equity multi-partner alliance between four partners, we examine how the alliance board can complement incomplete contracts for coordinated adaptation. We trace the interactions between the partners in order to explore the functioning of the alliance board in multi-partner alliances for coordinated adaptation. We found that alliance board can complement incomplete contract, ...

  2. Experimental studies of glued Aluminum-glass joints

    Science.gov (United States)

    Ligaj, B.; Wirwicki, M.; Karolewska, K.; Jasińska, A.

    2018-04-01

    Glued steel-glass or aluminum-glass joints are to be found, among other things, in vehicles (cars, buses, trains, trams) as windscreen assembly pieces for the supporting structure. For the purposes of the experiments, samples were made in which the top beam was made of the AW-2017A aluminum alloy and the bottom beam was made of thermally reinforced soda-lime glass whereas the glued joints were made of one-component polyurethane glue Körapur 175. The tests were performed under four-point bending conditions at monotonic incremental bending moment values on the Instron 5965 durability machine. The experimental study of the durability of glued joints under four-point bending conditions with the monotonic incremental bending moment allows to determine the values of stresses, whose value is related to initiation of damage of the tested joint.

  3. Heat Resistance of Glued Finger Joints in Spruce Wood Constructions

    Directory of Open Access Journals (Sweden)

    Martin Sviták

    2014-10-01

    Full Text Available The heat resistance of glued spruce wood was evaluated for different joint types and adhesives. Bending strength, modulus of elasticity, and also fracture evaluation were investigated on glued spruce samples made by the finger-jointed principle. Finger-jointed samples were glued with polyurethane (PUR and melamine-urea-formaldehyde (MUF adhesives. Heat loading was realized at temperatures 60, 80, and 110 °C and compared with wood with 20 °C. A static bending test with four-point flexural test was used. Elevated temperature and adhesive type had an important influence on the bending strength. On the other hand, adhesive type had a significant influence on the modulus of elasticity, but elevated temperature had no substantial influence.

  4. Comparison of kokumi γ-[Glu](n>1)-Val and γ-[Glu](n>1)-Met synthesized through transpeptidation catalyzed by glutaminase from Bacillus amyloliquefaciens.

    Science.gov (United States)

    Yang, Juan; Sun-Waterhouse, Dongxiao; Xie, Jin; Wang, Lan; Chen, Hong-Zhang; Cui, Chun; Zhao, Mouming

    2018-05-01

    A series of γ-[Glu] (n=2,3,4) -Val or γ-[Glu] (n=2,3,4) -Met were synthesized in the presence of donor (Gln) and corresponding acceptor (Val or Met) through transpeptidation catalyzed by the glutaminase from Bacillus amyloliquefaciens. Gln in excess significantly (p n>1) -Val/Met except for γ-Glu-Val/Met. The K m values for transpeptidase activity to yield γ-[Glu] (n=0,1,2,3) -Val increased with an elevated n, but remained essentially the same irrespective of n value for γ-[Glu] (n=0,1,2) -Met (which were 31-44% of that for γ-[Glu] 3 -Met). The highest K m value appearing when n = 3 (γ-[Glu] 3 -Val or γ-[Glu] 3 -Met) suggested the rising difficulty for synthesis when the number of donor increases. All the γ-[Glu] n -Val/Met substances exhibited kokumi properties and enhanced the continuity and umami taste of soy sauce as well as the thickness, mouthfulness and umaminess of model chicken broth. These results indicate the potential of the γ-[Glu] n -Val and γ-[Glu] n -Met as food flavor enhancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Neuroprotective activity of selective mGlu1 and mGlu5 antagonists in vitro and in vivo.

    Science.gov (United States)

    Szydlowska, Kinga; Kaminska, Bozena; Baude, Andrea; Parsons, Chris G; Danysz, Wojciech

    2007-01-05

    The neuroprotective potential of allosteric mGlu5 and mGlu1 antagonists such as 6-methyl-2-(phenylethynyl)-pyridin (MPEP)/[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), was tested in vitro in organotypic hippocampal cultures and in the middle cerebral artery occlusion model of stroke in vivo. Both classes of agent have high selectivity toward mGlu sub-types and are active in animal models of various diseases indicating satisfactory CNS penetration. In organotypic hippocampal cultures MPEP showed high neuroprotective potency against sub-chronic (12 days) insult produced by 3-NP with an IC50 of c.a. 70 nM. In contrast, although the mGlu1 antagonist EMQMCM was also protective, it seems to be weaker yielding an IC50 of c.a. 1 microM. Similarly, in the transient (90 min) middle cerebral artery occlusion model of ischaemia in rats, MTEP seems to be more effective than EMQMCM. MTEP, at 2.5 mg/kg and at 5 mg/kg provided 50 and 70% neuroprotection if injected 2 h after the onset of ischaemia. At a dose of 5 mg/kg, significant (50%) neuroprotection was also seen if the treatment was delayed by 4 h. EMQMCM was not protective at 5 mg/kg (given 2 h after occlusion) but at 10 mg/kg 50% of neuroprotection was observed. The present data support stronger neuroprotective potential of mGlu5 than mGlu1 antagonists.

  6. Interactions between Glu-1 and Glu-3 loci and associations of selected molecular markers with quality traits in winter wheat (Triticum aestivum L.) DH lines.

    Science.gov (United States)

    Krystkowiak, Karolina; Langner, Monika; Adamski, Tadeusz; Salmanowicz, Bolesław P; Kaczmarek, Zygmunt; Krajewski, Paweł; Surma, Maria

    2017-02-01

    The quality of wheat depends on a large complex of genes and environmental factors. The objective of this study was to identify quantitative trait loci controlling technological quality traits and their stability across environments, and to assess the impact of interaction between alleles at loci Glu-1 and Glu-3 on grain quality. DH lines were evaluated in field experiments over a period of 4 years, and genotyped using simple sequence repeat markers. Lines were analysed for grain yield (GY), thousand grain weight (TGW), protein content (PC), starch content (SC), wet gluten content (WG), Zeleny sedimentation value (ZS), alveograph parameter W (APW), hectolitre weight (HW), and grain hardness (GH). A number of QTLs for these traits were identified in all chromosome groups. The Glu-D1 locus influenced TGW, PC, SC, WG, ZS, APW, GH, while locus Glu-B1 affected only PC, ZS, and WG. Most important marker-trait associations were found on chromosomes 1D and 5D. Significant effects of interaction between Glu-1 and Glu-3 loci on technological properties were recorded, and in all types of this interaction positive effects of Glu-D1 locus on grain quality were observed, whereas effects of Glu-B1 locus depended on alleles at Glu-3 loci. Effects of Glu-A3 and Glu-D3 loci per se were not significant, while their interaction with alleles present at other loci encoding HMW and LMW were important. These results indicate that selection of wheat genotypes with predicted good bread-making properties should be based on the allelic composition both in Glu-1 and Glu-3 loci, and confirm the predominant effect of Glu-D1d allele on technological properties of wheat grains.

  7. Glutamate Receptors GluR1 and GluR4 in the Hamster Superior Colliculus: Distribution and Co-localization with Calcium-Binding Proteins and GABA

    International Nuclear Information System (INIS)

    Choi, Jae-Sik; Lee, Jea-Young; Jeon, Chang-Jin

    2009-01-01

    We investigated the distributions of AMPA glutamate receptor subtypes GluR1 and GluR4 in the hamster superior colliculus (SC) with antibody immunocytochemistry and the effect of enucleation on these distributions. We compared these labelings to those of GluR2/3 in our previous report (Park et al., 2004, Neurosci Res., 49:139–155) and calcium-binding proteins calbindin D28K, calretinin, parvalbumin, and GABA. Anti-GluR1-immunoreactive (IR) cells were scattered throughout the SC. By contrast, anti-GluR4-IR cells formed distinct clusters within the lower lateral stratum griseum intermediale (SGI) and lateral stratum album intermediale (SAI). The GluR1- and GluR4-IR neurons varied in size and morphology. The average diameter of the GluR1-IR cells was 13.00 µm, while the GluR4-IR cells was 20.00 µm. The large majority of IR neurons were round or oval cells, but they also included stellate, vertical fusiform and horizontal cells. Monocular enucleation appeared to have no effect on the GluR1 and GluR4 immunoreactivity. Some GluR1-IR cells expressed calbindin D28K (9.50%), calretinin (6.59%), parvalbumin (2.53%), and GABA (20.54%). By contrast, no GluR4-IR cells expressed calcium-binding proteins or GABA. Although the function of the AMPA receptor subunits in SC is not yet clear, the distinct segregation of the GluR subunits, its differential colocalization with calcium-binding proteins and GABA, and differential responses to enucleation suggest the functional diversity of the receptor subunits in visuo-motor integration in the SC

  8. Structural basis of subunit selectivity for competitive NMDA receptor antagonists with preference for GluN2A over GluN2B subunits

    Energy Technology Data Exchange (ETDEWEB)

    Lind, Genevieve E.; Mou, Tung-Chung; Tamborini, Lucia; Pomper, Martin G.; De Micheli, Carlo; Conti, Paola; Pinto, Andrea; Hansen, Kasper B. (JHU); (Milan); (Montana)

    2017-07-31

    NMDA-type glutamate receptors are ligand-gated ion channels that contribute to excitatory neurotransmission in the central nervous system (CNS). Most NMDA receptors comprise two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (GluN2A–D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]-4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive GluN2 antagonists, of which ST3 has a binding affinity of 52 nM at GluN1/2A and 782 nM at GluN1/2B receptors. This 15-fold preference of ST3 for GluN1/2A over GluN1/2B is improved compared with NVP-AAM077, a widely used GluN2A-selective antagonist, which we show has 11-fold preference for GluN1/2A over GluN1/2B. Crystal structures of the GluN1/2A agonist binding domain (ABD) heterodimer with bound ACEPC antagonists reveal a binding mode in which the ligands occupy a cavity that extends toward the subunit interface between GluN1 and GluN2A ABDs. Mutational analyses show that the GluN2A preference of ST3 is primarily mediated by four nonconserved residues that are not directly contacting the ligand, but positioned within 12 Å of the glutamate binding site. Two of these residues influence the cavity occupied by ST3 in a manner that results in favorable binding to GluN2A, but occludes binding to GluN2B. Thus, we reveal opportunities for the design of subunit-selective competitive NMDA receptor antagonists by identifying a cavity for ligand binding in which variations exist between GluN2A and GluN2B subunits. This structural insight suggests that subunit selectivity of glutamate-site antagonists can be mediated by mechanisms in addition to direct contributions of contact residues to binding affinity.

  9. In vivo phage display screening for tumor vascular targets in glioblastoma identifies a llama nanobody against dynactin-1-p150Glued.

    Science.gov (United States)

    van Lith, Sanne A M; Roodink, Ilse; Verhoeff, Joost J C; Mäkinen, Petri I; Lappalainen, Jari P; Ylä-Herttuala, Seppo; Raats, Jos; van Wijk, Erwin; Roepman, Ronald; Letteboer, Stef J; Verrijp, Kiek; Leenders, William P J

    2016-11-01

    Diffuse gliomas are primary brain cancers that are characterised by infiltrative growth. Whereas high-grade glioma characteristically presents with perinecrotic neovascularisation, large tumor areas thrive on pre-existent vasculature as well. Clinical studies have revealed that pharmacological inhibition of the angiogenic process does not improve survival of glioblastoma patients. Direct targeting of tumor vessels may however still be an interesting therapeutic approach as it allows pinching off the blood supply to tumor cells. Such tumor vessel targeting requires the identification of tumor-specific vascular targeting agents (TVTAs).Here we describe a novel TVTA, C-C7, which we identified via in vivo biopanning of a llama nanobody phage display library in an orthotopic mouse model of diffuse glioma. We show that C-C7 recognizes a subpopulation of tumor blood vessels in glioma xenografts and clinical glioma samples. Additionally, C-C7 recognizes macrophages and activated endothelial cells in atherosclerotic lesions. By using C-C7 as bait in yeast-2-hybrid (Y2H) screens we identified dynactin-1-p150Glued as its binding partner. The interaction was confirmed by co-immunostainings with C-C7 and a commercial anti-dynactin-1-p150Glued antibody, and via co-immunoprecipitation/western blot studies. Normal brain vessels do not express dynactin-1-p150Glued and its expression is reduced under anti-VEGF therapy, suggesting that dynactin-1-p150Glued is a marker for activated endothelial cells.In conclusion, we show that in vivo phage display combined with Y2H screenings provides a powerful approach to identify tumor-targeting nanobodies and their binding partners. Using this combination of methods we identify dynactin-1-p150Glued as a novel targetable protein on activated endothelial cells and macrophages.

  10. Stimulation of the metabotropic glutamate (mGlu) 2 receptor attenuates the MK-801-induced increase in the immobility time in the forced swimming test in rats.

    Science.gov (United States)

    Kawaura, Kazuaki; Karasawa, Jun-Ichi; Hikichi, Hirohiko

    2016-02-01

    Negative symptoms of schizophrenia are poorly managed using the currently available antipsychotics. Previous studies indicate that agonists of the metabotropic glutamate (mGlu) 2/3 receptors may provide a novel approach for the treatment of schizophrenia. However, the effects of mGlu2/3 receptor agonists or mGlu2 receptor positive allosteric modulators have not yet been clearly elucidated in animal models of the negative symptoms of schizophrenia. Recently, we reported that the forced swimming test in rats treated with subchronic MK-801, an NMDA receptor antagonist, may be regarded as a useful test to evaluate the activities of drugs against the negative symptoms of schizophrenia. We evaluated the effects of LY379268, an mGlu2/3 receptor agonist, and BINA, an mGlu2 receptor positive allosteric modulator, on the hyperlocomotion induced by acute administration of MK-801 (0.15mg/kg, sc) and on the increase in the immobility time in the forced swimming test induced by subchronic treatment with MK-801 (0.5mg/kg, sc, twice a day for 7 days) in rats. Both LY379268 (3mg/kg, sc) and BINA (100mg/kg, ip) attenuated the increase in the immobility time induced by subchronic treatment with MK-801 at the same doses at which they attenuated the MK-801-induced increase in locomotor activity, but had no effect on the immobility time in saline-treated rats. The present results suggest that stimulation of the mGlu2 receptor attenuates the increase in the immobility time in the forced swimming test elicited by subchronic administration of MK-801, and may be potentially useful for treatment of the negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Combinatorial Quantum Field Theory and Gluing Formula for Determinants

    NARCIS (Netherlands)

    Reshetikhin, N.; Vertman, B.

    2015-01-01

    We define the combinatorial Dirichlet-to-Neumann operator and establish a gluing formula for determinants of discrete Laplacians using a combinatorial Gaussian quantum field theory. In case of a diagonal inner product on cochains we provide an explicit local expression for the discrete

  12. Automatic Color Sorting of Hardwood Edge-Glued Panel Parts

    Science.gov (United States)

    D. Earl Kline; Richard Conners; Qiang Lu; Philip A. Araman

    1997-01-01

    This paper describes an automatic color sorting system for red oak edge-glued panel parts. The color sorting system simultaneously examines both faces of a panel part and then determines which face has the "best" color, and sorts the part into one of a number of color classes at plant production speeds. Initial test results show that the system generated over...

  13. GluR2 ligand-binding core complexes

    DEFF Research Database (Denmark)

    Kasper, C; Lunn, M-L; Liljefors, T

    2002-01-01

    X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic...

  14. Repair of white oak glued-laminated beams

    Science.gov (United States)

    Lawrence A. Soltis; Robert J. Ross

    1999-01-01

    Connections between steel side plates and white oak glued-laminated beams subjected to tension perpendicular-to-grain stresses were tested to failure. The beams were then repaired with five different configurations using two sizes of lag screws, with and without steel reinforcing plates. The repaired beams were re-tested to failure. Results indicate that in all...

  15. Endothelial nitric oxide synthase gene Glu298Asp polymorphism ...

    African Journals Online (AJOL)

    Administrator

    2011-09-12

    Sep 12, 2011 ... Figure 1. The Glu298Asp polymorphism of eNOS gene was shown by .... mechanisms by which eNOS Asp298 polymorphism ... Asp298 is exposed to selective proteolytic cleavage in ... grounds, inclusion and exclusion criteria for PE women ... attention to meta analysis study, it is more probable that.

  16. Subspace preservation, subspace locality, and gluing of completely positive maps

    International Nuclear Information System (INIS)

    Aaberg, Johan

    2004-01-01

    Three concepts concerning completely positive maps (CPMs) and trace preserving CPMs (channels) are introduced and investigated. These are named subspace preserving (SP) CPMs, subspace local (SL) channels, and gluing of CPMs. SP CPMs has, in the case of trace preserving CPMs, a simple interpretation as those which preserve probability weights on a given orthogonal sum decomposition of the Hilbert space of a quantum system. The proposed definition of subspace locality of quantum channels is an attempt to answer the question of what kind of restriction should be put on a channel, if it is to act 'locally' with respect to two 'locations', when these naturally correspond to a separation of the total Hilbert space in an orthogonal sum of subspaces, rather than a tensor product decomposition. As a description of the concept of gluings of quantum channels, consider a pair of 'evolution machines', each with the ability to evolve the internal state of a 'particle' inserted into its input. Each of these machines is characterized by a channel describing the operation the internal state has experienced when the particle is returned at the output. Suppose a particle is put in a superposition between the input of the first and the second machine. Here it is shown that the total evolution caused by a pair of such devices is not uniquely determined by the channels of the two machines. Such 'global' channels describing the machine pair are examples of gluings of the two single machine channels. Various expressions to generate the set of SP and SL channels, as well as expressions to generate the set of gluings of given channels, are deduced. We discuss conceptual aspects of the nature of these channels and the nature of the non-uniqueness of gluings

  17. Glued intrascleral fixation of posterior chamber intraocular lens in children.

    Science.gov (United States)

    Kumar, Dhivya Ashok; Agarwal, Amar; Prakash, Dimple; Prakash, Gaurav; Jacob, Soosan; Agarwal, Athiya

    2012-04-01

    To evaluate the short-term results of glued intrascleral fixation of posterior chamber intraocular lens (glued IOL) in children without adequate capsular support. Noncomparative retrospective observational case series. Institutional practice. Forty-one eyes of 33 children who underwent glued IOL implantation were retrospectively evaluated. The indications were postsurgical aphakia, subluxated cataract, ectopia lentis, traumatic subluxation, and decentered IOL. Visual acuity (VA), endothelial cell changes, intraoperative and postoperative complications. The mean age at the time of glued IOL was 10.7±3.6 years (range 5-15). The mean duration of follow-up after surgery was 17.5±8.5 months (range 12-36). The mean postoperative best spectacle-corrected visual acuity (BCVA in decimal equivalent) was 0.43±0.33 and there was significant change noted (P20/60 BCVA was obtained in 17.1% and 46.3% of eyes respectively. BCVA improvement more than 1 line was seen in 22 eyes (53.6%). The mean postoperative refraction was myopic (-1.19±0.7 diopters [D]) in 19 eyes and hyperopic (+1.02±0.7 D) in 22 eyes. The mean endothelial loss was 4.13% (range 1.3%-5.94%). The 3 causes of reduced BCVA were the preexisting corneal, retinal pathology, and amblyopia. Postoperative complications included optic capture in 1 eye (2.4%), macular edema in 2 eyes (4.8%), and clinical decentration in 2 eyes (4.8%). There was no postoperative retinal detachment, IOL dislocation, endophthalmitis, or glaucoma. Short-term results in children after glued IOL were favorable, with a low rate of complications. However, regular follow-ups are required since long-term risks are unknown. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. mGlu5 Receptor Functional Interactions and Addiction

    Directory of Open Access Journals (Sweden)

    Robyn eBrown

    2012-05-01

    Full Text Available The idea of ‘receptor mosaics’ suggests that proteins can form complex and dynamic networks, with respect to time and protein make up, which has the potential to make significant contributions to the diversity and specificity of GPCR signalling, particularly in neuropharmacology, where a few key receptors have been implicated in multiple neurological and psychiatric disorders such as addiction. Metabotropic glutamate type 5 receptors (mGlu5 have been shown to heterodimerise and form complexes with other GPCRs including adenosine A2A and dopamine D2 receptors. mGlu5-containing complexes are found in the striatum, a region of the brain known to be critical for mediating the rewarding and incentive motivational properties of drugs of abuse. Indeed, initial studies indicate a role for mGlu5-containing complexes in rewarding and conditioned effects of drugs, as well as drug-seeking behaviour. This is consistent with the substantial influence that mGlu5 complexes appear to have on striatal function, regulating both GABAergic output of striatopallidal neurons and glutamatergic input from corticostriatal afferents. Given their discrete localization, mGlu5-containing complexes represent a novel way in which to minimize the off-target effects and therefore provide us with an exciting therapeutic avenue for drug discovery efforts. Indeed, the therapeutic targeting of receptor mosaics in a tissue specific or temporal manner (for example, a sub-population of receptors in a ‘pathological state’ has the potential to dramatically reduce detrimental side effects that may otherwise impair vital brain function.

  19. Contract Renewal Information - all Contracts

    Data.gov (United States)

    Department of Housing and Urban Development — Multifamily Portfolio datasets (section 8 contracts) - The information has been compiled from multiple data sources within FHA or its contractors. HUD oversees more...

  20. Contract theory and EU Contract Law

    OpenAIRE

    Hesselink, M.W.; Twigg-Flesner, C.

    2016-01-01

    This paper explores the relationship between contract theory and European contract law. In particular, it confronts the leading contract law theories with the main characteristics of EU contract law. The conclusion is that the two do not match well. In particular, monist normative contract theories are largely irreconcilable with the contract law of the EU. The paper further addresses the main implications of this mismatch, both for contract theory and for EU contract law. It suggests that in...

  1. Potentiating mGluR5 Function with a Positive Allosteric Modulator Enhances Adaptive Learning

    Science.gov (United States)

    Xu, Jian; Zhu, Yongling; Kraniotis, Stephen; He, Qionger; Marshall, John J.; Nomura, Toshihiro; Stauffer, Shaun R.; Lindsley, Craig W.; Conn, P. Jeffrey; Contractor, Anis

    2013-01-01

    Metabotropic glutamate receptor 5 (mGluR5) plays important roles in modulating neural activity and plasticity and has been associated with several neuropathological disorders. Previous work has shown that genetic ablation or pharmacological inhibition of mGluR5 disrupts fear extinction and spatial reversal learning, suggesting that mGluR5…

  2. A pharmacological profile of the high-affinity GluK5 kainate receptor

    DEFF Research Database (Denmark)

    Møllerud, Stine; Kastrup, Jette Sandholm Jensen; Pickering, Darryl S

    2016-01-01

    -hydroxyisoxazol-4-yl)propionate (ATPA), dihydrokainate and (2 S,4 R)−4-methyl-glutamate (SYM2081) have higher affinity at GluK3 compared to GluK5. Since some studies have indicated that GluK5 is associated with various diseases in the central nervous system (e.g. schizophrenia, temporal lobe epilepsy, bipolar...

  3. Agile Contracts

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Pries-Heje, Lene

    2014-01-01

    with “endless” re-negotiation of the requirements; you need a more flexible way to develop IS. A new way of coping with many changes is to use an agile development approach and a fixed budget and resources contract. This paper presents an example case. We analyse the case and design a guideline for how......When you have stable and non-ambiguous requirements then a classic contract for IS between a supplier and a public sector institution based on a requirements specification may be well suited. However, if you have to accept many changes or have ambiguous requirements then you may end up...... to implement a fixed budget and resources contract in the public sector. The guideline includes elements to cope with challenges in a tender process such as transparency, criteria for supplier selection, and live assessment of resource skills and capabilities, as well as achieving the flexibility for change...

  4. Turnkey contracts

    International Nuclear Information System (INIS)

    Langetepe, G.

    1977-01-01

    To make energy available economically and in sufficient quantity is a main point for the future of an industrial and more for a developing country. The investment costs and the availability of a power plant and in particular for a nuclear power plant are the most significant factors in the economic operation of the plant. In the phase before signing the contract the essential decisions are made with high influence in the economic operation and the availability of the plant. A turn-key contract offers good possibilities to minimize the risks referring a) the plant quality and functionality, b) the plant investment cost, c) the plant completion date, d) the handling of the licensing procedures, e) the availability of the operation. The lecture mentions the points which are of high influence for a successful erection and operation period and which must be clarified before signing the contract between the buyer and supplier of the plant. (orig./HP) [de

  5. ABA renewal involves enhancements in both GluA2-lacking AMPA receptor activity and GluA1 phosphorylation in the lateral amygdala.

    Directory of Open Access Journals (Sweden)

    Kyungjoon Park

    Full Text Available Fear renewal, the context-specific relapse of fear following fear extinction, is a leading animal model of post-traumatic stress disorders (PTSD and fear-related disorders. Although fear extinction can diminish fear responses, this effect is restricted to the context where the extinction is carried out, and the extinguished fear strongly relapses when assessed in the original acquisition context (ABA renewal or in a context distinct from the conditioning and extinction contexts (ABC renewal. We have previously identified Ser831 phosphorylation of GluA1 subunit in the lateral amygdala (LA as a key molecular mechanism for ABC renewal. However, molecular mechanisms underlying ABA renewal remain to be elucidated. Here, we found that both the excitatory synaptic efficacy and GluA2-lacking AMPAR activity at thalamic input synapses onto the LA (T-LA synapses were enhanced upon ABA renewal. GluA2-lacking AMPAR activity was also increased during low-threshold potentiation, a potential cellular substrate of renewal, at T-LA synapses. The microinjection of 1-naphtylacetyl-spermine (NASPM, a selective blocker of GluA2-lacking AMPARs, into the LA attenuated ABA renewal, suggesting a critical role of GluA2-lacking AMPARs in ABA renewal. We also found that Ser831 phosphorylation of GluA1 in the LA was increased upon ABA renewal. We developed a short peptide mimicking the Ser831-containing C-tail region of GluA1, which can be phosphorylated upon renewal (GluA1S; thus, the phosphorylated GluA1S may compete with Ser831-phosphorylated GluA1. This GluA1S peptide blocked the low-threshold potentiation when dialyzed into a recorded neuron. The microinjection of a cell-permeable form of GluA1S peptide into the LA attenuated ABA renewal. In support of the GluA1S experiments, a GluA1D peptide (in which the serine at 831 is replaced with a phosphomimetic amino acid, aspartate attenuated ABA renewal when microinjected into the LA. These findings suggest that enhancements

  6. ABA renewal involves enhancements in both GluA2-lacking AMPA receptor activity and GluA1 phosphorylation in the lateral amygdala.

    Science.gov (United States)

    Park, Kyungjoon; Song, Beomjong; Kim, Jeongyeon; Hong, Ingie; Song, Sangho; Lee, Junuk; Park, Sungmo; Kim, Jihye; An, Bobae; Lee, Hyun Woo; Lee, Seungbok; Kim, Hyun; Lee, Justin C; Lee, Sukwon; Choi, Sukwoo

    2014-01-01

    Fear renewal, the context-specific relapse of fear following fear extinction, is a leading animal model of post-traumatic stress disorders (PTSD) and fear-related disorders. Although fear extinction can diminish fear responses, this effect is restricted to the context where the extinction is carried out, and the extinguished fear strongly relapses when assessed in the original acquisition context (ABA renewal) or in a context distinct from the conditioning and extinction contexts (ABC renewal). We have previously identified Ser831 phosphorylation of GluA1 subunit in the lateral amygdala (LA) as a key molecular mechanism for ABC renewal. However, molecular mechanisms underlying ABA renewal remain to be elucidated. Here, we found that both the excitatory synaptic efficacy and GluA2-lacking AMPAR activity at thalamic input synapses onto the LA (T-LA synapses) were enhanced upon ABA renewal. GluA2-lacking AMPAR activity was also increased during low-threshold potentiation, a potential cellular substrate of renewal, at T-LA synapses. The microinjection of 1-naphtylacetyl-spermine (NASPM), a selective blocker of GluA2-lacking AMPARs, into the LA attenuated ABA renewal, suggesting a critical role of GluA2-lacking AMPARs in ABA renewal. We also found that Ser831 phosphorylation of GluA1 in the LA was increased upon ABA renewal. We developed a short peptide mimicking the Ser831-containing C-tail region of GluA1, which can be phosphorylated upon renewal (GluA1S); thus, the phosphorylated GluA1S may compete with Ser831-phosphorylated GluA1. This GluA1S peptide blocked the low-threshold potentiation when dialyzed into a recorded neuron. The microinjection of a cell-permeable form of GluA1S peptide into the LA attenuated ABA renewal. In support of the GluA1S experiments, a GluA1D peptide (in which the serine at 831 is replaced with a phosphomimetic amino acid, aspartate) attenuated ABA renewal when microinjected into the LA. These findings suggest that enhancements in both the

  7. Managing the relational character of public-private partnership contracts

    Directory of Open Access Journals (Sweden)

    Cvetković Predrag

    2015-01-01

    Full Text Available A public-private partnership contract has the character of a relational contract. Relational contracts are incomplete agreements governing transactions where the contracting parties have mutually agreed that it is impossible or economically inefficient to contractually define ex ante possible difficulties and contingencies in the contract implementation, nor the difficulties and contingencies underlying the ex post control of contract performance by a third entity (court or arbitration. Considering the methodology of managing relational contracts, it is essential that the theory of relational contracts does not advocate for the establishment of relational contracts as a separate category of contracts, with specifically designated contractual instruments. This theory defines the relational contract as a category which legitimizes 'the relational mode' of a particular contract. The methodology of relational contracts is important for contracts on public-private partnership as it ensures that the contractual relationship is aligned with the changes in the immediate environment where the PPP contract operates. The aforementioned alignment has two aspects. The first one is the ex ante aspect of the alignment which is primarily aimed at preventing the detrimental effect of such alignment to the public partner's interests. Therefore, the intent to prevent such an effect shall be taken into account when defining the criteria for the selection of the most favorable private partner and the best offer. At the same time, it is essential to establish verifiable standards for measuring the private partner performance in the phase of contract implementation. For this goal to be achieved, it is crucial to specify the subject matter of the private partner's obligations, to establish the priority rank of PPP project objectives, to elaborate on the specific requirements governing the eligibility of private partners to participate in the bidding process, to specify

  8. New Partner Orientation

    Science.gov (United States)

    This EPA presentation provides information on the SmartWay Transport Partnership Program, including key information about EPA, Partners' roles, benefits, tools, partner recognition, awards, and brand value. Transcript available.

  9. Green Power Partner Resources

    Science.gov (United States)

    EPA Green Power Partners can access tools and resources to help promote their green power commitments. Partners use these tools to communicate the benefits of their green power use to their customers, stakeholders, and the general public.

  10. Pyrimidine and nucleoside gamma-esters of L-Glu-Sar

    DEFF Research Database (Denmark)

    Eriksson, André H; Elm, Peter L; Begtrup, Mikael

    2005-01-01

    -tetrahydrofuran-3-yl ester)-Sar (I), l-Glu(thymine-1-yl-methyl ester)-Sar (II) and l-Glu(acyclothymidine)-Sar (III) were synthesised and in vitro stability was studied in various aqueous and biological media. Affinity to and translocation via hPEPT1 was investigated in mature Caco-2 cell monolayers, grown......The aim of the present study was to improve the synthetic pathway of bioreversible dipeptide derivatives as well as evaluate the potential of using l-Glu-Sar as a pro-moiety for delivering three newly synthesised nucleoside and pyrimidine l-Glu-Sar derivatives. l-Glu(trans-2-thymine-1-yl...

  11. The research of glued frame-mounted wooden constructions

    Directory of Open Access Journals (Sweden)

    Muselemov Kh.M.

    2016-11-01

    Full Text Available the authors of this article note that the fast pace and modern construction make qualitatively new demands on building materials and structures. While great attention is paid to the production of glued wooden structures. Such designs on a number of technical and economic indicators are superior to metal and concrete have low component weight, relatively high strength and stiffness with sufficient reliability and durability. At the same time, negative characteristics of the wood (the dependence of the properties from its structure, defects, need for and considerable expense of quality timber, excessive massiveness of the cross-sections, creep under sustained loading, etc. restrict the scope and impair the indicators of glued wooden structures. One of the ways to address these shortcomings and increase techno-economic efficiency – reinforcement of sections of glued wooden structures and elements of steel or fiberglass reinforcement. This can significantly reduce the consumption of wood, reduce Assembly mass, to improve the quality and reliability of wooden structures, working mainly in bending and compression with bending.

  12. SKLUST device for high-precision gluing of MWPC

    International Nuclear Information System (INIS)

    Amaglobeli, N.S.; Burov, R.V.; Sakandelidze, R.M.; Sakhelashvili, T.M.; Chiladze, B.G.; Glonti, G.L.; Glonti, L.N.

    2005-01-01

    The SKLUST device has been created for gluing precision plane-parallel anode, cathode of spacer bars and integral anode and cathode frames of the MWPCs or flat surfaces of the large-area cathode planes for them in the case that thin copper clad stesalit or glass-cloth-base laminate is used as the cathode, for example, for the CSC chambers. In contrast to usual gluing, in this device the glued components are not pressed to each other. SKLUST allows making high-precision products in laboratory conditions without preliminarily machining its components and receiving a precision article practically for any area at the plane parallelism from ±0.030 up to ±0.006 mm using a non-calibrated sheet of the foiled (or unfoiled) stesalit, glass-cloth-base laminate or other flexible materials to a tolerance for the thickness ±0.2-0.5 mm or worse. On the biggest of the existing devices it is possible to fabricate an article with the maximal sizes 2400x250 mm 2 at the thickness accuracy (6±0.015) mm (maximum deviation). Whereas in the technological cycle machining of blanks to the thickness or application of exact blanks is completely excluded, the manufacturing process becomes simpler, and the price of the articles essentially reduces, especially for mass production

  13. Balancing Government Risks with Contractor Incentives in Performance-Based Logistics Contracts

    National Research Council Canada - National Science Library

    Gardner, Christopher P

    2008-01-01

    ...: the PBL goal of developing long-term partnerships that encourage investment from commercial partners is best achieved through lengthy, guaranteed contracts -- but such contracts increase the DoD's...

  14. M.S. independent research study : partnering on small construction project

    OpenAIRE

    Conley, Michael A

    1997-01-01

    This investigation will address the possibility that partnering concepts are underutilized in small government projects. If Government Contracting Officers utilized partnering concepts on small construction projects, there could be a potential for saving millions of dollars annually. The primary objective of this report is to inform Contracting Officers of the benefits of partnering on small construction projects. Small projects will be considered to have a value of less than $3 million, mid-...

  15. Contract theory and EU Contract Law

    NARCIS (Netherlands)

    Hesselink, M.W.; Twigg-Flesner, C.

    2016-01-01

    This paper explores the relationship between contract theory and European contract law. In particular, it confronts the leading contract law theories with the main characteristics of EU contract law. The conclusion is that the two do not match well. In particular, monist normative contract theories

  16. Muscle Contraction.

    Science.gov (United States)

    Sweeney, H Lee; Hammers, David W

    2018-02-01

    SUMMARYMuscle cells are designed to generate force and movement. There are three types of mammalian muscles-skeletal, cardiac, and smooth. Skeletal muscles are attached to bones and move them relative to each other. Cardiac muscle comprises the heart, which pumps blood through the vasculature. Skeletal and cardiac muscles are known as striated muscles, because the filaments of actin and myosin that power their contraction are organized into repeating arrays, called sarcomeres, that have a striated microscopic appearance. Smooth muscle does not contain sarcomeres but uses the contraction of filaments of actin and myosin to constrict blood vessels and move the contents of hollow organs in the body. Here, we review the principal molecular organization of the three types of muscle and their contractile regulation through signaling mechanisms and discuss their major structural and functional similarities that hint at the possible evolutionary relationships between the cell types. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  17. Contract design

    International Nuclear Information System (INIS)

    Bradley, P.

    2006-01-01

    The current state of the electric power industry in Ontario was discussed with particular reference to the procurement of contracts and why the Ontario Power Authority (OPA) must be contracting to resolve many of Ontario's electricity issues. As Ontario increasingly relies on imports and natural gas-fired generation, the price of electricity continues to rise given that supply is at a low level. In addition to the generation gap, there are also several transmission constrained areas in Ontario, particularly in the Greater Toronto Area (GTA). The OPA announced 2 projects totalling 1900 MW to relieve congestion. According to the Independent Electricity System Operator (IESO), the total potential opportunity for new generation by 2015 is about 5,000 to 7,000 megawatts. OPA is expected to launch procurement processes for up to 1000 MW of cogeneration, 250 MW of province-wide conservation initiatives, 1900 MW of generation in the western part of the GTA, and 600 MW of generation in downtown Toronto. New nuclear capacity is also anticipated in addition to renewables and conservation/demand management (CDM) initiatives. The OPA's competitive procurement processes will include requests for expressions of interest, requests for qualifications and requests for proposals. The challenge of balancing the technical complexities and realities of procuring generation assets with the need for a fair procurement process was discussed. Contracts will be designed to react to market signals and will include 3 styles: tariff style, tolling style and standard offer contract. OPA will make every effort to balance generator and ratepayer interests. 6 figs

  18. Pharmacology and Structural Analysis of Ligand Binding to the Orthosteric Site of Glutamate-Like GluD2 Receptors

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Hansen, Kasper B; Naur, Peter

    2016-01-01

    -term depression. Here, we investigate the pharmacology of the orthosteric binding site in GluD2 by examining the activity of analogs of D-Ser and GluN1 glycine site competitive antagonists at GluD2 receptors containing the lurcher mutation (GluD2(LC)), which promotes spontaneous channel activation. We identify...

  19. Mrica Hydroelectric Project: a study in partnering

    International Nuclear Information System (INIS)

    Loraine, R.K.; Bannmark, O.

    1993-01-01

    This paper describes the contractual and financial aspects of the Mrica Project. Of particular interest is the high degree of cooperation that developed between the various parties, and the effect this had on the progress and completion of the project. This relationship had its origin in the need to make the best use of the relatively scarce funds available. It was vitally important that problems were solved jointly and that costs did not escalate as a result of confrontation between the parties. In this respect, the project was an early manifestation of the contractual relationship now called partnering, and the procedures adopted at Mrica are very similar to those now widely used in partnering contracts. The paper is therefore structured to identify and analyse the key elements of co-operation, and their impact on both the negotiation of the contracts and the completion of the works. (Author)

  20. Retractable Contracts

    Directory of Open Access Journals (Sweden)

    Franco Barbanera

    2016-02-01

    Full Text Available In calculi for modelling communication protocols, internal and external choices play dual roles. Two external choices can be viewed naturally as dual too, as they represent an agreement between the communicating parties. If the interaction fails, the past agreements are good candidates as points where to roll back, in order to take a different agreement. We propose a variant of contracts with synchronous rollbacks to agreement points in case of deadlock. The new calculus is equipped with a compliance relation which is shown to be decidable.

  1. The Drosophila DmGluRA is required for social interaction and memory

    Directory of Open Access Journals (Sweden)

    Brian P. Schoenfeld

    2013-05-01

    Full Text Available Metabotropic glutamate receptors (mGluRs have well established roles in cognition andsocial behavior in mammals. Whether or not these roles have been conserved throughoutevolution from invertebrate species is less clear. Mammals have 8 mGluRs whereasDrosophila have a single DmGluRA, which has both Gi and Gq coupled signalingactivity. We have utilized Drosophila to examine the role of DmGluRA in social behaviorand various phases of memory. We have found that flies that are homozygous orheterozygous for loss of function mutations of DmGluRA have impaired social behaviorin male Drosophila. Futhermore, flies that are homozygous or heterozygous for loss offunction mutations of DmGluRA have impaired learning during training, immediate recallmemory, short-term memory and long-term memory as young adults. This workdemonstrates a role for metabotropic glutamate receptor activity in both social behaviorand memory in Drosophila.

  2. Paroxetine prevented the down-regulation of astrocytic L-Glu transporters in neuroinflammation

    Directory of Open Access Journals (Sweden)

    Koki Fujimori

    2015-01-01

    Full Text Available The extracellular L-glutamate (L-Glu concentration is elevated in neuroinflammation, thereby causing excitotoxicity. One of the mechanisms is down-regulation of astrocyte L-Glu transporters. Some antidepressants have anti-inflammatory effects. We therefore investigated effects of various antidepressants on the down-regulation of astrocyte L-Glu transporters in the in vitro neuroinflammation model. Among these antidepressants, only paroxetine was effective. We previously demonstrated that the down-regulation of astrocyte L-Glu transporters was caused by L-Glu released from activated microglia. We here clarified that only paroxetine inhibited L-Glu release from microglia. This is the novel action of paroxetine, which may bring advantages on the therapy of neuroinflammation.

  3. From Orchestration to Choreography through Contract Automata

    Directory of Open Access Journals (Sweden)

    Davide Basile

    2014-10-01

    Full Text Available We study the relations between a contract automata and an interaction model. In the former model, distributed services are abstracted away as automata - oblivious of their partners - that coordinate with each other through an orchestrator. The interaction model relies on channel-based asynchronous communication and choreography to coordinate distributed services. We define a notion of strong agreement on the contract model, exhibit a natural mapping from the contract model to the interaction model, and give conditions to ensure that strong agreement corresponds to well-formed choreography.

  4. Combined surgical management of capsular and iris deficiency with glued intraocular lens technique.

    Science.gov (United States)

    Kumar, Dhivya Ashok; Agarwal, Amar; Jacob, Soosan; Lamba, Mandeep; Packialakshmi, Sathiya; Meduri, Alessandro

    2013-05-01

    To determine the outcome after glued aniridia intraocular lens (IOL) and glued IOL with iridoplasty in eyes with combined lens capsular and iris deficiency. Twenty-seven eyes of 25 patients (6 had congenital aniridia with subluxated cataract and 19 had acquired lens/iris defects) were included. Glued IOL with aniridia IOL (Intra Ocular Care, Gujarat, India) was performed in eyes with total aniridia and iridoplasty with glued IOL with a three-piece foldable IOL (Sofport; Bausch & Lomb, Rochester, NY) was performed in eyes with partial aniridia. The postoperative outcomes were analyzed at follow-up examination (range: 6 to 48 months). Eleven eyes underwent glued aniridia IOL and 16 eyes underwent glued IOL with iridoplasty. There was significant improvement in (spectacle) corrected distance visual acuity (CDVA) (P = .002). Postoperatively, pigment dispersion on the IOL (n = 1) and raised intraocular pressure was seen in the glued aniridia IOL group and chronic uveitis (n = 1), cystoid macular edema (n = 1), and hyphema (n = 1) in the glued IOL with iridoplasty group. The CDVA remained unchanged in 14 eyes (51.8%) and improved in 13 eyes (48.1%). There was a difference in postoperative CDVA (P = .001) between eyes with glued aniridia IOL and glued IOL with iridoplasty. There was no IOL decentration, retinal detachment, corneal decompensation, or endophthalmitis. There was reduction in glare and photophobia. Both glued aniridia IOL and glued IOL/iridoplasty showed good functional and anatomical results with fewer complications in eyes with lens capsule and iris deficiency. However, long-term follow-up is required.[J Refract Surg. 2013;29(5):342-347.]. Copyright 2013, SLACK Incorporated.

  5. ANALYSIS OF EUCALYPTUS GLUED-LAMINATED TIMBER PORTICOS STRUCTURAL PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Sandra Maria Ferreira Couri Petrauski

    Full Text Available ABSTRACT This study evaluated the structural behavior of porticos made from eucalyptus glued boards, using wood of Eucalyptus sp and resorcinol formaldehyde adhesive. Three units, in real scale, of tri-articulated straight porticos, with a 5 meter porthole and a 26º inclination, capable to support tiles covering placement were designed, constructed and subjected to load testing, until rupture. The amount of adhesive used in the construction of the porticos was 250 g/m2 and the bonding pressure of 1.3 MPa. The Hankinson model was employed as an estimator of the glued joints strength, under different angles between the fibers. The average value for the last resistance of the structures was 4.63 times the design load, according to the criteria established by the ABNT, 1997. The structures showed satisfactory mechanical performance and deformations lower than the ones allowed by the standard. It was concluded there is technical feasibility to manufacture porticos fully bonded with small thickness veneers.

  6. Green Power Partnership Long-term Contracts

    Science.gov (United States)

    The U.S. EPA's Green Power Partnership is a voluntary program designed to reduce the environmental impact of electricity generation by promoting renewable energy. This page lists Partners that signed a contract to purchase green power for 5 years or more.

  7. Collaborative vaccine development: partnering pays.

    Science.gov (United States)

    Ramachandra, Rangappa

    2008-01-01

    Vaccine development, supported by infusions of public and private venture capital, is re-entering a golden age as one of the fastest growing sectors in the life-sciences industry. Demand is driven by great unmet need in underdeveloped countries, increased resistance to current treatments, bioterrorism, and for prevention indications in travelers, pediatric, and adult diseases. Production systems are becoming less reliant on processes such as egg-based manufacturing, while new processes can help to optimize vaccines. Expeditious development hinges on efficient study conduct, which is greatly enhanced through research partnerships with specialized contract research organizations (CROs) that are licensed and knowledgeable in the intricacies of immunology and with the technologic and scientific foundation to support changing timelines and strategies inherent to vaccine development. The CRO often brings a more objective assessment for probability of success and may offer alternative development pathways. Vaccine developers are afforded more flexibility and are free to focus on innovation and internal core competencies. Functions readily outsourced to a competent partner include animal model development, safety and efficacy studies, immunotoxicity and immunogenicity, dose response studies, and stability and potency testing. These functions capitalize on the CRO partner's regulatory and scientific talent and expertise, and reduce infrastructure expenses for the vaccine developer. Successful partnerships result in development efficiencies, elimination or reduced redundancies, and improved time to market. Keys to success include honest communications, transparency, and flexibility.

  8. Identification of AICP as a GluN2C-Selective N-Methyl-d-Aspartate Receptor Superagonist at the GluN1 Glycine Site

    DEFF Research Database (Denmark)

    Jessen, Maja; Frederiksen, Kristen; Yi, Feng

    2017-01-01

    N-methyl-d-aspartate (NMDA)-type ionotropic glutamate receptors mediate excitatory neurotransmission in the central nervous system and are critically involved in brain function. NMDA receptors are also implicated in psychiatric and neurological disorders and have received considerable attention....../2A-D), in which DCS is a superagonist at GluN2C-containing receptors compared with glycine and a partial agonist at GluN2B-containing receptors. Here, we identify (R)-2-amino-3-(4-(2-ethylphenyl)-1H-indole-2-carboxamido)propanoic acid (AICP) as a glycine site agonist with unique GluN2-dependent...

  9. To Bind or not to Bind: It’s in the Contract

    DEFF Research Database (Denmark)

    Tvarnø, Christina D.

    2015-01-01

    This article discusses the formalization of collaboration through partnering contracts in the construction industry in the USA, Great Britain and Denmark. The article compares the different types of collaborative partnering contracts in the three countries, and provides a conclusion on whether th...

  10. Types of contracts and contracting procedures

    International Nuclear Information System (INIS)

    Zijl, N.A. van

    1977-01-01

    Contracting for a nuclear power plant can be carried out in many different ways, from a bilateral agreement between two countries to an international open bidding competition. Also the kind of contracts (turnkey, split-package or multi-contract type) are discussed with their pros and cons as well as the contracting procedures which can be followed to come to the conclusion of a contract. (orig.) [de

  11. Effect of Glu-B3 Allelic Variation on Sodium Dodecyl Sulfate Sedimentation Volume in Common Wheat (Triticum aestivum L.

    Directory of Open Access Journals (Sweden)

    Hongqi Si

    2013-01-01

    Full Text Available Sodium dodecyl sulfate (SDS sedimentation volume has long been used to characterize wheat flours and meals with the aim of predicting processing and end-product qualities. In order to survey the influence of low-molecular-weight glutenin subunits (LMW-GSs at Glu-B3 locus on wheat SDS sedimentation volume, a total of 283 wheat (Triticum aestivum L. varieties including landraces and improved and introduced cultivars were analyzed using 10 allele-specific PCR markers at the Glu-B3 locus. The highest allele frequency observed in the tested varieties was Glu-B3i with 21.9% in all varieties, 21.1% in landraces, 25.5% in improved cultivars, and 12% in introduced cultivars. Glu-B3 locus represented 8.6% of the variance in wheat SDS sedimentation volume, and Glu-B3b, Glu-B3g, and Glu-B3h significantly heightened the SDS sedimentation volume, but Glu-B3a, Glu-B3c, and Glu-B3j significantly lowered the SDS sedimentation volume. For the bread-making quality, the most desirable alleles Glu-B3b and Glu-B3g become more and more popular and the least desirable alleles Glu-B3a and Glu-B3c got less and less in modern improved cultivars, suggesting that wheat grain quality in China has been significantly improved through breeding effort.

  12. Maintenance contract strategies for reliability at minimum cost

    International Nuclear Information System (INIS)

    Gamman, E.

    1992-01-01

    The conference paper deals with offshore contract philosophies concerning maintenance. The main philosophies of the contract should be built on the following key success factors: Safe operations and correct quality must be sustained at any time; the maintenance contractor should be viewed as a cooperation partner, not only as a supplier; optimum exploitation of learning curve effects and economies of scale. The paper illustrates the importance of each of them in a contract context with a few recommendations

  13. Collateral Intimate Partner Homicide

    Directory of Open Access Journals (Sweden)

    Emily Meyer

    2013-04-01

    Full Text Available Collateral intimate partner homicide (CIPH is an underinvestigated genre of intimate partner violence (IPV where an individual(s connected to the IPV victim is murdered. We conducted a content analysis of a statewide database of CIPH newspaper articles (1990-2007. Out of 111 collateral murder victims, there were 84 IPV female focal victims and 84 male perpetrators. The most frequently reported CIPH decedent was the focal victim’s new partner (30%; 45% of focal victims were themselves killed. News reports framed CIPH as the unexpected result of interpersonal conflict, despite evidence of a systematic pattern of coercion and violence that capitulated in murder.

  14. NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients

    Directory of Open Access Journals (Sweden)

    Manuela eMellone

    2015-07-01

    Full Text Available Levodopa-induced dyskinesias (LIDs are major complications in the pharmacological management of Parkinson’s disease (PD. Abnormal glutamatergic transmission in the striatum is considered a key factor in the development of LIDs. This work aims at i. characterizing NMDA receptor GluN2A/GluN2B subunit ratio as a common synaptic trait in rat and primate models of LIDs and in dyskinetic PD patients, and ii. validating the potential therapeutic effect of a cell-permeable peptide interfering with GluN2A synaptic localization on the dyskinetic behavior of these experimental models of LIDs. Here we demonstrate an altered ratio of synaptic GluN2A/GluN2B-containing NMDA receptors in the striatum of levodopa-treated dyskinetic rats and monkeys as well as in post-mortem tissue from dyskinetic PD patients. The modulation of synaptic NMDA receptor composition by a cell-permeable peptide interfering with GluN2A subunit interaction with the scaffolding protein PSD-95 leads to a reduction in the dyskinetic motor behavior in the two animal models of LIDs. Our results indicate that targeting synaptic NMDA receptor subunit composition may represent an intriguing therapeutic approach aimed at ameliorating levodopa motor side effects.

  15. Alaska birch for edge-glued panel production—considerations for wood products manufacturers

    Science.gov (United States)

    David. Nicholls

    2010-01-01

    Edge-glued panels could become a natural extension for the birch (Betula papyrifera Marsh.) lumber industry in Alaska, resulting in greater utilization of the birch resource while allowing producers to explore a wider variety of products and markets. Key advantages of edge-glued panel production include the relatively low cost of equipment, the...

  16. Structural Performance of the Second Oldest Glued-Laminated Structure in the United States

    Science.gov (United States)

    Douglas R. Rammer; Jorge de Melo Moura; Robert J. Ross

    2014-01-01

    The second glued-laminated structure built in the United States was constructed at the USDA Forest Products Laboratory (FPL) in 1934 to demonstrate the performance of wooden arch buildings. After 75 years of use the structure was decommissioned in 2010. Shortly after construction, researchers structurally evaluated the glued-laminated arch structure for uniform loading...

  17. Structural Evaluation of the Second Oldest Glued-Laminated Structure in the United States

    Science.gov (United States)

    Douglas R. Rammer; Jorge de Melo Moura

    2013-01-01

    The second glued-laminated structure built in the United States was constructed at the USDA Forest Products Laboratory (FPL) in 1934 to demonstrate the performance of wooden arch buildings. After decades of use the structure was decommissioned in 2010. Shortly after construction, researchers structurally evaluated the glued-laminated arch structure for uniform loading...

  18. Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor

    DEFF Research Database (Denmark)

    Bräuner-Osborne, H; Jensen, Anders A.; Krogsgaard-Larsen, P

    1999-01-01

    7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt) has previously been shown to be a selective non-competitive antagonist at the metabotropic glutamate (mGlu) receptor subtype 1. In this study we have tested the effect of CPCCOEt on mGlu1b, the calcium sensing receptor (...

  19. Exploring Valued-Added Options - Edge-Glued Panels and Blanks Offer Value-Added Opportunities

    Science.gov (United States)

    Bob Smith; Philip A. Araman

    1997-01-01

    As sawmills search for new opportunities to add value to rough sawn lumber, many consider producing dimension parts as one solution. Assembling dimension parts into edge-glued panels or standard blanks can add even further value. Blanks are defined as pieces of solid wood (which may be edge-glued) that are manufactured to a predetermined size. This article discusses...

  20. Reliability formulation for the strength and fire endurance of glued-laminated beams

    Science.gov (United States)

    D. A. Bender

    A model was developed for predicting the statistical distribution of glued-laminated beam strength and stiffness under normal temperature conditions using available long span modulus of elasticity data, end joint tension test data, and tensile strength data for laminating-grade lumber. The beam strength model predictions compared favorably with test data for glued-...

  1. A Virtual Research Partner

    National Research Council Canada - National Science Library

    Cowie, Jim; Guerrero, Felicia

    2006-01-01

    .... The goal was to investigate the feasibility of creating a software agent that would be able to interact with researchers and provide them with support at a level equivalent to a human research partner...

  2. Green Power Partner List

    Science.gov (United States)

    The U.S. EPA's Green Power Partnership is a voluntary program designed to reduce the environmental impact of electricity generation by promoting renewable energy. There are thousands of Green Power Partners, all listed on this page.

  3. CHP Partnership Partners

    Science.gov (United States)

    Partners of EPA's Combined Heat and Power Partnership include federal, state, and local government agencies and private organizations such as energy users, energy service companies, CHP project developers and consultants, and equipment manufacturers.

  4. Multiple sex partner

    African Journals Online (AJOL)

    User

    intercourse, about 60% reported having a single sexual partner and 40% reported having multiple ... masturbation, start having sex at a younger age, have sex with married people and/or .... sex were considered unacceptable by 89 vs.

  5. The lonely female partner

    DEFF Research Database (Denmark)

    Bruun, Poul; Pedersen, Birthe D; Osther, Palle J

    2011-01-01

    The aim of this qualitative study was to investigate the experiences of female partners to men with prostate cancer. The women found the capacity to manage their lives through mutual love in the family and through their faith.......The aim of this qualitative study was to investigate the experiences of female partners to men with prostate cancer. The women found the capacity to manage their lives through mutual love in the family and through their faith....

  6. Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4’s group III mGlu receptor functional potency and selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Schkeryantz, Jeffery M.; Chen, Qi; Ho, Joseph D.; Atwell, Shane; Zhang, Aiping; Vargas, Michelle C.; Wang, Jing; Monn, James A.; Hao, Junliang (Lilly)

    2018-02-01

    Here, L-2-Amino-4-phosphonobutyric acid (L-AP4) is a known potent and selective agonist for the Group III mGlu receptors. However, it does not show any selectivity among the individual group III mGlu subtypes. In order to understand the molecular basis for this group selectivity, we solved the first human mGlu8 amino terminal domain (ATD) crystal structures in complex with L-glu and L-AP4. In comparison with other published L-glu-bound mGlu ATD structures, we have observed L-glu binds in a significantly different manner in mGlu1. Furthermore, these new structures provided evidence that both the electronic and steric nature of the distal phosphate of L-AP4 contribute to its exquisite Group III functional agonist potency and selectivity.

  7. Intimate partner violence.

    Science.gov (United States)

    Cronholm, Peter F; Fogarty, Colleen T; Ambuel, Bruce; Harrison, Suzanne Leonard

    2011-05-15

    Intimate partner violence is a common source of physical, psychological, and emotional morbidity. In the United States, approximately 1.5 million women and 834,700 men annually are raped and/or physically assaulted by an intimate partner. Women are more likely than men to be injured, sexually assaulted, or murdered by an intimate partner. Studies suggest that one in four women is at lifetime risk. Physicians can use therapeutic relationships with patients to identify intimate partner violence, make brief office interventions, offer continuity of care, and refer them for subspecialty and community-based evaluation, treatment, and advocacy. Primary care physicians are ideally positioned to work from a preventive framework and address at-risk behaviors. Strategies for identifying intimate partner violence include asking relevant questions in patient histories, screening during periodic health examinations, and case finding in patients with suggestive signs or symptoms. Discussion needs to occur confidentially. Physicians should be aware of increased child abuse risk and negative effects on children's health observed in families with intimate partner violence. Physicians also should be familiar with local and national resources available to these patients.

  8. Synthesis and Sensory Characteristics of Kokumi γ-[Glu]n-Phe in the Presence of Glutamine and Phenylalanine: Glutaminase from Bacillus amyloliquefaciens or Aspergillus oryzae as the Catalyst.

    Science.gov (United States)

    Yang, Juan; Sun-Waterhouse, Dongxiao; Cui, Chun; Dong, Keming; Wang, Wei

    2017-10-04

    The transpeptidase activity of glutaminase from Bacillus amyloliquefaciens (GBA) and Aspergillus oryzae (GAO) to yield γ-[Glu] n -Phe peptides were verified for the first time. In the presence of Gln and Phe, γ-Glu-Phe and γ-Glu-γ-Glu-Phe were synthesized by GAO, and γ-Glu-Phe, γ-Glu-γ-Glu-Phe, γ-Glu-γ-Glu-γ-Glu-Phe, γ-Glu-γ-Glu-γ-Glu-γ-Glu-Phe, and γ-Glu-γ-Glu-γ-Glu-γ-Glu-γ-Glu-Phe were synthesized by GBA. The K m values for the transpeptidation catalyzed by GBA and GAO were 47.88 and 153.92 mM (Phe as the acceptor), 84.89 and 236.47 mM (γ-Glu-Phe as the acceptor), indicating that GBA had a greater affinity than GAO for Phe and γ-Glu-Phe in the transpeptidation reaction. The K m values for the transpeptidation catalyzed by GBA against acceptors, Phe and γ-[Glu] (1≤n<5) -Phe (47.88-206.47 mM), increased with an elevated number of γ-glutamyl residue within the acceptor. The optimal conditions for γ-[Glu] n -Phe synthesis were pH 10 and 37 °C for 3 h, 300 mM Gln, 100 mM Phe, 0.05 U/mL GBA. All the γ-[Glu] (1≤n≤5) -Phe exhibited astringency in water and imparted a kokumi taste to commercial soy sauce and model chicken broth. The astringent threshold values (2.5-3.92 mM) were approximately 3-fold of the kokumi threshold concentrations (0.78-1.53 mM). γ-[Glu] n -Phe or the post-enzymatic reaction mixture enhanced the umami intensity of commercial soy sauce and model chicken broth.

  9. Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs

    Directory of Open Access Journals (Sweden)

    Sanderson Thomas M

    2011-07-01

    Full Text Available Abstract The removal of AMPA receptors from synapses is a major component of long-term depression (LTD. How this occurs, however, is still only partially understood. To investigate the trafficking of AMPA receptors in real-time we previously tagged the GluA2 subunit of AMPA receptors with ecliptic pHluorin and studied the effects of NMDA receptor activation. In the present study we have compared the effect of NMDA receptor and group I mGluR activation, using GluA2 tagged with super ecliptic pHluorin (SEP-GluA2 expressed in cultured hippocampal neurons. Surprisingly, agonists of the two receptors, which are both able to induce chemical forms of LTD, had clearly distinct effects on AMPA receptor trafficking. In agreement with our previous work we found that transient NMDA receptor activation results in an initial decrease in surface GluA2 from extrasynaptic sites followed by a delayed reduction in GluA2 from puncta (putative synapses. In contrast, transient activation of group I mGluRs, using DHPG, led to a pronounced but more delayed decrease in GluA2 from the dendritic shafts. Surprisingly, there was no average change in the fluorescence of the puncta. Examination of fluorescence at individual puncta, however, indicated that alterations did take place, with some puncta showing an increase and others a decrease in fluorescence. The effects of DHPG were, like DHPG-induced LTD, prevented by treatment with a protein tyrosine phosphatase (PTP inhibitor. The electrophysiological correlate of the effects of DHPG in the SEP-GluA2 infected cultures was a reduction in mEPSC frequency with no change in amplitude. The implications of these findings for the initial mechanisms of expression of both NMDA receptor- and mGluR-induced LTD are discussed.

  10. Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD.

    Science.gov (United States)

    Zantomio, Daniela; Chana, Gursharan; Laskaris, Liliana; Testa, Renee; Everall, Ian; Pantelis, Christos; Skafidas, Efstratios

    2015-05-01

    The pathogenesis of Autism Spectrum Disorder (ASD), a serious neurodevelopmental disorder, is poorly understood. We review evidence for alterations in glutamatergic signalling in the aetiology of ASD, with a focus on the metabotropic glutamate receptor-5 (mGluR5). mGluR5 signalling is important for synapse formation, neuroplasticity and long term potentiation as well as neuroprotection and has been shown to have a regulatory role in neuroinflammation. Evidence for neuroinflammation in ASD is supported by increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid (CSF) and increased number and activation of microglia in postmortem dorsolateral prefrontal cortex (DLPFC). mGlur5 signalling has also been shown to downregulate microglial activation. Therefore, we focus on mGluR5 as a potential unifying explanation for synapse alteration and neuroinflammation seen in ASD. Data from mGluR5 knockout mouse models, and syndromic and non syndromic forms of ASD are discussed in relation to how alterations in mGluR5 are associated with ASD symptoms. This review supports altered mGluR5 functioning as a convergent point in ASD pathogenesis and indicates more research is warranted into mGluR5 as a potential therapeutic target. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Tyrosine dephosphorylation regulates AMPAR internalisation in mGluR-LTD.

    Science.gov (United States)

    Gladding, Clare M; Collett, Valerie J; Jia, Zhengping; Bashir, Zafar I; Collingridge, Graham L; Molnár, Elek

    2009-02-01

    Long-term depression (LTD) can be induced at hippocampal CA1 synapses by activation of either NMDA receptors (NMDARs) or group I metabotropic glutamate receptors (mGluRs), using their selective agonists NMDA and (RS)-3,5-dihydroxyphenylglycine (DHPG), respectively. Recent studies revealed that DHPG-LTD is dependent on activation of postsynaptic protein tyrosine phosphatases (PTPs), which transiently dephosphorylate tyrosine residues in AMPA receptors (AMPARs). Here we show that while both endogenous GluR2 and GluR3 AMPAR subunits are tyrosine phosphorylated at basal activity, only GluR2 is dephosphorylated in DHPG-LTD. The tyrosine dephosphorylation of GluR2 does not occur in NMDA-LTD. Conversely, while NMDA-LTD is associated with the dephosphorylation of GluR1-serine-845, DHPG-LTD does not alter the phosphorylation of this site. The increased AMPAR endocytosis in DHPG-LTD is PTP-dependent and involves tyrosine dephosphorylation of cell surface AMPARs. Together, these results indicate that the subunit selective tyrosine dephosphorylation of surface GluR2 regulates AMPAR internalisation in DHPG-LTD but not in NMDA-LTD in the hippocampus.

  12. mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.

    Directory of Open Access Journals (Sweden)

    Chris P Jew

    Full Text Available The group I metabotropic glutamate receptor 5 (mGluR5 has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.

  13. Strenght of the glue line of edge glued panels of Pinus taeda made with different adhesives

    Directory of Open Access Journals (Sweden)

    Merielen de Carvalho Lopes

    2013-12-01

    Full Text Available The study compares the strength of the glue line of edge glued panels of Pinus taeda made with different industrial adhesives. Three types of adhesives (poly(vinyl acetate (PVAc, emulsion polymer isocyanate (EPI and polyurethane (PU glued in two side gluing orientation (radial and tangential and analyzed after the conditioning tests (dry and wet were analyzed. The 360 specimens were prepared for determining the shear strength of edge glued panels of Pinus taeda, and these were tested in a universal testing machine called EMIC. The shear strength of the glue line at dry condition was lower in the tangential side for the three types of adhesives analyzed. The PU adhesive showed the highest values of shear strength in the applied conditions, differing from PVAc and EPI adhesive when tested on dry condition and did not differ from the others adhesives when tested on wet condition. The highest percentage of wood failure was observed after the shear strength test at dry condition to EPI adhesive glued in the radial side. And in the wet condition, the EPI adhesive and PU adhesive glued in tangential side showed higher mean values of wood failure. Thus, it was possible to conclude that the strength of the glue line of Pinus taeda wood was influenced by the type of adhesive and side gluing orientation, and showed differently behavior according to the condition of use (wet or dry.

  14. Identification of a novel signaling pathway and its relevance for GluA1 recycling.

    Directory of Open Access Journals (Sweden)

    Guiscard Seebohm

    Full Text Available We previously showed that the serum- and glucocorticoid-inducible kinase 3 (SGK3 increases the AMPA-type glutamate receptor GluA1 protein in the plasma membrane. The activation of AMPA receptors by NMDA-type glutamate receptors eventually leads to postsynaptic neuronal plasticity. Here, we show that SGK3 mRNA is upregulated in the hippocampus of new-born wild type Wistar rats after NMDA receptor activation. We further demonstrate in the Xenopus oocyte expression system that delivery of GluA1 protein to the plasma membrane depends on the small GTPase RAB11. This RAB-dependent GluA1 trafficking requires phosphorylation and activation of phosphoinositol-3-phosphate-5-kinase (PIKfyve and the generation of PI(3,5P(2. In line with this mechanism we could show PIKfyve mRNA expression in the hippocampus of wild type C57/BL6 mice and phosphorylation of PIKfyve by SGK3. Incubation of hippocampal slices with the PIKfyve inhibitor YM201636 revealed reduced CA1 basal synaptic activity. Furthermore, treatment of primary hippocampal neurons with YM201636 altered the GluA1 expression pattern towards reduced synaptic expression of GluA1. Our findings demonstrate for the first time an involvement of PIKfyve and PI(3,5P(2 in NMDA receptor-triggered synaptic GluA1 trafficking. This new regulatory pathway of GluA1 may contribute to synaptic plasticity and memory.

  15. Modes of strategic technology partnering Formy realizacji strategicznych partnerstw technologicznych

    Directory of Open Access Journals (Sweden)

    Łukasz Puślecki

    2008-06-01

    Full Text Available The aim of the article was to verify the organizational modes of strategic technological partnering. The author used a classification of modes of technology cooperation in terms of inter-organizational dependence to discuss major trends and characteristics of different forms of inter-firm partnering on the basis of the MERIT-CATI database. In the article the following forms of technological cooperation were presented: joint-ventures (JV, R&D pacts, technology exchange agreements and research contracts, customer-supplier relations, X-licensing as well as R&D contracts. The verification of such forms of technology partnering was made in years 1980-1996 on the basis of the empirical material taken from MERIT-CATI database.

  16. Are Emotions Transmitted From Work to Family? A Crossover Model of Psychological Contract Breach.

    Science.gov (United States)

    Liang, Huai-Liang

    2018-01-01

    Based on affective events theory and the crossover model, this study examines the effect of psychological contract breach on employee dysfunctional behavior and partner family undermining and explores the crossover effect of employee dysfunctional behavior on partner family undermining in work-family issues. This study collected 370 employee-partner dyads (277 male employees, 93 female employees, M age = 43.59 years) from a large manufacturing organization. The results of this study support the conception that employees' psychological contract breach results in frustration in the workplace. In addition, mediation analysis results reveal that psychological contract breach relates to employee dysfunctional behavior in the workplace. The findings show that partners' psychological strain mediates the relationship between employee dysfunctional behavior and partner family undermining. Furthermore, these findings provide investigations for the crossover model to display the value of psychological contract breach in family issues.

  17. Properties of GluR3 receptors tagged with GFP at the amino or carboxyl terminus.

    Science.gov (United States)

    Limon, Agenor; Reyes-Ruiz, Jorge Mauricio; Eusebi, Fabrizio; Miledi, Ricardo

    2007-09-25

    Anatomical visualization of neurotransmitter receptor localization is facilitated by tagging receptors, but this process can alter their functional properties. We have evaluated the distribution and properties of WT glutamate receptor 3 (GluR3) alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (WT GluR3) and two receptors in which GFP was tagged to the amino terminus (GFP-GluR3) or to the carboxyl terminus (GluR3-GFP). Although the fluorescence in Xenopus oocytes was stronger in the vegetal hemisphere because of localization of internal structures (probable sites of production, storage or recycling of receptors), the insertion of receptors into the plasma membrane was polarized to the animal hemisphere. The fluorescence intensity of oocytes injected with GluR3-GFP RNA was approximately double that of oocytes injected with GFP-GluR3 RNA. Accordingly, GluR3-GFP oocytes generated larger kainate-induced currents than GFP-GluR3 oocytes, with similar EC(50) values. Currents elicited by glutamate, or AMPA coapplied with cyclothiazide, were also larger in GluR3-GFP oocytes. The glutamate- to kainate-current amplitude ratios differed, with GluR3-GFP being activated more efficiently by glutamate than the WT or GFP-GluR3 receptors. This pattern correlates with the slower decay of glutamate-induced currents generated by GluR3-GFP receptors. These changes were not observed when GFP was tagged to the amino terminus, and these receptors behaved like the WT. The antagonistic effects of 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were not altered in any of the tagged receptors. We conclude that GFP is a useful and convenient tag for visualizing these proteins. However, the effects of different sites of tag insertion on receptor characteristics must be taken into account in assessing the roles played by these receptor proteins.

  18. Gas‒phase reactions of NO+ with Glu and γ‒Glu–Met

    OpenAIRE

    Wincel, H.; Fokkens, R. H.; Nibbering, N. M. M.

    2000-01-01

    The reactivity of the nitrosonium ion, NO+, with the amino acid Glu and the dipeptide γ‒Glu–Met in the gas phase has been investigated using the combination of chemical ionisation mass spectrometry and MS/MS. It is shown that NO+ reacts efficiently with both Glu and Glu–Met leading to the formation of the nitroso‒group containing ions at m/z 159 and 288.The formation of m/z 159, (GluNO‒18)+, is rationalized by a mechanism involving an electrophilic attack of NO+ upon the carbonyl oxygen atom ...

  19. Two Unique Cases with Anti-GluR Antibody-Positive Encephalitis

    Directory of Open Access Journals (Sweden)

    Kosuke Matsuzono

    2013-01-01

    Full Text Available We report two cases of anti-glutamic acid receptor (anti-GluR antibody-positive encephalitis in males with symptoms such as Parkinsonism, urinary retention, and paralytic ileus. Although non-herpetic encephalitis typically shows magnetic resonance imaging (MRI lesions in the limbic system during early stages, the present cases showed MRI lesions during later stages in the bilateral claustrum and pons. In both cases, anti-GluRε2 and δ2 antibodies were later shown to be positive in the cerebrospinal fluid but negative in the serum. Although early detection of anti-GluR antibodies is essential, early treatment may be significantly more important.

  20. Neurodevelopmental Expression Profile of Dimeric and Monomeric Group 1 mGluRs: Relevance to Schizophrenia Pathogenesis and Treatment.

    Science.gov (United States)

    Lum, Jeremy S; Fernandez, Francesca; Matosin, Natalie; Andrews, Jessica L; Huang, Xu-Feng; Ooi, Lezanne; Newell, Kelly A

    2016-10-10

    Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically declining at adolescence and adulthood (-97-99%). The mGluR regulators, Homer 1b/c and Norbin, significantly increased with age in the PFC and hippocampus. Perinatal PCP treatment significantly increased juvenile dimeric mGluR5 levels in the PFC and hippocampus (37-50%) but decreased hippocampal mGluR1α (-50-56%). Perinatal PCP treatment also reduced mGluR1α dimer levels in the PFC at adulthood (-31%). These results suggest that Group 1 mGluRs have distinct dimeric and monomeric neurodevelopmental patterns, which may impact their pharmacological profiles at specific ages. Perinatal PCP treatment disrupted the early expression of Group 1 mGluRs which may underlie neurodevelopmental alterations observed in this model.

  1. The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain

    Directory of Open Access Journals (Sweden)

    Amanda Lorraine Wright

    2012-04-01

    Full Text Available AMPA receptors are comprised of different combinations of GluR1-GluR4 (also known as GluA1-GluA4 and GluR-A to GluR-D subunits. The GluR2 subunit is subject to Q/R site RNA editing by the ADAR2 enzyme, which converts a codon for glutamine (Q, present in the GluR2 gene, to a codon for arginine (R found in the mRNA. AMPA receptors are calcium (Ca2+-permeable if they contain the unedited GluR2(Q subunit or if they lack the GluR2 subunit. While most AMPA receptors in the brain contain the edited GluR2(R subunit and are therefore Ca2+-impermeable, recent evidence suggests that Ca2+-permeable GluR2-lacking AMPA receptors are important in synaptic plasticity and learning. However, the presence of Ca2+-permeable AMPA receptors containing unedited GluR2 leads to excitotoxic cell loss. Recent studies have indicated that RNA editing of GluR2 is deregulated in diseases, such as amyotrophic lateral sclerosis (ALS, as well in acute neurodegenerative conditions, such as ischemia. More recently, studies have investigated the regulation of RNA editing and possible causes for its deregulation during disease. In this review, we will explore the role of GluR2 RNA editing in the healthy and diseased brain and outline new insights into the mechanisms that control this process.

  2. The Regulation of GluN2A by Endogenous and Exogenous Regulators in the Central Nervous System.

    Science.gov (United States)

    Sun, Yongjun; Zhan, Liying; Cheng, Xiaokun; Zhang, Linan; Hu, Jie; Gao, Zibin

    2017-04-01

    The NMDA receptor is the most widely studied ionotropic glutamate receptor, and it is central to many physiological and pathophysiological processes in the central nervous system. GluN2A is one of the two main types of GluN2 NMDA receptor subunits in the forebrain. The proper activity of GluN2A is important to brain function, as the abnormal regulation of GluN2A may induce some neuropsychiatric disorders. This review will examine the regulation of GluN2A by endogenous and exogenous regulators in the central nervous system.

  3. Pennsylvania's partnering process

    International Nuclear Information System (INIS)

    Latham, J.W.

    1996-01-01

    Pennsylvania is committed to finding a site for a low-level radioactive waste (LLRW) disposal facility through an innovative voluntary process. The Pennsylvania Department of Environmental Protection (DEP) and Chem-Nuclear Systems, Inc. (CNSI) developed the Community Partnering Plan with extensive public participation. The Community Partnering Plan outlines a voluntary process that empowers municipalities to evaluate the advantages and disadvantages of hosting the facility. DEP and CNSI began developing the Community Partnering Plan in July 1995. Before then, CNSI was using a screening process prescribed by state law and regulations to find a location for the facility. So far, approximately 78 percent of the Commonwealth has been identified as disqualified as a site for the LLRW disposal facility. The siting effort will now focus on identifying volunteer host municipalities in the remaining 22 percent of the state. This combination of technical screening and voluntary consideration makes Pennsylvania's process unique. A volunteered site will have to meet the same tough requirements for protecting people and the environment as a site chosen through the screening process. Protection of public health and safety continues to be the foundation of the state's siting efforts. The Community Partnering Plan offers a window of opportunity. If Pennsylvania does not find volunteer municipalities with suitable sites by the end of 1997, it probably will return to a technical screening process

  4. Intimate partner violence (IPV)

    DEFF Research Database (Denmark)

    Rasch, Vibeke; Van, Toan Ngo; Nguyen, Hanh Thi Thuy

    2018-01-01

    BACKGROUND: Intimate partner violence (IPV) is a global problem that affects one-third of all women. The present study aims to develop and determine the validity of a screening instrument for the detection of IPV in pregnant women in Tanzania and Vietnam and to determine the minimum number...

  5. Predictability of Conversation Partners

    Science.gov (United States)

    Takaguchi, Taro; Nakamura, Mitsuhiro; Sato, Nobuo; Yano, Kazuo; Masuda, Naoki

    2011-08-01

    Recent developments in sensing technologies have enabled us to examine the nature of human social behavior in greater detail. By applying an information-theoretic method to the spatiotemporal data of cell-phone locations, [C. Song , ScienceSCIEAS0036-8075 327, 1018 (2010)] found that human mobility patterns are remarkably predictable. Inspired by their work, we address a similar predictability question in a different kind of human social activity: conversation events. The predictability in the sequence of one’s conversation partners is defined as the degree to which one’s next conversation partner can be predicted given the current partner. We quantify this predictability by using the mutual information. We examine the predictability of conversation events for each individual using the longitudinal data of face-to-face interactions collected from two company offices in Japan. Each subject wears a name tag equipped with an infrared sensor node, and conversation events are marked when signals are exchanged between sensor nodes in close proximity. We find that the conversation events are predictable to a certain extent; knowing the current partner decreases the uncertainty about the next partner by 28.4% on average. Much of the predictability is explained by long-tailed distributions of interevent intervals. However, a predictability also exists in the data, apart from the contribution of their long-tailed nature. In addition, an individual’s predictability is correlated with the position of the individual in the static social network derived from the data. Individuals confined in a community—in the sense of an abundance of surrounding triangles—tend to have low predictability, and those bridging different communities tend to have high predictability.

  6. Predictability of Conversation Partners

    Directory of Open Access Journals (Sweden)

    Taro Takaguchi

    2011-09-01

    Full Text Available Recent developments in sensing technologies have enabled us to examine the nature of human social behavior in greater detail. By applying an information-theoretic method to the spatiotemporal data of cell-phone locations, [C. Song et al., Science 327, 1018 (2010SCIEAS0036-8075] found that human mobility patterns are remarkably predictable. Inspired by their work, we address a similar predictability question in a different kind of human social activity: conversation events. The predictability in the sequence of one’s conversation partners is defined as the degree to which one’s next conversation partner can be predicted given the current partner. We quantify this predictability by using the mutual information. We examine the predictability of conversation events for each individual using the longitudinal data of face-to-face interactions collected from two company offices in Japan. Each subject wears a name tag equipped with an infrared sensor node, and conversation events are marked when signals are exchanged between sensor nodes in close proximity. We find that the conversation events are predictable to a certain extent; knowing the current partner decreases the uncertainty about the next partner by 28.4% on average. Much of the predictability is explained by long-tailed distributions of interevent intervals. However, a predictability also exists in the data, apart from the contribution of their long-tailed nature. In addition, an individual’s predictability is correlated with the position of the individual in the static social network derived from the data. Individuals confined in a community—in the sense of an abundance of surrounding triangles—tend to have low predictability, and those bridging different communities tend to have high predictability.

  7. Metabotrobic Glutamate Receptor mGluR4 as a Novel Target for Parkinson's Disease

    National Research Council Canada - National Science Library

    Levey, Alan

    2000-01-01

    ...) as a novel target for the treatment of PD. We have localized mGluP4 in basal ganglia structures, and explored its role in mediating the electrophysiological effects of glutamate in rat brain slices...

  8. Metabotropic Glutamate Receptor mGluR4 as a Novel Target for Parkinson's Disease

    National Research Council Canada - National Science Library

    Levey, Allan

    2001-01-01

    ...) as a novel target for the treatment of PD. We have localized mGluR4 in basal ganglia structures, and explored its role in mediating the electrophysiological effects of glutamate in rat brain slices...

  9. BEHAVIOR OF GLUED JOINTS OF EUCALYPTUS sp. SAWN WOOD

    Directory of Open Access Journals (Sweden)

    Octávio Barbosa Plaster

    2008-09-01

    Full Text Available This research evaluated eucalypt wood adhesion capacity. The material evaluated was a commercial sawn wood composed by a blend of species of the genus Eucalyptus. The adhesives used were resorcinol-formaldehyde and polyvinila acetate (PVAc. The wood was segregated in three density with 0% of moisture content: class 1; 2 and 3 that, when combined (class1 x class1; 2x2; 3x3; 1x2; 1x3; 2x3 resulted in six treatments. The performance of the adhesion was evaluated by the shear strength to parallel compression and by wood failure in the glue line. The obtained results allowed to conclude that the adhesion of the combinations of wood/adhesive presented satisfactory performance. The average shear strength of the joints were shown equivalent to the shear strength of the solid wood with similar performance of adhesion in the two adhesives. In general, resorcinol-formaldheyde adhesive presented higher values (74.41% for wood failure in the joints, but similar to all treatments. The adhesion of samples of higher density presented lower performance probably when only the values of wood failure are considered. The values for the strength of glued joints, in general, were similar when analyzed the results achieved with the resorcinol-formaldehyde adhesive- base 140,56 Kgf/cm2. To polyvinila acetate the values of wood failure decrease when the density increase (65.94%, but the resistance in the glue line was positively affected (140.25 Kgf/cm2. In general, the density influenced the adhesion of the joints for the employed adhesives.

  10. Laser-based gluing of diamond-tipped saw blades

    Science.gov (United States)

    Hennigs, Christian; Lahdo, Rabi; Springer, André; Kaierle, Stefan; Hustedt, Michael; Brand, Helmut; Wloka, Richard; Zobel, Frank; Dültgen, Peter

    2016-03-01

    To process natural stone such as marble or granite, saw blades equipped with wear-resistant diamond grinding segments are used, typically joined to the blade by brazing. In case of damage or wear, they must be exchanged. Due to the large energy input during thermal loosening and subsequent brazing, the repair causes extended heat-affected zones with serious microstructure changes, resulting in shape distortions and disadvantageous stress distributions. Consequently, axial run-out deviations and cutting losses increase. In this work, a new near-infrared laser-based process chain is presented to overcome the deficits of conventional brazing-based repair of diamond-tipped steel saw blades. Thus, additional tensioning and straightening steps can be avoided. The process chain starts with thermal debonding of the worn grinding segments, using a continuous-wave laser to heat the segments gently and to exceed the adhesive's decomposition temperature. Afterwards, short-pulsed laser radiation removes remaining adhesive from the blade in order to achieve clean joining surfaces. The third step is roughening and activation of the joining surfaces, again using short-pulsed laser radiation. Finally, the grinding segments are glued onto the blade with a defined adhesive layer, using continuous-wave laser radiation. Here, the adhesive is heated to its curing temperature by irradiating the respective grinding segment, ensuring minimal thermal influence on the blade. For demonstration, a prototype unit was constructed to perform the different steps of the process chain on-site at the saw-blade user's facilities. This unit was used to re-equip a saw blade with a complete set of grinding segments. This saw blade was used successfully to cut different materials, amongst others granite.

  11. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition.

    Science.gov (United States)

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-08-11

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 ( GluR2 ) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2 . This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT.

  12. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition

    Science.gov (United States)

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2. This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT. PMID:28800112

  13. Expression, crystallization and preliminary crystallographic study of GluB from Corynebacterium glutamicum

    International Nuclear Information System (INIS)

    Liu, Qingbo; Li, Defeng; Hu, Yonglin; Wang, Da-Cheng

    2013-01-01

    GluB, a substrate-binding protein from C. glutamicum, was expressed, purified and crystallized, followed by X-ray diffraction data collection and preliminary crystallographic analysis. GluB is a substrate-binding protein (SBP) which participates in the uptake of glutamic acid in Corynebacterium glutamicum, a Gram-positive bacterium. It is part of an ATP-binding cassette (ABC) transporter system. Together with the transmembrane proteins GluC and GluD and the cytoplasmic protein GluA, which couples the hydrolysis of ATP to the translocation of glutamate, they form a highly active glutamate-uptake system. As part of efforts to study the amino-acid metabolism, especially the metabolism of glutamic acid by C. glutamicum, a bacterium that is widely used in the industrial production of glutamic acid, the GluB protein was expressed, purified and crystallized, an X-ray diffraction data set was collected to a resolution of 1.9 Å and preliminary crystallographic analysis was performed. The crystal belonged to space group P3 1 21 or P3 2 21, with unit-cell parameters a = b = 82.50, c = 72.69 Å

  14. Glu- and Lys-forms of plasminogen differentially affect phosphatidylserine exposure on the platelet surface

    Directory of Open Access Journals (Sweden)

    D. D. Zhernossekov

    2017-04-01

    Full Text Available Plasminogen/plasmin system is known for its ability to support hemostatic balance of blood. However, plasminogen may be considered as an adhesive ligand and in this way could affect the functioning of blood cells. We showed that exogenous Lys-plasminogen, but not its Glu-form, inhibited platelet aggregation and suppressed platelet α-granule secretion. The aim of this work was to investigate the influence of Glu- and Lys-form of plasminogen on the formation of platelet procoagulant surface using phosphatidylserine exposure as a marker. Human platelets were obtained from human platelet-rich plasma (donors were healthy volunteers, men aged 30-40 years by gel-filtration on Sepharose 2B. Phosphatidylserine exposure on the platelet surface was evaluated by flow cytometry with FITC-conjugated annexin A5. Glu- and Lys-plasminogen have different impact on the platelet functioning. Exogenous Lys-plasminogen has no significant effect on phosphatidylserine exposure, while Glu-plasminogen increases phosphatidylserine exposure on the surface of thrombin- and collagen-activated human platelets. Glu-plasminogen can be considered as a co-stimulator of agonist-induced platelet secretion and procoagulant surface formation. Meanwhile effects of Lys-plasminogen are probably directed at platelet-platelet interactions and not related to agonist-stimulated pro-apoptotic changes. The observed different effects of Glu- and Lys-plasminogen on phosphatidylserine exposure can be explained by their structural peculiarities.

  15. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    Energy Technology Data Exchange (ETDEWEB)

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J. (Medical College of Wisconsin, Milwaukee (USA))

    1989-11-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from (3H-nicotinamide)NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from (32P-adenylate)NAD (0.2 mol/mol of protein). Label from (3H-nicotinamide)NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with (3H-nicotinamide)NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

  16. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    International Nuclear Information System (INIS)

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J.

    1989-01-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from [3H-nicotinamide]NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from [32P-adenylate]NAD (0.2 mol/mol of protein). Label from [3H-nicotinamide]NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with [3H-nicotinamide]NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis

  17. Involvement of AMPA receptor GluR2 and GluR3 trafficking in trigeminal spinal subnucleus caudalis and C1/C2 neurons in acute-facial inflammatory pain.

    Directory of Open Access Journals (Sweden)

    Makiko Miyamoto

    Full Text Available To evaluate the involvement of trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR GluR2 and GluR3 subunits in an acute inflammatory orofacial pain, we analyzed nocifensive behavior, phosphorylated extracellular signal-regulated kinase (pERK and Fos expression in Vi/Vc, Vc and C1/C2 in GluR2 delta7 knock-in (KI, GluR3 delta7 KI mice and wild-type mice. We also studied Vc neuronal activity to address the hypothesis that trafficking of GluR2 and GluR3 subunits plays an important role in Vi/Vc, Vc and C1/C2 neuronal activity associated with orofacial inflammation in these mice. Late nocifensive behavior was significantly depressed in GluR2 delta7 KI and GluR3 delta7 KI mice. In addition, the number of pERK-immunoreactive (IR cells was significantly decreased bilaterally in the Vi/Vc, Vc and C1/C2 in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice at 40 min after formalin injection, and was also significantly smaller in GluR3 delta7 KI compared to GluR2 delta7 KI mice. The number of Fos protein-IR cells in the ipsilateral Vi/Vc, Vc and C1/C2 was also significantly smaller in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice 40 min after formalin injection. Nociceptive neurons functionally identified as wide dynamic range neurons in the Vc, where pERK- and Fos protein-IR cell expression was prominent, showed significantly lower spontaneous activity in GluR2 delta7 KI and GluR3 delta7 KI mice than wild-type mice following formalin injection. These findings suggest that GluR2 and GluR3 trafficking is involved in the enhancement of Vi/Vc, Vc and C1/C2 nociceptive neuronal excitabilities at 16-60 min following formalin injection, resulting in orofacial inflammatory pain.

  18. Reviving Ulysses contracts.

    Science.gov (United States)

    Spellecy, Ryan

    2003-12-01

    Ulysses contracts have faced paternalism objections since they first were proposed. Since the contracts are designed to override a present request from a legally competent patient in favor of a past request made by that patient, enforcement of these contracts was argued to be unjustifiable strong paternalism. Recent legal developments and new theories of practical reasoning suggest that the discussion of Ulysses contracts should be revived. This paper argues that with a proper understanding of the future-directed planning embodied in Ulysses contracts, the charge of strong paternalism can be answered, and the enforcement of some Ulysses contracts may be justified under the rubric of weak paternalism.

  19. ADMINISTRATIVE CONTRACTS. DELIMITATIONS

    Directory of Open Access Journals (Sweden)

    Liana Teodora PASCARIU

    2016-12-01

    Full Text Available Article examines whether all contracts of public persons are administrative contracts; in other words, if the administration may conclude contracts that, according to their legal nature, are not administrative. If we start from the definition of administrative contracts as it appears in Law no. 554/2004, these include contracts by public authorities which concern the enhancement of public property execution of works of public interest, public services, public procurement and other administrative contracts provided by special laws and subject to the jurisdiction of the administrative courts.

  20. Pacific Partners Wargame Analysis

    Science.gov (United States)

    2014-09-01

    such as medical qualifications and malpractice considerations, can be explored as part of interoperability. Partner nations are motivated to...prefers a medical research focus. Subsuming medical under HA/DR attempts to minimize those differences. There were dissenting views on the proposed...positive view of USARPAC engagement activities, they were still able to develop ideas for ways to improve engagement activities by modifying or

  1. Role of B13 Glu in insulin assembly. The hexamer structure of recombinant mutant (B13 Glu-->Gln) insulin.

    Science.gov (United States)

    Bentley, G A; Brange, J; Derewenda, Z; Dodson, E J; Dodson, G G; Markussen, J; Wilkinson, A J; Wollmer, A; Xiao, B

    1992-12-20

    The assembly of the insulin hexamer brings the six B13 glutamate side-chains at the centre into close proximity. Their mutual repulsion is unfavourable and zinc co-ordination to B10 histidine is necessary to stabilize the well known zinc-containing hexamers. Since B13 is always a carboxylic acid in all known sequences of hexamer forming insulins, it is likely to be important in the hormone's biology. The mutation of B13 Glu-->Gln leads to a stable zinc-free hexamer with somewhat reduced potency. The structures of the zinc-free B13 Gln hexamer and the 2Zn B13 insulin hexamer have been determined by X-ray analysis and refined with 2.5 A and 2.0 A diffraction data, respectively. Comparisons show that in 2Zn B13 Gln insulin, the hexamer structure (T6) is very like that of the native hormone. On the other hand, the zinc-free hexamer assumes a quaternary structure (T3/R3) seen in the native 4Zn insulin hexamer, and normally associated only with high chloride ion concentrations in the medium. The crystal structures show the B13 Gln side-chains only contact water in contrast to the B13 glutamate in 2Zn insulin. The solvation of the B13 Gln may be associated with this residue favouring helix at B1 to B8. The low potency of the B13 Gln insulin also suggests the residue influences the hormone's conformation.

  2. Interaction Quality during Partner Reading

    OpenAIRE

    Meisinger, Elizabeth B.; Schwanenflugel, Paula J.; Bradley, Barbara A.; Stahl, Steven A.

    2004-01-01

    The influence of social relationships, positive interdependence, and teacher structure on the quality of partner reading interactions was examined. Partner reading, a scripted cooperative learning strategy, is often used in classrooms to promote the development of fluent and automatic reading skills. Forty-three pairs of second grade children were observed during partner reading sessions taking place in 12 classrooms. The degree to which the partners displayed social cooperation (instrumental...

  3. Contracting: The modern way to work. A professional's perspective

    International Nuclear Information System (INIS)

    Banks, C.D.; Pavan, E.A.

    1991-01-01

    The relationship between employers and employees in the oil and gas industry has undergone some fundamental changes, including increasing use of contract professionals, work sharing, more work done at home, individuals partnering or in association with groups of professionals, and transfer of properties to subsidiaries or contract management organizations. The use of contract professionals and technical personnel within an existing corporate structure is examined. Reasons for individuals to choose contracting include career choice, early- or semi-retired status, between jobs, and family/personal reasons. Contracting provides a more open relationship between the professional and the contractor, allows professionals to pursue a career of choice, and gives time flexibility. By contracting through a linking company, a professional can earn about the same annual income as through regular employment if 220 days of work a year can obtained. 1 tab

  4. Partner personality in distressed relationships

    NARCIS (Netherlands)

    Barelds, D.P.H.; Barelds-Dijkstra, P.

    2006-01-01

    The present study examines the personality characteristics of partners receiving marital therapy. On the basis of previous research, we expected partners in distressed relationships to be more neurotic and more introverted and to have lower self-esteem than partners in non-distressed relationships.

  5. Contractibility of curves

    Directory of Open Access Journals (Sweden)

    Janusz Charatonik

    1991-11-01

    Full Text Available Results concerning contractibility of curves (equivalently: of dendroids are collected and discussed in the paper. Interrelations tetween various conditions which are either sufficient or necessary for a curve to be contractible are studied.

  6. Concept of contracting authority

    OpenAIRE

    Kasiliauskaitė, Vitalija

    2016-01-01

    Concept of Contracting Authority Law on Public Procurement the procurement concept implies the conclusion that public procurement be declared only such purchases are carried out by the contracting authority. The contracting authorities can be a subject of state and municipal management institutes, whose assignment authority is determined by a functional approach. Also, contracting authorities may be public and legal entities, but that the public interest and operates non-commercial activities...

  7. Inflation Forecast Contracts

    OpenAIRE

    Gersbach, Hans; Hahn, Volker

    2012-01-01

    We introduce a new type of incentive contract for central bankers: inflation forecast contracts, which make central bankers’ remunerations contingent on the precision of their inflation forecasts. We show that such contracts enable central bankers to influence inflation expectations more effectively, thus facilitating more successful stabilization of current inflation. Inflation forecast contracts improve the accuracy of inflation forecasts, but have adverse consequences for output. On balanc...

  8. Teaching about Contracts.

    Science.gov (United States)

    Froman, Michael; Kosnoff, Kathy

    1978-01-01

    Presents teaching strategies for introducing high school students to contract law. Offers as a case study a contract agreement between pro football players and team owners. Stresses basic elements of contracts (offer, acceptance, consideration, and understanding the bargaining process). Journal available from the American Bar Association, 1155…

  9. Contract law as fairness

    NARCIS (Netherlands)

    Klijnsma, J.

    2015-01-01

    This article examines the implications for contract law of Rawls' theory of justice as fairness. It argues that contract law as an institution is part of the basic structure of society and as such subject to the principles of justice. Discussing the basic structure in relation to contract law is

  10. 3 CFR - Government Contracting

    Science.gov (United States)

    2010-01-01

    ... contract oversight could reduce such sums significantly. Government outsourcing for services also raises... a risk that taxpayer funds will be spent on contracts that are wasteful, inefficient, subject to... mission. In such cases, the agency must ensure that the risks associated with noncompetitive contracts are...

  11. Contracting for nuclear fuels

    International Nuclear Information System (INIS)

    Schuessler, C.M.

    1981-10-01

    This paper deals with uranium sales contracts, i.e. with contractual arrangements in the first steps of the fuel cycle, which cover uranium production and conversion. The various types of contract are described and, where appropriate, their underlying business philosophy and their main terms and conditions. Finally, the specific common features of such contracts are reviewed. (NEA) [fr

  12. Other enrichment related contracts

    International Nuclear Information System (INIS)

    Hall, J.C.

    1978-01-01

    In addition to long-term enrichment contracts, DOE has other types of contracts: (1) short-term, fixed-commitment enrichment contract; (2) emergency sales agreement for enriched uranium; (3) feed material lease agreement; (4) enriched uranium storage agreement; and (5) feed material usage agreement

  13. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    Directory of Open Access Journals (Sweden)

    Sheng-Chun Mao

    Full Text Available Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5, but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95 and synapse-associated protein-97 (SAP97. Accordingly, delivery of Tat-GluR2(3Y, a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  14. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    Science.gov (United States)

    Mao, Sheng-Chun; Chang, Chih-Hua; Wu, Chia-Chen; Orejarena, M Juliana; Orejanera, Maria Juliana; Manzoni, Olivier J; Gean, Po-Wu

    2013-01-01

    Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR2(3Y), a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  15. Strength at Home Couples Program to Prevent Military Partner Violence

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0374 TITLE: Strength at Home Couples Program to Prevent Military Partner Violence PRINCIPAL INVESTIGATOR: Casey T...SUBTITLE 5a. CONTRACT NUMBER Strength at Home Couples Program to Prevent Military Partner Violence 5b. GRANT NUMBER W81XWH-15-1-0374 5c. PROGRAM...7 9. Appendices…………………………………………………………………………………..7 1 Annual Report for Period: Sep 30, 2016 to Sept 29, 2017 Strength at Home

  16. The Hidden Roles That Management Partners Play In Accountable Care Organizations.

    Science.gov (United States)

    Lewis, Valerie A; D'Aunno, Thomas; Murray, Genevra F; Shortell, Stephen M; Colla, Carrie H

    2018-02-01

    Accountable care organizations (ACOs) are often discussed and promoted as driven by physicians, hospitals, and other health care providers. However, because of the flexible nature of ACO contracts, management organizations may also become partners in ACOs. We used data from 2013-15 on 276 ACOs from the National Survey of Accountable Care Organizations to understand the prevalence of nonprovider management partners' involvement in ACOs, the services these partners provide, and the structure of ACOs that have such partners. We found that 37 percent of ACOs reported having a management partner, and two-thirds of these ACOs reported that the partner shared in the financial risks or rewards. Among ACOs with partners, 94 percent had data services provided by the partner, 87 percent received administrative services, 68 percent received educational services, and 66 percent received care coordination services. Half received all four of these services from their partner. ACOs with partners were more heavily primary care than other ACOs. ACOs with and without partners had similar performance on costs and quality in Medicare ACO programs. Our findings suggest that management partners play a central role in many ACOs, perhaps supplying smaller and physician-run ACOs with services or expertise perceived as necessary for ACO success.

  17. Care partner: A concept analysis.

    Science.gov (United States)

    Bennett, Paul N; Wang, Wei; Moore, Mel; Nagle, Cate

    The use of the term care partner has increased, particularly in the chronic disease literature; however, the concept has not been well defined. The purpose of this concept analysis was to define and assist nurses to better understand the concept of care partner. The method by Walker and Avant was used for this literature-based concept analysis. Care partnering includes providing assistance to an individual with a health condition to meet their self-care deficits, the commitment to a care partner relationship, and the recognition that people with self-care deficits are care partners contributing to their own care. Emphasizing the care partner dyad in nursing may contribute to improved patient care outcomes both in the acute and chronic settings. It is recommended that nurses view the person with the condition as a contributor and partner in their own care in the context of a larger care partnership. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. New partner - Forestland

    CERN Multimedia

    Staff Association

    2014-01-01

      New partner   Do you need a moment of relaxation and adventure?  Come to Divonne-les-bains and benefit of an immediate discount of 20% on all ropes courses of Forestland http://www.forestland.fr/ upon presentation of your Staff Association membership card. The park is open from 10h00 to 19h00 on Wednesday, Saturday, Sunday during the school period and public holidays (France and Switzerland) or every day during school holidays (France and Switzerland). Different levels of difficulty are available: children, juniors, adults, athletes.

  19. Benefiting through partnering

    International Nuclear Information System (INIS)

    Carr, T.J.

    2000-01-01

    As a consequence of dramatic changes in the world market in nuclear services over the last decade, BNFL has embarked on a comprehensive strategic review of its business. Central to this review has been the need for the company to achieve cost reduction and improved efficiency in all aspects of its business. An area where substantial benefits can be gained is in improved efficiency in the discharge of the capital expenditure programme. This paper focuses on the opportunity of profiting through partnering in capital project delivery. (author)

  20. Duration in Production Contracts

    OpenAIRE

    MacDonald, James M.; Korb, Penelope J.

    2006-01-01

    We use 2003 and 2004 ARMS data to analyze variations in contract duration among growers of broilers who hold production contracts. Most contracts cover just a single flock, but many extend for 1-2 years, and a significant minority of broiler contracts specify lengths of 5, 10, and even 15 years. We find that grower debt and production volume are inversely related to the choice of a short term (a year or less) contract, while lengthy prior experience with the contractor promotes short term con...

  1. The Role of GluK4 in Synaptic Plasticity and Affective Behavior in Mice

    Science.gov (United States)

    Catches, Justin Samuel

    Kainate receptors (KARs) are glutamate-gated ion channels that signal through both ionotropic and metabotropic pathways (Contractor et al., 2011). Combinations of five KAR subunits (GluK1-5) form tetrameric receptors with GluK1, GluK2, and GluK3 able to form functional homomeric channels. The high-affinity subunits, GluK4 and GluK5, do not form homomeric channels but modify the properties of heteromeric receptors. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs modulate synaptic plasticity. In this study, ablation of Grik4, which encodes GluK4, in mice reduced KAR synaptic currents and altered activation properties of postsynaptic receptors but left two forms of presynaptic short-term plasticity intact. Disruption of both Grik4 and Grik5 caused complete loss of the postsynaptic ionotropic KAR current and impaired presynaptic frequency facilitation. Additionally, KAR surface expression was altered at pre- and postsynaptic sites at the MF synapse. Despite the loss of ionotropic signaling, KAR-mediated inhibition of the slow afterhyperpolarization current, which is dependent on metabotropic signaling, was intact in CA3 neurons. Long-term potentiation at the MF-CA3 synapse was reduced, likely through a loss of KAR modulation of excitability of the presynaptic MF axons. Genetic variants in the human GRIK4 gene alter the susceptibility for affective disorders (Bloss and Hunter, 2010). We found that ablation of Grik4 in mice resulted in reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, and in two anxiogenic tests, marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim, a test of learned helplessness used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting

  2. Prenatal Exposure to Tributyltin Decreases GluR2 Expression in the Mouse Brain.

    Science.gov (United States)

    Ishida, Keishi; Saiki, Takashi; Umeda, Kanae; Miyara, Masatsugu; Sanoh, Seigo; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), a common environmental contaminant, is widely used as an antifouling agent in paint. We previously reported that exposure of primary cortical neurons to TBT in vitro decreased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate receptor 2 (GluR2) expression and subsequently increased neuronal vulnerability to glutamate. Therefore, to identify whether GluR2 expression also decreases after TBT exposure in vivo, we evaluated the changes in GluR2 expression in the mouse brain after prenatal or postnatal exposure to 10 and 25 ppm TBT through pellet diets. Although the mean feed intake and body weight did not decrease in TBT-exposed mice compared with that in control mice, GluR2 expression in the cerebral cortex and hippocampus decreased after TBT exposure during the prenatal period. These results indicate that a decrease in neuronal GluR2 may be involved in TBT-induced neurotoxicity, especially during the fetal period.

  3. Recent Advances in the Medicinal Chemistry of the Metabotropic Glutamate Receptor 1 (mGlu1)

    Science.gov (United States)

    2011-01-01

    This Review summarizes the medicinal chemistry found in publications on both orthosteric and allosteric modulators of the metabotropic glutamate receptor 1 (mGlu1) from 2005 to the present. The time period covered by the scope of this current review has been particularly rich in mGlu1-related publications with numbers quadrupling when compared to the preceding five year period of 2000−2005. Publications in the field peaked in 2007 with over 35 articles appearing in the peer reviewed literature in the course of that year. Given that glutamate is one of the primary excitatory neurotransmitters in the mammalian central nervous system (CNS), it is unsurprising that it acts upon several receptors that are considered to be of potential therapeutic interest for many indications. Orthosteric and allosteric modulation of the receptor is possible, with a logical extrapolation to the chemotypes used for each strategy. The last five years of publications have yielded many mGlu1 selective antagonist chemotypyes, most of which have shown efficacy in pain in vivo models. However, the primary impact of these compounds has been to highlight the mechanistic safety risks of mGlu1 antagonism, independent of chemotype. As a review in medicinal chemistry, the primary focus of this paper will be on the design and, to a lesser degree, synthetic strategies for the delivery of subtype selective, CNS penetrant, druglike compounds through a “medchem” program, targeting modulators of the mGlu1 receptor. PMID:22860168

  4. Effects of microwave exposure on motor learning and GluR2 phosphorylation in rabbit cerebellum

    International Nuclear Information System (INIS)

    Liu Yong; Wang Denggao; Zhang Guangbin; Zhou Wen; Yang Xuesen

    2007-01-01

    Objective: To investigate the effects of microwave exposure on motor learning and Glutamate receptor 2(GluR2) phosphorylation in rat cerebellum. Methods: The rabbits were trained for seven days to form eye-blink conditioning, and then divided randomly into control and microwave exposure group (at hours 0,3,24 and 72 subgroups after exposure, respectively). The rabbits were accepted 90 mW/cm 2 microwave exposure for 30 minutes, and the rectal temperature were detected immediately after exposure and specific absorption rate (SAR) value were calculated. Eye-blink conditioning were detected immediately after exposure, and cerebellar GluR2 protein and GluR2 phosphorylation were detected with Western blotting. Results: Rectal temperature of rabbits were increased by 3.02 degree C after exposure, and SAR value was 8.74 W/kg. The eye-blink conditioning decreased significantly after exposure, and cerebellar GluR2 protein expression had no significant alteration but phosphorylation reduced significantly after exposure. Conclusions: 90 mW/cm 2 microwave exposure has injurious effects on cerebellar GluR2 phosphorylation and motor learning. (authors)

  5. Lack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Coppedè, Fabio; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Mancuso, Michelangelo; Pasquali, Livia; Murri, Luigi; Migliore, Lucia; Siciliano, Gabriele

    2010-02-01

    Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population.

  6. Dough properties and bread-making quality-related characteristics of Yumechikara near-isogenic wheat lines carrying different Glu-B3 alleles.

    Science.gov (United States)

    Ito, Miwako; Maruyama-Funatsuki, Wakako; Ikeda, Tatsuya M; Nishio, Zenta; Nagasawa, Koichi; Tabiki, Tadashi

    2015-06-01

    We investigated the relationships of three allelic variations in Glu-B3 (ab, g, and h) with dough properties and bread-making quality-related characteristics using near-isogenic lines (NILs) of 'Yumechikara' that commonly carry Glu-A1a, Glu-B1b, Glu-D1d, Glu-A3f, Glu-B3ab and Glu-D3a. Measurement of peak time (PT) in a 2-g mixograph indicated that Glu-B3g was the most effective for a strong dough property, followed by Glu-B3ab, with Glu-B3h being the least effective. The results of measurement of mixing time during bread-making were similar to those for PTs, i.e., the lines carrying Glu-B3g showed the longest mixing time, followed by those of Glu-B3ab, and those of Glu-B3h showed the shortest mixing time. Since two parameters of bread-making quality, loaf volume (LV) and specific loaf volume (SLV), were affected by flour protein contents in all groups of the Glu-B3 genotype, we compared the effects of the three Glu-B3 alleles on those parameters using analysis of covariance (ANCOVA) to remove the effect of protein content. The results indicated that the Glu-B3h group showed the largest SLV, followed by the Glu-B3ab group, and the Glu-B3g group showed the smallest SLV. These results suggest that the introduction of Glu-B3h into 'Yumechikara' makes it possible to breed varieties with good bread-making quality-related characteristics.

  7. Development of a simple measurement method for GluR2 protein expression as an index of neuronal vulnerability

    Directory of Open Access Journals (Sweden)

    Chihiro Sugiyama

    2015-01-01

    Full Text Available In vitro estimating strategies for potential neurotoxicity are required to screen multiple substances. In a previous study, we showed that exposure to low-concentrations of some chemicals, such as organotin, decreased the expression of GluR2 protein, which is a subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA-type glutamate receptors, and led to neuronal vulnerability. This result suggested that GluR2 decreases as an index of neuronal cell sensitivity and vulnerability to various toxic insults. Accordingly, we developed a versatile method that is a large scale determination of GluR2 protein expression in the presence of environmental chemicals by means of AlphaLISA technology. Various analytical conditions were optimized, and then GluR2 protein amount was measured by the method using AlphaLISA. The GluR2 amounts were strongly correlated with that of measured by western blotting, which is currently used to determine GluR2 expression. An ideal standard curve could be written with the authentic GluR2 protein from 0 ng to 100 ng. Subsequently, twenty environmental chemicals were screened and nitenpyram was identified as a chemical which lead to decrease in GluR2 protein expression. This assay may provide a tool for detecting neurotoxic chemicals according to decreases in GluR2 protein expression.

  8. Therapeutic potential of mGluR5 targeting in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Anil eKumar

    2015-06-01

    Full Text Available Decades of research dedicated towards Alzheimer's disease (AD has culminated in much of the current understanding of the neurodegeneration associated with disease. However, delineating the pathophysiology and finding a possible cure for the disease is still wanting. This is in part due to the lack of knowledge pertaining to the connecting link between neurodegenerative and neuroinflammatory pathways. Consequently, the inefficacy and ill-effects of the drugs currently available for AD encourage the need for alternative and safe therapeutic intervention. In this review we highlight the potential of mGluR5, a metabotropic glutamatergic receptor, in understanding the mechanism underlying the neuronal death and neuroinflammation in AD. We also discuss the role of mGlu5 receptor in mediating the neuron-glia interaction in the disease. Finally, we discuss the potential of mGluR5 as target for treating AD.

  9. The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells.

    Science.gov (United States)

    Rubio, María E; Matsui, Ko; Fukazawa, Yugo; Kamasawa, Naomi; Harada, Harumi; Itakura, Makoto; Molnár, Elek; Abe, Manabu; Sakimura, Kenji; Shigemoto, Ryuichi

    2017-11-01

    The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.

  10. Cortical GluN2B deletion attenuates punished suppression of food reward-seeking.

    Science.gov (United States)

    Radke, Anna K; Nakazawa, Kazu; Holmes, Andrew

    2015-10-01

    Compulsive behavior, which is a hallmark of psychiatric disorders such as addiction and obsessive-compulsive disorder, engages corticostriatal circuits. Previous studies indicate a role for corticostriatal N-methyl-D-aspartate receptors (NMDARs) in mediating compulsive-like responding for drugs of abuse, but the specific receptor subunits controlling reward-seeking in the face of punishment remain unclear. The current study assessed the involvement of corticostriatal GluN2B-containing NMDARs in measures of persistent and punished food reward-seeking. Mice with genetic deletion of GluN2B in one of three distinct neuronal populations, cortical principal neurons, forebrain interneurons, or striatal medium spiny neurons, were tested for (1) sustained food reward-seeking when reward was absent, (2) reward-seeking under a progressive ratio schedule of reinforcement, and (3) persistent reward-seeking after a footshock punishment. Mutant mice with genetic deletion of GluN2B in cortical principal neurons demonstrated attenuated suppression of reward-seeking during punishment. These mice performed normally on other behavioral measures, including an assay for pain sensitivity. Mutants with interneuronal or striatal GluN2B deletions were normal on all behavioral assays. Current findings offer novel evidence that loss of GluN2B-containing NMDARs expressed on principal neurons in the cortex results in reduced punished food reward-seeking. These data support the involvement of GluN2B subunit in cortical circuits regulating cognitive flexibility in a variety of settings, with implications for understanding the basis of inflexible behavior in neuropsychiatric disorders including obsessive-compulsive disorders (OCD) and addictions.

  11. Fear extinction induces mGluR5-mediated synaptic and intrinsic plasticity in infralimbic neurons.

    Science.gov (United States)

    Sepulveda-Orengo, Marian T; Lopez, Ana V; Soler-Cedeño, Omar; Porter, James T

    2013-04-24

    Studies suggest that plasticity in the infralimbic prefrontal cortex (IL) in rodents and its homolog in humans is necessary for inhibition of fear during the recall of fear extinction. The recall of extinction is impaired by locally blocking metabotropic glutamate receptor type 5 (mGluR5) activation in IL during extinction training. This finding suggests that mGluR5 stimulation may lead to IL plasticity needed for fear extinction. To test this hypothesis, we recorded AMPA and NMDA currents, AMPA receptor (AMPAR) rectification, and intrinsic excitability in IL pyramidal neurons in slices from trained rats using whole-cell patch-clamp recording. We observed that fear extinction increases the AMPA/NMDA ratio, consistent with insertion of AMPARs into IL synapses. In addition, extinction training increased inward rectification, suggesting that extinction induces the insertion of calcium-permeable (GluA2-lacking) AMPARs into IL synapses. Consistent with this, selectively blocking calcium-permeable AMPARs with Naspm reduced the AMPA EPSCs in IL neurons to a larger degree after extinction. Extinction-induced changes in AMPA/NMDA ratio, rectification, and intrinsic excitability were blocked with an mGluR5 antagonist. These findings suggest that mGluR5 activation leads to consolidation of fear extinction by regulating the intrinsic excitability of IL neurons and modifying the composition of AMPARs in IL synapses. Therefore, impaired mGluR5 activity in IL synapses could be one factor that causes inappropriate modulation of fear expression leading to anxiety disorders.

  12. Mixed Partnering and Parenting

    DEFF Research Database (Denmark)

    Singla, Rashmi

    relationship is formed across two socially significant groups: ethnic, religious, region/caste, thus the present study has broad relevance. This proposal delineates the demographic details, intervention process of two ethnically mixed- marriage cases. Cases’ analyses are combined with relevant results from...... an empirical study (Singla, 2015) about intermarried couples to present lessons for counselling and psychotherapy good practices. The couples in the two cases and ten in-depth interviews based empirical study are formed across ethnic/religious borders - one partner is native Danish and the other originates...... from South Asia (India, Pakistan). Cultural historical psychology forms the background of the theoretical framework of the study, while a combination of intersectionality (Moodley, 2011), everyday life perspective and transnationalism forms the foreground. The lessons learnt for counselling...

  13. KNOWLEDGE SHARING IN PARTNERING

    DEFF Research Database (Denmark)

    Koch, Christian; Thuesen, Christian Langhoff

    . The diversity and disjunct feature of the practices is a condition of possibility of knowledge handling as it is a prerequisite for the synthesis of various forms of knowledge in the building construct. Here an orchestrated combination of relationbased interaction with boundary objects and brokers, requisite......This paper adopts practicebased theory for understanding interorganisational knowledge work and extents it with a discussion of the role of redundancy. The paper presents a case study of a project partnership in construction using the partnering concept. The project group responsible...... for the building design counts members from different companies like architects, engineers, and contractors. The paper discusses three central mechanisms for coordinating knowledge in a complex construction project, redundancy, relations, and governance. The knowledge relations is conceptualised through focusing...

  14. PICK1 uncoupling from mGluR7a causes absence-like seizures

    OpenAIRE

    Bertaso, Federica; Zhang, Chuansheng; Scheschonka, Astrid; de Bock, Frédéric; Fontanaud, Pierre; Marin, Philippe; Huganir, Richard L; Betz, Heinrich; Bockaert, Joël; Fagni, Laurent; Lerner-Natoli, Mireille

    2008-01-01

    Absence epilepsy is a neurological disorder that causes a recurrent loss of consciousness and generalized spike-and-wave discharges on an electroencephalogram (EEG). The role of metabotropic glutamate receptors (mGluRs) and associated scaffolding proteins in absence epilepsy has been unclear to date. We investigated a possible role for these proteins in absence epilepsy, focusing on the mGluR7a receptor and its PDZ-interacting protein, protein interacting with C kinase 1 (PICK1), in rats and ...

  15. New staff contract policy

    CERN Document Server

    HR Department

    2006-01-01

    Following discussion at TREF and on the recommendation of the Finance Committee, Council approved a new staff contract policy, which became effective on 1 January 2006. Its application is covered by a new Administrative Circular No. 2 (Rev. 3) 'Recruitment, appointment and possible developments regarding the contractual position of staff members'. The revised circular replaces the previous Circulars No. 9 (Rev. 3) 'Staff contracts' and No. 2 (Rev. 2) 'Guidelines and procedures concerning recruitment and probation period for staff members'. The main features of the new contract policy are as follows: The new policy provides chances for long-term employment for all staff recruits staying for four years without distinguishing between those assigned to long-term or short-term activities when joining CERN. In addition, it presents a number of simplifications for the award of ICs. There are henceforth only 2 types of contract: Limited Duration (LD) contracts for all recruitment and Indefinite Contracts (IC) for...

  16. Implementing a Rule-Based Contract Compliance Checker

    Science.gov (United States)

    Strano, Massimo; Molina-Jimenez, Carlos; Shrivastava, Santosh

    The paper describes the design and implementation of an independent, third party contract monitoring service called Contract Compliance Checker (CCC). The CCC is provided with the specification of the contract in force, and is capable of observing and logging the relevant business-to-business (B2B) interaction events, in order to determine whether the actions of the business partners are consistent with the contract. A contract specification language called EROP (for Events, Rights, Obligations and Prohibitions) for the CCC has been developed based on business rules, that provides constructs to specify what rights, obligation and prohibitions become active and inactive after the occurrence of events related to the execution of business operations. The system has been designed to work with B2B industry standards such as ebXML and RosettaNet.

  17. Copyright Preemption of Contracts

    OpenAIRE

    Bohannan, Christina

    2008-01-01

    This Article argues that both courts and scholars are wrong in their categorical approaches to preemption of contracts under the Copyright Act, and proposes an intermediate approach that recognizes the importance of both contract rights and federal policy in preemption analysis. First, it argues that both courts and scholars have misapplied preemption law to breach of contract claims. Although the two sides tend to favor opposite results, they take equally categorical approaches. Categori...

  18. Contracting for Public Services

    DEFF Research Database (Denmark)

    Greve, Carsten

    strategic purchasing understanding markets communicating the contracting decision designing and drafting the contract the role of the consumer the regulation of service provision Illustrated throughout with practitioner case-studies from a range of OECD countries, this book presents an important new......Insightful and comprehensive and covering new subjects like globalization and IT, this text, international in its approach, provides a thorough introduction to the key phases of the contracting process and the skills required by managers in its implementation. These include: policy for contracting...

  19. Smart contracts sobre Bitcoin

    OpenAIRE

    Andreu Alemany, Josep Miquel

    2016-01-01

    El present treball final de màster realitza una introducció als smart contracts. El treball introdueix el concepte de contracte intel·ligent, els seus usos i alguns exemples existents. Seguidament proporciona les nocions necessàries de les transaccions del protocol Bitcoin per poder implementar un contracte intel·ligent, usant la blockchain que ofereix el protocol. Per últim, s'explica la implementació d'un contracte intel·ligent usant bitcoin: un canal de micropagaments. El presente traba...

  20. It Is Time to Cancel Medicine's Social Contract Metaphor.

    Science.gov (United States)

    Harris, John M

    2017-09-01

    There is agreement that the complex relationship between medicine and society is best described as a metaphorical social contract and that professionalism is the medical profession's contribution to this contract. Metaphors can help clarify abstract concepts, but they can also be abused if the counterfactual attributes of a metaphor become attributed to its subject. This seems to be happening with medical professionalism, which has sometimes been reduced to a contracted deliverable and a bargaining chip. The undesirable attributes of the social contract metaphor may be hindering efforts to understand and teach medical professionalism.Despite its theoretical weaknesses, the social contract metaphor has historical credibility because of its alleged association with the 1847 Code of Medical Ethics and the subsequent ascension of regular (allopathic) medicine in the early 20th century. However, the record does not support an argument that the intended purpose of the 1847 Code was to create a social contract or that one ever arose. The alternative account that a contract did arise, but physicians were poor partners, is neither satisfying nor explanatory.As now used, medicine's social contract metaphor has serious theoretical and historic weaknesses. Medical educators should remove this narrow and overworked metaphor from their discussions of professionalism. By doing this, educators and the profession in general would only lose the ability to threaten themselves with the cancellation of their social contract. In return they would open the door to a more complex and fruitful consideration of medical professionalism and medicine's relationship with society.

  1. Deletion of the GluA1 AMPA Receptor Subunit Alters the Expression of Short-Term Memory

    Science.gov (United States)

    Sanderson, David J.; Sprengel, Rolf; Seeburg, Peter H.; Bannerman, David M.

    2011-01-01

    Deletion of the GluA1 AMPA receptor subunit selectively impairs short-term memory for spatial locations. We further investigated this deficit by examining memory for discrete nonspatial visual stimuli in an operant chamber. Unconditioned suppression of magazine responding to visual stimuli was measured in wild-type and GluA1 knockout mice.…

  2. Basal Levels of AMPA Receptor GluA1 Subunit Phosphorylation at Threonine 840 and Serine 845 in Hippocampal Neurons

    Science.gov (United States)

    Babiec, Walter E.; Guglietta, Ryan; O'Dell, Thomas J.

    2016-01-01

    Dephosphorylation of AMPA receptor (AMPAR) GluA1 subunits at two sites, serine 845 (S845) and threonine 840 (T840), is thought to be involved in NMDA receptor-dependent forms of long-term depression (LTD). Importantly, the notion that dephosphorylation of these sites contributes to LTD assumes that a significant fraction of GluA1 subunits are…

  3. Stereochemistry and molecular pharmacology of (S)-thio-ATPA, a new potent and selective GluR5 agonist

    DEFF Research Database (Denmark)

    Stensbøl, T B; Jensen, H S; Nielsen, B

    2001-01-01

    )-Glu) receptors (EC(50)=14 microM), comparable in potency with ATPA (EC(50)=34 microM). Recent findings, that (S)-ATPA is a potent (EC(50)=0.48 microM) and selective agonist at homomerically expressed ionotropic GluR5, prompted us to resolve thio-ATPA using chiral chromatography and pharmacologically characterize...

  4. Intimate Partner Violence. Prevention Update

    Science.gov (United States)

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2011

    2011-01-01

    The Centers for Disease Control and Prevention (CDC) defines intimate partner violence (IPV) as violence between two people in a close relationship, including current and former spouses and dating partners. IPV occurs on a continuum from a single episode to ongoing battering and can include physical violence, sexual violence, threats, emotional…

  5. Partnering with the NCPV (Brochure)

    Energy Technology Data Exchange (ETDEWEB)

    2013-06-01

    Brochure that explains the basic partnering opportunities that exist within the National Center for Photovoltaics for industry and university groups: non-proprietary partnering opportunities, competitive solicitations, Technology Partnership Agreements, seed fund to develop Technology Partnership Agreements, Hands-On PV Experience Workshop, and NCPV Fellowship Program.

  6. Partner selection and Hollywood Films

    DEFF Research Database (Denmark)

    Grodal, Torben Kragh; Kramer, Mette

    2012-01-01

    Based on cognitive, neurological and evolutionary based film theory the article describes the representation of partner selection in Hollywood films. It analyses paradigm scenarios of partner selection and love, It further describes some of those mechanisms that regulate the relation between...

  7. Allelic variation at Glu-1 loci and its association with grain quality of ...

    African Journals Online (AJOL)

    The high molecular weight glutenin subunits (HMW-GS) are important determinants of wheat flour quality. The HMW-GS patterns of the major released wheat cultivars in Sudan, in addition to some advanced lines, were analyzed using SDS-PAGE. The associations of the HMW-GS quality scores (Glu-1 QS) with the flour ...

  8. Automatic Color Sorting System for Hardwood Edge-Glued Panel Parts

    Science.gov (United States)

    Richard W. Conners; D.Earl Kline; Philip A. Araman

    1996-01-01

    The color sorting of edge-glued panel parts is becoming more important in the manufacture of hardwood products. Consumers, while admiring the natural appearance of hardwoods, do not like excessive color variation across product surfaces. Color uniformity is particularly important today because of the popularity of lightly stained products. Unfortunately, color sorting...

  9. 1997 Hardwood Research Award Winner: "Automatic Color Sorting of Hardwood Edge-Glued Panel Parts"

    Science.gov (United States)

    D. Earl Kline; Richard Conners; Qiang Lu; Philip A. Araman

    1997-01-01

    The National Hardwood Lumber Association's 1997 Hardwood Research Award was presented to D. Earl Kline, Richard Conners, Qiang Lu and Philip Araman at the 25th Annual Hardwood Symposium for developing an automatic system for color sorting hardwood edge-glued panel parts. The researchers comprise a team from Virginia Tech University and the USDA Forest Service in...

  10. Study of gluing and wire bonding for the Belle II Silicon Vertex Detector

    International Nuclear Information System (INIS)

    Kang, K.H.; Hara, K.; Higuchi, T.; Hyun, H.J.; Jeon, H.B.; Joo, C.W.; Kah, D.H.; Kim, H.J.; Mibe, T.; Onuki, Y.; Park, H.; Rao, K.K.; Sato, N.; Shimizu, N.; Tanida, K.; Tsuboyama, T.; Uozumi, S.

    2014-01-01

    This paper describes an investigation into gluing and wire bonding for assembling the Silicon Vertex Detector (SVD) for the Belle II experiment at KEK in Japan. Optimizing the gluing of the silicon microstrip sensors, the support frame, and the readout flex cables is important for achieving the required mechanical precision. The wire bonding between the sensors and the readout electronic chips also needs special care to maximize the physics capability of the SVD. The silicon sensors and signal fan out flex circuits (pitch adapters) are glued and connected using wire bonding. We determine that gluing quality is important for achieving good bonding efficiency. The standard deviation in the glue thickness for the best result is measured to be 3.11 μm. Optimal machine parameters for wire bonding are determined to be 70 mW power, 20 gf force, and 20 ms for the pitch adapter and 60 mW power, 20 gf force, and 20 ms for the silicon strip sensors; these parameters provide a pull force of (10.92±0.72) gf. With these settings, 75% of the pitch adapters and 25% of the strip sensors experience the neck-broken type of break

  11. Allelic variation at Glu-1 loci and its association with grain quality of ...

    African Journals Online (AJOL)

    Valued Acer Customer

    2011-11-09

    Nov 9, 2011 ... grain quality of wheat grown in an irrigated hot environment ... no significant associations were found between Glu-1 QS and other mixograph parameters such as mixograph peak ... amount of the two major components of gluten which are glutenin and ... composition and different quality attributes for wheat.

  12. Characterization and evolutionary implications of the triad Asp-Xxx-Glu in group II phosphopantetheinyl transferases.

    Science.gov (United States)

    Wang, Yue-Yue; Li, Yu-Dong; Liu, Jian-Bo; Ran, Xin-Xin; Guo, Yuan-Yang; Ren, Ni-Ni; Chen, Xin; Jiang, Hui; Li, Yong-Quan

    2014-01-01

    Phosphopantetheinyl transferases (PPTases), which play an essential role in both primary and secondary metabolism, are magnesium binding enzymes. In this study, we characterized the magnesium binding residues of all known group II PPTases by biochemical and evolutionary analysis. Our results suggested that group II PPTases could be classified into two subgroups, two-magnesium-binding-residue-PPTases containing the triad Asp-Xxx-Glu and three-magnesium-binding-residue-PPTases containing the triad Asp-Glu-Glu. Mutations of two three-magnesium-binding-residue-PPTases and one two-magnesium-binding-residue-PPTase indicate that the first and the third residues in the triads are essential to activities; the second residues in the triads are non-essential. Although variations of the second residues in the triad Asp-Xxx-Glu exist throughout the whole phylogenetic tree, the second residues are conserved in animals, plants, algae, and most prokaryotes, respectively. Evolutionary analysis suggests that: the animal group II PPTases may originate from one common ancestor; the plant two-magnesium-binding-residue-PPTases may originate from one common ancestor; the plant three-magnesium-binding-residue-PPTases may derive from horizontal gene transfer from prokaryotes.

  13. Residual Strength of Glued-in Bolts After 9 Years In Situ Loading

    DEFF Research Database (Denmark)

    Pedersen, Martin Bo Uhre; Clorius, Christian Odin; Damkilde, Lars

    1996-01-01

    In 1993 one of the wooden blades of the Nibe-B windmill was struck by lightning and subsequently demounted after 9 years of use. The mishap offered a unique opportunity to investigate the residual strength of the 28 glued-in bolts used to form the blade to rotor hub connection.The test method...

  14. Gluing operation and form factors of local operators in N = 4 Super Yang-Mills theory

    Science.gov (United States)

    Bolshov, A. E.

    2018-04-01

    The gluing operation is an effective way to get form factors of both local and non-local operators starting from different representations of on-shell scattering amplitudes. In this paper it is shown how it works on the example of form factors of operators from stress-tensor operator supermultiplet in Grassmannian and spinor helicity representations.

  15. Live load distribution on longitudinal glued-laminated timber deck bridges : final report : conclusions and recommendations

    Science.gov (United States)

    Fouad Fanous; Jeremy May; Terry Wipf; Michael Ritter

    2010-01-01

    Over the past few years the United States Department of Agriculture (USDA), Forest Products Laboratory (FPL), and the Federal Highway Administration (FHWA) have supported several research programs. This paper is a result of a study sponsored by FPL, with the objective of determining how truckloads are distributed to the deck panels of a longitudinal glued-laminated...

  16. Mutational analysis of Glu272 in elongation factor 1A of E. coli

    DEFF Research Database (Denmark)

    Mansilla, Francisco; Knudsen, Charlotte Rohde; Clark, Brian F. C.

    1998-01-01

    In our previous work (Mansilla et al. (1997) Protein Eng. 10, 927-934) we showed that Arg7 of Escherichia coli elongation factor Tu (EF1A) plays an essential role in aminoacyl-tRNA (aa-tRNA) binding. Substitution of Arg7 by Ala or Glu lost this activity. We proposed that Arg7 forms a salt bridge...

  17. Association of Gln27Glu polymorphism of the β-2- adrenergic ...

    African Journals Online (AJOL)

    A group of 66 patients with preeclampsia and 72 control subjects were analyzed for the Arg16Gly and Gln27Glu polymorphisms of the ADRB2 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comparisons of the ADRB2 genotypes or alleles between different groups were performed ...

  18. Craftsmen say "we want edge-glued, standard-size panels"

    Science.gov (United States)

    Philip A. Araman; Hugh W. Reynolds

    1983-01-01

    Wood craftsmen would like an alternative to hardwood lumber and plywood and softwood products. They are very interested in edge-glued, standard-size panels. These conclusions are based on interviews with craftsmen at two trade shows, and the results are included in this report along with our recommendations for optimum acceptance by craftsmen of this new product.

  19. Machine Vision System for Color Sorting Wood Edge-Glued Panel Parts

    Science.gov (United States)

    Qiang Lu; S. Srikanteswara; W. King; T. Drayer; Richard Conners; D. Earl Kline; Philip A. Araman

    1997-01-01

    This paper describes an automatic color sorting system for hardwood edge-glued panel parts. The color sorting system simultaneously examines both faces of a panel part and then determines which face has the "better" color given specified color uniformity and priority defined by management. The real-time color sorting system software and hardware are briefly...

  20. Mutational analysis of Glu272 in elongation factor 1A of E. coli

    DEFF Research Database (Denmark)

    Mansilla, Francisco; Knudsen, Charlotte Rohde; Clark, Brian F. C.

    1998-01-01

    In our previous work (Mansilla et al. (1997) Protein Eng. 10, 927-934) we showed that Arg7 of Escherichia coli elongation factor Tu (EF1A) plays an essential role in aminoacyl-tRNA (aa-tRNA) binding. Substitution of Arg7 by Ala or Glu lost this activity. We proposed that Arg7 forms a salt bridge ...

  1. Democratic contract law

    NARCIS (Netherlands)

    Hesselink, M.W.

    2015-01-01

    This article discusses the normative relationship between contract law and democracy. In particular, it argues that in order to be legitimate contract law needs to have a democratic basis. Private law is not different in this respect from public law. Thus, the first claim made in this article will

  2. Contract Teachers in India

    Science.gov (United States)

    Goyal, Sangeeta; Pandey, Priyanka

    2013-01-01

    In this paper, we use non-experimental data from government schools in Uttar Pradesh and Madhya Pradesh, two of the largest Indian states, to present average school outcomes by contract status of teachers. We find that contract teachers are associated with higher effort than civil service teachers with permanent tenures, before as well as after…

  3. Whither Performance Contracting?

    Science.gov (United States)

    Green, Norman S.

    This report describes briefly performance contracts; discusses their shortcomings, pitfalls, and advantages; and gives some insight into the future development of this new concept. Two shortcomings of performance contracting include (1) teaching to the test and (2) board abdication of its responsibility for making final decisions about educational…

  4. Comparing contracting performance

    DEFF Research Database (Denmark)

    Lindholst, Andrej Christian

    . Hypotheses are suggested for the role of culture, competition, contracts, capabilities and collaboration for contracting performance between and across the countries. Arguments are tested against data from on four comparable national surveys of private delivery of park and road maintenance services in local...

  5. BOT Outsourcing Contracts

    DEFF Research Database (Denmark)

    Ørberg Jensen, Peter D.; Petersen, Bent

    2012-01-01

    Build-operate-transfer (BOT) contracting has been widely usen in the engineering and construction industry, but has only recently been introduced in services industry domains. Notably, service provider firms from emerging markets have recently started offering BOT outsourcing contracts. In this p...

  6. Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine.

    Science.gov (United States)

    Ide, Soichiro; Ikekubo, Yuiko; Mishina, Masayoshi; Hashimoto, Kenji; Ikeda, Kazutaka

    2017-11-01

    We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA) receptor GluN2D subunit knockout (GluN2D-KO) mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS)-ketamine and (S)-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R)-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R)-ketamine. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  7. Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine

    Directory of Open Access Journals (Sweden)

    Soichiro Ide

    2017-11-01

    Full Text Available We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA receptor GluN2D subunit knockout (GluN2D-KO mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS-ketamine and (S-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R-ketamine.

  8. Drilling contracts and incentives

    International Nuclear Information System (INIS)

    Osmundsen, Petter; Sorenes, Terje; Toft, Anders

    2008-01-01

    Shortages of rigs and personnel have encouraged discussion of designing incentive contracts in the drilling sector. However, for the drilling contracts, there are not a large variety of contract types in use. This article describes and analyses incentives for drilling contractors. These are directly represented by the compensation formats utilised in the present and in the consecutive drilling contracts. Indirectly, incentives are also provided by the evaluation criteria that oil companies use for awarding drilling assignments. Changes in contract format pose a number of relevant questions relating to resource management, and the article takes an in-depth look at some of these. Do evaluation criteria for awarding drilling assignments encourage the development of new technology and solutions? How will a stronger focus on drilling efficiency influence reservoir utilisation?

  9. Drilling contract issues

    International Nuclear Information System (INIS)

    Davison, G.B.; Worden, D.R.; Borbridge, G.K.D.

    1997-01-01

    Some selected issues which are facing both operators and contractors in drilling for oil and gas, such as the allocation of risk by contract and by statute and the implementation of new technologies, were discussed. There are three varieties of written drilling contracts used in Canada: (1) day work and meterage contracts, (2) master drilling agreements, and (3) contracts that are used in construction projects that do not specifically relate to drilling. Issues relevant to the contractual allocation of risk, to implementing new drilling technologies, to reconciling contract and statute liability, and the formation of strategic alliances for mutual benefit, and the factors contributing to the success of such alliances were explored. 12 refs

  10. THE PSYCHOLOGICAL CONTRACT

    Directory of Open Access Journals (Sweden)

    Blanca Giorgiana GRAMA

    2015-04-01

    Full Text Available The psychological contract became known as a research paradigm within corporate research, providing a broad framework which explains the employee-company relations. Despite all this, there are still many debates on the concept and a series of criticism were expressed that led to the necessity of some more rigorous theoretical and empirical analysis. The psychological contract refers to the unwritten, implicit expectations that employees have from the company and vice versa; it is that which defines the things the employee expects from the employer. Consequently, each of the parties involved in the contract may have different perceptions on these commitments and obligations. Thus the psychological contract may be regarded as an exchange relation between the employer and the employee. Breaking the psychological contract affects the performance, the morale, and the motivation of the staff in a negative manner. The information presented in this paper is intended to contribute to the theoretical and methodological development of the concept.

  11. Patient preferences for partner notification.

    Science.gov (United States)

    Apoola, A; Radcliffe, K W; Das, S; Robshaw, V; Gilleran, G; Kumari, B S; Boothby, M; Rajakumar, R

    2006-08-01

    To identify patient preferences for notification of sexual contacts when a sexually transmitted infection (STI) is diagnosed. A questionnaire survey of 2544 patients attending three large genitourinary clinics at Derby, Birmingham, and Coventry in the United Kingdom. The median age of the respondents was 24 with 1474 (57.9%) women, 1835 (72.1%) white, 1826 (71.8%) single. The most favoured method of partner notification was patient referral, which was rated a "good" method by 65.8% when they had to be contacted because a sexual partner has an STI. Notifying contacts by letter as a method of provider partner notification is more acceptable than phoning, text messaging, or email. Respondents with access to mobile telephones, private emails, and private letters were more likely to rate a method of partner notification using that mode of communication as "good" compared to those without. With provider referral methods of partner notification respondents preferred to receive a letter, email, or text message asking them to contact the clinic rather than a letter, email or text message informing them that they may have an STI. Most respondents think that being informed directly by a partner is the best method of being notified of the risk of an STI. Some of the newer methods may not be acceptable to all but a significant minority of respondents prefer these methods of partner notification. The wording of letters, emails, or text messages when used for partner notification has an influence on the acceptability of the method and may influence success of the partner notification method. Services should be flexible enough to utilise the patients' preferred method of partner notification.

  12. Sustainable Markets Investment Briefings: Foreign investment contracts

    Energy Technology Data Exchange (ETDEWEB)

    Cotula, Lorenzo

    2007-08-15

    This is the fourth of a series of briefings which discuss the sustainable development issues raised by legal arrangements for the protection of foreign investment. The briefings are based on legal research by IIED and its partners. The goal is to provide accessible but accurate information for human rights, development and environmental organisations working on issues raised by foreign investment in low- and middle-income countries. Briefing 4 sets out some of the ways in which foreign investment contracts can impact on sustainable development.

  13. SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury

    Directory of Open Access Journals (Sweden)

    Emma V. Jones

    2018-02-01

    Full Text Available The proper formation and maintenance of functional synapses in the central nervous system (CNS requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood. Interestingly, SPARC has been shown to be upregulated in CNS injury and disease. However, the role of SPARC upregulation in these contexts is not fully understood. In this study, we investigated the effect of chronic SPARC administration on glutamate receptors on mature hippocampal neuron cultures and following CNS injury. We found that SPARC treatment increased the number of GluA1-containing AMPARs at synapses and enhanced synaptic function. Furthermore, we determined that the increase in synaptic strength induced by SPARC could be inhibited by Philanthotoxin-433, a blocker of homomeric GluA1-containing AMPARs. We then investigated the effect of SPARC treatment on neuronal health in an injury context where SPARC expression is upregulated. We found that SPARC levels are increased in astrocytes and microglia following middle cerebral artery occlusion (MCAO in vivo and oxygen-glucose deprivation (OGD in vitro. Remarkably, chronic pre-treatment with SPARC prevented OGD-induced loss of synaptic GluA1. Furthermore, SPARC treatment reduced neuronal death through Philanthotoxin-433 sensitive GluA1 receptors. Taken together, this study suggests a novel role for SPARC and GluA1 in promoting neuronal health and recovery following CNS damage.

  14. Contract Award Decisions Resulting in Contract Termination for Default

    National Research Council Canada - National Science Library

    1996-01-01

    .... Specifically, the audit focused on contracts terminated either for default or convenience and determined whether the contract terminations could have been averted based on information available before contract award...

  15. ENFORCEMENT OF MORTGAGE CONTRACT

    Directory of Open Access Journals (Sweden)

    Alisa A. BELU

    2016-07-01

    Full Text Available A chattel mortgage contract is the expression of a real guarantee that gives the creditor precedence over other creditors, in addition to the general pledge upon the belongings of the debtor. It refers to the sale of mortgaged movable assets, exclusively or prioritized in favor of the mortgaging creditor, in case the debtor does not comply with his / her commitments, under the signed mortgage contract. Beginning from this purpose, shared by both sides (as the chattel mortgage contract is synallagmatic, in case the debtor is unable to fulfill his / her commitments, the sides reach a situation of enforcement of the signed chattel mortgage contract. Given the legal status of the chattel mortgage contract [Art. 2387-2477 Noul Cod Civil , Universul Juridic, Bucureşti, 2016, ISBN 978-606-673-792-0], the principle of binding force of the contract and the principle according to which signed legal conventions will entail legal effects, the Romanian law maker developed the proper legal framework for the enforcement of the chattel mortgage contract. [art. 622 si urm. Noul Cod de Procedură Civilă, ed. Hamangiu, Bucureşti, 2016, ISBN 978-606-27-0459-9].

  16. JURIDICAL WILL IN CONTRACTS

    Directory of Open Access Journals (Sweden)

    Emilian CIONGARU

    2015-07-01

    Full Text Available In the business law, almost all judicial relationships of private law are obligational juridical relationships which are made up of legal acts and facts. The most important legal act is the contract since it is the basis of the social life in any community meaning that it represents the most important economic and juridical instrument for the participants to a contract. The persons are free and equal in society and, consequently, no power is valid and fundamental unless it relies on their consent, namely on a contract. So, the existence of a civil contract relies on the principles of consensualism, a perception based on moral rules to observe one’s promises, to have good faith and to observe the interests of your fellow creature. The exterior manifestation, the expression or declaration of the juridical will constitutes the consent of such person in making the structure of contract. The declared will must correspond to the person’s real will and the adoption and declaration of the juridical will must take place consciously. Any contract that does not derive from juridical will is null and the civilizing character is inexistent. The principles giving sense to consensualism is the one of agreement between parties so as to produce legal effects by itself and it is enough for the conclusion of a contract, regardless of the form in which it is exteriorized, a principle expressed by the Latin adagio pacta sunt servanda.

  17. Inhibition of GluR Current in Microvilli of Sensory Neurons via Na+-Microdomain Coupling Among GluR, HCN Channel, and Na+/K+ Pump

    Directory of Open Access Journals (Sweden)

    Yasuhiro Kawasaki

    2018-04-01

    Full Text Available Glutamatergic dendritic EPSPs evoked in cortical pyramidal neurons are depressed by activation of hyperpolarization-activated cyclic nucleotide-gated (HCN channels expressed in dendritic spines. This depression has been attributed to shunting effects of HCN current (Ih on input resistance or Ih deactivation. Primary sensory neurons in the rat mesencephalic trigeminal nucleus (MTN have the somata covered by spine-like microvilli that express HCN channels. In rat MTN neurons, we demonstrated that Ih enhancement apparently diminished the glutamate receptor (GluR current (IGluR evoked by puff application of glutamate/AMPA and enhanced a transient outward current following IGluR (OT-IGluR. This suggests that some outward current opposes inward IGluR. The IGluR inhibition displayed a U-shaped voltage-dependence with a minimal inhibition around the resting membrane potential, suggesting that simple shunting effects or deactivation of Ih cannot explain the U-shaped voltage-dependence. Confocal imaging of Na+ revealed that GluR activation caused an accumulation of Na+ in the microvilli, which can cause a negative shift of the reversal potential for Ih (Eh. Taken together, it was suggested that IGluR evoked in MTN neurons is opposed by a transient decrease or increase in standing inward or outward Ih, respectively, both of which can be caused by negative shifts of Eh, as consistent with the U-shaped voltage-dependence of the IGluR inhibition and the OT-IGluR generation. An electron-microscopic immunohistochemical study revealed the colocalization of HCN channels and glutamatergic synapses in microvilli of MTN neurons, which would provide a morphological basis for the functional interaction between HCN and GluR channels. Mathematical modeling eliminated the possibilities of the involvements of Ih deactivation and/or shunting effect and supported the negative shift of Eh which causes the U-shaped voltage-dependent inhibition of IGluR.

  18. Partnering for Success (OIT Customer Day Partner Recognition)

    Energy Technology Data Exchange (ETDEWEB)

    2002-04-01

    Office of Industrial Technologies document produced for 2002 Customer Day event, which features industry partners who have worked with OIT to achieve outstanding energy efficiency achievements from January 2001 to the present.

  19. Bottlenecks and contracts

    International Nuclear Information System (INIS)

    2001-01-01

    The report surveys the central points in the literature about contracts on geographical price differences and transmission rights in the power market. It is commonly believed that such contracts may reduce market power and contribute to better network investments. The theoretical debate is in part unfinished and largely based on very stylised assumptions. There is some indication that such contracts may not be very useful in practice. But they may be useful in some cases, perhaps in particular when power is transported outside limited surplus areas and for certain investment decisions where there is no systems operator with a natural responsibility

  20. Contract management survey 2002.

    Science.gov (United States)

    Hoppszallern, Suzanna

    2002-10-01

    Spending on clinical contracts continues to outpace spending on business services, but may be leveling off. The 12th annual Contract Management Survey shows that the performance of clinical vendors is now comparable to business service vendors in meeting savings targets. Both business and clinical vendors are receiving higher marks from hospital leaders, but execs quickly respond to low marks by bringing the service back in-house of changing vendors. This report examines trends in outsourcing, satisfaction levels, the decision-making process, contract features and performance, and spending.

  1. 2001 contract management survey.

    Science.gov (United States)

    2001-10-01

    For the second year running, hospitals are spending more on clinical outsourcing than on business services. The Eleventh Annual Contract Services Survey shows that, in clinical areas, executives use outsourcing to acquire specialized expertise with cost savings secondary. Reducing costs and FTEs are the primary reasons for outsourcing business operations. Business service contracts are more likely to meet expectations for cost savings. Overall, satisfaction levels are up, but in some areas there's still a lot of room for improvement. This report examines current trends in outsourcing, strategies for the future, satisfaction levels, the decisionmaking process, contract features, and costs.

  2. The contract - introduction

    International Nuclear Information System (INIS)

    Loeffler, G.

    1975-01-01

    The contract is the last and final step of project planning and the first step of project implementation. The contract has to specify in detail and to the point, as concisely as possible, the complete scope of supplies and work, define all technical particulars and requirements, put forward the conditions of legal, regulatory, administrative and financial procedure, prepare for operating and maintenance instructions to be issued after commissioning. In short, the contract is expected to be a reliable instrument during the manufacturing and construction period as well as a guide-book to assist the owner afterwards in the operation and maintenance of the plant. (orig./FW) [de

  3. Odor preference learning and memory modify GluA1 phosphorylation and GluA1 distribution in the neonate rat olfactory bulb: testing the AMPA receptor hypothesis in an appetitive learning model.

    Science.gov (United States)

    Cui, Wen; Darby-King, Andrea; Grimes, Matthew T; Howland, John G; Wang, Yu Tian; McLean, John H; Harley, Carolyn W

    2011-01-01

    An increase in synaptic AMPA receptors is hypothesized to mediate learning and memory. AMPA receptor increases have been reported in aversive learning models, although it is not clear if they are seen with memory maintenance. Here we examine AMPA receptor changes in a cAMP/PKA/CREB-dependent appetitive learning model: odor preference learning in the neonate rat. Rat pups were given a single pairing of peppermint and 2 mg/kg isoproterenol, which produces a 24-h, but not a 48-h, peppermint preference in the 7-d-old rat pup. GluA1 PKA-dependent phosphorylation peaked 10 min after the 10-min training trial and returned to baseline within 90 min. At 24 h, GluA1 subunits did not change overall but were significantly increased in synaptoneurosomes, consistent with increased membrane insertion. Immunohistochemistry revealed a significant increase in GluA1 subunits in olfactory bulb glomeruli, the targets of olfactory nerve axons. Glomerular increases were seen at 3 and 24 h after odor exposure in trained pups, but not in control pups. GluA1 increases were not seen as early as 10 min after training and were no longer observed 48 h after training when odor preference is no longer expressed behaviorally. Thus, the pattern of increased GluA1 membrane expression closely follows the memory timeline. Further, blocking GluA1 insertion using an interference peptide derived from the carboxyl tail of the GluA1 subunit inhibited 24 h odor preference memory providing causative support for our hypothesis. PKA-mediated GluA1 phosphorylation and later GluA1 insertion could, conjointly, provide increased AMPA function to support both short-term and long-term appetitive memory.

  4. Tenure security, social relations and contract choice: Endogenous matching in the Chinese land rental market

    Science.gov (United States)

    Ma, Xianlei; Zhou, Yuepeng; Shi, Xiaoping

    2017-04-01

    In China, land rental transactions have increased considerably since the 1990s, but there exists a high degree of segmentation and informal features. The rental transactions between partners with close social relations and the use of informal contracts remain a common phenomenon in many regions, which strongly reduce the potential of the land rental market to enhance productivity and equity. The current literature postulates that the insecurity of land property rights may restrict land transactions between members of same social relations. Studies conducted in China show that the land rentals between partners with closer social relations prefer informal contracts because these contracts are self-enforced based on trust and reputation. However, little literature has jointly examined the effect of land tenure security and social relations on joint decisions of partner and contract choice in the Chinese land rental market. Based on household data collected in Jiangxi and Liaoning provinces in 2015, this paper aims to examine the relationship between land tenure security perceptions, social relation and land rental contract choices in China. We differentiate between formal and informal contracts of land rental activities because they have different enforcement mechanisms and thus different risk-sharing strategy. With regards to social relations, we differ among relatives, villagers living in the same village and strangers according to social distance. In order to reduce estimation bias without accounting for endogenous matching between landlords and tenants, we investigate the joint partner and contract choices in the land rental market using a nested logit framework. The paper contributes to the literature on the effect of tenure security and social relations on land rental contracts by (i) taking into account endogenous matching between landlords and tenants, and estimating the joint decisions of partner and contract choice, and (ii) examining the effect of perceived

  5. The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region

    DEFF Research Database (Denmark)

    Tapken, Daniel; Steffensen, Thomas Bielefeldt; Leth, Rasmus

    2017-01-01

    Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D...

  6. The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis.

    Science.gov (United States)

    Üner, Aykut; Gonçalves, Gabriel H M; Li, Wenjing; Porceban, Matheus; Caron, Nicole; Schönke, Milena; Delpire, Eric; Sakimura, Kenji; Bjørbæk, Christian

    2015-10-01

    Hypothalamic agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) expressing neurons play critical roles in control of energy balance. Glutamatergic input via n-methyl-d-aspartate receptors (NMDARs) is pivotal for regulation of neuronal activity and is required in AgRP neurons for normal body weight homeostasis. NMDARs typically consist of the obligatory GluN1 subunit and different GluN2 subunits, the latter exerting crucial differential effects on channel activity and neuronal function. Currently, the role of specific GluN2 subunits in AgRP and POMC neurons on whole body energy and glucose balance is unknown. We used the cre-lox system to genetically delete GluN2A or GluN2B only from AgRP or POMC neurons in mice. Mice were then subjected to metabolic analyses and assessment of AgRP and POMC neuronal function through morphological studies. We show that loss of GluN2B from AgRP neurons reduces body weight, fat mass, and food intake, whereas GluN2B in POMC neurons is not required for normal energy balance control. GluN2A subunits in either AgRP or POMC neurons are not required for regulation of body weight. Deletion of GluN2B reduces the number of AgRP neurons and decreases their dendritic length. In addition, loss of GluN2B in AgRP neurons of the morbidly obese and severely diabetic leptin-deficient Lep (ob/ob) mice does not affect body weight and food intake but, remarkably, leads to full correction of hyperglycemia. Lep (ob/ob) mice lacking GluN2B in AgRP neurons are also more sensitive to leptin's anti-obesity actions. GluN2B-containing NMDA receptors in AgRP neurons play a critical role in central control of body weight homeostasis and blood glucose balance via mechanisms that likely involve regulation of AgRP neuronal survival and structure, and modulation of hypothalamic leptin action.

  7. Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

    Science.gov (United States)

    Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

    2014-09-05

    Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. (S)-homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Ahmadian, H; Nielsen, B; Bräuner-Osborne, Hans

    1997-01-01

    of the spectroscopic configurational assignments. The activities of 6 and 7 at ionotropic EAA (iGlu) receptors and at mGlu1-7 were studied. (S)-Homo-AMPA (6) was shown to be a specific agonist at mGlu6 (EC50 = 58 +/- 11 microM) comparable in potency with the endogenous mGlu agonist (S)-glutamic acid (EC50 = 20 +/- 3......Our previous publication (J. Med. Chem. 1996, 39, 3188-3194) described (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (Homo-AMPA) as a highly selective agonist at the mGlu6 subtype of metabotropic excitatory amino acid (EAA) receptors. Homo-AMPA has already become a standard agonist...... microM). Although Homo-AMPA did not show significant effects at iGlu receptors, (R)-Homo-AMPA (7), which was inactive at mGlu1-7, turned out to be a weak N-methyl-D-aspartic acid (NMDA) receptor antagonist (IC50 = 131 +/- 18 microM)....

  9. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure.

    Directory of Open Access Journals (Sweden)

    H Scott Swartzwelder

    Full Text Available Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70 from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further

  10. Establishing contract periods

    International Nuclear Information System (INIS)

    Huffman, F.C.

    1978-01-01

    The lead time for executing the Adjustable Fixed-Commitment (AFC) contract and exceptions which may be considered are discussed. The initial delivery period is also discussed. Delays, deferrals, and schedule adjustment charges are finally considered

  11. Industrial Services Contracts

    CERN Document Server

    2006-01-01

    This document gives an overview of Industrial Services contracts at CERN, including the probable expenditure in 2006 and the estimated expenditure for 2007. The Finance Committee is invited: - to take note of the revised amount in 2006 for Industrial Services contracts referred to in this document of 138.02 MCHF at 2006 prices compared to the previously anticipated amount of 122.67 MCHF at 2005 prices; - to take note that the estimated amount in 2007 for the contracts referred to in this document will be 112.54 MCHF at 2006 prices; - for the reasons set out in this document, the Finance Committee is also invited to approve the requests for the contracts presented and highlighted in the Annexes.

  12. Temporary labour contracts

    CERN Document Server

    2001-01-01

    At its September 2000 meeting, the Finance Committee approved a second one-year extension of the four existing temporary labour contracts (L020/PE, L021/PE, L022/PE, L023/PE) until 31 December 2001 for a total amount not exceeding 6 000 000 Swiss francs at 2000 prices. The Finance Committee is invited: - to take note that the estimated annual expenditure on temporary labour in 2001 will amount to approximately 4 500 000 Swiss francs against the previously estimated 6 000 000 Swiss francs; - to approve the extension of the four existing contracts by six months to 30 June 2002 for an overall amount not exceeding 1 500 000 Swiss francs; - to take note that new contracts for the Swiss part of the CERN site will be submitted for adjudication in December 2001 and that new contracts for the French part of the CERN site will be submitted for adjudication in the course of 2002.

  13. Temporary labour contracts

    CERN Document Server

    1999-01-01

    The five contracts for Temporary Labour assignments on the CERN site (L020/PE, L021/PE, L022/PE, L023/PE and L024/PE) approved by the Finance Committee in March 1996 (CERN/FC/3857) will reach the end of their initial three-year contractual period at the end of December 1999. Following the satisfactory execution of these contracts during this period, CERN requests approval to extend them from January 2000 for the first of the two years foreseen in the original adjudication. The Finance Committee is invited: - to take note that the three-year expenditure for Temporary Labour contracts from 1997 to 1999 will not exceed 19 100 000 Swiss francs, compared to the 18 900 000 Swiss francs estimated at the time of the adjudication in March 1996; - to approve an extension of the present Temporary Labour contracts for the year 2000 for a total amount not exceeding 6 000 000 Swiss francs.

  14. Managing Your China JV Partner

    Institute of Scientific and Technical Information of China (English)

    CHRIS; DEVONSHIRE-ELLIS

    2008-01-01

    Having critical management tools gives foreign investors the chance to maximize their investment, minimize their risk and develop a mutually profitable business with a Chinese partner. This concludes our series on this topic.

  15. Partners Against Crime (PAC) Districts

    Data.gov (United States)

    City and County of Durham, North Carolina — The Partners Against Crime (PAC) program promotes collaboration among police officers, Durham residents, and city and county government officials to find...

  16. Dynamic Changes in Striatal mGluR1 But Not mGluR5 during Pathological Progression of Parkinson's Disease in Human Alpha-Synuclein A53T Transgenic Rats: A Multi-PET Imaging Study.

    Science.gov (United States)

    Yamasaki, Tomoteru; Fujinaga, Masayuki; Kawamura, Kazunori; Furutsuka, Kenji; Nengaki, Nobuki; Shimoda, Yoko; Shiomi, Satoshi; Takei, Makoto; Hashimoto, Hiroki; Yui, Joji; Wakizaka, Hidekatsu; Hatori, Akiko; Xie, Lin; Kumata, Katsushi; Zhang, Ming-Rong

    2016-01-13

    Parkinson's disease (PD) is a prevalent degenerative disorder affecting the CNS that is primarily characterized by resting tremor and movement deficits. Group I metabotropic glutamate receptor subtypes 1 and 5 (mGluR1 and mGluR5, respectively) are important targets for investigation in several CNS disorders. In the present study, we investigated the in vivo roles of mGluR1 and mGluR5 in chronic PD pathology by performing longitudinal positron emission tomography (PET) imaging in A53T transgenic (A53T-Tg) rats expressing an abnormal human α-synuclein (ASN) gene. A53T-Tg rats showed a dramatic decline in general motor activities with age, along with abnormal ASN aggregation and striatal neuron degeneration. In longitudinal PET imaging, striatal nondisplaceable binding potential (BPND) values for [(11)C]ITDM (N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[(11)C]methylbenzamide), a selective PET ligand for mGluR1, temporarily increased before PD symptom onset and dramatically decreased afterward with age. However, striatal BPND values for (E)-[(11)C]ABP688 [3-(6-methylpyridin-2-ylethynyl)-cyclohex-2-enone-(E)-O-[(11)C]methyloxime], a specific PET ligand for mGluR5, remained constant during experimental terms. The dynamic changes in striatal mGluR1 BPND values also showed a high correlation in pathological decreases in general motor activities. Furthermore, declines in mGluR1 BPND values were correlated with decreases in BPND values for [(18)F]FE-PE2I [(E)-N-(3-iodoprop-2E-enyl)-2β-carbo-[(18)F]fluoroethoxy-3β-(4-methylphenyl) nortropane], a specific PET ligand for the dopamine transporter, a biomarker for dopaminergic neurons. In conclusion, our results have demonstrated for the first time that dynamic changes occur in mGluR1, but not mGluR5, that accompany pathological progression in a PD animal model. Synaptic signaling by glutamate, the principal excitatory neurotransmitter in the brain, is modulated by group I metabotropic glutamate

  17. Corrupt Relational Contracting

    OpenAIRE

    Johann Graf Lambsdorff; Sitki Utku Teksoz

    2002-01-01

    Because corruption must be hidden from the public and is not enforced by courts it entails transaction costs, which are larger than those from legal exchange. This suggests that corrupt contracts are primarily relational contracts where legal exchange serves as a basis for sealing and enforcing corrupt agreements. Legal exchange not only provides for corrupt opportunities, but for the necessary enforcement mechanisms. Examples of such legal exchange are long-term business exchange, belonging ...

  18. Contracting as a Science

    Science.gov (United States)

    2012-04-30

    disconfirmation of expectations theory to examine customer satisfaction in the procuring contracting officer (PCO)–program manager (PM) relationship in...marketing terms, finding that disconfirmed expectations lead to consumer satisfaction or dissatisfaction. The former approach presents the idea that if an...individual exerts effort, the expectation is that successful performance will occur leading to a desired result. In contracting, the theory might be

  19. Expansionary fiscal contractions

    DEFF Research Database (Denmark)

    Bergman, Ulf Michael; Hutchison, Michael

    2010-01-01

    The Expansionary Fiscal Contraction (EFC) hypothesis predicts that a major fiscal consolidation leads to an economic expansion under certain circumstances. We test this hypothesis, and the implied non-linear responses of the economy to large and small changes in fiscal policy, using data from...... that the exogenous fiscal contraction in Denmark was a credible regime shift and, together with other reforms undertaken at the time, increased both private consumption and aggregate output....

  20. NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.

    Science.gov (United States)

    Olszewski, Rafal T; Janczura, Karolina J; Bzdega, Tomasz; Der, Elise K; Venzor, Faustino; O'Rourke, Brennen; Hark, Timothy J; Craddock, Kirsten E; Balasubramanian, Shankar; Moussa, Charbel; Neale, Joseph H

    2017-09-01

    Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1.5 h) and long- (24 h) term novel object recognition tests were used to assess memory. Treatment with ZJ43 or 2-PMPA prior to acquisition trials increased long-term memory in mGluR2, but not mGluR3, ko mice. Nine month-old triple transgenic Alzheimer's disease model mice exhibited impaired short-term novel object recognition memory that was rescued by treatment with a NAAG peptidase inhibitor. NAAG peptidase inhibitors and the group II mGluR agonist, LY354740, reversed the short-term memory deficit induced by acute ethanol administration in wild type mice. 2-PMPA also moderated the effect of ethanol on short-term memory in mGluR2 ko mice but failed to do so in mGluR3 ko mice. LY354740 and ZJ43 blocked ethanol-induced motor activation. Both GCPII inhibitors and LY354740 also significantly moderated the loss of motor coordination induced by 2.1 g/kg ethanol treatment. These data support the conclusion that inhibitors of glutamate carboxypeptidase II are efficacious in object recognition models of normal memory and memory deficits via an mGluR3 mediated process, actions that could have widespread clinical applications.

  1. Deletion of the GluA1 AMPA receptor subunit impairs recency-dependent object recognition memory

    Science.gov (United States)

    Sanderson, David J.; Hindley, Emma; Smeaton, Emily; Denny, Nick; Taylor, Amy; Barkus, Chris; Sprengel, Rolf; Seeburg, Peter H.; Bannerman, David M.

    2011-01-01

    Deletion of the GluA1 AMPA receptor subunit impairs short-term spatial recognition memory. It has been suggested that short-term recognition depends upon memory caused by the recent presentation of a stimulus that is independent of contextual–retrieval processes. The aim of the present set of experiments was to test whether the role of GluA1 extends to nonspatial recognition memory. Wild-type and GluA1 knockout mice were tested on the standard object recognition task and a context-independent recognition task that required recency-dependent memory. In a first set of experiments it was found that GluA1 deletion failed to impair performance on either of the object recognition or recency-dependent tasks. However, GluA1 knockout mice displayed increased levels of exploration of the objects in both the sample and test phases compared to controls. In contrast, when the time that GluA1 knockout mice spent exploring the objects was yoked to control mice during the sample phase, it was found that GluA1 deletion now impaired performance on both the object recognition and the recency-dependent tasks. GluA1 deletion failed to impair performance on a context-dependent recognition task regardless of whether object exposure in knockout mice was yoked to controls or not. These results demonstrate that GluA1 is necessary for nonspatial as well as spatial recognition memory and plays an important role in recency-dependent memory processes. PMID:21378100

  2. An unsatisfactory contract policy

    CERN Multimedia

    Association du personnel

    2012-01-01

    For the last 15 years contract policy has been one of the top priorities of CERN staff, as expressed in successive surveys initiated by the Staff Association. In one’s professional life, having some forward vision of one’s career prospects is the key to loyalty and motivation. On the contrary, instability about the future is always at the root of anxiety, conflicts, or even health problems. A good employer must therefore balance the needs of the Company and those of its employees. CERN’s current contract policy, as described in the Administrative Circular No 2, states that staff members should first obtain a limited duration (LD) contract of up to five years. Then, if they want to stay in the Organization, staff members must apply, usually once a year, and before the end of their LD contract, for an indefinite contract (IC) post. All candidates for an IC post are considered by the Review Board for the award of indefinite contracts (Review Board) which will choose the most suita...

  3. When does ALS start? ADAR2-GluA2 hypothesis for the etiology of sporadic ALS

    Directory of Open Access Journals (Sweden)

    Takuto eHideyama

    2011-11-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most common adult-onset motor neuron disease. More than 90% of ALS cases are sporadic, and the majority of sporadic ALS patients do not carry mutations in genes causative of familial ALS; therefore, investigation specifically targeting sporadic ALS is needed to discover the pathogenesis. The motor neurons of sporadic ALS patients express unedited GluA2 mRNA at the Q/R site in a disease-specific and motor neuron-selective manner. GluA2 is a subunit of the AMPA receptor, and it has a regulatory role in the Ca2+-permeability of the AMPA receptor after the genomic Q codon is replaced with the R codon in mRNA by adenosine-inosine conversion, which is mediated by adenosine deaminase acting on RNA 2 (ADAR2. Therefore, ADAR2 activity may not be sufficient to edit all GluA2 mRNA expressed in the motor neurons of ALS patients. To investigate whether deficient ADAR2 activity plays pathogenic roles in sporadic ALS, we generated genetically modified mice (AR2 in which the ADAR2 gene was conditionally knocked out in the motor neurons. AR2 mice showed an ALS-like phenotype with the death of ADAR2-lacking motor neurons. Notably, the motor neurons deficient in ADAR2 survived when they expressed only edited GluA2 in AR2/GluR-BR/R (AR2res mice, in which the endogenous GluA2 alleles were replaced by the GluR-BR allele that encoded edited GluA2. In heterozygous AR2 mice with only one ADAR2 allele, approximately 20% of the spinal motor neurons expressed unedited GluA2 and underwent degeneration, indicating that half-normal ADAR2 activity is not sufficient to edit all GluA2 expressed in motor neurons. It is likely therefore that the expression of unedited GluA2 causes the death of motor neurons in sporadic ALS. We hypothesize that a progressive downregulation of ADAR2 activity plays a critical role in the pathogenesis of sporadic ALS and that the pathological process commences when motor neurons express unedited GluA2.

  4. Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons

    Science.gov (United States)

    Zhou, Chengwen; Sun, Hongyu; Klein, Peter M.; Jensen, Frances E.

    2015-01-01

    Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48–96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg2+ sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

  5. Optical modulation of neurotransmission using calcium photocurrents through the ion channel LiGluR

    Directory of Open Access Journals (Sweden)

    Mercè eIzquierdo-Serra

    2013-03-01

    Full Text Available A wide range of light-activated molecules (photoswitches and phototriggers have been used to the study of computational properties of an isolated neuron by acting pre and postsynaptically. However, new tools are being pursued to elicit a presynaptic calcium influx that triggers the release of neurotransmitters, most of them based in calcium-permeable Channelrhodopsin-2 mutants. Here we describe a method to control exocytosis of synaptic vesicles through the use of a light-gated glutamate receptor (LiGluR, which has recently been demonstrated that supports secretion by means of calcium influx in chromaffin cells. Expression of LiGluR in hippocampal neurons enables reversible control of neurotransmission with light, and allows modulating the firing rate of the postsynaptic neuron with the wavelength of illumination. This method may be useful for the determination of the complex transfer function of individual synapses.

  6. 海马神经元中TAT-GluR6-9c-dansyl小肽的荧光观察%Delivery of GluR6-9c into hippocampal neurons by TAT transduction domain

    Institute of Scientific and Technical Information of China (English)

    纵艳艳; 裴冬生; 孙亚峰; 张光毅

    2005-01-01

    目的研究TAT-GluR6-9c-dansyl荧光小肽是否可以进入细胞内部.方法在培养的海马神经元中加入TAT-GluR6-9c-dansyl荧光小肽和对照肽TAT38-48-dansyl.结果用10 μmol/L TAT-GluR6-9c-dansyl处理的海马神经元在荧光显微镜下可以观到绿色荧光的出现,而对照肽TAT38-48-dansyl无荧光出现.结论 TAT-GluR6-9c-dansyl荧光小肽可以进入细胞.

  7. Metabotropic Glutamate Receptor I (mGluR1) Antagonism Impairs Cocaine-Induced Conditioned Place Preference via Inhibition of Protein Synthesis

    OpenAIRE

    Yu, Fei; Zhong, Peng; Liu, Xiaojie; Sun, Dalong; Gao, Hai-qing; Liu, Qing-song

    2013-01-01

    Antagonism of group I metabotropic glutamate receptors (mGluR1 and mGluR5) reduces behavioral effects of drugs of abuse, including cocaine. However, the underlying mechanisms remain poorly understood. Activation of mGluR5 increases protein synthesis at synapses. Although mGluR5-induced excessive protein synthesis has been implicated in the pathology of fragile X syndrome, it remains unknown whether group I mGluR-mediated protein synthesis is involved in any behavioral effects of drugs of abus...

  8. On the ligand binding profile and desensitization of plant ionotropic glutamate receptor (iGluR)-like channels functioning in MAMP-triggered Ca2+ influx

    DEFF Research Database (Denmark)

    Kwaaitaal, Mark Adrianus Cornelis J; Maintz, Jens; Cavdar, Meltem

    2012-01-01

    in the putative agonist binding profile and potential mode of desensitization of MAMP-activated plant iGluRs. Based on results from pharmacological inhibition and desensitization experiments, we propose that plant iGluR complexes responsible for the MAMP-triggered Ca ( 2+) signature have a binding profile...... that combines the specificities of mammalian NMDA-and non-NMDA types of iGluRs, possibly reflecting the evolutionary history of plant and animal iGluRs. We further hypothesize that, analogous to the mammalian NMDA-NR1 receptor, desensitization of plant iGluR-like channels might involve binding of the ubiquitous...

  9. mGluR5 Positive Allosteric Modulation Enhances Extinction Learning Following Cocaine Self-Administration

    OpenAIRE

    Cleva, Richard M.; Hicks, Megan P.; Gass, Justin T.; Wischerath, Kelly C.; Plasters, Elizabeth T.; Widholm, John J.; Olive, M. Foster

    2011-01-01

    Extinction of classically and instrumentally conditioned behaviors, such as conditioned fear and drug-seeking behavior, is a process of active learning, and recent studies indicate that potentiation of glutamatergic transmission facilitates extinction learning. In this study we investigated the effects of the type 5 metabotropic glutamate receptors (mGluR5) positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction of cocaine-seeking behavior in ...

  10. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition

    OpenAIRE

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability ...

  11. Complications and visual outcomes after glued foldable intraocular lens implantation in eyes with inadequate capsules.

    Science.gov (United States)

    Kumar, Dhivya Ashok; Agarwal, Amar; Packiyalakshmi, Sathiya; Jacob, Soosan; Agarwal, Athiya

    2013-08-01

    To evaluate the complications and visual outcomes of glued intrascleral-fixated foldable intraocular lens (IOL) in eyes with deficient capsules. Dr Agarwal's Eye Hospital and Eye Research Centre, Chennai, India. Case series. Data were evaluated from the records of patients with a primary glued foldable IOL for intraoperative capsular loss or subluxated lens or secondary glued foldable IOL for aphakia. Exclusion criteria included preoperative glaucoma, aniridia, macular scar, traumatic subluxation, combined surgeries, incomplete operative medical records, and postoperative follow-up less than 6 months. The intraoperative and postoperative complication rates, reoperation rate, and visual outcomes were analyzed. The study comprised 208 eyes (185 patients). The mean follow-up was 16.7 months ± 10.2 (SD). The intraoperative complications were hyphema (0.4%), haptic breakage (0.4%), and deformed haptics (0.9%). Early complications occurred in 29 eyes (13.9%) and included corneal edema (5.7%), epithelial defect (1.9%), and grade 2 anterior chamber reaction (2.4%). Late complications occurred in 39 eyes (18.7%) and included optic capture (4.3%), IOL decentration (3.3%), haptic extrusion (1.9%), subconjunctival haptic (1.4%), macular edema (1.9%), and pigment dispersion (1.9%). Reoperation was required in 16 eyes (7.7%). Haptic position was altered in eyes with IOL decentration. Corrected distance visual acuity (CDVA) improved or remained unchanged in 84.6% of eyes. The postoperative CDVA was 20/40 or better and 20/60 or better in 38.9% and 48.5% of eyes, respectively. The foldable glued-IOL procedure showed satisfactory visual outcomes without serious complications. Intraocular lens decentration was due to haptic-related problems. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  12. Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes

    Science.gov (United States)

    2014-01-01

    Background We previously performed systematic association studies of glutamate receptor gene family members with schizophrenia, and found positive associations of polymorphisms in the GRM3 (a gene of metabotropic glutamate receptor 3: mGluR3) with the disorder. Physiological roles of GRM3 in brain functions and its functional roles in the pathogenesis of schizophrenia remain to be resolved. Results We generated mGluR3 knockout (KO) mice and conducted comprehensive behavioral analyses. KO mice showed hyperactivity in the open field, light/dark transition, and 24-hour home cage monitoring tests, impaired reference memory for stressful events in the Porsolt forced swim test, impaired contextual memory in cued and contextual fear conditioning test, and impaired working memory in the T-Maze forced alternation task test. Hyperactivity and impaired working memory are known as endophenotypes of schizophrenia. We examined long-term synaptic plasticity by assessing long-term potentiation (LTP) in the CA1 region in the hippocampi of KO and wild-type (WT) mice. We observed no differences in the amplitude of LTP between the two genotypes, suggesting that mGluR3 is not essential for LTP in the CA1 region of the mouse hippocampus. As hyperactivity is typically associated with increased dopaminergic transmission, we performed in vivo microdialysis measurements of extracellular dopamine in the nucleus accumbens of KO and WT mice. We observed enhancements in the methamphetamine (MAP)-induced release of dopamine in KO mice. Conclusions These results demonstrate that a disturbance in the glutamate-dopamine interaction may be involved in the pathophysiology of schizophrenia-like behavior, such as hyperactivity in mGluR3 KO mice. PMID:24758191

  13. Internal amplification control of PCR for the Glu1-Dx5 allele in wheat.

    Science.gov (United States)

    Heim, H N; Vieira, E S N; Polo, L R T; Lima, N K; Silva, G J; Linde, G A; Colauto, N B; Schuster, I

    2017-08-17

    One of the limiting factors in using dominant markers is the unique amplification of the target fragment. Therefore, failures in polymerase chain reaction (PCR) or non-amplifications can be interpreted as an absence of the allele. The possibility of false negatives implies in reduced efficiency in the selection process in genetic breeding programs besides the loss of valuable genetic material. Thus, this study aimed to evaluate the viability of a microsatellite marker as an internal amplification control with a dominant marker for the wheat Glu1-Dx5 gene. A population of 77 wheat cultivars/breeding lines was analyzed. Fourteen microsatellite markers were analyzed in silico regarding the formation of dimers and clamps. The biplex reaction conditions were optimized, and the Xbarc117 marker was selected as the internal amplification control with a Glu1-Dx5 marker in wheat. It was concluded that the Xbarc117 microsatellite marker was effective in the simultaneous amplification with a dominant Glu1-Dx5 marker, making biplex PCR viable in wheat for the studied markers.

  14. Differential regulation of GluA1 expression by ketamine and memantine.

    Science.gov (United States)

    Zhang, Ke; Yamaki, Vitor Nagai; Wei, Zhisheng; Zheng, Yu; Cai, Xiang

    2017-01-01

    Evidence from preclinical and clinical studies shows that ketamine, a noncompetitive NMDA receptor antagonist, exerts rapid and sustained antidepressant responses. However, ketamine's psychotomimetic side effects and abuse liability limit the clinical use of the compound. Interestingly, memantine, another NMDA receptor channel blocker, processes no defined antidepressant property but is much safer and clinical tolerated. Understanding why ketamine but not memantine exhibits rapid antidepressant responses is important to elucidate the cellular signaling underlying the fast antidepressant actions of ketamine and to design a new safer generation of fast-acting antidepressants. Here we show that ketamine but memantine caused a rapid and sustained antidepressant-like responses in forced swim test (FST). Both drugs enhanced GluA1 S845 phosphorylation and potentiated Schaffer collateral-CA1 synaptic transmission. However, ketamine but not memantine elevated the expression of GluA1. Incubating acutely prepared hippocampal slices with ketamine but not memantine enhanced mTOR phosphorylation in a time course parallel to the time course of GluA1 elevation. Our results suggest that distinct properties in regulation of mTOR phosphorylation and synaptic protein expression may underlie the differential effectiveness of ketamine and memantine in their antidepressant responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Schizophrenia: Evidence Implicating Hippocampal GluN2B protein and REST Epigenetics in Psychosis Pathophysiology

    Science.gov (United States)

    Tamminga, Carol A.; Zukin, R. Suzanne

    2017-01-01

    The hippocampus is strongly implicated in the psychotic symptoms of schizophrenia. Functionally, basal hippocampal activity (perfusion) is elevated in schizophrenic psychosis, as measured with positron emission tomography (PET) and with magnetic resonance (MR) perfusion techniques, while hippocampal activation to memory tasks is reduced. Subfield-specific hippocampal molecular pathology exists in human psychosis tissue which could underlie this neuronal hyperactivity, including increased GluN2B-containing NMDA receptors in hippocampal CA3, along with increased postsynaptic density protein-95 (PSD-95) along with augmented dendritic spines on the pyramidal neuron apical dendrites. We interpret these observations to implicate a reduction in the influence of a ubiquitous gene repressor, repressor element-1 silencing transcription factor (REST) in psychosis; REST is involved in the age-related maturation of the NMDA receptor from GluN2B- to GluN2A-containing NMDA receptors through epigenetic remodeling. These CA3 changes in psychosis leave the hippocampus liable to pathological increases in neuronal activity, feedforward excitation and false memory formation, sometimes with psychotic content. PMID:26211447

  16. INDEFINITE CONTRACT REVIEW 2000

    CERN Multimedia

    Division des ressources humaines

    2000-01-01

    The Director-General has decided to review staff members in professional categories 2 to 5 satisfying the criteria for consideration for the award of an indefinite contract, in accordance with Article R II 1.20 of the Staff Regulations. Staff members holding a fixed-term contract which it has been decided not to renew will not be considered. The following stages are foreseen:1.\tCandidates qualifying for review in accordance with Article R II 1.20 of the Staff Regulations and the Administrative Circular N° 9 will be contacted by Human Resources Division. 2.\tThe criteria as to when staff members qualify for review are described in Administrative Circular N° 9. These include the following:staff members who are in their fourth year of service on a fixed-term contract;in addition, for staff members having three years or more of previous relevant service in the Organization on a contract of limited duration (or term-contract) and upon proposal by the division leader concerned, consid...

  17. INDEFINITE CONTRACT REVIEW 2001

    CERN Multimedia

    Human Resources Division

    2001-01-01

    The Director-General has decided to review staff members in professional categories 2 to 5 satisfying the criteria for consideration for the award of an indefinite contract, in accordance with Article R II 1.20 of the Staff Regulations. Staff members holding a fixed-term contract which it has been decided not to renew will not be considered. The following stages are foreseen: 1. Candidates qualifying for review in accordance with Article R II 1.20 of the Staff Regulations and the Administrative Circular N° 9 will be contacted by Human Resources Division. 2. The criteria as to when staff members qualify for review are described in Administrative Circular N° 9. These include the following: staff members who are in their fourth year of service on a fixed-term contract; in addition, for staff members having three years or more of previous relevant service in the Organization on a contract of limited duration (or term-contract) and upon proposal by the division leader concerned, consideration fo...

  18. Temporary labour contracts

    CERN Document Server

    2000-01-01

    The five contracts for Temporary Labour assignments on the CERN site (L020/PE, L 021/PE, L 022/PE, L 023/PE and L 024/PE) approved by the Finance Committee in March 1996 (CERN/FC/3857) reached the end of their initial three-year contractual period at the end of December 1999. At CERN?s request, in September 1999 the Finance Committee approved an extension of these contracts for the year 2000 for a total amount not exceeding 6 000 000 Swiss francs (CERN/FC/4196). In December 1999, one of the five contractors, FIRCROFT, withdrew from its contract for 2000. Following the satisfactory execution of the four remaining contracts during 2000, CERN requests approval to extend them from January 2001 for the second of the two optional years provided for in the original adjudication. The Finance Committee is invited to approve the extension of the existing contracts until 31 December 2001 for a total amount not exceeding 6 000 000 Swiss francs at 2000 prices.

  19. Networks and informal contract law

    NARCIS (Netherlands)

    Tjong Tjin Tai, Eric; Brownsword, Roger; van Gestel, Rob A.J.; Micklitz, Hans-W.

    2017-01-01

    It is often argued that formal contract law cannot treat networks correctly. An analysis of networks in an informal contract law system shows that informal contract law is no panacea. Remaining problems require a different approach to legal regulation and contract practice.

  20. In vivo function of Pgβglu-1 in the release of acetophenones in white spruce

    Directory of Open Access Journals (Sweden)

    Melissa H. Mageroy

    2017-07-01

    Full Text Available Eastern spruce budworm (Choristoneura fumiferiana Clemens (ESBW is a major forest pest which feeds on young shoots of white spruce (Picea glauca and can cause landscape level economic and ecological losses. Release of acetophenone metabolites, piceol and pungenol, from their corresponding glycosides, picein and pungenin, can confer natural resistance of spruce to ESBW. A beta-glucosidase gene, Pgβglu-1, was recently discovered and the encoded enzyme was characterized in vitro to function in the release of the defensive acetophenone aglycons. Here we describe overexpression of Pgβglu-1 in a white spruce genotype whose metabolome contains the glucosylated acetophenones, but no detectable amounts of the aglycons. Transgenic overexpression of Pgβglu-1 resulted in release of the acetophenone aglycons in planta. This work provides in vivo evidence for the function of Pgβglu-1.

  1. Glued versus stapled anastomosis of the colon: An experimental study to determine comparative resistance to intraluminal pressure

    Directory of Open Access Journals (Sweden)

    Jiri Paral

    2014-07-01

    Conclusion: Healing with absorbable synthetic glue was as good as with staples. Glued anastomoses resisted pressures that were statistically significantly higher than physiological intraluminal colon pressures but lower than stapled ones.

  2. Synthesis, radiolabeling and biodistribution of a new opioid glucuronide derivative. Ethyl-morphine glucuronide (em-glu)

    International Nuclear Information System (INIS)

    Enginar, H.

    2012-01-01

    In current study, ethyl-morphine (em) was synthesized from the morphine and glucuronidated via enzymatic mechanism. The conjugated glucuronide ethyl-morphine (em-glu) was radiolabeled with 131 I using iodogen method. The quality control studies of radiolabeled compound ( 131 I-em-glu) were done with Thin Layer Radio Chromatography to confirm the radiolabeling efficiency. Biodistribution studies of 131 I labeled em-glu were run on healthy male Albino Wistar rats. The distribution figures demonstrated that 131 I-em-glu was eliminated through the small intestine, large intestine and accumulated in urinary bladder both receptor blocked and unblocked biodistribution studies. A greater uptake of the radiolabeled substance was observed in the m.pons, hypothalamus and mid brain than in the other branches of the rats' brains. (author)

  3. Structure-based discovery of antagonists for GluN3-containing N-methyl-D-aspartate receptors

    DEFF Research Database (Denmark)

    Kvist, Trine; Greenwood, Jeremy R; Hansen, Kasper B

    2013-01-01

    . In the subsequent pharmacological evaluation of 99 selected compounds, we identified 6-hydroxy-[1,2,5]oxadiazolo[3,4-b]pyrazin-5(4H)-one (TK80) a novel competitive antagonist with preference for the GluN3B subunit. Serendipitously, we also identified [2-hydroxy-5-((4-(pyridin-3-yl)thiazol-2-yl)amino]benzoic acid...... (TK13) and 4-(2,4-dichlorobenzoyl)-1H-pyrrole-2-carboxylic acid (TK30), two novel non-competitive GluN3 antagonists. These findings demonstrate that structural differences between the orthosteric binding site of GluN3 and GluN1 can be exploited to generate selective ligands....

  4. Targeting mGlu5 Metabotropic Glutamate Receptors in the Treatment of Cognitive Dysfunction in a Mouse Model of Phenylketonuria

    Directory of Open Access Journals (Sweden)

    Francesca Nardecchia

    2018-03-01

    Full Text Available We studied group-I metabotropic glutamate (mGlu receptors in Pahenu2 (ENU2 mice, which mimic the genetics and neurobiology of human phenylketonuria (PKU, a metabolic disorder characterized, if untreated, by autism, and intellectual disability (ID. Male ENU2 mice showed increased mGlu5 receptor protein levels in the hippocampus and corpus striatum (but not in the prefrontal cortex whereas the transcript of the mGlu5 receptor was unchanged. No changes in mGlu1 receptor mRNA and protein levels were found in any of the three brain regions of ENU2 mice. We extended the analysis to Homer proteins, which act as scaffolds by linking mGlu1 and mGlu5 receptors to effector proteins. Expression of the long isoforms of Homer was significantly reduced in the hippocampus of ENU2 mice, whereas levels of the short Homer isoform (Homer 1a were unchanged. mGlu5 receptors were less associated to immunoprecipitated Homer in the hippocampus of ENU2 mice. The lack of mGlu5 receptor-mediated long-term depression (LTD in wild-type mice (of BTBR strain precluded the analysis of hippocampal synaptic plasticity in ENU2 mice. We therefore performed a behavioral analysis to examine whether pharmacological blockade of mGlu5 receptors could correct behavioral abnormalities in ENU2 mice. Using the same apparatus we sequentially assessed locomotor activity, object exploration, and spatial object recognition (spatial novelty test after displacing some of the objects from their original position in the arena. Systemic treatment with the mGlu5 receptor antagonist, MPEP (20 mg/kg, i.p., had a striking effect in the spatial novelty test by substantially increasing the time spent in exploring the displaced objects in ENU2 mice (but not in wild-type mice. These suggest a role for mGlu5 receptors in the pathophysiology of ID in PKU and suggest that, also in adult untreated animals, cognitive dysfunction may be improved by targeting these receptors with an appropriate therapy.

  5. Age-dependent effects on social interaction of NMDA GluN2A receptor subtype-selective antagonism.

    Science.gov (United States)

    Green, Torrian L; Burket, Jessica A; Deutsch, Stephen I

    2016-07-01

    NMDA receptor-mediated neurotransmission is implicated in the regulation of normal sociability in mice. The heterotetrameric NMDA receptor is composed of two obligatory GluN1 and either two "modulatory" GluN2A or GluN2B receptor subunits. GluN2A and GluN2B-containing receptors differ in terms of their developmental expression, distribution between synaptic and extrasynaptic locations, and channel kinetic properties, among other differences. Because age-dependent differences in disruptive effects of GluN2A and GluN2B subtype-selective antagonists on sociability and locomotor activity have been reported in rats, the current investigation explored age-dependent effects of PEAQX, a GluN2A subtype-selective antagonist, on sociability, stereotypic behaviors emerging during social interaction, and spatial working memory in 4- and 8-week old male Swiss Webster mice. The data implicate an age-dependent contribution of GluN2A-containing NMDA receptors to the regulation of normal social interaction in mice. Specifically, at a dose of PEAQX devoid of any effect on locomotor activity and mouse rotarod performance, the social interaction of 8-week old mice was disrupted without any effect on the social salience of a stimulus mouse. Moreover, PEAQX attenuated stereotypic behavior emerging during social interaction in 4- and 8-week old mice. However, PEAQX had no effect on spontaneous alternations, a measure of spatial working memory, suggesting that neural circuits mediating sociability and spatial working memory may be discrete and dissociable from each other. Also, the data suggest that the regulation of stereotypic behaviors and sociability may occur independently of each other. Because expression of GluN2A-containing NMDA receptors occurs at a later developmental stage, they may be more involved in mediating the pathogenesis of ASDs in patients with histories of "regression" after a period of normal development than GluN2B receptors. Copyright © 2016 Elsevier Inc. All rights

  6. Changed circumstances and the renegotiation of foreign investment contracts

    Directory of Open Access Journals (Sweden)

    Dubajić Dušan

    2017-01-01

    Full Text Available Today's world is shaped by the processes of globalization and economic liberalization, which dominantly determine the social, economic, environmental and political conditions. As part of these processes, there is an increasing rhetoric about the activities of the state to build a legal system 'ideal for attracting' foreign investment, to establish state institutions in charge of 'attracting foreign investment', and to create a business environment conducive to 'attract' foreign investment. Faced with citizen requests and pressure to create conditions for employment, in initial negotiations with foreign investors state, authorities articulate their willingness to meet these requests. The affirmative stance of governments towards the investments of multinational companies easily can be changed. Once the investment begins, the pledges made by one contracting party to the other may prove to be unrealistic and economically unjustified. The tensions generated between the host state and foreign investors jeopardize the foreign investment contract concluded by the contracting parties. Further fulfillment of contractual obligations from foreign investment contracts will be possible if the contracting parties resolve the resulting conflict through mutual negotiations. Through negotiations, the contracting parties can depreciate the impact of the changed circumstances, including a range of economic, political, legislative and environmental conditions. Initiating negotiations at the right time and conducting them in good faith may lead to a solution. Even if an agreement is not reached, the renegotiation may contribute to a better understanding of contractual partners and redefining the positions of the contracting parties.

  7. The Regime of Contracts under Execution within the Insolvency Procedure

    Directory of Open Access Journals (Sweden)

    Cornelia Lefter

    2008-01-01

    Full Text Available According to the Romanian law the debtor that faces financial difficulties of a certain extent can be the object of the insolvency procedure, regulated by Law no. 85/2006 concerning the insolvency procedure. Because the insolvent debtor is no longer trustworthy to its contractual partners and cannot execute the assumed obligations, there is a risk that these contracts cease, or the services that are incumbent on contractual parties are not executed. This is why, it is very important to know within the insolvency procedure and, especially during the judicial reorganization period, what will be the treatment of contracts concluded prior to the opening of this procedure and still not executed, the so-called “contracts under execution”. Also, after clarifying the concept of contract under execution, it is important to establish who has the right to opt between their continuation, or their cancellation. On the other hand, there are presented the special rules provided by Law no. 85/2006 for some categories of contracts concluded prior to the opening of the insolvency procedure, such as: labor, lease, commission contracts, master of netting agreement or contracts concluded intuitu personae or by a debtor that is the owner of a leased building, etc.

  8. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

    Science.gov (United States)

    Zhao, Lan-Xue; Ge, Yan-Hui; Xiong, Cai-Hong; Tang, Ling; Yan, Ying-Hui; Law, Ping-Yee; Qiu, Yu; Chen, Hong-Zhuan

    2018-03-06

    M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

  9. Intimate Partner Violence May Be One Mechanism by Which Male Partner Socioeconomic Status and Substance Use Affect Female Partner Health

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2018-05-01

    Full Text Available Background: Although male partners' socioeconomic status (SES and substance use is associated with worse health of female partners, the mechanism behind this link is still unknown.Objectives: To investigate whether intimate partner violence (IPV is a mechanism by which male partners' SES and substance use influence female partners' self-rated health (SRH as victims and survivors of IPV.Materials and Methods: Fragile Families and Child Wellbeing Study (FFCWS is an ongoing population-based cohort. Male and female partners' SES, anxiety, depression, and substance use, and their relationship status were measured at baseline. IPV victimization was also asked among female partners' at baseline. Female partners' subjective health was measured 3 times (baseline−1998, 3 years later−2001, and 5 years later−2003. Using AMOS, we fitted two structural equation models (SEM for data analysis. In Model 1 we tested direct paths from male partners' SES and mental health to female partners' SRH, in the absence of IPV. In the Model 2 we conceptualized female partners' IPV victimization between male partners' SES and mental health and female partners' SRH. In both models we controlled for the effect of female partners' SES and mental health.Results: In Model 1, male partners' poor SES and substance use were associated with worse trajectory of SRH of female partner. In Model 2, male to female IPV was the mechanism by which male partners' SES and substance use were associated with female partners' SRH.Conclusions: IPV is one of the mechanisms by which male partners' SES and substance use can influence female partners' health. That is, IPV may operate as a vehicle by which male partners' social and psychological risk factors impact female partners' health. Thus, this study demonstrates how male partners' socio-ecological risk factors such as low SES and substance use impact female partners' health. Therefore, there is a need for broader socio-ecological approach

  10. Capitation, contracts, and control

    International Nuclear Information System (INIS)

    McIsaac, L.H.

    1987-01-01

    The radiology business manager in today's environment must become proficient in contract evaluations and negotiations. Health care is focusing on preventive medicine. Third-party payers are offering plans and programs to provide ''well-patient'' care. For prepaid (HMO-IPA-PTO) plans to succeed, demands for reduced fees and other entrepreneurial contractual arrangements are developed. This presentation will focus on specific items contained in most contracts. The issues of withhold, billing procedures, prompt-payment rewards, medical liability, capitation determinations, and modified capitation plans will be discussed. It is the intent of this presentation to share with the audience methods of evaluating contracts, the importance of negotiating specific terms, and an approach to determination of capitation amounts

  11. PROCUREMENT AND CONTRACT MANAGEMENT

    CERN Multimedia

    Training & Development Group; Linda Orr-Easo; Tel. 72460; Nathalie Dumeaux; Tel. 78144

    2001-01-01

    We are pleased to announce the launch of a new training on: Procurement and Contract Management (This seminar will be run by CERN experts in French or in English) Level 1 The aim is to raise awareness of the key issues involved. Date : 8 June 2001 This level is open to everyone. Participants should register via our Web page as soon as possible. Level 2 To develop the skills needed to effectively manage contracts, from the Technical, Commercial and Legal aspects. Dates : Three days, Autumn 2001 This Level is open to those who are/will be more directly responsible for procurement and contract management. Participants should have followed Level 1. For a description of the seminar, please consult:   Level 1: http://training.web.cern.ch/Training/MANCO/P9798/9-cm_e.htm Level 2: http://training.web.cern.ch/Training/MANCO/P9798/9-cm2_e.htm

  12. Amending Contracts for Choreographies

    Directory of Open Access Journals (Sweden)

    Laura Bocchi

    2011-07-01

    Full Text Available Distributed interactions can be suitably designed in terms of choreographies. Such abstractions can be thought of as global descriptions of the coordination of several distributed parties. Global assertions define contracts for choreographies by annotating multiparty session types with logical formulae to validate the content of the exchanged messages. The introduction of such constraints is a critical design issue as it may be hard to specify contracts that allow each party to be able to progress without violating the contract. In this paper, we propose three methods that automatically correct inconsistent global assertions. The methods are compared by discussing their applicability and the relationships between the amended global assertions and the original (inconsistent ones.

  13. Panel discussion : contract design

    Energy Technology Data Exchange (ETDEWEB)

    Vallas, A. [Sempra Energy Trading, Toronto, ON (Canada); Vegh, G. [MacLeod Dixon, Toronto, ON (Canada); McGee, M. [Energy Profiles Ltd., Etobicoke, ON (Canada); Zaremba, T. [Direct Energy Marketing, Calgary, AB (Canada); Seshan, A. [Larson and Toubro Information Technology, Toronto, ON (Canada); Harricks, P. [Gowlings, Toronto, ON (Canada); Bertoldi, L. [Borden Ladner Gervais, Toronto, ON (Canada); Taylor, R. [Hydro One Networks Inc., Markham, ON (Canada)

    2003-05-01

    This session presented highlights of the comments of 8 panelists who discussed the issue of contract design. The new electricity market in Ontario has introduced the energy trader, who enters into a contract with the consumer, based on the spot price set by the Independent Electricity Market Operator. Every contract has a fixed price payer as well as floating-price payers. If the floating price for a given amount of energy is higher than the fixed price, then the consumer gets the difference. Confusion, however, arises with the purchase of retail physical power in the market, particularly in deciding a fixed rate that the consumer will be paying. Different billing options were also discussed with emphasis on mid to large retail customers that have portfolios in the tens of MW and up to 100 MW or more. figs.

  14. Panel discussion : contract design

    International Nuclear Information System (INIS)

    Vallas, A.; Vegh, G.; McGee, M.; Zaremba, T.; Seshan, A.; Harricks, P.; Bertoldi, L.; Taylor, R.

    2003-01-01

    This session presented highlights of the comments of 8 panelists who discussed the issue of contract design. The new electricity market in Ontario has introduced the energy trader, who enters into a contract with the consumer, based on the spot price set by the Independent Electricity Market Operator. Every contract has a fixed price payer as well as floating-price payers. If the floating price for a given amount of energy is higher than the fixed price, then the consumer gets the difference. Confusion, however, arises with the purchase of retail physical power in the market, particularly in deciding a fixed rate that the consumer will be paying. Different billing options were also discussed with emphasis on mid to large retail customers that have portfolios in the tens of MW and up to 100 MW or more. figs

  15. Adding Concurrency to Smart Contracts

    OpenAIRE

    Dickerson, Thomas; Gazzillo, Paul; Herlihy, Maurice; Koskinen, Eric

    2017-01-01

    Modern cryptocurrency systems, such as Ethereum, permit complex financial transactions through scripts called smart contracts. These smart contracts are executed many, many times, always without real concurrency. First, all smart contracts are serially executed by miners before appending them to the blockchain. Later, those contracts are serially re-executed by validators to verify that the smart contracts were executed correctly by miners. Serial execution limits system throughput and fails ...

  16. Pharma partnering: other people's science.

    Science.gov (United States)

    Hofmann, Christian

    2017-01-01

    Partnering is an ideal field if someone is seeking to move from a scientific to a more business-oriented discipline. Partnering's goal is to identify and acquire external innovation. These discoveries are then included in a company's pipeline and help bring novel treatments to patients. Advanced scientific training is essential in the identification and evaluation of these external assets. Here I describe how partnering works in a pharmaceutical company and offer advice on how to make a successful transition from a PhD program to a business career. © 2017 Hofmann. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  17. Partnering models in Nordic construction

    DEFF Research Database (Denmark)

    Larsen, Jacob Norvig

    of local research and industry partners including major building clients. Data were collected by means of national reviews of partnering policies and practices, thematic analyses, and case studies. The concept partnering was introduced in a Nordic context in the 1990s and has since then been implemented...... in a large number of projects. Clients sought to establish a culture of openness and trust within the project and tried promoting this with various kinds of incentives. In some countries the move towards voluntary collaboration was, paradoxically, strongly advocated by public authorities. Generally, however......Traditionally, procurement and contractual policies adopted by building and construction clients produce a system in which clients procure design services separately from construction services, while operation and maintenance have been subject to further, separate procurement actions...

  18. Partnering and integrated supply management

    DEFF Research Database (Denmark)

    Bjarnø, Ole-Christian; Olsen, Anders; Thyssen, Mikael

    2003-01-01

    for strategic management of collaborative relationships on a line with the purchasing perspectives offered by Supply Chain Management. Based on a study of the literature and an in-depth case study carried out within a large Scandinavian contractor, this article gives a proposal for how Partnering can...... be supported by strategic purchasing, with the aim of achieving strategic Partnering. The contribution of this article is thus the development of a new purchasing perspective within Construction Supply Chain Management.......Developments in the construction industry, with a lack of productivity increases compared to manufacturing industry in general, have amongst other things led to the use of Partnering, which is a form of collaboration which attempts to counteract the distrust and the sub-optimisation which...

  19. Is Contract Law Necessary?

    OpenAIRE

    SCHWARTZ, Alan

    2010-01-01

    This lecture was delivered on 17 March 2010. Alan Schwartz, Sterling Professor of Law; Professor of Management, Yale University This Lecture argues that much of the contract law in the cases (the US, the UK and Canada) and in the codes (Europe and Latin America) is unnecessary. To say that a law is unnecessary is to say that it does not perform a useful social function. The argument below thus sets out the functions that contract laws today are thought to serve, and then shows that many of...

  20. Culture and Contract Laws

    DEFF Research Database (Denmark)

    Lando, Ole

    2007-01-01

    In the article it is argued that the wish to preserve the cultural values of national law should not prevent the EU from preparing a Code or an Optional Instrument. The no-code countries on the British Isles and in Scandinavia are the most ardent opponents to the idea of unifying European Contract...... Law by way of a code on Contracts. In both these regions however the absence of a code causes problems. In England a prominent writer has found that the major weakness of the judge-made law is its immense diffusion and the consequent difficulty of access to it and the Nordic countries face the same...

  1. Do contracts help?

    DEFF Research Database (Denmark)

    Tumennasan, Norovsambuu

    Economists perceive moral hazard as an undesirable problem because it undermines efficiency. Carefully designed contracts can mitigate the moral hazard problem, but this assumes that a team is already formed. This paper demonstrates that these contracts are sometimes the reason why teams do...... transfers, then moral hazard affects stability positively in a large class of games. For example, a stable team structure exists if teams produce public goods or if the quota is two. However, these existence results no longer hold if efforts are verifiable....

  2. Statutes and contracts

    DEFF Research Database (Denmark)

    Trosborg, Anna

    1995-01-01

    and commissive acts. The findings show that the language of the law characteristically selects patterns of regulative distinct from, for example, the patterns typically selected in everyday conversational English. The characteristics of the language of the law can be interpreted within the adherence to legal......This paper is concerned with the language used in legal speech acts in legislative texts and contracts in the field of English Contract Law. The central objects of study are regulative functions with a particular view to establishing realization patterns of the rhetorical functions of directive...

  3. Consensus, contracts, and committees.

    Science.gov (United States)

    Moreno, J D

    1991-08-01

    Following a brief account of the puzzle that ethics committees present for the Western Philosophical tradition, I will examine the possibility that social contract theory can contribute to a philosophical account of these committees. Passing through classical as well as contemporary theories, particularly Rawls' recent constructivist approach, I will argue that social contract theory places severe constraints on the authority that may legitimately be granted to ethics committees. This, I conclude, speaks more about the suitability of the theory to this level of analysis than about the ethics committee phenomenon itself.

  4. Impaired associative fear learning in mice with complete loss or haploinsufficiency of AMPA GluR1 receptors

    Directory of Open Access Journals (Sweden)

    Michael Feyder

    2007-12-01

    Full Text Available There is compelling evidence that L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA glutamate receptors containing the GluR1 subunit contribute to the molecular mechanisms associated with learning. AMPA GluR1 glutamate receptor knockout mice (KO exhibit abnormal hippocampal and amygdala plasticity, and deficits on various assays for cognition including Pavlovian fear conditioning. Here we examined associative fear learning in mice with complete absence (KO or partial loss (heterozygous mutant, HET of GluR1 on multiple fear conditioning paradigms. After multi-trial delay or trace conditioning, KO displayed impaired tone and context fear recall relative to WT, whereas HET were normal. After one-trial delay conditioning, both KO and HET showed impaired tone and context recall. HET and KO showed normal nociceptive sensitivity in the hot plate and tail flick tests. These data demonstrate that the complete absence of GluR1 subunit-containing receptors prevents the formation of associative fear memories, while GluR1 haploinsufficiency is sufficient to impair one-trial fear learning. These findings support growing evidence of a major role for GluR1-containing AMPA receptors in amygdalamediated forms of learning and memory.

  5. Selective kainate receptor (GluK1) ligands structurally based upon1H-Cyclopentapyrimidin-2,4(1H,3H)-dione: synthesis, molecular modeling, and pharmacological and biostructural characterization

    DEFF Research Database (Denmark)

    Venskutonyte, Raminta; Butini, Stefania; Coccone, Salvatore Sanna

    2011-01-01

    The physiological function of kainate receptors (GluK1- GluK5) in the central nervous system is not fully understood yet. With the aim of developing potent and selective GluK1 ligands, we have synthesized a series of new thiophene-based GluK1 agonists (6a-c) and antagonists (7a-d). Pharmacologica...

  6. Pupil-mimicry conditions trust in partners: moderation by oxytocin and group membership.

    Science.gov (United States)

    Kret, Mariska E; De Dreu, Carsten K W

    2017-03-15

    Across species, oxytocin, an evolutionarily ancient neuropeptide, facilitates social communication by attuning individuals to conspecifics' social signals, fostering trust and bonding. The eyes have an important signalling function; and humans use their salient and communicative eyes to intentionally and unintentionally send social signals to others, by contracting the muscles around their eyes and pupils. In our earlier research, we observed that interaction partners with dilating pupils are trusted more than partners with constricting pupils. But over and beyond this effect, we found that the pupil sizes of partners synchronize and that when pupils synchronously dilate, trust is further boosted. Critically, this linkage between mimicry and trust was bound to interactions between ingroup members. The current study investigates whether these findings are modulated by oxytocin and sex of participant and partner. Using incentivized trust games with partners from ingroup and outgroup whose pupils dilated, remained static or constricted, this study replicates our earlier findings. It further reveals that (i) male participants withhold trust from partners with constricting pupils and extend trust to partners with dilating pupils, especially when given oxytocin rather than placebo; (ii) female participants trust partners with dilating pupils most, but this effect is blunted under oxytocin; (iii) under oxytocin rather than placebo, pupil dilation mimicry is weaker and pupil constriction mimicry stronger; and (iv) the link between pupil constriction mimicry and distrust observed under placebo disappears under oxytocin. We suggest that pupil-contingent trust is parochial and evolved in social species in and because of group life. © 2017 The Authors.

  7. Cognition and Incomplete Contracts

    OpenAIRE

    Tirole, Jean

    2008-01-01

    Thinking about contingencies, designing covenants, and seeing through their implications is costly. Parties to a contract accordingly use heuristics and leave it incomplete. The paper develops a model of limited cognition and examines its consequences for contractual design. (JEL D23, D82, D86, L22)

  8. Validating Timed Component Contracts

    DEFF Research Database (Denmark)

    Le Guilly, Thibaut; Liu, Shaoying; Olsen, Petur

    2015-01-01

    This paper presents a technique for testing software components with contracts that specify functional behavior, synchronization, as well as timing behavior. The approach combines elements from unit testing with model-based testing techniques for timed automata. The technique is implemented...... in an online testing tool, and we demonstrate its use on a concrete use case....

  9. Turn key contracts

    International Nuclear Information System (INIS)

    Feretic, D.

    1975-01-01

    The aim of this summary is to point out some specific areas which have to be covered in a turn-key contract and which are of primarily interest to the buyer of a nuclear plant. It will be assumed that the buyer is utility company in a developing country and a plant supplier a company in an industrial country. (orig./FW) [de

  10. Startpoints via weak contractions

    OpenAIRE

    Agyingi, Collins Amburo; Gaba, Yaé Ulrich

    2018-01-01

    Startpoints (resp. endpoints) can be defined as "oriented fixed points". They arise naturally in the study of fixed for multi-valued maps defined on quasi-metric spaces. In this article, we give a new result in the startpoint theory for quasi-pseudometric spaces. The result we present is obtained via a generalized weakly contractive set-valued map.

  11. Copyright or Contract?

    Science.gov (United States)

    Okerson, Ann

    1997-01-01

    Most authors and publishers of electronic information believe that current copyright law does not address technical capabilities or reader uses and have turned to contracts or licenses to define the rights of owners and users. Discusses copyrights, fair use, and licenses and highlights licensing's unresolved issues: use and users; archiving;…

  12. GluN2C/GluN2D subunit-selective NMDA receptor potentiator CIQ reverses MK-801-induced impairment in prepulse inhibition and working memory in Y-maze test in mice

    Science.gov (United States)

    Suryavanshi, P S; Ugale, R R; Yilmazer-Hanke, D; Stairs, D J; Dravid, S M

    2014-01-01

    Background and Purpose Despite ample evidence supporting the N-methyl-d-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia, progress in the development of effective therapeutics based on this hypothesis has been limited. Facilitation of NMDA receptor function by co-agonists (d-serine or glycine) only partially alleviates the symptoms in schizophrenia; other means to facilitate NMDA receptors are required. NMDA receptor sub-types differ in their subunit composition, with varied GluN2 subunits (GluN2A-GluN2D) imparting different physiological, biochemical and pharmacological properties. CIQ is a positive allosteric modulator that is selective for GluN2C/GluN2D-containing NMDA receptors (Mullasseril et al.). Experimental Approach The effect of systemic administration of CIQ was tested on impairment in prepulse inhibition (PPI), hyperlocomotion and stereotypy induced by i.p. administration of MK-801 and methamphetamine. The effect of CIQ was also tested on MK-801-induced impairment in working memory in Y-maze spontaneous alternation test. Key Results We found that systemic administration of CIQ (20 mg·kg−1, i.p.) in mice reversed MK-801 (0.15 mg·kg−1, i.p.)-induced, but not methamphetamine (3 mg·kg−1, i.p.)-induced, deficit in PPI. MK-801 increased the startle amplitude to pulse alone, which was not reversed by CIQ. In contrast, methamphetamine reduced the startle amplitude to pulse alone, which was reversed by CIQ. CIQ also partially attenuated MK-801- and methamphetamine-induced hyperlocomotion and stereotyped behaviours. Additionally, CIQ reversed the MK-801-induced working memory deficit in spontaneous alternation in a Y-maze. Conclusion and Implications Together, these results suggest that facilitation of GluN2C/GluN2D-containing receptors may serve as an important therapeutic strategy for treating positive and cognitive symptoms in schizophrenia. PMID:24236947

  13. Researching and understanding your prospective partners

    International Nuclear Information System (INIS)

    Nichols, L.

    1999-01-01

    An overview is included of experience and working relationships of the author that were established with a First Nations people. Terracon first had the opportunity of cooperating and working with a First Nations company in 1966. This relationship originated in conjunction with the reclamation activities at an oil sand operations. This working relationship developed as part of translating landscape plans into final landscapes at the oil sand mine. The work required good team efforts with employees of the Aboriginal company. The initial contacts and working relationships were reasonably satisfactory but these tasks did not bring the author and his partners into direct contact with senior First Nation staff and management. More importantly, the contacts and working relationships made the author realize that there may be opportunities to form strategic alliances and/or joint ventures with Aboriginal companies, particularly in light of the oil sand operator's commitment to employ Aboriginals and Aboriginal owned companies. Several other companies approached the Fort McKay Group, but were unsuccessful. Terracon was successful because it: identified and dealt with the decision makers, had patience and persistence with a First Nation's democratic process, already developed a personal relationship and trust with the band, and started with several verbal agreements, leading to written contracts and then to the current partnership, Terracon-McKay Ltd

  14. The role of GluN2B-containing NMDA receptors in short- and long-term fear recall.

    Science.gov (United States)

    Mikics, Eva; Toth, Mate; Biro, Laszlo; Bruzsik, Biborka; Nagy, Boglarka; Haller, Jozsef

    2017-08-01

    N-methyl-d-aspartate (NMDA) receptors are crucial synaptic elements in long-term memory formation, including the associative learning of fearful events. Although NMDA blockers were consistently shown to inhibit fear memory acquisition and recall, the clinical use of general NMDA blockers is hampered by their side effects. Recent studies revealed significant heterogeneity in the distribution and neurophysiological characteristics of NMDA receptors with different GluN2 (NR2) subunit composition, which may have differential role in fear learning and recall. To investigate the specific role of NMDA receptor subpopulations with different GluN2 subunit compositions in the formation of lasting traumatic memories, we contrasted the effects of general NMDA receptor blockade with GluN2A-, GluN2B-, and GluN2C/D subunit selective antagonists (MK-801, PEAQX, Ro25-6981, PPDA, respectively). To investigate acute and lasting consequences, behavioral responses were investigated 1 and 28days after fear conditioning. We found that MK-801 (0.05 and 0.1mg/kg) decreased fear recall at both time points. GluN2B receptor subunit blockade produced highly similar effects, albeit efficacy was somewhat smaller 28days after fear conditioning. Unlike MK-801, Ro25-6981 (3 and 10mg/kg) did not affect locomotor activity in the open-field. In contrast, GluN2A and GluN2C/D blockers (6 and 20mg/kg PEAQX; 3 and 10mg/kg PPDA, respectively) had no effect on conditioned fear recall at any time point and dose. This sharp contrast between GluN2B- and other subunit-containing NMDA receptor function indicates that GluN2B receptor subunits are intimately involved in fear memory formation, and may provide a novel pharmacological target in post-traumatic stress disorder or other fear-related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. OLC Partners with the People.

    Science.gov (United States)

    Dellinger, Laura M.

    2001-01-01

    Discusses ways in which Oglala Lakota College (South Dakota) helps to strengthen the cultural fabric of the Lakota community and how it has partnered with other institutions of higher learning throughout the state. Reports that the college has a number of community-based initiatives that emphasize the relationship between academics and ancestral…

  16. Partnering in the Construction Industry

    DEFF Research Database (Denmark)

    Ditlev Bohnstedt, Kristian; Bejder, Erik; Haugbølle, Kim

    2013-01-01

    Huge efforts have been made in order to stimulate thorough improvements in the construction industry in terms of value for money, feasibility and consistency when facilitating a partnering approach. Despite this attention there is limited documentation on the development of research trends, thus...

  17. Beijing 2008 Olympic Games Partners

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ At Olympic times, many business giants try to expand their influence by sponsoring the Games. The Games is an opportunity for them to turn from a national to an international brand. Here are brief introductions to some of the Beijing 2008 Olympic Games partners.

  18. A parallel panning scheme used for selection of a GluA4-specific Fab targeting the ligand-binding domain

    DEFF Research Database (Denmark)

    Clausen, Rasmus P; Mohr, Andreas Ø; Riise, Erik

    2016-01-01

    A method for development of murine Fab fragments towards extracellular domains of a surface receptor is presented. The GluA4 ionotropic glutamate receptor is used as a model system. Recombinant GluA4 ectodomain comprising both the N-terminal domain (NTD) and the ligand-binding domain (LBD) in one...... molecule was used for immunization. A Fab-phage library was constructed and a parallel panning approach enabled selection of murine Fab fragments towards either intact ectodomain or the isolated LBD of the GluA4 receptor. One LBD-Fab (FabL9) showed exclusive selectivity for the GluA4 LBD, over a panel...... of LBDs from GluA2, GluK1, GluK2 and GluD2. Soluble FabL9 was produced in amounts suitable for characterization. Competitive ELISA and rat-brain immunoprecipitation experiments confirmed that the FabL9 epitope is conserved in the LBD and in the intact native receptor. By an alignment of GluA2 and GluA4...

  19. The separation of Gln and Glu in STEAM: a comparison study using short and long TEs/TMs at 3 and 7 T.

    Science.gov (United States)

    Dou, Weiqiang; Kaufmann, Jörn; Li, Meng; Zhong, Kai; Walter, Martin; Speck, Oliver

    2015-08-01

    This study aimed to determine the optimal echo time (TE) and mixing time (TM) for in vivo glutamine (Gln) and glutamate (Glu) separation in stimulated-echo acquisition mode at 3 and 7 T. We applied a short TE/TM (20/10 ms) for a high signal-to-noise-ratio and a field-specific long TE/TM (3 T: 72/6 ms; 7 T: 74/68 ms) for optimal Gln and Glu separation of the Carbon-4 proton resonances. Corresponding Gln and Glu spectra were simulated using VeSPA software, and measured in a phantom and human brains at 3 and 7 T. Higher spectral separation for Gln and Glu was achieved at 7 than 3 T. At 7 T, short TE/TM provided comparable spectral separation and in vitro Gln and Glu quantification compared to long TE/TM. Moreover, it showed greater reliability in in vivo Gln and Glu detection and separation than long TE/TM, with significantly lower Cramer-Rao lower bounds (Gln: 14.9 vs. 75.8; Glu: 3.8 vs. 6.5) and correlation between Gln and Glu (p = 0.004). Based on the optimal separation for Gln and Glu, a short TE/TM at 7 T is proposed for future in vivo Gln and Glu acquisition.

  20. Condom use with "casual" and "main" partners: what's in a name?

    Science.gov (United States)

    Lescano, Celia M; Vazquez, Elizabeth A; Brown, Larry K; Litvin, Erika B; Pugatch, David

    2006-09-01

    This study examined adolescents' attitudes about and behaviors toward condom use with "casual" vs. "main" sexual partners. Participants were sexually active adolescents aged 15-21 years (n = 1316) recruited from primary care clinics and through outreach activities in three major cities in the United States. Assessment of condom use within the past 90 days, relevant attitudes, substance use, and demographic data were obtained via audio computer-assisted self-interview (ACASI). Participants were divided into two groups: the 65% who reported main partners only (MP group) and the 35% who had at least one casual partner (CP group). Adolescents in the MP group were more likely to be female, whereas males were significantly more likely to report casual partners. Race/ethnicity, age, education level, household income, and sexually transmitted infection (STI) history were unrelated to group status (i.e., sexual partner type). Greater substance use and riskier attitudes were reported by teens in the CP group. The number of unprotected sex acts in the past 90 days was substantial and equivalent between the main and casual partner groups (19.2 vs. 21.5, respectively). Regression analyses revealed that perceptions of main partner attitudes toward condom use and condom use expectations were significantly related to condom use with MPs, but that attitudes were not related to condom use with CPs. Adolescents with either casual or main partners may be at continued risk for contracting human immunodeficiency virus (HIV) and STIs, given high rates of unprotected sex. Interventions that do not target attitudes and practices related to casual partners as compared with main partners may miss an opportunity to change risk behaviors. This study demonstrates the importance of understanding an adolescent's perception of partner types in order to design effective interventions.

  1. Employee contract issues for dermatologists.

    Science.gov (United States)

    Brown, Christopher E; Indest, George F

    2013-12-01

    Employees and employers routinely face negotiating and preparing physician employment contracts. It is important for both sides to know and understand the basic information on what a comprehensive employment contract for a dermatologist should contain. There are various employment contract provisions from both the employee's perspective and the employer's perspective that must be considered when preparing physician employment contracts. This article provides basic advice and recommendations on requirements that should be included in such contracts. It suggests legal pitfalls that can be avoided through various contract clauses.

  2. Reconciling Contracts and Relational Governance through Strategic Contracting

    DEFF Research Database (Denmark)

    Petersen, Bent; Østergaard, Kim

    2018-01-01

    on contract types, such as strategic versus conventional, may reconcile the enduring research controversy between the substitution and complements perspectives. Practical implications: Today, formal contracts with foreign distributors tend to resemble “prenuptial agreements”. The opportunity for relational...

  3. When your contract manufacturer becomes your competitor.

    Science.gov (United States)

    Arruñda, Benito; Vázquez, Xosé H

    2006-09-01

    PC maker Lenovo started out as a distributor of equipment made by IBM and other companies; now it has formed a joint venture with IBM and will eventually affix its own logo to its computers. Shanghai Automotive Industry Corporation (SAIC) started out manufacturing vehicles for Volkswagen and GM; now it's preparing to sell its own cars in China, Europe, and North America. Lenovo and SAIC represent a host of formerly anonymous makers of brand-name products that are breaking out of their defined roles and pushing the brands themselves aside. In this article, the authors explore the double-edged relationships original equipment manufacturers (OEMs) forge with their contract manufacturers (CMs). On the one hand, an OEM can reduce its labor costs, free up capital, and improve worker productivity by outsourcing all the manufacturing of a product. The company can then concentrate on value-adding activities--research and development, product design, and marketing, for instance. On the other hand, an OEM that retains a contract manufacturer may find itself immersed in a melodrama replete with promiscuity (the ambitious CM pursues liaisons with other OEMs), infidelity (the OEM's retailers and distributors shift their business to the upstart CM), and betrayal (the brazen CM transmits the OEM's intellectual property to the OEM's rivals or keeps it for itself when the contract is up). OEMs cannot simply terminate their outsourcing arrangements--they need contract manufacturers in order to keep specializing, adding value, and staying competitive. But OEMs can manage these relationships so that they don't become weak or the CMs too strong. Doing so requires modesty about revealing trade secrets; caution about whom one consorts with; and a judicious degree of intimacy, loyalty, and generosity toward partners and customers.

  4. Acceptance of referral for partners by clients testing positive for human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Netsanet F

    2013-01-01

    Full Text Available Fetene Netsanet,1 Ayalew Dessie21IMA World Health SuddHealth Multi Donor Trust Fund-Basic Package of Health Services Project, Juba, South Sudan; 2United States Agency for International Development, Private Health Sector Program, Abt Associates Inc, Addis Ababa, EthiopiaBackground: Human immunodeficiency virus (HIV-positive individuals who do not disclose their HIV status to their partners are more likely to present late for HIV and acquired immune deficiency syndrome (AIDS care than those who have disclosed their HIV status to their partners. A major area of challenge with regards to HIV counseling for clients is disclosure of their HIV status to their partners. The main methods of partner notification are patient referral, provider referral, contract referral, and outreach assistance. The emphasis on a plausible and comprehensive partner referral strategy for widespread positive case detection in resource-limited countries needs to be thought out and developed.Methods: A qualitative study was conducted among newly HIV-positive clients to identify partners for notification and acceptance of referral by their partners. Health service providers working in HIV testing and counseling clinics were also provided with semistructured questionnaires in order to assess their view towards partner notification strategies for clients testing positive for HIV.Results: Fifteen newly diagnosed HIV-positive clients were counseled to provide referral slips to their partners. All clients agreed and took the referral card. However, only eight were willing and actually provided the card to their partners. Five of the eight partners of clients who tested HIV-positive and who were provided with referral cards responded to the referral and were tested for HIV. Three were positive and two were negative. Nine of 11 counselors did not agree to requesting partner locator information from HIV-positive clients for contractual referral and/or outreach assistance. The findings

  5. Contracting with the Enemy: The Contracting Officer’s Dilemma

    Science.gov (United States)

    2015-06-01

    contracting command xv KO contracting officer KTR contractor LSC lead service component MGAA Mesopotamia Group Atlas Apache NAT National Afghanistan...and Contract Authority Understanding the roles of contracting versus command authority and command relationships is a fundamental that must be...Audit 12-7 (2012) described the CENTCOM-JTSCC (C- JTSCC) formation and command relationship : In April 2010, CENTCOM issued a fragmentary order to

  6. Positive Modulatory Interactions of NMDA Receptor GluN1/2B Ligand Binding Domains Attenuate Antagonists Activity

    Directory of Open Access Journals (Sweden)

    Douglas Bledsoe

    2017-05-01

    Full Text Available N-methyl D-aspartate receptors (NMDAR play crucial role in normal brain function and pathogenesis of neurodegenerative and psychiatric disorders. Functional tetra-heteromeric NMDAR contains two obligatory GluN1 subunits and two identical or different non-GluN1 subunits that include six different gene products; four GluN2 (A–D and two GluN3 (A–B subunits. The heterogeneity of subunit combination facilities the distinct function of NMDARs. All GluN subunits contain an extracellular N-terminal Domain (NTD and ligand binding domain (LBD, transmembrane domain (TMD and an intracellular C-terminal domain (CTD. Interaction between the GluN1 and co-assembling GluN2/3 subunits through the LBD has been proven crucial for defining receptor deactivation mechanisms that are unique for each combination of NMDAR. Modulating the LBD interactions has great therapeutic potential. In the present work, by amino acid point mutations and electrophysiology techniques, we have studied the role of LBD interactions in determining the effect of well-characterized pharmacological agents including agonists, competitive antagonists, and allosteric modulators. The results reveal that agonists (glycine and glutamate potency was altered based on mutant amino acid sidechain chemistry and/or mutation site. Most antagonists inhibited mutant receptors with higher potency; interestingly, clinically used NMDAR channel blocker memantine was about three-fold more potent on mutated receptors (N521A, N521D, and K531A than wild type receptors. These results provide novel insights on the clinical pharmacology of memantine, which is used for the treatment of mild to moderate Alzheimer's disease. In addition, these findings demonstrate the central role of LBD interactions that can be exploited to develop novel NMDAR based therapeutics.

  7. Power contracting between two different partners. Biogas combined heat and power plants; Energie-Contracting zweier unterschiedlicher Partner. Biogas-Blockheizkraftwerk

    Energy Technology Data Exchange (ETDEWEB)

    Lennartz, Marc Wilhelm

    2013-06-15

    An agricultural consortium in the Eifel (Federal Republic of Germany) has adopted a comprehensive supply of a 7,000 m{sup 2} comprising hotel complex with combined heat and power. The old oil-fired central heating plant has been replaced by a biogas-powered combined heat and power plant (CHP). The hotel was directly connected to the CHP plant by means of a new, approximately 300 m long local heating network including buffer storage. Overall, the hotel operator saves approximately 300,000 L of heating oil annually. The energy demand of the hotel operator will be covered by more than 90 % by means of CHP plants. Thus 20 % of the heating costs is saved.

  8. Contracting in a Foreign Country

    National Research Council Canada - National Science Library

    Rodeschin, Darrin

    1997-01-01

    .... This thesis investigates and compares the different contracting structures of the U.S. Army, the UN, and Apple as well as the duties and responsibilities of the contracting individuals within these organizations...

  9. Utility Energy Services Contracts Guide

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-09-01

    The UESC Guide is a compilation of samples and templates developed as a resource to help contracting officers implement task orders for UESCs under existing U.S. General Services Administration areawide contracts.

  10. Automatic Conflict Detection on Contracts

    Science.gov (United States)

    Fenech, Stephen; Pace, Gordon J.; Schneider, Gerardo

    Many software applications are based on collaborating, yet competing, agents or virtual organisations exchanging services. Contracts, expressing obligations, permissions and prohibitions of the different actors, can be used to protect the interests of the organisations engaged in such service exchange. However, the potentially dynamic composition of services with different contracts, and the combination of service contracts with local contracts can give rise to unexpected conflicts, exposing the need for automatic techniques for contract analysis. In this paper we look at automatic analysis techniques for contracts written in the contract language mathcal{CL}. We present a trace semantics of mathcal{CL} suitable for conflict analysis, and a decision procedure for detecting conflicts (together with its proof of soundness, completeness and termination). We also discuss its implementation and look into the applications of the contract analysis approach we present. These techniques are applied to a small case study of an airline check-in desk.

  11. Water and Muscle Contraction

    Directory of Open Access Journals (Sweden)

    Enrico Grazi

    2008-08-01

    Full Text Available The interaction between water and the protein of the contractile machinery as well as the tendency of these proteins to form geometrically ordered structures provide a link between water and muscle contraction. Protein osmotic pressure is strictly related to the chemical potential of the contractile proteins, to the stiffness of muscle structures and to the viscosity of the sliding of the thin over the thick filaments. Muscle power output and the steady rate of contraction are linked by modulating a single parameter, a viscosity coefficient. Muscle operation is characterized by working strokes of much shorter length and much quicker than in the classical model. As a consequence the force delivered and the stiffness attained by attached cross-bridges is much larger than usually believed.

  12. Energy contracting in Switzerland

    International Nuclear Information System (INIS)

    Muggli, C.

    2000-01-01

    The article discusses the status of energy contracting in Switzerland and compares it with the situation in USA, Germany and France, where it has been standard practice for many years. The fact that this financing and operating instrument is not widely used in Switzerland in spite of its benefits for users and suppliers is discussed, as are the obstacles placed in its way. The results of a study made by the Federal Office of Energy are presented, whereby some 220 existing contracting arrangements with a total investment volume of around CHF 200 million were noted and a further potential of around CHF 1.1 billion estimated. The author notes that in order to utilise this potential, great efforts must be made by all parties involved

  13. 48 CFR 937.7040 - Contract clauses.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clauses. 937.7040... CONTRACTING SERVICE CONTRACTING Protective Services Contracting 937.7040 Contract clauses. The contracting... services” in all protective services solicitations and contracts involving DOE-owned facilities requiring...

  14. Contracting for Complex Products

    Science.gov (United States)

    2010-05-01

    asymmetries, and barriers to market entry and exit (e.g., Mankiw , et al., 2002). Goods may be non-rivalrous or non-excludable so that transferable property...investments. Expenditures are asset specific to the extent they have no economic value outside the product being produced (Williamson, 2005). For...example, some research in the US space program produced economic value outside the contract (e.g., Tang), while other research produced little value

  15. Contract types - turnkey

    International Nuclear Information System (INIS)

    Loeffler, G.

    1975-01-01

    Turnkey or the turnkey type of contract refers to a system of management according to which one organization accepts total responsibility for completing all parts and all phases of a project. In the case of a power project the turnkey contractor undertakes to design the plant, supply or procure and erect the equipment, build the station and put it into operation. (orig./FW) [de

  16. Between Status and Contract?

    Directory of Open Access Journals (Sweden)

    Thorsten Keiser

    2013-01-01

    Full Text Available This contribution deals with unfree labour in Germany from the early modern age until the beginning of the 20th century. It presents the main conclusions of a book published in 2013 on this subject in German. Unfree labour is not identified in the first place with slavery or any other labour relationship based on status. Instead, this study aims at an analysis of freedom and coercion in contractual labour relationships. It will be argued that in Germany contractual labour relationships before 1800 were embedded in a legal system that strongly restricted contractual autonomy and aimed at the suppression of free labour markets. The scope of this legislation was to guarantee efficient labour performance, which was not only perceived as being in the personal interest of an employer, but as a fundamental element of the common good. After 1800 the system changed to more incentive-based legislation that established freedom of contract for labour relations. Nevertheless, coercion in order to perform the contractual duties of a work contract remained important for many groups of workers, especially farmhands and industrial workers. The last criminal sanctions for breaches of labour contracts were only abolished in the revolution of 1919. This development shows the difficulties German law had in extending the principles of private law to workers. When a system of free labour was fully established, the issue of unemployment and economic problems, especially in the Weimar Republic, required a new system of protective rules. The history of free market based labour contracts in Germany was therefore very short, with state intervention shi ing from control and coercion to social assistance.

  17. The interpretation of administrative contracts

    Directory of Open Access Journals (Sweden)

    Cătălin-Silviu SĂRARU

    2014-06-01

    Full Text Available The article analyzes the principles of interpretation for administrative contracts, in French law and in Romanian law. In the article are highlighted derogations from the rules of contract interpretation in common law. Are examined the exceptions to the principle of good faith, the principle of common intention (willingness of the parties, the principle of good administration, the principle of extensive interpretation of the administrative contract. The article highlights the importance and role of the interpretation in administrative contracts.

  18. Exit from contract

    Directory of Open Access Journals (Sweden)

    Oren Bar-Gill

    2016-01-01

    Full Text Available Objective to study the procedure of exiting the contract its costs and benefits. Methods statistical method comparative analysis. Results free exit from contract is one of the most powerful tools for the consumer rights protection. The procedure frees consumers from bad deals and keeps businesses honest. Yet consumers often choose transactions with lockin provisions trading off exit rights for other perks. This article examines the costs and benefits of free exit as compared to the lockin alternative. According to the authors the present regulation of exit penalties in the USA is poorly tailored to address concerns about lockin particularly in light of increasingly ubiquitous marketbased solutions. The article also calls regulatory attention to loyalty rewards which are shown to be as powerful as exit penalties and equally detrimental. Scientific novelty the article reveals a paradoxical state of the law exit regulations in the USA are used most where they are needed least. Termination penalties present an obvishyous target for regulatory intervention while loyalty programs seem benign not warranting any regulatory attention. Practical significance the article is of interest for the Russian juridical science and lawmaking authorities as in Russia the issue of exiting the contract is as topical as in the USA and requires solution which would impair neither the rights of consumers nor the rights of the sellers ofnbspproducts and services. nbsp

  19. CONTRACT FOLLOW UP TRAINING

    CERN Multimedia

    Technical Training; Tel. 74460

    2001-01-01

    SPL is organizing Training Sessions on the Contract Follow Up application. CFU is a Web based tool, developped and supported by the Administrative Information Services. It allows the creation of Divisional Requests and the follow up of their processing, from the Market Survey to the Invitation to Tender or Price Enquiry, approval by the Finance Committee, up to the actual signature of a Contract, acccording to the CERN Purchasing procedures. It includes a document management component. It also provides link with other AIS applications such as BHT and EDH. The course is primarily intended for DPOs, Contract Technical responsibles in the division and their assistants, but is beneficial to anybody involved in the follow up of such Purchasing Procedures. This course is free of charge, but application is necessary. The details of the course may be found at http://training.web.cern.ch/Training/ENSTEC/P2001/Bureautique/cfu4_f.htm General information of CFU may be found at http://ais.cern.ch/apps/cfu/ The dates of t...

  20. Non-turnkey contract

    International Nuclear Information System (INIS)

    Shimoyama, Shunji

    1975-01-01

    A turnkey contract is recommended to such a country which is in the initial stage of nuclear power development with respect to a few plants being constructed earlier. The prime contractor may not necessarily be a reactor supplier. In some cases an architect engineering company may be a contractor. If this arrangement is not possible and the contract had to be a non-turnkey type, there might be some advantage to such a developing country capable of undertaking some major portions of the project works. Even if she might face with troubles and difficulties during construction of the first nuclear power station, she might have chance of aquiring technical kowledge and experience which would later enable her to make the plant of her own manufacture. In such a case it is advisable to limit the number of main contracts as small as possible and to utilize an organization to assist the owner in project management or to assume this function in his behalf. (orig./FW) [de

  1. Non-turnkey contract

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, S

    1975-01-01

    A turnkey contract is recommended to such a country which is in the initial stage of nuclear power development with respect to a few plants being constructed earlier. The prime contractor may not necessarily be a reactor supplier. In some cases an architect engineering company may be a contractor. If this arrangement is not possible and the contract had to be a non-turnkey type, there might be some advantage to such a developing country capable of undertaking some major portions of the project works. Even if she might face troubles and difficulties during construction of the first nuclear power station, she might have a chance of aquiring technical kowledge and experience which would later enable her to make the plant of her own manufacture. In such a case it is advisable to limit the number of main contracts as small as possible and to utilize an organization to assist the owner in project management or to assume this function in his behalf.

  2. Practical guide on contract of technology

    International Nuclear Information System (INIS)

    Choi, Chiho

    1991-12-01

    This book gives descriptions of practical guide on contract of technology, which deals with basic of contract like meaning, function term, singing and sealing, contract and stamp tax, common things on contract of research like keeping secret and prevention and treat of dispute, compensation for damages, notice, expiration date of contract and measurement at end of contract, contract of joint research such as meaning and necessity, note at contract, check list at contract, and return of the research product.

  3. Group I mGlu receptors potentiate synaptosomal [3H]glutamate release independently of exogenously applied arachidonic acid

    International Nuclear Information System (INIS)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J.

    1999-01-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [ 3 H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 μM) increased 4AP-evoked [ 3 H]glutamate release (143.32±2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC 50 =1.60±0.25 μM; E max =147.61±10.96% control) 4AP-evoked [ 3 H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu 1 receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 μM) and was BSA-insensitive. The selective mGlu 5 receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300μM) was without effect. DHPG (100 μM) also potentiated both 30 mM and 50 mM K + -evoked [ 3 H]glutamate release (121.60±12.77% and 121.50±4.45% control, respectively). DHPG (100 μM) failed to influence both 4AP-stimulated 45 Ca 2+ influx and 50 mM K + -induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A 1 receptor, group II/III mGlu receptors or GABA B receptor activity is unlikely since 4AP-evoked [ 3 H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-α-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu 1 receptor-like' receptor potentiates [ 3 H]glutamate release from cerebrocortical synaptosomes in the absence of exogenously applied arachidonic acid. This PKC dependent effect is unlikely to be via modulation of synaptosomal membrane

  4. Why radiologists lose their hospital contracts: is your contract secure?

    Science.gov (United States)

    Muroff, Lawrence R

    2010-03-01

    Previously, a hospital contract meant tenure for the incumbent group of radiologists; however, those days are long gone. Exclusive contracts have morphed into exclusive contracts with carve-outs. Turf erosion has become a fact of life for radiology practices. Now radiologists are losing their hospital contracts in record numbers. Group size, though helpful for a variety of reasons, does not ensure that a practice will be secure in its hospital setting. The reasons that groups lose their hospital contracts are varied, and in this paper, the author discusses the most common ones. Suggestions to help practices avoid this unfortunate fate are presented.

  5. Contracting between firms: empirical evidence

    NARCIS (Netherlands)

    Iyer, R.; Sautner, Z.

    2014-01-01

    We analyse 185 contracts signed between a buyer and 89 suppliers to test how moral-hazard and hold-up problems affect contract design. Our data allow us to study both static and dynamic effects. If a supplier’s products are more critical to the buyer, contracts contain more clauses that address

  6. Static Verification for Code Contracts

    Science.gov (United States)

    Fähndrich, Manuel

    The Code Contracts project [3] at Microsoft Research enables programmers on the .NET platform to author specifications in existing languages such as C# and VisualBasic. To take advantage of these specifications, we provide tools for documentation generation, runtime contract checking, and static contract verification.

  7. Transnational Law of Public Contracts

    NARCIS (Netherlands)

    Audit, M.; Schill, S.W.

    2016-01-01

    Public contracts were traditionally conceived as instruments of domestic public law and used within markets confined to the territory of the state party to the contract. Globalization, however, subjects public contracting to an increasing number of processes that take place at a transnational level

  8. Service quality in contracted facilities.

    Science.gov (United States)

    Rabbani, Fauziah; Pradhan, Nousheen Akber; Zaidi, Shehla; Azam, Syed Iqbal; Yousuf, Farheen

    2015-01-01

    The purpose of this paper is to explore the readiness of contracted and non-contracted first-level healthcare facilities in Pakistan to deliver quality maternal and neonatal health (MNH) care. A balanced scorecard (BSC) was used as the assessment framework. Using a cross-sectional study design, two rural health centers (RHCs) contracted out to Aga Khan Health Service, Pakistan were compared with four government managed RHCs. A BSC was designed to assess RHC readiness to deliver good quality MNH care. In total 20 indicators were developed, representing five BSC domains: health facility functionality, service provision, staff capacity, staff and patient satisfaction. Validated data collection tools were used to collect information. Pearson χ2, Fisher's Exact and the Mann-Whitney tests were applied as appropriate to detect significant service quality differences among the two facilities. Contracted facilities were generally found to be better than non-contracted facilities in all five BSC domains. Patients' inclination for facility-based delivery at contracted facilities was, however, significantly higher than non-contracted facilities (80 percent contracted vs 43 percent non-contracted, p=0.006). The study shows that contracting out initiatives have the potential to improve MNH care. This is the first study to compare MNH service delivery quality across contracted and non-contracted facilities using BSC as the assessment framework.

  9. Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson's disease mouse model.

    Science.gov (United States)

    Zhang, YanFang; Chen, YiMei; Li, Lin; Hölscher, Christian

    2015-10-15

    Glucagon-like peptide 1 (GLP-1) is a hormone and a growth factor. GLP-1 mimetics are currently on the market as treatments for type 2 diabetes. They also have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a first clinical trial in PD patients showed promising results. (Val8)GLP-1-glu-PAL is a new GLP-1 analogue which has a longer biological half-life than exendin-4. We previously showed that (Val8)GLP-1-glu-PAL has neuroprotective properties. Here we tested the drug in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected (30mg/kg i.p.) along with (Val8)GLP-1-glu-PAL (25nmol/kg i.p.) once-daily for 8 days. (Val8)GLP-1-glu-PAL showed good effects in preventing the MPTP-induced motor impairment (Rotarod, open field locomotion, swim test), reduction in tyrosine hydroxylase levels (dopamine synthesis) in the substantia nigra, a reduction of activated caspase 3 levels, of TUNEL positive cell numbers, of the pro-apoptotic signaling molecule BAX and an increase in the growth signaling molecule Bcl-2. The results demonstrate that (Val8)GLP-1-glu-PAL shows promise as a novel treatment of PD. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Gentiopicroside attenuates morphine rewarding effect through downregulation of GluN2B receptors in nucleus accumbens.

    Science.gov (United States)

    Liu, Shui-Bing; Ma, Lan; Guo, Hong-Ju; Feng, Bin; Guo, Yan-Yan; Li, Xiao-Qiang; Sun, Wen-Ji; Zheng, Lian-He; Zhao, Ming-Gao

    2012-08-01

    Gentiopicroside (Gent) is one of the secoiridoid compound isolated from Gentiana lutea. This compound exhibits analgesic activities and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex in mice. Nucleus accumbens (NAc) is a forebrain structure known for its role in drug addiction. However, little is known about the role of Gent on morphine dependence and synaptic transmission changes in the NAc. Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate drug-seeking related behaviors. Brain slices containing NAc were prepared, and whole-cell patch-clamp recordings were performed to record the excitatory postsynaptic currents (EPSCs). Expression of proteins was detected by Western blot analysis. Systemic administration of Gent attenuated the CPP effect induced by morphine, but had no effect on morphine-induced behavioral sensitization. Gent significantly reversed overexpression of GluN2B-containing NMDA receptors and dopamine D2 receptors in NAc during the first week of morphine withdrawal. However, the compound did not affect the overexpression of GluN2A-containing NMDA receptors, GluA1, and dopamine D1 receptors. Lastly, Gent significantly reduced NMDA receptors-mediated EPSCs in the NAc. Our study provides strong evidence that Gent inhibits morphine dependence through downregulation of GluN2B-containing NMDA receptors in the NAc. © 2012 Blackwell Publishing Ltd.

  11. Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.

    Science.gov (United States)

    Holst, Sebastian C; Sousek, Alexandra; Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich; Tafti, Mehdi; Landolt, Hans-Peter

    2017-10-05

    Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep.

  12. Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation

    Science.gov (United States)

    Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich

    2017-01-01

    Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep. PMID:28980941

  13. Genital Herpes in Marital Partners

    Directory of Open Access Journals (Sweden)

    Mary Jacob

    1988-01-01

    Full Text Available During 1983-86, 225 patients were clinically diagnosed to have genital herpes (GH at our clinic. Of these, 90 men and 55 women were currently married. All the spouses were screened clinically and through standardized techniques for isolation and typing of herpes simplex virus, serological testing and Papanicolaou smear. There were 90 couples in whom at least one spouse had GH and in 38 (42% couples both partners had GH. Clinically, 49% of wives and 75% of husbands of GH patients were diagnosed to have the disease. The spouses of recurrent GH patients had a higher frequency of the disease than spouses of primary GH patients. Among spouses who were clinically asymptomatic, 40% had high serological titres suggestive of GH. Wives generally experienced more severe symptoms, especially pain in the lesions. Majority of lesions in both the partners were vesicles and ulcers. Prodromata were more among recurrent GH patients in both the partners. The frequency of recurrences wasalso similar in spouses. Seventy percent of wives and 40% of husbands could not identify any precipitating factor. Intercourse, physical stress and rich food were cited as possible factors in the remaining. All the wives had acquired the diseases through their husbands who were promiscuous. Fifty percent of husbands had been infected before marriage. Given the fact that asymptomatic carriers exist, it is better to consider all marital partners of GH as infected. Repeated and long-term follow, - up examination, particularly of wives of GH patients is therefore essential as an important socio-preventive aspect of this disease.

  14. Behaviour of glued fibre composite sandwich structure in flexure: Experiment and Fibre Model Analysis

    International Nuclear Information System (INIS)

    Manalo, Allan; Aravinthan, Thiru

    2012-01-01

    Highlights: ► Fibre Model Analysis is used to examine the flexural behaviour of sandwich beams. ► Theoretical prediction using FMA is in good agreement with the experiment. ► Using the constituent materials in FMA predicted accurately the beam’s behaviour. ► FMA can be used for analysing sandwich beams with high-strength core in flexure. -- Abstract: The behaviour of glued composite sandwich beams in flexure was investigated with a view of using this material for structural and civil engineering applications. The building block of this glue-laminated beam is a new generation composite sandwich structure made up of glass fibre reinforced polymer skins and a high strength phenolic core material. A simplified Fibre Model Analysis (FMA) usually used to analyse a concrete beam section is adopted to theoretically describe the flexural behaviour of the innovative sandwich beam structure. The analysis included the flexural behaviour of the glued sandwich beams in the flatwise and the edgewise positions. The FMA accounted for the non-linear behaviour of the phenolic core in compression, the cracking of the core in tension and the linear elastic behaviour of the fibre composite skin. The results of the FMA showed a good agreement with the experimental data showing the efficiency and practical applications of the simplified FMA in analysing and designing sandwich structures with high strength core material.

  15. [NMDA-GluR Subunit Antibody-Positive Encephalitis: A Clinical Analysis of Five Cases].

    Science.gov (United States)

    Kaneko, Chikako; Shakespear, Norshalena; Tuchiya, Mario; Kubo, Jin; Yamamoto, Teiji; Katayama, Soichi; Takahashi, Yukitoshi

    2016-09-01

    Five consecutive cases of anti-NMDA-receptor encephalitis that we encountered were marked by a rapidly fluctuating level of consciousness associated with psychotic and delirious mental states. Opisthotonus, catatonia, and rhythmic and non-rhythmic involuntary movements of the mouth and jaw were also characteristic features of these particular cases. Serious and potentially fatal problems included epilepsia partialis continua, partial and generalized seizures, and respiratory depression, resembling the symptoms of encephalitis lethargica. An epidemic of encephalitis lethargica, also known of Economo encephalitis, occurred around 1917. Magnetic resonance imaging revealed edema of the neocortex in two cases and electroencephalography showed polymorphic and monomorphic delta slowing in the acute stage, although electroencephalographic seizure activity were not apparent. Routine cerebrospinal fluid analyses revealed lymphocyte-dominant pleocytosis in three cases, but antibodies against the NMDA-GluR subunit, GluN2B N-terminal, were at a high level in the fluid. All patients recovered without apparent sequelae. Two patients found to have ovarian teratoma underwent surgery for tumor removal. Treatments included pulse intravenous methylprednisolone, high-dose immunoglobulin, and plasma exchange together with seizure control and respiratory support. However, rituximab and or cyclophosphamide pulse therapy should also be considered for intractable cases, as indicated by recent reports. (Received February 16, 2016; Accepted May 2, 2016; Published September 1, 2016).

  16. Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo

    Science.gov (United States)

    Deng, Yan; Wang, Wei; Yu, Pingfeng; Xi, Zhijiang; Xu, Lijian; Li, Xiaolong; He, Nongyue

    2013-04-01

    The purpose of this study is to determine if amino acid neurotransmitters such as gamma-aminobutyric acid (GABA), taurine, glutamate (Glu), and aspartate (Asp) can scavenge activated carbonyl toxicants. In vitro, direct reaction between malondialdehyde (MDA) and amino acids was researched using different analytical methods. The results indicated that scavenging activated carbonyl function of taurine and GABA is very strong and that of Glu and Asp is very weak in pathophysiological situations. The results provided perspective into the reaction mechanism of taurine and GABA as targets of activated carbonyl such as MDA in protecting nerve terminals. In vivo, we studied the effect of taurine and GABA as antioxidants by detecting MDA concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. It was shown that MDA concentration was decreased significantly, and the activities of SOD and GSH-Px were increased significantly in the cerebral cortex and hippocampus of acute epileptic state rats, after the administration of taurine and GABA. The results indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against activated carbonyl in vivo and in vitro.

  17. Multistability and gluing bifurcation to butterflies in coupled networks with non-monotonic feedback

    International Nuclear Information System (INIS)

    Ma Jianfu; Wu Jianhong

    2009-01-01

    Neural networks with a non-monotonic activation function have been proposed to increase their capacity for memory storage and retrieval, but there is still a lack of rigorous mathematical analysis and detailed discussions of the impact of time lag. Here we consider a two-neuron recurrent network. We first show how supercritical pitchfork bifurcations and a saddle-node bifurcation lead to the coexistence of multiple stable equilibria (multistability) in the instantaneous updating network. We then study the effect of time delay on the local stability of these equilibria and show that four equilibria lose their stability at a certain critical value of time delay, and Hopf bifurcations of these equilibria occur simultaneously, leading to multiple coexisting periodic orbits. We apply centre manifold theory and normal form theory to determine the direction of these Hopf bifurcations and the stability of bifurcated periodic orbits. Numerical simulations show very interesting global patterns of periodic solutions as the time delay is varied. In particular, we observe that these four periodic solutions are glued together along the stable and unstable manifolds of saddle points to develop a butterfly structure through a complicated process of gluing bifurcations of periodic solutions

  18. Stiffness analysis of glued connection of the timber-concrete structure

    Science.gov (United States)

    Daňková, Jana; Mec, Pavel; Majstríková, Tereza

    2016-01-01

    This paper presents results of experimental and mathematical analysis of stiffness characteristics of a composite timber-concrete structure. The composite timberconcrete structure presented herein is non-typical compared to similar types of building structures. The interaction between the timber and concrete part of the composite cross-section is not based on metal connecting elements, but it is ensured by a glued-in perforated mesh made of plywood. The paper presents results of experimental and mathematical analysis for material alternatives of the solution of the glued joint. The slip modulus values were determined experimentally. Data obtained from the experiment evaluated by means of regression analysis. Test results were also used as input data for the compilation of a 3D model of a composite structure by means of the 3D finite element model. On the basis of result evaluation, it can be stated that the stress-deformation behaviour at shear loading of this specific timber-concrete composite structure can be affected by the type of glue used. Parameters of the 3D model of both alternative of the structure represent well the behaviour of the composite structure and the model can be used for predicting design parameters of a building structure.

  19. Phenotypic heterogeneity associated with a novel mutation (Gly112Glu) in the Norrie disease protein.

    Science.gov (United States)

    Allen, R C; Russell, S R; Streb, L M; Alsheikheh, A; Stone, E M

    2006-02-01

    To determine the molecular pathology and clinical severity of two pedigrees with a history of early retinal detachment and peripheral retinal vascular abnormalities. Longitudinal cohort study. A longitudinal clinical study and DNA analysis was performed on 49 family members of two pedigrees. Nine individuals were found to be hemizygous for a mutation at codon 112 (Gly112Glu) of the Norrie disease protein (NDP) in one pedigree. Significant phenotypic heterogeneity was found. The proband presented with a unilateral subtotal retinal detachment at the age of 3 years, and subsequently developed a slowly progressive tractional retinal detachment involving the macula in the contralateral eye at the age of 4 years. One individual had only mild peripheral retinal pigmentary changes with normal vision at the age of 79 years. The remaining seven individuals had varying degrees of peripheral retinal vascular abnormalities and anterior segment findings. Seven affected members of a second pedigree affected by a previously reported mutation, Arg74Cys, also demonstrated wide ocular phenotypic variation. A novel mutation (Gly112Glu), which represents the most carboxy located, NDP mutation reported, results in significant phenotypic heterogeneity. These data support the contention that the spectrum of ocular disease severity associated with these NDP mutations is broad. Use of terms that characterize this entity by phenotypic appearance, such as familial exudative vitreoretinopathy, do not adequately communicate the potential spectrum of severity of this disorder to affected or carrier family members.

  20. Tips for Postpartum Dads and Partners

    Science.gov (United States)

    ... Blues: Partners Interview with Wade Bowen Coping with Suicide & Loss Tips for Postpartum Dads and Partners Pregnancy and postpartum mood and anxiety disorders affect the whole family. Here are some tips ...

  1. Intimate Partner Violence, 1993-2010

    Science.gov (United States)

    ... 2015 Special Report NCJ 2392 03 Intimate Partner Violence, 1993–2010 Shannan Catalano, Ph.D., BJS Statistician ... to 2010, the overall rate of intimate partner violence in the United States declined by 64%, from ...

  2. Sexual risk behavior and type of sexual partners in transnational indigenous migrant workers.

    Science.gov (United States)

    Caballero-Hoyos, Ramiro; Villaseñor-Sierra, Alberto; Millán-Guerrero, Rebeca; Trujillo-Hernández, Benjamín; Monárrez-Espino, Joel

    2013-06-01

    Indigenous migrant workers (IMWs) have a high vulnerability to HIV and STDs due to poverty and marginalization. This study examined factors associated with sexual risk behavior (SRB) according to type of partner in transnational young male IMWs at a sugar cane agro-industrial complex in western Mexico. A total of 192 sexually active IMWs were recruited from four laborer shelters to participate in a sexual partner survey. The IMWs were interviewed about their sexual partners and practices over the last 12 months during which it emerged that they had had a total of 360 sexual partners. Multiple linear regression analyses were performed to identify factors related to SRB in 222 main (spouse, mistress and girlfriend) and 138 casual partners (colleague, friend, casual encounter and sex worker). Results showed a significantly higher SRB score with casual partners. For the main partner regression model, prior exposure to HIV- and STD-preventive information and sexual intercourse with higher employment status partners (formal workers vs. self-employed in informal activities and unemployed) were associated with lower SRB scores, but if the sexual relations occurred in Mexico (vs. the U.S.), the SRB scores increased. For the casual partner model, the practice of survival sex (sex in exchange for basic needs), sexual relations in Mexico (vs. the U.S.), and being a circular migrant (person traveling for temporary work to return home when the contract is over) were related to higher SRB scores. Findings support the implementation of preventive interventions using different messages depending on the type of partners, main or casual, within the labor migrant context.

  3. Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors.

    Directory of Open Access Journals (Sweden)

    Yusuke Takeuchi

    Full Text Available The AMPA-type glutamate receptor (AMPAR, which is a tetrameric complex composed of four subunits (GluA1-4 with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc, human natural killer-1 (HNK-1 carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. However, evidence that the HNK-1 epitope on N-glycans of GluA2 directly affects these phenomena is lacking. Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413 within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER in HEK293 cells. Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. The N370S mutant and wild-type GluA2 were co-immunoprecipitated with GluA1, suggesting that N370S was properly associated with GluA1. Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR.

  4. Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines.

    Science.gov (United States)

    Abe, Masahito; Seto, Mabel; Gogliotti, Rocco G; Loch, Matthew T; Bollinger, Katrina A; Chang, Sichen; Engelberg, Eileen M; Luscombe, Vincent B; Harp, Joel M; Bubser, Michael; Engers, Darren W; Jones, Carrie K; Rodriguez, Alice L; Blobaum, Anna L; Conn, P Jeffrey; Niswender, Colleen M; Lindsley, Craig W

    2017-10-12

    Herein, we report the structure-activity relationships within a series of mGlu 7 PAMs based on a pyrazolo[1,5- a ]pyrimidine core with excellent CNS penetration ( K p s > 1 and K p,uu s > 1). Analogues in this series proved to display a range of Group III mGlu receptor selectivity, but VU6005649 emerged as the first dual mGlu 7/8 PAM, filling a void in the Group III mGlu receptor PAM toolbox and demonstrating in vivo efficacy in a mouse contextual fear conditioning model.

  5. Barriers to Screening for Intimate Partner Violence

    NARCIS (Netherlands)

    Sprague, Sheila; Madden, Kim; Simunovic, Nicole; Godin, Katelyn; Pham, Ngan K.; Bhandari, Mohit; Goslings, J. C.

    2012-01-01

    Background: Health care providers play a vital role in the detection of intimate partner violence among their patients. Despite the recommendations for routine intimate partner violence screening in various medical settings, health care providers do not routinely screen for intimate partner

  6. Positive illusions about one's partner's physical attractiveness

    NARCIS (Netherlands)

    Barelds-Dijkstra, Pieternel; Barelds, Dick P. H.

    This study examined couples' ratings of self and partner physical attractiveness. On the basis of the theory of positive illusions, it was expected that individuals would rate their partners as more attractive than their partners would rate themselves. Both members of 93 heterosexual couples, with a

  7. Analysis of foreign petroleum contracts

    International Nuclear Information System (INIS)

    Moran, S.S.

    1991-01-01

    Most foreign exploration and production contracts are of two basic types: Production-Sharing contracts in which a portion of oil revenues, 'cost oil,' is available to the contractor for recoupment of exploration and production costs with the remainder, 'profit oil,' being shared according to an agreed-upon formula, and the familiar Tax-Royalty contract in which a share of petroleum revenues goes to the host country 'off the top' as royalties, and operating profits are taxed at the going rate. Bottom line splits of profits between host governments and contractors, which are approximately 50-50 in the United States, are typically in the 60-40 to 85-15 range elsewhere, with lower profit shares being offset by the higher volume potential and lower costs that may be associated with less mature exploration areas. Foreign contract qualities can be grossly compared by walking typical field models through the contracts to arrive at the bottom line profit splits. Variations within the contract forms include government participation, sliding scale contract elements, special taxes related to rates of return, etc. Often, contract terms are subject to negotiation and the tradeoffs between contract elements must be understood. Contract life, amortization schedules, fund repatriation, currency exchange rates, and the interaction of foreign and United States tax regimens are among the other factors that must be considered. Final decisions on foreign ventures must combine consideration of contracts, economic projections, hydrocarbon volumes, exploration cost estimates, and the estimated probability of success into an overall project assessment

  8. The Lanthanide Contraction Revisited

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, Michael; Oliver, Allen G.; Raymond, Kenneth N.

    2007-04-19

    A complete, isostructural series of lanthanide complexes (except Pm) with the ligand TREN-1,2-HOIQO has been synthesized and structurally characterized by means of single-crystal X-ray analysis. All complexes are 1D-polymeric species in the solid state, with the lanthanide being in an eight-coordinate, distorted trigonal-dodecahedral environment with a donor set of eight unique oxygen atoms. This series constitutes the first complete set of isostructural lanthanide complexes with a ligand of denticity greater than two. The geometric arrangement of the chelating moieties slightly deviates across the lanthanide series, as analyzed by a shape parameter metric based on the comparison of the dihedral angles along all edges of the coordination polyhedron. The apparent lanthanide contraction in the individual Ln-O bond lengths deviates considerably from the expected quadratic decrease that was found previously in a number of complexes with ligands of low denticity. The sum of all bond lengths around the trivalent metal cation, however, is more regular, showing an almost ideal quadratic behavior across the entire series. The quadratic nature of the lanthanide contraction is derived theoretically from Slater's model for the calculation of ionic radii. In addition, the sum of all distances along the edges of the coordination polyhedron show exactly the same quadratic dependency as the Ln-X bond lengths. The universal validity of this coordination sphere contraction, concomitant with the quadratic decrease in Ln-X bond lengths, was confirmed by reexamination of four other, previously published, almost complete series of lanthanide complexes. Due to the importance of multidentate ligands for the chelation of rare-earth metals, this result provides a significant advance for the prediction and rationalization of the geometric features of the corresponding lanthanide complexes, with great potential impact for all aspects of lanthanide coordination.

  9. Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

    Directory of Open Access Journals (Sweden)

    Rachel D. Moloney

    2015-01-01

    Full Text Available Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8 are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need.

  10. 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.

  11. Muscle contraction and force

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline; Risbo, Jens; Pierzynowski, Stefan G.

    2008-01-01

    Muscle contraction studies often focus solely on myofibres and the proteins known to be involved in the processes of sarcomere shortening and cross-bridge cycling, but skeletal muscle also comprises a very elaborate ancillary network of capillaries, which not only play a vital role in terms...... of nutrient delivery and waste product removal, but are also tethered to surrounding fibres by collagen "wires". This paper therefore addresses aspects of the ancillary network of skeletal muscle at both a microscopic and functional level in order to better understand its role holistically as a considerable...

  12. Bunker purchasing with contracts

    DEFF Research Database (Denmark)

    Plum, Christian Edinger Munk; Neergaard Jensen, Peter; Pisinger, David

    2014-01-01

    The cost for bunker fuel represents a major part of the daily running costs of liner shipping vessels. The vessels, sailing on a fixed roundtrip of ports, can lift bunker at these ports, having differing and fluctuating prices. The stock of bunker on a vessel is subject to a number of operational...... optimally to reduce overall costs. The Bunker Purchasing with Contracts Problem has been formulated as a mixed integer programme, which has been Dantzig-Wolfe decomposed. To solve it, a novel column generation algorithm has been developed. The algorithm has been run on a series of real-world instances...

  13. Contractions from grading

    Science.gov (United States)

    Krishnan, Chethan; Raju, Avinash

    2018-04-01

    We note that large classes of contractions of algebras that arise in physics can be understood purely algebraically via identifying appropriate Zm-gradings (and their generalizations) on the parent algebra. This includes various types of flat space/Carroll limits of finite and infinite dimensional (A)dS algebras, as well as Galilean and Galilean conformal algebras. Our observations can be regarded as providing a natural context for the Grassmann approach of Krishnan et al. [J. High Energy Phys. 2014(3), 36]. We also introduce a related notion, which we call partial grading, that arises naturally in this context.

  14. Tendering specification and contracting

    International Nuclear Information System (INIS)

    Koch, E. von

    1975-01-01

    The lecture tendering, specification and contracting is prepared in two parts: This first part deals with technical aspects while part two features the commercial and legal situation in the partnership of two: the supplier of the fuel bundles and the utility. In this lecture a look is given on the way how a supplier can offer its fuel and some certain points are mentioned which are important to compare the bid of one competitor to the other. The major points are summarized which are or at least should be in an offer so as to find out which offer is the best. (orig./FW) [de

  15. The Danish Contracting System

    DEFF Research Database (Denmark)

    Bonke, Sten; Levring, Peter

    The paper is mainly concerned with the institutional framework of the Danish construction industry, describing structures, rules and actors' roles within a perspective of nationally defined procedural guidelines on construction projects. These aspects are treated under the concept of a "contracting...... system". After a short introduction to the structure and activities of the industry the post-war development is reviewed, in particular emphasising the importance of the early industrialisation process which in an international perspective represents quite unique features. Furthermore the most recent...

  16. NMDA and mGluR1 receptor subtypes as major players affecting depotentiation in the hippocampal CA1-region

    Directory of Open Access Journals (Sweden)

    Amira Latif-Hernandez

    2014-03-01

    Full Text Available Neurons have the ability to modify their structure and function which ultimately serves for learning (Abraham and Bear, 1996. Dendritic events provide a major contribution to such modifications. For example, natural and artificial patterns of afferent activation have been shown to induce persistent forms of synaptic plasticity, such as long-term potentiation (LTP and long-term depression (LTD at distinct dendritic synapses. LTP and LTD are both assumed to occur during the physiological processes of learning and memory formation and to sustain the latter (Abraham, 2008. In recent years, there has been a burgeoning interest in the understanding of metaplasticity, which refers to the plasticity of synaptic plasticity (Abraham and Bear, 1996. In particular, depotentiation (DP is the mechanism by which synapses that have recently undergone LTP can reverse their synaptic strengthening in response to low frequency stimulation (LFS; Abraham, 2008. Typically, DP is thought to prevent the saturation of synaptic potentiation by resetting synapses into a more efficient state to store new information. The detailed mechanisms that underlie DP still remain unclear. Bortolotto et al. (1994 first identified metabotropic glutamate receptors (mGluRs as being involved in DP. Experimental evidence indicates that both subtypes of group I mGluRs (mGluR1 and mGluR5 have distinct functions in synaptic plasticity in the hippocampal CA1 region (Gladding et al., 2008. However, their role in DP was not addressed yet in detail and appear to be distinct from those involved in NMDAR-dependent DP (Zho et al., 2002. Therefore, we investigated the precise mechanisms responsible for NMDAR and mGluR-dependent DP by combining electrophysiological recordings in vitro and pharmacological approach. Transverse hippocampal slices (400 µm thick were prepared from the right hippocampus with a tissue chopper and placed into a submerged-type chamber, where they were continuously perfused

  17. Blocking Synaptic Removal of GluA2-Containing AMPA Receptors Prevents the Natural Forgetting of Long-Term Memories.

    Science.gov (United States)

    Migues, Paola Virginia; Liu, Lidong; Archbold, Georgina E B; Einarsson, Einar Ö; Wong, Jacinda; Bonasia, Kyra; Ko, Seung Hyun; Wang, Yu Tian; Hardt, Oliver

    2016-03-23

    The neurobiological processes underpinning the natural forgetting of long-term memories are poorly understood. Based on the critical role of GluA2-containing AMPA receptors (GluA2/AMPARs) in long-term memory persistence, we tested in rats whether their synaptic removal underpins time-dependent memory loss. We found that blocking GluA2/AMPAR removal with the interference peptides GluA23Y or G2CT in the dorsal hippocampus during a memory retention interval prevented the normal forgetting of established, long-term object location memories, but did not affect their acquisition. The same intervention also preserved associative memories of food-reward conditioned place preference that would otherwise be lost over time. We then explored whether this forgetting process could play a part in behavioral phenomena involving time-dependent memory change. We found that infusing GluA23Y into the dorsal hippocampus during a 2 week retention interval blocked generalization of contextual fear expression, whereas infusing it into the infralimbic cortex after extinction of auditory fear prevented spontaneous recovery of the conditioned response. Exploring possible physiological mechanisms that could be involved in this form of memory decay, we found that bath application of GluA23Y prevented depotentiation, but not induction of long-term potentiation, in a hippocampal slice preparation. Together, these findings suggest that a decay-like forgetting process that involves the synaptic removal of GluA2/AMPARs erases consolidated long-term memories in the hippocampus and other brain structures over time. This well regulated forgetting process may critically contribute to establishing adaptive behavior, whereas its dysregulation could promote the decline of memory and cognition in neuropathological disorders. The neurobiological mechanisms involved in the natural forgetting of long-term memory and its possible functions are not fully understood. Based on our previous work describing the

  18. Potentiation of glucose-induced insulin release in islets by desHis1[Glu9]glucagon amide

    DEFF Research Database (Denmark)

    Kofod, Hans; Unson, C G; Merrifield, R B

    1988-01-01

    Glucagon and secretin and some of their hybrid analogs potentiate glucose-induced release of insulin from isolated mouse pancreatic islets. It was recently shown that the synthetic glucagon analog, desHis1[Glu9]glucagon amide, does not stimulate the formation of cyclic adenosine monophosphate...... in the rat hepatocyte membrane, but binds well to the glucagon receptor and is a good competitive antagonist of glucagon. In the present study the effect of this analog on isolated islets was examined. desHis1-[Glu9]glucagon amide at 3 x 10(-7) M, in the presence of 0.01 M D-glucose, increased the release...

  19. Positive illusions about one's partner's physical attractiveness.

    Science.gov (United States)

    Barelds-Dijkstra, Pieternel; Barelds, Dick P H

    2008-03-01

    This study examined couples' ratings of self and partner physical attractiveness. On the basis of the theory of positive illusions, it was expected that individuals would rate their partners as more attractive than their partners would rate themselves. Both members of 93 heterosexual couples, with a mean relationship length of about 14 years, provided ratings of both their own and their partner's physical attractiveness. Results support the theory that individuals hold positive illusions about their partner's physical attractiveness. Implications of these results in terms of relationship-enhancing biases are discussed.

  20. HIV Partner Notification Values and Preferences Among Sex Workers, Fishermen, and Mainland Community Members in Rakai, Uganda: A Qualitative Study.

    Science.gov (United States)

    Quinn, Caitlin; Nakyanjo, Neema; Ddaaki, William; Burke, Virginia M; Hutchinson, Naadiya; Kagaayi, Joseph; Wawer, Maria J; Nalugoda, Fred; Kennedy, Caitlin E

    2018-01-25

    HIV partner notification involves contacting sexual partners of people who test HIV positive and referring them to HIV testing, treatment, and prevention services. To understand values and preferences of key and general populations in Rakai, Uganda, we conducted 6 focus group discussions and 63 in-depth interviews in high prevalence fishing communities and low prevalence mainland communities. Participants included fishermen and sex workers in fishing communities, male and female mainland community members, and healthcare providers. Questions explored three approaches: passive referral, provider referral, and contract referral. Qualitative data were coded and analyzed using a team-based matrix approach. Participants agreed that passive referral was most suitable for primary partners. Provider referral was acceptable in fishing communities for notifying multiple, casual partners. Healthcare providers voiced concerns about limited time, resources, and training for provider-assisted approaches. Options for partner notification may help people overcome barriers to HIV serostatus disclosure and help reach key populations.

  1. Maternal Re-Partnering and New-Partner Fertility: Associations with Nonresident Father Investments in Children

    Science.gov (United States)

    Berger, Lawrence M.; Cancian, Maria; Meyer, Daniel R.

    2011-01-01

    Research suggests that paternal re-partnering and new-partner fertility are associated with decreased nonresident father investments in children. Few studies, however, have examined the influence of maternal re-partnering and new-partner births on nonresident father investments. We use data from the National Longitudinal Survey of Youth to examine associations of maternal re-partnering (through cohabitation or marriage with a new partner) and new-partner births with nonresident father visitation and child support payments. Results suggest that maternal re-partnering is associated with a decrease in both yearly father-child contact and child support received by the mother. New-partner fertility for mothers who are co-residing with a partner is associated with an additional decrease in monthly father-child contact, but does not have an additional influence on yearly father-child contact or child support receipt. PMID:22581998

  2. IPP fuel contracts - creating certain contracts for uncertain times

    Energy Technology Data Exchange (ETDEWEB)

    Coddington, I. [Coddington International Pty. Ltd., Milsons Point, NSW (Australia)

    1998-12-31

    Coal contracts for the new Asian Independent Power Producers (IPPs) are examined. Since most IPPs will be selling to state electricity utilities, often in competition with power plant using other fuels, coal based IPPs must negotiate advantageous coal supply contracts several years before the commissioning of a plant, and must ensure security of supply for at least the life of the construction loan. A more recent trend in the developed world is the Merchant IPP, where there is no guaranteed electricity sale. Lenders are wary of IPPs relying an imported coal, and insist on binding fuel contracts, while coal companies are wary of the quantity of information demanded by these lenders. A full understanding of the risks involved is needed; and a method of price indexation for the contracts. Contracts must also specify security of supply, coal quality, freight contracts and other details. 2 figs.

  3. Characteristics of nuclear contracts. Pt. 1

    International Nuclear Information System (INIS)

    Blanchard, R.

    1976-01-01

    While the object of nuclear contracts is specific, these contracts are concluded according to proven techniques based on general regulations on contracts. Following a review of contract classification, they are differentiated according to the nature of the co-contracting parties, the purpose of the contract itself, the procedure for drawing up the contracts, and payment. The operations prior to the contract vary in that they may include a call for tenders, an option for delays or a letter of intent. (NEA) [fr

  4. Experimental analysis of bonding in steel bars glued into chestnut and tali timber

    Directory of Open Access Journals (Sweden)

    Otero Chans, D.

    2010-03-01

    Full Text Available This article summarizes the results of an extensive experiment designed to determine the effect of geometric and mechanical parameters on the axial strength of the bonds formed when threaded steel bars are glued into sawn hardwood timber. The studies conducted to date on glued wood joints have focused primarily on softwood glued laminated timber or glulam. In the present study, specimens made from two hardwood species with very different physical and mechanical properties were used to evaluate the effect of wood characteristics on the axial strength of such bonds. Several geometries were tested by loading a total of 190 specimens to failure. The ultimate load values found for the specimens were compared to the design values proposed in the final draft version of Eurocode 5 (prEN 1995-1-1(2001.

    En el presente artículo se resumen los resultados de una amplia campaña experimental encaminada a evaluar la influencia de los distintos parámetros geométricos y mecánicos en la capacidad resistente de uniones realizadas con barras roscadas de acero encoladas en madera aserrada de frondosa. Los estudios existentes en el campo de las uniones encoladas en madera se han centrado fundamentalmente en el análisis de uniones realizadas en madera laminada de especies coníferas. Con objeto de evaluar la influencia de las características de la madera en la capacidad resistente de la unión se ensayaron probetas realizadas con dos especies de madera frondosa de características físicas y mecánicas muy diferentes. Se utilizaron diversas configuraciones geométricas. Un total de 190 probetas han sido ensayadas hasta rotura. Los valores de carga de rotura alcanzados por las probetas se han comparado además con los valores de cálculo propuestos por el Eurocódigo 5, en su versión de borrador final prEN 1995-1-1(2001.

  5. Hemolysin coregulated protein 1 as a molecular gluing unit for the assembly of nanoparticle hybrid structures

    Directory of Open Access Journals (Sweden)

    Tuan Anh Pham

    2016-03-01

    Full Text Available Hybrid nanoparticle (NP structures containing organic building units such as polymers, peptides, DNA and proteins have great potential in biosensor and electronic applications. The nearly free modification of the polymer chain, the variation of the protein and DNA sequence and the implementation of functional moieties provide a great platform to create inorganic structures of different morphology, resulting in different optical and magnetic properties. Nevertheless, the design and modification of a protein structure with functional groups or sequences for the assembly of biohybrid materials is not trivial. This is mainly due to the sensitivity of its secondary, tertiary and quaternary structure to the changes in the interaction (e.g., hydrophobic, hydrophilic, electrostatic, chemical groups between the protein subunits and the inorganic material. Here, we use hemolysin coregulated protein 1 (Hcp1 from Pseudomonas aeruginosa as a building and gluing unit for the formation of biohybrid structures by implementing cysteine anchoring points at defined positions on the protein rim (Hcp1_cys3. We successfully apply the Hcp1_cys3 gluing unit for the assembly of often linear, hybrid structures of plasmonic gold (Au NP, magnetite (Fe3O4 NP, and cobalt ferrite nanoparticles (CoFe2O4 NP. Furthermore, the assembly of Au NPs into linear structures using Hcp1_cys3 is investigated by UV–vis spectroscopy, TEM and cryo-TEM. One key parameter for the formation of Au NP assembly is the specific ionic strength in the mixture. The resulting network-like structure of Au NPs is characterized by Raman spectroscopy, showing surface-enhanced Raman scattering (SERS by a factor of 8·104 and a stable secondary structure of the Hcp1_cys3 unit. In order to prove the catalytic performance of the gold hybrid structures, they are used as a catalyst in the reduction reaction of 4-nitrophenol showing similar catalytic activity as the pure Au NPs. To further extend the

  6. Metabotropic glutamate receptor I (mGluR1) antagonism impairs cocaine-induced conditioned place preference via inhibition of protein synthesis.

    Science.gov (United States)

    Yu, Fei; Zhong, Peng; Liu, Xiaojie; Sun, Dalong; Gao, Hai-Qing; Liu, Qing-Song

    2013-06-01

    Antagonism of group I metabotropic glutamate receptors (mGluR1 and mGluR5) reduces behavioral effects of drugs of abuse, including cocaine. However, the underlying mechanisms remain poorly understood. Activation of mGluR5 increases protein synthesis at synapses. Although mGluR5-induced excessive protein synthesis has been implicated in the pathology of fragile X syndrome, it remains unknown whether group I mGluR-mediated protein synthesis is involved in any behavioral effects of drugs of abuse. We report that group I mGluR agonist DHPG induced more pronounced initial depression of inhibitory postsynaptic currents (IPSCs) followed by modest long-term depression (I-LTD) in dopamine neurons of rat ventral tegmental area (VTA) through the activation of mGluR1. The early component of DHPG-induced depression of IPSCs was mediated by the cannabinoid CB1 receptors, while DHPG-induced I-LTD was dependent on protein synthesis. Western blotting analysis indicates that mGluR1 was coupled to extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling pathways to increase translation. We also show that cocaine conditioning activated translation machinery in the VTA via an mGluR1-dependent mechanism. Furthermore, intra-VTA microinjections of mGluR1 antagonist JNJ16259685 and protein synthesis inhibitor cycloheximide significantly attenuated or blocked the acquisition of cocaine-induced conditioned place preference (CPP) and activation of translation elongation factors. Taken together, these results suggest that mGluR1 antagonism inhibits de novo protein synthesis; this effect may block the formation of cocaine-cue associations and thus provide a mechanism for the reduction in CPP to cocaine.

  7. Ionotropic Glutamate Receptor GluR1 in the Visual Cortex of Hamster: Distribution and Co-Localization with Calcium-Binding Proteins and GABA

    International Nuclear Information System (INIS)

    Ye, Eun-Ah; Kim, Tae-Jin; Choi, Jae-Sik; Jin, Mi-Joo; Jeon, Young-Ki; Kim, Moon-Sook; Jeon, Chang-Jin

    2006-01-01

    The subunit composition of the AMPA receptor is critical to its function. AMPA receptors that display very low calcium permeability include the GluR2 subunit, while AMPA receptors that contain other subunits, such as GluR1, display high calcium permeability. We have studied the distribution and morphology of neurons containing GluR1 in the hamster visual cortex with antibody immunocytochemistry. We compared this labeling to that for calbindin D28K, parvalbumin, and GABA. Anti-GluR1-immunoreactive (IR) neurons were located in all layers. The highest density of GluR1-IR neurons was found in layers II/III. The labeled neurons were non-pyramidal neurons, but were varied in morphology. The majority of the labeled neurons were round or oval cells. However, stellate, vertical fusiform, pyriform, and horizontal neurons were also labeled with the anti-GluR1 antibody. Two-color immunofluorescence revealed that many of the GluR1-IR neurons in the hamster visual cortex were double-labeled with either calbindin D28K (31.50%), or parvalbumin (22.91%), or GABA (63.89%). These results indicate that neurons in the hamster visual cortex express GluR1 differently according to different layers and selective cell types, and that many of the GluR1-IR neurons are limited to neurons that express calbindin D28K, parvalbumin, or GABA. The present study elucidates the neurochemical structure of GluR1, a useful clue in understanding the differential vulnerability of GluR1-containing neurons with regard to calcium-dependent excitotoxic mechanisms

  8. 48 CFR 315.371 - Contract preparation and award.

    Science.gov (United States)

    2010-10-01

    ... CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Source Selection 315.371 Contract... the contract until the finance office certifies that the funds are available for obligation. ...

  9. TraceContract

    Science.gov (United States)

    Kavelund, Klaus; Barringer, Howard

    2012-01-01

    TraceContract is an API (Application Programming Interface) for trace analysis. A trace is a sequence of events, and can, for example, be generated by a running program, instrumented appropriately to generate events. An event can be any data object. An example of a trace is a log file containing events that a programmer has found important to record during a program execution. Trace - Contract takes as input such a trace together with a specification formulated using the API and reports on any violations of the specification, potentially calling code (reactions) to be executed when violations are detected. The software is developed as an internal DSL (Domain Specific Language) in the Scala programming language. Scala is a relatively new programming language that is specifically convenient for defining such internal DSLs due to a number of language characteristics. This includes Scala s elegant combination of object-oriented and functional programming, a succinct notation, and an advanced type system. The DSL offers a combination of data-parameterized state machines and temporal logic, which is novel. As an extension of Scala, it is a very expressive and convenient log file analysis framework.

  10. Contracts in Public Administration

    Directory of Open Access Journals (Sweden)

    Agnieszka GRZESIOK-HOROSZ

    2011-03-01

    Full Text Available Objectives: The present makes a contribution to the discussion on contracts in administration under Polish law. It concentrates on theoretical issues, but ones of considerable practical significance. Prior Work though relatively poorly explored, field. This paper is a result of academic considerations on the classical institution of civil law, namely a bilateral juridical act significance of this area may be demonstrated by the fact that one scientific conference and a collection of papers have been devoted to contracts in administration. as research method, the analysis of jurisprudence and doctrinal writings referring to law currently in force. The paper discusses as well the draft of the administrative law, and includes comparative remarks. put forward certain comments pertainin legislation. The authors formulate as well outline theses interesting but complicated matters. As a voice in the doctrinal dispute it can als useful for law students. Value composition. Starting from gener the binding law and proposed amendments. The functioning in foreign countries and proposals of regulatory solutions.

  11. UKAEA'S evolving contract philosophy

    International Nuclear Information System (INIS)

    Nicol, R. D.

    2003-01-01

    The United Kingdom Atomic Energy Authority (UKAEA) has gone through fundamental change over the last ten years. At the heart of this change has been UKAEA's relationship with the contracting and supply market. This paper describes the way in which UKAEA actively developed the market to support the decommissioning programme, and how the approach to contracting has evolved as external pressures and demands have changed. UKAEA's pro-active approach to industry has greatly assisted the development of a healthy, competitive market for services supporting decommissioning in the UK. There have been difficult changes and many challenges along the way, and some retrenchment was necessary to meet regulatory requirements. Nevertheless, UKAEA has sustained a high level of competition - now measured in terms of competed spend as a proportion of competable spend - with annual out-turns consistently over 80%. The prime responsibility for market development will pass to the new Nuclear Decommissioning Authority (NDA) in 2005, as the owner, on behalf of the Government, of the UK's civil nuclear liabilities. The preparatory work for the NDA indicates that the principles established by UKAEA will be carried forward. (author)

  12. 48 CFR 1316.406 - Contract clauses.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clauses. 1316.406 Section 1316.406 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE CONTRACTING METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Incentive Contracts 1316.406 Contract clauses. Insert a clause...

  13. 48 CFR 716.406 - Contract clauses.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clauses. 716.406 Section 716.406 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT CONTRACTING METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Cost Reimbursement Contracts 716.406 Contract clauses. The...

  14. 48 CFR 916.307 - Contract clauses.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clauses. 916.307 Section 916.307 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CONTRACTING METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Cost-Reimbursement Contracts 916.307 Contract clauses. (g) Insert the...

  15. 48 CFR 732.111 - Contract clauses.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clauses. 732.111... CONTRACTING REQUIREMENTS CONTRACT FINANCING General 732.111 Contract clauses. (a) [Reserved] (b) USAID may... Agency-specific indefinite quantity contracts that are a combination of contract types. Rather than using...

  16. 48 CFR 935.071 - Contract clause.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clause. 935.071... CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 935.071 Contract clause. The contracting officer must insert the clause at 952.235-71, Research Misconduct, in contracts, including management and operating...

  17. Switch in the expression of mGlu1 and mGlu5 metabotropic glutamate receptors in the cerebellum of mice developing experimental autoimmune encephalomyelitis and in autoptic cerebellar samples from patients with multiple sclerosis

    NARCIS (Netherlands)

    Fazio, F.; Notartomaso, S.; Aronica, E.; Storto, M.; Battaglia, G.; Vieira, E.; Gatti, S.; Bruno, V.; Biagioni, F.; Gradini, R.; Nicoletti, F.; Di Marco, R.

    2008-01-01

    Recent evidence suggests that changes in the expression of membrane receptors/ion channels in cerebellar Purkinje cells contribute to the onset of cerebellar motor symptoms in patients with multiple sclerosis (MS). We examined the expression of group-I metabotropic glutamate receptors (mGlu1 and

  18. The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Aykut Üner

    2015-10-01

    Conclusions: GluN2B-containing NMDA receptors in AgRP neurons play a critical role in central control of body weight homeostasis and blood glucose balance via mechanisms that likely involve regulation of AgRP neuronal survival and structure, and modulation of hypothalamic leptin action.

  19. Management Control of Market Transactions: The Relation Between Transaction Characteristics, Incomplete Contract Design and Subsequent Performance

    NARCIS (Netherlands)

    Anderson, S.W.; Dekker, H.C.

    2005-01-01

    Using an unusually comprehensive database on 858 transactions for information technology products and accompanying services, we study how close partners who are exposed to opportunistic hazards structure and control a significant transaction. We analyze data on the terms of contracting to determine

  20. The content and role of formal contracts in high-tech alliances

    NARCIS (Netherlands)

    de Jong, Gjalt; Woolthuis, Rosalinde Ja Klein

    2009-01-01

    In this study we investigate the governance structure of innovation processes in high-tech alliances, focusing on the content and role of formal contracts. The design of a formal agreement is one of the most important strategic decisions for alliance partners. Drawing upon transaction cost arguments

  1. IVO Group wins its first operation and maintenance contract in Indonesia

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    Indonesia is one of the world's fastest growing power markets, with electricity demand rising by some 13 % annually: Finland's IVO has recently teamed up with an Indonesian partner to tap into this lucrative and competitive market. IVO's contract signed in March 1997, covers the operation and maintenance of two coal-fired power plants for a period of ten years

  2. The prospect of the DOE - CNPP bilateral contracts at the decommissioning stage

    International Nuclear Information System (INIS)

    Neretin, Yu.A.

    2002-01-01

    Obviously, the priority is the effective and purposeful consumption of the state accounts and foreign partners' funds at the CNPP decommissioning. Thereupon, it is expedient to use DOE and CNPP bilateral contracts experience in order to provide the decommissioning task performance at the schedule date

  3. The role of Glu259 in Escherichia coli elongation factor Tu in ternary complex formation

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Rattenborg, Thomas; Knudsen, Charlotte Rohde

    1998-01-01

    Determination of the crystal structure of the ternary complex formed between elongation factor Tu:GTP and aminoacylated tRNA revealed three regions of interaction between elongation factor Tu and tRNA. The structure indicates that the conserved glutamic acid at position 271 in Thermus aquaticus EF-Tu...... could be involved in the binding of the 3' CCA-Phe end of the aminoacylated tRNA. Therefore, the corresponding residue, Glu259, of Escherichia coli EF-Tu was mutated into alanine, aspartic acid, glutamine and tyrosine, in order to substantiate the crystallographic structural evidence and to obtain...... of interaction with tRNA, while mutation to tyrosine abolished completely the interaction with tRNA. Finally, mutation to glutamine resulted in an elongation factor Tu variant behaving like the wild type. In conclusion, the environment around the site binding the CCA-Phe end of the tRNA is very restricted...

  4. Oxygen binding properties of hemoglobin from the white rhinoceros (beta 2-GLU) and the tapir.

    Science.gov (United States)

    Baumann, R; Mazur, G; Braunitzer, G

    1984-04-01

    The beta-chain of rhinoceros hemoglobin contains glutamic acid at position beta 2, and important site for the binding of organic phosphates. We have investigated the oxygen binding properties of this hemoglobin and its interaction with ATP, 2,3-diphosphoglycerate, CO2 and chloride. The results show that the presence of GLU at position beta 2 nearly abolishes the effect of organic phosphates and CO2, whereas the oxygen-linked binding of chloride is not affected. Thus rhinoceros hemoglobin has only protons and chloride anions as major allosteric effectors for the control of its oxygen affinity. From the results obtained with hemoglobin solutions it can be calculated that the blood oxygen affinity of the rhinoceros must be rather high with a P50 of about 20 torr at pH 7.4 and 37 degrees C, which conforms with observations obtained for other large mammals.

  5. Compositional specification of commercial contracts

    DEFF Research Database (Denmark)

    Andersen, Jesper; Elsborg, Ebbe; Henglein, Fritz

    2006-01-01

    -definable analysis of their state before, during and after execution. We provide several realistic examples of commercial contracts and their analyses. A variety of (real) contracts can be expressed in such a fashion as to support their integration, management and analysis in an operational environment......We present a declarative language for compositional specification of contracts governing the exchange of resources. It extends Eber and Peyton Jones’s declarative language for specifying financial contracts (Jones et al. in The Fun of Programming. 2003) to the exchange of money, goods and services...... amongst multiple parties and complements McCarthy’s Resources, Events and Agents (REA) accounting model (McCarthy in Account Rev. LVII(3), 554–578, 1982) with a view- independent formal contract model that supports definition of user-defined contracts, automatic monitoring under execution and user...

  6. Hippocampal GluA1-containing AMPA receptors mediate context-dependent sensitization to morphine.

    Science.gov (United States)

    Xia, Yan; Portugal, George S; Fakira, Amanda K; Melyan, Zara; Neve, Rachael; Lee, H Thomas; Russo, Scott J; Liu, Jie; Morón, Jose A

    2011-11-09

    Glutamatergic systems, including AMPA receptors (AMPARs), are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic AMPAR expression in the hippocampus, a brain area that is critically involved in learning and memory. These changes could be observed 1 week after the treatment, but only when mice developed context-dependent behavioral sensitization to morphine in which morphine treatment was associated with drug administration environment. Context-dependent behavioral sensitization to morphine was also associated with increased basal synaptic transmission and disrupted hippocampal long-term potentiation (LTP), whereas these effects were less robust when morphine administration was not paired with the drug administration environment. Interestingly, some effects may be related to the prior history of morphine exposure in the drug-associated environment, since alterations of AMPAR expression, basal synaptic transmission, and LTP were observed in mice that received a saline challenge 1 week after discontinuation of morphine treatment. Furthermore, we demonstrated that phosphorylation of GluA1 AMPAR subunit plays a critical role in the acquisition and expression of context-dependent behavioral sensitization, as this behavior is blocked by a viral vector that disrupts GluA1 phosphorylation. These data provide evidence that glutamatergic signaling in the hippocampus plays an important role in context-dependent sensitization to morphine and supports further investigation of glutamate-based strategies for treating opiate addiction.

  7. Mutation at Glu23 eliminates the neuron growth inhibitory activity of human metallothionein-3

    International Nuclear Information System (INIS)

    Ding Zhichun; Teng Xinchen; Cai Bin; Wang Hui; Zheng Qi; Wang Yang; Zhou Guoming; Zhang Mingjie; Wu Houming; Sun Hongzhe; Huang Zhongxian

    2006-01-01

    Human metallothionein-3 (hMT3), first isolated and identified as a neuronal growth inhibitory factor (GIF), is a metalloprotein expressed predominantly in brain. However, untill now, the exact mechanism of the bioactivity of hMT3 is still unknown. In order to study the influence of acid-base catalysis on S-nitrosylation of hMT3, we constructed the E23K mutant of hMT3. During the course of bioassay, we found out unexpectedly that mutation at E23 of hMT3 eliminates the neuronal growth inhibitory activity completely. To the best of our knowledge, it is First report that other residues, besides the TCPCP motif, in the β-domain can alter the bioactivity of hMT3. In order to figure out the causes for the loss of bioactivity of the E23K mutant, the biochemical properties were characterized by UV-vis spectroscopy, CD spectroscopy, pH titration, DTNB reaction, EDTA reaction, and SNOC reaction. All data demonstrated that stability of the metal-thiolate cluster and overall structure of the E23K mutant were not altered too much. However, the reaction of the E23K mutant with SNOC exhibited biphasic kinetics and the mutant protein released zinc ions much faster than hMT3 in the initial step, while hMT3 exhibited single kinetic process. The 2D [ 1 H- 15 N] HSQC was also employed to characterize structural changes during the reaction of hMT3 with varying mounts of nitric oxide. It was shown that the resonance of Glu23 disappeared at a molar ratio of NO to protein of 4. Based on these results, we suggest that mutation at Glu23 may alter the NO metabolism and/or affect zinc homeostasis in brain, thus altering the neuronal growth inhibitory activity

  8. Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats

    NARCIS (Netherlands)

    D'Amore, V.; Santolini, I.; Rijn, C.M. van; Biagioni, F.; Molinaro, G.; Prete, A.; Conn, P.J.; Lindsley, C.W.; Zhou, Y.; Vinson, P.N.; Rodriguez, A.L.; Jones, C.K.; Stauffer, S.R.; Nicoletti, F.; Luijtelaar, E.L.J.M. van; Ngomba, R.T.

    2013-01-01

    Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat

  9. [Beta]-Adrenergic Receptor Activation Rescues Theta Frequency Stimulation-Induced LTP Deficits in Mice Expressing C-Terminally Truncated NMDA Receptor GluN2A Subunits

    Science.gov (United States)

    Moody, Teena D.; Watabe, Ayako M.; Indersmitten, Tim; Komiyama, Noboru H.; Grant, Seth G. N.; O'Dell, Thomas J.

    2011-01-01

    Through protein interactions mediated by their cytoplasmic C termini the GluN2A and GluN2B subunits of NMDA receptors (NMDARs) have a key role in the formation of NMDAR signaling complexes at excitatory synapses. Although these signaling complexes are thought to have a crucial role in NMDAR-dependent forms of synaptic plasticity such as long-term…

  10. Effects of the mGluR2/3 agonist LY379268 on ketamine-evoked behaviours and neurochemical changes in the dentate gyrus of the rat

    NARCIS (Netherlands)

    Imre, Gabor; Salomons, Amber; Jongsma, Minke; Fokkema, Dirk S.; Den Boer, Johan A.; Ter Horst, Gert J.

    One of the functions of group 11 metabotropic glutamate receptors (mGluR2/3) is to modulate glutamate release. Thus, targeting mGluR2/3s might be a novel treatment for several psychiatric disorders associated with inappropriate glutamatergic neurotransmission, such as schizophrenia. In an effort to

  11. Essential role of NMDA receptor channel ε4 subunit (GluN2D in the effects of phencyclidine, but not methamphetamine.

    Directory of Open Access Journals (Sweden)

    Yoko Hagino

    Full Text Available Phencyclidine (PCP, a noncompetitive N-methyl-D-aspartate (NMDA receptor antagonist, increases locomotor activity in rodents and causes schizophrenia-like symptoms in humans. Although activation of the dopamine (DA pathway is hypothesized to mediate these effects of PCP, the precise mechanisms by which PCP induces its effects remain to be elucidated. The present study investigated the effect of PCP on extracellular levels of DA (DA(ex in the striatum and prefrontal cortex (PFC using in vivo microdialysis in mice lacking the NMDA receptor channel ε1 or ε4 subunit (GluRε1 [GluN2A] or GluRε4 [GluN2D] and locomotor activity. PCP significantly increased DA(ex in wildtype and GluRε1 knockout mice, but not in GluRε4 knockout mice, in the striatum and PFC. Acute and repeated administration of PCP did not increase locomotor activity in GluRε4 knockout mice. The present results suggest that PCP enhances dopaminergic transmission and increases locomotor activity by acting at GluRε4.

  12. A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A

    NARCIS (Netherlands)

    Jensen, V.; Kaiser, K.M.M.; Borchardt, T.; Adelmann, G.; Rozov, A.; Burnashev, N.; Brix, C.; Frotscher, M.; Anderson, P.; Hvalby, O.; Sakmann, B.; Seeburg, P.H.; Sprengel, R.

    2003-01-01

    In adult mice, long-term potentiation (LTP) of synaptic transmission at CA3-to-CA1 synapses induced by tetanic stimulation requires L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors containing GluR-A subunits. Here, we report a GluR-A-independent form of LTP, which is comparable in

  13. NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin

    Science.gov (United States)

    Alagarsamy, Sudar; Saugstad, Julie; Warren, Lee; Mansuy, Isabelle M.; Gereau, Robert W.; Conn, P. Jeffrey

    2010-01-01

    Previous reports have shown that activation of N-methyl-D-aspartate (NMDA) receptors potentiates responses to activation of the group I metabotropic glutamate receptor mGluR5 by reversing PKC-mediated desensitization of this receptor. NMDA-induced reversal of mGluR5 desensitization is dependent on activation of protein phosphatases. However, the specific protein phosphatase involved and the precise mechanism by which NMDA receptor activation reduces mGluR desensitization are not known. We have performed a series of molecular, biochemical, and genetic studies to show that NMDA-induced regulation of mGluR5 is dependent on activation of calcium-dependent protein phosphatase 2B/calcineurin (PP2B/CaN). Furthermore, we report that purified calcineurin directly dephosphorylates the C-terminal tail of mGluR5 at sites that are phosphorylated by PKC. Finally, immunoprecipitation and GST fusion protein pull-down experiments reveal that calcineurin interacts with mGluR5, suggesting that these proteins could be colocalized in a signaling complex. Taken together with previous studies, these data suggest that activation of NMDA receptors leads to activation of calcineurin and that calcineurin modulates mGluR5 function by directly dephosphorylating mGluR5 at PKC sites that are involved in desensitization of this receptor. 2005 Elsevier Ltd. All rights reserved. PMID:16005030

  14. Contracting in specialists for emergency obstetric care- does it work in rural India?

    Directory of Open Access Journals (Sweden)

    Randive Bharat

    2012-12-01

    Full Text Available Abstract Background Contracting in private sector is promoted in developing countries facing human resources shortages as a challenge to reduce maternal mortality. This study explored provision, practice, performance, barriers to execution and views about contracting in specialists for emergency obstetric care (EmOC in rural India. Methods Facility survey was conducted in all secondary and tertiary public health facilities (44 in three heterogeneous districts in Maharashtra state of India. Interviews (42 were conducted with programme managers and district and block level officials and with public and private EmOC specialists. Locations of private obstetricians in the study districts were identified and mapped. Results Two schemes, namely Janani Suraksha Yojana and Indian Public Health standards (IPHS provided for contracting in EmOC specialists. The IPHS provision was chosen for use mainly due to greater sum for contracting in (US $ 30/service episode vs.300 US$/month. The positions of EmOC specialists were vacant in 83% of all facilities that hence had a potential for contracting in EmOC specialists. Private specialists were contracted in at 20% such facilities. The contracting in of specialists did not greatly increase EmOC service outputs at facilities, except in facilities with determined leadership. Contracting in specialists was useful for non emergency conditions, but not for obstetric emergencies. The contracts were more of a relational nature with poor monitoring structures. Inadequate infrastructure, longer distance to private specialists, insufficient financial provision for contracting in, and poor management capacities were barriers to effective implementation of contracting in. Dependency on the private sector was a concern among public partners while the private partners viewed contracting in as an opportunity to gain experience and credibility. Conclusions Density and geographic distribution of private specialists are important

  15. Contracting in specialists for emergency obstetric care- does it work in rural India?

    Science.gov (United States)

    Randive, Bharat; Chaturvedi, Sarika; Mistry, Nerges

    2012-12-31

    Contracting in private sector is promoted in developing countries facing human resources shortages as a challenge to reduce maternal mortality. This study explored provision, practice, performance, barriers to execution and views about contracting in specialists for emergency obstetric care (EmOC) in rural India. Facility survey was conducted in all secondary and tertiary public health facilities (44) in three heterogeneous districts in Maharashtra state of India. Interviews (42) were conducted with programme managers and district and block level officials and with public and private EmOC specialists. Locations of private obstetricians in the study districts were identified and mapped. Two schemes, namely Janani Suraksha Yojana and Indian Public Health standards (IPHS) provided for contracting in EmOC specialists. The IPHS provision was chosen for use mainly due to greater sum for contracting in (US $ 30/service episode vs.300 US$/month). The positions of EmOC specialists were vacant in 83% of all facilities that hence had a potential for contracting in EmOC specialists. Private specialists were contracted in at 20% such facilities. The contracting in of specialists did not greatly increase EmOC service outputs at facilities, except in facilities with determined leadership. Contracting in specialists was useful for non emergency conditions, but not for obstetric emergencies. The contracts were more of a relational nature with poor monitoring structures. Inadequate infrastructure, longer distance to private specialists, insufficient financial provision for contracting in, and poor management capacities were barriers to effective implementation of contracting in. Dependency on the private sector was a concern among public partners while the private partners viewed contracting in as an opportunity to gain experience and credibility. Density and geographic distribution of private specialists are important influencing factors in determining feasibility and use of

  16. Corrective justice and contract law

    Directory of Open Access Journals (Sweden)

    Martín Hevia

    2010-06-01

    Full Text Available This article suggests that the central aspects of contract law in various jurisdictions can be explained within the idea of corrective justice. The article is divided into three parts. The first part distinguishes between corrective justice and distributive justice. The second part describes contract law. The third part focuses on actions for breach of contract and within that context reflects upon the idea of corrective justice.

  17. Incentive contracts and time use

    OpenAIRE

    Tor Viking Eriksson; Jaime Ortega

    2011-01-01

    Empirical studies on incentive contracts have primarily been concerned with the effects on employees’ productivity and earnings. The productivity increases associated with such contracts may, however, come at the expense of quality of life at or outside work. In this paper we study the effect on the employees’ non-work activities, testing whether incentive contracts lead to a change in the allocation of time across work and non-work activities. In doing so, we distinguish between two effects,...

  18. Methodological remarks on contraction theory

    DEFF Research Database (Denmark)

    Jouffroy, Jerome; Slotine, Jean-Jacques E.

    Because contraction analysis stems from a differential and incremental framework, the nature and methodology of contraction-based proofs are significantly different from those of their Lyapunov-based counterparts. This paper specifically studies this issue, and illustrates it by revisiting some c...... classical examples traditionally addressed using Lyapunov theory. Even in these cases, contraction tools can often yield significantly simplified analysis. The examples include adaptive control, robotics, and a proof of convergence of the deterministic Extended Kalman Filter....

  19. Judges, commerce and contract law

    OpenAIRE

    Gava, John

    2010-01-01

    John Gava, Reader at Adelaide Law School, considers the question how should judges decide commercial cases, in particular, contract cases? He looks at the circumstances and impact of the use of contract law, with attention on common law contract and market needs. Published in Amicus Curiae – Journal of the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies. The Journal is produced by SALS at the IALS (Institute of Advanced Legal Studies, School of Advanced Study, Un...

  20. On Permuting Cut with Contraction

    OpenAIRE

    Borisavljevic, Mirjana; Dosen, Kosta; Petric, Zoran

    1999-01-01

    The paper presents a cut-elimination procedure for intuitionistic propositional logic in which cut is eliminated directly, without introducing the multiple-cut rule mix, and in which pushing cut above contraction is one of the reduction steps. The presentation of this procedure is preceded by an analysis of Gentzen's mix-elimination procedure, made in the perspective of permuting cut with contraction. It is also shown that in the absence of implication, pushing cut above contraction doesn't p...

  1. Corrective justice and contract law

    OpenAIRE

    Martín Hevia

    2010-01-01

    This article suggests that the central aspects of contract law in various jurisdictions can be explained within the idea of corrective justice. The article is divided into three parts. The first part distinguishes between corrective justice and distributive justice. The second part describes contract law. The third part focuses on actions for breach of contract and within that context reflects upon the idea of corrective justice.

  2. Forthcoming indefinite contract review procedure

    CERN Multimedia

    Human Resources Department

    2011-01-01

    The vacancy notices for posts opened with a view to the award of an indefinite contract will be published in early April 2011. In the meantime, the list of posts to be opened this spring is available at the following address: Indefinite contract posts - spring 2011 A second exercise will take place in autumn 2011 and, as of 2012, the indefinite contract award procedure will only be held once a year, in autumn. For more information please consult: https://hr-recruit.web.cern.ch/hr-recruit/staff/IndefiniteContracts.asp  

  3. Work and minor work contracts

    CERN Document Server

    1999-01-01

    The Work and Minor Work contracts are all of the result-oriented type. The work is specified by CERN and the contractor is given full responsibility for its performance. The contracts are thus very similar to supply contracts. The re-tendering of the existing contracts is almost complete, except for some building maintenance contracts. A new cycle of re-tendering for some activities will be launched in the next twelve months. The total estimated expenditure in the year 2000 for the contracts referred to in this document is 27 750 000 Swiss francs at 1999 prices. The Finance Committee is invited: - to approve the proposed expenditure for the extension of contracts for which the estimated amount for the year 2000 exceeds 750 000 Swiss francs, namely those under references 1, 2, 3, 5, 7, 8, 9 and 23, highlighted in Table I; - to take note that all Work and Minor Work contracts have been tendered since 1 January 1994, except the small contracts shown under references 12 and 16 in Table I; - to take note that the ...

  4. URGENSI STUDI TENTANG PROCUREMENT CONTRACT

    Directory of Open Access Journals (Sweden)

    Yohanes Sogar Simamora

    2006-01-01

    Full Text Available Contractualization is kind of goverment activity in acquiring goods, services and infrastructure as well. Procurement contract has several important function especially in enhancing economic development in a state. In Indonesia, this kind of contract also has function in empowering micro economic scale. Since the aim of procurement study is to provide equal protection between public fund interest in one hand and privat sector in the other hand, general principle of contract law must be taken into consideration together with transparency as the most important principle in government contract.

  5. Male self-disclosure of HIV-positive serostatus to sex partners: a review of the literature.

    Science.gov (United States)

    Sullivan, Kathleen M

    2005-01-01

    HIV-positive men face multiple challenges when deciding whether to disclose their serostatus to sex partners. The purpose of this literature review (1996-2004) is to identify valid and reliable research results that identify factors influencing serostatus disclosure to sex partners by men who are HIV-positive. Articles included in the review were identified through an electronic search using pertinent terms related to disclosure to sex partners, followed by a search of references for additional articles. A compilation of research results for 17 articles is presented under the headings of background, contextual, and psychosocial factors influencing disclosure. An analysis of the data suggests that differences in disclosure rates vary based on sex partner factors including serostatus, relationship status, and number of sex partners. Rates of disclosure to primary sex partners ranged from 67% to 88%, suggesting that nearly one third of main sex partners were not disclosed to and were at risk of contracting HIV, whereas a pattern of lower disclosure among casual partners was evident. As the number of sex partners increased, the likelihood of disclosure to all sex partners decreased, ranging from one quarter (25%) to slightly over half (58%). In addition, perceived efficaciousness and positive outcome expectations were the most frequent theoretical constructs embedded in the research associated with disclosure, suggesting that these factors play an important role in the process of disclosure to sex partners. Interpersonal factors that positively influenced self-disclosure included spousal support, emotional investment, and communication about safe sex, including asking about a partner's serostatus. Self-disclosure was not consistently associated with safer sex. Recommendations for future research are presented, based on the results included in this review.

  6. Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP

    DEFF Research Database (Denmark)

    Mathiesen, Jesper Mosolff; Svendsen, Nannette; Bräuner-Osborne, Hans

    2003-01-01

    We have identified 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893) and 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP) as positive allosteric modulators for the hmGluR4. SIB-1893 and MPEP enhanced the potency and efficacy of L-2-amino-4-phophonobutyrate (L-AP4) in guanosine 5'-O-(3-[(35)S...

  7. Effects of anions on the zwitterion stability of Glu, His and Arg investigated by IRMPD spectroscopy and theory

    NARCIS (Netherlands)

    O'Brien, J.T.; Prell, J.S.; Berden, G.; Oomens, J.; Williams, E.R.

    2010-01-01

    Interactions of halide anions (Cl-, Br-, and I-) with glutamic acid (Glu), histidine (His), and arginine (Arg) and their effects on stabilizing the zwitterionic form of these amino acids were investigated using infrared multiple photon dissociation (IRMPD) spectroscopy between 850 and 1900 cm(-1)

  8. Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2

    DEFF Research Database (Denmark)

    Krintel, Christian; Frydenvang, Karla; Olsen, Lars

    2012-01-01

    Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the ligand-binding domain and stabilize the agonist-bound conformation slow...

  9. Concentration change of DA, DOPAC, Glu and GABA in brain tissues in schizophrenia developmental model rats induced by MK-801.

    Science.gov (United States)

    Liu, Yong; Tang, Yamei; Pu, Weidan; Zhang, Xianghui; Zhao, Jingping

    2011-08-01

    To explore the related neurobiochemical mechanism by comparing the concentration change of dopamine (DA), dihydroxy-phenyl acetic acid (DOPAC), glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain tissues in schizophrenia (SZ) developmental model rats and chronic medication model rats. A total of 60 neonatal male Spragur-Dawley (SD) rats were randomly assigned to 3 groups at the postnatal day 6: an SZ developmental rat model group (subcutaneous injection with MK-801 at the postnatal day 7-10, 0.1 mg/kg, Bid), a chronic medication model group (intraperitoneal injection at the postnatal day 47-60, 0.2 mg/kg,Qd), and a normal control group (injection with 0.9% normal saline during the corresponding periods). DA, DOPAC, Glu, and GABA of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray electrochemic detection by high performance liquid chromatogram technique. The utilization rate of DA and Glu was calculated. Compared with the normal control group, the concentration of DA and DOPAC in the mPFC and the hippocampus in the SZ developmental model group significantly decreased (PGABA concentration and Glu utilization rate in the mPFC also decreased (PGABA system decrease in the mPFC and the DA system function reduces in the hippocampus of SZ developmental rats.

  10. Hippocampal mGluR5 predicts an occurrence of helplessness behavior after repetitive exposure to uncontrollable stress.

    Science.gov (United States)

    Yim, Yeong Shin; Lee, Jinu; Kim, Gun-Tae; Song, Teresa; Kim, Chul Hoon; Kim, Dong Goo

    2012-06-21

    An individual's behavior is generally based on genetic blueprint and previous experiences. A coping strategy, affected by personal interpretation of past events, can be determined by behavioral controllability of stress. In this study, we examined the relationship between the hippocampal mGluR5 expression and coping strategies to stress. Rats were exposed to stress via inescapable and unpredictable footshocks on PNDs 14 and 90. Coping strategies to stress were also measured. Hippocampal mGluR5 was found to be linked to the behavioral coping strategy, as it increased in rats that showed helplessness behavior (HL (+) group) and decreased in those that did not (HL (-) group). Also, the HL (+) group showed a lack of adaptation in a novel environment but the HL (-) group did not. The results suggest that mGluR5 has a pivotal role in the controllability-based coping strategy. Hippocampal mGluR5 could be a target molecule in the manipulation of neuropsychiatric conditions for which maladaptation is a part of behavioral consequences. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. 75 FR 67629 - Federal Travel Regulation (FTR); Terms and Definitions for “Dependent”, “Domestic Partner...

    Science.gov (United States)

    2010-11-03

    ... to public property, loans, grants, benefits, or contracts (5 U.S.C. 553(a)(2)). However, this is... adding the words ``or domestic partner's'' after the word ``spouse's''. PART 301-31--THREATENED LAW... follows: Authority: 5 U.S.C. 5707. Sec. 301-31.2 [Amended] 0 6. Amend Sec. 301-31.2 by adding the words...

  12. Unfair contract terms in B2C contracts

    NARCIS (Netherlands)

    Hesselink, M.W.; Loos, M.B.M.

    2012-01-01

    Because of its textual similarity to the Unfair Terms Directive 1993, Chapter 8 of the proposed CESL, on ‘Unfair contract terms’, can benefit from two decades of interpretative experience which is likely to provide a comparably high degree of instant legal certainty to contracting parties.

  13. Women as Partners of Development

    Directory of Open Access Journals (Sweden)

    Ajeesh Sebastian

    2016-07-01

    Full Text Available Developing Partnership with the stakeholders and giving space for planning, implementing, monitoring and evaluating the project for their own development is an ideal situation of participatory development. It is the popular as well as effective way of development and leads to sustainable progress. When this partnership involves strong participation from the part of women folk, the dynamism of the developmental changes takes in a drastic form. SPED III (sustainability through participation, empowerment and decentralization is a five-year project funded by CIDA and implemented by Save A Family Plan Trust India through their 28 partner NGOs and in 520 villages across India. The methodology of the SPED III is based on the decentralized planning, implementation, monitoring and evaluation. In this process, women are taking important stand and new partnership brings about fundamental changes when it is analyzed from the point of view of stakeholders. The researcher analyses and seeks to find out the comprehensive, multilevel process by which the stakeholders or partners in the development especially women develop, leverage and manage the partnership. The researcher has taken five cases of exemplary changes occurred as part of a participatory development programme. Descriptive design using case study method is applied to do in depth analysis of the cases. The primary data has collected through interview schedule and FGD with shortlisted cases and secondary through sources such as case studies and annual and bi-annual reports of the CIDA programme. The researcher observed the development of perceived need into felt need where the people especially women get involved into the village issue and the spirit that takes them into transformative leadership and partners in development. It was also observed that the when women gets resources to overcome the binding chains, they came out of the culture of silence and they move far ahead in achieving the hierarchy

  14. The Relationship between the Employment Contract and other Civil Contracts

    Directory of Open Access Journals (Sweden)

    Răzvan Radu Popescu

    2015-05-01

    Full Text Available The employment relationship is a contractual one and as such must have all the basic elements of an enforceable contract to make it legally binding. In strict contractual terms, the offer is made by the employer and formally accepted by the employee. Once the acceptance has taken place, there is a legally binding agreement and an action will lie against the party who breaches that agreement, even though it may only just have come into existence. An employment contract, however, is unlike most other contracts. Although the parties will have negotiated the main terms, we shall see that a large number of terms will be implied into the agreement from all sorts of different sources and will not have been individually negotiated by the parties at all. This is what makes an employment contract so different from other contracts. We think this article is an important step in the disclosure of the problem eraised by these two concepts.

  15. Compensatory molecular and functional mechanisms in nervous system of the Grm1(crv4) mouse lacking the mGlu1 receptor: a model for motor coordination deficits.

    Science.gov (United States)

    Rossi, Pia Irene Anna; Musante, Ilaria; Summa, Maria; Pittaluga, Anna; Emionite, Laura; Ikehata, Masami; Rastaldi, Maria Pia; Ravazzolo, Roberto; Puliti, Aldamaria

    2013-09-01

    The metabotropic glutamate type 1 (mGlu1) and type 5 (mGlu5) receptors, the only members of group I mGlu receptors, are implicated in synaptic plasticity and mechanisms of feedback control of glutamate release. They exhibit nearly complementary distributions throughout the central nervous system, well evident in the cerebellum, where mGlu1 receptor is most intensely expressed while mGlu5 receptor is not. Despite their different distribution, they show a similar subcellular localization and use common transducing pathways. We recently described the Grm1(crv4) mouse with motor coordination deficits and renal anomalies caused by a spontaneous mutation inactivating the mGlu1 receptor. To define the neuropathological mechanisms in these mice, we evaluated expression and function of the mGlu5 receptor in cerebral and cerebellar cortices. Western blot and immunofluorescence analyses showed mGlu5 receptor overexpression. Quantitative reverse transcriptase-polymerase chain reaction results indicated that the up-regulation is already evident at RNA level. Functional studies confirmed an enhanced glutamate release from cortical cerebral and cerebellar synaptosomes when compared with wild-type that is abolished by the mGlu5 receptor-specific inhibitor, 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP). Finally, acute MPEP treatment of Grm1(crv4/crv4) mice induced an evident although incomplete improvement of motor coordination, suggesting that mGlu5 receptors enhanced activity worsens, instead of improving, the motor-coordination defects in the Grm1(crv4/crv4) mice.

  16. NOS3 Glu298Asp genotype and blood pressure response to endurance training: the HERITAGE family study.

    Science.gov (United States)

    Rankinen, T; Rice, T; Pérusse, L; Chagnon, Y C; Gagnon, J; Leon, A S; Skinner, J S; Wilmore, J H; Rao, D C; Bouchard, C

    2000-11-01

    Endothelium-dependent vasodilation is a mechanism that may affect blood pressure response to endurance training. Because NO plays a central role in this process, the endothelial NO synthase gene is a good candidate for the regulation of exercise blood pressure. We investigated the associations between an endothelial NO synthase gene polymorphism (Glu298Asp) and endurance training-induced changes in resting and submaximal exercise blood pressure in 471 white subjects of the HERITAGE Family Study. Two submaximal exercise tests at 50 W were conducted both before and after a 20-week endurance training program. Steady-state exercise blood pressure was measured twice in each test with an automated unit. The Glu298Asp polymorphism was typed with a PCR-based method and digestion with BAN:II. Both systolic and diastolic blood pressure at 50 W decreased in response to the training program, whereas resting blood pressure remained unchanged. The decrease in diastolic blood pressure at 50 W was greater (P=0.0005, adjusted for age, gender, baseline body mass index, and baseline diastolic blood pressure at 50 W) in the Glu/Glu homozygotes (4.4 [SEM 0.4] mm Hg, n=187) than in the heterozygotes (3.1 [0.4] mm Hg, n=213) and the Asp/Asp homozygotes (1.3 [0.7] mm Hg, n=71). The genotype accounted for 2.3% of the variance in diastolic blood pressure at 50 W training response. Both the Glu298 homozygotes and the heterozygotes had a greater (P=0.013) training-induced reduction in rate-pressure product at 50 W than the Asp298 homozygotes. These data suggest that DNA sequence variation in the endothelial NO synthase gene locus is associated with the endurance training-induced decreases in submaximal exercise diastolic blood pressure and rate-pressure product in sedentary normotensive white subjects.

  17. Pressure drop in contraction flow

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Koblitz

    This note is a supplement to Dynamic of Polymeric Liquids (DPL) page 178. DPL gives an equation for the pressure drop in a tapered (and circular) contraction, valid only at low angles. Here the general definition of contraction flow (the Bagley correction) and a more general method to find...

  18. Contract Mining versus Owner Mining

    African Journals Online (AJOL)

    Owner

    mining companies can concentrate on their core businesses while using specialists for ... 2 Definition of Contract and Owner. Mining ... equipment maintenance, scheduling and budgeting ..... No. Region. Amount Spent on. Contract Mining. ($ billion). Percent of. Total. 1 ... cost and productivity data based on a large range.

  19. Army Contract Writing System (ACWS)

    Science.gov (United States)

    2016-03-01

    2016 Major Automated Information System Annual Report Army Contract Writing System (ACWS) Defense Acquisition Management Information Retrieval...Information 4 Responsible Office 4 References 4 Program Description 5 Business Case 5 Program Status 6 Schedule 7 Performance...Program Information Program Name Army Contract Writing System (ACWS) DoD Component Army Responsible Office Program Manager References MAIS

  20. CONTRACT ADMINISTRATIVE TRACKING SYSTEM (CATS)

    Science.gov (United States)

    The Contract Administrative Tracking System (CATS) was developed in response to an ORD NHEERL, Mid-Continent Ecology Division (MED)-recognized need for an automated tracking and retrieval system for Cost Reimbursable Level of Effort (CR/LOE) Contracts. CATS is an Oracle-based app...

  1. On CNC Commuting Contractive Tuples

    Indian Academy of Sciences (India)

    The characteristic function has been an important tool for studying completely non-unitary contractions on Hilbert spaces. In this note, we consider completely non-coisometric contractive tuples of commuting operators on a Hilbert space H . We show that the characteristic function, which is now an operator-valued analytic ...

  2. Adding a partner or associate to your professional practice.

    Science.gov (United States)

    Horowitz, J E; Abramowitz, R L

    1986-11-01

    Written partnership agreements, employment contracts and related documents may seem to complicate what appears to be a straightforward arrangement, and can make a close relationship somewhat more impersonal. The decision to add a partner, however, is fundamentally a professional and business consideration, and raises many economic and practical issues that either aren't initially apparent or which may only become relevant after the passage of time. In addition, the tax laws may cause two seemingly similar approaches to have significantly different results. It is worth the time and effort to think through your objectives and the price you are willing to pay to realize them, and to recognize that your new associate will have some legitimate concerns that need to be addressed. A well thought-out written arrangement will provide both of you with a degree of certainty and the comfort of knowing that you and your associate have the same understanding of your common venture.

  3. Alternative staffing services. Contract transcription.

    Science.gov (United States)

    Tessier, C

    1992-03-01

    Contract medical transcription services can be of great assistance in meeting the demands for transcription, without jeopardizing patient, physician, or institutional confidentiality. You simply must require the contract service to provide at least the same degree of protection and preservation of confidentiality that you should require inhouse. To achieve this you must make these requirements explicit, comprehensive, comprehensible, believable, and enforceable. Discuss the requirements with prospective contractors. Review them at least annually with existing contractors and when contracts are due for renewal. Be sure to specify the consequence of breaching confidentiality, and if there are breaches, enforce the terms of the contract. Consult your institution's legal counsel both in developing the contract and in enforcing its provisions. Take into consideration your department's and institution's policies, AHIMA's statement on confidentiality, as well as local, state, and federal laws. Above all, never lose sight of the patient. Ultimately, it is not patient information that you are obligated to protect. It is the patient.

  4. Choreography Synthesis as Contract Agreement

    Directory of Open Access Journals (Sweden)

    Julien Lange

    2013-10-01

    Full Text Available We propose a formal model for distributed systems, where each participant advertises its requirements and obligations as behavioural contracts, and where multiparty sessions are started when a set of contracts allows to synthesise a choreography. Our framework is based on the CO2 calculus for contract-oriented computing, and borrows concepts and results from the session type literature. It supports sessions where the number of participants is not determined beforehand, and keeps CO2's ability to rule out participants that are culpable if contracts are not fulfilled at runtime. We show that we have progress and session fidelity in CO2, as a result of the honesty of participants — i.e., their ability to always adhere to their contracts.

  5. Meeting sex partners through the Internet, risky sexual behavior, and HIV testing among sexually transmitted infections clinic patients.

    Science.gov (United States)

    Brown, Monique J; Pugsley, River; Cohen, Steven A

    2015-02-01

    The Internet has now become a popular venue to meet sex partners. People who use the Internet to meet sex partners may be at a higher risk for contracting HIV and STIs. This study examined the association between meeting sex partners from the Internet, and HIV testing, STI history, and risky sexual behavior. Data were obtained from the Virginia Department of Health STD Surveillance Network. Logistic regression models were used to obtain crude and adjusted odds ratios, and 95 % confidence intervals for the associations between meeting sex partners through the Internet and ever tested for HIV, HIV testing in the past 12 months, STI history, and risky sexual behavior. Logistic regression was also used to determine if gender and men who have sex with men interaction terms significantly improved the model. Women who met a sex partner from the Internet were more likely to have had an HIV test in the past 12 months than women who did not meet a partner in this way. On the other hand, men who met a sex partner through the Internet were more likely to have ever had an HIV test than other men, but this was only seen for heterosexual men. All populations who met a sex partner from the Internet were more likely to take part in risky sexual behavior. HIV prevention strategies should emphasize annual testing for all populations.

  6. Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Diana L Price

    2010-11-01

    Full Text Available Dementia with Lewy bodies (DLB and Parkinson's Disease (PD are neurodegenerative disorders of the aging population characterized by the abnormal accumulation of alpha-synuclein (alpha-syn. Previous studies have suggested that excitotoxicity may contribute to neurodegeneration in these disorders, however the underlying mechanisms and their relationship to alpha-syn remain unclear. For this study we proposed that accumulation of alpha-syn might result in alterations in metabotropic glutamate receptors (mGluR, particularly mGluR5 which has been linked to deficits in murine models of PD. In this context, levels of mGluR5 were analyzed in the brains of PD and DLB human cases and alpha-syn transgenic (tg mice and compared to age-matched, unimpaired controls, we report a 40% increase in the levels of mGluR5 and beta-arrestin immunoreactivity in the frontal cortex, hippocampus and putamen in DLB cases and in the putamen in PD cases. In the hippocampus, mGluR5 was more abundant in the CA3 region and co-localized with alpha-syn aggregates. Similarly, in the hippocampus and basal ganglia of alpha-syn tg mice, levels of mGluR5 were increased and mGluR5 and alpha-syn were co-localized and co-immunoprecipitated, suggesting that alpha-syn interferes with mGluR5 trafficking. The increased levels of mGluR5 were accompanied by a concomitant increase in the activation of downstream signaling components including ERK, Elk-1 and CREB. Consistent with the increased accumulation of alpha-syn and alterations in mGluR5 in cognitive- and motor-associated brain regions, these mice displayed impaired performance in the water maze and pole test, these behavioral alterations were reversed with the mGluR5 antagonist, MPEP. Taken together the results from study suggest that mGluR5 may directly interact with alpha-syn resulting in its over activation and that this over activation may contribute to excitotoxic cell death in select neuronal regions. These results highlight the

  7. Genome-wide identification, characterization and classification of ionotropic glutamate receptor genes (iGluRs) in the malaria vector Anopheles sinensis (Diptera: Culicidae).

    Science.gov (United States)

    Wang, Ting-Ting; Si, Feng-Ling; He, Zheng-Bo; Chen, Bin

    2018-01-15

    Ionotropic glutamate receptors (iGluRs) are conserved ligand-gated ion channel receptors, and ionotropic receptors (IRs) were revealed as a new family of iGluRs. Their subdivision was unsettled, and their characteristics are little known. Anopheles sinensis is a major malaria vector in eastern Asia, and its genome was recently well sequenced and annotated. We identified iGluR genes in the An. sinensis genome, analyzed their characteristics including gene structure, genome distribution, domains and specific sites by bioinformatic methods, and deduced phylogenetic relationships of all iGluRs in An. sinensis, Anopheles gambiae and Drosophila melanogaster. Based on the characteristics and phylogenetics, we generated the classification of iGluRs, and comparatively analyzed the intron number and selective pressure of three iGluRs subdivisions, iGluR group, Antenna IR and Divergent IR subfamily. A total of 56 iGluR genes were identified and named in the whole-genome of An. sinensis. These genes were located on 18 scaffolds, and 31 of them (29 being IRs) are distributed into 10 clusters that are suggested to form mainly from recent gene duplication. These iGluRs can be divided into four groups: NMDA, non-NMDA, Antenna IR and Divergent IR based on feature comparison and phylogenetic analysis. IR8a and IR25a were suggested to be monophyletic, named as Putative in the study, and moved from the Antenna subfamily in the IR family to the non-NMDA group as a sister of traditional non-NMDA. The generated iGluRs of genes (including NMDA and regenerated non-NMDA) are relatively conserved, and have a more complicated gene structure, smaller ω values and some specific functional sites. The iGluR genes in An. sinensis, An. gambiae and D. melanogaster have amino-terminal domain (ATD), ligand binding domain (LBD) and Lig_Chan domains, except for IR8a that only has the LBD and Lig_Chan domains. However, the new concept IR family of genes (including regenerated Antenna IR, and Divergent

  8. Standard form contracts and a smart contract future

    Directory of Open Access Journals (Sweden)

    Kristin B. Cornelius

    2018-05-01

    Full Text Available With a budding market of widespread smart contract implementation on the horizon, there is much conversation about how to regulate this new technology. Discourse on standard form contracts (SFCs and how they have been adopted in a digital environment is useful toward predicting how smart contracts might be interpreted. This essay provides a critical review of the discourse surrounding digitised SFCs and applies it to issues in smart contract regulation. An exploration of the literature surrounding specific instances SFCs finds that it lacks a close examination of the textual and documentary aspects of SFCs, which are particularly important in a digital environment as a shift in medium prompts a different procedural process. Instead, common perspectives are either based on outdated notions of paper versions of these contracts or on ideologies of industry and business that do not sufficiently address the needs of consumers/users in the digital age. Most importantly, noting the failure of contract law to address the inequities of SFCs in this environment can help prevent them from being codified further with smart contracts.

  9. [Ulysses contract in psychiatry].

    Science.gov (United States)

    Daverio, Andrea; Piazzi, Gioia; Saya, Anna

    2017-01-01

    Over the last twenty years we have witnessed a growing focus on the rights of the ill people. The debate on informed consent and a new redefinition of the therapeutic relationship is constantly evolving. With this article, we propose a critical literature review of the so-called "Ulysses contract" or "psychiatric advance directives". It refers to the will that a subject expresses in writing, or orally, about the treatments he or she wishes or does not wish to be subject to if the time comes when it may be impossible to express his/her consent. This can especially occur in those with psychiatric disorders with serious clinical involvement and remitting-relapse (typically bipolar disorder, but also chronic delusional disorders and schizophrenia). In this context, the question is whether during intercritical periods the patient may or may not leave instructions to their care-givers. This aspect opens up to a series of interdisciplinary problems. In this article, we want to show the complexity of this debate from a clinical, ethical, legal and psychodynamic point of view, emphasizing the strengths and the major criticisms of the psychiatric advance directives for each area.

  10. Landsat 6 contract signed

    Science.gov (United States)

    Maggs, William Ward

    A new agreement provides $220 million for development and construction of the Landsat 6 remote sensing satellite and its ground systems. The contract, signed on March 31, 1988, by the Department of Commerce (DOC) and the Earth Observation Satellite (EOSAT) Company of Lanham, Md., came just days after approval of DOC's Landsat commercialization plan by subcommittees of the House and Senate appropriations committees.The Landsat 6 spacecraft is due to be launched into orbit on a Titan II rocket in June 1991 from Vandenburg Air Force Base, Calif. The satellite will carry an Enhanced Thematic Mapper (ETM) sensor, an instrument sensitive to electromagnetic radiation in seven ranges or bands of wavelengths. The satellite's payload will also include the Sea Wide Field Sensor (Sea-WiFS), designed to provide information on sea surface temperature and ocean color. The sensor is being developed in a cooperative effort by EOSAT and the National Aeronautics and Space Administration (NASA). A less certain passenger is a proposed 5-m resolution, three-band sensor sensitive to visible light. EOSAT is trying to find both private financing for the device and potential buyers of the high-resolution imagery that it could produce. The company has been actively courting U.S. television networks, which have in the past used imagery from the European Système Probatoire d'Observation de la Terre (SPOT) satellite for news coverage.

  11. INFINITY construction contract signed

    Science.gov (United States)

    2010-01-01

    Key state and community leaders celebrated April 6 with the signing of a construction contract for the state-of-the-art INFINITY Science Center planned near John C. Stennis Space Center in south Mississippi. Gulfport Mayor George Schloegel (l to r), chair of non-profit INFINITY Science Center Inc., was joined for the signing ceremony at the Hancock Bank in Gulfport by Virginia Wagner, sister of late Hancock Bank President Leo Seal Jr.; and Roy Anderson III, president and CEO of Roy Anderson Corp. Seal was the first chair of INFINITY Science Center Inc., which has led in development of the project. Roy Anderson Corp. plans to begin construction on the 72,000-square-foot, $28 million science and education center in May. The Mississippi Department of Transportation (MDOT) also is set to begin construction of a $2 million access road to the new center. The April 6 ceremony was attended by numerous officials, including former Stennis Space Center Directors Jerry Hlass and Roy Estess; Mississippi Senate President Pro Tempore Billy Hewes, R-Gulfport; Mississippi Rep. Diane Peranich, D-Pass Christian; and MDOT Southern District Commissioner Wayne Brown.

  12. Is the jury still out on PFI contracts?

    Science.gov (United States)

    Baillie, Jonathan

    2012-02-01

    Last September Andrew Lansley claimed that some NHS Trusts occupying PFI healthcare facilities had been 'landed with deals they could not afford', seemingly attributing much of the blame for a scenario where the Department of Health said 22 Trusts in England alone could be at significant financial risk to Labour, which, in the 1990s, greatly expanded a public/private funding partnership originally introduced by the Tories a decade earlier. Two key factors critics claim have put such Trusts 'at risk' are the 'inflexibility' of some PFI contracts, which makes varying terms difficult mid-contract, and the fact that many of the earlier deals were inexpertly negotiated by the 'public sector side'. HEJ editor Jonathan Baillie sought the views of Malcolm Austwick, a partner at top commercial law firm, DAC Beachcroft (see panel below), with extensive experience in the legal complexities of PFI, on whether or not the initiative's 'pros' do indeed outweigh the 'cons'.

  13. Group I mGlu receptors potentiate synaptosomal [{sup 3}H]glutamate release independently of exogenously applied arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J. [Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD (United Kingdom)

    1999-04-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [{sup 3}H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 {mu}M) increased 4AP-evoked [{sup 3}H]glutamate release (143.32{+-}2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC{sub 50}=1.60{+-}0.25 {mu}M; E{sub max}=147.61{+-}10.96% control) 4AP-evoked [{sup 3}H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu{sub 1} receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 {mu}M) and was BSA-insensitive. The selective mGlu{sub 5} receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300{mu}M) was without effect. DHPG (100 {mu}M) also potentiated both 30 mM and 50 mM K{sup +}-evoked [{sup 3}H]glutamate release (121.60{+-}12.77% and 121.50{+-}4.45% control, respectively). DHPG (100 {mu}M) failed to influence both 4AP-stimulated {sup 45}Ca{sup 2+} influx and 50 mM K{sup +}-induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A{sub 1} receptor, group II/III mGlu receptors or GABA{sub B} receptor activity is unlikely since 4AP-evoked [{sup 3}H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-{alpha}-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu{sub 1} receptor-like' receptor potentiates [{sup 3}H]glutamate release from cerebrocortical synaptosomes in the absence of

  14. 7 CFR 631.14 - Contract violations.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE LONG TERM CONTRACTING GREAT PLAINS CONSERVATION PROGRAM Contracts § 631.14 Contract violations. Contract violations, determinations and appeals will be handled in accordance with the terms of the... 7 Agriculture 6 2010-01-01 2010-01-01 false Contract violations. 631.14 Section 631.14 Agriculture...

  15. 48 CFR 46.314 - Transportation contracts.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Transportation contracts... MANAGEMENT QUALITY ASSURANCE Contract Clauses 46.314 Transportation contracts. The contracting officer shall insert the clause at 52.246-14, Inspection of Transportation, in solicitations and contracts for freight...

  16. 24 CFR 891.560 - HAP contract.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HAP contract. 891.560 Section 891... Assistance § 891.560 HAP contract. (a) HAP contract. The housing assistance payments contract sets forth.... (b) HAP contract execution. (1) Upon satisfactory completion of the project, the Borrower and HUD...

  17. 77 FR 3288 - International Mail Contract

    Science.gov (United States)

    2012-01-23

    ... as the baseline contract for future functional equivalence analyses of the GREP Contracts 1 product... Classification Schedule language for GREP Contracts 1. The Postal Service identifies general contract terms that... methodology, the relevant characteristics of this GREP contract are similar, if not the same, as the relevant...

  18. 77 FR 71458 - New International Mail Contract

    Science.gov (United States)

    2012-11-30

    ... Contract AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... Contracts 1. This document invites public comments on the request and addresses several related procedural... Reseller Expedited Package (GREP) contract (Contracts 1).\\1\\ It seeks to have the instant Contract included...

  19. 48 CFR 926.7104 - Contract clause.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clause. 926.7104... 1993. 926.7104 Contract clause. The contracting officer shall insert the clause at 48 CFR (DEAR) 952.226-74, Displaced Employee Hiring Preference, in contracts (except for contracts for commercial items...

  20. 48 CFR 837.403 - Contract clause.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clause. 837.403... OF CONTRACTING SERVICE CONTRACTING Nonpersonal Health Care Services 837.403 Contract clause. The contracting officer shall insert the clause at 852.237-7, Indemnification and medical liability insurance, in...

  1. 48 CFR 822.305 - Contract clause.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clause. 822.305... PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Contract Work Hours and Safety Standards Act 822.305 Contract clause. The contracting officer shall insert the clause at 852.222-70, Contract Work...

  2. 48 CFR 811.503 - Contract clause.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clause. 811.503... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Liquidated Damages 811.503 Contract clause. When the contracting... contracting officer must include the clause in 852.211-74, Liquidated damages, in the contract. ...

  3. Ontologies for commitment-based smart contracts

    NARCIS (Netherlands)

    de Kruijff, Joost; Weigand, Hans; Panetto, H; Debruyne, C.; Gaaloul, W.; Papazoglou, M.; Paschke, A.; Ardagna, C.A.; Meersman, R.

    2017-01-01

    Smart contracts gain rapid exposure since the inception of blockchain technology. Yet there is no unified ontology for smart contracts. Being categorized as coded contracts or substitutes of conventional legal contracts, there is a need to reduce the conceptual ambiguity of smart contracts. We

  4. Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO)

    DEFF Research Database (Denmark)

    Bjerrum, Esben J; Kristensen, Anders S; Pickering, Darryl S

    2003-01-01

    On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. ...

  5. Adaptive Evolution of Signaling Partners

    Science.gov (United States)

    Urano, Daisuke; Dong, Taoran; Bennetzen, Jeffrey L.; Jones, Alan M.

    2015-01-01

    Proteins that interact coevolve their structures. When mutation disrupts the interaction, compensation by the partner occurs to restore interaction otherwise counterselection occurs. We show in this study how a destabilizing mutation in one protein is compensated by a stabilizing mutation in its protein partner and their coevolving path. The pathway in this case and likely a general principle of coevolution is that the compensatory change must tolerate both the original and derived structures with equivalence in function and activity. Evolution of the structure of signaling elements in a network is constrained by specific protein pair interactions, by requisite conformational changes, and by catalytic activity. The heterotrimeric G protein-coupled signaling is a paragon of this protein interaction/function complexity and our deep understanding of this pathway in diverse organisms lends itself to evolutionary study. Regulators of G protein Signaling (RGS) proteins accelerate the intrinsic GTP hydrolysis rate of the Gα subunit of the heterotrimeric G protein complex. An important RGS-contact site is a hydroxyl-bearing residue on the switch I region of Gα subunits in animals and most plants, such as Arabidopsis. The exception is the grasses (e.g., rice, maize, sugarcane, millets); these plants have Gα subunits that replaced the critical hydroxyl-bearing threonine with a destabilizing asparagine shown to disrupt interaction between Arabidopsis RGS protein (AtRGS1) and the grass Gα subunit. With one known exception (Setaria italica), grasses do not encode RGS genes. One parsimonious deduction is that the RGS gene was lost in the ancestor to the grasses and then recently acquired horizontally in the lineage S. italica from a nongrass monocot. Like all investigated grasses, S. italica has the Gα subunit with the destabilizing asparagine residue in the protein interface but, unlike other known grass genomes, still encodes an expressed RGS gene, SiRGS1. SiRGS1

  6. Analysis of the 314th Contracting Squadrons Contract Management Capability Using the Contract Management Maturity Model (CMMM)

    National Research Council Canada - National Science Library

    Jackson, Jr, Carl J

    2007-01-01

    .... The purpose of this research project is to analyze the 314th Contracting Squadron contracting processes and requirement target areas for improvement efforts by the application of the Contract Management Maturity Model (CMMM...

  7. The effect of the mGlu5 negative allosteric modulator MTEP and NMDA receptor partial agonist D-cycloserine on Pavlovian conditioned fear.

    Science.gov (United States)

    Handford, Charlotte E; Tan, Shawn; Lawrence, Andrew J; Kim, Jee Hyun

    2014-09-01

    The metabotropic glutamate receptor 5 (mGlu5) and N-methyl-D-aspartate (NMDA) receptor are critical for processes underlying synaptic plasticity, such as long-term potentiation. mGlu5 signaling increases neuronal excitability and potentiates NMDA receptor currents in the amygdala and the hippocampus. The present study examined the involvement of mGlu5 in the acquisition and consolidation of conditioned fear to a tone and context in mice, and explored the functional relationship between mGlu5 and NMDA receptors in this regard. Experiment 1 showed that systemic administration of the mGlu5 negative allosteric modulator 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) prior to conditioning significantly attenuated cue-elicited freezing during fear conditioning, which suggests that mGlu5 is necessary for the formation of a tone-shock association. This effect was dose-related (Experiment 2) and not due to any effects of MTEP on shock sensitivity or state-dependency (Experiment 3). Post-conditioning injection of MTEP had no effects (Experiment 4). Although post-conditioning injection of the NMDA receptor partial agonist D-cycloserine (DCS) alone facilitated consolidation of conditioned fear (Experiment 6), it was not able to rescue the acquisition deficit caused by MTEP (Experiment 5). Taken together, these findings indicate a crucial role for mGlu5 signaling in acquisition and NMDA receptor signaling in consolidation of conditioned fear.

  8. Ghrelin upregulates the phosphorylation of the GluN2B subunit of the NMDA receptor by activating GHSR1a and Fyn in the rat hippocampus.

    Science.gov (United States)

    Berrout, Liza; Isokawa, Masako

    2018-01-01

    Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity. However, it depended on the activation of GHSR1a and Fyn as it was blocked by D-Lys3-GHRP-6 and PP2, respectively. Inhibitors for G-protein-regulated second messengers, such as Rp-cAMP, H89, TBB, ryanodine, and thapsigargin, unexpectedly enhanced GluN2B phosphorylation, suggesting that cAMP, PKA, casein kinase II, and cytosolic calcium signaling may oppose to the effect of ghrelin on the phosphorylation of GluN2B. Our findings suggest that 1) GluN2B is likely a molecular target of ghrelin and GHSR1a-driven signaling cascades, and 2) the ghrelin-mediated phosphorylation of GluN2B depends on Fyn activation under complex negative regulation by other second messengers. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A conceptual model of psychological contracts in construction projects

    Directory of Open Access Journals (Sweden)

    Yongjian Ke

    2016-09-01

    Full Text Available The strategic importance of relationship style contracting is recognised in the construction industry. Both public and private sector clients are stipulating more integrated and collaborative forms of procurement. Despite relationship and integrated contractual arrangement being available for some time, it is clear that construction firms have been slow to adopt them. Hence it is timely to examine how social exchanges, via unwritten agreement and behaviours, are being nurtured in construction projects. This paper adopted the concept of Psychological Contracts (PC to describe unwritten agreement and behaviours. A conceptual model of the PC is developed and validated using the results from a questionnaire survey administered to construction professionals in Australia. The results uncovered the relationships that existed amongst relational conditions and relational benefits, the PC and the partners’ satisfaction. The results show that all the hypotheses in the conceptual model of the PC are supported, suggesting the PC model is important and may have an effect on project performance and relationship quality among contracting parties. A validated model of the PC in construction was then developed based on the correlations among each component. The managerial implications are that past relationships and relationship characteristics should be taken into account in the selection of procurement partners and the promise of future resources, support and tangible relational outcomes are also vital. It is important for contracting parties to pay attention to unwritten agreements (the PC and behaviours when managing construction projects.

  10. Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes

    Science.gov (United States)

    Chiocchetti, Annalisa; Miglio, Gianluca; Mesturini, Riccardo; Varsaldi, Federica; Mocellin, Marco; Orilieri, Elisabetta; Dianzani, Chiara; Fantozzi, Roberto; Dianzani, Umberto; Lombardi, Grazia

    2006-01-01

    The effects of L-glutamate on activation-induced cell death (AICD) of human activated (1 μg ml−1 phytohemagglutinin plus 2 U ml−1 interleukin-2; 8 days) T lymphocytes were studied by measuring anti-CD3 monoclonal antibody (10 μg ml−1; 18 h)-induced cell apoptosis (Annexin V and propidium iodide staining). L-Glutamate (1 × 10−8–1 × 10−4 M) significantly (P⩽0.01) inhibited AICD in a concentration-dependent manner (EC50=6.3 × 10−8 M; maximum inhibition 54.8±6.3% at 1 × 10−6 M). The L-glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC50 values were: 3.2 × 10−7 M for (1S,3R)-ACPD; 4.5 × 10−8 M for quisqualate; 1.0 × 10−6 M for (S)-3,5-DHPG; 2.0 × 10−5 M for CHPG. Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10−6 M. The IC50 values calculated were: 8.7 × 10−5, 4.3 × 10−6 and 6.3 × 10−7 M for AIDA, LY 367385 and MPEP, respectively. L-Glutamate (1 × 10−6 M; 18 h) significantly (P⩽0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling. Expression of both mGlu1 and mGlu5 receptor mRNA by T lymphocytes and T-cell lines, as demonstrated by reverse transcriptase–PCR analysis, suggests that L-glutamate-mediated inhibition of AICD was exerted on T cells. These data depict a novel role for L-glutamate in the regulation of the immune response through group I mGlu receptor-mediated mechanisms. PMID:16751798

  11. Food and drink serving contract

    Directory of Open Access Journals (Sweden)

    Veselinović Janko

    2012-01-01

    Full Text Available Food and drink catering service is almost as old as the civilization itself. Even though this vocation is a part of the catering activity, Serbian law does not foresee this contract section as personalized. Key legal sources for this kind of contract are business customs. Food and drink serving contract is a mixed-type contract and its legal nature is very interesting due to its complexity. Specific for this contract is the fact that it is not an ordinary service, but also an activity which requires a degree of culinary skills, knowledge of customs of other nations, as well as other skills. The very category of a good professional in business economy / hospitality industry is very dynamic, as it needs to be evaluated according to all given circumstances, which may be rather unpredictable. By considering the legal nature, but also the rights and obligations of the contracting parties, we tried to point to the questions that require a special attention. Legal sources that indirectly refer to food and drink serving contracts were taken into account. Apart from the Law on Obligatory Relations, we also considered here the Law on Tourism also pointing to the comparative law and jurisprudence.

  12. nth roots of normal contractions

    International Nuclear Information System (INIS)

    Duggal, B.P.

    1992-07-01

    Given a complex separable Hilbert space H and a contraction A on H such that A n , n≥2 some integer, is normal it is shown that if the defect operator D A = (1 - A * A) 1/2 is of the Hilbert-Schmidt class, then A is similar to a normal contraction, either A or A 2 is normal, and if A 2 is normal (but A is not) then there is a normal contraction N and a positive definite contraction P of trace class such that parallel to A - N parallel to 1 = 1/2 parallel to P + P parallel to 1 (where parallel to · parallel to 1 denotes the trace norm). If T is a compact contraction such that its characteristics function admits a scalar factor, if T = A n for some integer n≥2 and contraction A with simple eigen-values, and if both T and A satisfy a ''reductive property'', then A is a compact normal contraction. (author). 16 refs

  13. Physics of muscle contraction

    Science.gov (United States)

    Caruel, M.; Truskinovsky, L.

    2018-03-01

    In this paper we report, clarify and broaden various recent efforts to complement the chemistry-centered models of force generation in (skeletal) muscles by mechanics-centered models. The physical mechanisms of interest can be grouped into two classes: passive and active. The main passive effect is the fast force recovery which does not require the detachment of myosin cross-bridges from actin filaments and can operate without a specialized supply of metabolic fuel (ATP). In mechanical terms, it can be viewed as a collective folding-unfolding phenomenon in the system of interacting bi-stable units and modeled by near equilibrium Langevin dynamics. The active force generation mechanism operates at slow time scales, requires detachment and is crucially dependent on ATP hydrolysis. The underlying mechanical processes take place far from equilibrium and are represented by stochastic models with broken time reversal symmetry implying non-potentiality, correlated noise or multiple reservoirs. The modeling approaches reviewed in this paper deal with both active and passive processes and support from the mechanical perspective the biological point of view that phenomena involved in slow (active) and fast (passive) force generation are tightly intertwined. They reveal, however, that biochemical studies in solution, macroscopic physiological measurements and structural analysis do not provide by themselves all the necessary insights into the functioning of the organized contractile system. In particular, the reviewed body of work emphasizes the important role of long-range interactions and criticality in securing the targeted mechanical response in the physiological regime of isometric contractions. The importance of the purely mechanical micro-scale modeling is accentuated at the end of the paper where we address the puzzling issue of the stability of muscle response on the so called ‘descending limb’ of the isometric tetanus.

  14. Physics of muscle contraction.

    Science.gov (United States)

    Caruel, M; Truskinovsky, L

    2018-03-01

    In this paper we report, clarify and broaden various recent efforts to complement the chemistry-centered models of force generation in (skeletal) muscles by mechanics-centered models. The physical mechanisms of interest can be grouped into two classes: passive and active. The main passive effect is the fast force recovery which does not require the detachment of myosin cross-bridges from actin filaments and can operate without a specialized supply of metabolic fuel (ATP). In mechanical terms, it can be viewed as a collective folding-unfolding phenomenon in the system of interacting bi-stable units and modeled by near equilibrium Langevin dynamics. The active force generation mechanism operates at slow time scales, requires detachment and is crucially dependent on ATP hydrolysis. The underlying mechanical processes take place far from equilibrium and are represented by stochastic models with broken time reversal symmetry implying non-potentiality, correlated noise or multiple reservoirs. The modeling approaches reviewed in this paper deal with both active and passive processes and support from the mechanical perspective the biological point of view that phenomena involved in slow (active) and fast (passive) force generation are tightly intertwined. They reveal, however, that biochemical studies in solution, macroscopic physiological measurements and structural analysis do not provide by themselves all the necessary insights into the functioning of the organized contractile system. In particular, the reviewed body of work emphasizes the important role of long-range interactions and criticality in securing the targeted mechanical response in the physiological regime of isometric contractions. The importance of the purely mechanical micro-scale modeling is accentuated at the end of the paper where we address the puzzling issue of the stability of muscle response on the so called 'descending limb' of the isometric tetanus.

  15. 76 FR 66012 - Partner's Distributive Share

    Science.gov (United States)

    2011-10-25

    ...-level tax. To achieve this goal of a flexible economic arrangement, partners are generally permitted to... has substantial economic effect involves a two-part analysis that is made as of the end of the... be consistent with the underlying economic arrangement of the partners. This means that, in the event...

  16. The partner selection process : Steps, effectiveness, governance

    NARCIS (Netherlands)

    Duisters, D.; Duijsters, G.M.; de Man, A.P.

    2011-01-01

    Selecting the right partner is important for creating value in alliances. Even though prior research suggests that a structured partner selection process increases alliance success, empirical research remains scarce. This paper presents an explorative empirical study that shows that some steps in

  17. The partner selection process : steps, effectiveness, governance

    NARCIS (Netherlands)

    Duisters, D.; Duysters, G.M.; Man, de A.P.

    2011-01-01

    Selecting the right partner is important for creating value in alliances. Even though prior research suggests that a structured partner selection process increases alliance success, empirical research remains scarce. This paper presents an explorative empirical study that shows that some steps in

  18. Partner selection in the mycorrhizal mutualism

    NARCIS (Netherlands)

    Werner, G.D.A.; Kiers, E.T.

    2015-01-01

    Partner selection in the mycorrhizal symbiosis is thought to be a key factor stabilising the mutualism. Both plant hosts and mycorrhizal fungi have been shown to preferentially allocate resources to higher quality partners. This can help maintain underground cooperation, although it is likely that

  19. Contraction ionization waves in the argon contracted discharge

    International Nuclear Information System (INIS)

    Golubovskij, Yu.B.; Kulikov, V.V.; Nekutchaev, V.O.

    1985-01-01

    An investigation of ionization waves in the argon contracted discharge and a definition of their arising propagation mechanism accounting for the specificity of elementary pocesses characteristic of argon are presented. (author)

  20. Defense Threat Reduction Agency > Contracts > Contract Award Data

    Science.gov (United States)

    Integration Command Senior Enlisted Leader Media News News Archive Strategic Plan Videos Mission Research Support Center Contact Us FAQ Sheet Links Success Stories Contracts Business Opportunities Current Justifications & Approvals Careers Who We Are Our Values Strategic Recruiting Programs Professional

  1. Viral-mediated knockdown of mGluR7 in the nucleus accumbens mediates excessive alcohol drinking and increased ethanol-elicited conditioned place preference in rats.

    Science.gov (United States)

    Bahi, Amine

    2013-10-01

    Whether metabotropic glutamate 7 (mGluR7) -activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that systemic mGluR7 activation reduced alcohol consumption and preference as well as locomotor-stimulating and rewarding properties of ethanol. In this study, we further examined the contribution of mGluR7 on the effect of ethanol within the nucleus accumbens (NAcc), a neural target for many drugs of abuse. Using short hairpin RNA (shRNA)-expressing lentiviral vectors (LV) to alter locally the activity of mGluR7 in male rats, we have shown that blocking mGluR7 expression increased ethanol consumption and preference in a two-bottle choice drinking paradigm with no effect either on saccharin or on quinine used for taste discrimination. In addition, mGluR7 knockdown increases preference for environments previously paired with low doses of ethanol in the conditioned place preference (CPP) test, as it shifted the dose-response curve for ethanol CPP to the left, indicating alterations in the rewarding effects of alcohol. More importantly, mGluR7 blockade in the dorsal striatum (DS) neither affected ethanol consumption nor ethanol-elicited CPP. These results show that levels of mGluR7 in the NAcc regulate responsiveness to alcohol. Taken together, these findings clearly demonstrate that mGluR7 signaling within the NAcc is a key modulator of functional responses to ethanol and offer an important target for regulating the addictive effects of alcohol.

  2. Pola Kemitraan Contract Farming Antara Petani Cluster Dan PT Mitratani Agro Unggul (PT Mau) Di Kabupaten Lampung Selatan

    OpenAIRE

    Maliki, Azhari; Ismono, R Hanung; Yanfika, Helvi

    2013-01-01

    This research aimed to know the partnership pattern of contract farming between cluster farmers and PT Mitratani Agro Unggul and the partnership benefits for the farmers. This research was conducted in South Lampung Regency in October 2012, in which 12 farmers joined this partnership program as respondents. The data was analyzed by descriptive and farming income analysis. The results showed that the related partners to contract farming partnership covered: capital assistance, marketing, an...

  3. Teleportation with Multiple Accelerated Partners

    International Nuclear Information System (INIS)

    Sagheer, A.; Hamdoun, H.; Metwally, N.

    2015-01-01

    As the current revolution in communication is underway, quantum teleportation can increase the level of security in quantum communication applications. In this paper, we present a quantum teleportation procedure that capable to teleport either accelerated or non-accelerated information through different quantum channels. These quantum channels are based on accelerated multi-qubit states, where each qubit of each of these channels represents a partner. Namely, these states are the W state, Greenberger–Horne–Zeilinger (GHZ) state, and the GHZ-like state. Here, we show that the fidelity of teleporting accelerated information is higher than the fidelity of teleporting non-accelerated information, both through a quantum channel that is based on accelerated state. Also, the comparison among the performance of these three channels shows that the degree of fidelity depends on type of the used channel, type of the measurement, and value of the acceleration. The result of comparison concludes that teleporting information through channel that is based on the GHZ state is more robust than teleporting information through channels that are based on the other two states. For future work, the proposed procedure can be generalized later to achieve communication through a wider quantum network. (paper)

  4. The Relationship between the Employment Contract and other Civil Contracts

    OpenAIRE

    Răzvan Radu Popescu

    2015-01-01

    The employment relationship is a contractual one and as such must have all the basic elements of an enforceable contract to make it legally binding. In strict contractual terms, the offer is made by the employer and formally accepted by the employee. Once the acceptance has taken place, there is a legally binding agreement and an action will lie against the party who breaches that agreement, even though it may only just have come into existence. An employment contract, however, is...

  5. Advice from working women with retired partners.

    Science.gov (United States)

    Cooley, Eileen L; Adorno, Gail

    2016-01-01

    in the 21st century, as more women are employed full-time and couples increasingly share egalitarian values, more women continue employment after their partners have voluntarily retired. However, we know very little about the experiences of this growing population of women. We asked working women with retired partners to share their advice for other women who may face this developmental transition. Open-ended responses from 97 women were analyzed to identify pertinent issues and themes. Four primary content areas were identified: time management, division of household labor, financial planning, and communication. Communication between partners was both a topic of concern as well as the solution suggested to resolve conflicts or differences that may arise when women live with a retired partner. It is expected that future changes in the workforce and improvements in the gender balance within relationships will continue to impact experiences for working women with retired partners.

  6. Sex Differences in Attitudes toward Partner Infidelity

    Directory of Open Access Journals (Sweden)

    Michael J. Tagler

    2013-10-01

    Full Text Available Sex differences in reactions to partner infidelity have often been studied by comparing emotional reactions to scenarios of sexual versus emotional infidelity. Men, relative to women, tend to react with more distress to partner sexual infidelity than to emotional infidelity. Evolutionary theorists interpret this difference as evidence of sexually dimorphic selection pressures. In contrast, focusing only on the simple effects within each sex, social-cognitive theorists suggest that men and women do not differ in their reactions to partner infidelity. As evidenced by recent rival meta-analytic reports, these diverging perspectives remain largely unresolved and contentious. The present study was designed to take a new approach by measuring attitudes toward partner infidelity. Results were consistent with the evolutionary perspective: Men, to a significantly larger degree than women, evaluated partner sexual infidelity more negatively than emotional infidelity.

  7. Sex differences in attitudes toward partner infidelity.

    Science.gov (United States)

    Tagler, Michael J; Jeffers, Heather M

    2013-08-06

    Sex differences in reactions to partner infidelity have often been studied by comparing emotional reactions to scenarios of sexual versus emotional infidelity. Men, relative to women, tend to react with more distress to partner sexual infidelity than to emotional infidelity. Evolutionary theorists interpret this difference as evidence of sexually dimorphic selection pressures. In contrast, focusing only on the simple effects within each sex, social-cognitive theorists suggest that men and women do not differ in their reactions to partner infidelity. As evidenced by recent rival meta-analytic reports, these diverging perspectives remain largely unresolved and contentious. The present study was designed to take a new approach by measuring attitudes toward partner infidelity. Results were consistent with the evolutionary perspective: Men, to a significantly larger degree than women, evaluated partner sexual infidelity more negatively than emotional infidelity.

  8. The North Sea contracting industry

    International Nuclear Information System (INIS)

    Wright, P.J.C.

    1996-09-01

    The North Sea Contracting Industry provides in-depth profiles of major contracting organisations including manpower, facilities, expertise, future directions and financial details. It addresses key issues such as: how will the role of operators and contractors change toward 2000 and beyond?; how will the contractor-operator relationship develop?; will the contractors take a more speculative role in projects such as leasing and contract to produce?; does the future belong to broad skilled providers or small specialised niche players, or both?; and how will rapid technological improvements affect the industry? (author)

  9. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

    International Nuclear Information System (INIS)

    Baek, Yi-Yong; Lee, Dong-Keon; So, Ju-Hoon; Kim, Cheol-Hee; Jeoung, Dooil; Lee, Hansoo; Choe, Jongseon; Won, Moo-Ho; Ha, Kwon-Soo; Kwon, Young-Guen; Kim, Young-Myeong

    2015-01-01

    Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC 50 of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases

  10. EVALUATION OF STRENGTH TO SHEAR AND DELAMINATION IN GLUED LAMINATED WOOD

    Directory of Open Access Journals (Sweden)

    Carlito Calil Neto

    2014-12-01

    Full Text Available The Glued Laminated Wood has a large range of applications. In Brazil, its employment as cross-piece poles for overhead electrical power has attracted the attention of companies in the industry, motivated by the potential use of this material. Among the factors that influence the mechanical performance of Glulam solutions stand out efficiency and affinity of the adhesives to the species of wood used, the type of treatment and moisture content of wood veneer, motivating the development of new research on this topic. This research aimed to investigate, by Design of Experiments (DOE, the influence of wood (pinus, teca, eucalipto, adhesive (Purbond; Cascophen and treatment (CCA, CCB, CCBS in the variable responses shear strength and delamination, consisting in the same combination factors evaluated in ANEEL/EESC-PD220-07 project: Head Crosshead Glulam Series. The results of the statistical analysis showed that the species factor expressed significant effect for both response variables evaluated, did not occur with adhesive and treatment factors. Moisture content was significant in the wood evaluated when analyzed the shear strength, and the teca wood showed the highest shear strength and also relating to the delamination.

  11. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Yi-Yong; Lee, Dong-Keon [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); So, Ju-Hoon; Kim, Cheol-Hee [Department of Biology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Jeoung, Dooil [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Lee, Hansoo [Department of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Choe, Jongseon [Department of Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Won, Moo-Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Ha, Kwon-Soo [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Kwon, Young-Guen [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-752 (Korea, Republic of); Kim, Young-Myeong, E-mail: ymkim@kangwon.ac.kr [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of)

    2015-08-07

    Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC{sub 50} of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases.

  12. mGluR5 stimulating Homer–PIKE formation initiates icariin induced cardiomyogenesis of mouse embryonic stem cells by activating reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Limin; Huang, Yujie; Zhang, Yingying [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China); Zhao, Qingwei [The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qing Chun Road, Hangzhou 310003 (China); Zheng, Bei; Lou, Yijia [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China); Zhu, Danyan, E-mail: zdyzxb@zju.edu.cn [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China)

    2013-06-10

    Icariin (ICA) has been reported to facilitate cardiac differentiation of mouse embryonic stem (ES) cells; however, the mechanism by which ICA induced cardiomyogenesis has not been fully elucidated yet. Here, an underlying signaling network including metabotropic glutamate receptor 5 (mGluR5), Homer, phosphatidylinositol 3-Kinase Enhancer (PIKE), phosphatidylinositol 3-Kinase (PI3K), reactive oxygen species (ROS) and nuclear factor-kappaB (NF-κB) was investigated in ICA induced cardiomyogenesis. Our results showed that the co-expression of mGluR5 together with α-actinin or Troponin T in embryoid bodies (EBs) treated with ICA was elevated to 10.86% and 9.62%, compared with the case in the control (4.04% and 3.45%, respectively). Exposure of EBs to ICA for 2 h remarkably increased the dimeric form of mGluR5, which was inhibited by small interfering RNA targeting mGluR5 (si-mGluR5). Moreover, the extracellular glutamate concentration in ICA treatment medium was elevated to 28.9±3.5 μM. Furthermore, the activation of mGluR5 by ICA triggered the formation of Homer–PIKE complex and activated PI3K, stimulating ROS generation and NF-κB nuclear translocation. Knockdown of mGluR5 or inhibition of PI3K by LY294002 blocked ICA induced cardiomyogenesis via repressing mGluR5 pathway, reducing ROS and NF-κB activation. These results revealed that the inducible mechanisms of ICA were related to activate mGluR5 pathway. -- Highlights: • ICA increased mGluR5 expression in cardiac differentiation of ES cells. • ICA enhanced the glutamate level and the receptor mGluR5 dimerization, stimulating the formation of Homer–PIKE complex. • Knockdown of mGluR5 or inhibition of PI3K by LY294002 inhibited ICA induced ROS generation and NF-κB nuclear translocation.

  13. Signal Transduction Mechanisms Underlying Group I mGluR-mediated Increase in Frequency and Amplitude of Spontaneous EPSCs in the Spinal Trigeminal Subnucleus Oralis of the Rat

    Directory of Open Access Journals (Sweden)

    Ahn Dong-Kuk

    2009-09-01

    Full Text Available Abstract Group I mGluRs (mGluR1 and 5 pre- and/or postsynaptically regulate synaptic transmission at glutamatergic synapses. By recording spontaneous EPSCs (sEPSCs in the spinal trigeminal subnucleus oralis (Vo, we here investigated the regulation of glutamatergic transmission through the activation of group I mGluRs. Bath-applied DHPG (10 μM/5 min, activating the group I mGluRs, increased sEPSCs both in frequency and amplitude; particularly, the increased amplitude was long-lasting. The DHPG-induced increases of sEPSC frequency and amplitude were not NMDA receptor-dependent. The DHPG-induced increase in the frequency of sEPSCs, the presynaptic effect being further confirmed by the DHPG effect on paired-pulse ratio of trigeminal tract-evoked EPSCs, an index of presynaptic modulation, was significantly but partially reduced by blockades of voltage-dependent sodium channel, mGluR1 or mGluR5. Interestingly, PKC inhibition markedly enhanced the DHPG-induced increase of sEPSC frequency, which was mainly accomplished through mGluR1, indicating an inhibitory role of PKC. In contrast, the DHPG-induced increase of sEPSC amplitude was not affected by mGluR1 or mGluR5 antagonists although the long-lasting property of the increase was disappeared; however, the increase was completely inhibited by blocking both mGluR1 and mGluR5. Further study of signal transduction mechanisms revealed that PLC and CaMKII mediated the increases of sEPSC in both frequency and amplitude by DHPG, while IP3 receptor, NO and ERK only that of amplitude during DHPG application. Altogether, these results indicate that the activation of group I mGluRs and their signal transduction pathways differentially regulate glutamate release and synaptic responses in Vo, thereby contributing to the processing of somatosensory signals from orofacial region.

  14. Crystal structure and pharmacological characterization of a novel N-methyl-D-aspartate (NMDA) receptor antagonist at the GluN1 glycine binding site

    DEFF Research Database (Denmark)

    Kvist, Trine; Steffensen, Thomas Bielefeldt; Greenwood, Jeremy R

    2013-01-01

    NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission in the brain. They are tetrameric complexes composed of glycine-binding GluN1 and GluN3 subunits together with glutamate-binding GluN2 subunits. Subunit-selective antagonists that discriminate between the glyci...... screening. Furthermore, the structure reveals that the imino acetamido group of TK40 acts as an α-amino acid bioisostere, which could be of importance in bioisosteric replacement strategies for future ligand design....

  15. 77 FR 76091 - International Mail Contract

    Science.gov (United States)

    2012-12-26

    ... an expired International Business Reply Service (IBRS) competitive contract.\\1\\ The Postal Service... International Business Reply Service Competitive Contract 1 Negotiated Service Agreement, December 14, 2012... history. The Commission added International Business Reply Service Contract 1 to the competitive product...

  16. 78 FR 11699 - International Mail Contract

    Science.gov (United States)

    2013-02-19

    ... additional International Business Reply Service (IBRS) Competitive Contract 3 negotiated service agreement... International Business Reply Service Competitive Contract 3 Negotiated Service Agreement, February 11, 2013.... 684, Order Approving International Business Reply Service Competitive Contract 3 Negotiated Service...

  17. 48 CFR 542.1107 - Contract clause.

    Science.gov (United States)

    2010-10-01

    ... MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT SERVICES Production Surveillance and Reporting 542.1107 Contract... clause may be used in indefinite-delivery definite-quantity contracts for Stock or Special Order Program...

  18. 42 CFR 422.504 - Contract provisions.

    Science.gov (United States)

    2010-10-01

    ...) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Application Procedures and Contracts for Medicare Advantage... determinations of amounts payable under the contract. (iv) Properly reflect all direct and indirect costs claimed..., contracts, and subcontracts. (vi) Franchise, marketing, and management agreements. (vii) Schedules of...

  19. Bottomland Hardwood Planting: Example Contract Specifications

    National Research Council Canada - National Science Library

    Humprey, Monica

    2002-01-01

    This technical note provides an example of contract specifications that can be used as a template by USACE biologists, engineers, or contracting officers for contracting the planting of bottomland hardwood (BLH) seedlings...

  20. Utility Energy Services Contracts: Enabling Documents

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-05-01

    Utility Energy Services Contracts: Enabling Documents provides materials that clarify the authority for Federal agencies to enter into utility energy services contracts (UESCs), as well as sample documents and resources to ease utility partnership contracting.

  1. Cost Analysis and Performance Assessment of Partner Services for Human Immunodeficiency Virus and Sexually Transmitted Diseases, New York State, 2014.

    Science.gov (United States)

    Johnson, Britney L; Tesoriero, James; Feng, Wenhui; Qian, Feng; Martin, Erika G

    2017-12-01

    To estimate the programmatic costs of partner services for HIV, syphilis, gonorrhea, and chlamydial infection. New York State and local health departments conducting partner services activities in 2014. A cost analysis estimated, from the state perspective, total program costs and cost per case assignment, patient interview, partner notification, and disease-specific key performance indicator. Data came from contracts, a time study of staff effort, and statewide surveillance systems. Disease-specific costs per case assignment (mean: $580; range: $502-$1,111), patient interview ($703; $608-$1,609), partner notification ($1,169; $950-$1,936), and key performance indicator ($2,697; $1,666-$20,255) varied across diseases. Most costs (79 percent) were devoted to gonorrhea and chlamydial infection investigations. Cost analysis complements cost-effectiveness analysis in evaluating program performance and guiding improvements. © Health Research and Educational Trust.

  2. 24 CFR 983.206 - HAP contract amendments (to add or substitute contract units).

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HAP contract amendments (to add or... Contract § 983.206 HAP contract amendments (to add or substitute contract units). (a) Amendment to substitute contract units. At the discretion of the PHA and subject to all PBV requirements, the HAP contract...

  3. 23 CFR 635.121 - Contract time and contract time extensions.

    Science.gov (United States)

    2010-04-01

    ... TRAFFIC OPERATIONS CONSTRUCTION AND MAINTENANCE Contract Procedures § 635.121 Contract time and contract time extensions. (a) The STD should have adequate written procedures for the determination of contract... 23 Highways 1 2010-04-01 2010-04-01 false Contract time and contract time extensions. 635.121...

  4. Price management mechanisms and the gas contract

    International Nuclear Information System (INIS)

    Dickson, D.J.

    1996-01-01

    Pricing objectives and risk management strategies that can be achieved through the proper use of the standard gas contract, were discussed. Main topics of discussion were: (1) gas sales contract and convertible pricing, (2) gas contract and imbedded hedging, gas contracts and exchange traded instruments, (4) gas contracts fixed for floating swaps, and OTC options and exotics, (5) options and exotic price structures, and (6) advantages and disadvantages of using the gas contract versus the swap agreement

  5. Supracapsular glued intraocular lens in progressive subluxated cataracts: Technique to retain an intact vitreous face.

    Science.gov (United States)

    Jacob, Soosan; Narasimhan, Smita; Agarwal, Amar; Mazzotta, Cosimo; Rechichi, Miguel; Agarwal, Athiya

    2017-03-01

    We describe a technique to prevent late intraocular lens (IOL) subluxation and dislocation that can be associated with progressive zonulopathy. Supracapsular glued IOL fixation is done to retain an intact anterior hyaloid face and avoid vitreous disturbance while providing stable long-term IOL fixation. Phacoemulsification is followed by glued IOL implantation above intact anterior and posterior capsules. Sclerotomies are created ab interno in a supracapsular plane under diametrically opposite lamellar scleral flaps without entering the vitreous cavity. Haptics are externalized in the supracapsular plane and tucked into intrascleral tunnels. Intraoperative or postoperative posterior capsulorhexis or capsulotomy and anterior capsule relaxing cuts can prevent capsule phimosis. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  6. Principles of European Contract Law

    DEFF Research Database (Denmark)

    Lando, Ole; Beale, Hugh

    This text provides a comprehensive guide to the principles of European contract law. They have been drawn up by an independent body of experts from each Member State of the EU, under a project supported by the European Commission and many other organizations. The principles are stated in the form...... of articles, with a detailed commentary explaining the purpose and operation of each article and its relation to the remainder. Each article also has extensive comparative notes surveying the national laws and other international provisions on the topic. "The Principles of European Contract Law Parts I &...... in developing a common European legal culture. The European Parliament has twice called for the creation of a European Civil Code. The principles of European contract law are essential steps in these projects. This text provides a comprehensive guide to the Principles of European contract law. They have been...

  7. Framework for Structuring Procurement Contracts

    Directory of Open Access Journals (Sweden)

    Lena Borg

    2014-12-01

    Full Text Available The aim of this paper is to propose a new framework for structuring contract types and payment methods. Concerning procurement contracts, the first important new feature of this framework is a stepwise structure with three main steps in the contract design: (1 what will be procured—should the contract only include construction, or should it include both construction and operation/maintenance (2 who will do the detailed design of the premise and (3 how many contractors will the client use? The second important new feature of this framework is that both step 2 and step 3 include a continuum of alternatives. Concerning payment methods, the new framework is primarily based on how the specific risks of the project are shared. These frameworks can be useful for policy formulation in that they can help to avoid some problematic ways of formulating policies.

  8. Contracting and Performance in Agencies

    DEFF Research Database (Denmark)

    Bjørnholt, Bente; Houlberg Salomonsen, Heidi; Rennison, Betina Wolfgang

    As part of New Public Management (NPM), contracting represents a supplement to the traditional hierarchical and rule-based managing of relations between actors in order to improve performance (Fortin and van Hassel 2000; Greve and Ejersbo 2002; Drewry et al. 2005; Verhoest 2005). To various degrees...... higher goal attainment when agency head experience that the department balance dialogue and autonomy with some element of control in the process of internal contracting (Bjørnholt and Salomonsen 2011). This implies, that effective steering include a combination of decentralized management...... and how a balanced use of internal contracting leads to a better performance. These findings are then theoretically interpreted based upon a combination of literature on agencification as well as public management. We compare contracting across all Danish agencies based on a combination of survey...

  9. Contract Reform Self Assessment Report

    National Research Council Canada - National Science Library

    1997-01-01

    The primary objective of this self assessment is to report on the Department of Energy's progress in implementing the Contract Reform initiative launched in February 1994 and to discuss remaining challenges...

  10. Contraction of the solar nebula

    International Nuclear Information System (INIS)

    Rawal, J.J.

    1984-01-01

    The concept of Roche limit is applied to the Laplacian theory of the origin of the solar system to study the contraction of a spherical gas cloud (solar nebula). In the process of contraction of the solar nebula, it is assumed that the phenomenon of supersonic turbulent convection is operative and brings about the halt at various stages of contraction. It is found that the radius of the contracting solar nebula follows the Titius-Bode law. The consequences of the relation are also discussed. The aim is to attempt to explain, on the basis of the concept of Roche limit, the distribution of planets in the solar system and try to understand the physics underlying it. (Auth.)

  11. Construction contracts law and management

    CERN Document Server

    Hughes, Will; Murdoch, John

    2015-01-01

    The fifth edition of this bestselling textbook has been thoroughly revised to provide the most up-to-date and comprehensive coverage of the legislation, administration and management of construction contracts. It now includes comparisons of working with JCT, NEC3, and FIDIC contracts throughout. Introducing this topic at the core of construction law and management, this book provides students with a one-stop reference on construction contracts. Significant new material covers: procurement tendering developments in dispute settlement commentary on all key legislation, case law and contract amendments In line with new thinking in construction management research, this authoritative guide is essential reading for every construction undergraduate and an extremely useful source of reference for practitioners.

  12. Multifamily Assistance Section 8 Contracts

    Data.gov (United States)

    Department of Housing and Urban Development — he information regarding the Multifamily Assistance and Section 8 contracts, and properties is being furnished for the convenience of interested parties. The...

  13. Non-renewal of contracts

    CERN Multimedia

    Association du personnel

    2007-01-01

    A new illegal practice is appearing in certain sectors of the Organization: the non-renewal of renewable three-year limited-duration (LD) contracts, despite a more than satisfactory performance and an obvious commitment to the Organization.

  14. Contractions of quantum algebraic structures

    International Nuclear Information System (INIS)

    Doikou, A.; Sfetsos, K.

    2010-01-01

    A general framework for obtaining certain types of contracted and centrally extended algebras is reviewed. The whole process relies on the existence of quadratic algebras, which appear in the context of boundary integrable models. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  15. Next Indefinite Contract review exercise

    CERN Multimedia

    2013-01-01

    Dear Colleagues, We are pleased to inform you that the 2013 LD2IC exercise (selection process for the conversion of limited-duration contracts to indefinite contracts) was officially launched last week.  The vacancy notices for posts opened with a view to the award of indefinite contracts will be published on 9 August 2013 for a period of four weeks (until 8 September 2013). The CERN Contract Review Boards (candidate interviews) will be held between the end of September and mid-November. The LD to IC procedure, Frequently Asked Questions and a calendar for the exercise are now available in the Admin e-guide. In addition, general information sessions on the procedure will be organised for candidates on the following dates: Information on the location of these sessions will be provided in due course on the CERN announcements page. HR Department

  16. Partners in health? Exploring resemblance in health between partners in married and cohabiting couples.

    Science.gov (United States)

    Monden, Christiaan

    2007-04-01

    Sociological theories on family formation and families and health suggest that married and cohabiting partners will resemble each other in health status, positively or negatively. The family is often seen as a health-enhancing agent for individuals. However, there are large health differences among families. This study aims to answer the question whether it is the case that the healthy live with the healthy and individuals with poor health have partners who are also in poor health. Moreover, it examines whether resemblance in health is a consequence of partner choice--educational homogamy in particular--behaviour or shared circumstances. Younger and older couples are compared to investigate whether health resemblance increases over the lifecourse. Analyses of a nationally representative sample of almost 12,000 Dutch couples show that partners are indeed significantly alike with regard to several health indicators. Respondents whose partner reports poor health are almost three times more likely to report poor health than respondents whose partner is in good health. There is a strong accumulation of health problems within households. Partner selection with regard to education causes part of the partner resemblance in health. Less support is found for the hypotheses that risk behaviour, mutual influence or the effects of shared circumstances cause similarity between partners' health status. Surprisingly, partners in older couples, who have been together for a longer time, do not resemble each other significantly more than partners in younger couples. The implications of these findings for sociological theory and social inequalities in health are discussed.

  17. Witnessing Partner Violence: Exploring the Role of Partner Preferences on Dating Violence.

    Science.gov (United States)

    Gonzalez-Mendez, Rosaura; Yanes, José M; Ramírez-Santana, Gustavo

    2015-06-02

    Research has shown that witnessing partner violence (WPV) increases the likelihood of experiencing or perpetrating violence in later romantic relationships, but little is known about the mechanisms underlying this process. This study examines the relationships between preference for unsuitable partners and teen dating violence (TDV) among adolescents who have witnessed parental violence or not. Attachment was also considered. Participants were 356 adolescents, both witnesses and non-witnesses of partner violence. Results showed no difference in preferences (for good, risky, or loving partners) between the two groups. However, preference for unsuitable partners did significantly predict TDV perpetration and victimization, but only among witnesses. Also, loving-partner preference moderates the relationship between WPV and TDV perpetration among highly avoidant witnesses. Findings indicate a new avenue for prevention through targeting partner preferences. © The Author(s) 2015.

  18. Male partner selectivity, romantic confidence, and media depictions of partner scarcity.

    Science.gov (United States)

    Taylor, Laramie D

    2013-01-18

    An experiment was conducted to explore the effects of exposure to partner scarcity or abundance messages on men's partner selectivity, romantic confidence, and self-assessed attractiveness. Undergraduate male participants watched a soap opera narrative featuring either two men competing over one potential female partner (partner scarcity) or two women competing over one potential male partner (partner abundance). Relative to control subjects, watching either narrative reduced romantic confidence. Experimental condition also affected partner selectivity and self-assessed attractiveness, though both effects were moderated by endorsement of traditional masculine ideology. Viewing the abundance narrative resulted in greater selectivity and self-assessed attractiveness for men high in endorsement of traditional masculinity but diminished selectivity and self-assessed attractiveness for men low in endorsement of traditional masculine identity.

  19. Male Partner Selectivity, Romantic Confidence, and Media Depictions of Partner Scarcity

    Directory of Open Access Journals (Sweden)

    Laramie D. Taylor

    2013-01-01

    Full Text Available An experiment was conducted to explore the effects of exposure to partner scarcity or abundance messages on men's partner selectivity, romantic confidence, and self-assessed attractiveness. Undergraduate male participants watched a soap opera narrative featuring either two men competing over one potential female partner (partner scarcity or two women competing over one potential male partner (partner abundance. Relative to control subjects, watching either narrative reduced romantic confidence. Experimental condition also affected partner selectivity and self-assessed attractiveness, though both effects were moderated by endorsement of traditional masculine ideology. Viewing the abundance narrative resulted in greater selectivity and self-assessed attractiveness for men high in endorsement of traditional masculinity but diminished selectivity and self-assessed attractiveness for men low in endorsement of traditional masculine identity.

  20. Reciprocity in group-living animals: partner control versus partner choice.

    Science.gov (United States)

    Schino, Gabriele; Aureli, Filippo

    2017-05-01

    Reciprocity is probably the most debated of the evolutionary explanations for cooperation. Part of the confusion surrounding this debate stems from a failure to note that two different processes can result in reciprocity: partner control and partner choice. We suggest that the common observation that group-living animals direct their cooperative behaviours preferentially to those individuals from which they receive most cooperation is to be interpreted as the result of the sum of the two separate processes of partner control and partner choice. We review evidence that partner choice is the prevalent process in primates and propose explanations for this pattern. We make predictions that highlight the need for studies that separate the effects of partner control and partner choice in a broader variety of group-living taxa. © 2016 Cambridge Philosophical Society.