Science.gov

Sample records for bioclim deliverable d2

  1. Bioclimate and city planning - open space planning

    NASA Astrophysics Data System (ADS)

    Mertens, Elke

    The planning and using of open spaces in urban areas very much depend on the shading of the surrounding building structures. This article presents a method for the investigation of the sunlight and the bioclimatic conditions in dependence on the surrounding buildings. It is illustrated for typical courtyards in Berlin, Germany, as one type of open spaces. The programme HelioDat determines the shading of any spot of an open space. It gives the possible duration of direct sunlight for the selected spot for each day of the year. The sunlight conditions in the courtyards differ from one another a lot in dependence on their size the tallness of the surrounding buildings. The calculation of the PMV on the basis of the results of the programme HelioDat determine the bioclimatic situation in the discussed courtyards. Although the results of HelioDat are only one input among the weather conditions and the personal characteristics of the test-person, the bioclimatic conditions correlate very much with the sunlight conditions. In a projected building structure, the sunlight conditions vary a lot between the present situation and the two architectural alternatives. Since the bioclimatic situation is correlated to the sunlight conditions, this example demonstrates the importance for the investigation of the sunlight conditions and the bioclimate already during the planning process of buildings.

  2. Do bioclimate variables improve performance of climate envelope models?

    USGS Publications Warehouse

    Watling, James I.; Romañach, Stephanie S.; Bucklin, David N.; Speroterra, Carolina; Brandt, Laura A.; Pearlstine, Leonard G.; Mazzotti, Frank J.

    2012-01-01

    Climate envelope models are widely used to forecast potential effects of climate change on species distributions. A key issue in climate envelope modeling is the selection of predictor variables that most directly influence species. To determine whether model performance and spatial predictions were related to the selection of predictor variables, we compared models using bioclimate variables with models constructed from monthly climate data for twelve terrestrial vertebrate species in the southeastern USA using two different algorithms (random forests or generalized linear models), and two model selection techniques (using uncorrelated predictors or a subset of user-defined biologically relevant predictor variables). There were no differences in performance between models created with bioclimate or monthly variables, but one metric of model performance was significantly greater using the random forest algorithm compared with generalized linear models. Spatial predictions between maps using bioclimate and monthly variables were very consistent using the random forest algorithm with uncorrelated predictors, whereas we observed greater variability in predictions using generalized linear models.

  3. QUEST2: Sysdtem architecture deliverable set

    SciTech Connect

    Braaten, F.D.

    1995-02-27

    This document contains the system architecture and related documents which were developed during the Preliminary Analysis/System Architecture phase of the Quality, Environmental, Safety T-racking System redesign (QUEST2) project. Each discreet document in this deliverable set applies to a analytic effort supporting the architectural model of QUEST2. The P+ methodology cites a list of P+ documents normally included in a ``typical`` system architecture. Some of these were deferred to the release development phase of the project. The documents included in this deliverable set represent the system architecture itself. Related to that architecture are some decision support documents which provided needed information for management reviews that occurred during April. Consequently, the deliverables in this set were logically grouped and provided to support customer requirements. The remaining System Architecture Phase deliverables will be provided as a ``Supporting Documents`` deliverable set for the first release.

  4. Understanding global climate change scenarios through bioclimate stratification

    NASA Astrophysics Data System (ADS)

    Soteriades, A. D.; Murray-Rust, D.; Trabucco, A.; Metzger, M. J.

    2017-08-01

    Despite progress in impact modelling, communicating and understanding the implications of climatic change projections is challenging due to inherent complexity and a cascade of uncertainty. In this letter, we present an alternative representation of global climate change projections based on shifts in 125 multivariate strata characterized by relatively homogeneous climate. These strata form climate analogues that help in the interpretation of climate change impacts. A Random Forests classifier was calculated and applied to 63 Coupled Model Intercomparison Project Phase 5 climate scenarios at 5 arcmin resolution. Results demonstrate how shifting bioclimate strata can summarize future environmental changes and form a middle ground, conveniently integrating current knowledge of climate change impact with the interpretation advantages of categorical data but with a level of detail that resembles a continuous surface at global and regional scales. Both the agreement in major change and differences between climate change projections are visually combined, facilitating the interpretation of complex uncertainty. By making the data and the classifier available we provide a climate service that helps facilitate communication and provide new insight into the consequences of climate change.

  5. Thermal bioclimate in idealized urban street canyons in Campinas, Brazil

    NASA Astrophysics Data System (ADS)

    Abreu-Harbich, Loyde V.; Labaki, Lucila C.; Matzarakis, Andreas

    2014-01-01

    Among several urban design parameters, the height-to-width ratio (H/W) and orientation are important parameters strongly affecting thermal conditions in cities. This paper quantifies changes in thermal comfort due to typical urban canyon configurations in Campinas, Brazil, and presents urban guidelines concerning H/W ratios and green spaces to adapt urban climate change. The study focuses on thermal comfort issues of humans in urban areas and performs evaluation in terms of physiologically equivalent temperature (PET), based on long-term data. Meteorological data of air temperature, relative humidity, wind speed and solar radiation over a 7-year period (2003-2010) were used. A 3D street canyon model was designed with RayMan Pro software to simulate the influence of urban configuration on urban thermal climate. The following configurations and setups were used. The model canyon was 500 m in length, with widths 9, 21, and 44 m. Its height varied in steps of 2.5 m, from 5 to 40 m. The canyon could be rotated in steps of 15°. The results show that urban design parameters such as width, height, and orientation modify thermal conditions within street canyons. A northeast-southwest orientation can reduce PET during daytime more than other scenarios. Forestry management and green areas are recommended to promote shade on pedestrian areas and on façades, and to improve bioclimate thermal stress, in particular for H/W ratio less than 0.5. The method and results can be applied by architects and urban planners interested in developing responsive guidelines for urban climate issues.

  6. Adapting forest management to climate change using bioclimate models with topographic drivers

    Treesearch

    Gerald E. Rehfeldt; James J. Worrall; Suzanne B. Marchetti; Nicholas L. Crookston

    2015-01-01

    Bioclimate models incorporating topographic predictors as surrogates for microclimate effects are developed for Populus tremuloides and Picea engelmannii to provide the fine-grained specificity to local terrain required for adapting management of three Colorado (USA) national forests (1.28 million ha) and their periphery to climate change. Models were built with the...

  7. Quantification of thermal bioclimate for the management of urban design in Mediterranean climate of Barcelona, Spain.

    PubMed

    Rodríguez Algeciras, José Abel; Matzarakis, Andreas

    2016-08-01

    In order to contribute to the sustainability of the outdoor environment, knowledge about the urban thermal bioclimate should be transferred into climatic guidelines for planning. The general framework of this study responds to the need of analyzing thermal bioclimate in Mediterranean climate regions and its influence as an urban design factor. The paper analyzes the background of the urban climate and thermal bioclimate conditions in Barcelona (Spain), through the effect of shade conditions and wind speed variations. Simulations of shade and wind speed variations were performed to evaluate changes in thermal bioclimate due to modifications in urban morphology. Air temperature, relative humidity, wind speed, and solar radiation for the period from January, 2001 to January, 2015 were used to calculate physiologically equivalent temperature (PET) using the RayMan model. The results demonstrate that shade is the most important strategy to improve urban microclimatic conditions. In Barcelona, human thermal comfort conditions can be improved by shade and wind speed increase in terms of PET above 23 °C and by a wind speed decrease for thresholds of PET below 18 °C. Heat stress situations can be mitigated by shade and wind speed increase in conditions above 35 and 45 °C, respectively. The results of the study are an important contribution for urban planners, due to their possibilities and potential for the description of microclimatic conditions in Mediterranean climate regions. The knowledge is useful for improved human thermal comfort conditions, from the suitable configuration of urban form and architecture.

  8. Quantification of thermal bioclimate for the management of urban design in Mediterranean climate of Barcelona, Spain

    NASA Astrophysics Data System (ADS)

    Rodríguez Algeciras, José Abel; Matzarakis, Andreas

    2016-08-01

    In order to contribute to the sustainability of the outdoor environment, knowledge about the urban thermal bioclimate should be transferred into climatic guidelines for planning. The general framework of this study responds to the need of analyzing thermal bioclimate in Mediterranean climate regions and its influence as an urban design factor. The paper analyzes the background of the urban climate and thermal bioclimate conditions in Barcelona (Spain), through the effect of shade conditions and wind speed variations. Simulations of shade and wind speed variations were performed to evaluate changes in thermal bioclimate due to modifications in urban morphology. Air temperature, relative humidity, wind speed, and solar radiation for the period from January, 2001 to January, 2015 were used to calculate physiologically equivalent temperature (PET) using the RayMan model. The results demonstrate that shade is the most important strategy to improve urban microclimatic conditions. In Barcelona, human thermal comfort conditions can be improved by shade and wind speed increase in terms of PET above 23 °C and by a wind speed decrease for thresholds of PET below 18 °C. Heat stress situations can be mitigated by shade and wind speed increase in conditions above 35 and 45 °C, respectively. The results of the study are an important contribution for urban planners, due to their possibilities and potential for the description of microclimatic conditions in Mediterranean climate regions. The knowledge is useful for improved human thermal comfort conditions, from the suitable configuration of urban form and architecture.

  9. Evaluation of thermal bioclimate based on observational data and numerical simulations: an application to Greece.

    PubMed

    Giannaros, Theodore M; Melas, Dimitrios; Matzarakis, Andreas

    2015-02-01

    The evaluation of thermal bioclimate can be conducted employing either observational or modeling techniques. The advantage of the numerical modeling approach lies in that it can be applied in areas where there is lack of observational data, providing a detailed insight on the prevailing thermal bioclimatic conditions. However, this approach should be exploited carefully since model simulations can be frequently biased. The aim of this paper is to examine the suitability of a mesoscale atmospheric model in terms of evaluating thermal bioclimate. For this, the numerical weather prediction Weather Research and Forecasting (WRF) model and the radiation RayMan model are employed for simulating thermal bioclimatic conditions in Greece during a 1-year time period. The physiologically equivalent temperature (PET) is selected as an index for evaluating thermal bioclimate, while synoptic weather station data are exploited for verifying model performance. The results of the present study shed light on the strengths and weaknesses of the numerical modeling approach. Overall, it is shown that model simulations can provide a useful alternative tool for studying thermal bioclimate. Specifically for Greece, the WRF/RayMan modeling system was found to perform adequately well in reproducing the spatial and temporal variations of PET.

  10. Evaluation of thermal bioclimate based on observational data and numerical simulations: an application to Greece

    NASA Astrophysics Data System (ADS)

    Giannaros, Theodore M.; Melas, Dimitrios; Matzarakis, Andreas

    2015-02-01

    The evaluation of thermal bioclimate can be conducted employing either observational or modeling techniques. The advantage of the numerical modeling approach lies in that it can be applied in areas where there is lack of observational data, providing a detailed insight on the prevailing thermal bioclimatic conditions. However, this approach should be exploited carefully since model simulations can be frequently biased. The aim of this paper is to examine the suitability of a mesoscale atmospheric model in terms of evaluating thermal bioclimate. For this, the numerical weather prediction Weather Research and Forecasting (WRF) model and the radiation RayMan model are employed for simulating thermal bioclimatic conditions in Greece during a 1-year time period. The physiologically equivalent temperature (PET) is selected as an index for evaluating thermal bioclimate, while synoptic weather station data are exploited for verifying model performance. The results of the present study shed light on the strengths and weaknesses of the numerical modeling approach. Overall, it is shown that model simulations can provide a useful alternative tool for studying thermal bioclimate. Specifically for Greece, the WRF/RayMan modeling system was found to perform adequately well in reproducing the spatial and temporal variations of PET.

  11. Heat deliverability of homogeneous geothermal reservoirs

    SciTech Connect

    Iglesias, Eduardo R.; Moya, Sara L.

    1991-01-01

    For the last two decades, the petroleum industry has been successfully using simple inflow performance relationships (IPR's) to predict oil deliverability. In contrast, the geothermal industry lacked a simple and reliable method to estimate geothermal wells' heat deliverability. To address this gap in the standard geothermal-reservoir-assessment arsenal, we developed generalized dimensionless geothermal inflow performance relationships (GIPR's). These ''reference curves'' may be regarded as an approximate general solution of the equations describing the practically important case of radial 2-phase inflow. Based on this approximate solution, we outline a straightforward approach to estimate the reservoir contribution to geothermal wells heat and mass deliverability for 2-phase reservoirs. This approach is far less costly and in most cases as reliable as numerically modeling the reservoir, which is the alternative for 2-phase inflow.

  12. "Deliverance": The Anatomy of a Challenge.

    ERIC Educational Resources Information Center

    Mitoraj, Suzanne O.

    2000-01-01

    Describes how an English department and a school district responded to a parental challenge to the use of James Dickey's novel "Deliverance" in a senior English class. Offers a 2-month chronology of events, beginning with a letter of complaint to the principal, continuing through responses, meetings, media coverage, and the meeting and…

  13. Adaptive interpretation of gas well deliverability tests

    NASA Astrophysics Data System (ADS)

    Sergeev, V. L.; Thac Hoai Phuong, Nguyen; Strelnikova, A. B.

    2016-09-01

    The paper considers topical issues of improving accuracy of data obtained from gas well deliverability tests, decreasing the number of test stages and well test time, and reducing gas emissions. The aim of the research is to develop the method of adaptive interpretation of gas well deliverability tests with resulting IPR curve conducted in gas wells with steady-state filtration, which allows obtaining and taking into account additional a priori data on the formation pressure and flow coefficients, setting the number of test stages adequate for efficient well testing and reducing test time. The present research is based on the previous theoretical and practical findings in the spheres of gas well deliverability tests, systems analysis, system identification, function optimization and linear algebra. To test the method, the authors used the field data of deliverability tests run in the Urengoy gas and condensate field, Tyumen Oblast. The authors suggest the method of adaptive interpretation of gas well deliverability tests with resulting IPR curve, which is based on the law for gas filtration with variables dependent on the number of test stage and account of additional a priori data. The suggested method allows defining the estimates of the formation pressure and flow coefficients, optimal in terms of preassigned measures of quality, and setting the adequate number of test stages in the course of well testing. The case study of IPR curve data processing has indicated that adaptive interpretation provides more accurate estimates on the formation pressure and flow coefficients, as well as reduces the number of test stages.

  14. Bio-Climate Change between 1951-1980 and 1981-2010 in Spanish mainland

    NASA Astrophysics Data System (ADS)

    Lopez, Maria Luisa; Peña-Angulo, Dhais; Marco, Ricardo; Soledad López, Maria; González-Hidalgo, José Carlos

    2016-04-01

    The paper analyzes the spatial distribution of bioclimatic changes between the two climate normal periods (1951-1980 y 1981-2010) in Spanish mainland. The analyses is permorfed using high density monthly dataset of precipitation and mean temperatures: MOPREDAS (for precipitation) and MOTEDAS (for temperatures). Both dataset cover the period of 1951-2010 and have been analysed in their grid versión (10x10 km). The characterization of the total amount of pixels (5234) followed the "Global Bioclimatics" from Rivas-Martinez to identify its Continentality, Macrobioclimate, Bioclimatic Variant, Bioclimate, Thermotype and Ombrotype. The results were quantified in spatial percentages of occupancy for each of bioclimatic units and for each normal period. The most prominent changes observed between 1951-1980 and 1981-2010 are as follows: • Clear increase in Continentality, ie increased annual thermal range; • The Mediterranean Macrobioclimate increased in the same proportion as the Temperate Macrobioclimate decreased which means that the summer xericity increases; • Slight decrease in the percentage of total land occupied by the Bioclimatic Variants Steppic and Submediterranean; • Increase of all Mediterranean Bioclimates, especially Mediterranean Pluviseasonal Oceanic type and decrease of the Temperate Bioclimates (Temperate Hyperoceanic and Temperate Oceanic) • Clear increase of the warm Thermotypes both Mediterranean and Temperate in áreas previously under fresh or cold Thermotypes; the highest percentage of change are in the Mediterranean Macrobioclima than in the Temperate. • General increase towards xericity. • During the second period Continentality, summer xericity, extension of all Mediterranean Bioclimates, thermicity and dry ombrotypes increased. Spatial comparison between the two periods suggest consistent gradual changes between bioclimatic levels, and spatial coherence.

  15. Oilwell deliverability monitoring: A case history

    SciTech Connect

    Thrasher, T.S.; Fetkovich, E.J.; Scott, S.L.

    1994-12-31

    This paper presents a case history study that demonstrates a method to monitor wellhead deliverability performance for flowing oil wells in a manner similar to gas wells. Separator test data measured for production allocation are used along with the material balance relationship and multiphase flow analysis to develop a wellhead backpressure curve for flowing oil wells. An equivalent wellhead static pressure for flowing oil wells is described and shown to be a function of reservoir depletion and multiphase flow rate. Determination of the equivalent wellhead static pressure extends the understanding of wellhead backpressure analysis for both flowing oil and flowing gas wells.

  16. Oilwell deliverability monitoring: A case history

    SciTech Connect

    Thrasher, T.S.; Fetkovich, E.J.; Scott, S.L.

    1995-11-01

    This paper presents a case history study that demonstrates a method to monitor wellhead-deliverability performance for flowing oil wells in a manner similar to gas wells. Separator test data measured for production allocation are used along with the material-balance relationship and multiphase-flow analysis to develop a wellhead backpressure curve for flowing oil wells. An equivalent wellhead static pressure for flowing oil wells is described and shown to be a function of reservoir depletion and multiphase-flow rate. Determination of the equivalent wellhead static pressure extends the understanding of wellhead backpressure analysis for both flowing oil and gas wells. A case history example demonstrating the application of the methods described in the paper is developed with the separator test data from Point Arguello field wells. The resulting wellhead backpressure curves clearly defined individual well deliverability and proved to be valuable diagnostic tools to monitor well performance and to quantify production potential. The authors show that the procedures developed in this paper are directly equivalent to procedures applied to conventional gaswell wellhead backpressure analysis commonly used in the industry to monitor gaswell performance. By monitoring flowing oilwell performance with the methods described in this paper, operators can address the challenge of maintaining well productivity and field production plateau.

  17. QUEST2: Release 1: Project plan deliverable set

    SciTech Connect

    Braaten, F.D.

    1995-02-10

    This Project Management Plan combines the project management deliverables from the P+ methodology which are applicable to Release 1 of the QUEST2 work. This consolidation reflects discussions with WHC QA regarding an appropriate method for ensuring that P+ deliverables fulfill the intent of WHC-CM-3-10 and QR-19.

  18. 49 CFR 22.25 - Lender deliverables and delivery schedule.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Lender deliverables and delivery schedule. 22.25 Section 22.25 Transportation Office of the Secretary of Transportation SHORT-TERM LENDING PROGRAM (STLP) Participating Lenders § 22.25 Lender deliverables and delivery schedule. All Participating Lenders must adhere...

  19. Molecular Science: Network-Deliverable Curricula

    NASA Astrophysics Data System (ADS)

    Russell, Arlene; Chapman, Orville; Wegner, Patrick

    1998-05-01

    The Molecular Science systemic reform project, which has just begun its third year, is developing network-deliverable curricula for the first two years of Chemistry.1 The goals of the project are to prepare students who have a deep understanding of chemistry concepts and principles, have learned collaboration skills, can use the modern-technology tools of the chemist, and can write about chemistry. In addition, the project is integrating technology and telecommunications into the instructional process and shifting the instruction from lecture to active student learning. Faculty from six institutions (Crossroads School, East Los Angeles College, Pasadena City College, Mt. San Antonio College, California State University, Fullerton [CSUF], and the University of California, Los Angeles [UCLA]) form the core of the project. This cross-section represents the common and shared responsibility that exists for teaching the first two years of chemistry and the diversity of students in the nation.

  20. Present, future, and novel bioclimates of the San Francisco, California region

    USGS Publications Warehouse

    Torregrosa, Alicia; Taylor, Maxwell D.; Flint, Lorraine E.; Flint, Alan L.

    2013-01-01

    Bioclimates are syntheses of climatic variables into biologically relevant categories that facilitate comparative studies of biotic responses to climate conditions. Isobioclimates, unique combinations of bioclimatic indices (continentality, ombrotype, and thermotype), were constructed for northern California coastal ranges based on the Rivas-Martinez worldwide bioclimatic classification system for the end of the 20th century climatology (1971–2000) and end of the 21st century climatology (2070–2099) using two models, Geophysical Fluid Dynamics Laboratory (GFDL) model and the Parallel Climate Model (PCM), under the medium-high A2 emission scenario. The digitally mapped results were used to 1) assess the relative redistribution of isobioclimates and their magnitude of change, 2) quantify the loss of isobioclimates into the future, 3) identify and locate novel isobioclimates projected to appear, and 4) explore compositional change in vegetation types among analog isobioclimate patches. This study used downscaled climate variables to map the isobioclimates at a fine spatial resolution −270 m grid cells. Common to both models of future climate was a large change in thermotype. Changes in ombrotype differed among the two models. The end of 20th century climatology has 83 isobioclimates covering the 63,000 km2 study area. In both future projections 51 of those isobioclimates disappear over 40,000 km2. The ordination of vegetation-bioclimate relationships shows very strong correlation of Rivas-Martinez indices with vegetation distribution and composition. Comparisons of vegetation composition among analog patches suggest that vegetation change will be a local rearrangement of species already in place rather than one requiring long distance dispersal. The digitally mapped results facilitate comparison with other Mediterranean regions. Major remaining challenges include predicting vegetation composition of novel isobioclimates and developing metrics to compare

  1. Present, Future, and Novel Bioclimates of the San Francisco, California Region

    PubMed Central

    Torregrosa, Alicia; Taylor, Maxwell D.; Flint, Lorraine E.; Flint, Alan L.

    2013-01-01

    Bioclimates are syntheses of climatic variables into biologically relevant categories that facilitate comparative studies of biotic responses to climate conditions. Isobioclimates, unique combinations of bioclimatic indices (continentality, ombrotype, and thermotype), were constructed for northern California coastal ranges based on the Rivas-Martinez worldwide bioclimatic classification system for the end of the 20th century climatology (1971–2000) and end of the 21st century climatology (2070–2099) using two models, Geophysical Fluid Dynamics Laboratory (GFDL) model and the Parallel Climate Model (PCM), under the medium-high A2 emission scenario. The digitally mapped results were used to 1) assess the relative redistribution of isobioclimates and their magnitude of change, 2) quantify the loss of isobioclimates into the future, 3) identify and locate novel isobioclimates projected to appear, and 4) explore compositional change in vegetation types among analog isobioclimate patches. This study used downscaled climate variables to map the isobioclimates at a fine spatial resolution −270 m grid cells. Common to both models of future climate was a large change in thermotype. Changes in ombrotype differed among the two models. The end of 20th century climatology has 83 isobioclimates covering the 63,000 km2 study area. In both future projections 51 of those isobioclimates disappear over 40,000 km2. The ordination of vegetation-bioclimate relationships shows very strong correlation of Rivas-Martinez indices with vegetation distribution and composition. Comparisons of vegetation composition among analog patches suggest that vegetation change will be a local rearrangement of species already in place rather than one requiring long distance dispersal. The digitally mapped results facilitate comparison with other Mediterranean regions. Major remaining challenges include predicting vegetation composition of novel isobioclimates and developing metrics to compare

  2. Present, future, and novel bioclimates of the San Francisco, California region.

    PubMed

    Torregrosa, Alicia; Taylor, Maxwell D; Flint, Lorraine E; Flint, Alan L

    2013-01-01

    Bioclimates are syntheses of climatic variables into biologically relevant categories that facilitate comparative studies of biotic responses to climate conditions. Isobioclimates, unique combinations of bioclimatic indices (continentality, ombrotype, and thermotype), were constructed for northern California coastal ranges based on the Rivas-Martinez worldwide bioclimatic classification system for the end of the 20(th) century climatology (1971-2000) and end of the 21(st) century climatology (2070-2099) using two models, Geophysical Fluid Dynamics Laboratory (GFDL) model and the Parallel Climate Model (PCM), under the medium-high A2 emission scenario. The digitally mapped results were used to 1) assess the relative redistribution of isobioclimates and their magnitude of change, 2) quantify the loss of isobioclimates into the future, 3) identify and locate novel isobioclimates projected to appear, and 4) explore compositional change in vegetation types among analog isobioclimate patches. This study used downscaled climate variables to map the isobioclimates at a fine spatial resolution -270 m grid cells. Common to both models of future climate was a large change in thermotype. Changes in ombrotype differed among the two models. The end of 20(th) century climatology has 83 isobioclimates covering the 63,000 km(2) study area. In both future projections 51 of those isobioclimates disappear over 40,000 km(2). The ordination of vegetation-bioclimate relationships shows very strong correlation of Rivas-Martinez indices with vegetation distribution and composition. Comparisons of vegetation composition among analog patches suggest that vegetation change will be a local rearrangement of species already in place rather than one requiring long distance dispersal. The digitally mapped results facilitate comparison with other Mediterranean regions. Major remaining challenges include predicting vegetation composition of novel isobioclimates and developing metrics to compare

  3. Influences Determining European Coal Seam Gas Deliverability

    NASA Astrophysics Data System (ADS)

    Clark, G.

    2009-04-01

    Technically the coal basins of Europe have generated significant Gas In Place figures that has historically generated investor's interest in the development of this potential coal seam gas (CSG) resource. In the early 1980's, a wave of international, principally American, companies arrived, established themselves, drilled and then left with a poor record of success and disappointed investors. Recently a second wave of investment started after 2002, with the smaller companies leading the charge but have the lesson been learned from the past failures? To select a CSG investment project the common European approach has been to: 1. Find an old mining region; 2. Look to see if it had a coal mine methane gas problem; 3. Look for the non-mined coal seams; and 4. Peg the land. This method is perhaps the reason why the history of CSG exploration in Europe is such a disappointment as generally the coal mining regions of Europe do not have commercial CSG reservoir attributes. As a result, investors and governments have lost confidence that CSG will be a commercial success in Europe. New European specific principles for the determination of commercial CSG prospects have had to be delineated that allow for the selection of coal basins that have a strong technical case for deliverability. This will result in the return of investor confidence.

  4. Strategic planning for information management: what are the deliverables?

    PubMed Central

    Olsen, A. J.; Stead, W. W.

    1995-01-01

    This paper describes the deliverables framework developed by Vanderbilt University Medical Center (VUMC) in its IAIMS planning process. The key deliverables include: visions for the future; mission, goals, and objectives for the information management function; critical functions for IAIMS; categorized projects; priority recommendations; and a straw man project sequence reflecting dependencies. The paper also discusses how the plan will be used and how it interacts with direction-setting for the Medical Center. PMID:8563398

  5. D-2 acceleration characterization

    NASA Astrophysics Data System (ADS)

    Hamacher, Hans; Bluemel, U.

    1994-07-01

    During the second German Spacelab Mission D-2, extensive onboard measurements of the residual acceleration were performed. The payload was equipped with accelerometer packages distributed over the entire Spacelab module. The microgravity measurement assembly (MMA) was the core system comprising fixed mounted as well as mobile sensor packages. Additional autonomous accelerometer systems were mounted within the payload elements MEDEA and Werkstofflabor. On-board video recording has been performed to correlate the measured accelerations to mission events. The D-2 microgravity characterization program also included numerical calculations to predict low frequency effects due to atmospheric drag, tidal force, and spacecraft rotation. Results of characteristic quiet mission phases show that the microgravity level is essentially below the requirements defined for the space station. Other results of some other mission phases revealed that a wealth can be done by improving payload design and operation to improve the microgravity quality of Spacelab missions.

  6. Integrating bioclimate with population models to improve forecasts of species extinctions under climate change

    PubMed Central

    Brook, Barry W.; Akçakaya, H. Resit; Keith, David A.; Mace, Georgina M.; Pearson, Richard G.; Araújo, Miguel B.

    2009-01-01

    Climate change is already affecting species worldwide, yet existing methods of risk assessment have not considered interactions between demography and climate and their simultaneous effect on habitat distribution and population viability. To address this issue, an international workshop was held at the University of Adelaide in Australia, 25–29 May 2009, bringing leading species distribution and population modellers together with plant ecologists. Building on two previous workshops in the UK and Spain, the participants aimed to develop methodological standards and case studies for integrating bioclimatic and metapopulation models, to provide more realistic forecasts of population change, habitat fragmentation and extinction risk under climate change. The discussions and case studies focused on several challenges, including spatial and temporal scale contingencies, choice of predictive climate, land use, soil type and topographic variables, procedures for ensemble forecasting of both global climate and bioclimate models and developing demographic structures that are realistic and species-specific and yet allow generalizations of traits that make species vulnerable to climate change. The goal is to provide general guidelines for assessing the Red-List status of large numbers of species potentially at risk, owing to the interactions of climate change with other threats such as habitat destruction, overexploitation and invasive species. PMID:19625300

  7. A first approach to calculate BIOCLIM variables and climate zones for Antarctica

    NASA Astrophysics Data System (ADS)

    Wagner, Monika; Trutschnig, Wolfgang; Bathke, Arne C.; Ruprecht, Ulrike

    2017-02-01

    For testing the hypothesis that macroclimatological factors determine the occurrence, biodiversity, and species specificity of both symbiotic partners of Antarctic lecideoid lichens, we present a first approach for the computation of the full set of 19 BIOCLIM variables, as available at http://www.worldclim.org/ for all regions of the world with exception of Antarctica. Annual mean temperature (Bio 1) and annual precipitation (Bio 12) were chosen to define climate zones of the Antarctic continent and adjacent islands as required for ecological niche modeling (ENM). The zones are based on data for the years 2009-2015 which was obtained from the Antarctic Mesoscale Prediction System (AMPS) database of the Ohio State University. For both temperature and precipitation, two separate zonings were specified; temperature values were divided into 12 zones (named 1 to 12) and precipitation values into five (named A to E). By combining these two partitions, we defined climate zonings where each geographical point can be uniquely assigned to exactly one zone, which allows an immediate explicit interpretation. The soundness of the newly calculated climate zones was tested by comparison with already published data, which used only three zones defined on climate information from the literature. The newly defined climate zones result in a more precise assignment of species distribution to the single habitats. This study provides the basis for a more detailed continental-wide ENM using a comprehensive dataset of lichen specimens which are located within 21 different climate regions.

  8. Basic analysis of climate and urban bioclimate of Dar es Salaam, Tanzania

    NASA Astrophysics Data System (ADS)

    Ndetto, Emmanuel L.; Matzarakis, Andreas

    2013-10-01

    Better understanding of urban microclimate and bioclimate of any city is imperative today when the world is constrained by both urbanisation and global climate change. Urbanisation generally triggers changes in land cover and hence influencing the urban local climate. Dar es Salaam city in Tanzania is one of the fast growing cities. Assessment of its urban climate and the human biometeorological conditions was done using the easily available synoptic meteorological data covering the period 2001-2011. In particular, the physiologically equivalent temperature (PET) was calculated using the RayMan software and results reveal that the afternoon period from December to February (DJF season) is relatively the most thermal stressful period to human beings in Dar es Salaam where PET values of above 35 °C were found. Additionally, the diurnal cycle of the individual meteorological elements that influence the PET index were analysed and found that air temperature of 30-35 °C dominate the afternoon period from 12:00 to 15:00 hours local standard time at about 60 % of occurrence. The current results, though considered as preliminary to the ongoing urban climate study in the city, provide an insight on how urban climate research is of significant importance in providing useful climatic information for ensuring quality of life and wellbeing of city dwellers.

  9. Integrating bioclimate with population models to improve forecasts of species extinctions under climate change.

    PubMed

    Brook, Barry W; Akçakaya, H Resit; Keith, David A; Mace, Georgina M; Pearson, Richard G; Araújo, Miguel B

    2009-12-23

    Climate change is already affecting species worldwide, yet existing methods of risk assessment have not considered interactions between demography and climate and their simultaneous effect on habitat distribution and population viability. To address this issue, an international workshop was held at the University of Adelaide in Australia, 25-29 May 2009, bringing leading species distribution and population modellers together with plant ecologists. Building on two previous workshops in the UK and Spain, the participants aimed to develop methodological standards and case studies for integrating bioclimatic and metapopulation models, to provide more realistic forecasts of population change, habitat fragmentation and extinction risk under climate change. The discussions and case studies focused on several challenges, including spatial and temporal scale contingencies, choice of predictive climate, land use, soil type and topographic variables, procedures for ensemble forecasting of both global climate and bioclimate models and developing demographic structures that are realistic and species-specific and yet allow generalizations of traits that make species vulnerable to climate change. The goal is to provide general guidelines for assessing the Red-List status of large numbers of species potentially at risk, owing to the interactions of climate change with other threats such as habitat destruction, overexploitation and invasive species.

  10. 48 CFR 452.247-71 - Marking Deliverables.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Marking Deliverables. 452.247-71 Section 452.247-71 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 452.247-71...

  11. 20 CFR 638.300 - Eligibility for funds and eligible deliverers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Funding, Site Selection... made available by the Secretary to eligible deliverers for the operation of centers and for the provision of Job Corps operational support services. (b) Eligible deliverers for the operation of centers...

  12. 20 CFR 638.300 - Eligibility for funds and eligible deliverers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Eligibility for funds and eligible deliverers. 638.300 Section 638.300 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF..., and Facilities Management § 638.300 Eligibility for funds and eligible deliverers. (a) Funds shall...

  13. Project deliverables - a waste of time or a chance for knowledge transfer and dissemination?

    NASA Astrophysics Data System (ADS)

    Walter, Sylvia

    2016-04-01

    Deliverables are a common tool to measure a distinct output of a project. They should be meaningful in terms of the project's objectives and are normally constituted by e.g. a written report or document, a developed tool or software, an organized training or conference. They can be scientific or technical. The number of deliverables must be reasonable and commensurate to the project and its content. Deliverables as contractual obligations are often time consuming and often seen as a waste of "research" time, as one more administrative task without any use. However, deliverables are needed to verify the progress of a project and to convince the sponsor that the project is going in the right direction and the money well-invested. The presentation will deal with the question on how to use a deliverable in a profitable way for the project and what are the possibilities of use.

  14. D2PC sensitivity analysis

    SciTech Connect

    Lombardi, D.P.

    1992-08-01

    The Chemical Hazard Prediction Model (D2PC) developed by the US Army will play a critical role in the Chemical Stockpile Emergency Preparedness Program by predicting chemical agent transport and dispersion through the atmosphere after an accidental release. To aid in the analysis of the output calculated by D2PC, this sensitivity analysis was conducted to provide information on model response to a variety of input parameters. The sensitivity analysis focused on six accidental release scenarios involving chemical agents VX, GB, and HD (sulfur mustard). Two categories, corresponding to conservative most likely and worst case meteorological conditions, provided the reference for standard input values. D2PC displayed a wide variety of sensitivity to the various input parameters. The model displayed the greatest overall sensitivity to wind speed, mixing height, and breathing rate. For other input parameters, sensitivity was mixed but generally lower. Sensitivity varied not only with parameter, but also over the range of values input for a single parameter. This information on model response can provide useful data for interpreting D2PC output.

  15. Deliverable navigation for multicriteria step and shoot IMRT treatment planning

    NASA Astrophysics Data System (ADS)

    Craft, David; Richter, Christian

    2013-01-01

    We consider Pareto surface based multi-criteria optimization for step and shoot IMRT planning. By analyzing two navigation algorithms, we show both theoretically and in practice that the number of plans needed to form convex combinations of plans during navigation can be kept small (much less than the theoretical maximum number needed in general, which is equal to the number of objectives for on-surface Pareto navigation). Therefore a workable approach for directly deliverable navigation in this setting is to segment the underlying Pareto surface plans and then enforce the mild restriction that only a small number of these plans are active at any time during plan navigation, thus limiting the total number of segments used in the final plan.

  16. Deliverability on the interstate natural gas pipeline system

    SciTech Connect

    1998-05-01

    Deliverability on the Interstate Natural Gas Pipeline System examines the capability of the national pipeline grid to transport natural gas to various US markets. The report quantifies the capacity levels and utilization rates of major interstate pipeline companies in 1996 and the changes since 1990, as well as changes in markets and end-use consumption patterns. It also discusses the effects of proposed capacity expansions on capacity levels. The report consists of five chapters, several appendices, and a glossary. Chapter 1 discusses some of the operational and regulatory features of the US interstate pipeline system and how they affect overall system design, system utilization, and capacity expansions. Chapter 2 looks at how the exploration, development, and production of natural gas within North America is linked to the national pipeline grid. Chapter 3 examines the capability of the interstate natural gas pipeline network to link production areas to market areas, on the basis of capacity and usage levels along 10 corridors. The chapter also examines capacity expansions that have occurred since 1990 along each corridor and the potential impact of proposed new capacity. Chapter 4 discusses the last step in the transportation chain, that is, deliverability to the ultimate end user. Flow patterns into and out of each market region are discussed, as well as the movement of natural gas between States in each region. Chapter 5 examines how shippers reserve interstate pipeline capacity in the current transportation marketplace and how pipeline companies are handling the secondary market for short-term unused capacity. Four appendices provide supporting data and additional detail on the methodology used to estimate capacity. 32 figs., 15 tabs.

  17. Audit of departmental receipt of final deliverables for grant awards

    SciTech Connect

    1997-12-04

    To help meet legislatively mandated and programmatic mission requirements, the Department of Energy (DOE) awards grants to colleges and universities, state and local governments, individuals, small businesses, and non-profit corporations. As of July 15, 1996, the DOE was responsible for administering over 7,400 grants with purposes ranging from basic research to weatherizing homes. The Government`s share of these grants was about $8 billion. The objective of this audit was to determine whether the DOE received final deliverables, detailing grantee accomplishments and expenditure of funds, in accordance with Federal and Departmental policies and procedures. The Code of Federal Regulations requires that grants benefit the general public. This is demonstrated through technical and/or financial reports that each grantee is usually required to deliver. These reports describe the final results of the grant effort. In spite of this requirement, many grantees did not provide final technical and/or financial reports. For example, at the five procurement offices audited, it is projected that the Department had not received final deliverables on 718 inactive grants valued at about $232 million. In other cases, officials inappropriately extended performance periods so that the grant instrument would continue to be classified as active. This non-reporting occurred because the Department did not effectively implement existing procedures or establish other monitoring procedures that ensured grantees fulfilled their grant obligations. Specifically, the Department did not establish procedures to withhold payment if a grantee failed to comply with grant terms and conditions. In addition, the Department did not defer additional awards to grantees that had not met the tenons and conditions of prior grants and inappropriately extended grant performance periods for excessive periods of time. Further, Departmental personnel waived reporting requirements in order to close out grant awards.

  18. Possibilities for a valorisation of geomorphologic research deliverables

    NASA Astrophysics Data System (ADS)

    Geilhausen, M.; Götz, J.; Otto, J.-C.; Schrott, L.

    2009-04-01

    Many geomorphological studies focus on fundamental research questions in large parts, although there are lots of applied fields like landslide hazard assessment or water framework directive. As fundamental research is a common property, their outcomes should be more "open" and accessible to the public. This means that scientists have to find new ways presenting their results and outcomes besides publishing in scientific journals. This paper shows possibilities for a valorisation of geomorphologic research deliverables using print as well as digital media. Geotrails explain remarkable and exciting landscape features using information boards and become more and more popular and important for tourism in many parts of the world. With the growing interest in environmental change and outdoor activities, print media like field guides reach an increasing number of people. Field guides and Geotrails can be coupled in order to arise awareness about geomorphological landforms and to deliver more specific information on the site beyond the information given on the boards in the field. As field guides are designed for the general public they can be used for educational purposes as well. Today, this information can also be found in the internet offering virtual trips through landscapes using dynamic maps. Here, server side GIS technologies (WebGIS) using standardised interfaces provide new possibilities to show geomorphic data to the public and to share them with the scientific community. Furthermore, data formats like XML or KML are powerful tools for data exchange and can be used in interactive data viewers like Google Earth. We will present the Geotrail "Geomorphologischer Lehrpfad am Fuße der Zugspitze. Das Reintal - Eine Wanderung durch Raum und Zeit" (Bavarian Alps, Germany). Additionally, three geomorphologic WebGIS applications (Geomorphologic map Turtmanntal, Permafrostmap of Austria, Geomorphologic maps of Germany) will exemplify how geomorphologic information and

  19. D2 Inertial Measurement Unit

    NASA Astrophysics Data System (ADS)

    Dewar, Patrick; Gido, Joseph; Carroll, Joseph

    1993-06-01

    The D2 Hypervelocity Projectile is a Strategic Defense Initiative sponsored technology program that is designed to provide low endo-atmospheric, kinetic kill defense against strategic reentry vehicles. The D2 program is funded through the U.S. Army Space and Strategic Defense Command (SSDC) in Huntsville, AL and contracted through the U.S. Army Armament Research and Development Engineering Center (ARDEC) at Picatinny Arsenal, NJ. In GFY 93 the program began an integration and flight demonstration phase with the Hypervelocity Fire Control System (HVFC) and the Solid Propellant Electro Thermal Chemical (SPETC) launcher. The Inertial Measurement Unit (IMU) necessary to perform the autopilot and guidance data gathering must be extremely small, lightweight and shock hardened. The IMU is comprised of three Honeywell GG1308 miniature Ring Laser Gyros (RLG), and three Endevco 7290-M19 miniature silicon accelerometers. The IMU has self-contained high voltage Power Supply (HVPS) processor and memory electronics providing a complete stand alone, three axis measurement package. This Inertial Cluster Assembly (ICA) is then packaged into a cylindrical housing, approximately 1.9 inches in diameter and 1.3 inches in length.

  20. FY2004 Progress Summary and FY2005 Program Plan Statement of Work and Deliverables

    SciTech Connect

    Meier, W; Bibeau, C

    2006-01-23

    FY2004 progress summary and FY2005 program plan statement of work and deliverables for development of high average power diode-pumped solid state lasers, and complementary technologies for applications in energy and defense.

  1. QUEST2: Release 1, SA/Release 1 supporting documents deliverable set

    SciTech Connect

    Braaten, F.D.

    1995-02-27

    This document contains deliverables which reflect the last of the System Architecture phase analysis for the Quality, Environmental, Safety Tracking System redesign (QUEST2) project. These deliverables are focused on the final insights required to start functional design of the first QUEST2 release. They include the data definitions, conversion rules, standards for design and user interface, performance criteria, and rules to be followed during the prototyping activity described in the Project Management Plan.

  2. Modelling the effects of climate change on the distribution and production of marine fishes: accounting for trophic interactions in a dynamic bioclimate envelope model.

    PubMed

    Fernandes, Jose A; Cheung, William W L; Jennings, Simon; Butenschön, Momme; de Mora, Lee; Frölicher, Thomas L; Barange, Manuel; Grant, Alastair

    2013-08-01

    Climate change has already altered the distribution of marine fishes. Future predictions of fish distributions and catches based on bioclimate envelope models are available, but to date they have not considered interspecific interactions. We address this by combining the species-based Dynamic Bioclimate Envelope Model (DBEM) with a size-based trophic model. The new approach provides spatially and temporally resolved predictions of changes in species' size, abundance and catch potential that account for the effects of ecological interactions. Predicted latitudinal shifts are, on average, reduced by 20% when species interactions are incorporated, compared to DBEM predictions, with pelagic species showing the greatest reductions. Goodness-of-fit of biomass data from fish stock assessments in the North Atlantic between 1991 and 2003 is improved slightly by including species interactions. The differences between predictions from the two models may be relatively modest because, at the North Atlantic basin scale, (i) predators and competitors may respond to climate change together; (ii) existing parameterization of the DBEM might implicitly incorporate trophic interactions; and/or (iii) trophic interactions might not be the main driver of responses to climate. Future analyses using ecologically explicit models and data will improve understanding of the effects of inter-specific interactions on responses to climate change, and better inform managers about plausible ecological and fishery consequences of a changing environment. © 2013 John Wiley & Sons Ltd.

  3. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under any...

  4. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under any...

  5. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under any...

  6. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  7. Adaptive interpretation of gas well deliverability tests with generating data of the IPR curve

    NASA Astrophysics Data System (ADS)

    Sergeev, V. L.; Phuong, Nguyen T. H.; Krainov, A. I.

    2017-01-01

    The paper considers topical issues of improving accuracy of estimated parameters given by data obtained from gas well deliverability tests, decreasing test time, and reducing gas emissions into the atmosphere. The aim of the research is to develop the method of adaptive interpretation of gas well deliverability tests with a resulting IPR curve and using a technique of generating data, which allows taking into account additional a priori information, improving accuracy of determining formation pressure and flow coefficients, reducing test time. The present research is based on the previous theoretical and practical findings in the spheres of gas well deliverability tests, systems analysis, system identification, function optimization and linear algebra. To test the method, the authors used the field data of deliverability tests of two wells, run in the Urengoy gas and condensate field, Tyumen Oblast. The authors suggest the method of adaptive interpretation of gas well deliverability tests with the resulting IPR curve and the possibility of generating data of bottomhole pressure and a flow rate at different test stages. The suggested method allows defining the estimates of the formation pressure and flow coefficients, optimal in terms of preassigned measures of quality, and setting the adequate number of test stages in the course of well testing. The case study of IPR curve data processing has indicated that adaptive interpretation provides more accurate estimates on the formation pressure and flow coefficients, as well as reduces the number of test stages.

  8. Landscape-scale learning: from lectures to professional deliverables

    NASA Astrophysics Data System (ADS)

    Follain, S.; Devaux, N.; Colin, F.

    2009-04-01

    Earth Science ingenieers (Master degree) need to be trained in multidisciplinary approaches but also to learn how to combine theoretical and practical knowledge. Nevertheless we notice it is not always easy to combine in a same lecture, theoretical and practical issues. In order to build bridges between these instructions we propose to student a new teaching unit: "Sustainability Diagnosis". Its originalities are i) to be couple to an other (theoretical) teaching unit dealing with landscape-scale learning ii) to be performed under a project mode and iii) to provide deliverables ordered by professional users, e.g. farmers, catchment managers. The landscape-scale learning is a classical learning period with lectures provided by specialists in various disciplines e.g. Soil Science, Hydrology, Agronomy, which focus on a common spatial scale, the landscape. It explicitly develops knowledge on energy and matter transfers between landscape components and explains potential effects of human-induced disturbances on both landscape and fluxes evolution. The deliverables for the farmer (chosen professional user) concern issues on his crop system sustainability. It requires a diagnosis in one hand on soil use and management potentialities and in another hand on environmental externalities (soil and water conservation) induced by the cropping system. The communication will present the work done by 14 students during this new teaching unit (Sustainability Diagnosis) of two weeks. This first attempt expertized a one square kilometer area located in Saint-Chinian vineyard region (South of France). This production area with guarantee of origin (AOC) has productivity constraints linked to landscape properties which directly impact farmer decisions. In the same time it has been shown that vineyard crop system induces water pollution by pesticides and increases soil degradation; in a sustainability perspective, these environmental impacts need to be reduced. The learning period was

  9. In Silico Discovery of High Deliverable Capacity Metal-Organic Frameworks

    NASA Astrophysics Data System (ADS)

    Bao, Yi; Martin, Richard; Simon, Cory; Haranczyk, Maciej; Smit, Berend; Deem, Michael; Michael W. Deem Team; Maciej Haranczyk Team; Berend Smit Team

    2015-03-01

    Metal organic frameworks (MOFs) are actively being explored as potential adsorbed natural gas storage materials for small vehicles. Experimental exploration of potential materials is limited by the throughput of synthetic chemistry. We here describe a computational methodology to complement and guide these experimental efforts. The method uses known chemical transformations in silico to identify MOFs with high methane deliverable capacity. The procedure explicitly considers synthesizability with geometric requirements on organic linkers. We efficiently search the composition and conformation space of organic linkers for nine MOF networks, finding 48 materials with higher predicted deliverable capacity (at 65 bar storage, 5.8 bar depletion, and 298 K) than MOF-5 in four of the nine networks. The best material has a predicted deliverable capacity 8% higher than that of MOF-5. US Department of Energy.

  10. Mars Reconnaissance Orbiter, Ground Data System, Receivables and Deliverables (REC/DELs)

    NASA Technical Reports Server (NTRS)

    Carlton, Magdi

    2006-01-01

    This paper presents one JPL element manager's approach to describe a complex Ground Data System (GDS) with its receivables and deliverables (REC/DEL). The Mars Reconnaissance Orbiter (MRO) Ground Data System is the integrated set of ground software, hardware, facilities and networks that support mission operation. REC/DEL is a powerful tool for specifying hierarchy of commitments among systems and teams. Receivable of a system is a deliverable of another system. Focusing on tangible products enables the manager to objectively measure progress in a schedule. The Jet Propulsion Laboratory mandates the use of REC/DEL for flight projects. Tutorial and training is provided for managers to create an integrated REC/DEL database using automated systems. Project schedules are based on REC/DELs. This paper is not focusing on the mechanics of REC/DEL database creation, but it provides a guideline how one systematically creates categories of deliverables and receivables for ground data system components...

  11. Mars Reconnaissance Orbiter, Ground Data System, Receivables and Deliverables (REC/DELs)

    NASA Technical Reports Server (NTRS)

    Carlton, Magdi

    2006-01-01

    This paper presents one JPL element manager's approach to describe a complex Ground Data System (GDS) with its receivables and deliverables (REC/DEL). The Mars Reconnaissance Orbiter (MRO) Ground Data System is the integrated set of ground software, hardware, facilities and networks that support mission operation. REC/DEL is a powerful tool for specifying hierarchy of commitments among systems and teams. Receivable of a system is a deliverable of another system. Focusing on tangible products enables the manager to objectively measure progress in a schedule. Jet Propulsion Laboratory mandates the use of REC/DEL for flight projects. Tutorial and training is provided for managers to create integrated REC/DEL database using automated systems. Project schedules are based on REC/DELs. This paper is not focusing on the mechanics of REC/DEL database creation, but it provides a guideline how one systematically creates categories of deliverables and receivables for ground data system components.

  12. Mars Reconnaissance Orbiter, Ground Data System, Receivables and Deliverables (REC/DELs)

    NASA Technical Reports Server (NTRS)

    Carlton, Magdi

    2006-01-01

    This paper presents one JPL element manager's approach to describe a complex Ground Data System (GDS) with its receivables and deliverables (REC/DEL). The Mars Reconnaissance Orbiter (MRO) Ground Data System is the integrated set of ground software, hardware, facilities and networks that support mission operation. REC/DEL is a powerful tool for specifying hierarchy of commitments among systems and teams. Receivable of a system is a deliverable of another system. Focusing on tangible products enables the manager to objectively measure progress in a schedule. The Jet Propulsion Laboratory mandates the use of REC/DEL for flight projects. Tutorial and training is provided for managers to create an integrated REC/DEL database using automated systems. Project schedules are based on REC/DELs. This paper is not focusing on the mechanics of REC/DEL database creation, but it provides a guideline how one systematically creates categories of deliverables and receivables for ground data system components...

  13. Mars Reconnaissance Orbiter, Ground Data System, Receivables and Deliverables (REC/DELs)

    NASA Technical Reports Server (NTRS)

    Carlton, Magdi

    2006-01-01

    This paper presents one JPL element manager's approach to describe a complex Ground Data System (GDS) with its receivables and deliverables (REC/DEL). The Mars Reconnaissance Orbiter (MRO) Ground Data System is the integrated set of ground software, hardware, facilities and networks that support mission operation. REC/DEL is a powerful tool for specifying hierarchy of commitments among systems and teams. Receivable of a system is a deliverable of another system. Focusing on tangible products enables the manager to objectively measure progress in a schedule. Jet Propulsion Laboratory mandates the use of REC/DEL for flight projects. Tutorial and training is provided for managers to create integrated REC/DEL database using automated systems. Project schedules are based on REC/DELs. This paper is not focusing on the mechanics of REC/DEL database creation, but it provides a guideline how one systematically creates categories of deliverables and receivables for ground data system components.

  14. Computational Design of Metal-Organic Frameworks with High Methane Deliverable Capacity

    NASA Astrophysics Data System (ADS)

    Bao, Yi; Martin, Richard; Simon, Cory; Haranczyk, Maciej; Smit, Berend; Deem, Michael; Deem Team; Haranczyk Team; Smit Team

    Metal-organic frameworks (MOFs) are a rapidly emerging class of nanoporous materials with largely tunable chemistry and diverse applications in gas storage, gas purification, catalysis, etc. Intensive efforts are being made to develop new MOFs with desirable properties both experimentally and computationally in the past decades. To guide experimental synthesis with limited throughput, we develop a computational methodology to explore MOFs with high methane deliverable capacity. This de novo design procedure applies known chemical reactions, considers synthesizability and geometric requirements of organic linkers, and evolves a population of MOFs with desirable property efficiently. We identify about 500 MOFs with higher deliverable capacity than MOF-5 in 10 networks. We also investigate the relationship between deliverable capacity and internal surface area of MOFs. This methodology can be extended to MOFs with multiple types of linkers and multiple SBUs. DE-FG02- 12ER16362.

  15. Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

    PubMed Central

    Gantz, Stephanie C; Robinson, Brooks G; Buck, David C; Bunzow, James R; Neve, Rachael L; Williams, John T; Neve, Kim A

    2015-01-01

    D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors. DOI: http://dx.doi.org/10.7554/eLife.09358.001 PMID:26308580

  16. 20 CFR 638.812 - State and local taxation of Job Corps deliverers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false State and local taxation of Job Corps... LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.812 State and local taxation of Job Corps deliverers. The Act provides that transactions conducted...

  17. 20 CFR 638.812 - State and local taxation of Job Corps deliverers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false State and local taxation of Job Corps... LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.812 State and local taxation of Job Corps deliverers. The Act provides that transactions conducted...

  18. 20 CFR 638.812 - State and local taxation of Job Corps deliverers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false State and local taxation of Job Corps deliverers. 638.812 Section 638.812 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.812 State and local taxation of...

  19. Application of new and novel fracture stimulation technologies to enhance the deliverability of gas storage wells

    SciTech Connect

    1995-04-01

    Based on the information presented in this report, our conclusions regarding the potential for new and novel fracture stimulation technologies to enhance the deliverability of gas storage wells are as follows: New and improved gas storage well revitalization methods have the potential to save industry on the order of $20-25 million per year by mitigating deliverability decline and reducing the need for costly infill wells Fracturing technologies have the potential to fill this role, however operators have historically been reluctant to utilize this approach due to concerns with reservoir seal integrity. With advanced treatment design tools and methods, however, this risk can be minimized. Of the three major fracturing classifications, namely hydraulic, pulse and explosive, two are believed to hold potential to gas storage applications (hydraulic and pulse). Five particular fracturing technologies, namely tip-screenout fracturing, fracturing with liquid carbon dioxide, and fracturing with gaseous nitrogen, which are each hydraulic methods, and propellant and nitrogen pulse fracturing, which are both pulse methods, are believed to hold potential for gas storage applications and will possibly be tested as part of this project. Field evidence suggests that, while traditional well remediation methods such as blowing/washing, mechanical cleaning, etc. do improve well deliverability, wells are still left damaged afterwards, suggesting that considerable room for further deliverability enhancement exists. Limited recent trials of hydraulic fracturing imply that this approach does in fact provide superior deliverability results, but further RD&D work is needed to fully evaluate and demonstrate the benefits and safe application of this as well as other fracture stimulation technologies.

  20. Purification of brain D2 dopamine receptor.

    PubMed Central

    Williamson, R A; Worrall, S; Chazot, P L; Strange, P G

    1988-01-01

    D2 dopamine receptors have been extracted from bovine brain using the detergent cholate and purified approximately 20,000-fold by affinity chromatography on haloperidol-sepharose and wheat germ agglutinin-agarose columns. The purified preparation contains D2 dopamine receptors as judged by the pharmacological specificity of [3H]spiperone binding to the purified material. The sp. act. of [3H]spiperone binding in the purified preparation is 2.5 nmol/mg protein. The purified preparation shows a major diffuse band at Mr 95,000 upon SDS-polyacrylamide gel electrophoresis and there is evidence for microheterogeneity either at the protein or glycosylation level. Photoaffinity labelling of D2 dopamine receptors also shows a species of Mr 95,000. The D2 dopamine receptor therefore is a glycoprotein of Mr 95,000. Images PMID:3243275

  1. Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression.

    PubMed

    Schlenker, Evelyn H; Del Rio, Rodrigo; Schultz, Harold D

    2014-03-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age-matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters.

  2. Hypothyroidism Affects D2 Receptor-mediated Breathing without altering D2 Receptor Expression

    PubMed Central

    Schlenker, Evelyn H.; Rio, Rodrigo Del; Schultz, Harold D.

    2015-01-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age- matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters. PMID:24434437

  3. THz spectroscopy of D2H+

    NASA Astrophysics Data System (ADS)

    Yu, S.; Pearson, J. C.; Amano, T.; Matsushima, F.

    2017-01-01

    We extended the measurements of the rotational transitions of D2H+ up to 3 THz by using the JPL frequency multiplier chains and a TuFIR system at Toyama. D2H+ was generated in an extended negative glow discharge cell cooled to liquid nitrogen temperature. We observed five new THz lines. All the available rotational transition frequencies together with the combination differences derived from the three fundamental bands were subject to least square analysis to determine the molecular constants. New THz measurements are definitely useful for better characterization of spectroscopic properties. The improved molecular constants provide better predictions of other unobserved rotational transitions.

  4. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer, or employee of the United States Department of Agriculture shall, on the ground of race, color... program or activity conducted by the United States Department of Agriculture. (b) No person shall...

  5. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee of...

  6. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee of...

  7. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee of...

  8. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee of...

  9. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee of...

  10. Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

    PubMed Central

    Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

    2013-01-01

    Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

  11. Neptune's small dark spot (D2)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This bulls-eye view of Neptune's small dark spot (D2) was obtained by Voyager 2's narrow-angle camera. Banding surrounding the feature indicates unseen strong winds, while structures within the bright spot suggest both active upwelling of clouds and rotation about the center. A rotation rate has not yet been measured, but the V-shaped structure near the right edge of the bright area indicates that the spot rotates clockwise. Unlike the Great Red Spot on Jupiter, which rotates counterclockwise, if the D2 spot on Neptune rotates clockwise, the material will be descending in the dark oval region. The fact that infrared data will yield temperature information about the region above the clouds makes this observation especially valuable. The Voyager Mission is conducted by JPL for NASA's Office of Space Science and Applications.

  12. Shuttle orbiter Ku-band radar/communications system design evaluation. Deliverable test equipment evaluation

    NASA Technical Reports Server (NTRS)

    Maronde, R. G.

    1980-01-01

    The Ku-band test equipment, known as the Deliverable System Test equipment (DSTE), is reviewed and evaluated. The DSTE is semiautomated and computer programs were generated for 14 communication mode tests and 17 radar mode tests. The 31 test modules provide a good cross section of tests with which to exercise the Ku-band system; however, it is very limited when being used to verify Ku-band system performance. More detailed test descriptions are needed, and a major area of concern is the DSTE sell-off procedure which is inadequate.

  13. Shuttle orbiter Ku-band radar/communications system design evaluation. Deliverable test equipment evaluation

    NASA Astrophysics Data System (ADS)

    Maronde, R. G.

    1980-07-01

    The Ku-band test equipment, known as the Deliverable System Test equipment (DSTE), is reviewed and evaluated. The DSTE is semiautomated and computer programs were generated for 14 communication mode tests and 17 radar mode tests. The 31 test modules provide a good cross section of tests with which to exercise the Ku-band system; however, it is very limited when being used to verify Ku-band system performance. More detailed test descriptions are needed, and a major area of concern is the DSTE sell-off procedure which is inadequate.

  14. Time resolved spectroscopic investigation of SiD2 + D2: kinetic study

    NASA Astrophysics Data System (ADS)

    Al-Rubaiey, Najem A.; Walsh, Robin

    2017-03-01

    Silylenes (silanediyls) have made an important impact on organosilicon chemistry even if it is of more recent foundation than carbenes in organic chemistry and much less complete. These species are highly reactive intermediates. They play a central role in the chemical vapour deposition (CVD) of various silicon-containing thin films which have a technological importance in microelectronics as well as in the dry etching processes of silicon wafers. Spectroscopic methods have been developed to observe these species, a necessary pre-requisite to their direct monitoring. In this work, deuterated phenylsilane precursor, PhSiD3 was chosen for SiD2 because its analogue phenylsilane, PhSiH3 proved to be a good precursor for SiH2 and the high quality decay signals observed revealed that SiD2 be readily detected from PhSiD3 and that if other decomposition pathways (e.g. PhSiD + D2) are occurring, they do not effect measurements of the rate constants for SiD2. The absorption spectrum of SiD2 formed from the flash photolysis of a mixture of PhSiD3 and SF6 at 193nm were found in the region 17384-17391 cm-1 with strong band at 17387.07 cm-1. This single rotational line of pQ1 was chosen to monitor SiD2 removal. Time-resolved studies of SiD2 have been carried out to obtain rate constants for its bimolecular reactions with D2. The reactions were studied over the pressure range 5-100 Torr (in SF6 bath gas) at four temperatures in the range 298-498K. Single decay from 10 photolysis laser shots were averaged and found to give reasonable first-order kinetics fits. Second order kinetics were obtained by pressure dependence of the pseudo first order decay constants and substance D2 pressures within experimental error. The reaction was found to be weakly pressure dependent at all temperatures, consistent with a third-body mediated association process. In addition, SiH2+ H2 reaction is approximately ca. 60% faster than SiD2+D2 reaction. Theoretical extrapolations (using Lindemann

  15. Cauchy Conformal Fields in Dimensions {d > 2}

    NASA Astrophysics Data System (ADS)

    Friedan, Daniel; Keller, Christoph A.

    2016-12-01

    Holomorphic fields play an important role in 2d conformal field theory. We generalize them to {d > 2} by introducing the notion of Cauchy conformal fields, which satisfy a first order differential equation such that they are determined everywhere once we know their value on a codimension 1 surface. We classify all the unitary Cauchy fields. By analyzing the mode expansion on the unit sphere, we show that all unitary Cauchy fields are free in the sense that their correlation functions factorize on the 2-point function. We also discuss the possibility of non-unitary Cauchy fields and classify them in d = 3 and 4.

  16. LANL12-RS-107J PYTHON Radiography Analysis Tool (PyRAT). Mid-Year Deliverable Report for FY15

    SciTech Connect

    Temple, Brian Allen; Armstrong, Jerawan Chudoung

    2015-04-14

    This document is a mid-year report on a deliverable for the PYTHON Radiography Analysis Tool (PyRAT) for project LANL12-RS-107J in FY15. The deliverable is deliverable number 2 in the work package and is titled “Add the ability to read in more types of image file formats in PyRAT”. Right now PyRAT can only read in uncompressed TIF files (tiff files). It is planned to expand the file formats that can be read by PyRAT, making it easier to use in more situations. A summary of the file formats added include jpeg, jpg, png and formatted ASCII files.

  17. Cost savings deliverables and criteria for the OST technology decision process

    SciTech Connect

    McCown, A.

    1997-04-01

    This document has been prepared to assist focus area (FA) technical and management teams in understanding the cost savings deliverables associated with a technology system during its research and development (R and D) phases. It discusses the usefulness of cost analysis in the decision-making process, and asserts that the level of confidence and data quality of a cost analysis is proportional to the maturity of the technology system`s development life cycle. Suggestions of specific investment criteria or cost savings metrics that a FA might levy on individual research projects are made but the final form of these elements should be stipulated by the FA management based on their rationale for a successful technology development project. Also, cost savings deliverables for a single FA will be more detailed than those for management of the Office of Science and Technology (OST). For example, OST management may want an analysis of the overall return on investment for each FA, while the FA program manager may want this analysis and the return on investment metrics for each technology research activity the FA supports.

  18. SU-E-T-597: Influence of Smoothing Parameters on Dynamic IMRT Plan Quality and Deliverability.

    PubMed

    Manigandan, D; Sharma, S; Gandhi, A; Subramani, V; Sharma, D; Kumar, P; Julka, P; Rath, G

    2012-06-01

    To study the impact of different smoothing parameters on IMRT plan quality and deliverabilityMethods: Five previously treated patients of carcinoma cervix were chosen. Planning target volume (PTV) and organ at risk (OAR) i.e. bladder and rectum were contoured. In each case, five different dynamic IMRT plans with 6MV photon beam were created in eclipse TPS for Varian 2300C/D linear accelerator. During optimization, dose volume constraints and priorities were kept constant and smoothing parameters were varied as follows: 10/5, 40/30 (TPS default value), 80/60, 100/80 and 200/150 in x/y direction. Total dose was 5040cGy in 28 fractions and prescribed at 95% isodose. Plan quality was analyzed by means of coverage index (CI=PTV covered by prescription dose/PTV), OAR mean doses and total monitor units (MUs) required to deliver a plan. In each case, deliverability of treatment plans were verified with I'matriXX ion-chamber array and compared with TPS dose-plane using gamma index of 3% dose difference and 3mm distance to agreement criteria. The CI values were 0.9435±0.032, 0.9418±0.034, 0.9380±0.041, 0.9330±0.047 and 0.8681±0.072 for 10/5, 40/30, 80/60, 100/80 and 200/150 in x/y direction. PTV dose maximum decreases with the increase of smoothing parameters and values were 5724.38±106.08 5723.30±131.60, 5708.44±1 16.74, 5697.92±116.82 and 5587.50±189.50cGy. The bladder mean doses were 4027.46±630.40, 3821.62±420.62, 3819.58±427.08, 3813.42±435.02 and 3814.78±438.0cGy. Rectum mean doses were 3839.88±466.02, 3835.52±473.18, 3837.52±472.88, 3839.10±471.20 and 3918.94±469.76cGy. Similarly, Total MUs were 1588±205, 1573±214, 1513±274, 1456±335 and 1219±68. Gamma pass rate increases with the increase of smoothing parameters and values were 99.16±0.21%, 99.07±0.19%, 99.24±0.28%, 99.29±0.29% and 99.75±0.15%. When smoothing parameters decreased below TPS default value, plan quality increases, but deliverability decreases. If smoothing parameters

  19. Thz Spectroscopy of D_2H^+

    NASA Astrophysics Data System (ADS)

    Yu, Shanshan; Pearson, John; Amano, Takayoshi

    2015-06-01

    Pure rotational transitions of D_2H^+ observed by high-resolution spectroscopy have been limited so far to the J = 110-101 transition at 691.7 GHz, J=220-211 at 1.370 THz, and J=111-000 at 1.477 THz. As this ion is a light asymmetric-top molecule, spectroscopic characterization and prediction of other rotational transition frequencies are not straightforward. In this presentation, we extended the measurements up to 2 THz by using the JPL frequency multiplier chains, and observed three new THz lines and re-measured the three known transitions. D_2H^+ was generated in an extended negative glow discharge cell cooled to liquid nitrogen temperature. Six rotational transition frequencies together with the combination differences derived from three fundamental bands were subject to least square analysis to determine the molecular constants. New THz measurements are definitely useful for better characterization of spectroscopic properties. The improved molecular constants provide better predictions of other unobserved rotational transitions. T. Hirao and T. Amano, Ap. J.,597, L85 (2003) K. M. Evenson et al cited by O. L. Polyansky and A. R. W. McKellar, J. Chem. Phys., 92, 4039 (1990) O. Asvany et al, Phys. Rev. Lett., 100, 233004 (2008)

  20. Assessment Report Sandia National Laboratories Fuel Cycle Technologies Quality Assurance Evaluation of FY15 SNL FCT M2 Milestone Deliverables

    SciTech Connect

    Appel, Gordon John

    2016-05-01

    Sandia National Laboratories (SNL) Fuel Cycle Technologies (FCT) program activities are conducted in accordance with FCT Quality Assurance Program Document (FCT-QAPD) requirements. The FCT-QAPD interfaces with SNL approved Quality Assurance Program Description (SNL-QAPD) as explained in the Sandia National Laboratories QA Program Interface Document for FCT Activities (Interface Document). This plan describes SNL's FY16 assessment of SNL's FY15 FCT M2 milestone deliverable's compliance with program QA requirements, including SNL R&A requirements. The assessment is intended to confirm that SNL's FY15 milestone deliverables contain the appropriate authenticated review documentation and that there is a copy marked with SNL R&A numbers.

  1. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical...

  2. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical...

  3. Binding Interactions of Dopamine and Apomorphine in D2High and D2Low States of Human Dopamine D2 Receptor Using Computational and Experimental Techniques.

    PubMed

    Durdagi, Serdar; Salmas, Ramin Ekhteiari; Stein, Matthias; Yurtsever, Mine; Seeman, Philip

    2016-02-17

    We have recently reported G-protein coupled receptor (GPCR) model structures for the active and inactive states of the human dopamine D2 receptor (D2R) using adrenergic crystal structures as templates. Since the therapeutic concentrations of dopamine agonists that suppress the release of prolactin are the same as those that act at the high-affinity state of the D2 receptor (D2High), D2High in the anterior pituitary gland is considered to be the functional state of the receptor. In addition, the therapeutic concentrations of anti-Parkinson drugs are also related to the dissociation constants in the D2High form of the receptor. The discrimination between the high- and low-affinity (D2Low) components of the D2R is not obvious and requires advanced computer-assisted structural biology investigations. Therefore, in this work, the derived D2High and D2Low receptor models (GPCR monomer and dimer three-dimensional structures) are used as drug-binding targets to investigate binding interactions of dopamine and apomorphine. The study reveals a match between the experimental dissociation constants of dopamine and apomorphine at their high- and low-affinity sites of the D2 receptor in monomer and dimer and their calculated dissociation constants. The allosteric receptor-receptor interaction for dopamine D2R dimer is associated with the accessibility of adjacent residues of transmembrane region 4. The measured negative cooperativity between agonist ligand at dopamine D2 receptor is also correctly predicted using the D2R homodimerization model.

  4. A Quantitative Study into the Information Technology Project Portfolio Practice: The Impact on Information Technology Project Deliverables

    ERIC Educational Resources Information Center

    Yu, Wei

    2013-01-01

    This dissertation applied the quantitative approach to the data gathered from online survey questionnaires regarding the three objects: Information Technology (IT) Portfolio Management, IT-Business Alignment, and IT Project Deliverables. By studying this data, this dissertation uncovered the underlying relationships that exist between the…

  5. A Quantitative Study into the Information Technology Project Portfolio Practice: The Impact on Information Technology Project Deliverables

    ERIC Educational Resources Information Center

    Yu, Wei

    2013-01-01

    This dissertation applied the quantitative approach to the data gathered from online survey questionnaires regarding the three objects: Information Technology (IT) Portfolio Management, IT-Business Alignment, and IT Project Deliverables. By studying this data, this dissertation uncovered the underlying relationships that exist between the…

  6. From Field Work to Deliverables. Experiences on the Tin House Courtyard Documentation

    NASA Astrophysics Data System (ADS)

    Bello Caballero, L.; Mezzino, D.; Federman, A.; Santana Quintero, M.

    2017-08-01

    The Tin House Courtyard is a property of the National Capital Commission (NCC) in Ottawa, Canada. The site is located within the `Mile of History', a historical route running from Parliament Hill to the Governor General's residence. Currently, existing assets are under intervention works that include several preservation and renewal actions. Within the broader project, one of the tasks before construction works started was the documentation of the set of facades. The Carleton Immersive Media Studio (CIMS) at Carleton University in Ottawa was commissioned by NCC to conduct the recording of the area. This paper describes the process undertaken from field work to the final deliverable to the client, as well as the issues faced in between. Nowadays, up to date surveying technologies have revolutionized the methodologies for cultural heritage documentation. In this regard, the recording strategy employed encompassed the use of photogrammetry, laser scanner, total station, as well as different pre and post processing software in order to generate the desired outcomes.

  7. Weighted linear regression using D2H and D2 as the independent variables

    Treesearch

    Hans T. Schreuder; Michael S. Williams

    1998-01-01

    Several error structures for weighted regression equations used for predicting volume were examined for 2 large data sets of felled and standing loblolly pine trees (Pinus taeda L.). The generally accepted model with variance of error proportional to the value of the covariate squared ( D2H = diameter squared times height or D...

  8. Predicting deliverability of volumetric-modulated arc therapy (VMAT) plans using aperture complexity analysis.

    PubMed

    Younge, Kelly C; Roberts, Don; Janes, Lindsay A; Anderson, Carlos; Moran, Jean M; Matuszak, Martha M

    2016-07-08

    The purpose of this study was to evaluate the ability of an aperture complexity metric for volumetric-modulated arc therapy (VMAT) plans to predict plan delivery accuracy. We developed a complexity analysis tool as a plug-in script to Varian's Eclipse treatment planning system. This script reports the modulation of plans, arcs, and individual control points for VMAT plans using a previously developed complexity metric. The calculated complexities are compared to that of 649 VMAT plans previously treated at our institution from 2013 to mid-2015. We used the VMAT quality assurance (QA) results from the 649 treated plans, plus 62 plans that failed pretreatment QA, to validate the ability of the complexity metric to predict plan deliverability. We used a receiver operating characteristic (ROC) analysis to determine an appropriate complexity threshold value above which a plan should be considered for reoptimization before it moves further through our planning workflow. The average complexity metric for the 649 treated plans analyzed with the script was 0.132 mm-1 with a standard deviation of 0.036 mm-1. We found that when using a threshold complexity value of 0.180 mm-1, the true positive rate for correctly identifying plans that failed QA was 44%, and the false-positive rate was 7%. Used clinically with this threshold, the script can identify overly modulated plans and thus prevent a significant portion of QA failures. Reducing VMAT plan complexity has a number of important clinical benefits, including improving plan deliverability and reducing treatment time. Use of the complexity metric during both the planning and QA processes can reduce the number of QA failures and improve the quality of VMAT plans used for treatment. © 2016 The Authors

  9. Improving the driving practices of pizza deliverers: Response generalization and moderating effects of driving history

    PubMed Central

    Ludwig, Timothy D.; Geller, E. Scott

    1991-01-01

    A practical intervention program, targeting the safety belt use of pizza deliverers at two stores, increased significantly the use of both safety belts (143% above baseline) and turn signals (25% above baseline). Control subjects (i.e., pizza deliverers at a third no-intervention store and patrons driving to the pizza stores) showed no changes in belt or turn signal use over the course of 7-month study. The intervention program was staggered across two pizza stores and consisted of a group meeting wherein employees discussed the value of safety belts, received feedback regarding their low safety belt use, offered suggestions for increasing their belt use, and made a personal commitment to buckle up by signing buckle-up promise cards. Subsequently, employee-designed buckle-up reminder signs were placed in the pizza stores. By linking license plate numbers to individual driving records, we examined certain aspects of driving history as moderators of pre- and postintervention belt use. Although baseline belt use was significantly lower for drivers with one or more driving demerits or accidents in the previous 5 years, after the intervention these risk groups increased their belt use significantly and at the same rate as drivers with no demerits or accidents. Whereas baseline belt use was similar for younger (under 25) and older (25 or older) drivers, younger drivers were markedly more influenced by the intervention than were older drivers. Individual variation in belt use during baseline, intervention, and follow-up phases indicated that some drivers require more effective and costly intervention programs to motivate their safe driving practices. PMID:16795743

  10. Improving the driving practices of pizza deliverers: Response generalization and moderating effects of driving history.

    PubMed

    Ludwig, T D; Geller, E S

    1991-01-01

    A practical intervention program, targeting the safety belt use of pizza deliverers at two stores, increased significantly the use of both safety belts (143% above baseline) and turn signals (25% above baseline). Control subjects (i.e., pizza deliverers at a third no-intervention store and patrons driving to the pizza stores) showed no changes in belt or turn signal use over the course of 7-month study. The intervention program was staggered across two pizza stores and consisted of a group meeting wherein employees discussed the value of safety belts, received feedback regarding their low safety belt use, offered suggestions for increasing their belt use, and made a personal commitment to buckle up by signing buckle-up promise cards. Subsequently, employee-designed buckle-up reminder signs were placed in the pizza stores. By linking license plate numbers to individual driving records, we examined certain aspects of driving history as moderators of pre- and postintervention belt use. Although baseline belt use was significantly lower for drivers with one or more driving demerits or accidents in the previous 5 years, after the intervention these risk groups increased their belt use significantly and at the same rate as drivers with no demerits or accidents. Whereas baseline belt use was similar for younger (under 25) and older (25 or older) drivers, younger drivers were markedly more influenced by the intervention than were older drivers. Individual variation in belt use during baseline, intervention, and follow-up phases indicated that some drivers require more effective and costly intervention programs to motivate their safe driving practices.

  11. Genetic algorithm based deliverable segments optimization for static intensity-modulated radiotherapy.

    PubMed

    Li, Yongjie; Yao, Jonathan; Yao, Dezhong

    2003-10-21

    The static delivery technique (also called step-and-shoot technique) has been widely used in intensity-modulated radiotherapy (IMRT) because of the simple delivery and easy quality assurance. Conventional static IMRT consists of two steps: first to calculate the intensity-modulated beam profiles using an inverse planning algorithm, and then to translate these profiles into a series of uniform segments using a leaf-sequencing tool. In order to simplify the procedure and shorten the treatment time of the static mode, an efficient technique, called genetic algorithm based deliverable segments optimization (GADSO), is developed in our work, which combines these two steps into one. Taking the pre-defined beams and the total number of segments per treatment as input, the number of segments for each beam, the segment shapes and weights are determined automatically. A group of interim modulated beam profiles quickly calculated using a conjugate gradient (CG) method are used to determine the segment number for each beam and to initialize segment shapes. A modified genetic algorithm based on a two-dimensional binary coding scheme is used to optimize the segment shapes, and a CG method is used to optimize the segment weights. The physical characters of a multileaf collimator, such as the leaves interdigitation limitation and leaves maximum over-travel distance, are incorporated into the optimization. The algorithm is applied to some examples and the results demonstrate that GADSO is able to produce highly conformal dose distributions using 20-30 deliverable segments per treatment within a clinically acceptable computation time.

  12. Predicting deliverability of volumetric-modulated arc therapy (VMAT) plans using aperture complexity analysis.

    PubMed

    Younge, Kelly C; Roberts, Don; Janes, Lindsay A; Anderson, Carlos; Moran, Jean M; Matuszak, Martha M

    2016-07-01

    The purpose of this study was to evaluate the ability of an aperture complexity metric for volumetric-modulated arc therapy (VMAT) plans to predict plan delivery accuracy. We developed a complexity analysis tool as a plug-in script to Varian's Eclipse treatment planning system. This script reports the modulation of plans, arcs, and individual control points for VMAT plans using a previously developed complexity metric. The calculated complexities are compared to that of 649 VMAT plans previously treated at our institution from 2013 to mid-2015. We used the VMAT quality assurance (QA) results from the 649 treated plans, plus 62 plans that failed pretreatment QA, to validate the ability of the complexity metric to predict plan deliverability. We used a receiver operating characteristic (ROC) analysis to determine an appropriate complexity threshold value above which a plan should be considered for reoptimization before it moves further through our planning workflow. The average complexity metric for the 649 treated plans analyzed with the script was 0.132 mm-1 with a standard deviation of 0.036 mm-1. We found that when using a threshold complexity value of 0.180 mm-1, the true positive rate for correctly identifying plans that failed QA was 44%, and the false-positive rate was 7%. Used clinically with this threshold, the script can identify overly modulated plans and thus prevent a significant portion of QA failures. Reducing VMAT plan complexity has a number of important clinical benefits, including improving plan deliverability and reducing treatment time. Use of the complexity metric during both the planning and QA processes can reduce the number of QA failures and improve the quality of VMAT plans used for treatment. PACS number(s): 87.55.de, 87.55.Qr, 87.56.jk. © 2016 The Authors.

  13. Incorporating deliverable monitor unit constraints into spot intensity optimization in intensity-modulated proton therapy treatment planning

    NASA Astrophysics Data System (ADS)

    Cao, Wenhua; Lim, Gino; Li, Xiaoqiang; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

    2013-08-01

    The purpose of this study is to investigate the feasibility and impact of incorporating deliverable monitor unit (MU) constraints into spot intensity optimization (SIO) in intensity-modulated proton therapy (IMPT) treatment planning. The current treatment planning system (TPS) for IMPT disregards deliverable MU constraints in the SIO routine. It performs a post-processing procedure on an optimized plan to enforce deliverable MU values that are required by the spot scanning proton delivery system. This procedure can create a significant dose distribution deviation between the optimized and post-processed deliverable plans, especially when small spot spacings are used. In this study, we introduce a two-stage linear programming approach to optimize spot intensities and constrain deliverable MU values simultaneously, i.e., a deliverable SIO (DSIO) model. Thus, the post-processing procedure is eliminated and the associated optimized plan deterioration can be avoided. Four prostate cancer cases at our institution were selected for study and two parallel opposed beam angles were planned for all cases. A quadratic programming based model without MU constraints, i.e., a conventional SIO (CSIO) model, was also implemented to emulate commercial TPS. Plans optimized by both the DSIO and CSIO models were evaluated for five different settings of spot spacing from 3 to 7 mm. For all spot spacings, the DSIO-optimized plans yielded better uniformity for the target dose coverage and critical structure sparing than did the CSIO-optimized plans. With reduced spot spacings, more significant improvements in target dose uniformity and critical structure sparing were observed in the DSIO than in the CSIO-optimized plans. Additionally, better sparing of the rectum and bladder was achieved when reduced spacings were used for the DSIO-optimized plans. The proposed DSIO approach ensures the deliverability of optimized IMPT plans that take into account MU constraints. This eliminates the post

  14. D2 to M2 procedure for D2-brane DBI effective action

    NASA Astrophysics Data System (ADS)

    Klusoň, J.

    2009-02-01

    We apply the procedure that was suggested in [B. Ezhuthachan, S. Mukhi, C. Papageorgakis, arxiv:/0806.1639] to the case of abelian D2-brane Dirac-Born-Infeld effective action and discuss its limitation. Then we suggest an alternative form of this procedure that is based on an existence of interpolating action proposed in [T. Ortin, hep-th/9707113, Y. Lozano, hep-th/9707011].

  15. 21 CFR 172.381 - Vitamin D2 bakers yeast.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin D2 bakers yeast. 172.381 Section 172.381... CONSUMPTION Special Dietary and Nutritional Additives § 172.381 Vitamin D2 bakers yeast. Vitamin D2 bakers yeast may be used safely in foods as a source of vitamin D2 and as a leavening agent in accordance with...

  16. 21 CFR 172.381 - Vitamin D2 bakers yeast.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin D2 bakers yeast. 172.381 Section 172.381... Additives § 172.381 Vitamin D2 bakers yeast. Vitamin D2 bakers yeast may be used safely in foods as a source...) Vitamin D2 bakers yeast is the substance produced by exposing bakers yeast (Saccharomyces cerevisiae) to...

  17. 26 CFR 1.1503(d)-2 - Domestic use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Domestic use. 1.1503(d)-2 Section 1.1503(d)-2...) INCOME TAXES Administrative Provisions and Other Rules § 1.1503(d)-2 Domestic use. A domestic use of a... offset, directly or indirectly, the income of a domestic affiliate (other than the dual...

  18. 26 CFR 1.1503(d)-2 - Domestic use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 12 2011-04-01 2011-04-01 false Domestic use. 1.1503(d)-2 Section 1.1503(d)-2...) INCOME TAXES (CONTINUED) Administrative Provisions and Other Rules § 1.1503(d)-2 Domestic use. A domestic... available to offset, directly or indirectly, the income of a domestic affiliate (other than the...

  19. 26 CFR 1.337(d)-2 - Loss limitation rules.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 4 2014-04-01 2014-04-01 false Loss limitation rules. 1.337(d)-2 Section 1.337(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Effects on Corporation § 1.337(d)-2 Loss limitation rules. (a) Loss...

  20. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is generally...

  1. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  2. 21 CFR 582.5950 - Vitamin D 2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin D 2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D 2. (a) Product. Vitamin D2. (b) Conditions of use. This substance...

  3. 21 CFR 582.5950 - Vitamin D 2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin D 2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D 2. (a) Product. Vitamin D2. (b) Conditions of use. This substance...

  4. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  5. TU-C-17A-06: Evaluating IMRT Plan Deliverability Via PTV Shape and MLC Motion

    SciTech Connect

    McGurk, R; Smith, VA; Price, M

    2014-06-15

    Purpose: For step-and-shoot intensity-modulated radiation therapy (IMRT) plans, the dosimetry and deliverability can be affected by the number and shape of the segments used. Thus, plan deliverability is likely related to target volume and shape. We investigated whether the sphericity of target volumes and the previously proposed Modulation Complexity Score (MCS) could be used together to improve the detection of IMRT fields that failed quality assurance (QA). Methods: 526 and 353 IMRT fields from 32 prostate and 28 head-and-neck (H'N) patients, respectively, were analyzed. MCS was used to quantify the complexity of multi-leaf collimator shapes and motion patterns for each field. Sphericity was calculated using the surface area and volume of each patient’s planning target volume (PTV). Logistic regression models with MCS-alone or MCS and sphericity terms were fit to PlanUNC IMRT pass/fail results (5% dose difference, 4mm distance-to-agreement criteria) using SAS 9.3 (Cary, NC). Model concordance, discordance and area under the curve (AUC) were used to quantify model accuracy. Results: Mean (±1 standard deviation) MCS for prostate and H'N were 0.58(±0.15) and 0.40 (±0.14), respectively. Mean sphericity scores were 0.75(±0.05) for prostate and 0.63 (±0.12) for H'N. Both metrics were significantly different between treatment locations (p<0.01, Wilcoxon Rank Sum Test) indicating greater complexity in shape and variations for H'N PTVs. For prostate, concordance, discordance and AUC using MCS alone were 80.8%, 18.7% and 0.811. Including sphericity in the model improved these to 81.7%, 17.7% and 0.820. For H'N, the original concordance, discordance and AUC were of 72.9%, 26.9% and 0.729. Including sphericity into the model improved these metrics to 76.5%, 23.2% and 0.729. Conclusion: Sphericity provides a quantitative measure of PTV shape. While improvement in IMRT QA failure detection was modest for both prostate and H'N plans, including sphericity in the model

  6. Dopamine agonist radioligand binds to both D2High and D2Low receptors, explaining why alterations in D2High are not detected in human brain scans.

    PubMed

    Seeman, Philip

    2012-01-01

    The features of schizophrenia are consistent with increased sensitivity to endogenous dopamine. Animal models of schizophrenia reveal an increase in the in vitro proportion of striatal dopamine D2 receptors in the high-affinity state for dopamine (i.e., D2High), as measured by dopamine/[(3) H]domperidone competition. However, in vivo studies did not reveal the dopamine agonist [(11) C](+)PHNO to be elevated in amphetamine-sensitized rats. Also, no increase was found in the in vivo binding of [(11) C](+)PHNO in schizophrenia patients. This work was done to resolve the contradictory findings. It was found that the in vitro density of rat striatal D2 receptors was 18 pmol/g for [(3) H]raclopride and 12 pmol/g for [(3) H](+)PHNO; most of the latter sites disappeared in the presence of guanine nucleotide. Using 2 nM [(3) H](+)PHNO (K(d) of 0.72 nM at D2) to label D2 receptors in the striata and the human D2 clone, 10 nM to 100 nM dopamine inhibited 10-20% of the [(3) H](+)PHNO bound, representing high-affinity binding of [(3) H](+)PHNO, with the remainder inhibited above 100 nM dopamine, representing low-affinity binding of [(3) H](+)PHNO. It was found that (+)PHNO and (-)NPA dissociated from the D2 clone with half-times of 96 and 600 s, respectively. These rates are slower than the reported sub-second dissociation of the G protein from a receptor, suggesting that these two ligands still occupy the D2Low receptor after the G protein has separated. Thus, the radio-agonist label for (+)PHNO is not selective for dopamine D2High receptors, but also binds to the D2Low state of the dopamine receptor. Copyright © 2011 Wiley Periodicals, Inc.

  7. Dynamic quantum molecular sieving separation of D2 from H2-D2 mixture with nanoporous materials.

    PubMed

    Niimura, Subaru; Fujimori, Toshihiko; Minami, Daiki; Hattori, Yoshiyuki; Abrams, Lloyd; Corbin, Dave; Hata, Kenji; Kaneko, Katsumi

    2012-11-14

    Quantum molecular sieving separability of D(2) from an H(2)-D(2) mixture was measured at 77 K for activated carbon fiber, carbon molecular sieve, zeolite and single wall carbon nanotube using a flow method. The amount of adsorbed D(2) was evidently larger than H(2) for all samples. The maximum adsorption ratio difference between D(2) and H(2) was 40% for zeolite (MS13X), yielding a selectivity for D(2) with respect to H(2) of 3.05.

  8. Tuning ethylene gas adsorption via metal node modulation: Cu-MOF-74 for a high ethylene deliverable capacity.

    PubMed

    Liao, Yijun; Zhang, Lin; Weston, Mitchell H; Morris, William; Hupp, Joseph T; Farha, Omar K

    2017-08-17

    M-MOF-74s were examined for potential applications in ethylene abatement and/or storage/delivery. Due to labile binding resulting from a Jahn-Teller distortion, Cu-MOF-74 exhibits a gradual initial uptake that, in turn, translates into the highest deliverable capacity among the MOFs examined (3.6 mmol g(-1)). In contrast, Co-MOF-74 is the most promising candidate for ethylene abatement due to the sharp uptake at low pressure.

  9. Record of principal work activities/deliverables. Final technical report, September 28, 1984--September 27, 1989

    SciTech Connect

    Not Available

    1989-09-01

    Over the five year period of performance, thirteen task assignments were issued by the DOE to ARINC Research. During the two year base period seven tasks were assigned. Two task assignments were issued for each of the three consecutive one year option periods. Associated with all task assignments were multiple subtasks, some of which required significant effort. These subtasks are appropriately cited in this report under their respective task assignments as principal work activities or deliverables. The technical and management support provided to the DOE under this contract focused on two general areas: (1) appraisal activities and (2) non-appraisal activities. Support to appraisals included planning, document review, developing lines-of-inquiry, interviewing, data collection, report writing, and follow-up. Such work was executed both on-site at the DOE facility under review and off-site. Non-appraisal support was varied and included such areas as document review, data base development, technical assessments. statistical analysis, policy analysis, reliability engineering, and workshop and conference planning and execution.

  10. Silver deposited carboxymethyl chitosan-grafted magnetic nanoparticles as dual action deliverable antimicrobial materials.

    PubMed

    Vo, Duc-Thang; Sabrina, Sabrina; Lee, Cheng-Kang

    2017-04-01

    Carboxymethyl chitosan (CMCS) was known to have a much better antimicrobial activity than chitosan due to the increased cationic -NH3(+) groups resulted from the intra- and intermolecular interactions between the carboxyl and amino groups. CMCS was grafted onto the surface of silica coated magnetic nanoparticles (MNPs) to obtain magnetically retrievable and deliverable antimicrobial nanoparticles (MNPs@CMCS). The presence of carboxylate groups in CMCS not only enhanced antimicrobial activity but also enabled Ag ions chelating ability to induce the in situ formation of Ag nanoparticles (AgNPs). The deposition of AgNPs on the surface of MNPs@CMCS could significantly increase its antimicrobial activity against planktonic cells due to the dual action of CMCS and AgNPs. Due to its high magnetism, the as-prepared MNPs@CMCS-Ag could be efficiently delivered into an existing biofilm under the guidance of an applied magnetic field. Without direct contact, the Ag ions and/or radical oxygen species (ROS) released from the deposited Ag nanoparticles could effectively kill the bacteria embedded in the extracellular polymeric substances (EPS) matrix of biofilm.

  11. Interactions of D2O with methane and fluoromethane surfaces.

    PubMed

    Souda, R; Kawanowa, H; Kondo, M; Gotoh, Y

    2004-03-22

    TOF-SIMS is used to investigate the interactions between D2O and hydrophobic molecules, such as CH4, CH3F, CH2F2, CHF3, and CF4, at cryogenic temperatures (15 K). By irradiation with a 1.5-keV He+ beam, the D(+)(D2O)n ions are ejected efficiently from the D2O nanoclusters physisorbed on the CF4 layer due to Coulomb explosion: the ion yields are by about two orders of magnitude higher than those from a thick D2O layer via the kinetic sputtering. The D(+)(D2O)n yields decrease on the CHnF(4-n) layer with increasing the number of the C-H group. This is because the Coulombic fission is quenched due to the delocalization of valence holes through the C-H...H-C and C-H...D2O contacts. A pure D2O film is hardly grown on the CH4 layer as a consequence of intermixing whereas the D2O molecules basically adsorb on the surfaces of fluoromethanes, suggesting the attractive (water-repellent) interactions in the C-H...D2O (C-F...D2O) contacts. The C-H...O bond behaves like a conventional O-H...O hydrogen bond as far as the collision-induced proton transfer reaction is concerned.

  12. Case study: Hydraulic fracturing with cross-linked gels in the Oriskany formation to improve gas storage deliverability

    SciTech Connect

    Stiles, E.K.; Reese, R.R.

    1995-12-31

    During the summer and fall of 1994, CNG Transmission Corporation fracture-stimulated thirty (30) gas storage wells with a cross-linked gel fluid system. The work was done to increase late season field deliverability. Individual well tests taken to date have shown that, on average, per-well deliverability has increased by a factor of five. The text that follows will detail the engineering and geologic aspects, procedures, results, and analysis of the project. A discussion of the strategic placement of the storage fields involved will be presented, along with a review of FERC Order 636 and it`s impact on the current gas storage business mechanics. Overviews are presented on the geology, reservoir properties, and characteristics of the storage fields involved in the project. General well design and well completion configuration are discussed. Fracturing/refracturing candidate selection criteria are presented. Basic fracturing design criteria are discussed including: fluid parameters, geometry, proppant selection, and concentration. Discussions of observations and minor changes in treatment designs which occurred between the different fields are discussed. The treatments are summarized and compared on a pre and post fracturing deliverability test analysis. Explanations are offered for wells with exceptional results, as well as marginally successful treatments.

  13. Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

    PubMed Central

    Calipari, Erin S; Sun, Haiguo; Eldeeb, Khalil; Luessen, Deborah J; Feng, Xin; Howlett, Allyn C; Jones, Sara R; Chen, Rong

    2014-01-01

    Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [35S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction. PMID:24513972

  14. Amphetamine self-administration attenuates dopamine D2 autoreceptor function.

    PubMed

    Calipari, Erin S; Sun, Haiguo; Eldeeb, Khalil; Luessen, Deborah J; Feng, Xin; Howlett, Allyn C; Jones, Sara R; Chen, Rong

    2014-07-01

    Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [(35)S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction.

  15. Energy Efficiency of D2D Multi-User Cooperation.

    PubMed

    Zhang, Zufan; Wang, Lu; Zhang, Jie

    2017-03-28

    The Device-to-Device (D2D) communication system is an important part of heterogeneous networks. It has great potential to improve spectrum efficiency, throughput and energy efficiency cooperation of multiple D2D users with the advantage of direct communication. When cooperating, D2D users expend extraordinary energy to relay data to other D2D users. Hence, the remaining energy of D2D users determines the life of the system. This paper proposes a cooperation scheme for multiple D2D users who reuse the orthogonal spectrum and are interested in the same data by aiming to solve the energy problem of D2D users. Considering both energy availability and the Signal to Noise Ratio (SNR) of each D2D user, the Kuhn-Munkres algorithm is introduced in the cooperation scheme to solve relay selection problems. Thus, the cooperation issue is transformed into a maximum weighted matching (MWM) problem. In order to enhance energy efficiency without the deterioration of Quality of Service (QoS), the link outage probability is derived according to the Shannon Equation by considering the data rate and delay. The simulation studies the relationships among the number of cooperative users, the length of shared data, the number of data packets and energy efficiency.

  16. 26 CFR 1.1092(d)-2 - Personal property.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Personal property. 1.1092(d)-2 Section 1.1092(d... (CONTINUED) INCOME TAXES Wash Sales of Stock Or Securities § 1.1092(d)-2 Personal property. (a) Special rules for stock. Under section 1092(d)(3)(B), personal property includes any stock that is part of a...

  17. 26 CFR 1.1092(d)-2 - Personal property.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Personal property. 1.1092(d)-2 Section 1.1092(d... (CONTINUED) INCOME TAXES (CONTINUED) Wash Sales of Stock Or Securities § 1.1092(d)-2 Personal property. (a) Special rules for stock. Under section 1092(d)(3)(B), personal property includes any stock that is part of...

  18. Energy Efficiency of D2D Multi-User Cooperation

    PubMed Central

    Zhang, Zufan; Wang, Lu; Zhang, Jie

    2017-01-01

    The Device-to-Device (D2D) communication system is an important part of heterogeneous networks. It has great potential to improve spectrum efficiency, throughput and energy efficiency cooperation of multiple D2D users with the advantage of direct communication. When cooperating, D2D users expend extraordinary energy to relay data to other D2D users. Hence, the remaining energy of D2D users determines the life of the system. This paper proposes a cooperation scheme for multiple D2D users who reuse the orthogonal spectrum and are interested in the same data by aiming to solve the energy problem of D2D users. Considering both energy availability and the Signal to Noise Ratio (SNR) of each D2D user, the Kuhn-Munkres algorithm is introduced in the cooperation scheme to solve relay selection problems. Thus, the cooperation issue is transformed into a maximum weighted matching (MWM) problem. In order to enhance energy efficiency without the deterioration of Quality of Service (QoS), the link outage probability is derived according to the Shannon Equation by considering the data rate and delay. The simulation studies the relationships among the number of cooperative users, the length of shared data, the number of data packets and energy efficiency. PMID:28350374

  19. Learning Curve for D2 Lymphadenectomy in Gastric Cancer

    PubMed Central

    Rebasa, Pere; Montmany, Sandra; Navarro, Salvador

    2013-01-01

    Background. D2 lymphadenectomy is a demanding technique which is associated with high morbidity in the West. We report our experience with D2 lymphadenectomy after a training period in Japan. Methods. Prospective, descriptive study in 133 consecutive patients undergoing radical gastrectomy for gastric adenocarcinoma from 2005 to 2011. We analysed the number of lymph nodes removed, observed morbidity/mortality compared with the predictions of POSSUM and O-POSSUM, survival, and disease-free interval for patients with D1 and D2 lymphadenectomy. Results. The morbidity rate in patients with D1 lymphadenectomy was 59.4%. For D2 it was 47.7%. The mortality rate in patients with D1 was 6.7%. In the D2 group it was 6.8%. Median survival was 42.9 months in D1 and 55 months in D2. The disease-free interval was 49 months for D1 and 58 months for D2. Conclusion. The learning curve for D2 lymphadenectomy presents acceptable rates of morbidity and mortality, providing that the technique is learnt at a center with extensive experience. PMID:23844296

  20. Hydrogen bonding induced proton exchange reactions in dense D2-NH3 and D2-CH4 mixtures.

    PubMed

    Borstad, Gustav M; Yoo, Choong-Shik

    2014-01-28

    We have investigated high-pressure behaviors of simple binary mixtures of NH3 and D2 to 50 GPa and CH4 and D2 to 30 GPa using confocal micro-Raman spectroscopy. The spectral data indicate strong proton exchange reactions occur in dense D2-NH3 mixture, producing different isotopes of ammonia such as NH3, NH2D, NHD2, and ND3. In contrast, the proton exchange process in dense D2-CH4 mixture is highly limited, and no vibration feature is apparent for deuterated methane. The vibrational modes of H2 isotopes in D2-NH3 are blue shifted from those of pure H2 isotopes, whereas the modes of D2-CH4 show overall agreement with those in pure D2 and CH4. In turn, this result advocates the presence of strong repulsion and thereby internal pressure in D2-NH3 mixture, which are absent in D2-CH4. In fact, the bond length of hydrogen molecules in D2-NH3, calculated from the present spectral data, is shorter than that observed in pure hydrogen - supporting the enhanced intermolecular interaction in the mixture. Comparing the present spectral results with those previously observed in D2-H2O mixtures further suggests that the strength of repulsive interaction or the magnitude of internal pressure in the mixtures is proportional to the strength of hydrogen bonding in H2O, NH3, and CH4 in decreasing order. Hence, we suggest that the proton exchange is assisted by hydrogen bonding in these molecules.

  1. D2-40/podoplanin expression in the human placenta.

    PubMed

    Wang, Y; Sun, J; Gu, Y; Zhao, S; Groome, L J; Alexander, J S

    2011-01-01

    Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placenta, and how it is altered developmentally and pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin was determined by Western blot in placentas from normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Extrastriatal dopamine D2-receptor availability in social anxiety disorder.

    PubMed

    Plavén-Sigray, Pontus; Hedman, Erik; Victorsson, Pauliina; Matheson, Granville J; Forsberg, Anton; Djurfeldt, Diana R; Rück, Christian; Halldin, Christer; Lindefors, Nils; Cervenka, Simon

    2017-05-01

    Alterations in the dopamine system are hypothesized to influence the expression of social anxiety disorder (SAD) symptoms. However, molecular imaging studies comparing dopamine function between patients and control subjects have yielded conflicting results. Importantly, while all previous investigations focused on the striatum, findings from activation and blood flow studies indicate that prefrontal and limbic brain regions have a central role in the pathophysiology. The objective of this study was to investigate extrastriatal dopamine D2-receptor (D2-R) availability in SAD. We examined 12 SAD patients and 16 healthy controls using positron emission tomography and the high-affinity D2-R radioligand [(11)C]FLB457. Parametric images of D2-R binding potential were derived using the Logan graphical method with cerebellum as reference region. Two-tailed one-way independent ANCOVAs, with age as covariate, were used to examine differences in D2-R availability between groups using both region-based and voxel-wise analyses. The region-based analysis showed a medium effect size of higher D2-R levels in the orbitofrontal cortex (OFC) in patients, although this result did not remain significant after correction for multiple comparisons. The voxel-wise comparison revealed elevated D2-R availability in patients within OFC and right dorsolateral prefrontal cortex after correction for multiple comparisons. These preliminary results suggest that an aberrant extrastriatal dopamine system may be part of the disease mechanism in SAD. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. [D-2-hydroxyglutaric aciduria. Report of two cases].

    PubMed

    Mahfoud, Antionieta; Domínguez, Carmen Luisa; Rashed, Mohamed; Durán, Marinus; Rodríguez, Tania; Rodríguez, Daniel; Landa, Vanesa

    2009-09-01

    D-2-hydroxyglutaric aciduria (D-2-HGA) is a cerebral organic aciduria characterized by the accumulation of abnormal amounts of D-2-hydroxyglutaric acid in cerebrospinal fluid, blood, and urine. The clinical phenotype varies widely from neonatal severe epileptic encephalopathy to asymptomatic. Magnetic resonance imaging of affected patients typically show signs of delayed cerebral maturation, ventricular abnormalities and the presence of sub-ependymal cysts in the first months of life. We present clinical, biochemical and brain magnetic resonance imaging data of two pediatric patients with D-2-hydroxyglutaric aciduria. One patient presented with severe early infantile-onset epileptic encephalopathy, marked hypotonia, visual deficit, developmental delay and abnormal neuroradiological findings; while the other had hypotonia and development delay. Our findings reinforce the described phenotype of this rare neurometabolic inherited disorder. The diagnostic approach is based on clinical findings and the neuroimaging pattern and is established by the detection of D-2-hydroxyglutaric acid in body fluids. We suggest considering D-2-hydroxyglutaric aciduria in the differential diagnosis of any neonate or infant with epileptic encephalopathy and CNS dysfunction of unknown origin.

  4. Photoaffinity ligand for dopamine D2 receptors: azidoclebopride

    SciTech Connect

    Niznik, H.B.; Guan, J.H.; Neumeyer, J.L.; Seeman, P.

    1985-02-01

    In order to label D2 dopamine receptors selectively and covalently by means of a photosensitive compound, azidoclebopride was synthesized directly from clebopride. The dissociation constant (KD) of clebopride for the D2 dopamine receptor (canine brain striatum) was 1.5 nM, while that for azidoclebopride was 21 nM. The affinities of both clebopride and azidoclebopride were markedly reduced in the absence of sodium chloride. In the presence of ultraviolet light, azidoclebopride inactivated D2 dopamine receptors irreversibly, as indicated by the inability of the receptors to bind (/sup 3/H)spiperone. Maximal photoinactivation of about 60% of the D2 dopamine receptors occurred at 1 microM azidoclebopride; 30% of the receptors were inactivated at 80 nM azidoclebopride (pseudo-IC50). Dopamine agonists selectively protected the D2 receptors from being inactivated by azidoclebopride, the order of potency being (-)-N-n-propylnorapomorphine greater than apomorphine greater than (+/-)-6,7-dihydroxy-2-aminotetralin greater than (+)-N-n-propylnorapomorphine greater than dopamine greater than noradrenaline greater than serotonin. Similarly, dopaminergic antagonists prevented the photoinactivation of D2 receptors by azidoclebopride with the following order of potency: spiperone greater than (+)-butaclamol greater than haloperidol greater than clebopride greater than (-)-sulpiride greater than (-)-butaclamol.

  5. Oscillation of Branching Ratios Between the D (2 s )+D (1 s ) and the D (2 p )+D (1 s ) Channels in Direct Photodissociation of D2

    NASA Astrophysics Data System (ADS)

    Wang, Jie; Meng, Qingnan; Mo, Yuxiang

    2017-08-01

    The direct photodissociation of D2 at excitation energies above 14.76 eV occurs via two channels, D (2 s )+D (1 s ) and D (2 p )+D (1 s ) . The branching ratios between the two have been measured from the dissociation threshold to 3200 cm-1 above it, and it is found that they show cosine oscillations as a function of the fragment wave vector magnitudes. The oscillation is due to an interference effect and can be simulated using the phase difference between the wave functions of the two channels, analogous to Young's double-slit experiment. By fitting the measured branching ratios, we have determined the depths and widths of the effective spherical potential wells related to the two channels, which are in agreement with the effective depths and widths of the ab initio interaction potentials. The results of this Letter illustrate the importance of the relative phase between the fragments in controlling the branching ratios of the photodissociation channels.

  6. Polymerization and gelation of fibrinogen in D2O.

    PubMed

    Larsson, U

    1988-05-16

    The solution properties of fibrinogen and the thrombin-induced activation and gelation of fibrinogen in 95% D2O at pH 7.4 were compared to those in H2O under similar conditions. The initial release rates of fibrinopeptides A and B in D2O were slightly slower than those in H2O. However, the values of the Michaelis-Menten parameters Km and V for the release of the two peptides in D2O and H2O in the presence of 0.5 M NaCl were about the same. From turbidity measurements at 450 nm it is obvious that fibrinogen is soluble in a slightly more narrow range of NaCl concentration and that the fibrin gels have a higher degree of lateral aggregation in D2O than in H2O. The variation of fibrinogen concentration, thrombin concentration, pH and ionic a strength have a similar dependence on the final gel structure and clotting time in D2O and H2O. SDS-gel electrophoresis on fibrin samples, which were cross-linked by factor XIII, yielded results where the cross-linking of the gamma-chain appeared to be the same in D2O and H2O. The alpha-chain cross-linking was somewhat faster in D2O than in H2O. When fibrinogen solutions in 95% D2O were incubated at 20 mM CaCl2, a slow gelation of fibrinogen was observed, which was found to be induced by trace amounts of factor XIII. The final gel turbidity appeared to be about the same for this gelation as for that induced by thrombin. The differences in solubility for fibrinogen, kinetics for the enzyme reaction and optical properties for the fibrin gels in D2O and H2O may be explained by differences in electrostatic interactions, hydrogen bonding and hydration of fibrinogen in these two media.

  7. Upgraded immersive input display device (I2D2)

    NASA Astrophysics Data System (ADS)

    Tremper, David; Brosky, Andy

    2007-04-01

    In an effort to reduce the effects of ambient light on the read-ability of military displays, the Naval Research Lab began investigating and developing advanced hand-held displays. Analysis and research of display technologies with consideration for vulnerability to environmental conditions resulted in the complete design and fabrication of the handheld Immersive Input Display Device (I2D2) monocular. The I2D2 combines an OLED SVGA micro-display with an optics configuration and a rubber pressure-eyecup which allows view-ability only when the eyecup is depressed. This feature allows the I2D2 to be used during the day, while not allowing ambient light to affect the readability. It simultaneously controls light leakage, effectively eliminating the illumination, and thus preserving the tactical position, of the user in the dark. This paper will focus on the upgraded I2D2 system as it compares to the I2D2 presented at SPIE 2006.

  8. Quantum dynamics of the D2+OH reaction

    NASA Astrophysics Data System (ADS)

    Zhang, Dong H.; Yang, Minghui; Lee, Soo-Y.

    2002-02-01

    This paper presents fully converged integral cross sections for the D2(j1=0,2,4)+OH(j2=0,2,4)→HOD+D reaction on the YZCL2 potential energy surface. It is found that the influence of reagent rotation excitation on reactivity is relatively mild compared with that of the D2 vibration excitation, but is fairly important to the thermal rate constant at low temperature. In general, the OH rotation excitation tends to hinder the reaction, and the D2 rotation excitation tends to enhance the reactivity. The simultaneous reagent rotation has some correlated effect, with the influence of the D2 rotation excitation considerably dependent on the OH rotation excitation. It is also found that the reaction is strongly dependent on j12 (the coupled angular momentum between j1 and j2), K0 (the projection of the reagent rotation on the body fixed axis), and the parity of the system, in particular for either the OH or D2 rotationally excited initial states, but this dependence becomes relatively weaker as the collision energy increases. Excellent agreement achieved between theory and experiment on the thermal rate coefficients for temperatures up to 400 K clearly shows that the YZCL2 potential energy surface is capable of producing "quantitatively" accurate results for the title reaction.

  9. Role of Dopamine D2 Receptors in Human Reinforcement Learning

    PubMed Central

    Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

    2014-01-01

    Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well. PMID:24713613

  10. Role of dopamine D2 receptors in human reinforcement learning.

    PubMed

    Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

    2014-09-01

    Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.

  11. D2-D1 phase transition of columnar liquid crystals

    NASA Astrophysics Data System (ADS)

    Sun, Y. F.; Swift, J.

    1986-04-01

    The D2-D1 phase transition in columnar liquid crystals of the HAT series [e.g., HAT11 (triphenelene hexa-n-dodecanoate)] is discussed within the framework of Landau theory. The order parameters which describe the transition are abstracted from a tensor density function, and are associated with two irreducible representations of the symmetry group of the high-temperature D2 phase. A mechanism for a first-order transition is then suggested in accordance with both theoretical considerations and the experimental result for the D2-D1 transition. Two possible arrangements of the herringbone structure of the D1 phase are obtained, each of which gives six orientational states in the low-temperature D1 phase.

  12. Neuroleptic-induced catalepsy: a D2 blockade phenomenon?

    PubMed

    Klemm, W R

    1985-12-01

    Typical neuroleptics, such as haloperidol, are cataleptogenic. But since such drugs block both D1 and D2 receptors, it is not clear if there is a differential receptor role in catalepsy. To test this issue in a mouse model of catalepsy, these experiments tested molindone, a D2-blocking neuroleptic with almost no ability to block D1 receptors. If D1 receptor blockade is necessary for catalepsy, molindone should not cause catalepsy. But molindone was cataleptogenic, albeit less potent than haloperidol. There was also a "training effect" with haloperidol, but not saline or molindone, in that the catalepsy produced by 5 mg/kg of haloperidol was much greater when tests were performed repeatedly at short intervals after injection. Concurrent administration of apomorphine (4 or 8 mg/kg) markedly potentiated haloperidol catalepsy, but had no effect on molindone catalepsy. Such results are not readily interpretable solely in terms of current concepts of D1 and D2 receptors.

  13. L(d,2,1)-labeling of sun graphs

    NASA Astrophysics Data System (ADS)

    Indriati, Diari; Martini, Titin S.; Herlinawati, Novita

    2014-03-01

    For positive integer d, L(d,2,1)-labeling of a graph G is a function f from V(G) to the positive integers, f:V(G)→{1,2,...} such that |f(u)-f(v)|≥d if the distance between any 2 vertices u and v is 1 (D(u,v) = 1), |f(u)-f(v)|≥2 if D(u,v) = 2, and |f(u)-f(v)|≥1 if D(u,v) = 3. The L(d,2,1)-labeling number kd(G) of a graph G is the smallest positive integer kd such that G has an L(d,2,1)-labeling with kd as the maximum label. This paper presents a general kd-value of sun graphs Sn for any d ≥ 3 and n ≥ 3.

  14. Evidence against dopamine D1/D2 receptor heteromers

    PubMed Central

    Frederick, Aliya L.; Yano, Hideaki; Trifilieff, Pierre; Vishwasrao, Harshad D.; Biezonski, Dominik; Mészáros, József; Sibley, David R.; Kellendonk, Christoph; Sonntag, Kai C.; Graham, Devon L.; Colbran, Roger J.; Stanwood, Gregg D.; Javitch, Jonathan A.

    2014-01-01

    Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer (BRET), ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq knockout mice, as well as in knock-in mice expressing a mutant Ala286-CaMKIIα, that cannot autophosphorylate to become active. Moreover, we found that in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1–D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies. PMID:25560761

  15. Molecular dynamics simulations of D2O ice photodesorption

    NASA Astrophysics Data System (ADS)

    Arasa, C.; Andersson, S.; Cuppen, H.; van Dishoeck, E. F.; Kroes, G. J.

    2011-05-01

    We present results of MD calculations performed to study the photodissociation of D2O in an amorphous ice at different ice temperatures in order to investigate isotope effects on the photodesorption processes. In dense interstellar clouds, small dust particles of micrometer silicates are covered by ice mantles, mainly consisting of H2O and also of CO, CO2. Previous MD calculations of H2O ice at Tice=10-90 K show that the photodesorption of H while OH remains trapped is the main outcome in the first three monolayers (MLs). On the other hand, the H and OH photofragments released recombine or are trapped at separate positions in the deeper MLs and can react with other species in the ice. Desorption and trapping probabilities have been calculated following photoexcitation of D2O amorphous ice at 10, 20, 60 and 90 K, and the main conclusions agree with previous calculations of H2O ice. But, the average D photodesorption probability is smaller than that of the H atom, whereas the average OD radical photodesorption probability is larger than that of OH, and the average D2O photodesorption probability is larger than that for H2O due to the D2O kick-out mechanism. The total (OD + D2O) yield has been compared with experiments and the total (OH + H2O) yield from previous simulations. We find better agreement when we compare experimental yields with calculated yields for D2O ice than when we compare with calculated yields for H2O ice.

  16. Detection of Interstellar Ortho-D2H+ with SOFIA

    NASA Astrophysics Data System (ADS)

    Harju, Jorma; Sipilä, Olli; Brünken, Sandra; Schlemmer, Stephan; Caselli, Paola; Juvela, Mika; Menten, Karl M.; Stutzki, Jürgen; Asvany, Oskar; Kamiński, Tomasz; Okada, Yoko; Higgins, Ronan

    2017-05-01

    We report on the detection of the ground-state rotational line of ortho-D2H+ at 1.477 THz (203 μm) using the German REceiver for Astronomy at Terahertz frequencies (GREAT) on board the Stratospheric Observatory For Infrared Astronomy (SOFIA). The line is seen in absorption against far-infrared continuum from the protostellar binary IRAS 16293-2422 in Ophiuchus. The para-D2H+ line at 691.7 GHz was not detected with the APEX telescope toward this position. These D2H+ observations complement our previous detections of para-H2D+ and ortho-H2D+ using SOFIA and APEX. By modeling chemistry and radiative transfer in the dense core surrounding the protostars, we find that the ortho-D2H+ and para-H2D+ absorption features mainly originate in the cool (T < 18 K) outer envelope of the core. In contrast, the ortho-H2D+ emission from the core is significantly absorbed by the ambient molecular cloud. Analyses of the combined D2H+ and H2D+ data result in an age estimate of ˜5 × 105 yr for the core, with an uncertainty of ˜2 × 105 yr. The core material has probably been pre-processed for another 5 × 105 years in conditions corresponding to those in the ambient molecular cloud. The inferred timescale is more than 10 times the age of the embedded protobinary. The D2H+ and H2D+ ions have large and nearly equal total (ortho+para) fractional abundances of ˜10-9 in the outer envelope. This confirms the central role of {{{H}}}3+ in the deuterium chemistry in cool, dense gas, and adds support to the prediction of chemistry models that also {{{D}}}3+ should be abundant in these conditions.

  17. Evidence against dopamine D1/D2 receptor heteromers.

    PubMed

    Frederick, A L; Yano, H; Trifilieff, P; Vishwasrao, H D; Biezonski, D; Mészáros, J; Urizar, E; Sibley, D R; Kellendonk, C; Sonntag, K C; Graham, D L; Colbran, R J; Stanwood, G D; Javitch, J A

    2015-11-01

    Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation, because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer, ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout (KO) mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq KO mice, as well as in knock-in mice expressing a mutant Ala(286)-CaMKIIα that cannot autophosphorylate to become active. Moreover, we found that, in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1/D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies.

  18. Identification of D-2 dopaminergic receptors in bovine adrenal cortex

    SciTech Connect

    Missale, C.; Liberini, P.; Memo, M.; Carruba, M.O.; Spano, P.

    1985-12-30

    Dopamine receptors in bovine adrenal cortex have been studied by using /sup 3/H-(-) atsulpiride as selective ligand. The specific binding is saturable and the Scatchard analysis reveals a single component with a Kd of 6.2 nM and a Bmax of 8 fmoles/mg protein. The characterization indicates that the binding is rapid, reversible, stereospecific, Na/sup +/ - and temperature-dependent. Moreover its pharmacological profile is superimposable to that of D-2 receptors in the striatum, thus suggesting that central and peripheral D-2 receptors are identical. 27 references, 6 figures, 1 table.

  19. SU-E-T-199: How Number of Control Points Influences the Dynamic IMRT Plan Quality and Deliverability

    SciTech Connect

    Sharma, S; Manigandan, D; Chander, S; Subramani, V; Julka, P; Rath, G

    2014-06-01

    Purpose: To study the influence of number of control points on plan quality and deliverability. Methods: Five previously treated patients of carcinoma of rectum were selected. Planning target volume (PTV) and organs at risk (OARs) i.e. bladder and bowel were contoured. Dynamic IMRT plans (6MV, 7-fields, 45Gy/25 fractions and prescribed at 95% isodose) were created in Eclipse (Varian medical system, Palo Alto, CA) treatment planning system (TPS) for Varian CL2300C/D linear-accelerator. Base plan was calculated with 166 control points, variable mode (Eclipse Default). For generating other plans, all parameters were kept constant, only number of control points (Fixed mode) was varied as follows: 100, 166 and 200. Then, plan quality was analyzed in terms of maximum and mean dose received by the PTV and OARs. For plan deliverability, TPS calculated fluence was verified with I’matriXX (IBA Dosimetry, Germany) array and compared with TPS dose-plane using gamma index criteria of 3% dose difference and 3mm distance to agreement (DTA). Total number of monitor units (MU) required to deliver a plan was also noted. Results: The maximum variation for the PTV maximum with respect to eclipse default control point (166) was 0.28% (0.14Gy). Similarly, PTV mean varied only up to 0.22 %( 0.11Gy). Bladder maximum and bladder mean varied up to 0.51% (0.24Gy) and 0.16% (0.06Gy). The variation for the bowel maximum and bowel mean was also only 0.39% (0.19Gy) and 0.33% (0.04Gy). Total MU was within 0.32 % (4MU). Average gamma pass rate using different control points for five patients are 98.75±0.33%, 99.37±0.09%, 99.29±0.12%, 98.14±0.13% and 99.25±0.14% respectively. Conclusion: Slight variation (<1%) in PTV and OARs maximum and mean doses was observed with varying number of control points. Monitor unit was also not varied much. Reducing number of control points did not showed any comprise in plan deliverability in terms of gamma index pass rate.

  20. 3-Chlorotyramine Acting as Ligand of the D2 Dopamine Receptor. Molecular Modeling, Synthesis and D2 Receptor Affinity.

    PubMed

    Angelina, Emilio; Andujar, Sebastian; Moreno, Laura; Garibotto, Francisco; Párraga, Javier; Peruchena, Nelida; Cabedo, Nuria; Villecco, Margarita; Cortes, Diego; Enriz, Ricardo D

    2015-01-01

    We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2 -DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2 -DR to that reported for DA. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Novel Bivalent Ligands for D2/D3 Dopamine Receptors: Significant Cooperative Gain in D2 Affinity and Potency

    PubMed Central

    2012-01-01

    This report describes development of a series of novel bivalent molecules with a pharmacophore derived from the D2/D3 agonist 5-OH-DPAT. The spacer length in the bivalent compounds had a pronounced influence on affinity for D2 receptors. A 23-fold increase of D2 affinity was observed at a spacer length of 9 or 10 (compounds 11d and 14b) as compared to monovalent 5-OH-DPAT (Ki; 2.5 and 2.0 vs 59 nM for 11d and 14b vs 5-OH-DPAT, respectively). The functional potency of 11d and 14b indicated a 24- and 94-fold increase in potency at the D2 receptor as compared to 5-OH-DPAT (EC50; 1.7 and 0.44 vs 41 nM for 11d and 14b vs 5-OH-DPAT, respectively). These are the most potent bivalent agonists for the D2 receptor known to date. This synergism is consonant with cooperative interaction at the two orthosteric binding sites in the homodimeric receptor. PMID:23275802

  2. Association of Dopamine D2 Receptor Gene with Creative Ideation

    ERIC Educational Resources Information Center

    Yu, Qi; Zhang, Shun; Zhang, Jinghuan H.

    2017-01-01

    Although several studies suggest that dopamine D2 receptor (DRD2) gene may contribute to creativity, the relationship between DRD2 and creativity still needs to be further validated. To further test the relevance of DRD2 and creativity, this study explored the association between DRD2 and creative ideation in 483 unrelated healthy Chinese…

  3. Neptune Dark Spot D2 at High Resolution

    NASA Image and Video Library

    1996-01-29

    This bulls-eye view of Neptune small dark spot D2 was obtained by NASA s Voyager 2 narrow-angle camera on Aug. 24, 1989, when Voyager 2 was within 1.1 million km 680,000 miles of the planet. http://photojournal.jpl.nasa.gov/catalog/PIA00064

  4. 12 CFR 563d.2 - Mailing requirements for securities filings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 6 2012-01-01 2012-01-01 false Mailing requirements for securities filings... SECURITIES OF SAVINGS ASSOCIATIONS Regulations § 563d.2 Mailing requirements for securities filings. Any... than one Region, the Region where the association's home office is located. Such copies shall be marked...

  5. 12 CFR 563d.2 - Mailing requirements for securities filings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Mailing requirements for securities filings... SECURITIES OF SAVINGS ASSOCIATIONS Regulations § 563d.2 Mailing requirements for securities filings. Any... than one Region, the Region where the association's home office is located. Such copies shall be marked...

  6. 12 CFR 563d.2 - Mailing requirements for securities filings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 6 2013-01-01 2012-01-01 true Mailing requirements for securities filings... SECURITIES OF SAVINGS ASSOCIATIONS Regulations § 563d.2 Mailing requirements for securities filings. Any... than one Region, the Region where the association's home office is located. Such copies shall be marked...

  7. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin D2. 172.379 Section 172.379 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special...

  8. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172...

  9. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special...

  10. SU-F-BRB-07: A Plan Comparison Tool to Ensure Robustness and Deliverability in Online-Adaptive Radiotherapy

    SciTech Connect

    Hill, P; Labby, Z; Bayliss, R A; Geurts, M; Bayouth, J

    2015-06-15

    Purpose: To develop a plan comparison tool that will ensure robustness and deliverability through analysis of baseline and online-adaptive radiotherapy plans using similarity metrics. Methods: The ViewRay MRIdian treatment planning system allows export of a plan file that contains plan and delivery information. A software tool was developed to read and compare two plans, providing information and metrics to assess their similarity. In addition to performing direct comparisons (e.g. demographics, ROI volumes, number of segments, total beam-on time), the tool computes and presents histograms of derived metrics (e.g. step-and-shoot segment field sizes, segment average leaf gaps). Such metrics were investigated for their ability to predict that an online-adapted plan reasonably similar to a baseline plan where deliverability has already been established. Results: In the realm of online-adaptive planning, comparing ROI volumes offers a sanity check to verify observations found during contouring. Beyond ROI analysis, it has been found that simply editing contours and re-optimizing to adapt treatment can produce a delivery that is substantially different than the baseline plan (e.g. number of segments increased by 31%), with no changes in optimization parameters and only minor changes in anatomy. Currently the tool can quickly identify large omissions or deviations from baseline expectations. As our online-adaptive patient population increases, we will continue to develop and refine quantitative acceptance criteria for adapted plans and relate them historical delivery QA measurements. Conclusion: The plan comparison tool is in clinical use and reports a wide range of comparison metrics, illustrating key differences between two plans. This independent check is accomplished in seconds and can be performed in parallel to other tasks in the online-adaptive workflow. Current use prevents large planning or delivery errors from occurring, and ongoing refinements will lead to

  11. An alternative pathway of vitamin D2 metabolism Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2

    PubMed Central

    Slominski, Andrzej; Semak, Igor; Wortsman, Jacobo; Zjawiony, Jordan; Li, Wei; Zbytek, Blazej; Tuckey, Robert C.

    2007-01-01

    We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol·min−1·mol−1 P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol·min−1·mol−1. In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes). PMID:16817851

  12. Reconstruction-based 3D/2D image registration.

    PubMed

    Tomazevic, Dejan; Likar, Bostjan; Pernus, Franjo

    2005-01-01

    In this paper we present a novel 3D/2D registration method, where first, a 3D image is reconstructed from a few 2D X-ray images and next, the preoperative 3D image is brought into the best possible spatial correspondence with the reconstructed image by optimizing a similarity measure. Because the quality of the reconstructed image is generally low, we introduce a novel asymmetric mutual information similarity measure, which is able to cope with low image quality as well as with different imaging modalities. The novel 3D/2D registration method has been evaluated using standardized evaluation methodology and publicly available 3D CT, 3DRX, and MR and 2D X-ray images of two spine phantoms, for which gold standard registrations were known. In terms of robustness, reliability and capture range the proposed method outperformed the gradient-based method and the method based on digitally reconstructed radiographs (DRRs).

  13. SU-F-P-64: The Impact of Plan Complexity Parameters On the Plan Quality and Deliverability of Volumetric Modulated Arc Therapy with Canonical Correlation Analysis

    SciTech Connect

    Jin, X; Yi, J; Xie, C

    2016-06-15

    Purpose: To evaluate the impact of complexity indices on the plan quality and deliverability of volumetric modulated arc therapy (VMAT), and to determine the most significant parameters in the generation of an ideal VMAT plan. Methods: A multi-dimensional exploratory statistical method, canonical correlation analysis (CCA) was adopted to study the correlations between VMAT parameters of complexity, quality and deliverability, as well as their contribution weights with 32 two-arc VMAT nasopharyngeal cancer (NPC) patients and 31 one-arc VMAT prostate cancer patients. Results: The MU per arc (MU/Arc) and MU per control point (MU/CP) of NPC were 337.8±25.2 and 3.7±0.3, respectively, which were significantly lower than those of prostate cancer patients (MU/Arc : 506.9±95.4, MU/CP : 5.6±1.1). The plan complexity indices indicated that two-arc VMAT plans were more complex than one-arc VMAT plans. Plan quality comparison confirmed that one-arc VMAT plans had a high quality than two-arc VMAT plans. CCA results implied that plan complexity parameters were highly correlated with plan quality with the first two canonical correlations of 0.96, 0.88 (both p<0.001) and significantly correlated with deliverability with the first canonical correlation of 0.79 (p<0.001), plan quality and deliverability was also correlated with the first canonical correlation of 0.71 (p=0.02). Complexity parameters of MU/CP, segment area (SA) per CP, percent of MU/CP less 3 and planning target volume (PTV) were weighted heavily in correlation with plan quality and deliveability . Similar results obtained from individual NPC and prostate CCA analysis. Conclusion: Relationship between complexity, quality, and deliverability parameters were investigated with CCA. MU, SA related parameters and PTV volume were found to have strong effect on the plan quality and deliverability. The presented correlation among different quantified parameters could be used to improve the plan quality and the efficiency

  14. Electron Solvation Dynamics at D2O Ice and Na/D2O/Metal Interfaces

    NASA Astrophysics Data System (ADS)

    Wolf, Martin

    2009-03-01

    Electron transfer (ET) across interfaces is of vital importance in different areas of physics, chemistry and biology. Using time-resolved two-photon-photoemission spectroscopy we have studied the ultrafast dynamics of interfacial ET and solvation processes in amorphous and crystalline D2O layers on single crystal metal substrates and the influence of coadsorbed Na ions. In these experiments, photoinjection of electrons from the metal into the adsorbate conduction band is followed by ultrafast localization and solvation of the excess electrons. The subsequent energetic stabilization of these solvated electrons due to nuclear rearrangements of the polar molecular environment is accompanied by an increasing degree of localization. The observed ET rates strongly depend on the local structure of the ice. In crystalline D2O layers we monitor the stabilization of trapped electrons at the ice vacuum interface continuously from femtoseconds up to minutes. This behavior observed for crystalline ice is fundamentally different from amorphous D2O layers where the excess electrons have a much lower survival probability, which lifetimes of the order of 100 fs, which extend to several 10 ps if Na ions are coadsorbed at the ice surface.

  15. How the NDA Provides Transparency and Visibility of the Technical Deliverability of the R and D Programme - 13303

    SciTech Connect

    Seed, Ian; James, Paula; Brownridge, Melanie; McMinn, Mervin

    2013-07-01

    The Nuclear Decommissioning Authority (NDA) was created under the UK Energy Act 2004 to ensure the UK historic civil public sector nuclear legacy sites are decommissioned safely, securely, cost effectively and in ways that protect the environment. The delivery will involve carrying out many unique projects within a high hazard environment requiring the very highest standards in safety, security and environmental management. Unique problems require unique solutions and there is a substantial amount of research and development required for each project. The NDA's R and D strategic objective is to ensure that delivery of the NDA's mission is technically underpinned by sufficient and appropriate research and development. This drives a requirement to provide transparency and visibility of the technical deliverability of the programme through the technical baseline and accompanying research and development requirements. The NDA need to have confidence in the technical deliverability of the Site License Companies (SLCs) plans, provide overall visibility of R and D across the NDA Estate and ensure that appropriate R and D is being carried out in a timely manner. They need to identify where coordinated R and D programmes may be advantageous as a result of common needs, risks and opportunities and ensure key R and D needs across NDA are identified, prioritised and work programmes are costed and scheduled in the Lifetime Plans for individual sites and SLCs. Evidence of the Site License Company's approach and their corresponding technical underpinning programmes is achieved through submission of a number of outputs collectively known as TBuRDs (Technical Baseline and Underpinning Research and Development Requirements). This paper is a summary of the information generated by an independent review of those TBuRDs. It highlights some of the key messages, synergies and common R and D activities across the estate. It demonstrates the value of a consistent approach to collecting R

  16. D2 dopamine receptor regulation of learning, sleep and plasticity.

    PubMed

    França, A S C; Lobão-Soares, B; Muratori, L; Nascimento, G; Winne, J; Pereira, C M; Jeronimo, S M B; Ribeiro, S

    2015-04-01

    Dopamine and sleep have been independently linked with hippocampus-dependent learning. Since D2 dopaminergic transmission is required for the occurrence of rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by way of changes in post-acquisition REM sleep. To investigate this hypothesis, we first assessed whether D2 dopaminergic modulation in mice affects novel object preference, a hippocampus-dependent task. Animals trained in the dark period, when sleep is reduced, did not improve significantly in performance when tested 24h after training. In contrast, animals trained in the sleep-rich light period showed significant learning after 24h. When injected with the D2 inverse agonist haloperidol immediately after the exploration of novel objects, animals trained in the light period showed reduced novelty preference upon retesting 24h later. Next we investigated whether haloperidol affected the protein levels of plasticity factors shown to be up-regulated in an experience-dependent manner during REM sleep. Haloperidol decreased post-exploration hippocampal protein levels at 3h, 6h and 12h for phosphorylated Ca(2+)/calmodulin-dependent protein kinase II, at 6h for Zif-268; and at 12h for the brain-derived neurotrophic factor. Electrophysiological and kinematic recordings showed a significant decrease in the amount of REM sleep following haloperidol injection, while slow-wave sleep remained unaltered. Importantly, REM sleep decrease across animals was strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012). Altogether, the results suggest that the dopaminergic regulation of REM sleep affects learning by modulating post-training levels of calcium-dependent plasticity factors.

  17. Generating generalized G{sub D-2} solutions

    SciTech Connect

    Breton, N.; Lopez, L. A.; Feinstein, A.

    2008-06-15

    We show how one can systematically construct vacuum solutions to Einstein field equations with D-2 commuting Killing vectors in D>4 dimensions. The construction uses Einstein-scalar field seed solutions in four dimensions and is performed both for the case when all the Killing directions are spacelike, as well as when one of the Killing vectors is timelike. The later case corresponds to generalizations of stationary axially symmetric solutions to higher dimensions. Some examples representing generalizations of known higher dimensional stationary solutions are discussed in terms of their rod structure and horizon locations and deformations.

  18. Coupling of D2R Short but not D2R Long receptor isoform to the Rho/ROCK signaling pathway renders striatal neurons vulnerable to mutant huntingtin.

    PubMed

    Galan-Rodriguez, Beatriz; Martin, Elodie; Brouillet, Emmanuel; Déglon, Nicole; Betuing, Sandrine; Caboche, Jocelyne

    2017-01-01

    Huntington's disease, an inherited neurodegenerative disorder, results from abnormal polyglutamine extension in the N-terminal region of the huntingtin protein. This mutation causes preferential degeneration of striatal projection neurons. We previously demonstrated, in vitro, that dopaminergic D2 receptor stimulation acted in synergy with expanded huntingtin to increase aggregates formation and striatal death through activation of the Rho/ROCK signaling pathway. In vivo, in a lentiviral-mediated model of expanded huntingtin expression in the rat striatum, we found that the D2 antagonist haloperidol protects striatal neurons against expanded huntingtin-mediated toxicity. Two variant transcripts are generated by alternative splicing of the of D2 receptor gene, the D2R-Long and the D2R-Short, which are thought to play different functional roles. We show herein that overexpression of D2R-Short, but not D2R-Long in cell lines is associated with activation of the RhoA/ROCK signaling pathway. In striatal neurons in culture, the selective D2 agonist Quinpirole triggers phosphorylation of cofilin, a downstream effector of ROCK, which is abrogated by siRNAs that knockdown both D2R-Long and D2R-Short, but not by siRNAs targeting D2R-Long alone. Aggregate formation and neuronal death induced by expanded huntingtin, were potentiated by Quinpirole. This D2 agonist-mediated effect was selectively inhibited by the siRNA targeting both D2R-Long and D2R-Short but not D2R-Long alone. Our data provide evidence for a specific coupling of D2R-Short to the RhoA/ROCK/cofilin pathway, and its involvement in striatal vulnerability to expanded huntingtin. A new route for targeting Rho-ROCK signaling in Huntington's disease is unraveled with our findings. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Dopamine D2 Receptor antagonism suppresses tau aggregation and neurotoxicity

    PubMed Central

    McCormick, Allyson V.; Wheeler, Jeanna M.; Guthrie, Chris R.; Liachko, Nicole F.; Kraemer, Brian C.

    2012-01-01

    Background Tauopathies, including Alzheimer’s disease (AD) and frontotemporal dementia, are diseases characterized by the formation of pathological tau protein aggregates in the brain and progressive neurodegeneration. Presently no effective disease modifying treatments exist for tauopathies. Methods To identify drugs targeting tau neurotoxicity, we have used a C. elegans model of tauopathy to screen a drug library containing 1120 compounds approved for human use for the ability to suppress tau-induced behavioral effects. Results One compound, the typical antipsychotic azaperone, improved the motility of tau transgenic worms, reduced levels of insoluble tau, and was protective against neurodegeneration. We found that azaperone reduces insoluble tau in a human cell culture model of tau aggregation, and that other antipsychotic drugs (flupenthixol, perphenazine, and zotepine) also ameliorate the effects of tau expression in both models. Conclusions Reduction of dopamine signaling through the dopamine D2 receptor with the use of gene knockouts in C. elegans or RNAi knockdown in human cell culture have similar protective effects against tau toxicity. These results suggest dopamine D2 receptor antagonism holds promise as a potential neuroprotective strategy for targeting tau aggregation and neurotoxicity. PMID:23140663

  20. Chiral Potts spin glass in d=2 and 3 dimensions.

    PubMed

    Çağlar, Tolga; Berker, A Nihat

    2016-09-01

    The chiral spin-glass Potts system with q=3 states is studied in d=2 and 3 spatial dimensions by renormalization-group theory and the global phase diagrams are calculated in temperature, chirality concentration p, and chirality-breaking concentration c, with determination of phase chaos and phase-boundary chaos. In d=3, the system has ferromagnetic, left-chiral, right-chiral, chiral spin-glass, and disordered phases. The phase boundaries to the ferromagnetic, left- and right-chiral phases show, differently, an unusual, fibrous patchwork (microreentrances) of all four (ferromagnetic, left-chiral, right-chiral, chiral spin-glass) ordered phases, especially in the multicritical region. The chaotic behavior of the interactions, under scale change, are determined in the chiral spin-glass phase and on the boundary between the chiral spin-glass and disordered phases, showing Lyapunov exponents in magnitudes reversed from the usual ferromagnetic-antiferromagnetic spin-glass systems. At low temperatures, the boundaries of the left- and right-chiral phases become thresholded in p and c. In d=2, the chiral spin-glass Potts system does not have a spin-glass phase, consistently with the lower-critical dimension of ferromagnetic-antiferromagnetic spin glasses. The left- and right-chirally ordered phases show reentrance in chirality concentration p.

  1. Marginal fluctuations as instantons on M2/D2-branes

    NASA Astrophysics Data System (ADS)

    Naghdi, M.

    2014-03-01

    We introduce some (anti-) M/D-branes through turning on the corresponding field strengths of the 11- and 10-dimensional supergravity theories over spaces, where we use and for the internal spaces. Indeed, when we add M2/D2-branes on the same directions with the near horizon branes of the Aharony-Bergman-Jafferis-Maldacena model, all symmetries and supersymmetries are preserved trivially. In this case, we obtain a localized object just in the horizon. This normalizable bulk massless scalar mode is a singlet of and , and it agrees with a marginal boundary operator of the conformal dimension of . However, after performing a special conformal transformation, we see that the solution is localized in the Euclideanized space and is attributable to the included anti-M2/D2-branes, which are also necessary to ensure that there is no back-reaction. The resultant theory now breaks all supersymmetries to , while the other symmetries are so preserved. The dual boundary operator is then set up from the skew-whiffing of the representations and for the supercharges and scalars, respectively, while the fermions remain fixed in of the original theory. Besides, we also address another alternate bulk to boundary matching procedure through turning on one of the gauge fields of the full gauge group along the same lines with a similar situation to the one faced in the AdS/CFT correspondence. The latter approach covers the difficulty already faced with in the bulk-boundary matching procedure for as well.

  2. Regression/Eradication of gliomas in mice by a systemically-deliverable ATF5 dominant-negative peptide

    PubMed Central

    Cates, Charles C.; Arias, Angelo D.; Wong, Lynn S. Nakayama; Lamé, Michael W.; Sidorov, Maxim; Cayanan, Geraldine; Rowland, Douglas J.; Fung, Jennifer; Karpel-Massler, Georg; Siegelin, Markus D.; Greene, Lloyd A.; Angelastro, James M.

    2016-01-01

    Malignant gliomas have poor prognosis and urgently require new therapies. Activating Transcription Factor 5 (ATF5) is highly expressed in gliomas, and interference with its expression/function precipitates targeted glioma cell apoptosis in vitro and in vivo. We designed a novel deliverable truncated-dominant-negative (d/n) form of ATF5 fused to a cell-penetrating domain (Pen-d/n-ATF5-RP) that can be intraperitoneally/subcutaneously administered to mice harboring malignant gliomas generated; (1) by PDGF-B/sh-p53 retroviral transformation of endogenous neural progenitor cells; and (2) by human U87-MG xenografts. In vitro Pen-d/n-ATF5-RP entered into glioma cells and triggered massive apoptosis. In vivo, subcutaneously-administered Pen-d/n-ATF5-RP passed the blood brain barrier, entered normal brain and tumor cells, and then caused rapid selective tumor cell death. MRI verified elimination of retrovirus-induced gliomas within 8-21 days. Histopathology revealed growth-suppression of intracerebral human U87-MG cells xenografts. For endogenous PDGF-B gliomas, there was no recurrence or mortality at 6-12 months versus 66% mortality in controls at 6 months. Necropsy and liver-kidney blood enzyme analysis revealed no adverse effects on brain or other tissues. Our findings thus identify Pen-d/n-ATF5-RP as a potential therapy for malignant gliomas. PMID:26863637

  3. Infrared spectra and tunneling dynamics of the N2-D2O and OC-D2O complexes in the v2 bend region of D2O.

    PubMed

    Zhu, Yu; Zheng, Rui; Li, Song; Yang, Yu; Duan, Chuanxi

    2013-12-07

    The rovibrational spectra of the N2-D2O and OC-D2O complexes in the v2 bend region of D2O have been measured in a supersonic slit jet expansion using a rapid-scan tunable diode laser spectrometer. Both a-type and b-type transitions were observed for these two complexes. All transitions are doubled, due to the heavy water tunneling within the complexes. Assuming the tunneling splittings are the same in K(a) = 0 and K(a) = 1, the band origins, all three rotational and several distortion constants of each tunneling state were determined for N2-D2O in the ground and excited vibrational states, and for OC-D2O in the excited vibrational state, respectively. The averaged band origin of OC-D2O is blueshifted by 2.241 cm(-1) from that of the v2 band of the D2O monomer, compared with 1.247 cm(-1) for N2-D2O. The tunneling splitting of N2-D2O in the ground state is 0.16359(28) cm(-1), which is about five times that of OC-D2O. The tunneling splittings decrease by about 26% for N2-D2O and 23% for OC-D2O, respectively, upon excitation of the D2O bending vibration, indicating an increase of the tunneling barrier in the excited vibrational state. The tunneling splittings are found to have a strong dependence on intramolecular vibrational excitation as well as a weak dependence on quantum number K(a).

  4. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Water Heaters-Electric D2 Appendix D2 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS... LABELING RULEâ) Pt. 305, App. D2 Appendix D2 to Part 305—Water Heaters—Electric Range Information...

  5. On relating multiple M2 and D2-branes

    NASA Astrophysics Data System (ADS)

    Gran, U.; Nilsson, B. E. W.; Petersson, C.

    2008-10-01

    Due to the difficulties of finding superconformal Lagrangian theories for multiple M2-branes, we will in this paper instead focus on the field equations. By relaxing the requirement of a Lagrangian formulation we can explore the possibility of having structure constants fABCD satisfying the fundamental identity but which are not totally antisymmetric. We exemplify this discussion by making use of an explicit choice of a non-antisymmetric fABCD constructed from the Lie algebra structure constants fabc of an arbitrary gauge group. Although this choice of fABCD does not admit an obvious Lagrangian description, it does reproduce the correct SYM theory for a stack of N D2-branes to leading order in gYM-1 upon reduction and, moreover, it sheds new light on the centre of mass coordinates for multiple M2-branes.

  6. Secondary-Proton Spectra from D_2-Filled OMEGA Targets

    NASA Astrophysics Data System (ADS)

    Séguin, F. H.; Frenje, J. A.; Li, C. K.; Hicks, D. G.; Green, K. M.; Petrasso, R. D.; Glebov, V. Yu.; Stoeckl, C.; Radha, P. B.; Soures, J. M.; Meyerhofer, D. D.; Roberts, S.; Sorce, C.; Sangster, T. C.; Padalino, S.; Fletcher, K.

    2000-10-01

    Spectroscopic measurements of secondary fusion protons of imploded D_2-filled capsules in ICF experiments are now carried out with magnet-based charged-particle spectrometers and with a new type of ``range filter''-based detector utilizing special filters and CR39 nuclear track detectors. The mean proton energy determines the capsule's total areal density (ρR). Measurement of proton yield, in combination with the primary and secondary neutron yield, provides an estimate of fuel parameters. Recent data from OMEGA implosions will be presented. This work was performed in part at the LLE National Laser Users' Facility (NLUF), and was supported in part by the U.S. DOE Contract DE-FG03-99SF21782, LLE subcontract PO410025G, LLNL subcontract B313975, and by the U.S. DOE Office of ICF under Coop. Agreem. No. DE-FC03-92SF19460.

  7. Submillimeter D2O-18 molecular laser with optical pumping

    NASA Astrophysics Data System (ADS)

    Svich, V. A.; Pokormiakho, N. G.; Topkov, A. N.

    1980-11-01

    In the considered investigation, nine new emission lines of the D2O-18 molecule were observed over the wavelength range from 96 to 140 micrometers. In the experiments, a CO2 TEA laser was used for optical pumping. The TEA laser was operated at atmospheric pressure with an output energy up to 2 J and a pulse length of 100 ns. A gaseous mixture with a composition of CO2:N2:He = 1:1:4 was excited by means of a pulsed transverse discharge. A resonator with a length of 1 m was formed by a spherical mirror with a radius of curvature of 10 m, and a gold-plated echelette grating with 100 lines/mm. The submillimeter cell consisted of a glass tube with an inside diameter of 80 mm and a length of 1270 mm, and the spherical mirrors of the submillimeter resonator.

  8. Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor

    PubMed Central

    Bulwa, Zachary B.; Sharlin, Jordan A.; Clark, Peter J.; Bhattacharya, Tushar K.; Kilby, Chessa N.; Wang, Yanyan; Rhodes, Justin S.

    2011-01-01

    Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or over-representation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose- dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that over-representation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards. PMID:21803530

  9. Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor.

    PubMed

    Bulwa, Zachary B; Sharlin, Jordan A; Clark, Peter J; Bhattacharya, Tushar K; Kilby, Chessa N; Wang, Yanyan; Rhodes, Justin S

    2011-11-01

    Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or overrepresentation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that overrepresentation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards.

  10. Cyclin D2 Protein Stability Is Regulated in Pancreatic β-Cells

    PubMed Central

    He, Lu Mei; Sartori, Daniel J.; Teta, Monica; Opare-Addo, Lynn M.; Rankin, Matthew M.; Long, Simon Y.; Diehl, J. Alan; Kushner, Jake A.

    2009-01-01

    The molecular determinants of β-cell mass expansion remain poorly understood. Cyclin D2 is the major D-type cyclin expressed in β-cells, essential for adult β-cell growth. We hypothesized that cyclin D2 could be actively regulated in β-cells, which could allow mitogenic stimuli to influence β-cell expansion. Cyclin D2 protein was sharply increased after partial pancreatectomy, but cyclin D2 mRNA was unchanged, suggesting posttranscriptional regulatory mechanisms influence cyclin D2 expression in β-cells. Consistent with this hypothesis, cyclin D2 protein stability is powerfully regulated in fibroblasts. Threonine 280 of cyclin D2 is phosphorylated, and this residue critically limits D2 stability. We derived transgenic (tg) mice with threonine 280 of cyclin D2 mutated to alanine (T280A) or wild-type cyclin D2 under the control of the insulin promoter. Cyclin D2 T280A protein was expressed at much higher levels than wild-type cyclin D2 protein in β-cells, despite equivalent expression of tg mRNAs. Cyclin D2 T280A tg mice exhibited a constitutively nuclear cyclin D2 localization in β-cells, and increased cyclin D2 stability in islets. Interestingly, threonine 280-mutant cyclin D2 tg mice had greatly reduced β-cell apoptosis, with suppressed expression of proapoptotic genes. Suppressed β-cell apoptosis in threonine 280-mutant cyclin D2 tg mice resulted in greatly increased β-cell area in aged mice. Taken together, these data indicate that cyclin D2 is regulated by protein stability in pancreatic β-cells, that signals that act upon threonine 280 limit cyclin D2 stability in β-cells, and that threonine 280-mutant cyclin D2 overexpression prolongs β-cell survival and augments β-cell mass expansion. PMID:19628581

  11. Absolute state-selected total cross sections for the ion-molecule reactions O + (4S,2D,2P)+H2(D2)

    NASA Astrophysics Data System (ADS)

    Li, X.; Huang, Y.-L.; Flesch, G. D.; Ng, C. Y.

    1997-01-01

    Absolute total cross sections for the state-selected reactions of O+(4S,2D,2P)+H2 (D2) have been measured in the center-of-mass collision energy (Ec.m.) range of 0.02-12 eV. The cross sections for OH+ (OD+) from O+(2D)+H2 (D2) are slightly higher than those from O+(4S)+H2 (D2), whereas the OH+ (OD+) cross sections from O+ (2P)+H2 (D2) are ≈40% lower than those from O+(4S)+H2 (D2) and O+ (2D)+H2 (D2). At Ec.m.<0.5 eV, the total cross sections for OH+ (OD+) from O+ (4S)+H2 (D2) and O+(2D)+H2 (D2) are in accord with those predicted by the Langevin-Gioumousis-Stevenson model. Significantly higher cross sections are observed for H+ (D+) and H2+ (D2+) from O+(2D)+H2 (D2) and O+(2P)+H2 (D2), as compared to those from O+(4S)+H2 (D2). The exothermic nature of the O+(2D,2P)+H2 (D2) charge transfer collisions accounts for the high cross sections observed for H2+ (D2+). While the H+ (D+) ions observed in the O+(4S)+H2 (D2) reaction are identified with the H+ (D+)+O+H channel, the H+ (D+) ions from the reactions involving O+(2D) and O+(2P) are associated mostly with the H+ (D+)+OH (OD) channel, the formation of which obeys the spin-conservation rule. The comparison of the sum (σT) of cross sections for OH+ (OD+), H2+ (D2+), and H+ (D+) from O+(4S)+H2 (D2) to those from O+(2D)+H2 (D2) and O+(2P)+H2 (D2) shows that the σTs for O+(4S)+H2 (D2), O+(2D)+H2 (D2), and O+(2P)+H2 (D2) at Ec.m.<0.5 eV are comparable. At Ec.m.>0.5 eV, the σTs for O+(2P)+H2 (D2) are greater than those for O+(2D)+H2 (D2), which in turn are greater than those for O+(4S)+H2 (D2). This observation is attributed to the increase in the number of accessible product channels for reactions involving the excited O+(2D) and O+(2P) reactant ions.

  12. Analysis of [3',3'-d(2)]-nicotine and [3',3'-d(2)]-cotinine by capillary liquid chromatography-electrospray tandem mass spectrometry.

    PubMed

    Murphy, Sharon E; Villalta, Peter; Ho, Sing-Wei; von Weymarn, Linda B

    2007-09-15

    A selective and sensitive LC/MS/MS assay was developed for the quantification of d(2)-nicotine and d(2)-cotinine in plasma of current and past smokers administered d(2)-nicotine. After solid phase extraction and liquid-liquid extraction, HPLC separation was achieved on a capillary hydrophilic interaction chromatography phase column. The analytes were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated for d(2)-nicotine (0.03-6.0 ng/ml plasma) and d(2)-cotinine (0.15-25 ng/ml plasma). The lower limits of quantitation were 0.15 ng/ml and 0.25 ng/ml for d(2)-nicotine and d(2)-cotinine, respectively. The coefficient of variation was 3.7% for d(2)-nicotine and 2.5% for d(2)-cotinine. The method was applied to two ongoing studies of d(2)-nicotine metabolism in prior and current smokers. Preliminary analysis of a subset of subjects from these studies detected a significantly lower rate of nicotine conversion to cotinine by past smokers compared to current smokers.

  13. Simulation of Porous Medium Hydrogen Storage - Estimation of Storage Capacity and Deliverability for a North German anticlinal Structure

    NASA Astrophysics Data System (ADS)

    Wang, B.; Bauer, S.; Pfeiffer, W. T.

    2015-12-01

    Large scale energy storage will be required to mitigate offsets between electric energy demand and the fluctuating electric energy production from renewable sources like wind farms, if renewables dominate energy supply. Porous formations in the subsurface could provide the large storage capacities required if chemical energy carriers such as hydrogen gas produced during phases of energy surplus are stored. This work assesses the behavior of a porous media hydrogen storage operation through numerical scenario simulation of a synthetic, heterogeneous sandstone formation formed by an anticlinal structure. The structural model is parameterized using data available for the North German Basin as well as data given for formations with similar characteristics. Based on the geological setting at the storage site a total of 15 facies distributions is generated and the hydrological parameters are assigned accordingly. Hydraulic parameters are spatially distributed according to the facies present and include permeability, porosity relative permeability and capillary pressure. The storage is designed to supply energy in times of deficiency on the order of seven days, which represents the typical time span of weather conditions with no wind. It is found that using five injection/extraction wells 21.3 mio sm³ of hydrogen gas can be stored and retrieved to supply 62,688 MWh of energy within 7 days. This requires a ratio of working to cushion gas of 0.59. The retrievable energy within this time represents the demand of about 450000 people. Furthermore it is found that for longer storage times, larger gas volumes have to be used, for higher delivery rates additionally the number of wells has to be increased. The formation investigated here thus seems to offer sufficient capacity and deliverability to be used for a large scale hydrogen gas storage operation.

  14. Loqs depends on R2D2 to localize in D2 body-like granules and functions in RNAi pathways in silkworm cells.

    PubMed

    Zhu, Li; Tatsuke, Tsuneyuki; Xu, Jian; Li, Zhiqing; Mon, Hiroaki; Lee, Jae Man; Kusakabe, Takahiro

    2015-09-01

    The phenomenon of RNA interference (RNAi) has been found in various organisms. However, the proteins implicated in RNAi pathway in different species show distinct roles. Knowledge on the underlying mechanism of lepidopteron RNAi is quite lacking such as the roles of Loquacious (Loqs) and R2D2, the dsRNA-binding proteins in silkworm RNAi pathway. Here, we report that Loqs and R2D2 protein depletion affected efficiency of dsRNA-mediated RNAi pathway. Besides, Loqs was found to co-localize with Dicer2 to some specific cytoplasmic foci, which were looked like D2-bodies marked by R2D2 and Dicer2 in Fly cells, thereby calling the foci as D2 body-like granules. Using RNAi methods, Loqs was found to be the key protein in these granules, although R2D2 determined the localization of Loqs in D2 body-like granules. Interestingly, in the R2D2-depeted silkworm cells, the formation of processing bodies, another cytoplasmic foci, was affected. These data indicated R2D2 regulated these two kinds of cytoplasmic foci. Domain deletion analysis demonstrated that dsRBD 1 and 2 were required for Loqs in D2 body-like granules and dsRBD 2 and 3 were required for Loqs to interact with R2D2 and Ago1, respectively. Altogether, our observations provide important information for further study on D2 body-like granules, the newly found cytoplasmic foci in silkworm cells.

  15. 17 CFR 240.11d2-1 - Exemption from Section 11(d)(2) for certain broker-dealers effecting transactions for customers...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption from Section 11(d)(2... accounts. 240.11d2-1 Section 240.11d2-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... section 4f(a)(1) of the Commodity Exchange Act (7 U.S.C. 6f(a)(1)), to the extent that it effects...

  16. Higher derivative massive spin-3 models in D =2 +1

    NASA Astrophysics Data System (ADS)

    Dalmazi, D.; Mendonça, E. L.

    2016-07-01

    We find new higher derivative models describing a parity doublet of massive spin-3 modes in D =2 +1 dimensions. One of them is of fourth order in derivatives while the other one is of sixth order. They are complete, in the sense that they contain the auxiliary scalar field required to remove spurious degrees of freedom. Both of them are obtained through the master action technique starting with the usual (second-order) spin-3 Singh-Hagen model, which guarantees that they are ghost free. The fourth- and sixth-order terms are both invariant under (transverse) Weyl transformations, quite similarly to the fourth-order K -term of the "new massive gravity." The sixth-order term slightly differs from the product of the Schouten by the Einstein tensor, both of third order in derivatives. It is also possible to write down the fourth-order term as a product of a Schouten-like by an Einstein-like tensor (both of second order in derivatives) in close analogy with the K -term.

  17. Macroscopic Behavior of Nematics with D2d Symmetry

    NASA Astrophysics Data System (ADS)

    Pleiner, Harald; Brand, Helmut R.

    2010-03-01

    We discuss the symmetry properties and the macroscopic behavior of a nematic liquid crystal phase with D2d symmetry. Such a phase is a prime candidate for nematic phases made from banana-shaped molecules where the usual quadrupolar order coexists with octupolar (tetrahedratic) order. The resulting nematic phase is non-polar. While this phase could resemble the classic D∞h nematic in the polarizing microscope, it has many static as well as reversible and irreversible properties unknown to non-polar nematics without octupolar order. In particular, there is a linear gradient term in the free energy that selects parity leading to ambidextrously helical ground states when the molecules are achiral. In addition, there are static and irreversible coupling terms of a type only met otherwise in macroscopically chiral liquid crystals, e.g. the ambidextrous analogues of Lehmann-type effects known from cholesteric liquid crystals. Finally, we discuss certain nonlinear aspects of the dynamics related to the non-commutativity of three-dimensional finite rotations as well as other structural nonlinear hydrodynamic effects.

  18. Dissociation of D2+ by UV and THz light pulses

    NASA Astrophysics Data System (ADS)

    Xu, Tian-Yu; He, Feng

    2013-10-01

    The dissociation of D2+ in the few-cycle UV and THz light pulses is studied by numerically simulating the time-dependent Schrödinger equation. With only the UV pulse, we find the dissociation probability does not increase monotonously with the increasing of the UV pulse intensity or duration. The UV-triggered dissociation is streaked by the time-delayed THz light pulse, i.e., the nuclear momentum oscillates with the half of the THz period when the UV-THz time delay or the carrier envelope phase of the THz pulse is scanned. The difference of the maximum and minimum nuclear momenta equals the THz laser vector potential. The classical calculation of the Newtonian equation for a mass point moving on the THz light-modified molecular potential curves reproduces the quantum simulation results and therefore intuitively explores the physical scenario: The nuclear wave packets propagate along the THz field-dressed molecular potential curves adiabatically but make a fully diabatic transition, while the THz electric field changes direction. This study offers a visual angle to understand the molecular dissociation in the strong laser field with very long wavelengths.

  19. Control and imaging of O(1D2) precession.

    PubMed

    Wu, Shiou-Min; Radenovic, Dragana Č; van der Zande, Wim J; Groenenboom, Gerrit C; Parker, David H; Vallance, Claire; Zare, Richard N

    2011-01-01

    Larmor precession of a quantum mechanical angular momentum vector about an applied magnetic field forms the basis for a range of magnetic resonance techniques, including nuclear magnetic resonance spectroscopy and magnetic resonance imaging. We have used a polarized laser pump-probe scheme with velocity-map imaging detection to visualize, for the first time, the precessional motion of a quantum mechanical angular momentum vector. Photodissociation of O(2) at 157 nm provides a clean source of fast-moving O((1)D(2)) atoms, with their electronic angular momentum vector strongly aligned perpendicular to the recoil direction. In the presence of an external magnetic field, the distribution of atomic angular momenta precesses about the field direction, and polarization-sensitive images of the atomic scattering distribution recorded as a function of field strength yield 'time-lapse-photography' style movies of the precessional motion. We present movies recorded in various experimental geometries, and discuss potential consequences and applications in atmospheric chemistry and reaction dynamics.

  20. MOLECULAR DETERMINANTS OF A2AR-D2R ALLOSTERISM: ROLE OF THE INTRACELLULAR LOOP 3 OF THE D2R

    PubMed Central

    Fernández-Dueñas, Víctor; Gómez-Soler, Maricel; Jacobson, Kenneth A.; Kumar, T. Santhosh; Fuxe, Kjell; Borroto-Escuela, Dasiel O.; Ciruela, Francisco

    2012-01-01

    In the central nervous system (CNS), an antagonistic interaction has been shown between adenosine A2A and dopamine D2 receptors (A2ARs and D2Rs) that may be relevant both in normal and pathological conditions (i.e. Parkinson’s disease). Thus, the molecular determinants mediating this receptor-receptor interaction have recently been explored, since the fine tuning of this target (namely the A2AR/D2R oligomer) could possibly improve the treatment of certain CNS diseases. Here, we used a fluorescence resonance energy transfer (FRET)-based approach to examine the allosteric modulation of the D2R within the A2AR/D2R oligomer and the dependence of this receptor-receptor interaction on two regions rich in positive charges on intracellular loop 3 (IL3) of the D2R. Interestingly, we observed a negative allosteric effect of the D2R agonist quinpirole on A2AR ligand binding and activation. However, these allosteric effects were abolished upon mutation of specific arginine residues (217–222 and 267–269) on IL3 of the D2R, thus demonstrating a major role of these positively-charged residues in mediating the observed receptor-receptor interaction. Overall, these results provide structural insights to better understand the functioning of the A2AR/D2R oligomer in living cells. PMID:22924752

  1. Satisfactory surgical outcome of T2 gastric cancer after modified D2 lymphadenectomy.

    PubMed

    Zhang, Shupeng; Wu, Liangliang; Wang, Xiaona; Ding, Xuewei; Liang, Han

    2017-04-01

    Though D2 lymphadenectomy has been increasingly regarded as standard surgical procedure for advanced gastric cancer (GC), the modified D2 (D1 + 7, 8a and 9) lymphadenectomy may be more suitable than D2 dissection for T2 stage GC. The purpose of this study is to elucidate whether the surgical outcome of modified D2 lymphadenectomy was comparable to that of standard D2 dissection in T2 stage GC patients. A retrospective cohort study with 77 cases and 77 controls matched for baseline characteristics was conducted. Patients were categorized into two groups according to the extent of lymphadenectomy: the modified D2 group (mD2) and the standard D2 group (D2). Surgical outcome and recurrence date were compared between the two groups. The 5-year overall survival (OS) rate was 71.4% for patients accepted mD2 lymphadenectomy and 70.1% for those accepted standard D2, respectively, and the difference was not statistically significant. Multivariate survival analysis revealed that curability, tumor size, TNM stage and postoperative complications were independently prognostic factors for T2 stage GC patients. Patients in the mD2 group tended to have less intraoperative blood loss (P=0.001) and shorter operation time (P<0.001) than those in the D2 group. While there were no significant differences in recurrence rate and types, especially lymph node recurrence, between the two groups. The surgical outcome of mD2 lymphadenectomy was equal to that of standard D2, and the use of mD2 instead of standard D2 can be a better option for T2 stage GC.

  2. Effect of C-Terminal S-Palmitoylation on D2 Dopamine Receptor Trafficking and Stability.

    PubMed

    Ebersole, Brittany; Petko, Jessica; Woll, Matthew; Murakami, Shoko; Sokolina, Kate; Wong, Victoria; Stagljar, Igor; Lüscher, Bernhard; Levenson, Robert

    2015-01-01

    We have used bioorthogonal click chemistry (BCC), a sensitive non-isotopic labeling method, to analyze the palmitoylation status of the D2 dopamine receptor (D2R), a G protein-coupled receptor (GPCR) crucial for regulation of processes such as mood, reward, and motor control. By analyzing a series of D2R constructs containing mutations in cysteine residues, we found that palmitoylation of the D2R most likely occurs on the C-terminal cysteine residue (C443) of the polypeptide. D2Rs in which C443 was deleted showed significantly reduced palmitoylation levels, plasma membrane expression, and protein stability compared to wild-type D2Rs. Rather, the C443 deletion mutant appeared to accumulate in the Golgi, indicating that palmitoylation of the D2R is important for cell surface expression of the receptor. Using the full-length D2R as bait in a membrane yeast two-hybrid (MYTH) screen, we identified the palmitoyl acyltransferase (PAT) zDHHC4 as a D2R interacting protein. Co-immunoprecipitation analysis revealed that several other PATs, including zDHHC3 and zDHHC8, also interacted with the D2R and that each of the three PATs was capable of affecting the palmitoylation status of the D2R. Finally, biochemical analyses using D2R mutants and the palmitoylation blocker, 2-bromopalmitate indicate that palmitoylation of the receptor plays a role in stability of the D2R.

  3. Effect of C-Terminal S-Palmitoylation on D2 Dopamine Receptor Trafficking and Stability

    PubMed Central

    Ebersole, Brittany; Petko, Jessica; Woll, Matthew; Murakami, Shoko; Sokolina, Kate; Wong, Victoria; Stagljar, Igor; Lüscher, Bernhard; Levenson, Robert

    2015-01-01

    We have used bioorthogonal click chemistry (BCC), a sensitive non-isotopic labeling method, to analyze the palmitoylation status of the D2 dopamine receptor (D2R), a G protein-coupled receptor (GPCR) crucial for regulation of processes such as mood, reward, and motor control. By analyzing a series of D2R constructs containing mutations in cysteine residues, we found that palmitoylation of the D2R most likely occurs on the C-terminal cysteine residue (C443) of the polypeptide. D2Rs in which C443 was deleted showed significantly reduced palmitoylation levels, plasma membrane expression, and protein stability compared to wild-type D2Rs. Rather, the C443 deletion mutant appeared to accumulate in the Golgi, indicating that palmitoylation of the D2R is important for cell surface expression of the receptor. Using the full-length D2R as bait in a membrane yeast two-hybrid (MYTH) screen, we identified the palmitoyl acyltransferase (PAT) zDHHC4 as a D2R interacting protein. Co-immunoprecipitation analysis revealed that several other PATs, including zDHHC3 and zDHHC8, also interacted with the D2R and that each of the three PATs was capable of affecting the palmitoylation status of the D2R. Finally, biochemical analyses using D2R mutants and the palmitoylation blocker, 2-bromopalmitate indicate that palmitoylation of the receptor plays a role in stability of the D2R. PMID:26535572

  4. Microstructural Quantification of Rapidly Solidified Undercooled D2 Tool Steel

    NASA Astrophysics Data System (ADS)

    Valloton, J.; Herlach, D. M.; Henein, H.; Sediako, D.

    2017-10-01

    Rapid solidification of D2 tool steel is investigated experimentally using electromagnetic levitation (EML) under terrestrial and reduced gravity conditions and impulse atomization (IA), a drop tube type of apparatus. IA produces powders 300 to 1400 μm in size. This allows the investigation of a large range of cooling rates ( 100 to 10,000 K/s) with a single experiment. On the other hand, EML allows direct measurements of the thermal history, including primary and eutectic nucleation undercoolings, for samples 6 to 7 mm in diameter. The final microstructures at room temperature consist of retained supersaturated austenite surrounded by eutectic of austenite and M7C3 carbides. Rapid solidification effectively suppresses the formation of ferrite in IA, while a small amount of ferrite is detected in EML samples. High primary phase undercoolings and high cooling rates tend to refine the microstructure, which results in a better dispersion of the eutectic carbides. Evaluation of the cell spacing in EML and IA samples shows that the scale of the final microstructure is mainly governed by coarsening. Electron backscattered diffraction (EBSD) analysis of IA samples reveals that IA powders are polycrystalline, regardless of the solidification conditions. EBSD on EML samples reveals strong differences between the microstructure of droplets solidified on the ground and in microgravity conditions. While the former ones are polycrystalline with many different grains, the EML sample solidified in microgravity shows a strong texture with few much larger grains having twinning relationships. This indicates that fluid flow has a strong influence on grain refinement in this system.

  5. Measurement of the rubidium D2 natural transition linewidth

    NASA Astrophysics Data System (ADS)

    Schultz, Brad E.

    A new technique was developed to measure the natural linewidth of an optical transition. It tunes the frequency of a laser precisely across the resonance using an acousto-optic modulator. The transmission of the laser through a cloud of atoms was monitored using a CCD camera. This work studied the 5S1/2→5P3/2 transition or D2 line of 87Rb. The rubidium atoms were first cooled to a temperature of 50 muK using a magneto-optical trap. The transition linewidth was then given by the natural linewidth as the Doppler width is negligible at such low temperatures. Indeed, the observed lineshape was very well fit by a Lorentzian function. The full width at half maximum linewidth was examined as a function of the probe laser intensity and atom density. The natural linewidth was determined to be 6.069 +/- 0.016 MHz which corresponds to a lifetime of 26.22 +/- 0.07 nsec for the 5P 3/2 state. This lifetime is one of only a handful known to an accuracy of 3 parts in 103. It is in excellent agreement with results found using different experimental techniques. An important advantage of this technique is that it does not require a detector be placed relatively close to the atoms to be sensitive to fluorescence emitted into a large solid angle, as is the case with experiments that measure the temporal decay of fluorescence. All of the experimentally determined lifetimes for the 5P 3/2 state are about 1% less (3sigma) than the result of a relativistic many-body perturbation calculation.

  6. Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Bitencourt, Claudia da Silva; dos Santos, Daiane Fernanda; Nicolete, Roberto; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-10-12

    Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects.

  7. Effects of community-deliverable exercise on pain and physical function in adults with arthritis and other rheumatic diseases: a meta-analysis.

    PubMed

    Kelley, George A; Kelley, Kristi S; Hootman, Jennifer M; Jones, Dina L

    2011-01-01

    To use the meta-analytic approach to determine the effects of community-deliverable exercise on pain and physical function in adults with arthritis and other rheumatic diseases (AORD). Data sources consisted of 6 electronic databases, cross-referencing from retrieved studies and expert review. Study selection included 1) randomized controlled trials; 2) ≥ 1 exercise intervention group; 3) community-deliverable exercise interventions ≥ 4 weeks in duration; 4) control group; 5) adults ages ≥ 18 years with rheumatoid arthritis, osteoarthritis, fibromyalgia, lupus, gout, or ankylosing spondylitis; 6) published and unpublished studies; 7) studies published in any language between January 1, 1980, and January 1, 2008; and 8) data available for pain and/or physical function. Data abstraction included dual coding by 2 of the authors. Standardized effect sizes (g) and random-effects models were used to pool pain and physical function outcomes. Data were analyzed according to per-protocol and intent-to-treat (ITT) results. The minimally clinically important difference (MCID) and number needed to treat (NNT) were also calculated. Thirty-three studies representing 3,180 men and women (1,857 exercise, 1,323 control) with rheumatoid arthritis, osteoarthritis, and fibromyalgia were included. Statistically significant and clinically important improvements were observed for pain (per-protocol g = -0.37 [95% confidence interval (95% CI) -0.53, -0.21], MCID -18%; ITT g = -0.20 [95% CI -0.33, -0.07], MCID -9%, NNT 9) and physical function (per-protocol g = 0.37 [95% CI 0.21, 0.52], MCID 15%; ITT g = 0.34 [95% CI 0.25, 0.43], MCID 10%, NNT 5). Community-deliverable exercise improves pain and physical function in adults with the types of AORD included in the analysis. Dose-response as well as studies in those with other types of AORD is needed. Copyright © 2011 by the American College of Rheumatology.

  8. Measurement of astrophysical S factors and electron screening potentials for d( d, n)3He reaction In ZrD2, TiD2, D2O, and CD2 targets in the ultralow energy region using plasma accelerators

    NASA Astrophysics Data System (ADS)

    Bystritsky, V. M.; Bystritskii, Vit. M.; Dudkin, G. N.; Filipowicz, M.; Gazi, S.; Huran, J.; Kobzev, A. P.; Mesyats, G. A.; Nechaev, B. A.; Padalko, V. N.; Parzhitskii, S. S.; Pen'kov, F. M.; Philippov, A. V.; Kaminskii, V. L.; Tuleushev, Yu. Zh.; Wozniak, J.

    2012-01-01

    The paper is devoted to study electron screening effect influence on the rate of d( d, n)3He reaction in the ultralow deuteron collision energy range in the deuterated polyethylene (CD2), frozen heavy water (D2O) and deuterated metals (ZrD2 and TiD2). The ZrD2 and TiD2 targets were fabricated via magnetron sputtering of titanium and zirconium in gas (deuterium) environment. The experiments have been carried out using high-current plasma pulsed accelerator with forming of inverse Z pinch (HCEIRAS, Russia) and pulsed Hall plasma accelerator (NPI at TPU, Russia). The detection of neutrons with energy of 2.5MeV from dd reaction was done with plastic scintillation spectrometers. As a result of the experiments the energy dependences of astrophysical S factor for the dd reaction in the deuteron collision energy range of 2-7 keV and the values of the electron screening potential U e of interacting deuterons have been measured for the indicated above target: U e (CD2) ⩽ 40 eV; U e (D2O) ⩽ 26 eV; U e (ZrD2) = 157 ± 43 eV; U e (TiD2) = 125±34 eV. The value of astrophysical S factor, corresponding to the deuteron collision energy equal to zero, in the experiments with D2O target is found: S b (0) = 58.6 ± 3.6 keV b. The paper compares our results with other available published experimental and calculated data.

  9. Implantation of Energetic D+ Ions into Carbon Dioxide Ices and Implications for our Solar System: Formation of D2O and D2CO3

    NASA Astrophysics Data System (ADS)

    Bennett, Chris J.; Ennis, Courtney P.; Kaiser, Ralf I.

    2014-10-01

    Carbon dioxide (CO2) ices were irradiated with energetic D+ ions to simulate the exposure of oxygen-bearing solar system ices to energetic protons from the solar wind and magnetospheric sources. The formation of species was observed online and in situ by exploiting FTIR spectroscopy. Molecular products include ozone (O3), carbon oxides (CO3(C 2v , D 3h ), CO4, CO5, CO6), D2-water (D2O), and D2-carbonic acid (D2CO3). Species released into the gas phase were sampled via a quadrupole mass spectrometer, and possible minor contributions from D2-formaldehyde (D2CO), D4-methanol (CD3OD), and D2-formic acid (DCOOD) were additionally identified. The feasibility of several reaction networks was investigated by determining their ability to fit the observed temporal column densities of 10 key species that were quantified during the irradiation period. Directly relevant to the CO2-bearing ices of comets, icy satellites in the outer solar system, and the ice caps on Mars, this work illustrates for the first time that D2-water is formed as a product of the exposure of CO2 ices to D+ ions. These findings provide strong support for water formation from oxygen-bearing materials via non-thermal hydrogen atoms, and predict reaction pathways that are likely to be unfolding on the surfaces of asteroids and the Moon.

  10. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Water Heaters-Electric D2 Appendix D2 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range of...

  11. D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2

    PubMed Central

    Lin, An-Ping; Abbas, Saman; Kim, Sang-Woo; Ortega, Manoela; Bouamar, Hakim; Escobedo, Yissela; Varadarajan, Prakash; Qin, Yuejuan; Sudderth, Jessica; Schulz, Eduard; Deutsch, Alexander; Mohan, Sumitra; Ulz, Peter; Neumeister, Peter; Rakheja, Dinesh; Gao, Xiaoli; Hinck, Andrew; Weintraub, Susan T.; DeBerardinis, Ralph J.; Sill, Heinz; Dahia, Patricia L. M.; Aguiar, Ricardo C. T.

    2015-01-01

    Isocitrate dehydrogenases (IDH) convert isocitrate to alpha-ketoglutarate (α-KG). In cancer, mutant IDH1/2 reduces α-KG to D2-hydroxyglutarate (D2-HG) disrupting α-KG-dependent dioxygenases. However, the physiological relevance of controlling the interconversion of D2-HG into α-KG, mediated by D2-hydroxyglutarate dehydrogenase (D2HGDH), remains obscure. Here we show that wild-type D2HGDH elevates α-KG levels, influencing histone and DNA methylation, and HIF1α hydroxylation. Conversely, the D2HGDH mutants that we find in diffuse large B-cell lymphoma are enzymatically inert. D2-HG is a low-abundance metabolite, but we show that it can meaningfully elevate α-KG levels by positively modulating mitochondrial IDH activity and inducing IDH2 expression. Accordingly, genetic depletion of IDH2 abrogates D2HGDH effects, whereas ectopic IDH2 rescues D2HGDH-deficient cells. Our data link D2HGDH to cancer and describe an additional role for the enzyme: the regulation of IDH2 activity and α-KG-mediated epigenetic remodelling. These data further expose the intricacies of mitochondrial metabolism and inform on the pathogenesis of D2HGDH-deficient diseases. PMID:26178471

  12. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Water Heaters-Electric D2 Appendix D2 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  13. 26 CFR 301.6104(d)-2 - Making applications and returns widely available.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... from public disclosure. (See section 6104(d)(3) and § 301.6104(d)-3(b)(3) and (4)); and (C) any... available. 301.6104(d)-2 Section 301.6104(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Returns and Records § 301.6104(d)-2 Making applications and returns widely available. (a) In general. A...

  14. Preliminary abatement device evaluation: 1D-2D KGM cyclone design

    USDA-ARS?s Scientific Manuscript database

    Cyclones are predominately used in controlling cotton gin particulate matter (PM) emissions. The most commonly used cyclone designs are the 2D-2D and 1D-3D; however other designs such as the 1D-2D KGM have or are currently being used. A 1D-2D cyclone has a barrel length equal to the barrel diamete...

  15. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Water Heaters-Electric D2 Appendix D2 to... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  16. Serum Concentrations of 1,25-Dihydroxyvitamin D2 and 1,25-Dihydroxyvitamin D3 in Response to Vitamin D2 and Vitamin D3 Supplementation

    PubMed Central

    Biancuzzo, Rachael M.; Clarke, Nigel; Reitz, Richard E.; Travison, Thomas G.

    2013-01-01

    Objective: The purpose of this study was to determine 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] levels in healthy adults consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeks. Subjects and Design: Blood from 34 healthy male and female adults, aged 18 to 79 years, from a placebo-controlled, double-blind study who received a placebo, 1000 IU vitamin D3, or 1000 IU vitamin D2 daily for 11 weeks at end of winter was analyzed. Serum levels of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25(OH)2D2, and 1,25(OH)2D3 were determined by liquid chromatography–tandem mass spectroscopy. Results: Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4–10.3) in 1,25(OH)2D2, which was accompanied by a mean decrease of 9.9 pg/mL (−15.8 to −4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3. Conclusion: Vitamin D2 and vitamin D3 were effective in raising and maintaining total serum concentrations of 25(OH)D. Ingestion of vitamin D2 also resulted in an increase in serum concentrations of 1,25(OH)2D2. This increase was accompanied by a comparable decrease in serum concentrations of 1,25(OH)2D3; therefore, the total 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations did not significantly change after 11 weeks compared with baseline levels. Ingestion of vitamin D3 did not alter serum concentrations of 1,25(OH)2D3 or total 1,25(OH)2D. Therefore, ingestion of 1000 IU vitamin D2 or vitamin D3 for 11 weeks was effective in raising total serum concentrations of 25(OH)D as well as sustaining serum

  17. Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementation.

    PubMed

    Biancuzzo, Rachael M; Clarke, Nigel; Reitz, Richard E; Travison, Thomas G; Holick, Michael F

    2013-03-01

    The purpose of this study was to determine 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] levels in healthy adults consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeks. Blood from 34 healthy male and female adults, aged 18 to 79 years, from a placebo-controlled, double-blind study who received a placebo, 1000 IU vitamin D3, or 1000 IU vitamin D2 daily for 11 weeks at end of winter was analyzed. Serum levels of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25(OH)2D2, and 1,25(OH)2D3 were determined by liquid chromatography-tandem mass spectroscopy. Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4-10.3) in 1,25(OH)2D2, which was accompanied by a mean decrease of 9.9 pg/mL (-15.8 to -4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3. Vitamin D2 and vitamin D3 were effective in raising and maintaining total serum concentrations of 25(OH)D. Ingestion of vitamin D2 also resulted in an increase in serum concentrations of 1,25(OH)2D2. This increase was accompanied by a comparable decrease in serum concentrations of 1,25(OH)2D3; therefore, the total 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations did not significantly change after 11 weeks compared with baseline levels. Ingestion of vitamin D3 did not alter serum concentrations of 1,25(OH)2D3 or total 1,25(OH)2D. Therefore, ingestion of 1000 IU vitamin D2 or vitamin D3 for 11 weeks was effective in raising total serum concentrations of 25(OH)D as well as sustaining serum concentrations of total 1,25(OH)2D.

  18. Cryogenic DT and D2 Targets for Inertial Confinement Fusion

    NASA Astrophysics Data System (ADS)

    Sangster, T. C.

    2006-10-01

    Nearly all inertial confinement fusion ignition target designs are based on a spherical ablator containing a solid, cryogenic-DT-fuel layer. The uniformity of the inner surface of this layer is a critical factor in determining target performance. This talk will describe how cryogenic targets are made, characterized, and imploded on the 60-beam OMEGA laser. While cryogenic D2 targets have been routinely imploded for several years, only recently have targets containing DT-fuel layers been possible. Several of these targets have been imploded on OMEGA and most have had inner-ice-surface uniformity between 1- and 2-μm rms (very close to the ignition specification). These are the first laser-imploded targets to be formed exclusively using beta layering. The creation of these high-uniformity DT layers depends on understanding and controlling many diverse physics processes. These include sublimation and condensation at the inner ice surface (the heart of the layering process), phase transitions of multi-isotopic hydrogen ice, heat flow in the ice, heat flow in the exchange gas surrounding the ice, the geometry of the layering sphere that surrounds the target, and the time that the target is exposed to ambient radiation before being irradiated. In addition, a unique optical shadowgraphic technique has been developed to accurately characterize the 3-D ice-layer-thickness distribution for model comparisons and input to multidimensional hydrocode simulations. The talk will be placed in a historical context, describing previous approaches that worked with smaller targets and, more importantly, the approach being followed for the National Ignition Facility (NIF). It will describe the mutual constraints that target-design requirements and cryogenic system practicalities impose upon each other, for both direct and indirect drive, and how lessons learned on OMEGA can be used to improve the prospects for a successful ignition campaign on the NIF. Finally, implosion results from

  19. For Earth into space: The German Spacelab Mission D-2

    NASA Astrophysics Data System (ADS)

    Sahm, P. R.; Keller, M. H.; Schiewe, B.

    The Spacelab Mission D-2 successfully lifted off from Kennedy Space Center on April 26, 1993. With 88 experiments on board covering eleven different research disciplines it was a very ambitious mission. Besides materials and life science subjects, the mission also encompassed astronomy, earth observation, radiation physics and biology, telecommunication, automation and robotics. Notable results were obtained in almost all cases. To give some examples of the scientific output, building upon results obtained in previous missions (FSLP, D1) diffusion in melts was broadly represented delivering most precise data on the atomic mobility within various liquids, and crystal growth experiments (the largest gallium arsenide crystal grown by the floating zone technique, so far obtained anywhere, was one of the results), biological cell growth experiments were continued (for example, beer yeast cultures, continuing their growth on earth, delivered a qualitatively superior brewery result), the human physiology miniclinic configuration ANTHRORACK gave novel insights concerning cardiovascular, pulmonary, and renal (fluid volume determining) factors. Astronomical experiments yielded insights into our own galaxy within the ultra violet spectrum, earth observation experiments delivered the most precise resolution data superimposed by thematic mapping of many areas of the Earth, and the robotics experiment brought a remarkable feature in that a flying object was caught by the space robot, which was only achieved through several innovative advances during the time of experiment preparation. The eight years of preparation were also beneficial in another sense. Several discoveries have been made, and various technology transfers into ground-based processes were verified. To name the outstanding ones, in the materials science a novel bearing materials production process was developped, a patent granted for an improved high temperature heating chamber; with life sciences a new hormone

  20. Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes

    PubMed Central

    Werneck-de-Castro, Joao P.; Fonseca, Tatiana L.; Ignacio, Daniele L.; Fernandes, Gustavo W.; Andrade-Feraud, Cristina M.; Lartey, Lattoya J.; Ribeiro, Marcelo B.; Ribeiro, Miriam O.; Gereben, Balazs

    2015-01-01

    The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers. PMID:26214036

  1. The stay green mutations d1 and d2 increase water stress susceptibility in soybeans.

    PubMed

    Luquez, Virginia M; Guiamét, Juan J

    2002-06-01

    The stay green mutant genotype d1d1d2d2 inhibits the breakdown of chloroplast components in senescing leaves of soybean (Glycine max L. Merr.). Together with G (a gene that preserves chlorophyll in the seed coat) they may extend photosynthetic activity in some conditions. While wild-type soybeans maintain high leaf water potentials right up to abscission, leaves of (GG)d1d1d2d2 dehydrate late in senescence, which suggests that water relations may be altered in the mutant. Three-week-old plants were subjected to a moderate water deficit (soil water potential=-0.7 MPa) for 7-10 d. Leaf water potential and relative water content decreased significantly more in response to water deficit in unifoliate leaves of GGd1d1d2d2 than in a near-isogenic wild-type line. Down-regulation of stomatal conductance in response to drought was similar in mutant and wild-type leaves. Likewise, exogenously applied ABA reduced stomatal conductance to a similar extent in the mutant and the wild type, and applied ABA failed to restore water deficit tolerance in GGd1d1d2d2. Experiments with explants lacking roots indicate that the accelerated dehydration of GGd1d1d2d2 is probably not due to alterations in the roots. In a comparison of near-isogenic lines carrying different combinations of d1, d2 and G, only d1d1d2d2 and GGd1d1d2d2 (i.e. the genotypes that cause the stay green phenotype) were more susceptible to water deficit than the wild type. These data suggest that pathways involved in chloroplast disassembly and in the regulation of stress responses may be intertwined and controlled by the same factors.

  2. Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes.

    PubMed

    Werneck-de-Castro, Joao P; Fonseca, Tatiana L; Ignacio, Daniele L; Fernandes, Gustavo W; Andrade-Feraud, Cristina M; Lartey, Lattoya J; Ribeiro, Marcelo B; Ribeiro, Miriam O; Gereben, Balazs; Bianco, Antonio C

    2015-10-01

    The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers.

  3. Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation

    PubMed Central

    Trifilieff, Pierre; Feng, Bo; Urizar, Eneko; Winiger, Vanessa; Ward, Ryan D.; Taylor, Kathleen M.; Martinez, Diana M.; Moore, Holly; Balsam, Peter D.; Simpson, Eleanor H.; Javitch, Jonathan A.

    2014-01-01

    A decrease in dopamine D2 receptor (D2R) binding in the striatum is one of the most common findings in disorders that involve a dysregulation of motivation, including obesity, addiction, and attention deficit hyperactivity disorder. Since disruption of D2R signaling in the ventral striatum – including the Nucleus Accumbens (NAc) - impairs motivation, we sought to determine whether potentiating postsynaptic D2R-dependent signaling in the NAc would improve motivation. In this study, we used a viral vector strategy to overexpress postsynaptic D2Rs in either the NAc or the dorsal striatum. We investigated the effects of D2R overexpression on instrumental learning, willingness to work, use of reward value representations and modulation of motivation by reward associated cues. Overexpression of postsynaptic D2R in the NAc selectively increased motivation without altering consummatory behavior, the representation of the value of the reinforcer, or the capacity to use reward associated cues in flexible ways. In contrast, D2R overexpression in the dorsal striatum did not alter performance on any of the tasks. Thus, consistent with numerous studies showing that reduced D2R signaling impairs motivated behavior, our data show that post-synaptic D2R overexpression in the NAc specifically increases an animal’s willingness to expend effort to obtain a goal. Taken together, these results provide insight into the potential impact of future therapeutic strategies that enhance D2R signaling in the NAc. PMID:23711983

  4. The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning

    PubMed Central

    Lin, Chin-Hsing; Hansen, Stacey; Wang, Zhenshan; Storm, Daniel R.; Tapscott, Stephen J.; Olson, James M.

    2005-01-01

    The amygdala is centrally involved in formation of emotional memory and response to fear or risk. We have demonstrated that the lateral and basolateral amygdala nuclei fail to form in neuroD2 null mice and neuroD2 heterozygotes have fewer neurons in this region. NeuroD2 heterozygous mice show profound deficits in emotional learning as assessed by fear conditioning. Unconditioned fear was also diminished in neuroD2 heterozygotes compared to wild-type controls. Several key molecular regulators of emotional learning were diminished in the brains of neuroD2 heterozygotes including Ulip1, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and GABAA receptor. Thus, neuroD2 is essential for amygdala development and genes involved in amygdala function are altered in neuroD2-deficient mice. PMID:16203979

  5. Low bioaccessibility of vitamin D2 from yeast-fortified bread compared to crystalline D2 bread and D3 from fluid milks.

    PubMed

    Lipkie, Tristan E; Ferruzzi, Mario G; Weaver, Connie M

    2016-11-09

    The assessment of the efficacy of dietary and supplemental vitamin D tends to be confounded by differences in the serum 25-hydroxyvitamin D response between vitamin D2 and vitamin D3. Serum response differences from these vitamers may be due to differences in bioavailability. To address this specifically, the bioaccessibility was assessed for vitamin D2 from breads fortified with UV-treated yeast, and a benchmark against staple vitamin D3 fortified foods including bovine milks and infant formula, as well as crystalline vitamin D2 fortified bread. Fortified foods were subjected to a three-stage static in vitro digestion model, and vitamin D was analyzed by HPLC-MS. Vitamin D bioaccessibility was significantly greater from bovine milks and infant formula (71-85%) than from yeast-fortified sandwich breads (6-7%). Bioaccessibility was not different between whole wheat and white wheat bread (p > 0.05), but was ∼4× lower from yeast-fortified bread than from crystalline vitamin D2 fortified bread (p < 0.05). Intact yeast cells were observed in the digesta of yeast fortified bread. These results indicate that the low bioavailability of yeast D2 in comparison to other vitamin D2 sources is likely due to entrapment within a less digestible yeast matrix and not only to metabolic differences between vitamins D2 and D3.

  6. Threshold ionization spectroscopy of H2O, HDO and D2O and low-lying vibrational levels of HDO+ and D2O+

    NASA Astrophysics Data System (ADS)

    Lauzin, Clément; Jacovella, Ugo; Merkt, Frédéric

    2015-12-01

    Rotationally resolved photoelectron spectra of jet-cooled H2O, HDO and D2O have been recorded near the origin of the ? photoionising transition following single-photon ionization using the complementary techniques of mass-analysed threshold-ionization (MATI) and pulsed-field-ionization zero-kinetic-energy (PFI-ZEKE) photoelectron spectroscopy. A gas mixture of H2O, HDO and D2O with Ar was obtained by mixing H2O (ℓ) and D2O (ℓ) in a reservoir and bubbling Ar gas through the mixture. To unambiguously assign the photoelectron bands to H2O, HDO or D2O, the PFI-ZEKE photoelectron spectra of the mixture were compared to MATI spectra and to spectra of H2O. Analysis of the rotational structure of the origin bands (v+1 = 0, v2+ = 0, v+3 = 0) ← (v1 = 0, v2 = 0, v3 = 0) of H2O, HDO and D2O and of the transitions to the (010), (020) and (100) levels of D2O+ and the first excited level of the O-D stretching mode of HDO+ provided new information on the photoionization dynamics of water and the energy level structure of HDO+ and D2O+.

  7. Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist.

    PubMed

    Sánchez-Soto, Marta; Bonifazi, Alessandro; Cai, Ning Sheng; Ellenberger, Michael P; Newman, Amy Hauck; Ferré, Sergi; Yano, Hideaki

    2016-04-01

    The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR > D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays.

  8. Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist

    PubMed Central

    Sánchez-Soto, Marta; Bonifazi, Alessandro; Cai, Ning Sheng; Ellenberger, Michael P.; Newman, Amy Hauck

    2016-01-01

    The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR >> D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays. PMID:26843180

  9. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

    PubMed

    Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

    2014-01-03

    Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Dopamine-Induced Apoptosis of Lactotropes Is Mediated by the Short Isoform of D2 Receptor

    PubMed Central

    Radl, Daniela Betiana; Ferraris, Jimena; Boti, Valeria; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel

    2011-01-01

    Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process. PMID:21464994

  11. SU-E-T-492: Influence of Clipping PTV in Build-Up Region On IMRT Plan Quality and Deliverability

    SciTech Connect

    Sharma, S; Manigandan, D; Sahai, P; Biswas, A; Subramani, V; Chander, S; Julkha, P; Rath, G

    2015-06-15

    Purpose: To study the influence of clipping PTV from body contour on plan quality and deliverability in build-up region for superficial target. Methods: Five previously treated patients of post-operative carcinoma of parotid were re-planned for IMRT (6MV X-rays, sliding window technique, five fields and 60Gy/30 fractions) using eclipse treatment planning system (TPS) by keeping dose volume constraints and all other parameters constant, only PTV was clipped from body contour by 0mm, 1mm, 2mm and 3mm respectively. Planned fluence was transferred to previously scanned solid water phantom by placing I’matriXX array at 0.5cm depth (2mm slab+3mm inherent). Fluence was delivered by Varian CL2300C/D linac at 99.5cm source to detector distance. Measured fluence was compared with TPS dose plane using 2D gamma evaluation using 3%/3mm DTA criteria. Total MU (monitor unit) required to deliver a plan was also noted. For plan quality, PTV, maximum-dose, minimum-dose, coverage index (CI=PTV volume covered by prescription dose/PTV) and heterogeneity index HI=D5/D95 were analyzed using dose volume histogram (DVH). Results: The Result of gamma function analysis for I’matriXX and TPS were 97.63±1.79%, 97.48±0.99, 98.08±0.89% and 98.01±0.78% at 0.5cm build-up depth for 0, 1, 2 and 3mm PTV clipping, respectively. I’matriXX measured dose was higher compared to TPS. Total MU required for delivering a plan were 552±61, 503±47, 436±24 and 407±22. Maximum-dose to PTV was 6635.80±62.01cGy, 6635.80±40.60cGy, 6608.43±51.07cGy and 6564.20±28.51cGy. Similarly, minimum-dose to PTV was 3306.23±458.56cGy, 3546.57±721.01cGy, 4591.43±298.81cGy and 4861.90±412.40cGy. CI was 0.9347±0.020, 0.9398±0.021, 0.9448±0.022 and 0.9481±0.021. Similarly, HI was 1.089±0.015, 1.084±0.014, 1.078±0.009 and 1.074±0.008 for 0, 1, 2 and 3mm PTV clipping, respectively. Conclusion: Gamma function analysis resulted in almost similar results. However, I’matriXX was overestimating the dose

  12. Sequential hydroxylation of vitamin D2 by a genetically engineered CYP105A1.

    PubMed

    Hayashi, Keiko; Yasuda, Kaori; Yogo, Yuya; Takita, Teisuke; Yasukawa, Kiyoshi; Ohta, Miho; Kamakura, Masaki; Ikushiro, Shinichi; Sakaki, Toshiyuki

    2016-05-13

    Our previous studies revealed that the double variants of CYP105A1- R73A/R84A and R73V/R84A-show high levels of activity with respect to conversion of vitamin D3 to its biologically active form, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). In this study, we found that both the double variants were also capable of converting vitamin D2 to its active form, that is, 1α,25-dihydroxyvitamin D2 (1α,25(OH)2D2), via 25(OH)D2, whereas its 1α-hydroxylation activity toward 25(OH)D2 was much lower than that toward 25(OH)D3. Comparison of the wild type and the double variants revealed that the amino acid substitutions remarkably enhanced both 25- and 26-hydroxylation activity toward vitamin D2. After 25-hydroxylation of vitamin D2, further hydroxylation at C26 may occur frequently without the release of 25(OH)D2 from the substrate-binding pocket. Thus, the double variants of CYP105A1 are quite useful to produce 25,26(OH)2D2 that is one of the metabolites of vitamin D2 detected in human serum. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Mistletoe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2

    PubMed Central

    Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; Leavy, O; McNeela, E; Mills, K H G; O'Hagan, D T

    2002-01-01

    The mucosal adjuvant properties of the three type 2 ribosome-inactivating proteins (RIPs) from the European mistletoe, Viscum album L., were investigated. Mistletoe lectins were compared with cholera toxin (CT) as adjuvants when delivered nasotracheally together with herpes simplex virus glycoprotein D2 (gD2). All three mistletoe lectins (MLI, MLII, MLIII) were potent mucosal adjuvants. Co-administration of MLI, MLII or MLIII with gD2 led to significantly higher levels of gD2-specific mucosal immunoglobulin A (IgA) and systemic immunoglobulin G (IgG) antibody than when the antigen was delivered alone. The levels of antibodies induced were similar to those generated in mice immunized with gD2 and the potent mucosal adjuvant CT. Administration of ML1 with gD2 enhanced the antigen-specific splenic T-cell proliferative response. Interleukin-5 (IL-5), but not interferon-γ (IFN-γ), was detected in supernatants from splenocytes stimulated in vitro with gD2. This indicates that MLI enhanced type 2 T-helper cell (Th2) responses to the bystander antigen, gD2. Analysis of the gD2- and lectin-specific IgG subclass titres in mice immunized with gD2 and MLI, MLII or MLIII revealed a high ratio of IgG1 : IgG2a, which is compatible with the selective induction of Th2-type immune responses. PMID:12383207

  14. Blockade of neuronal dopamine D2 receptor attenuates morphine tolerance in mice spinal cord

    PubMed Central

    Dai, Wen-Ling; Xiong, Feng; Yan, Bing; Cao, Zheng-Yu; Liu, Wen-Tao; Liu, Ji-Hua; Yu, Bo-Yang

    2016-01-01

    Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro. Blockade of D2DR with its antagonist (sulpiride and L-741,626, i.t.) attenuated morphine antinociceptive tolerance without affecting basal pain perception. Sulpiride (i.t.) also down-regulated the expression of phosphorylation of NR1, PKC, MAPKs and suppressed the activation of astrocytes and microglia induced by chronic morphine administration. Particularly, D2DR was found to interact with μ opioid receptor (MOR) in neurons, and chronic morphine treatment enhanced the MOR/D2DR interactions. Sulpiride (i.t.) could disrupt the MOR/D2DR interactions and attenuate morphine tolerance, indicating that neuronal D2DR in the spinal cord may be involved in morphine tolerance possibly by interacting with MOR. These results may present new opportunities for the treatment and management of morphine-induced antinociceptive tolerance which often observed in clinic. PMID:28004735

  15. Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory.

    PubMed

    Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D; Riklund, Katrine; Lövdén, Martin; Lindenberger, Ulman; Bäckman, Lars

    2016-07-12

    D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [(11)C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions.

  16. Flap loop of GluD2 binds to Cbln1 and induces presynaptic differentiation.

    PubMed

    Kuroyanagi, Tomoaki; Hirano, Tomoo

    2010-07-30

    Glutamate receptor delta2 (GluD2) is selectively expressed on the postsynaptic spines at parallel-fiber (PF)-Purkinje neuron (PN) synapses. GluD2 knockout mice show a reduced number of PF-PN synapses, suggesting that GluD2 is involved in synapse formation. Recent studies revealed that GluD2 induces presynaptic differentiation in a manner dependent on its N-terminal domain (NTD) through binding of Cbln1 secreted from cerebellar granule neurons. However, the underlying mechanism of the specific binding of the NTD to Cbln1 remains elusive. Here, we have identified the flap loop (Arg321-Trp339) in the NTD of GluD2 (GluD2-NTD) as a crucial region for the binding to Cbln1 and the induction of presynaptic differentiation. Both induction of presynaptic differentiation and binding of Cbln1 were abolished in the HEK cells expressing not wild-type GluD2 but GluD2 with mutations in the flap loop. Especially, single amino acid substitution of either Arg321 or Trp323 to alanine was sufficient to disable the GluD2 function. Finally, a homology model of GluD2-NTD suggested that the flap loop is located at the distal end, which appears consistent with an interaction with Cbln1 and a presynaptic varicosity.

  17. Cyclin D2 is sufficient to drive beta cell self-renewal and regeneration.

    PubMed

    Tschen, Shuen-Ing; Zeng, Chun; Field, Loren; Dhawan, Sangeeta; Bhushan, Anil; Georgia, Senta

    2017-08-01

    Diabetes results from an inadequate mass of functional beta cells, due to either beta cell loss caused by autoimmune destruction (Type I diabetes) or beta cell failure in response to insulin resistance (Type II diabetes). Elucidating the mechanisms that regulate beta cell mass may be key to developing new techniques that foster beta cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal beta cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive beta cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in beta cells, we show that cyclin D2 overexpression increases beta cell self-renewal post-weaning and results in increased beta cell mass. Beta cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. Beta cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive beta cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in beta cells of cyclin D2(-/-) mice. Transgenic overexpression of cyclin D2 in cyclin D2(-)(/)(-) beta cells was sufficient to restore beta cell mass, maintain normoglycaemia, and improve regenerative capacity when compared to cyclin D2(-/-) littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate beta cell self-renewal and that manipulation of its expression could be used to enhance beta cell regeneration.

  18. Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine

    PubMed Central

    Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

    2016-01-01

    The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos. Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R+-MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits. PMID:27671625

  19. Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter

    PubMed Central

    Bouchard, Caroline; Dittrich, Oliver; Kiermaier, Astrid; Dohmann, Karen; Menkel, Annette; Eilers, Martin; Lüscher, Bernhard

    2001-01-01

    Myc oncoproteins promote cell cycle progression in part through the transcriptional up-regulation of the cyclin D2 gene. We now show that Myc is bound to the cyclin D2 promoter in vivo. Binding of Myc induces cyclin D2 expression and histone acetylation at a single nucleosome in a MycBoxII/TRRAP-dependent manner. Down-regulation of cyclin D2 mRNA expression in differentiating HL60 cells is preceded by a switch of promoter occupancy from Myc/Max to Mad/Max complexes, loss of TRRAP binding, increased HDAC1 binding, and histone deacetylation. Thus, recruitment of TRRAP and regulation of histone acetylation are critical for transcriptional activation by Myc. PMID:11511535

  20. Results of an attempt to measure increased rates of the reaction D-2 + D-2 yields He-3 + n in a nonelectrochemical cold fusion experiment

    NASA Technical Reports Server (NTRS)

    Fralick, Gustave C.; Decker, Arthur J.; Blue, James W.

    1989-01-01

    An experiment was performed to look for evidence of deuterium fusion in palladium. The experiment, which involved introducing deuterium into the palladium filter of a hydrogen purifier, was designed to detect neutrons produced in the reaction D-2 + D-2 yields He-3 + n as well as heat production. The neutron counts for deuterium did not differ significantly from background or from the counts for a hydrogen control. Heat production was detected when deuterium, but not hydrogen, was pumped from the purifier.

  1. Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects.

    PubMed

    Wager, Travis T; Chappie, Thomas; Horton, David; Chandrasekaran, Ramalakshmi Y; Samas, Brian; Dunn-Sims, Elizabeth R; Hsu, Cathleen; Nawreen, Nawshaba; Vanase-Frawley, Michelle A; O'Connor, Rebecca E; Schmidt, Christopher J; Dlugolenski, Keith; Stratman, Nancy C; Majchrzak, Mark J; Kormos, Bethany L; Nguyen, David P; Sawant-Basak, Aarti; Mead, Andy N

    2017-01-18

    Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6). In addition to good physicochemical properties, 3 exhibited low nanomolar affinity for the D3R (D3 Ki = 3.1 nM), good subtype selectivity over D2R (D2 Ki = 692 nM), and high selectivity for D3R versus other biogenic amine receptors. In vivo, 3 dose-dependently attenuated opioid self-administration and opioid drug-seeking behavior in a rat operant reinstatement model using animals trained to self-administer fentanyl. Further, traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents, suggesting that compound 3 has a unique in vivo profile. Collectively, our data support further investigation of dual D3R and D2R antagonists for the treatment of drug addiction.

  2. Vitamin D2, Ergosterol, and Vitamin B2 Content in Commercially Dried Mushrooms Marketed in China and Increased Vitamin D2 Content Following UV-C Irradiation.

    PubMed

    Huang, Guocheng; Cai, Weixi; Xu, Baojun

    2016-11-21

    Mushrooms are a great source of vitamin D and vitamin B2; however, the content of these vitamins in dried mushrooms has not fully been investigated. Thus, the objectives of this study were to determine the contents of vitamin D2, ergosterol, and vitamin B2 in commercially dried edible mushrooms in China and to investigate the effect of UV-C irradiation on fresh mushrooms. Among the 35 species of dried mushrooms considered for this study, the average ergosterol content was 1.98 mg/g, while the average vitamin D2 content was 16.88 µg/g. The average vitamin B2 content in dried mushrooms was 12.68 µg/g. Fresh shaggy ink caps and oyster mushrooms, when exposed to UV-C at 254 nm at a dose of 0.25 J/cm(2) for 10, 30, and 60 min, showed significantly (p < 0.05) increased vitamin D2 content (229.7 and 67.0 µg/g, respectively) as compared to its fresh counterparts. The conversion of ergosterol to vitamin D2 induced by UV-C irradiation at 0.25 J/cm(2) was significant (p < 0.05). In conclusion, dried commercial mushrooms have higher contents of ergosterol and vitamin D2 than fresh mushrooms. UV-C radiation can be used to increase vitamin D2 content in mushrooms.

  3. Effect of pd and dd reactions enhancement in deuterides TiD2, ZrD2 and Ta2D in the astrophysical energy range

    NASA Astrophysics Data System (ADS)

    Bystritskii, V. M.; Dudkin, G. N.; Filipowicz, M.; Huran, J.; Krylov, A. R.; Nechayev, B. A.; Padalko, V. N.; Pen'kov, F. M.; Philippov, A. V.; Tuleushev, Yu. Zh.

    2016-01-01

    Investigation of the pd-and dd-reactions in the ultralow energy (~keV) range is of great interest in the aspect of nuclear physics and astrophysics for developing of correct models of burning and evolution of stars. This report presents compendium of experimental results obtained at the pulsed plasma Hall accelerator (TPU, Tomsk). Most of those results are new, such as • temperature dependence of the neutron yield in the D( d, n)3He reaction in the ZrD2, Ta2D, TiD2 • potentials of electron screening and respective dependence of astrophysical S-factors in the dd-reaction for the deuteron collision energy in the range of 3-6 keV, with ZrD2, Ta2D temperature in the range of 20-200°C [1] • characteristics of the reaction d( p, γ)3He in the ultralow collision proton-deuterons energy range of 4-13 keV [2, 3] in ZrD2, Ta2D and TiD2 • observation of the neutron yield enhancement in the reaction D( d, n)3He at the ultralow deuteron collision energy due to channeling of deuterons in microscopic TiD2 with a face-centered cubic lattice type TiD1.73, oriented in the [100] direction [4]. The report includes discussion and comparison of the collected experimental results with the global data and calculations.

  4. Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia

    PubMed Central

    Borroto-Escuela, Dasiel O.; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

    2016-01-01

    The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2–N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of

  5. Nuclear spin-polarized HD, D2, HT and DT solids, liquids and high density gases

    NASA Astrophysics Data System (ADS)

    1985-06-01

    Success is reported in attaining extremely pure o-D2 in the 0.997 to 0.999 range by symmetry species conversion at a temperature of 4K on a partially activated charcoal catalyst. Spin-lattice relaxation times were improved to over 1 minute. Long storage times and the possibility of liquefaction without depolarizing the o-D2 are expected. Super pure o-D2 may also be used to probe magnetic impurities on surfaces. In addition, 50 kV white spectrum X-ray irradiated solid D2 experiments have yielded information on defect generation rates and defect lifetimes, as well as their effect on para-ortho D2 conversion. Experiments were also begun in epitaxial deposition of D2 on HD, and HD on mostly p-H2. Tests of a dilution refrigerator were completed.

  6. Multivalent approaches and beyond: novel tools for the investigation of dopamine D2 receptor pharmacology.

    PubMed

    Kopinathan, Anitha; Scammells, Peter J; Lane, J Robert; Capuano, Ben

    2016-07-01

    The dopamine D2 receptor (D2R) has been implicated in the symptomology of disorders such as schizophrenia and Parkinson's disease. Multivalent ligands provide useful tools to investigate emerging concepts of G protein-coupled receptor drug action such as allostery, bitopic binding and receptor dimerization. This review focuses on the approaches taken toward the development of multivalent ligands for the D2R recently and highlights the challenges associated with each approach, their utility in probing D2R function and approaches to develop new D2R-targeting drugs. Furthermore, we extend our discussion to the possibility of designing multitarget ligands. The insights gained from such studies may provide the basis for improved therapeutic targeting of the D2R.

  7. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

    PubMed

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J

    2016-06-23

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.

  8. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

    PubMed Central

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  9. Translational Modeling in Schizophrenia: Predicting Human Dopamine D2 Receptor Occupancy.

    PubMed

    Johnson, Martin; Kozielska, Magdalena; Pilla Reddy, Venkatesh; Vermeulen, An; Barton, Hugh A; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M M; Danhof, Meindert; Proost, Johannes H

    2016-04-01

    To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs. A hybrid PBPKPD model, previously developed using information on plasma concentrations, brain exposure and D2RO in rats, was used as the basis for the prediction of D2RO in human. The rat pharmacokinetic and brain physiology parameters were substituted with human population pharmacokinetic parameters and human physiological information. To predict the passive transport across the human blood-brain barrier, apparent permeability values were scaled based on rat and human brain endothelial surface area. Active efflux clearance in brain was scaled from rat to human using both human brain endothelial surface area and MDR1 expression. Binding constants at the D2 receptor were scaled based on the differences between in vitro and in vivo systems of the same species. The predictive power of this physiology-based approach was determined by comparing the D2RO predictions with the observed human D2RO of six antipsychotics at clinically relevant doses. Predicted human D2RO was in good agreement with clinically observed D2RO for five antipsychotics. Models using in vitro information predicted human D2RO well for most of the compounds evaluated in this analysis. However, human D2RO was under-predicted for haloperidol. The rat hybrid PBPKPD model structure, integrated with in vitro information and human pharmacokinetic and physiological information, constitutes a scientific basis to predict the time course of D2RO in man.

  10. ISCCP-D2like-Day Terra Ed3A

    Atmospheric Science Data Center

    2017-03-15

    ISCCP-D2like-Day Terra Ed3A Project Title:  CERES Discipline:  ... Earthdata Search Guide Documents:  Day/Nit Description/Abstract Detailed CERES ISCCP-D2like Product ... Data Products Catalog:  DPC_ISCCP-D2like-Day-Nit_R5V3  (PDF) Readme Files:  Readme Day-Nit ...

  11. The Implementation of C-ID, R2D2 Model on Learning Reading Comprehension

    ERIC Educational Resources Information Center

    Rayanto, Yudi Hari; Rusmawan, Putu Ngurah

    2016-01-01

    The purposes of this research are to find out, (1) whether C-ID, R2D2 model is effective to be implemented on learning Reading comprehension, (2) college students' activity during the implementation of C-ID, R2D2 model on learning Reading comprehension, and 3) college students' learning achievement during the implementation of C-ID, R2D2 model on…

  12. RecD2 Helicase Limits Replication Fork Stress in Bacillus subtilis

    PubMed Central

    Walsh, Brian W.; Bolz, Samantha A.; Wessel, Sarah R.; Schroeder, Jeremy W.; Keck, James L.

    2014-01-01

    DNA helicases have important roles in genome maintenance. The RecD helicase has been well studied as a component of the heterotrimeric RecBCD helicase-nuclease enzyme important for double-strand break repair in Escherichia coli. Interestingly, many bacteria lack RecBC and instead contain a RecD2 helicase, which is not known to function as part of a larger complex. Depending on the organism studied, RecD2 has been shown to provide resistance to a broad range of DNA-damaging agents while also contributing to mismatch repair (MMR). Here we investigated the importance of Bacillus subtilis RecD2 helicase to genome integrity. We show that deletion of recD2 confers a modest increase in the spontaneous mutation rate and that the mutational signature in ΔrecD2 cells is not consistent with an MMR defect, indicating a new function for RecD2 in B. subtilis. To further characterize the role of RecD2, we tested the deletion strain for sensitivity to DNA-damaging agents. We found that loss of RecD2 in B. subtilis sensitized cells to several DNA-damaging agents that can block or impair replication fork movement. Measurement of replication fork progression in vivo showed that forks collapse more frequently in ΔrecD2 cells, supporting the hypothesis that RecD2 is important for normal replication fork progression. Biochemical characterization of B. subtilis RecD2 showed that it is a 5′-3′ helicase and that it directly binds single-stranded DNA binding protein. Together, our results highlight novel roles for RecD2 in DNA replication which help to maintain replication fork integrity during normal growth and when forks encounter DNA damage. PMID:24443534

  13. Recording Cultural Heritage Using Terrestrial Laserscanning - Dealing with the System, the Huge Datasets they Create and Ways to Extract the Necessary Deliverables you can Work with

    NASA Astrophysics Data System (ADS)

    Christofori, E.; Bierwagen, J.

    2013-07-01

    Recording Cultural Heritage objects using terrestrial laserscanning becomes more and more popular over the last years. Since terrestrial Laserscanning System (TLS) Manufacturers have strongly increased the amount and speed of data captured with a single scan at each system upgrade and cutting down system costs the use of TLS Systems for recording cultural heritage is an option for recording worth to think about beside traditional methods like Photogrammetric. TLS Systems can be a great tool for capturing complex cultural heritage object within a short amount of time beside the traditional methods but can be a nightmare to handle for further process if not used right while capturing. Furthermore TLS Systems still have to be recognized as survey equipment, even though some of the manufactures promote them as everyday tool. They have to be used in an intelligent way having in mind the clients and the individual cultural objects needs. Thus the efficient way to use TLS Systems for data recording becomes a relevant topic to deal with the huge Amount of data the Systems collect while recording. Already small projects can turn into huge Pointcloud Datasets that End user, like Architects or Archaeologist neither can't deal with as their technical equipment doesn't fit the requirements of the Dataset nor do they have the software tools to use the Data as the current software tools still are high prized. Even the necessary interpretation of the Dataset can be a tough task if the people who have to work on with the Pointcloud aren't educated right in order to understand TLS and the results it creates. The use of TLS Systems has to have in mind the project requirements of the individual Heritage Object, like the required accuracy, standards for Levels of Details (e.g. "Empfehlungen für die Baudokumentation, Günther Eckstein, Germany"), the required kind of Deliverables (Visualization, 2D Drawings, True Deformation Drawings, 3D Models, BIM or 4D - Animations) as well as the

  14. Antineoplastic Agents. 565. Synthesis of Combretastatin D-2 Phosphate and Dihydro-combretastatin D-21

    PubMed Central

    Pettit, George R.; Quistorf, Peter D.; Fry, Jeremy A.; Herald, Delbert L.; Hamel, Ernest; Chapuis, Jean-Charles

    2009-01-01

    A modified synthetic route to combretastatin D-2 (5) was devised in order to further evaluate its biological activity, for its conversion to phosphate prodrugs (25–28), and as a route to obtaining dihydro-combretastatin D-2 (42). A parallel first total synthesis of dihydro-combretastatin D-2 was completed, proceeding from a saturated 3-phenylpropionic ester intermediate via the Ullmann biaryl ether reaction (39–41). In contrast to the cancer cell growth inhibitory activity exhibited by combretastatin D-2, relatively minor structural modifications (41, 42) caused elimination of those properties. PMID:20161135

  15. PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor

    PubMed Central

    2015-01-01

    Peptide nucleic acid scaffolds represent a promising tool to interrogate the multivalent effects of ligand binding to a membrane receptor. Dopamine D2 receptors (D2R) are a class of G-protein coupled receptors (GPCRs), and the formation of higher-ordered structures of these receptors has been associated with the progression of several neurological diseases. In this Letter, we describe the synthesis of a library of ligand-modified PNAs bearing a known D2R agonist, (±)-PPHT. The D2R activity for each construct was assessed, and the multivalent effects were evaluated. PMID:25893044

  16. Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT.

    PubMed

    Schlegel, S; Schlösser, R; Hiemke, C; Nickel, O; Bockisch, A; Hahn, K

    1996-04-01

    By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminergic pathways.

  17. Prominence of the dopamine D2 short isoform in dopaminergic pathways

    PubMed Central

    Khan, Zafar U.; Mrzljak, Ladislav; Gutierrez, Antonia; de la Calle, Adelaida; Goldman-Rakic, Patricia S.

    1998-01-01

    As a result of alternative splicing, the D2 gene of the dopamine receptor family exists in two isoforms. The D2 long is characterized by the insertion of 29 amino acids in the third cytoplasmic loop, which is absent in the short isoform. We have produced subtype-specific antibodies against both the D2 short and D2 long isoforms and found a unique compartmentalization between these two isoforms in the primate brain. The D2 short predominates in the cell bodies and projection axons of the dopaminergic cell groups of the mesencephalon and hypothalamus, whereas the D2 long is more strongly expressed by neurons in the striatum and nucleus accumbens, structures targeted by dopaminergic fibers. These results show that the splice variants of the dopamine D2 receptor are differentially distributed and possess distinct functions. The strategic localization of the D2 short isoform in dopaminergic cell bodies and axons strongly suggests that this isoform is the likely dopamine autoreceptor, whereas the D2 long isoform is primarily a postsynaptic receptor. PMID:9636219

  18. Protein Kinase C Beta Regulates the D2-Like Dopamine Autoreceptor

    PubMed Central

    Luderman, Kathryn D.; Chen, Rong; Ferris, Mark J.; Jones, Sara R.; Gnegy, Margaret E.

    2014-01-01

    The focus of this study was the regulation of the D2-like dopamine autoreceptor (D2 autoreceptor) by protein kinase Cβ, a member of the protein kinase C (PKC) family. Together with the dopamine transporter, the D2 autoreceptor regulates the level of extracellular dopamine and thus dopaminergic signaling. PKC regulates neuronal signaling via several mechanisms, including desensitizing autoreceptors to increase the release of several different neurotransmitters. Here, using both PKCβ−/− mice and specific PKCβ inhibitors, we demonstrated that a lack of PKCβ activity enhanced the D2 autoreceptor-stimulated decrease in dopamine release following both chemical and electrical stimulations. Inhibition of PKCβ increased surface localization of D2R in mouse striatal synaptosomes, which could underlie the greater sensitivity to quinpirole following inhibition of PKCβ. PKCβ−/− mice displayed greater sensitivity to the quinpirole-induced suppression of locomotor activity, demonstrating that the regulation of the D2 autoreceptor by PKCβ is physiologically significant. Overall, we have found that PKCβ downregulates the D2 autoreceptor, providing an additional layer of regulation for dopaminergic signaling. We propose that in the absence of PKCβ activity, surface D2 autoreceptor localization and thus D2 autoreceptor signaling is increased, leading to less dopamine in the extracellular space and attenuated dopaminergic signaling. PMID:25446677

  19. Experimental Studies on the Formation of D2O and D2O2 by Implantation of Energetic D+ Ions into Oxygen Ices

    NASA Astrophysics Data System (ADS)

    Bennett, Chris J.; Ennis, Courtney P.; Kaiser, Ralf I.

    2014-02-01

    The formation of water (H2O) in the interstellar medium is intrinsically linked to grain-surface chemistry; thought to involve reactions between atomic (or molecular) hydrogen with atomic oxygen (O), molecular oxygen (O2), and ozone (O3). Laboratory precedent suggests that H2O is produced efficiently when O2 ices are exposed to H atoms (~100 K). This leads to the sequential generation of the hydroxyperoxyl radical (HO2), then hydrogen peroxide (H2O2), and finally H2O and a hydroxyl radical (OH); despite a barrier of ~2300 K for the last step. Recent detection of the four involved species toward ρ Oph A supports this general scenario; however, the precise formation mechanism remains undetermined. Here, solid O2 ice held at 12 K is exposed to a monoenergetic beam of 5 keV D+ ions. Products formed during the irradiation period are monitored through FTIR spectroscopy. O3 is observed through seven archetypal absorptions. Three additional bands found at 2583, 2707, and 1195 cm -1 correspond to matrix isolated DO2 (ν1) and D2O2 (ν1, ν5), and D2O (ν2), respectively. During subsequent warming, the O2 ice sublimates, revealing a broad band at 2472 cm-1 characteristic of amorphous D2O (ν1, ν3). Sublimating D2, D2O, D2O2, and O3 products were confirmed through their subsequent detection via quadrupole mass spectrometry. Reaction schemes based on both thermally accessible and suprathermally induced chemistries were developed to fit the observed temporal profiles are used to elucidate possible reaction pathways for the formation of D2-water. Several alternative schemes to the hydrogenation pathway (O2→HO2→H2O2→H2O) were identified; their astrophysical implications are briefly discussed.

  20. Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys

    PubMed Central

    Czoty, Paul W.; Gage, H. Donald; Garg, Pradeep K.; Garg, Sudha; Nader, Michael A.

    2013-01-01

    Rationale Chronic treatment with dopamine (DA) receptor agonists and antagonists can differentially affect measures of DA D2/D3 receptor number and function, but the effects of chronic treatment with a partial D2/D3 receptor agonist are not clear. Objective We used a within-subjects design in male cynomolgus monkeys to determine the effects of repeated (17-day) treatment with the D2/D3 receptor partial agonist aripiprazole (ARI; 0.03 mg/kg and 0.1 mg/kg i.m.) on food-reinforced behavior (n=5) and on D2/D3 receptor availability as measured with positron emission tomography (PET; n=9). Methods Five monkeys responded under a fixed-ratio 50 schedule of food reinforcement and D2/D3 receptor availability was measured before and four days after ARI treatment using PET and the D2/D3 receptor-selective radioligand [18F]fluoroclebopride (FCP). Four additional monkeys were studied using [11C]raclopride and treated sequentially with each dose of ARI for 17 days. Results ARI decreased food-maintained responding with minimal evidence of tolerance. Repeated ARI administration increased FCP and raclopride distribution volume ratios (DVRs) in the caudate nucleus and putamen in most monkeys, but decreases were observed in monkeys with the highest baseline DVRs. Conclusions The results indicate that repeated treatment with a low efficacy DA receptor partial agonist produces effects on brain D2/D3 receptor availability that are qualitatively different from those of both high-efficacy receptor agonists and antagonists, and suggest that the observed individual differences in response to ARI treatment may reflect its partial agonist activity. PMID:24077804

  1. Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking

    PubMed Central

    Neuhofer, Daniela N.; Griffin, William C.; Siegel, Griffin S.; Bobadilla, Ana-Clara; Kupchik, Yonatan M.

    2017-01-01

    Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs. Because D1- and D2-MSNs innervate overlapping populations of ventral pallidal neurons, we next used optogenetics to examine whether changes in synaptic plasticity in D1- versus D2-MSN GABAergic synapses in the ventral pallidum could explain the differential regulation of VP activity. In mice trained to self-administer cocaine, GABAergic LTD was abolished in D2-, but not in D1-MSN synapses. A μ opioid receptor antagonist restored GABA currents in D2-, but not D1-MSN synapses of cocaine-trained mice, indicating that increased enkephalin tone on presynaptic μ opioid receptors was responsible for occluding the LTD. These results identify a behavioral function for D1-MSN innervation of the ventral pallidum, and suggest that losing LTDGABA in D2-MSN, but not D1-MSN input to ventral pallidum may promote cue-induced reinstatement of cocaine-seeking. SIGNIFICANCE STATEMENT More than 90% of ventral striatum is composed of two cell types, those expressing dopamine D1 or D2 receptors, which exert opposing roles on motivated behavior. Both cell types send GABAergic projections to the ventral pallidum and were found to differentially promote cue-induced reinstatement of cocaine seeking via the ventral pallidum. Furthermore, after cocaine self

  2. Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking.

    PubMed

    Heinsbroek, Jasper A; Neuhofer, Daniela N; Griffin, William C; Siegel, Griffin S; Bobadilla, Ana-Clara; Kupchik, Yonatan M; Kalivas, Peter W

    2017-01-25

    Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs. Because D1- and D2-MSNs innervate overlapping populations of ventral pallidal neurons, we next used optogenetics to examine whether changes in synaptic plasticity in D1- versus D2-MSN GABAergic synapses in the ventral pallidum could explain the differential regulation of VP activity. In mice trained to self-administer cocaine, GABAergic LTD was abolished in D2-, but not in D1-MSN synapses. A μ opioid receptor antagonist restored GABA currents in D2-, but not D1-MSN synapses of cocaine-trained mice, indicating that increased enkephalin tone on presynaptic μ opioid receptors was responsible for occluding the LTD. These results identify a behavioral function for D1-MSN innervation of the ventral pallidum, and suggest that losing LTDGABA in D2-MSN, but not D1-MSN input to ventral pallidum may promote cue-induced reinstatement of cocaine-seeking. More than 90% of ventral striatum is composed of two cell types, those expressing dopamine D1 or D2 receptors, which exert opposing roles on motivated behavior. Both cell types send GABAergic projections to the ventral pallidum and were found to differentially promote cue-induced reinstatement of cocaine seeking via the ventral pallidum. Furthermore, after cocaine self-administration, synaptic

  3. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers

    PubMed Central

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [11C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  4. Hypoparathyroidism: Less Severe Hypocalcemia With Treatment With Vitamin D2 Compared With Calcitriol.

    PubMed

    Streeten, Elizabeth A; Mohtasebi, Yasaman; Konig, Manige; Davidoff, Lisa; Ryan, Kathleen

    2017-05-01

    Options for chronic treatment of hypoparathyroidism include calcitriol, recombinant human parathyroid hormone, and high-dose vitamin D (D2). D2 is used in a minority of patients because of fear of prolonged hypercalcemia and renal toxicity. There is a paucity of recent data about D2 use in hypoparathyroidism. Compare renal function, hypercalcemia, and hypocalcemia in patients with hypoparathyroidism treated chronically with either D2 (D2 group) or calcitriol. A retrospective study of patients with hypoparathyroidism treated at the University of Maryland Hospital. Participants were identified by a billing record search with diagnosis confirmed by chart review. Thirty patients were identified; 16 were treated chronically with D2, 14 with calcitriol. Data were extracted from medical records. Serum creatinine and calcium, hospitalizations, and emergency department (ED) visits for hypercalcemia and hypocalcemia. D2 and calcitriol groups were similar in age (58.9 ± 16.7 vs 50.9 ± 22.6 years, P = 0.28), sex, and treatment duration (17.8 ± 14.2 vs 8.5 ± 4.4 years, P = 0.076). Hospitalization or ED visits for hypocalcemia occurred in none of the D2 group vs four of 14 in the calcitriol group (P = 0.03); three in the calcitriol group had multiple ED visits. There were no differences between D2 and calcitriol groups in hospitalizations or ED visits for hypercalcemia, serum creatinine or calcium, or kidney stones. We found less morbidity from hypocalcemia in hypoparathyroid patients treated chronically with D2 compared with calcitriol and found no difference in renal function or morbidity from hypercalcemia. Treatment with D2 should be considered in patients with hypoparathyroidism, particularly in those who experience recurrent hypocalcemia.

  5. Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene.

    PubMed

    Gay, Maresha S; Dasgupta, Chiranjib; Li, Yong; Kanna, Angela; Zhang, Lubo

    2016-08-01

    Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene. Copyright © 2016 by The American Society for Pharmacology and

  6. Dopamine D2 Receptors Regulate Collateral Inhibition between Striatal Medium Spiny Neurons

    PubMed Central

    van der Goes, Marie-Sophie; Partridge, John G.; Vicini, Stefano

    2013-01-01

    The principle neurons of the striatum are GABAergic medium spiny neurons (MSNs), whose collateral synapses onto neighboring neurons play critical roles in striatal function. MSNs can be divided by dopamine receptor expression into D1-class and D2-class MSNs, and alterations in D2 MSNs are associated with various pathological states. Despite overwhelming evidence for D2 receptors (D2Rs) in maintaining proper striatal function, it remains unclear how MSN collaterals are specifically altered by D2R activation. Here, we report that chronic D2R stimulation regulates MSN collaterals in vitro by presynaptic and postsynaptic mechanisms. We used corticostriatal cultures from mice in which MSN subtypes were distinguished by fluorophore expression. Quinpirole, an agonist for D2/3 receptors, was used to chronically activate D2Rs. Quinpirole increased the rate and strength of collateral formation onto D2R-containing MSNs as measured by dual whole-cell patch-clamp recordings. Additionally, these neurons were more sensitive to low concentrations of GABA and exhibited an increase in gephyrin puncta density, suggesting increased postsynaptic GABAA receptors. Last, quinpirole treatment increased presynaptic GABA release sites, as shown by increased frequency of sIPSCs and mIPSCs, correlating with increased VGAT (vesicular GABA transporter) puncta. Combined with the observation that there were no detectable differences in sensitivity to specific GABAA receptor modulators, we provide evidence that D2R activation powerfully transforms MSN collaterals via coordinated presynaptic and postsynaptic alterations. As the D2 class of MSNs is highly implicated in Parkinson's disease and other neurological disorders, our findings may contribute to understanding and treating the changes that occur in these pathological states. PMID:23986243

  7. Vitamin D2 versus vitamin D3 supplementation in hemodialysis patients: a comparative pilot study.

    PubMed

    Daroux, Maïté; Shenouda, Milhad; Bacri, Jean-Louis; Lemaitre, Vincent; Vanhille, Philippe; Bataille, Pierre

    2013-01-01

    In patients with chronic kidney disease, vitamin D insufficiency is highly prevalent. It can be corrected by supplementation with either vitamin D(2) or vitamin D3. Recent studies in patients without impaired kidney function suggest that vitamin D(3) is more efficient than vitamin D(2) in correcting vitamin D insufficiency. However, no direct comparison has been made in hemodialysis (HD) patients. Thirty-nine HD patients with serum 25-hydroxyvitamin D (25(OH)D) levels =20 ng/mL were enrolled in this comparative, prospective pilot study. They were divided into 3 groups and treated over a 3-month period. Each patient received oral doses of 200,000 international units (IU) vitamin D per month according to the following treatment schedule: (i) vitamin D(2) in small fractionated doses at each HD session, 3 times per week (group D2S); (ii) vitamin D(2) once a month (group D2M); or (iii) vitamin D(3) once a month (group D3M). Changes in serum 25(OH)D levels were measured at the end of the study. Posttreatment serum 25(OH)D levels increased significantly in all groups. The mean ± SD serum 25(OH)D value for group D3M patients (40 ± 13 ng/mL) was significantly higher than that for groups D2M (25 ± 9 ng/mL, p<0.01) and D2S patients (25 ± 9 ng/mL, p<0.01). Serum 25(OH)D increased to levels >30 ng/mL in 84% of group D3M patients, but in only 15% and 27% of group D2M and D2S subjects, respectively. Vitamin D(3) is more effective than vitamin D(2) in providing adequate 25(OH)D serum levels in HD patients.

  8. D-2-hydroxyglutarate metabolism is linked to photorespiration in the shm1-1 mutant.

    PubMed

    Kuhn, A; Engqvist, M K M; Jansen, E E W; Weber, A P M; Jakobs, C; Maurino, V G

    2013-07-01

    The Arabidopsis mutant shm1-1 is defective in mitochondrial serine hydroxymethyltransferase 1 activity and displays a lethal photorespiratory phenotype at ambient CO2 concentration but grows normally at high CO2 . After transferring high CO2 -grown shm1-1 plants to ambient CO2 , the younger leaves remain photosynthetically active while developed leaves display increased yellowing and decreased FV /FM values. Metabolite analysis of plants transferred from high CO2 to ambient air indicates a massive light-dependent (photorespiratory) accumulation of glycine, 2-oxoglutarate (2OG) and D-2-hydroxyglutarate (D-2HG). Amino acid markers of senescence accumulated in ambient air in wild-type and shm1-1 plants maintained in darkness and also build up in shm1-1 in the light. This, together with an enhanced transcription of the senescence marker SAG12 in shm1-1, suggests the initiation of senescence in shm1-1 under photorespiratory conditions. Mitochondrial D-2HG dehydrogenase (D-2HGDH) converts D-2HG into 2OG. In vitro studies indicate that 2OG exerts competitive inhibition on D-2HGDH with a Ki of 1.96 mm. 2OG is therefore a suitable candidate as inhibitor of the in vivo D-2HGDH activity, as 2OG is produced and accumulates in mitochondria. Inhibition of the D-2HGDH by 2OG is likely a mechanism by which D-2HG accumulates in shm1-1, however it cannot be ruled out that D-2HG may also accumulate due to an active senescence programme that is initiated in these plants after transfer to photorespiratory conditions. Thus, a novel interaction of the photorespiratory pathway with cellular processes involving D-2HG has been identified.

  9. SD-D2 "Swadana" Upgrading Program [D2 PGSD Swandana]. Summary Preliminary Report, D2-PGSD Program Economic Aspects [and] Report on Study of Economic Aspects. Educational Policy and Planning Project.

    ERIC Educational Resources Information Center

    Cobbe, James; Musa, Ibrahim

    The first of the two reports contained in this document is a preliminary analysis, by Dr. James Cobbe, of the data collected on an extension of a study of the upgrading program for primary school (Sekolah Dasar, or SD) to Diploma Dua (D2) using the Swadana (fully self-financed) delivery system. The extension of the study covers the six current…

  10. 17 CFR 240.17d-2 - Program for allocation of regulatory responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Program for allocation of regulatory responsibility. 240.17d-2 Section 240.17d-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules...

  11. 26 CFR 301.6104(d)-2 - Making applications and returns widely available.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... available. 301.6104(d)-2 Section 301.6104(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... the document on a World Wide Web page that the tax-exempt organization establishes and maintains or by..., on a World Wide Web page established and maintained by another entity. The document will be...

  12. Antiparkinson therapeutic potencies correlate with their affinities at dopamine D2(High) receptors.

    PubMed

    Seeman, Philip

    2007-12-01

    To determine whether antiparkinson dopamine agonists preferentially act on the high-affinity or the low-affinity states of dopamine D1 and D2 receptors, the agonist potencies were obtained by competition against [(3)H]SCH23390 for D1(High) and D1(Low), and against [(3)H]domperidone for D2(High) and D2(Low). N-propylnorapomorphine and cabergoline were the most potent at D2(High), with dissociation constants of 0.18 and 0.36 nM, respectively. Other agonists had D2(High)K(i) values of 0.52 nM for quinagolide, 0.6 nM for (+)PHNO, 0.9 for bromocriptine, 1.8 nM for apomorphine, 2.4 nM for pergolide, 3 nM for quinpirole, and 6.2 nM for lergotrile. There was a clear correlation between the K(i) values at D2(High) and their therapeutic concentrations in the plasma water, as derived from the known concentrations after correction for the fraction bound to the human plasma proteins. The data suggest that D2(High) is the primary and common target for the antiparkinson action of dopamine agonists. Bromocriptine, cabergoline, lergotrile, pergolide, and pramipexole had no affinity for D1(High), consistent with the clinical observations that the D2-selective bromocriptine and pramipexole elicit low levels of dyskinesia.

  13. STS-55 Payload Specialist Schlegel collects fungi sample at SL-D2 Rack 1

    NASA Image and Video Library

    1993-05-06

    STS055-106-037 (26 April-6 May 1993) --- Hans Schlegel works with a fungi experiment in the Spacelab D-2 Science Module onboard the Earth-orbiting Space Shuttle Columbia. Schlegel was one of two payload specialists representing the German Aerospace Research Establishment (DLR) on the 10-day Spacelab D-2 mission.

  14. UvrD2 is essential in Mycobacterium tuberculosis, but its helicase activity is not required.

    PubMed

    Williams, Alan; Güthlein, Carolin; Beresford, Nicola; Böttger, Erik C; Springer, Burkhard; Davis, Elaine O

    2011-09-01

    UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in bacteria. Mycobacterium tuberculosis has two annotated UvrD homologues; here we investigate the role of UvrD2. The uvrD2 gene at its native locus could be knocked out only in the presence of a second copy of the gene, demonstrating that uvrD2 is essential. Analysis of the putative protein domain structure of UvrD2 shows a distinctive domain architecture, with an extended C terminus containing an HRDC domain normally found in SF2 family helicases and a linking domain carrying a tetracysteine motif. Truncated constructs lacking the C-terminal domains of UvrD2 were able to compensate for the loss of the chromosomal copy, showing that these C-terminal domains are not essential. Although UvrD2 is a functional helicase, a mutant form of the protein lacking helicase activity was able to permit deletion of uvrD2 at its native locus. However, a mutant protein unable to hydrolyze ATP or translocate along DNA was not able to compensate for lack of the wild-type protein. Therefore, we concluded that the essential role played by UvrD2 is unlikely to involve its DNA unwinding activity and is more likely to involve DNA translocation and, possibly, protein displacement.

  15. Dopamine D2High receptors measured ex vivo are elevated in amphetamine-sensitized animals.

    PubMed

    Seeman, Philip

    2009-03-01

    Although dopamine supersensitivity is a fundamental aspect of diseases such as schizophrenia and Parkinson's disease, the molecular basis of dopamine supersensitivity is not known. Because behavioral dopamine supersensitivity is associated with a marked elevation of striatal dopamine D2(High) receptors in vitro, it is important to develop methods to measure D2(High) receptors in vivo. The present ex vivo study found that the dopamine agonist NPA ([-]-N-propyl-norapomorphine) inhibited the binding of the agonist [(3)H](+)PHNO to rat striatal D2 receptors significantly more than the D2 antagonist [(3)H]raclopride, when NPA was coinjected i.v. with each radioligand. These results suggest that the greater sensitivity of [(3)H](+)PHNO to inhibition by the coinjected NPA reflects in vivo competition at D2(High) receptors. Using rats that had been sensitized to amphetamine, this ex vivo method found that the specific binding of [(3)H](+)PHNO that was displaced by 10 microg/kg of NPA was 2.4-fold higher than that for control rats. These data agree with in vitro data showing a marked increase in D2(High) sites after amphetamine sensitization. Therefore, it is recommended that this method of co-injecting the D2 radioligand and the dopamine agonist displacer be used in human positron tomography to detect D2(High) receptors in health and disease.

  16. Hypoxia transduction by carotid body chemoreceptors in mice lacking dopamine D(2) receptors.

    PubMed

    Prieto-Lloret, J; Donnelly, D F; Rico, A J; Moratalla, R; González, C; Rigual, R J

    2007-10-01

    Hypoxia-induced dopamine (DA) release from carotid body (CB) glomus cells and activation of postsynaptic D(2) receptors have been proposed to play an important role in the neurotransmission process between the glomus cells and afferent nerve endings. To better resolve the role of D(2) receptors, we examined afferent nerve activity, catecholamine content and release, and ventilation of genetically engineered mice lacking D(2) receptors (D(2)(-/-) mice). Single-unit afferent nerve activities of D(2)(-/-) mice in vitro were significantly reduced by 45% and 25% compared with wild-type (WT) mice during superfusion with saline equilibrated with mild hypoxia (Po(2) approximately 50 Torr) or severe hypoxia (Po(2) approximately 20 Torr), respectively. Catecholamine release in D(2)(-/-) mice was enhanced by 125% in mild hypoxia and 75% in severe hypoxia compared with WT mice, and the rate of rise was increased in D(2)(-/-) mice. We conclude that CB transduction of hypoxia is still present in D(2)(-/-) mice, but the response magnitude is reduced. However, the ventilatory response to acute hypoxia is maintained, perhaps because of an enhanced processing of chemoreceptor input by brain stem respiratory nuclei.

  17. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Illustration of the provisions of section 643. 1.643(d)-2 Section 1.643(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Illustration of the provisions of section 643. (a) The provisions of section 643 may be illustrated by...

  18. Vitamins D2 and D3 in new world primates: influence on calcium absorption.

    PubMed

    Hunt, R D; Garcia, F G; Hegsted, D M; Kaplinsky, N

    1967-08-25

    In Cebus albifrons monkeys it was demonstrated that vitamin D(3) promotes the intestinal absorption of calcium-47 and that vitamin D(2) does not increase absorption above that seen in monkeys deficient in vitamin D. These data support previous observations that vitamin D(2) is not effective in preventing metabolic bone disease in this species.

  19. D2 receptor regulation of synaptic burst firing in prefrontal cortical pyramidal neurons

    PubMed Central

    Wang, Yun; Goldman-Rakic, Patricia S.

    2004-01-01

    The efficacy of antipsychotics in the treatment of schizophrenia depends on their ability to block dopamine (DA) D2 receptors. D2 receptor excitatory mediation of glutamatergic receptors has been implicated in in vivo studies. However, D2 receptor enhancement of glutamatergic transmission has rarely been reported in slice recordings. Instead, D2 receptor depression of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) action was obtained in previous slice studies. To obtain insight into this paradox, we examined DA's actions on synaptic responses of layer V pyramidal cells to minimal extracellular stimulation in layer III of ferret prefrontal cortical slices under NMDA and γ-aminobutyric acid type A blockade. This experimental design models the proposed hypofunction of NMDA receptor and γ-aminobutyric acid type A deficiency in schizophrenia. We found that DA and D2 receptor agonists promoted burst firing in a subset of pyramidal cells, which was reversed by haloperidol, a D2 antagonist and a D3 agonist, compounds having antipsychotic efficacy. In contrast, a D4 antagonist, which has not proven clinically effective, was not effective in blocking DA-promoted bursts. These results revealed excitatory effects of DA mediated mainly via D2 receptors, potentially providing a cellular mechanism for the D2 antagonism in treating schizophrenia. PMID:15051874

  20. An astroglia-linked dopamine D2-receptor action in prefrontal cortex

    PubMed Central

    Khan, Zafar U.; Koulen, Peter; Rubinstein, Marcelo; Grandy, David K.; Goldman-Rakic, Patricia S.

    2001-01-01

    Typical neuroleptic drugs elicit their antipsychotic effects mainly by acting as antagonists at dopamine D2 receptors. Much of this activity is thought to occur in the cerebral cortex, where D2 receptors are found largely in inhibitory GABAergic neurons. Here we confirm this localization at the electron microscopic level, but additionally show that a subset of cortical interneurons with low or undetectable expression of D2 receptor isoforms are surrounded by astrocytic processes that strongly express D2 receptors. Ligand binding of isolated astrocyte preparations indicate that cortical astroglia account for approximately one-third of the total D2 receptor binding sites in the cortex, a proportion that we found conserved among rodent, monkey, and human tissues. Further, we show that the D2 receptor-specific agonist, quinpirole, can induce Ca2+ elevation in isolated cortical astrocytes in a pharmacologically reversible manner, thus implicating this receptor in the signaling mechanisms by which astrocytes communicate with each other as well as with neurons. The discovery of D2 receptors in astrocytes with a selective anatomical relationship to interneurons represents a neuron/glia substrate for cortical dopamine action in the adult cerebral cortex and a previously unrecognized site of action for antipsychotic drugs with affinities at the D2 receptor. PMID:11172059

  1. Discovery, Optimization, and Characterization of Novel D2 Dopamine Receptor Selective Antagonists

    PubMed Central

    2015-01-01

    The D2 dopamine receptor (D2 DAR) is one of the most validated drug targets for neuropsychiatric and endocrine disorders. However, clinically approved drugs targeting D2 DAR display poor selectivity between the D2 and other receptors, especially the D3 DAR. This lack of selectivity may lead to undesirable side effects. Here we describe the chemical and pharmacological characterization of a novel D2 DAR antagonist series with excellent D2 versus D1, D3, D4, and D5 receptor selectivity. The final probe 65 was obtained through a quantitative high-throughput screening campaign, followed by medicinal chemistry optimization, to yield a selective molecule with good in vitro physical properties, metabolic stability, and in vivo pharmacokinetics. The optimized molecule may be a useful in vivo probe for studying D2 DAR signal modulation and could also serve as a lead compound for the development of D2 DAR-selective druglike molecules for the treatment of multiple neuropsychiatric and endocrine disorders. PMID:24666157

  2. Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.

    PubMed

    Chandra, Ramesh; Francis, T Chase; Nam, Hyungwoo; Riggs, Lace M; Engeln, Michel; Rudzinskas, Sarah; Konkalmatt, Prasad; Russo, Scott J; Turecki, Gustavo; Iniguez, Sergio D; Lobo, Mary Kay

    2017-07-05

    Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility.SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

  3. Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry.

    PubMed

    Cazorla, Maxime; de Carvalho, Fernanda Delmondes; Chohan, Muhammad O; Shegda, Mariya; Chuhma, Nao; Rayport, Stephen; Ahmari, Susanne E; Moore, Holly; Kellendonk, Christoph

    2014-01-08

    Structural plasticity in the adult brain is essential for adaptive behavior. We have found a remarkable anatomical plasticity in the basal ganglia of adult mice that is regulated by dopamine D2 receptors (D2Rs). By modulating neuronal excitability, striatal D2Rs bidirectionally control the density of direct pathway collaterals in the globus pallidus that bridge the direct pathway with the functionally opposing indirect pathway. An increase in bridging collaterals is associated with enhanced inhibition of pallidal neurons in vivo and disrupted locomotor activation after optogenetic stimulation of the direct pathway. Chronic blockade with haloperidol, an antipsychotic medication used to treat schizophrenia, decreases the extent of bridging collaterals and rescues the locomotor imbalance. These findings identify a role for bridging collaterals in regulating the concerted balance of striatal output and may have important implications for understanding schizophrenia, a disease involving excessive activation of striatal D2Rs that is treated with D2R blockers.

  4. Dopamine D2 receptors regulate the anatomical balance of basal ganglia circuitry

    PubMed Central

    Cazorla, Maxime; de Carvalho, Fernanda Delmondes; Chohan, Muhammad O.; Shegda, Mariya; Chuhma, Nao; Rayport, Stephen; Ahmari, Susanne E.; Moore, Holly; Kellendonk, Christoph

    2013-01-01

    Summary Structural plasticity in the adult brain is essential for adaptive behavior. We have found a remarkable anatomical plasticity in the basal ganglia of adult mice that is regulated by dopamine D2 receptors (D2Rs). By modulating neuronal excitability, striatal D2Rs bi-directionally control the density of direct pathway collaterals in the globus pallidus that bridge the direct pathway with the functionally opposing indirect pathway. An increase in bridging collaterals is associated with enhanced inhibition of pallidal neurons in vivo and disrupted locomotor activation after optogenetic stimulation of the direct pathway. Remarkably, chronic blockade with haloperidol, an antipsychotic medication used to treat schizophrenia decreases the extent of bridging collaterals and rescues the locomotor imbalance. These findings identify a role for bridging collaterals in regulating the concerted balance of striatal output, and may have important implications for understanding schizophrenia, a disease involving excessive activation of striatal D2Rs that is treated with D2R blockers. PMID:24411738

  5. The dopamine D2 receptor is expressed in GH3 cells.

    PubMed

    Johnston, J M; Wood, D F; Bolaji, E A; Johnston, D G

    1991-10-01

    Some pituitary tumours respond to dopamine by decreasing the release of prolactin and/or GH and by inhibition of tumour growth. Certain tumours are unresponsive. Dopamine D2 receptor high-affinity binding is impaired in these tumours, and the rat GH3 cell line behaves in a similar way. The hypothesis that the dopamine-binding defect results from impaired D2 receptor gene expression has been tested in the present study. On Northern blots, D2 receptor mRNA was present in both normal rat pituitary cells and in GH3 cells. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis identified a putative D2 receptor protein in normal and GH3 cell membranes. The lack of effect of dopamine in GH3 cells does not reflect the absence of D2 receptor gene expression.

  6. The Dopamine D2 Receptor Gene in Lamprey, Its Expression in the Striatum and Cellular Effects of D2 Receptor Activation

    PubMed Central

    Robertson, Brita; Huerta-Ocampo, Icnelia; Ericsson, Jesper; Stephenson-Jones, Marcus; Pérez-Fernández, Juan; Bolam, J. Paul; Diaz-Heijtz, Rochellys; Grillner, Sten

    2012-01-01

    All basal ganglia subnuclei have recently been identified in lampreys, the phylogenetically oldest group of vertebrates. Furthermore, the interconnectivity of these nuclei is similar to mammals and tyrosine hydroxylase-positive (dopaminergic) fibers have been detected within the input layer, the striatum. Striatal processing is critically dependent on the interplay with the dopamine system, and we explore here whether D2 receptors are expressed in the lamprey striatum and their potential role. We have identified a cDNA encoding the dopamine D2 receptor from the lamprey brain and the deduced protein sequence showed close phylogenetic relationship with other vertebrate D2 receptors, and an almost 100% identity within the transmembrane domains containing the amino acids essential for dopamine binding. There was a strong and distinct expression of D2 receptor mRNA in a subpopulation of striatal neurons, and in the same region tyrosine hydroxylase-immunoreactive synaptic terminals were identified at the ultrastructural level. The synaptic incidence of tyrosine hydroxylase-immunoreactive boutons was highest in a region ventrolateral to the compact layer of striatal neurons, a region where most striatal dendrites arborise. Application of a D2 receptor agonist modulates striatal neurons by causing a reduced spike discharge and a diminished post-inhibitory rebound. We conclude that the D2 receptor gene had already evolved in the earliest group of vertebrates, cyclostomes, when they diverged from the main vertebrate line of evolution (560 mya), and that it is expressed in striatum where it exerts similar cellular effects to that in other vertebrates. These results together with our previous published data (Stephenson-Jones et al. 2011, 2012) further emphasize the high degree of conservation of the basal ganglia, also with regard to the indirect loop, and its role as a basic mechanism for action selection in all vertebrates. PMID:22563388

  7. The dopamine D2 receptor gene in lamprey, its expression in the striatum and cellular effects of D2 receptor activation.

    PubMed

    Robertson, Brita; Huerta-Ocampo, Icnelia; Ericsson, Jesper; Stephenson-Jones, Marcus; Pérez-Fernández, Juan; Bolam, J Paul; Diaz-Heijtz, Rochellys; Grillner, Sten

    2012-01-01

    All basal ganglia subnuclei have recently been identified in lampreys, the phylogenetically oldest group of vertebrates. Furthermore, the interconnectivity of these nuclei is similar to mammals and tyrosine hydroxylase-positive (dopaminergic) fibers have been detected within the input layer, the striatum. Striatal processing is critically dependent on the interplay with the dopamine system, and we explore here whether D2 receptors are expressed in the lamprey striatum and their potential role. We have identified a cDNA encoding the dopamine D2 receptor from the lamprey brain and the deduced protein sequence showed close phylogenetic relationship with other vertebrate D2 receptors, and an almost 100% identity within the transmembrane domains containing the amino acids essential for dopamine binding. There was a strong and distinct expression of D2 receptor mRNA in a subpopulation of striatal neurons, and in the same region tyrosine hydroxylase-immunoreactive synaptic terminals were identified at the ultrastructural level. The synaptic incidence of tyrosine hydroxylase-immunoreactive boutons was highest in a region ventrolateral to the compact layer of striatal neurons, a region where most striatal dendrites arborise. Application of a D2 receptor agonist modulates striatal neurons by causing a reduced spike discharge and a diminished post-inhibitory rebound. We conclude that the D2 receptor gene had already evolved in the earliest group of vertebrates, cyclostomes, when they diverged from the main vertebrate line of evolution (560 mya), and that it is expressed in striatum where it exerts similar cellular effects to that in other vertebrates. These results together with our previous published data (Stephenson-Jones et al. 2011, 2012) further emphasize the high degree of conservation of the basal ganglia, also with regard to the indirect loop, and its role as a basic mechanism for action selection in all vertebrates.

  8. Specific regulation of N-CAM/D2-CAM cell adhesion molecule during skeletal muscle development.

    PubMed Central

    Moore, S E; Walsh, F S

    1985-01-01

    The expression of the N-CAM/D2-CAM cell adhesion molecule was studied in skeletal muscle. In cell cultures derived from adult human muscle N-CAM/D2-CAM was found at the cell surface of myoblasts and myotubes but not fibroblasts, showing that N-CAM/D2-CAM is a specific gene product of muscle. Western blots showed that the anti N-CAM/D2-CAM antibody reacted with a single protein band of 180 000 daltons in these cultures that differed in mobility from the broad band of 150 000-200 000 daltons found in brain. N-CAM/D2-CAM is also expressed by muscle at certain stages of development. Human foetal muscle of 10 and 20 weeks gestation showed N-CAM/D2-CAM around developing myofibres while both fast and slow adult muscle fibres did not express N-CAM/D2-CAM, suggesting that the protein is down regulated during myofibre maturation. This was studied further in developing rat muscle where N-CAM/D2-CAM was found on myofibres in the day 1 neonate, but had disappeared by day 9. N-CAM/D2-CAM is, however, re-expressed in human muscle disease where there is muscle regeneration such as in polymyositis, and here is associated with classic regenerating myofibres. N-CAM/D2-CAM expression is temporally regulated and is expressed only at times of synapse formation consistent with the idea that it may be involved in early nerve-muscle interactions. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:3891323

  9. Intermolecular potential and rovibrational states of the H2O-D2 complex

    NASA Astrophysics Data System (ADS)

    van der Avoird, Ad; Scribano, Yohann; Faure, Alexandre; Weida, Miles J.; Fair, Joanna R.; Nesbitt, David J.

    2012-05-01

    A five-dimensional intermolecular potential for H2O-D2 was obtained from the full nine-dimensional ab initio potential surface of Valiron et al. [P. Valiron, M. Wernli, A. Faure, L. Wiesenfeld, C. Rist, S. Kedžuch, J. Noga, J. Chem. Phys. 129 (2008) 134306] by averaging over the ground state vibrational wave functions of H2O and D2. On this five-dimensional potential with a well depth De of 232.12 cm-1 we calculated the bound rovibrational levels of H2O-D2 for total angular momentum J = 0-3. The method used to compute the rovibrational levels is similar to a scattering approach—it involves a basis of coupled free rotor wave functions for the hindered internal rotations and the overall rotation of the dimer—while it uses a discrete variable representation of the intermolecular distance coordinate R. The basis was adapted to the permutation symmetry associated with the para/ortho (p/o) nature of both H2O and D2, as well as to inversion symmetry. As expected, the H2O-D2 dimer is more strongly bound than its H2O-H2 isotopologue [cf. A. van der Avoird, D.J. Nesbitt, J. Chem. Phys. 134 (2011) 044314], with dissociation energies D0 of 46.10, 50.59, 67.43, and 73.53 cm-1 for pH2O-oD2, oH2O-oD2, pH2O-pD2, and oH2O-pD2. A rotationally resolved infrared spectrum of H2O-D2 was measured in the frequency region of the H2O bend mode. The ab initio calculated values of the rotational and distortion constants agree well with the values extracted from this spectrum.

  10. The Triple Functions of D2 Silencing in Treatment of Periapical Disease.

    PubMed

    Pan, Jie; Wang, Jue; Hao, Liang; Zhu, Guochun; Nguyen, Diep N; Li, Qian; Liu, Yuehua; Zhao, Zhihe; Li, Yi-Ping; Chen, Wei

    2017-02-01

    Dental caries is the most widespread chronic infectious disease. Inflammation in pulp tissues caused by dental caries will lead to periapical granulomas, bone erosion, loss of the tooth, and severe pain. Despite numerous efforts in recent studies to develop effective treatments for dental caries, the need for a potent therapy is still urgent. In this study, we applied a gene-based therapy approach by administering recombinant adeno-associated virus (AAV)-mediated Atp6v0d2 (d2) RNA interference knockdown of d2 gene expression to prevent periapical bone loss and suppress periapical inflammation simultaneously. The results showed that d2 depletion is simultaneously capable of reducing bone resorption with 75% protection through reducing osteoclasts, enhancing bone formation by increasing osterix expression, and inhibiting inflammation by decreasing T-cell infiltration. Notably, AAV-mediated gene therapy of d2 knockdown significantly reduced proinflammatory cytokine expression, including tumor necrosis factor α, interferon-γ, interleukin-1α, and interleukin 6 levels in periapical diseases caused by bacterial infection. Quantitative real-time polymerase chain reaction revealed that d2 knockdown reduced osteoclast-specific functional genes (ie, Acp5 and Ctsk) and increased osteoblast marker genes (ie, Osx and Opg) in periapical tissues. Collectively, our results showed that AAV-mediated d2 depletion in the periapical lesion area can prevent the progression of endodontic disease and bone erosion while significantly reducing the inflammatory over-response. These findings show that the depletion of d2 simultaneously reduces bone resorption, enhances bone formation, and inhibits inflammation caused by periapical diseases and provide significant insights into the potential effectiveness of AAV-sh-d2-mediated d2 silencing gene therapy as a major endodontic treatment. Copyright © 2016. Published by Elsevier Inc.

  11. Identification of resolvin D2 receptor mediating resolution of infections and organ protection

    PubMed Central

    Chiang, Nan; Dalli, Jesmond; Colas, Romain A.

    2015-01-01

    Endogenous mechanisms that orchestrate resolution of acute inflammation are essential in host defense and the return to homeostasis. Resolvin (Rv)D2 is a potent immunoresolvent biosynthesized during active resolution that stereoselectively stimulates resolution of acute inflammation. Here, using an unbiased G protein–coupled receptor-β-arrestin–based screening and functional sensing systems, we identified a receptor for RvD2, namely GPR18, that is expressed on human leukocytes, including polymorphonuclear neutrophils (PMN), monocytes, and macrophages (MΦ). In human MΦ, RvD2-stimulated intracellular cyclic AMP was dependent on GPR18. RvD2-stimulated phagocytosis of Escherichia coli and apoptotic PMN (efferocytosis) were enhanced with GPR18 overexpression and significantly reduced by shRNA knockdown. Specific binding of RvD2 to recombinant GPR18 was confirmed using a synthetic 3H-labeled-RvD2. Scatchard analysis gave a Kd of ∼10 nM consistent with RvD2 bioactive concentration range. In both E. coli and Staphylococcus aureus infections, RvD2 limited PMN infiltration, enhanced phagocyte clearance of bacteria, and accelerated resolution. These actions were lost in GPR18-deficient mice. During PMN-mediated second organ injury, RvD2’s protective actions were also significantly diminished in GPR18-deficient mice. Together, these results provide evidence for a novel RvD2–GPR18 resolution axis that stimulates human and mouse phagocyte functions to control bacterial infections and promote organ protection. PMID:26195725

  12. Age-related changes in dopamine D2 receptors in rat heart and coronary vessels.

    PubMed

    Cavallotti, Carlo; Nuti, Federica; Bruzzone, Paolo; Mancone, Massimo

    2002-01-01

    1. The distribution of dopamine D2 receptors in rat heart and coronary vessels and the possible age-related changes in D2 receptor density were studied. The pharmacological characteristics and the anatomical location of dopamine D2-like receptor sites in rat heart and coronary vessels were investigated using combined binding techniques and light microscopy autoradiography. 2. Samples of heart and coronary vessels were harvested from young and old rats. On frozen slices, dopaminergic D2 receptors were labelled by means of a selective D2 ligand, namely [3H]-spiroperidol (spiperone). Inhibition studies were performed using unlabelled agonists and/or labelled and unlabelled antagonists to define pharmacological specificity of the binding. Physiological experiments were performed to demonstrate the selective antagonism between D2 receptors and many dopaminergic drugs. 3. [3H]-Spiroperidol was bound to sections of rat heart and coronary artery (in a manner consistent with the labelling of dopamine D2-like receptors) with an equilibrium dissociation constant of approximately 2.4 +/- 0.7 nmol/L and a maximum capacity of binding sites of 65.8 +/- 4.5 fmol/mg protein. Experiments performed on sections of coronary veins did not allow the evaluation of specific binding. Autoradiography, observed with light microscopy, showed the development of specific silver grains within the whole wall of rat heart and coronary artery. The greater sensitivity to displacement by amisulpride, bromocriptine, domperidone, haloperidol, raclopride and L-sulpiride than to displacement by N-propyl-norapomorphine, quinpirole and clozapine suggests that the binding sites observed in these experiments are likely to belong to the dopamine D2 receptor subtype. 4. Comparing results in young and old rats, we observed numerous significant age-related changes, including a decrease in D2 receptors localized in rat heart and coronary artery wall. These D2 receptors show a specific location, in close

  13. The dopaminergic stabilizer ASP2314/ACR16 selectively interacts with D2(High) receptors.

    PubMed

    Seeman, Philip; Tokita, Kenichi; Matsumoto, Mitsuyuki; Matsuo, Ayako; Sasamata, Masao; Miyata, Keiji

    2009-10-01

    Dopaminergic stabilizers are recognized as compounds that can either enhance or antagonize dopamine (DA)-dependent behaviors depending on the prevailing dopaminergic tone. The dopaminergic stabilizer ASP2314 is being tested clinically and has been reported to have antipsychotic effects in a clinical trial as an add on medication. To elucidate the mechanisms of action of this dopaminergic stabilizer, its potency on the functional dopamine D2(High) receptors was examined. In competition with D2 receptors selectively labeled by [3H]domperidone, ASP2314 had a dissociation constant, Ki(High), of 1.62 microM for D2(High) in human cloned D2Long receptors and 0.83 muM for rat homogenized striata. Using the D2 agonist ligand [3H](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ((+)PHNO), ASP2314 had a high-affinity Ki of 32 nM for D2(High) for rat homogenized striata. ASP2314 stimulated the incorporation of [35S]GTP-gamma-S into rat striata by 50% at 43 nM, and into the cloned D2Long membranes by 50% at 3.2 microM (compared to 100% stimulation by 10 microM dopamine). With similar concentrations of ASP2314 inhibiting the binding of ligands at D2(High) and stimulating [35S]GTP-gamma-S incorporation, the data indicate that the dopaminergic stabilizing action of ASP2314 may be related to the selectivity for the D2(high) state of the D2 receptor.

  14. Tctex1d2 Is a Negative Regulator of GLUT4 Translocation and Glucose Uptake.

    PubMed

    Shimoda, Yoko; Okada, Shuichi; Yamada, Eijiro; Pessin, Jeffrey E; Yamada, Masanobu

    2015-10-01

    Tctex1d2 (Tctex1 domain containing 2) is an open reading frame that encodes for a functionally unknown protein that contains a Tctex1 domain found in dynein light chain family members. Examination of gene expression during adipogenesis demonstrated a marked increase in Tctex1d2 protein expression that was essentially undetectable in preadipocytes and markedly induced during 3T3-L1 adipocyte differentiation. Tctex1d2 overexpression significantly inhibited insulin-stimulated glucose transporter 4 (GLUT4) translocation and 2-deoxyglucose uptake. In contrast, Tctex1d2 knockdown significantly increased insulin-stimulated GLUT4 translocation and 2-deoxyglucose uptake. However, acute insulin stimulation (up to 30 min) in 3T3-L1 adipocytes with overexpression or knockdown of Tctex1d2 had no effect on Akt phosphorylation, a critical signal transduction target required for GLUT4 translocation. Although overexpression of Tctex1d2 had no significant effect on GLUT4 internalization, Tctex1d2 was found to associate with syntaxin 4 in an insulin-dependent manner and inhibit Doc2b binding to syntaxin 4. In addition, glucose-dependent insulinotropic polypeptide rescued the Tctex1d2 inhibition of insulin-stimulated GLUT4 translocation by suppressing the Tctex1d2-syntaxin 4 interaction and increasing Doc2b-Synatxin4 interactions. Taking these results together, we hypothesized that Tctex1d2 is a novel syntaxin 4 binding protein that functions as a negative regulator of GLUT4 plasma membrane translocation through inhibition of the Doc2b-syntaxin 4 interaction.

  15. Evidence that antipsychotic drugs are inverse agonists at D2 dopamine receptors.

    PubMed

    Hall, D A; Strange, P G

    1997-06-01

    1. The effects of a number of D2-like dopamine receptor antagonists have been determined on forskolin-stimulated cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing the human D2short dopamine receptor (CHO-D2S cells). 2. Dopamine inhibited the effect of forskolin (as expected for a D2 receptor). However, all of the antagonists tested, apart from UH232 and (-)-butaclamol, were able to increase cyclic AMP accumulation above the forskolin control level. (+)-Butaclamol elicited a similar stimulation of forskolin-stimulated cyclic AMP accumulation in a CHO cell line expressing human D2long dopamine receptors whereas it exhibited no stimulating effect on forskolin-stimulated cyclic AMP accumulation in untransfected CHO-K1 cells. 3. There was a strong correlation between the EC50 values of these compounds for potentiation of cyclic AMP accumulation and their Ki values from radioligand binding experiments in CHO-D2S cells. 4. The effects of both (+)-butaclamol and dopamine in CHO-D2S cells were inhibited by pre-treatment with pertussis toxin indicating a role for Gi/Go proteins. 5. UH232 did not significantly affect forskolin-stimulated cyclic AMP accumulation but this substance was able to inhibit the effects of both dopamine and (+)-butaclamol in a concentration-dependent manner. Thus the effects of (+)-butaclamol on forskolin-stimulated cyclic AMP accumulation are mediated directly via the D2 receptor rather than by reversal of the effects of an endogenous agonist. 6. These data suggest that the D2 dopamine receptor antagonists tested here, many of which are used clinically as antipsychotic drugs, are in fact inverse agonists at human D2 dopamine receptors.

  16. Agonist signalling properties of radiotracers used for imaging of dopamine D2/3 receptors

    PubMed Central

    2014-01-01

    Background Dopamine D2/3 receptor (D2/3R) agonist radiopharmaceuticals are considered superior to antagonists to detect dopamine release, e.g. induced by amphetamines. Agonists bind preferentially to the high-affinity state of the dopamine D2R, which has been proposed as the reason why agonists are more sensitive to detect dopamine release than antagonist radiopharmaceuticals, but this theory has been challenged. Interestingly, not all agonists similarly activate the classic cyclic adenosine mono phosphate (cAMP) and the ?-arrestin-2 pathway, some stimulate preferentially one of these pathways; a phenomenon called biased agonism. Because these pathways can be affected separately by pathologies or drugs (including dopamine releasers), it is important to know how agonist radiotracers act on these pathways. Therefore, we characterized the intracellular signalling of the well-known D2/3R agonist radiopharmaceuticals NPA and PHNO and of several novel D2/3R agonists. Methods cAMP accumulation and ?-arrestin-2 recruitment were measured on cells expressing human D2R. Results All tested agonists showed (almost) full agonism in both pathways. Conclusions The tested D2/3R agonist radiopharmaceuticals did not exhibit biased agonism in vitro. Consequently, it is likely that drugs (including psychostimulants like amphetamines) and/or pathologies that influence the cAMP and/or the ?-arrestin-2 pathway may influence the binding of these radiopharmaceuticals. PMID:25977878

  17. Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation.

    PubMed

    de Jong, Johannes W; Roelofs, Theresia J M; Mol, Frédérique M U; Hillen, Anne E J; Meijboom, Katharina E; Luijendijk, Mieneke C M; van der Eerden, Harrie A M; Garner, Keith M; Vanderschuren, Louk J M J; Adan, Roger A H

    2015-08-01

    Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior.

  18. Structure-Based Virtual Screening for Dopamine D2 Receptor Ligands as Potential Antipsychotics.

    PubMed

    Kaczor, Agnieszka A; Silva, Andrea G; Loza, María I; Kolb, Peter; Castro, Marián; Poso, Antti

    2016-04-05

    Structure-based virtual screening using a D2 receptor homology model was performed to identify dopamine D2 receptor ligands as potential antipsychotics. From screening a library of 6.5 million compounds, 21 were selected and were subjected to experimental validation. From these 21 compounds tested, ten D2 ligands were identified (47.6% success rate, among them D2 receptor antagonists, as expected) that have additional affinity for other receptors tested, in particular 5-HT2A receptors. The affinity (Ki values) of the compounds ranged from 58 nm to about 24 μM. Similarity and fragment analysis indicated a significant degree of structural novelty among the identified compounds. We found one D2 receptor antagonist that did not have a protonatable nitrogen atom, which is a key structural element of the classical D2 pharmacophore model necessary for interaction with the conserved Asp(3.32) residue. This compound exhibited greater than 20-fold binding selectivity for the D2 receptor over the D3 receptor. We provide additional evidence that the amide hydrogen atom of this compound forms a hydrogen bond with Asp(3.32), as determined by tests of its derivatives that cannot maintain this interaction. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

    PubMed

    Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2017-08-01

    The dopamine D2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D2 receptor. D2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D2 receptors. D2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

  20. Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines.

    PubMed

    Nair, Venugopalan D; Olanow, C Warren; Sealfon, Stuart C

    2003-07-01

    Whereas dopamine agonists are known to provide symptomatic benefits for Parkinson's disease, recent clinical trials suggest that they might also be neuroprotective. Laboratory studies demonstrate that dopamine agonists can provide neuroprotective effects in a number of model systems, but the role of receptor-mediated signalling in these effects is controversial. We find that dopamine agonists have robust, concentration-dependent anti-apoptotic activity in PC12 cells that stably express human D(2L) receptors from cell death due to H(2)O(2) or trophic withdrawal and that the protective effects are abolished in the presence of D(2)-receptor antagonists. D(2) agonists are also neuroprotective in the nigral dopamine cell line SN4741, which express endogenous D(2) receptors, whereas no anti-apoptotic activity is observed in native PC12 cells, which do not express detectable D(2) receptors. Notably, the agonists studied differ in their relative efficacy to mediate anti-apoptotic effects and in their capacity to stimulate [(35)S]guanosine 5'-[gamma-thio]triphosphate ([(35)S]GTP[S]) binding, an indicator of G-protein activation. Studies with inhibitors of phosphoinositide 3-kinase (PI 3-kinase), extracellular-signal-regulated kinase or p38 mitogen-activated protein kinase indicate that the PI 3-kinase pathway is required for D(2) receptor-mediated cell survival. These studies indicate that certain dopamine agonists can complex with D(2) receptors to preferentially transactivate neuroprotective signalling pathways and to mediate increased cell survival.

  1. Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation

    PubMed Central

    de Jong, Johannes W; Roelofs, Theresia J M; Mol, Frédérique M U; Hillen, Anne E J; Meijboom, Katharina E; Luijendijk, Mieneke C M; van der Eerden, Harrie A M; Garner, Keith M; Vanderschuren, Louk J M J; Adan, Roger A H

    2015-01-01

    Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior. PMID:25735756

  2. Dopamine D2/3 receptor antagonism reduces activity-based anorexia

    PubMed Central

    Klenotich, S J; Ho, E V; McMurray, M S; Server, C H; Dulawa, S C

    2015-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by severe hypophagia and weight loss, and an intense fear of weight gain. Activity-based anorexia (ABA) refers to the weight loss, hypophagia and paradoxical hyperactivity that develops in rodents exposed to running wheels and restricted food access, and provides a model for aspects of AN. The atypical antipsychotic olanzapine was recently shown to reduce both AN symptoms and ABA. We examined which component of the complex pharmacological profile of olanzapine reduces ABA. Mice received 5-HT2A/2C, 5-HT3, dopamine D1-like, D2, D3 or D2/3 antagonist treatment, and were assessed for food intake, body weight, wheel running and survival in ABA. D2/3 receptor antagonists eticlopride and amisulpride reduced weight loss and hypophagia, and increased survival during ABA. Furthermore, amisulpride produced larger reductions in weight loss and hypophagia than olanzapine. Treatment with either D3 receptor antagonist SB277011A or D2 receptor antagonist L-741,626 also increased survival. All the other treatments either had no effect or worsened ABA. Overall, selective antagonism of D2 and/or D3 receptors robustly reduces ABA. Studies investigating the mechanisms by which D2 and/or D3 receptors regulate ABA, and the efficacy for D2/3 and/or D3 antagonists to treat AN, are warranted. PMID:26241351

  3. Dopamine D2 receptor mRNA measured in serial sections of the rat anterior pituitary.

    PubMed

    Piano, J Z; Pogacnik, A

    2001-01-01

    Dopamine D2 receptors (D2-Rs) on lactotrophs in the pituitary gland are targets for dopamine to inhibit prolactin synthesis and release. The aim of our study was to examine if subpopulations of cells in the anterior pituitary that respond differently to dopamine show different pattern of D2-R mRNA expression. Therefore, we have used quantitative in situ hybridization technique to study the localisation of D2-R mRNA in the rat adenohypophysis. Pituitary tissue was obtained from mature and 18 days old rats. Riboprobe was transcribed from rat pituitary cDNA clone encoding D2-R and hybridized in situ with the serial sections of the pituitaries. Our results show that, although the anterior lobe of the pituitary gland contains a variety of cell types distributed in clusters, D2-R mRNA is relatively evenly distributed through the adenohypophysis. Level of expression of D2-R mRNA in the pituitary is slightly higher in mature than in young rats.

  4. Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors

    PubMed Central

    Bello, Estefanía P; Mateo, Yolanda; Gelman, Diego M; Noaín, Daniela; Shin, Jung H; Low, Malcolm J; Alvarez, Verónica A; Lovinger, David M; Rubinstein, Marcelo

    2011-01-01

    Dopamine (DA) D2 receptors expressed in DA neurons (D2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2loxP/loxP; Dat+/IRES-cre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine. PMID:21743470

  5. Discovery of G Protein-Biased D2 Dopamine Receptor Partial Agonists.

    PubMed

    Chen, Xin; McCorvy, John D; Fischer, Matthew G; Butler, Kyle V; Shen, Yudao; Roth, Bryan L; Jin, Jian

    2016-12-08

    Biased ligands (also known as functionally selective ligands) of G protein-coupled receptors are valuable tools for dissecting the roles of G protein-dependent and independent signaling pathways in health and disease. Biased ligands have also been increasingly pursued by the biomedical community as promising therapeutics with improved efficacy and reduced side effects compared with unbiased ligands. We previously discovered first-in-class β-arrestin-biased agonists of dopamine D2 receptor (D2R) by extensively exploring multiple regions of aripiprazole, a balanced D2R agonist. In our continuing efforts to identify biased agonists of D2R, we unexpectedly discovered a G protein-biased agonist of D2R, compound 1, which is the first G protein-biased D2R agonist from the aripiprazole scaffold. We designed and synthesized novel analogues to explore two regions of 1 and conducted structure-functional selectivity relationship (SFSR) studies. Here we report the discovery of 1, findings from our SFSR studies, and characterization of novel G protein-biased D2R agonists.

  6. A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.

    PubMed

    Su, Ping; Liu, Fang

    2017-09-01

    Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels. Here we found that an interfering peptide (DAT-S1) disrupting the D2R-DAT interaction protects neurons against dopamine neurotoxicity, and this effect is mediated by inhibiting DAT cell surface expression and inhibiting both caspase-3 and PARP-1 cleavage. This study demonstrates the role of the D2R-DAT complex in dopamine neurotoxicity and investigated the potential mechanisms, which might help better understand the mechanisms of dopamine neurotoxicity. The peptide may provide some insights to improve treatments for dopamine neurotoxicity and related diseases, such as Parkinson's disease, as well as methamphetamine- and 3,4-methsylenedioxy methamphetamine-induced neurotoxicity. Copyright © 2017. Published by Elsevier Inc.

  7. Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours.

    PubMed

    Sim, Hye-Ri; Choi, Tae-Yong; Lee, Hyo Jin; Kang, Eun Young; Yoon, Sehyoun; Han, Pyung-Lim; Choi, Se-Young; Baik, Ja-Hyun

    2013-01-01

    Dopaminergic systems are implicated in stress-related behaviour. Here we investigate behavioural responses to chronic stress in dopamine D2 receptor knockout mice and find that anxiety-like behaviours are increased compared with wild-type mice. Repeated stress exposure suppresses cocaine-induced behavioural sensitization, cocaine-seeking and relapse behaviours in dopamine D2 receptor knockout mice. Cocaine challenge after drug withdrawal in cocaine-experienced wild-type or dopamine D2 receptor knockout mice is associated with inhibition of long-term depression in the nucleus accumbens, and chronic stress during withdrawal prevents inhibition after cocaine challenge in cocaine-experienced dopamine D2 receptor knockout mice, but not in wild-type mice. Lentiviral-induced knockdown of dopamine D2 receptors in the nucleus accumbens of wild-type mice does not affect basal locomotor activity, but confers stress-induced inhibition of the expression of cocaine-induced behavioural sensitization. Stressed mice depleted of dopamine D2 receptors do not manifest long-term depression inhibition. Our results suggest that dopamine D2 receptors have roles in regulating synaptic modification triggered by stress and drug addiction.

  8. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose

    PubMed Central

    Seeman, P

    2016-01-01

    Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects. PMID:27754480

  9. Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.

    PubMed

    Kahnt, Thorsten; Weber, Susanna C; Haker, Helene; Robbins, Trevor W; Tobler, Philippe N

    2015-03-04

    The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs.

  10. Deficient dopamine D2 receptor function causes renal inflammation independently of high blood pressure.

    PubMed

    Zhang, Yanrong; Cuevas, Santiago; Asico, Laureano D; Escano, Crisanto; Yang, Yu; Pascua, Annabelle M; Wang, Xiaoyan; Jones, John E; Grandy, David; Eisner, Gilbert; Jose, Pedro A; Armando, Ines

    2012-01-01

    Renal dopamine receptors participate in the regulation of blood pressure. Genetic factors, including polymorphisms of the dopamine D(2) receptor gene (DRD2) are associated with essential hypertension, but the mechanisms of their contribution are incompletely understood. Mice lacking Drd2 (D(2)-/-) have elevated blood pressure, increased renal expression of inflammatory factors, and renal injury. We tested the hypothesis that decreased dopamine D(2) receptor (D(2)R) function increases vulnerability to renal inflammation independently of blood pressure, is an immediate cause of renal injury, and contributes to the subsequent development of hypertension. In D(2)-/- mice, treatment with apocynin normalized blood pressure and decreased oxidative stress, but did not affect the expression of inflammatory factors. In mouse RPTCs Drd2 silencing increased the expression of TNFα and MCP-1, while treatment with a D(2)R agonist abolished the angiotensin II-induced increase in TNF-α and MCP-1. In uni-nephrectomized wild-type mice, selective Drd2 silencing by subcapsular infusion of Drd2 siRNA into the remaining kidney produced the same increase in renal cytokines/chemokines that occurs after Drd2 deletion, increased the expression of markers of renal injury, and increased blood pressure. Moreover, in mice with two intact kidneys, short-term Drd2 silencing in one kidney, leaving the other kidney undisturbed, induced inflammatory factors and markers of renal injury in the treated kidney without increasing blood pressure. Our results demonstrate that the impact of decreased D(2)R function on renal inflammation is a primary effect, not necessarily associated with enhanced oxidant activity, or blood pressure; renal damage is the cause, not the result, of hypertension. Deficient renal D(2)R function may be of clinical relevance since common polymorphisms of the human DRD2 gene result in decreased D(2)R expression and function.

  11. Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil.

    PubMed

    Seeman, Philip; Guan, Hong-Chang; Hirbec, Hélène

    2009-08-01

    Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 receptors in homogenates of rat brain striatum. This study, therefore, examined whether phencyclidine and other hallucinogens and psychostimulants could stimulate the incorporation of [(35)S]GTP-gamma-S into D2 receptors in homogenates of rat brain striatum, using the same conditions as previously used to study the cloned D2 receptors. Using 10 microM dopamine to define 100% stimulation, phencyclidine elicited a maximum incorporation of 46% in rat striata, with a half-maximum concentration of 70 nM for phencyclidine, when compared with 80 nM for dopamine, 89 nM for salvinorin A (48 nM for D2Long), 105 nM for lysergic acid diethylamide (LSD), 120 nM for R-modafinil, 710 nM for dizocilpine, 1030 nM for ketamine, and >10,000 nM for S-modafinil. These compounds also inhibited the binding of the D2-selective ligand [(3)H]domperidone. The incorporation was inhibited by the presence of 200 microM guanylylimidodiphosphate and also by D2 blockade, using 10 microM S-sulpiride, but not by D1 blockade with 10 microM SCH23390. Hypertonic buffer containing 150 mM NaCl inhibited the stimulation by phencyclidine, which may explain negative results by others. It is concluded that phencyclidine and other psychostimulants and hallucinogens can stimulate dopamine D2 receptors at concentrations related to their behavioral actions.

  12. Quantitative Imaging of D-2-Hydroxyglutarate in Selected Histological Tissue Areas by a Novel Bioluminescence Technique.

    PubMed

    Voelxen, Nadine F; Walenta, Stefan; Proescholdt, Martin; Dettmer, Katja; Pusch, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    Patients with malignant gliomas have a poor prognosis with average survival of less than 1 year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite that was discovered first in this tumor entity. D2HG is generated in large amounts due to various "gain-of-function" mutations in the isocitrate dehydrogenases IDH1 and IDH2. Meanwhile, D2HG has been detected in several other tumor entities, including intrahepatic bile-duct cancer, chondrosarcoma, acute myeloid leukemia, and angioimmunoblastic T-cell lymphoma. D2HG is barely detectable in healthy tissue (<0.1 mM), but its concentration increases up to 35 mM in malignant tumor tissues. Consequently, the "oncometabolite" D2HG has gained increasing interest in the field of tumor metabolism. To facilitate its quantitative measurement without loss of spatial resolution at a microscopical level, we have developed a novel bioluminescence assay for determining D2HG in sections of snap-frozen tissue. The assay was verified independently by photometric tests and liquid chromatography/mass spectrometry. The novel technique allows the microscopically resolved determination of D2HG in a concentration range of 0-10 μmol/g tissue (wet weight). In combination with the already established bioluminescence imaging techniques for ATP, glucose, pyruvate, and lactate, the novel D2HG assay enables a comparative characterization of the metabolic profile of individual tumors in a further dimension.

  13. Vitamin D(3) is more potent than vitamin D(2) in humans.

    PubMed

    Heaney, Robert P; Recker, Robert R; Grote, James; Horst, Ronald L; Armas, Laura A G

    2011-03-01

    Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2) (D2) and D(3) (D3) are biologically equivalent. Published studies yield mixed results. The aim of the study was to compare the potencies of D2 and D3. The trial used a single-blind, randomized design in 33 healthy adults. Calciferols were dosed at 50,000 IU/wk for 12 wk. Principal outcome variables were area under the curve for incremental total 25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat. Incremental mean (sd) 25(OH)D area under the curve at 12 wk was 1366 ng · d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P < 0.001). Mean (sd) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2 (10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fat content of D2 rose by 50 μg/kg in the D2-treated group, and D3 content rose by 104 μg/kg in the D3-treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated, whereas it rose by 104 μg/kg in the D3-treated group. Extrapolating to total body fat D3, storage amounted to just 17% of the administered dose. D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.

  14. Withdrawal from continuous or intermittent cocaine administration: changes in D2 receptor function.

    PubMed

    King, G R; Ellinwood, E H; Silvia, C; Joyner, C M; Xue, Z; Caron, M G; Lee, T H

    1994-05-01

    Intermittent cocaine administration produces sensitization, whereas the continuous administration of cocaine produces tolerance to the effects of subsequent cocaine administration during withdrawal. The present study examined whether the effects of these two dosing regimens are related to alterations in the functional status of dopamine (DA) D2 receptors. In all experiments, rats were withdrawn for 7 days from a 14-day pretreatment regimen involving either continuous or intermittent cocaine administration. Experiments examined changes in the behavioral response to an autoreceptor-selective dose of apomorphine, the effects of sulpiride on electrically stimulated DA release in striatal brain slices and striatal D2 receptor binding, and mRNA levels. The results indicate that the continuous administration of cocaine produces findings consistent with D2 autoreceptor supersensitivity; there was enhanced inhibition of behavior after the autoreceptor-selective dose of apomorphine, decreased electrically stimulated DA release in the absence of sulpiride, and enhanced electrically stimulated DA release in the presence of sulpiride. However, there were no changes in postsynaptic D2 receptor binding or mRNA levels. Intermittent cocaine administration did not produce evidence of D2 autoreceptor subsensitivity: there was no decrease in inhibition of behavior after the autoreceptor-selective dose of apomorphine, no changes in electrically stimulated DA release in the absence or presence of D2 receptor blockade, and no change in the levels of D2 receptor binding; however, D2 mRNA levels were decreased by 22%. Overall, the present results are consistent with the hypothesis that the expression of tolerance induced by continuous cocaine administration is associated with D2 autoreceptor supersensitivity.

  15. 3D-2D ultrasound feature-based registration for navigated prostate biopsy: a feasibility study.

    PubMed

    Selmi, Sonia Y; Promayon, Emmanuel; Troccaz, Jocelyne

    2016-08-01

    The aim of this paper is to describe a 3D-2D ultrasound feature-based registration method for navigated prostate biopsy and its first results obtained on patient data. A system combining a low-cost tracking system and a 3D-2D registration algorithm was designed. The proposed 3D-2D registration method combines geometric and image-based distances. After extracting features from ultrasound images, 3D and 2D features within a defined distance are matched using an intensity-based function. The results are encouraging and show acceptable errors with simulated transforms applied on ultrasound volumes from real patients.

  16. Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling☆

    PubMed Central

    Drigo, Rafael Arrojo; Fonseca, Tatiana L.; Werneck-de-Castro, Joao Pedro Saar; Bianco, Antonio C.

    2016-01-01

    Scope of the review This review covers the recent advances in D2 biology, a member of the iodothyronine deiodinase family, thioredoxin fold-containing selenoenzymes that modify thyroid hormone signaling in a time- and cell-specific manner. The type II (D2) deiodinase catalyzes T4-to-T3 conversion as opposed to the type III (D3) deiodinase that terminates thyroid hormone action. Major conclusions D2-catalyzed T3 production increases thyroid hormone signaling whereas blocking D2 activity or disruption of the Dio2 gene leads to a state of localized hypothyroidism. D2 expression is regulated by different developmental, metabolic or environmental cues such as the hedgehog pathway, the adrenergic-and the TGR5-activated cAMP pathway, by xenobiotic molecules such as flavonols and by stress in the endoplasmic reticulum, which specifically reduces de novo synthesis of D2 via an eIF2a-mediated mechanism. Thus, D2 plays a central role in important physiological processes such as determining T3 content in developing tissues and in the adult brain, and promoting adaptive thermogenesis in brown adipose tissue. Notably, D2 is critical in the T4-mediated negative feed-back at the pituitary and hypothalamic levels, whereby T4 inhibits TSH and TRH expression, respectively. Notably, ubiquitination is a major step in the control of D2 activity, whereby T4 binding to and/or T4 catalysis triggers D2 inactivation by ubiquitination that is mediated by the E3 ubiquitin ligases WSB-1 and/or TEB4. Ubiquitinated D2 can be either targeted to proteasomal degradation or reactivated by deubiquitination, a process that is mediated by the deubiquitinases USP20/33 and is important in adaptive thermogenesis. General significance Here we review the recent advances in the understanding of D2 biology focusing on the mechanisms that regulate its expression and their biological significance in metabolically relevant tissues. This article is part of a Special Issue entitled Thyroid hormone signalling. PMID

  17. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

    PubMed Central

    Schmidts, Miriam; Hou, Yuqing; Cortés, Claudio R.; Mans, Dorus A.; Huber, Celine; Boldt, Karsten; Patel, Mitali; van Reeuwijk, Jeroen; Plaza, Jean-Marc; van Beersum, Sylvia E. C.; Yap, Zhi Min; Letteboer, Stef J. F.; Taylor, S. Paige; Herridge, Warren; Johnson, Colin A.; Scambler, Peter J.; Ueffing, Marius; Kayserili, Hulya; Krakow, Deborah; King, Stephen M.; Beales, Philip L.; Al-Gazali, Lihadh; Wicking, Carol; Cormier-Daire, Valerie; Roepman, Ronald; Mitchison, Hannah M.; Witman, George B.; Al-Turki, Saeed; Anderson, Carl; Anney, Richard; Antony, Dinu; Asimit, Jennifer; Ayub, Mohammad; Barrett, Jeff; Barroso, Inês; Bentham, Jamie; Bhattacharya, Shoumo; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick; Boustred, Chris; Breen, Gerome; Brion, Marie-Jo; Brown, Andrew; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Chen, Lu; Cirak, Sebhattin; Clapham, Peter; Clement, Gail; Coates, Guy; Collier, David; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Daly, Allan; Danecek, Petr; Smith, George Davey; Day-Williams, Aaron; Day, Ian; Durbin, Richard; Edkins, Sarah; Ellis, Peter; Evans, David; Farooqi, I. Sadaf; Fatemifar, Ghazaleh; Fitzpatrick, David; Flicek, Paul; Floyd, Jamie; Foley, A. Reghan; Franklin, Chris; Futema, Marta; Gallagher, Louise; Gaunt, Tom; Geschwind, Daniel; Greenwood, Celia; Grozeva, Detelina; Guo, Xiaosen; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey; Holmans, Peter; Huang, Jie; Humphries, Steve E.; Hurles, Matt; Hysi, Pirro; Jackson, David; Jamshidi, Yalda; Jewell, David; Chris, Joyce; Kaye, Jane; Keane, Thomas; Kemp, John; Kennedy, Karen; Kent, Alastair; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lee, Irene; Li, Rui; Li, Yingrui; Ryan, Liu; Lönnqvist, Jouko; Lopes, Margarida; MacArthur, Daniel G.; Massimo, Mangino; Marchini, Jonathan; Maslen, John; McCarthy, Shane; McGuffin, Peter; McIntosh, Andrew; McKechanie, Andrew; McQuillin, Andrew; Memari, Yasin; Metrustry, Sarah; Min, Josine; Moayyeri, Alireza; Morris, James; Muddyman, Dawn; Muntoni, Francesco; Northstone, Kate; O'Donovan, Michael; O'Rahilly, Stephen; Onoufriadis, Alexandros; Oualkacha, Karim; Owen, Michael; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Perry, John; Pietilainen, Olli; Plagnol, Vincent; Quail, Michael A.; Quaye, Lydia; Raymond, Lucy; Rehnström, Karola; Brent Richards, J.; Ring, Sue; Ritchie, Graham R S; Savage, David B.; Schoenmakers, Nadia; Semple, Robert K.; Serra, Eva; Shihab, Hashem; Shin, So-Youn; Skuse, David; Small, Kerrin; Smee, Carol; Soler, Artigas María; Soranzo, Nicole; Southam, Lorraine; Spector, Tim; St Pourcain, Beate; St. Clair, David; Stalker, Jim; Surdulescu, Gabriela; Suvisaari, Jaana; Tachmazidou, Ioanna; Tian, Jing; Timpson, Nic; Tobin, Martin; Valdes, Ana; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Wain, Louise; Walter, Klaudia; Wang, Jun; Ward, Kirsten; Wheeler, Ellie; Whittall, Ros; Williams, Hywel; Williamson, Kathy; Wilson, Scott G.; Wong, Kim; Whyte, Tamieka; ChangJiang, Xu; Zeggini, Eleftheria; Zhang, Feng; Zheng, Hou-Feng

    2015-01-01

    The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions. PMID:26044572

  18. D5 dopamine receptor carboxyl tail involved in D5-D2 heteromer formation

    PubMed Central

    O’Dowd, Brian F.; Nguyen, Tuan; Ji, Xiaodong; George, Susan R.

    2013-01-01

    We have demonstrated that D5 and D2 dopamine receptors exist as heteromers in cells, and determined these receptor interact through amino acids in the cytoplasmic regions of each receptor. Specifically involved in heteromer formation we identified in the carboxyl tail of the D5 receptor three adjacent glutamic acid residues, and in intracellular loop 3 of the D2 receptor two adjacent arginine residues. Any pairing of these three D5 receptor glutamic acids were sufficient for heteromer formation. These identified residues in D5 and D2 receptors are oppositely charged and likely interact by electrostatic interactions. PMID:23318175

  19. Chronic social defeat stress increases dopamine D2 receptor dimerization in the prefrontal cortex of adult mice.

    PubMed

    Bagalkot, T R; Jin, H-M; Prabhu, V V; Muna, S S; Cui, Y; Yadav, B K; Chae, H-J; Chung, Y-C

    2015-12-17

    The present study aimed to examine the effects of chronic social defeat stress on the dopamine receptors and proteins involved in post-endocytic trafficking pathways. Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. Western blot analysis was used to measure the protein expression levels of dopamine D2 receptors (D2Rs), a short (D2S) and a long form (D2L) and, D2R monomers and dimers, dopamine D1 receptors (D1Rs), neuronal calcium sensor-1 (NCS-1) and G protein-coupled receptor-associated sorting protein-1 (GASP-1), and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of D2S, D2L, D2R monomers and dimers, and D1Rs in different brain areas. We observed increased expression of D2S, D2L and D2Rs dimers in the prefrontal cortex (PFC) of susceptible and/or unsusceptible mice compared with controls. The only significant findings with regard to mRNA expression levels were lower expression of D2S mRNA in the amygdala (AMYG) of susceptible and unsusceptible mice compared with controls. The present study demonstrated that chronic social defeat stress induced increased expression of D2S, D2L, and D2R dimers in the PFC of susceptible and/or unsusceptible mice.

  20. D2 to D2

    NASA Astrophysics Data System (ADS)

    Ezhuthachan, Bobby; Mukhi, Sunil; Papageorgakis, Constantinos

    2008-07-01

    Starting from maximally supersymmetric (2+1)d Yang-Mills theory and using a duality transformation due to de Wit, Nicolai and Samtleben, we obtain the ghost-free Lorentzian 3-algebra theory that has recently been proposed to describe M2-branes. Our derivation does not invoke any properties of 3-algebras. Being derivable from SYM, the final theory is manifestly equivalent to it on-shell and should not be thought of as the IR limit that describes M2-branes, though it does have enhanced R-symmetry as well as superconformal symmetry off-shell.

  1. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED UNDER THE ENERGY POLICY AND CONSERVATION ACT (âAPPLIANCE LABELING RULEâ) Pt. 305, App. D2...

  2. Near infrared second overtone cw-cavity ringdown spectroscopy of D2H+ ions

    NASA Astrophysics Data System (ADS)

    Hlavenka, P.; Plasil, R.; Bano, G.; Korolov, I.; Gerlich, D.; Ramanlal, J.; Tennyson, J.; Glosik, J.

    2006-09-01

    A study of D2H+ ions in their lowest rotational states is presented. The ions are generated in pulsed discharge in liquid N2 cooled He/Ar/H2/D2 gas mixture. Near infrared (NIR) second overtone transitions in the 6534-6536 cm-1 (1.529-1.530 [mu]m) region are used to identify the ions and determine their degree of rotational excitation. The data were obtained using NIR cavity ringdown absorption spectroscopy (NIR-CRDS). The sensitivity obtained was typically 5 x 10-9 cm-1. The measured second overtone transition frequencies are in very good agreement (better than 0.02 cm-1) with ab initio predictions. From the Doppler broadening the kinetic temperature of ions is estimated to be (220 +/- 50) K. The absolute number density of D2H+ as a function of H2/D2 mixing ratio and time is measured.

  3. STS-55 Columbia, Orbiter Vehicle (OV) 102, payload bay with SL-D2 module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Spacelab Deutsche 2 (SL-D2) science module and spacelab (SL) long tunnel is documented in the payload bay (PLB) of the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102. The support struts and handrails on the SL joggle section are visible in the foreground with the SL-D2 flex section and interface behind it. On the SL-D2 module foward end cone applied to the thermal blanket cover are the insignias of the European Space Agency (ESA) (left) and the SL-D2 payload. In the background are OV-102's vertical tail and the two orbital maneuvering system (OMS) pods backdropped against the cloud-covered Earth surface and the blackness of space.

  4. Production of the excited charm mesons D1 and D2* at HERA

    NASA Astrophysics Data System (ADS)

    Abramowicz, H.; Abt, I.; Adamczyk, L.; Adamus, M.; Aggarwal, R.; Antonelli, S.; Antonioli, P.; Antonov, A.; Arneodo, M.; Arslan, O.; Aushev, V.; Aushev, Y.; Bachynska, O.; Bamberger, A.; Barakbaev, A. N.; Barbagli, G.; Bari, G.; Barreiro, F.; Bartosik, N.; Bartsch, D.; Basile, M.; Behnke, O.; Behr, J.; Behrens, U.; Bellagamba, L.; Bertolin, A.; Bhadra, S.; Bindi, M.; Blohm, C.; Bokhonov, V.; Bołd, T.; Bondarenko, K.; Boos, E. G.; Borras, K.; Boscherini, D.; Bot, D.; Brock, I.; Brownson, E.; Brugnera, R.; Brümmer, N.; Bruni, A.; Bruni, G.; Brzozowska, B.; Bussey, P. J.; Bylsma, B.; Caldwell, A.; Capua, M.; Carlin, R.; Catterall, C. D.; Chekanov, S.; Chwastowski, J.; Ciborowski, J.; Ciesielski, R.; Cifarelli, L.; Cindolo, F.; Contin, A.; Cooper-Sarkar, A. M.; Coppola, N.; Corradi, M.; Corriveau, F.; Costa, M.; D'Agostini, G.; Dal Corso, F.; del Peso, J.; Dementiev, R. K.; De Pasquale, S.; Derrick, M.; Devenish, R. C. E.; Dobur, D.; Dolgoshein, B. A.; Dolinska, G.; Doyle, A. T.; Drugakov, V.; Durkin, L. S.; Dusini, S.; Eisenberg, Y.; Ermolov, P. F.; Eskreys, A.; Fang, S.; Fazio, S.; Ferrando, J.; Ferrero, M. I.; Figiel, J.; Foster, B.; Gach, G.; Galas, A.; Gallo, E.; Garfagnini, A.; Geiser, A.; Gialas, I.; Gizhko, A.; Gladilin, L. K.; Gladkov, D.; Glasman, C.; Gogota, O.; Golubkov, Yu. A.; Göttlicher, P.; Grabowska-Bołd, I.; Grebenyuk, J.; Gregor, I.; Grigorescu, G.; Grzelak, G.; Gueta, O.; Guzik, M.; Gwenlan, C.; Haas, T.; Hain, W.; Hamatsu, R.; Hart, J. C.; Hartmann, H.; Hartner, G.; Hilger, E.; Hochman, D.; Hori, R.; Hüttmann, A.; Ibrahim, Z. A.; Iga, Y.; Ingbir, R.; Ishitsuka, M.; Jakob, H.-P.; Januschek, F.; Jones, T. W.; Jüngst, M.; Kadenko, I.; Kahle, B.; Kananov, S.; Kanno, T.; Karshon, U.; Karstens, F.; Katkov, I. I.; Kaur, M.; Kaur, P.; Keramidas, A.; Khein, L. A.; Kim, J. Y.; Kisielewska, D.; Kitamura, S.; Klanner, R.; Klein, U.; Koffeman, E.; Kondrashova, N.; Kononenko, O.; Kooijman, P.; Korol, Ie.; Korzhavina, I. A.; Kotański, A.; Kötz, U.; Kowalski, H.; Kuprash, O.; Kuze, M.; Lee, A.; Levchenko, B. B.; Levy, A.; Libov, V.; Limentani, S.; Ling, T. Y.; Lobodzinska, E.; Lohmann, W.; Löhr, B.; Lohrmann, E.; Long, K. R.; Longhin, A.; Lontkovskyi, D.; Lukina, O. Yu.; Maeda, J.; Magill, S.; Makarenko, I.; Malka, J.; Mankel, R.; Margotti, A.; Marini, G.; Martin, J. F.; Mastroberardino, A.; Mattingly, M. C. K.; Melzer-Pellmann, I.-A.; Mergelmeyer, S.; Miglioranzi, S.; Mohamad Idris, F.; Monaco, V.; Montanari, A.; Morris, J. D.; Mujkic, K.; Musgrave, B.; Nagano, K.; Namsoo, T.; Nania, R.; Nigro, A.; Ning, Y.; Nobe, T.; Notz, D.; Nowak, R. J.; Nuncio-Quiroz, A. E.; Oh, B. Y.; Okazaki, N.; Olkiewicz, K.; Onishchuk, Yu.; Papageorgiu, K.; Parenti, A.; Paul, E.; Pawlak, J. M.; Pawlik, B.; Pelfer, P. G.; Pellegrino, A.; Perlański, W.; Perrey, H.; Piotrzkowski, K.; Pluciński, P.; Pokrovskiy, N. S.; Polini, A.; Proskuryakov, A. S.; Przybycień, M.; Raval, A.; Reeder, D. D.; Reisert, B.; Ren, Z.; Repond, J.; Ri, Y. D.; Robertson, A.; Roloff, P.; Rubinsky, I.; Ruspa, M.; Sacchi, R.; Samson, U.; Sartorelli, G.; Savin, A. A.; Saxon, D. H.; Schioppa, M.; Schlenstedt, S.; Schleper, P.; Schmidke, W. B.; Schneekloth, U.; Schönberg, V.; Schörner-Sadenius, T.; Schwartz, J.; Sciulli, F.; Shcheglova, L. M.; Shehzadi, R.; Shimizu, S.; Singh, I.; Skillicorn, I. O.; Słomiński, W.; Smith, W. H.; Sola, V.; Solano, A.; Son, D.; Sosnovtsev, V.; Spiridonov, A.; Stadie, H.; Stanco, L.; Stefaniuk, N.; Stern, A.; Stewart, T. P.; Stifutkin, A.; Stopa, P.; Suchkov, S.; Susinno, G.; Suszycki, L.; Sztuk-Dambietz, J.; Szuba, D.; Szuba, J.; Tapper, A. D.; Tassi, E.; Terrón, J.; Theedt, T.; Tiecke, H.; Tokushuku, K.; Tomaszewska, J.; Trusov, V.; Tsurugai, T.; Turcato, M.; Turkot, O.; Tymieniecka, T.; Vázquez, M.; Verbytskyi, A.; Viazlo, O.; Vlasov, N. N.; Walczak, R.; Wan Abdullah, W. A. T.; Whitmore, J. J.; Wichmann, K.; Wiggers, L.; Wing, M.; Wlasenko, M.; Wolf, G.; Wolfe, H.; Wrona, K.; Yagües-Molina, A. G.; Yamada, S.; Yamazaki, Y.; Yoshida, R.; Youngman, C.; Zabiegalov, O.; Żarnecki, A. F.; Zawiejski, L.; Zenaiev, O.; Zeuner, W.; Zhautykov, B. O.; Zhmak, N.; Zichichi, A.; Zolkapli, Z.; Zotkin, D. S.; ZEUS Collaboration

    2013-01-01

    The production of the excited charm mesons D1(2420) and D2*(2460) in ep collisions has been measured with the ZEUS detector at HERA using an integrated luminosity of 373 pb. The masses of the neutral and charged states, the widths of the neutral states, and the helicity parameter of D1(2420 were determined and compared with other measurements and with theoretical expectations. The measured helicity parameter of the D10 allows for some mixing of S- and D-waves in its decay to Dπ∓. The result is also consistent with a pure D-wave decay. Ratios of branching fractions of the two decay modes of the D2*(2460 and D2*(2460 states were measured and compared with previous measurements. The fractions of charm quarks hadronising into D1 and D2* were measured and are consistent with those obtained in e+e- annihilations.

  5. Myocardial accumulation of a dopamine D2 receptor-binding radioligand, 2'-iodospiperone.

    PubMed

    Saji, H; Yonekura, Y; Tanahashi, K; Iida, Y; Iwasaki, Y; Magata, Y; Konishi, J; Yokoyama, A

    1993-08-01

    125I-2'-iodospiperone (2'-ISP), which has a high and selective affinity for dopamine D2 receptors, produced a high myocardial accumulation of radioactivity in the early phase after intravenous injection into mice. A human scintigraphic study also showed that the myocardium was clearly visualized soon after intravenous injection of the tracer. Analysis of the myocardial homogenate obtained from mice showed that 125I-2'-ISP was metabolically stable and was taken up the myocardium in its intact form. Administration of spiperone significantly reduced the myocardial uptake of 125I-2'-ISP in mice. Treatment with haloperidol and (+) butaclamol, which have a high affinity for dopamine D2 receptors, also tended to reduce the myocardial uptake of radioactivity, while (-)-butaclamol, which has no affinity for dopamine D2 receptors, caused no change in uptake. These findings suggest that the myocardial accumulation of 2'-ISP occurred in association with dopamine D2 (DA2) receptors.

  6. Vitamin D2 Supplementation Amplifies Eccentric Exercise-Induced Muscle Damage in NASCAR Pit Crew Athletes

    PubMed Central

    Nieman, David C.; Gillitt, Nicholas D.; Shanely, R. Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

    2013-01-01

    This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n = 13) and placebo (n = 15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p < 0.001, p = 0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p = 0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p < 0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise. PMID:24362707

  7. Role of D2 dopamine receptors of the ventral pallidum in inhibitory avoidance learning.

    PubMed

    Lénárd, László; Ollmann, Tamás; László, Kristóf; Kovács, Anita; Gálosi, Rita; Kállai, Veronika; Attila, Tóth; Kertes, Erika; Zagoracz, Olga; Karádi, Zoltán; Péczely, László

    2017-03-15

    In our present experiments, the role of D2 dopamine (DA) receptors of the ventral pallidum (VP) was investigated in one trial step-through inhibitory avoidance paradigm. Animals were shocked 3 times in the conditioning trial, with 0.5mA current for 1s. Subsequently bilateral microinjection of the D2 DA receptor agonist quinpirole was administered into the VP in three doses (0.1μg, 1.0μg or 5.0μg in 0.4μl saline). We also applied the D2 DA receptor antagonist sulpiride (0.4μg in 0.4μl saline) alone or 15min prior to the agonist treatment to elucidate whether the agonist effect was specific for the D2 DA receptors. Control animals received saline. In a supplementary experiment, it was also investigated whether application of the same conditioning method leads to the formation of short-term memory in the experimental animals. In the experiment with the D2 DA receptor agonist, only the 0.1μg quinpirole increased significantly the step-through latency during the test trials: retention was significant compared to the controls even 2 weeks after conditioning. The D2 DA receptor antagonist sulpiride pretreatment proved that the effect was due to the agonist induced activation of the D2 DA receptors of the VP. The supplementary experiment demonstrated that short-term memory is formed after conditioning in the experimental animals, supporting that the agonist enhanced memory consolidation in the first two experiments. Our results show that the activation of the D2 DA receptors in the VP facilitates memory consolidation as well as memory-retention in inhibitory avoidance paradigm. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Dopaminergic isoquinolines with hexahydrocyclopenta[ij]-isoquinolines as D2-like selective ligands.

    PubMed

    Párraga, Javier; Andujar, Sebastián A; Rojas, Sebastián; Gutierrez, Lucas J; El Aouad, Noureddine; Sanz, M Jesús; Enriz, Ricardo D; Cabedo, Nuria; Cortes, Diego

    2016-10-21

    Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D1 and D2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the β-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the β-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D2-DR since the Ki D1/D2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D2 DR than with D1 DR, which further supports to the encountered enhanced selectivity to D2 DR. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Evaluation of the recurrence pattern of gastric cancer after laparoscopic gastrectomy with D2 lymphadenectomy.

    PubMed

    Kawamura, Yuichiro; Satoh, Seiji; Umeki, Yusuke; Ishida, Yoshinori; Suda, Koichi; Uyama, Ichiro

    2016-01-01

    The aim of this study was to analyze the oncological aspects of gastric cancer following laparoscopic gastrectomy with D2 lymphadenectomy (LG-D2). We retrospectively evaluated the long-term outcomes of 354 patients who underwent LG-D2 for primary gastric cancer. Recurrence patterns and predictors of peritoneal metastasis were analyzed. Median follow-up time was 43.8 months. Five-year overall survival rates for yp/pStages I, II, and III gastric cancer were 93.7, 78.5, and 42.2 %, respectively. Recurrence was observed in 86 patients. Peritoneal metastasis was the most frequent recurrence pattern (n = 51), followed by hepatic metastasis (n = 17). Lymphatic recurrence at distant sites was observed in 10 patients. No locoregional lymph node metastasis or local recurrence was seen. Nine of 51 cases of peritoneal recurrence were detected by probe laparoscopy. Peritoneal recurrence rates were significantly higher in yp/pT4 and yp/pN3 diseases compared with yp/pT ≤ 3 and yp/pN ≤ 2 diseases. Multivariate analyses demonstrated that yp/pT4, yp/pN3, tumor size ≥70 mm, vascular invasion, and undifferentiated tumors were predictors of peritoneal recurrence following LG-D2. Long-term outcomes of gastric cancer following LG-D2, including recurrence patterns and predictors of peritoneal metastasis, were comparable to those following open D2 gastrectomy. LG-D2 showed good local control. Probe laparoscopy after LG may be effective in detecting peritoneal recurrence, which is not determined with less invasive examinations, including a CT scan. Future large-scale prospective studies are desirable to evaluate not only surgical but also oncological benefits and safety of LG-D2 for advanced gastric cancer.

  10. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

    PubMed

    Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

    2015-04-14

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

  11. D2: major subgenotype of hepatitis B virus in Russia and the Baltic region.

    PubMed

    Tallo, Tatjana; Tefanova, Valentina; Priimägi, Ljudmilla; Schmidt, Jelena; Katargina, Olga; Michailov, Michail; Mukomolov, Sergey; Magnius, Lars; Norder, Heléne

    2008-08-01

    Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13 genotype A and 42 genotype D strains from the former USSR. The strains were classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype-specific residues, and a region spanning residues 58-128 in the spacer region of the P gene could be used to distinguish between D1 and D4. This enabled the allocation to subgenotype of strains with partially sequenced genomes. D2 was dominating, while D3 was found in low frequency in the whole region. D1 was most prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively. The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and D3, respectively. All D1 and D3 strains encoded subtype ayw2, whereas most D2 strains encoded ayw3. Two D2 strains encoded ayw4. Strains with identical S genes were closely related at the level of complete genomes and formed geographically specific clades with low intraclade divergences, possibly indicating past iatrogenic spread. It is not clear whether the finding of four subgenotypes in the area corresponds to separate introductions of the virus or to previous population migrations into the area. An earlier introduction of D3 compared with D2 was supported by its higher intra-subgenotype divergence, while the lower divergence within D1 is probably due to a more recent emergence.

  12. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

    PubMed Central

    Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

    2015-01-01

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors. PMID:25871974

  13. Effect of supplementation with vitamin D2-enhanced mushrooms on vitamin D status in healthy adults.

    PubMed

    Stepien, Magdalena; O'Mahony, Louise; O'Sullivan, Aifric; Collier, John; Fraser, William D; Gibney, Michael J; Nugent, Anne P; Brennan, Lorraine

    2013-01-01

    Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40-65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D2 or placebo mushroom powder) and capsule study (15 µg vitamin D3 or placebo capsules). Consumption of vitamin D2-enhanced mushrooms increased serum 25-hydroxyvitamin D2 (25(OH)D2) by 128 % from baseline (3·9 (sd 1·9) nmol/l; P < 0·05). Serum 25(OH)D3 increased significantly in the vitamin D3 capsule group (a 55 % increase from a baseline of 44.0 (sd 17·1) nmol/l; P < 0·05). Vitamin D status (25(OH)D) was affected only in the vitamin D3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D2 intake. Vitamin D2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D2 concentration with no significant effect on 25(OH)D3 or total 25(OH)D.

  14. Bacterial Ice Nucleation in Monodisperse D2O and H2O-in-Oil Emulsions.

    PubMed

    Weng, Lindong; Tessier, Shannon N; Smith, Kyle; Edd, Jon F; Stott, Shannon L; Toner, Mehmet

    2016-09-13

    Ice nucleation is of fundamental significance in many areas, including atmospheric science, food technology, and cryobiology. In this study, we investigated the ice-nucleation characteristics of picoliter-sized drops consisting of different D2O and H2O mixtures with and without the ice-nucleating bacteria Pseudomonas syringae. We also studied the effects of commonly used cryoprotectants such as ethylene glycol, propylene glycol, and trehalose on the nucleation characteristics of D2O and H2O mixtures. The results show that the median freezing temperature of the suspension containing 1 mg/mL of a lyophilized preparation of P. syringae is as high as -4.6 °C for 100% D2O, compared to -8.9 °C for 100% H2O. As the D2O concentration increases every 25% (v/v), the profile of the ice-nucleation kinetics of D2O + H2O mixtures containing 1 mg/mL Snomax shifts by about 1 °C, suggesting an ideal mixing behavior of D2O and H2O. Furthermore, all of the cryoprotectants investigated in this study are found to depress the freezing phenomenon. Both the homogeneous and heterogeneous freezing temperatures of these aqueous solutions depend on the water activity and are independent of the nature of the solute. These findings enrich our fundamental knowledge of D2O-related ice nucleation and suggest that the combination of D2O and ice-nucleating agents could be a potential self-ice-nucleating formulation. The implications of self-nucleation include a higher, precisely controlled ice seeding temperature for slow freezing that would significantly improve the viability of many ice-assisted cryopreservation protocols.

  15. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

    DOE PAGES

    Volkow, N. D.; Wang, G. -J.; Logan, J.; ...

    2015-04-14

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release inmore » striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.« less

  16. Vitamin D2 supplementation amplifies eccentric exercise-induced muscle damage in NASCAR pit crew athletes.

    PubMed

    Nieman, David C; Gillitt, Nicholas D; Shanely, R Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

    2013-12-20

    This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n=13) and placebo (n=15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p<0.001, p=0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p=0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p<0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise.

  17. Cariprazine exerts antimanic properties and interferes with dopamine D2 receptor β-arrestin interactions

    PubMed Central

    Gao, Yonglin; Peterson, Sean; Masri, Bernard; Hougland, M Tyler; Adham, Nika; Gyertyán, Istvan; Kiss, Béla; Caron, Marc G; El-Mallakh, Rif S

    2015-01-01

    Activation of dopamine D2 receptors (D2R) modulates G protein/cAMP-dependent signaling and also engages Akt-GSK-3 signaling through D2R/β-arrestin 2 scaffolding of Akt and PP2A. This G protein-independent pathway may be important in mediating the antimanic effects of mood stabilizers and antipsychotics. The mood stabilizer lithium influences behavior and Akt/GSK-3 signaling in mice and many antipsychotics have been shown to more potently antagonize the activity of the β-arrestin-2 pathway relative to the G protein-dependent pathway. Cariprazine, an antipsychotic with potent D3R/D2R partial agonist activity and preferential binding to D3R, was investigated for its effects on the mediators of D2R pathways in vitro and its efficacy in animal models of mania. Effects on G protein-dependent activity were measured via inhibition of isoproterenol-induced cAMP production; effects on D2R/β-arrestin 2 signaling were determined using bioluminescence resonance energy transfer (BRET). Cariprazine was tested in vivo for antimanic-like activity, using the ouabain-induced hyperactivity model in rats. Cariprazine was more potent than aripiprazole in inhibiting isoproterenol-induced cAMP although both compounds showed similar maximum efficacy. In assays of D2R/β-arrestin 2-dependent interactions, cariprazine showed very weak partial agonist activity, unless the levels of receptor kinase were increased; as an antagonist it showed similar potency to haloperidol and ∼fivefold greater potency than aripiprazole. In an animal model of mania, cariprazine showed similar efficacy as lithium in attenuating the effects of ouabain-induced hyperactivity. In summary, the differential effects of cariprazine on D2R G protein and β-arrestin 2 mediators of signal transduction pathways could contribute to its potent antimanic-like activity. PMID:25692006

  18. Cariprazine exerts antimanic properties and interferes with dopamine D2 receptor β-arrestin interactions.

    PubMed

    Gao, Yonglin; Peterson, Sean; Masri, Bernard; Hougland, M Tyler; Adham, Nika; Gyertyán, Istvan; Kiss, Béla; Caron, Marc G; El-Mallakh, Rif S

    2015-02-01

    Activation of dopamine D2 receptors (D2R) modulates G protein/cAMP-dependent signaling and also engages Akt-GSK-3 signaling through D2R/β-arrestin 2 scaffolding of Akt and PP2A. This G protein-independent pathway may be important in mediating the antimanic effects of mood stabilizers and antipsychotics. The mood stabilizer lithium influences behavior and Akt/GSK-3 signaling in mice and many antipsychotics have been shown to more potently antagonize the activity of the β-arrestin-2 pathway relative to the G protein-dependent pathway. Cariprazine, an antipsychotic with potent D3R/D2R partial agonist activity and preferential binding to D3R, was investigated for its effects on the mediators of D2R pathways in vitro and its efficacy in animal models of mania. Effects on G protein-dependent activity were measured via inhibition of isoproterenol-induced cAMP production; effects on D2R/β-arrestin 2 signaling were determined using bioluminescence resonance energy transfer (BRET). Cariprazine was tested in vivo for antimanic-like activity, using the ouabain-induced hyperactivity model in rats. Cariprazine was more potent than aripiprazole in inhibiting isoproterenol-induced cAMP although both compounds showed similar maximum efficacy. In assays of D2R/β-arrestin 2-dependent interactions, cariprazine showed very weak partial agonist activity, unless the levels of receptor kinase were increased; as an antagonist it showed similar potency to haloperidol and ∼fivefold greater potency than aripiprazole. In an animal model of mania, cariprazine showed similar efficacy as lithium in attenuating the effects of ouabain-induced hyperactivity. In summary, the differential effects of cariprazine on D2R G protein and β-arrestin 2 mediators of signal transduction pathways could contribute to its potent antimanic-like activity.

  19. Allosteric mechanisms within the adenosine A2A-dopamine D2 receptor heterotetramer.

    PubMed

    Ferré, Sergi; Bonaventura, Jordi; Tomasi, Dardo; Navarro, Gemma; Moreno, Estefanía; Cortés, Antonio; Lluís, Carme; Casadó, Vicent; Volkow, Nora D

    2016-05-01

    The structure constituted by a G protein coupled receptor (GPCR) homodimer and a G protein provides a main functional unit and oligomeric entities can be viewed as multiples of dimers. For GPCR heteromers, experimental evidence supports a tetrameric structure, comprised of two different homodimers, each able to signal with its preferred G protein. GPCR homomers and heteromers can act as the conduit of allosteric interactions between orthosteric ligands. The well-known agonist/agonist allosteric interaction in the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer, by which A2AR agonists decrease the affinity of D2R agonists, gave the first rationale for the use of A2AR antagonists in Parkinson's disease. We review new pharmacological findings that can be explained in the frame of a tetrameric structure of the A2AR-D2R heteromer: first, ligand-independent allosteric modulations by the D2R that result in changes of the binding properties of A2AR ligands; second, differential modulation of the intrinsic efficacy of D2R ligands for G protein-dependent and independent signaling; third, the canonical antagonistic Gs-Gi interaction within the frame of the heteromer; and fourth, the ability of A2AR antagonists, including caffeine, to also exert the same allosteric modulations of D2R ligands than A2AR agonists, while A2AR agonists and antagonists counteract each other's effects. These findings can have important clinical implications when evaluating the use of A2AR antagonists. They also call for the need of monitoring caffeine intake when evaluating the effect of D2R ligands, when used as therapeutic agents in neuropsychiatric disorders or as probes in imaging studies. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. Published by Elsevier Ltd.

  20. Interactions between Histamine H3 and Dopamine D2 Receptors and the Implications for Striatal Function

    PubMed Central

    Ferrada, Carla; Ferré, Sergi; Casadó, Vicent; Cortés, Antonio; Justinova, Zuzana; Barnes, Chanel; Canela, Enric I.; Goldberg, Steven R.; Leurs, Rob; Lluis, Carme; Franco, Rafael

    2008-01-01

    The striatum contains a high density of histamine H3 receptors, but their role in striatal function is poorly understood. Previous studies have demonstrated antagonistic interactions between striatal H3 and dopamine D1 receptors at the biochemical level, while contradictory results have been reported about interactions between striatal H3 and dopamine D2 receptors. In the present study, by using reserpinized mice, we demonstrate the existence of behaviorally significant antagonistic postsynaptic interactions between H3 and D1 and also between H3 and dopamine D2 receptors. The selective H3 receptor agonist imetit inhibited, while the H3 receptor antagonist thioperamide potentiated locomotor activation induced by either the D1 receptor agonist SKF 38393 or the D2 receptor agonist quinpirole. High scores of locomotor activity were obtained with H3 receptor blockade plus D1 and D2 receptor co-activation, i.e., when thioperamide was co-administered with both SKF 38393 and quinpirole. Radioligand binding experiments in striatal membrane preparations showed the existence of a strong and selective H3-D2 receptor interaction at the membrane level. In agonist/antagonist competition experiments stimulation of H3 receptors with several H3 receptor agonists significantly decreased the affinity of D2 receptors for the agonist. This kind of intramembrane receptor-receptor interactions are a common biochemical property of receptor heteromers. In fact, by using Bioluminescence Resonance Energy Transfer techniques in co-transfected HEK-293 cells, H3 (but not H4) receptors were found to form heteromers with D2 receptors. The present study demonstrates an important role of postsynaptic H3 receptors in the modulation of dopaminergic transmission by means of a negative modulation of D2 receptor function. PMID:18547596

  1. Zero-temperature phase diagram of D2 physisorbed on graphane

    NASA Astrophysics Data System (ADS)

    Carbonell-Coronado, C.; De Soto, F.; Cazorla, C.; Boronat, J.; Gordillo, M. C.

    2013-11-01

    We determined the zero-temperature phase diagram of D2 physisorbed on graphane using the diffusion Monte Carlo method. The substrate used was C-graphane, an allotropic form of the compound that has been experimentally obtained through hydrogenation of graphene. We found that the ground state is the δ phase, a commensurate structure observed experimentally when D2 is adsorbed on graphite, and not the registered \\sqrt{3}\\times \\sqrt{3} structure characteristic of H2 on the same substrate.

  2. Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.

    PubMed

    Perez, Stephanie M; Lodge, Daniel J

    2012-11-01

    Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

  3. Resolvin D1 and Resolvin D2 Govern Local Inflammatory Tone in Obese Fat1

    PubMed Central

    Clària, Joan; Dalli, Jesmond; Yacoubian, Stephanie; Gao, Fei; Serhan, Charles N.

    2012-01-01

    The unprecedented rise in the prevalence of obesity and obesity-related disorders is causally linked to a chronic state of low-grade inflammation in adipose tissue. Timely resolution of inflammation and return of this tissue to homeostasis are key to reducing obesity-induced metabolic dysfunctions. Here, with inflamed adipose, we investigated the biosynthesis, conversion and actions of Resolvin (Rv) D1 and RvD2, potent anti-inflammatory and pro-resolving lipid mediators (LM), and their ability to regulate monocyte interactions with adipocytes. LM-metabololipidomics identified RvD1 and RvD2 from endogenous sources in human and mouse adipose tissues. We also identified pro-resolving receptors (i.e. ALX/FPR2, ChemR23 and GPR32) in these tissues. Compared to lean tissue, obese adipose showed a deficit of these endogenous anti-inflammatory signals. With inflamed obese adipose tissue, RvD1 and RvD2 each rescued impaired expression and secretion of adiponectin in a time- and concentration-dependent manner while decreasing pro-inflammatory adipokine production including leptin, TNFα, IL-6 and IL-1β. RvD1 and RvD2 each reduced MCP-1 and leukotriene B4-stimulated monocyte adhesion to adipocytes and their transadipose migration. Adipose tissue rapidly converted both resolvins to novel oxo-resolvins. RvD2 was enzymatically converted to 7-oxo-RvD2 as its major metabolic route that retained adipose-directed RvD2 actions. These results indicate, in adipose, D-series resolvins (RvD1 and RvD2) are potent pro-resolving mediators that counteract both local adipokine production and monocyte accumulation in obesity-induced adipose inflammation. PMID:22844113

  4. Early Induction of Cyclin D2 Expression in Phorbol Ester–responsive B-1 Lymphocytes

    PubMed Central

    Tanguay, Debra A.; Colarusso, Thomas P.; Pavlovic, Sandra; Irigoyen, Macarena; Howard, Robert G.; Bartek, Jiri; Chiles, Thomas C.; Rothstein, Thomas L.

    1999-01-01

    B-1 lymphocytes represent a distinct B cell subset with characteristic features that include self-renewing capacity and unusual mitogenic responses. B-1 cells differ from conventional B cells in terms of the consequences of phorbol ester treatment: B-1 cells rapidly enter S phase in response to phorbol ester alone, whereas B-2 cells require a calcium ionophore in addition to phorbol ester to trigger cell cycle progression. To address the mechanism underlying the varied proliferative responses of B-1 and B-2 cells, we evaluated the expression and activity of the G1 cell cycle regulator, cyclin D2, and its associated cyclin-dependent kinases (Cdks). Cyclin D2 expression was upregulated rapidly, within 2–4 h, in phorbol ester–stimulated B-1 cells, in a manner dependent on intact transcription/translation, but was not increased in phorbol ester– stimulated B-2 cells. Phorbol ester–stimulated cyclin D2 expression was accompanied by the formation of cyclin D2–Cdk4, and, to a lesser extent, cyclin D2–Cdk6, complexes; cyclin D2– containing complexes were found to be catalytically functional, in terms of their ability to phosphorylate exogenous Rb in vitro and to specifically phosphorylate endogenous Rb on serine780 in vivo. These results strongly suggest that the rapid induction of cyclin D2 by a normally nonmitogenic phorbol ester stimulus is responsible for B-1 cell progression through G1 phase. The ease and rapidity with which cyclin D2 responds in B-1 cells may contribute to the proliferative features of this subset. PMID:10359571

  5. Dopamine D2 receptor over-expression alters behavior and physiology in Drd2-EGFP mice

    PubMed Central

    Kramer, Paul F.; Christensen, Christine H.; Hazelwood, Lisa A.; Dobi, Alice; Bock, Roland; Sibley, David R.; Mateo, Yolanda; Alvarez, Veronica A.

    2011-01-01

    BAC transgenic mice expressing the fluorescent reporter protein EGFP under the control of the D1 and D2 dopamine receptor promoters (Drd1-EGFP and Drd2-EGFP) have been widely used to study striatal function and have contributed to our understanding of the physiological and pathological function of the basal ganglia. These tools were produced and promptly made available to address questions in a cell-specific manner that has transformed the way we frame hypotheses in neuroscience. However, these mice have not been fully characterized until now. We found that Drd2-EGFP mice display a ~40% increase in membrane expression of the dopamine D2 receptor (D2R) and a two-fold increase in D2R mRNA levels in the striatum when compared to wild-type and Drd1-EGFP mice D2R over-expression was accompanied by behavioral hypersensitivity to D2R-like agonists, as well as enhanced electrophysiological responses to D2R activation in midbrain dopaminergic neurons. DA transients evoked by stimulation in the nucleus accumbens showed slower clearance in Drd2-EGFP mice and cocaine actions on DA clearance were impaired in these mice. Thus, it was not surprising to find that Drd2-EGFP mice were hyperactive when exposed to a novel environment and locomotion was suppressed by acute cocaine administration. All together, this study demonstrates that Drd2-EGFP mice over-express D2R and have altered dopaminergic signaling that fundamentally differentiates them from wild-type and Drd1-EGFP mice. PMID:21209197

  6. Phasic dopamine release drives rapid activation of striatal D2-receptors

    PubMed Central

    Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

    2014-01-01

    Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

  7. Sex Differences in Midbrain Dopamine D2-Type Receptor Availability and Association with Nicotine Dependence.

    PubMed

    Okita, Kyoji; Petersen, Nicole; Robertson, Chelsea L; Dean, Andy C; Mandelkern, Mark A; London, Edythe D

    2016-11-01

    Women differ from men in smoking-related behaviors, among them a greater difficulty in quitting smoking. Unlike female smokers, male smokers have lower striatal dopamine D2-type receptor availability (binding potential, BPND) than nonsmokers and exhibit greater smoking-induced striatal dopamine release. Because dopamine D2-type autoreceptors in the midbrain influence striatal dopamine release, a function that has been linked to addiction, we tested for sex differences in midbrain dopamine D2-type receptor BPND and in relationships between midbrain BPND, nicotine dependence and striatal dopamine D2-type receptor BPND. Positron emission tomography was used with [(18)F]fallypride to measure BPND in a midbrain region, encompassing the substantia nigra and ventral tegmental area, in 18 daily smokers (7 women, 11 men) and 19 nonsmokers (10 women, 9 men). A significant sex-by-group interaction reflected greater midbrain BPND in female but not male smokers than in corresponding nonsmokers (F1, 32=5.089, p=0.03). Midbrain BPND was positively correlated with BPND in the caudate nucleus and putamen in nonsmokers and female smokers but not in male smokers and with nicotine dependence in female but not in male smokers. Striatal BPND was correlated negatively with nicotine dependence and smoking exposure. These findings extend observations on dopamine D2-type receptors in smokers and suggest a sex difference in how midbrain dopamine D2-type autoreceptors influence nicotine dependence.

  8. Imaging diffraction oscillations for inelastic collisions of NO radicals with He and D2

    NASA Astrophysics Data System (ADS)

    de Jongh, Tim; Karman, Tijs; Vogels, Sjoerd N.; Besemer, Matthieu; Onvlee, Jolijn; Suits, Arthur G.; Thompson, James O. F.; Groenenboom, Gerrit C.; van der Avoird, Ad; van de Meerakker, Sebastiaan Y. T.

    2017-07-01

    We present state-to-state differential cross sections for collisions of NO molecules (X2Π1 /2 ,j =1 /2 ,f ) with He atoms and ortho-D2 (j = 0) molecules as a function of collision energy. A high angular resolution obtained using the combination of Stark deceleration and velocity map imaging allows for the observation of diffraction oscillations in the angular scattering distributions. Differences in the differential cross sections and, in particular, differences in the angular spacing between individual diffraction peaks are observed. Since the masses of D2 and He are almost equal and since D2(j = 0) may be considered as a pseudo-atom, these differences directly reflect the larger size of D2 as compared to He. The observations are in excellent agreement with the cross sections obtained from quantum close-coupling scattering calculations based on accurate ab initio NO-He and NO-D2 potential energy surfaces. For the latter, we calculated a new NO-D2 potential energy surface.

  9. D2-Thr92Ala, thyroid hormone levels and biochemical hypothyroidism in preeclampsia.

    PubMed

    Procopciuc, Lucia Maria; Caracostea, Gabriela; Hazi, Georgeta; Nemeti, Georgiana; Stamatian, Florin

    2017-02-01

    To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia. We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA. Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia. The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

  10. Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex

    PubMed Central

    2015-01-01

    Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders. PMID:25393953

  11. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis.

    PubMed

    Sicinski, P; Donaher, J L; Geng, Y; Parker, S B; Gardner, H; Park, M Y; Robker, R L; Richards, J S; McGinnis, L K; Biggers, J D; Eppig, J J; Bronson, R T; Elledge, S J; Weinberg, R A

    1996-12-05

    THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.

  12. Cyclin D2 induces proliferation of cardiac myocytes and represses hypertrophy

    SciTech Connect

    Busk, Peter K. . E-mail: pkbu@novonordisk.com; Hinrichsen, Rebecca; Bartkova, Jirina; Hansen, Ane H.; Christoffersen, Tue E.H.; Bartek, Jiri; Haunso, Stig

    2005-03-10

    The myocytes of the adult mammalian heart are considered unable to divide. Instead, mitogens induce cardiomyocyte hypertrophy. We have investigated the effect of adenoviral overexpression of cyclin D2 on myocyte proliferation and morphology. Cardiomyocytes in culture were identified by established markers. Cyclin D2 induced DNA synthesis and proliferation of cardiomyocytes and impaired hypertrophy induced by angiotensin II and serum. At the molecular level, cyclin D2 activated CDK4/6 and lead to pRB phosphorylation and downregulation of the cell cycle inhibitors p21{sup Waf1/Cip1} and p27{sup Kip1}. Expression of the CDK4/6 inhibitor p16 inhibited proliferation and cyclin D2 overexpressing myocytes became hypertrophic under such conditions. Inhibition of hypertrophy by cyclin D2 correlated with downregulation of p27{sup Kip1}. These data show that hypertrophy and proliferation are highly related processes and suggest that cardiomyocyte hypertrophy is due to low amounts of cell cycle activators unable to overcome the block imposed by cell cycle inhibitors. Cell cycle entry upon hypertrophy may be converted to cell division by increased expression of activators such as cyclin D2.

  13. CO and D2O chemistry on continuous and discontinuous samaria thin films on Pt(111)

    NASA Astrophysics Data System (ADS)

    Jhang, Jin-Hao; Keil, Simona; Schaefer, Andreas; Zielasek, Volkmar; Bäumer, Marcus

    2016-08-01

    The chemistry of CO and D2O, individually adsorbed or co-adsorbed, on epitaxial thin films of samaria on Pt(111) was studied by temperature-programmed desorption spectroscopy (TPD). Continuous thin films as well as discontinuous films composed of samaria islands on bare Pt(111) were prepared. Their comparative study indicates that Sm2O3 islands provide lattice oxygen at their perimeter for CO oxidation on adjacent exposed Pt area where CO adsorption takes place. CO2 production was observed only on as-prepared discontinuous films. While, in particular on thermally reduced samaria islands, TPD after D2O adsorption revealed D2 production which indicates a pathway for D2O dissociation, no evidence for the water gas shift reaction of CO and residual OD species on the surface was found after co-adsorption of CO and D2O. Instead, interaction between CO and OD species at the perimeter of islands on reduced discontinuous SmOx thin films obviously promotes D2 formation without yielding CO2 as desorbing product.

  14. Loss of dopamine D2 receptors increases parvalbumin-positive interneurons in the anterior cingulate cortex.

    PubMed

    Graham, Devon L; Durai, Heather H; Garden, Jamie D; Cohen, Evan L; Echevarria, Franklin D; Stanwood, Gregg D

    2015-02-18

    Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders.

  15. High pressure-assisted encapsulation of vitamin D2 in reassembled casein micelles

    NASA Astrophysics Data System (ADS)

    Menéndez-Aguirre, O.; Stuetz, W.; Grune, T.; Kessler, A.; Weiss, J.; Hinrichs, J.

    2011-03-01

    For the encapsulation of vitamin D2, native casein micelles and vitamin D2 with or without additional Ca2+-Pi were treated at 600 MPa and 37 °C for 60 min. The pressure release rate was set at 20 or 600 MPa/min. Vitamin D2 was quantified by reversed-phase high-performance liquid chromatography, and physical properties of the micelles were analysed by photon correlation spectroscopy. The results demonstrate that simultaneous application of Ca2+-Pi and high pressure treatment with a fast release rate significantly increased loading of vitamin D2 per casein by 6.9-fold. The addition of Ca2+-Pi enhanced micelle aggregation and the vitamin was entrapped within the formed aggregates. However, high pressure treatment without Ca2+-Pi with a slow pressure release rate revealed similar results, increasing vitamin D2 per casein by 6.7-fold. The vitamin D2 loading in reassembled casein micelles is supposed to be due to hydrophobic interactions between the hydrophobic domains of the micelles.

  16. EFFECTS OF SMOKING ON D2/D3 STRIATAL RECEPTOR AVAILABILITY IN ALCOHOLICS AND SOCIAL DRINKERS

    PubMed Central

    Albrecht, Daniel S.; Kareken, David A.; Yoder, Karmen K.

    2013-01-01

    Objective Studies have reported lower striatal D2/D3 receptor availability in both alcoholics and cigarette smokers relative to healthy controls. These substances are commonly co-abused, yet the relationship between comorbid alcohol/tobacco abuse and striatal D2/D3 receptor availability has not been examined. We sought to determine the degree to which dual abuse of alcohol and tobacco is associated with lower D2/D3 receptor availability. Method Eighty-one subjects (34 nontreatment-seeking alcoholic smokers [NTS-S], 21 social-drinking smokers [SD-S], and 26 social-drinking non-smokers [SD-NS]) received baseline [11C]raclopride scans. D2/D3 binding potential (BPND ≡ Bavail/KD) was estimated for ten anatomically defined striatal regions of interest (ROIs). Results Significant group effects were detected in bilateral pre-commissural dorsal putamen, bilateral pre-commissural dorsal caudate; and bilateral post-commissural dorsal putamen. Post-hoc testing revealed that, regardless of drinking status, smokers had lower D2/D3 receptor availability than non-smoking controls. Conclusions Chronic tobacco smokers have lower striatal D2/D3 receptor availability than non-smokers, independent of alcohol use. Additional studies are needed to identify the mechanisms by which chronic tobacco smoking is associated with striatal dopamine receptor availability. PMID:23649848

  17. Pituitary tumours: the sst/D2 receptors as molecular targets.

    PubMed

    Hofland, Leo J; Feelders, Richard A; de Herder, Wouter W; Lamberts, Steven W J

    2010-09-15

    Somatostatin (SS) and dopamine (DA) are among the key regulators of hormone secretion by the anterior pituitary gland. Concordantly, SS and DA receptors are expressed in the different pituitary cell types. SS receptors (sst) have a predominant inhibitory role in the regulation of growth hormone (GH) secretion, although the secretion of other pituitary hormones, e.g. prolactin (PRL), thyroid stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) is regulated by SS as well. DA receptors, in particular the D2 receptor (D2), has an important regulatory role in the control of PRL secretion. The inhibitory effects by SS and DA may be influenced by physiological feedback mechanisms, in part also involving modulation of pituitary sst and D2 expression. Pituitary tumours express both sst and/or D2 receptors. Targeting SS and DA receptors is used clinically to control hormonal hypersecretion by pituitary tumours, as well as tumour growth. The sst subtype, as well as the co-expression of sst and D2, has significant impact on the possibility to treat patients with pituitary tumours with SS analogues and DA agonists. In this review the current knowledge on the expression and functional roles of sst and D2 in pituitary tumours is discussed. 2010 Elsevier Ireland Ltd. All rights reserved.

  18. Nuclear Magnetic Resonance Evidence using D2O for Structured Water in Muscle and Brain

    PubMed Central

    Cope, Freeman W.

    1969-01-01

    The electric quadrupole moment of the deuterium nucleus provides a nuclear magnetic resonance (NMR) probe of electric field gradients, and thereby of organization of tissue water. 8-17% of H2O in rat muscle and brain was replaced by D2O from 50% deuterated drinking water. The peak height of the steady-state NMR spectrum of D in muscle water was 74% lower than that of an equal concentration of D2O in liquid water. Longitudinal NMR relaxation times (T1) of D in water of muscle and brain averaged 0.092 and 0.131 sec, respectively, compared with 0.47 sec in D2O in liquid water. Transverse NMR relaxation times (T2) averaged 0.009 and 0.022 sec in D2O of muscle and brain, respectively, compared with 0.45 sec in D2O in liquid water. These differences cannot be explained by paramagnetic ions or by magnetic inhomogeneities, which leaves increased organization of tissue water as the only tenable hypothesis. Evidence was also obtained that 27% of muscle water and 13% of brain water exist as a separate fraction with T2 of D2O less than 2 × 10-3 sec, which implies an even higher degree of structure. Each of the two fractions may consist of multiple subfractions of differing structure. PMID:5780710

  19. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism

    SciTech Connect

    Noble, E.P.; Blum, K.; Ritchie, T.; Montgomery, A.; Sheridan, P.J. )

    1991-07-01

    The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd (binding affinity) and Bmax (number of binding sites)) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

  20. Measurement of 25-hydroxyvitamin D2&3 and 1, 25-dihydroxyvitamin D2&3 by Tandem Mass Spectrometry: A Primate Multispecies Comparison

    PubMed Central

    Ziegler, Toni E.; Kapoor, Amita; Hedman, Curtis J.; Binkley, Neil; Kemnitz, Joseph W.

    2015-01-01

    Vitamin D metabolites are widely studied for their roles in bone health, immune functions and other potential physiologic roles in humans. However, the optimal blood levels of vitamin D metabolites are still unclear. Various methods for measuring vitamin D metabolites have been used and recently liquid chromatography tandem mass spectroscopy (LC-MS/MS) has been adopted as the gold standard for vitamin D metabolite measurement. Here we report the use of LC-MS/MS to measure 25-hydroxyvitamin D (25(OH)D2&3), and 1,25-dihydroxyvitamin D (1,25(OH)2D2&3), in three laboratory nonhuman primate species: common marmoset (Callithrix jacchus), rhesus macaque (Macaca mulatta), and cynomolgus macaque (Macaca fascicularis), and compare them to humans using the same technique. The nonhuman primates showed blood levels for 25(OH)D3 and 1,25(OH)2D3 significantly higher than human values with marmosets having the highest levels. Marmoset samples showed significantly more variability among individuals than those from macaques for both metabolites, but all three nonhuman primate species exhibited large variation within species for both 25(OH)D2&3 and 1,25(OH)2D2&3. Marmoset females had significantly lower values than the males for 25(OH)D3, while rhesus males showed a significant decrease in 25(OH)D3 with age. The most striking finding is the variation within species for vitamin D levels even in laboratory primates that have a controlled diet, UV exposure, and in some cases, genetic constraints. Similar variation in 25(OH)D responses to a fixed dose of oral vitamin D supplementation has been reported in humans. We suggest that these species can provide primate models for examining the factors influencing variation in the levels of vitamin D necessary for human and nonhuman primate health. PMID:25845705

  1. Effects of the rotational excitation of D2 and of the potential energy surface on the H+ + D2 --> HD + D+ reaction.

    PubMed

    González-Lezana, T; Honvault, P; Jambrina, P G; Aoiz, F J; Launay, J-M

    2009-07-28

    The H(+) + D(2) --> HD + D(+) reaction has been theoretically investigated by means of an exact quantum mechanical approach, a quasiclassical trajectory method, and two statistical methods based in the propagation of either wave functions or trajectories. The study addresses the possible changes on the overall dynamics of the title reaction when the D(2) diatom is rotationally excited to its v = 0, j = 1 state. In addition, the reactivity for the ground rotational state on two different potential energy surfaces (PESs), namely, the surface by Aguado et al. [J. Chem. Phys. 112, 1240 (2000)] and the PES by Kamisaka et al. [J. Chem. Phys. 116, 654 (2002)], is examined. Reaction probabilities and cross sections at 0.524 and 0.1 eV collision energies are calculated. The major differences with respect to the reaction initiated with D(2) in its ground rovibrational state are observed for the lowest collision energy E(c) = 0.1 eV. Differential cross sections have been found to depend to some extend on the PES employed. In addition, at E(c) = 0.1 eV further discrepancies in the total and rotational cross sections are noticeable.

  2. Mechanisms of inverse agonism of antipsychotic drugs at the D(2) dopamine receptor: use of a mutant D(2) dopamine receptor that adopts the activated conformation.

    PubMed

    Wilson, J; Lin, H; Fu, D; Javitch, J A; Strange, P G

    2001-04-01

    The antipsychotic drugs have been shown to be inverse agonists at the D(2) dopamine receptor. We have examined the mechanism of this inverse agonism by making mutations in residue T343 in the base of the sixth transmembrane spanning region of the receptor. T343R, T343S and T343K mutant D(2) dopamine receptors were made and the T343R mutant characterized in detail. The T343R mutant D(2) dopamine receptor exhibits properties of a receptor that resides more in the activated state, namely increased agonist binding affinity (independent of G-protein coupling and dependent on agonist efficacy), increased agonist potency in functional tests (adenylyl cyclase inhibition) and increased inverse agonist effects. The binding of agonists to the mutant receptor also shows sensitivity to sodium ions, unlike the native receptor, so that isomerization of the receptor to its inactive state may be driven by sodium ions. The binding of inverse agonists to the receptor is, however, unaffected by the mutation. We conclude that inverse agonism at this receptor is not achieved by the inverse agonist binding preferentially to the non-activated state of the receptor over the activated state. Rather the inverse agonist appears to bind to all forms of the receptor but then renders the receptor inactive.

  3. Coupling between d-3-phosphoglycerate dehydrogenase and d-2-hydroxyglutarate dehydrogenase drives bacterial l-serine synthesis.

    PubMed

    Zhang, Wen; Zhang, Manman; Gao, Chao; Zhang, Yipeng; Ge, Yongsheng; Guo, Shiting; Guo, Xiaoting; Zhou, Zikang; Liu, Qiuyuan; Zhang, Yingxin; Ma, Cuiqing; Tao, Fei; Xu, Ping

    2017-09-05

    l-Serine biosynthesis, a crucial metabolic process in most domains of life, is initiated by d-3-phosphoglycerate (d-3-PG) dehydrogenation, a thermodynamically unfavorable reaction catalyzed by d-3-PG dehydrogenase (SerA). d-2-Hydroxyglutarate (d-2-HG) is traditionally viewed as an abnormal metabolite associated with cancer and neurometabolic disorders. Here, we reveal that bacterial anabolism and catabolism of d-2-HG are involved in l-serine biosynthesis in Pseudomonas stutzeri A1501 and Pseudomonas aeruginosa PAO1. SerA catalyzes the stereospecific reduction of 2-ketoglutarate (2-KG) to d-2-HG, responsible for the major production of d-2-HG in vivo. SerA combines the energetically favorable reaction of d-2-HG production to overcome the thermodynamic barrier of d-3-PG dehydrogenation. We identified a bacterial d-2-HG dehydrogenase (D2HGDH), a flavin adenine dinucleotide (FAD)-dependent enzyme, that converts d-2-HG back to 2-KG. Electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETFQO) are also essential in d-2-HG metabolism through their capacity to transfer electrons from D2HGDH. Furthermore, while the mutant with D2HGDH deletion displayed decreased growth, the defect was rescued by adding l-serine, suggesting that the D2HGDH is functionally tied to l-serine synthesis. Substantial flux flows through d-2-HG, being produced by SerA and removed by D2HGDH, ETF, and ETFQO, maintaining d-2-HG homeostasis. Overall, our results uncover that d-2-HG-mediated coupling between SerA and D2HGDH drives bacterial l-serine synthesis.

  4. GluD2 Endows Parallel Fiber-Purkinje Cell Synapses with a High Regenerative Capacity.

    PubMed

    Ichikawa, Ryoichi; Sakimura, Kenji; Watanabe, Masahiko

    2016-04-27

    Although injured axons usually do not regenerate in the adult CNS, parallel fibers (PFs) regenerate synaptic connections onto cerebellar Purkinje cells (PCs). In this study, we investigated the role of GluD2 in this regenerative process after PF transection using GluD2-knock-out (KO) mice. All dendritic spines on distal dendrites were innervated by PFs in sham-operated wild-type controls, whereas one-third were devoid of innervation in GluD2-KO mice. In both genotypes, a steep drop in the number of PF synapses occurred with a reciprocal surge in the number of free spines on postlesion day 1, when the PF territory aberrantly expanded toward the proximal dendrites. In wild-type mice, the territory and number of PF synapses were nearly fully restored to normal on postlesion day 7, although PF density remained low. Moreover, presynaptic and postsynaptic elements were markedly enlarged, and the PF terminal-to-PC spine contact ratio increased from 1:1 to 1:2 at most synapses. On postlesion day 30, the size and contact ratio of PF synapses returned to sham-operated control values and PF density recovered through the sprouting and elongation of PF collaterals. However, GluD2-KO mice showed neither a hypertrophic response nor territorial restoration 7 d postlesion, nor the recovery of PF axons or synapses on postlesion day 30. This suggests that PF wiring regenerates initially by inducing hypertrophic responses in surviving synaptic elements (hypertrophic phase), followed by collateral formation by PF axons and retraction of PF synapses (remodeling phase). Without GluD2, no transition to these regenerative phases occurs. The glutamate receptor GluD2 expressed at parallel fiber (PF)-Purkinje cell (PC) synapses regulates the formation and maintenance of the synapses. To investigate the role of GluD2 in their extraordinarily high regenerative capacity, the process after surgical transection of PFs was compared between wild-type and GluD2-knock-out mice. We discovered that, in

  5. Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.

    PubMed

    Yapo, Cedric; Nair, Anu G; Clement, Lorna; Castro, Liliana R; Hellgren Kotaleski, Jeanette; Vincent, Pierre

    2017-08-07

    Brief dopamine events are critical actors of reward-mediated learning in the striatum; the intracellular cAMP-protein kinase A (PKA) response of striatal medium spiny neurons to such events was studied dynamically using a combination of biosensor imaging in mouse brain slices and in silico simulations. Both D1 and D2 medium spiny neurons can sense brief dopamine transients in the sub-micromolar range. While dopamine transients profoundly change cAMP levels in both types of medium spiny neurons, the PKA-dependent phosphorylation level remains unaffected in D2 neurons. At the level of PKA-dependent phosphorylation, D2 unresponsiveness depends on protein phosphatase-1 (PP1) inhibition by DARPP-32. Simulations suggest that D2 medium spiny neurons could detect transient dips in dopamine level. The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D2 than on D1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a 'tone-sensing' mode, allowing them to detect transient dips in basal dopamine. Overall

  6. An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2.

    PubMed

    Slominski, Andrzej; Semak, Igor; Wortsman, Jacobo; Zjawiony, Jordan; Li, Wei; Zbytek, Blazej; Tuckey, Robert C

    2006-07-01

    We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol x min(-1) x mol(-1) P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol x min(-1) x mol(-1). In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes).

  7. Countrywide digital elevation models for the Islamic Republic of Mauritania—SRTM and ASTER (phase V, deliverable 65): Chapter F in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

    USGS Publications Warehouse

    Lee, Gregory K.

    2015-01-01

    A digital elevation model (DEM) of the entire country of the Islamic Republic of Mauritania was produced using Shuttle Radar Topography Mission (SRTM) data as required for deliverable 65 of the contract. In addition, because of significant recent advancements of availability, seamlessness, and validity of Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) global elevation data, the U.S. Geological Survey (USGS) extended its efforts to include a higher resolution countrywide ASTER DEM as value added to the required Deliverable 63, which was limited to five areas within the country. Both SRTM and ASTER countrywide DEMs have been provided in ERDAS Imagine (.img) format that is also directly compatible with ESRI ArcMap, ArcGIS Explorer, and other GIS applications.

  8. Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

    PubMed

    Jiang, Quan; Lian, Anji; He, Qi

    2016-07-01

    Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Postsynaptic D2 dopamine receptor supersensitivity in the striatum of mice lacking TAAR1.

    PubMed

    Espinoza, Stefano; Ghisi, Valentina; Emanuele, Marco; Leo, Damiana; Sukhanov, Ilya; Sotnikova, Tatiana D; Chieregatti, Evelina; Gainetdinov, Raul R

    2015-06-01

    Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor (GPCR) known to modulate dopaminergic system through several mechanisms. Mice lacking this receptor show a higher sensitivity to dopaminergic stimuli, such as amphetamine; however, it is not clear whether D1 or D2 dopamine receptors and which associated intracellular signaling events are involved in this modulation. In the striatum of TAAR1 knock out (TAAR1-KO mice) we found that D2, but not D1, dopamine receptors were over-expressed, both in terms of mRNA and protein levels. Moreover, the D2 dopamine receptor-related G protein-independent AKT/GSK3 signaling pathway was selectively activated, as indicated by the decrease of phosphorylation of AKT and GSK3β. The decrease in phospho-AKT levels, suggesting an increase in D2 dopamine receptor activity in basal conditions, was associated with an increase of AKT/PP2A complex, as revealed by co-immunoprecipitation experiments. Finally, we found that the locomotor activation induced by the D2 dopamine receptor agonist quinpirole, but not by the full D1 dopamine receptor agonist SKF-82958, was increased in TAAR1-KO mice. These data demonstrate pronounced supersensitivity of postsynaptic D2 dopamine receptors in the striatum of TAAR1-KO mice and indicate that a close interaction of TAAR1 and D2 dopamine receptors at the level of postsynaptic structures has important functional consequences. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. In vivo dopamine agonist properties of rotigotine: Role of D1 and D2 receptors.

    PubMed

    Fenu, Sandro; Espa, Elena; Pisanu, Augusta; Di Chiara, Gaetano

    2016-10-05

    Rotigotine acts in vitro as a full agonist of dopamine D1 receptors at concentrations almost superimposable to those at which it acts on D2 receptors. However in vivo evidence of the differences between the agonist activity of rotigotine at D1 receptors from that on the D2 receptors has not been provided yet. In order to test the ability of rotigotine to stimulate dopamine D1 and D2 receptors in vivo, we studied the effect of SCH39166 and eticlopride, selective dopamine D1 and D2/D3 receptor antagonists respectively, on rotigotine-induced contralateral turning behavior in 6-hydroxydopamine lesioned rats. Furthermore, the expression of the immediate-early gene c-fos in the caudate-putamen, was evaluated. As a comparison, we tested the D2/D3 agonist pramipexole. In primed rats, rotigotine (0.035, 0.1 and 0.35mg/kg) induced dose-dependent contralateral turning. Turning induced by 0.1mg/kg of rotigotine was reduced by pretreatment with the D1 antagonist SCH39166 and the D2 antagonist eticlopride. In drug-naive rats, rotigotine was less effective in eliciting turning but SCH39166 still reduced turning induced by rotigotine (0.35mg/kg). Pramipexole induced contralateral turning only in primed rats. SCH39166 potentiated and eticlopride abolished pramipexole-induced turning. Rotigotine induced Fos expression in the caudate-putamen and SCH39166 completely blocked it. Pramipexole failed to induce Fos. These results indicate that rotigotine acts in vivo as an agonist of D1 and D2 receptors while pramipexole is devoid of D1 activity in vivo. Given their differing DA receptor profiles, rotigotine and pramipexole might differ in their spectrum of application to the therapy of Parkinson's disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Dopamine D2 receptor availability in opiate addicts at baseline and during naloxone precipitated withdrawal

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Logan, J. ||

    1996-05-01

    To determine if changes in dopamine activity contribute to the clinical presentation of opiate withdrawal we assessed dopamine (DA) D2 receptor availability in opiate-dependent subjects at baseline and during naloxone-precipitated withdrawal. DA D2 receptor availability was evaluated in eleven male heroine and methadone users using positron emission tomography (PET) and [11-C]raclopride and compared to eleven age matched male control subjects. Nine of the opiate-dependent subjects and two of the control were tested twice after placebo and naloxone (0.02 mg/kg) iv injection 7-10 min. prior to [11-C]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen and ventral striatum) to that in the cerebellum which is a function of B{sub max}/K{sub d}. DA D2 receptor availability in putamen was significantly lower in opiate-dependent subjects (3.44 {plus_minus} 0.4) than that in controls (3.97 {plus_minus} 0.45, p {ge} 0.009). Naloxone induced a short lasting withdrawal in all of the opiate-dependent subjects (79 {plus_minus} 17% of maximum withdrawal), but not in controls, with significant increase in pulse (p {le} 0.006), blood pressure (p {le} 0.0001), lacrimation (p {le} 0.01), muscle twitches (p {le} 0.01), annoyance (p {le} 0.005), anxiety (p {le} 0.0006), restlessness (p {le} 0.0005) and unhappiness (p {le} 0.001). DA D2 receptor availability in basal ganglia after naloxone administration was not different from that of baseline. These results document abnormalities in DA D2 receptors in opiate-dependent subjects. However, DA D2 availability did not change with naloxone-precipitated withdrawal.

  12. A case series of individuals with analytically confirmed acute diphenyl-2-pyrrolidinemethanol (D2PM) toxicity.

    PubMed

    Wood, David M; Puchnarewicz, Malgorzata; Johnston, Atholl; Dargan, Paul I

    2012-04-01

    There is increasing interest in the use of pipradrol and pipradrol derivatives, such as diphenylproplinol [diphenyl-2-pyrrolidinemethanol (D2PM)] and desoxypipradrol [2-diphenylmethylpiperidine (2-DPMP)], as recreational drugs. There is limited information on the acute toxicity related to both D2PM and 2-DPMP. We report here a case series of five individuals with acute toxicity related to the use of D2PM. Five patients aged between 21 and 33 years old presented to the Emergency Department (ED) on unrelated occasions having used a range of different novel psychoactive substances; none had actually purchased D2PM. They presented with ongoing prolonged neuropsychiatric symptoms of agitation, anxiety and insomnia lasting 24-96 h post-ingestion. None had evidence of sympathomimetic toxicity on presentation to the ED. All were reassured and discharged home after review. TOXICOLOGICAL SCREENING: Urine collection at the time of presentation to the ED was subsequently analysed by gas chromatography-mass spectrometry (GC-MS). All of the urine samples tested positive for D2PM and benzophenone. Additional screening by liquid chromatography tandem mass-spectrometry (LC-MS-MS) demonstrated that the benzophenone detected was an analytical artefact due to the high-injection temperature of the GC-MS analysis. This descriptive case series provides more detailed information on the acute toxicity related to the use of D2PM. This information is useful for clinical pharmacologists and clinicians managing these individuals to be able to provide more appropriate advice on the acute toxicity associated with the use of D2PM, particularly in relation to the prolonged neuropsychiatric symptoms seen.

  13. Infrared Spectra of He-, Ne-, and Ar-C_2D_2 Complexes

    NASA Astrophysics Data System (ADS)

    Rezai, M.; Moazzen-Ahmadi, N.; McKellar, A. R. W.; Fernandez, Berta; Farrelly, David

    2012-06-01

    Remarkably, there are no previously published experimental spectra of the helium-acetylene van der Waals complex. Apparently, infrared spectra of He-C_2H_2 were recorded around 1990 in Roger Miller's lab, but a detailed rotational assignment was not possible even with the help of two extensive sets of theoretical predictions. Here, we study rare gas-C_2D_2 complexes in the νb{3} region (˜2439 wn) using a rapid-scan tuneable diode laser spectrometer to probe a pulsed supersonic slit-jet expansion. The He-C_2D_2 assignment problem is readily apparent: most of the absorption is piled-up in a very narrow region around 2440.85 wn, close to the R(0) line of the C_2D_2 monomer. This pile-up is a signature of very weak anisotropy in the helium-acetylene intermolecular potential, leading to almost free internal rotation of the C_2D_2. We are able to achieve a convincing rotational assignment with the help of theoretical energy level calculations based on the intermolecular potential surface of Munteanu and Fernández. So far the results are limited to He-C_2D_2 transitions which correlate with the monomer R(0) transition. Ne-C_2D_2 also shows a free-rotation pile-up of lines near R(0) which makes assignment tricky. In contrast, Ar-C_2D_2 exhibits more conventional behavior and a normal asymmetric rotor analysis is possible. [1] T. Slee, R.J. Le Roy, and C.E. Chuaqui, Mol. Phys. 77, 111 (1992); R. Moszynski, P.E.S. Wormer, and A. van der Avoird, J. Chem. Phys. 102, 8385 (1995). [2] R. Munteanu and B. Fernández, J. Chem. Phys. 123, 014309 (2005).

  14. Progress in Understanding the Infrared Spectra of He- and Ne-C_2D_2

    NASA Astrophysics Data System (ADS)

    Moazzen-Ahmadi, Nasser; McKellar, Bob

    2014-06-01

    Infrared spectra of He-C_2H_2 were recorded around 1990 in Roger Miller's lab, but detailed rotational assignment was apparently not possible even with the help of theoretical predictions. So there were no published experimental spectra of helium-acetylene van der Waals complexes until our recent work on He-C_2D_2 in the νb{3} region (˜2440 wn). The problem is that this complex lies close to the free rotor limit, so that most of the intensity in the spectrum piles up in tangles of closely spaced lines located close to the monomer rotational transitions, R(0), P(1), etc. Our previous He-C_2D_2 assignments were limited to the R(0) region, that is, the j = 1 ← 0 subband, where j represents C_2D_2 rotation. Here, we extend the analysis to j = 0 ← 1 and 2 ← 1 transitions with the help of new spectra obtained using a tunable OPO laser probe and a cooled supersonic jet nozzle. These subbands are weaker, not only because of the Boltzmann factor, but also the 2:1 nuclear spin statistics of j" = even:odd C_2D_2 levels. Moreover, the j = 0 ← 1 subband is overlapped by strong (C_2D_2)_2 transitions. We use a term value approach, obtaining a self-consistent set of ``experimental" energy levels which can be directly compared with theory or fitted in terms of a Coriolis model. Challenges also arise with Ne-C_2D_2, which is not quite so close to the free rotor limit, but still has many overlapping lines. Insights gained here help in assigning the tricky R(1) region for Ne-C_2D_2. M. Rezaei, N. Moazzen-Ahmadi, A.R.W. McKellar, B. Fernández, and D. Farrelly, Mol. Phys. 110, 2743 (2012).

  15. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    SciTech Connect

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  16. Poster - Thur Eve - 72: Conversion of helical tomotherapy plans into clinically favourable step-and-shoot IMRT plans deliverable on a c-arm linac.

    PubMed

    Studinski, Rcn; Alexander, A; La Russa, D

    2012-07-01

    The treatment planning software SharePlan is designed to convert dose distributions generated by the TomoTherapy planning station into step-and-shoot IMRT plans deliverable on a c-arm linear accelerator. Five anal canal patients who were planned for TomoTherapy treatments were exported into a SharePlan system and plans were generated for delivery on an Elekta Synergy unit. A total of 80 plans were generated for those five patients, with either seven, nine, eleven or twenty-one gantry angles and different priorities between focusing on matching either the target doses or healthy tissue sparing of the TomoTherapy plan. The plans generated by SharePlan, while often not matching target coverage at prescription, matched well the TomoTherapy coverage at 95% and 105% of the prescription dose. Organ at risk dose, when heavily emphazied in the SharePlan calculations matched or bettered the TomoTherapy dose due to the placement of the beams and the sharper sup-inf fall off of the dose distribution on a linac. For one of the patients, it was possible to produce a better DVH with SharePlan than the original TomoTherapy plan for those reasons. The TomoTherapy plans boasted significantly shorter delivery times than the plans generated with SharePlan. © 2012 American Association of Physicists in Medicine.

  17. Community-deliverable exercise and anxiety in adults with arthritis and other rheumatic diseases: a protocol for a systematic review and meta-analysis of randomised controlled trials

    PubMed Central

    Kelley, George A; Kelley, Kristi S; Callahan, Leigh F

    2017-01-01

    Introduction While anxiety is a major public health problem in adults with arthritis and other rheumatic diseases (AORD), the effects of exercise on anxiety in adults are not well established despite numerous studies on this topic. The purpose of this study is to conduct a systematic review with an aggregate data meta-analysis to determine the effects of community-deliverable exercise interventions (aerobic, strength training or both) on anxiety in adults with AORD. Methods and analysis Randomised controlled exercise intervention trials ≥4 weeks and published in any language up to 31 December 2016 will be included. Studies will be retrieved by searching 8 electronic databases, cross-referencing and expert review. Dual selection and abstraction of data will occur. The primary outcome will be changes in anxiety. Risk of bias will be assessed using the Cochrane risk of bias assessment instrument while confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. Standardised effect sizes for anxiety will be calculated from each study and then pooled using the inverse variance heterogeneity (IVhet) model. Meta-regression based on the IVhet model will be used to examine the relationship between changes in anxiety and selected covariates. Dissemination The results of this study will be presented at a professional conference and published in a peer-reviewed journal. Trial registration number CRD42016048728. PMID:28264834

  18. Threshold of Dopamine D2/3 Receptor Occupancy for Hyperprolactinemia in Older Patients With Schizophrenia.

    PubMed

    Iwata, Yusuke; Nakajima, Shinichiro; Caravaggio, Fernando; Suzuki, Takefumi; Uchida, Hiroyuki; Plitman, Eric; Chung, Jun Ku; Mar, Wanna; Gerretsen, Philip; Pollock, Bruce G; Mulsant, Benoit H; Rajji, Tarek K; Mamo, David C; Graff-Guerrero, Ariel

    2016-12-01

    Although hyperprolactinemia carries a long-term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean ± SD age = 60.2 ± 6.7 years) taking olanzapine or risperidone. Subjects underwent [¹¹C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels. The relationship between prolactin levels and D2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests. Prolactin levels decreased following dose reduction (mean ± SD = 24.1 ± 30.2 ng/mL to 17.2 ± 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D2/3R occupancy (β = .23, P = .04). Those with D2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers. Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects. ClinicalTrials.gov identifier: NCT00716755.

  19. Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy.

    PubMed

    Luckey, Stephen W; Haines, Chris D; Konhilas, John P; Luczak, Elizabeth D; Messmer-Kratzsch, Antke; Leinwand, Leslie A

    2017-01-01

    A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1(-/-)), and mice deficient in cyclin D2 (cyclin D2(-/-)). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2(-/-) mice. Cardiac function was not impacted in the cyclin D2(-/-) mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2(-/-) mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise

  20. D2 dissection in laparoscopic and open gastrectomy for gastric cancer

    PubMed Central

    Cui, Ming; Xing, Jia-Di; Yang, Wei; Ma, Yi-Yuan; Yao, Zhen-Dan; Zhang, Nan; Su, Xiang-Qian

    2012-01-01

    AIM: To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. METHODS: Clinicopathological data from 209 patients with gastric cancer, who underwent radical gastrectomy with D2 dissection between January 2007 and February 2011, were analyzed retrospectively. Among these patients, 131 patients underwent laparoscopy-assisted gastrectomy (LAG) and 78 underwent open gastrectomy (OG). The parameters analyzed included operative time, blood loss, blood transfusion, morbidity, mortality, the number of harvested lymph nodes (HLNs), and pathological stage. RESULTS: There were no significant differences in sex, age, types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)], and stages between the LAG and OG groups (P > 0.05). Among the two groups, 127 cases (96.9%) and 76 cases (97.4%) had 15 or more HLNs, respectively. The average number of HLNs was 26.1 ± 11.4 in the LAG group and 24.2 ± 9.3 in the OG group (P = 0.233). In the same type of radical resection, there were no significant differences in the number of HLNs between the two groups (PG + D2: 21.7 ± 7.5 vs 22.4 ± 9.3; DG + D2: 25.7 ± 11.0 vs 22.3 ± 7.9; TG + D2: 30.9 ± 13.4 vs 29.3 ± 10.4; P > 0.05 for all comparisons). Tumor free margins were obtained in all cases. Compared with OG group, the LAG group had significantly less blood loss, but a longer operation time (P < 0.001). The morbidity of the LAG group was 9.9%, which was not significantly different from the OG group (7.7%) (P = 0.587). The mortality was zero in both groups. CONCLUSION: Laparoscopic D2 dissection is equivalent to OG in the number of HLNs, regardless of tumor location. Thus, this procedure can achieve the same radicalness as OG. PMID:22371644

  1. Age-dependent kinetics of dentate gyrus neurogenesis in the absence of cyclin D2

    PubMed Central

    2012-01-01

    Background Adult neurogenesis continuously adds new neurons to the dentate gyrus and the olfactory bulb. It involves the proliferation and subsequent differentiation of neuronal progenitors, and is thus closely linked to the cell cycle machinery. Cell cycle progression is governed by the successive expression, activation and degradation of regulatory proteins. Among them, D-type cyclins control the exit from the G1 phase of the cell cycle. Cyclin D2 (cD2) has been shown to be required for the generation of new neurons in the neurogenic niches of the adult brain. It is differentially expressed during hippocampal development, and adult cD2 knock out (cD2KO) mice virtually lack neurogenesis in the dentate gyrus and olfactory bulb. In the present study we examined the dynamics of postnatal and adult neurogenesis in the dentate gyrus (DG) of cD2KO mice. Animals were injected with bromodeoxyuridine at seven time points during the first 10 months of life and brains were immunohistochemically analyzed for their potential to generate new neurons. Results Compared to their WT litters, cD2KO mice had considerably reduced numbers of newly born granule cells during the postnatal period, with neurogenesis becoming virtually absent around postnatal day 28. This was paralleled by a reduction in granule cell numbers, in the volume of the granule cell layer as well as in apoptotic cell death. CD2KO mice did not show any of the age-related changes in neurogenesis and granule cell numbers that were seen in WT litters. Conclusions The present study suggests that hippocampal neurogenesis becomes increasingly dependent on cD2 during early postnatal development. In cD2KO mice, hippocampal neurogenesis ceases at a time point at which the tertiary germinative matrix stops proliferating, indicating that cD2 becomes an essential requirement for ongoing neurogenesis with the transition from developmental to adult neurogenesis. Our data further support the notion that adult neurogenesis

  2. The Roles of Dopamine D2 Receptor in the Social Hierarchy of Rodents and Primates

    PubMed Central

    Yamaguchi, Yoshie; Lee, Young-A.; Kato, Akemi; Jas, Emanuel; Goto, Yukiori

    2017-01-01

    Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially housed Japanese macaques attenuated social dominance when the drug was given to high social class macaques. A similar attenuation of social dominance was observed in high social class mice with D2 antagonist administration. In contrast, D2 antagonist administration in low social class macaque resulted in more stable social hierarchy of the group, whereas such effect was not observed in mouse social group. These results suggest that D2 receptor signaling may play important roles in establishment and maintenance of social hierarchy in social groups of several species of animals. PMID:28233850

  3. Dopamine D2 receptors preferentially regulate the development of light responses of the inner retina

    PubMed Central

    Tian, Ning; Xu, Hong-ping; Wang, Ping

    2014-01-01

    Retinal light responsiveness measured via electroretinography undergoes developmental modulation and is thought to be critically regulated by both visual experience and dopamine. The primary goal of this study is to determine whether the dopamine D2 receptor regulates the visual experience-dependent functional development of the retina. Accordingly, we recorded electroretinograms from wild type mice and mice with a genetic deletion of the gene that encodes the dopamine D2 receptor raised under normal cyclic light conditions and constant darkness. Our results demonstrate that mutation of the dopamine D2 receptors preferentially increases the amplitude of the inner retinal light responses evoked by high intensity light measured as oscillatory potentials in adult mice. During postnatal development, all three major components of electroretinograms, the a-wave, b-wave and oscillatory potentials, increase with age. Comparatively, mutation of the dopamine D2 receptors preferentially reduces the age-dependent increase of b-waves evoked by low intensity light. Light deprivation from birth reduces the amplitude of b-waves and completely diminishes the increased amplitude of oscillatory potentials. Taken together, these results demonstrate that the dopamine D2 receptor plays an important role in the activity-dependent functional development of the mouse retina. PMID:25393815

  4. Memory and frontal lobe functions; possible relations with dopamine D2 receptors in the hippocampus.

    PubMed

    Takahashi, Hidehiko; Kato, Motoichiro; Hayashi, Mika; Okubo, Yoshiro; Takano, Akihiro; Ito, Hiroshi; Suhara, Tetsuya

    2007-02-15

    Cerebral cortical regions are thought to be important for cognitive functions such as memory and executive function. Although the functional associations between dopamine D2 receptors and motor and cognitive functions have been extensively examined in the striatum using positron emission tomography (PET), the role of dopamine D2 receptors in extrastriatal regions has been unexplored. We aimed to investigate the relationship between dopamine D2 receptors in extrastriatal regions and the performance of a broad spectrum of cognitive functions including memory, language, attention, and executive function in healthy subjects. Extrastriatal dopamine D2 receptors were measured in 25 male subjects using PET with [(11)C]FLB457. After the PET scans, a battery of neuropsychological tests was administered to all subjects. We found that the binding potential (BP) of [(11)C]FLB457 in the hippocampus was positively correlated with memory function. Furthermore, BP of [(11)C]FLB457 in the hippocampus, but not in the prefrontal cortex, was associated with frontal lobe functions such as executive function and verbal fluency. Our findings suggest that dopamine D2 receptors in the hippocampus might affect the local hippocampal function, but also brain functions outside the hippocampus such as the prefrontal cortex.

  5. Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor

    PubMed Central

    Wang, Xiong; Ma, Li; Zhang, En-jing; Zou, Ji-li; Guo, Hao; Peng, Si-wei; Wu, Jin-hu

    2014-01-01

    Objective. Fructus Hordei Germinatus is widely used in treating hyperprolactinemia (hyperPRL) as a kind of Chinese traditional herb in China. In this study, we investigated the anti-hyperPRL activity of water extract of Fructus Hordei Germinatus (WEFHG) and mechanism of action. Methods. Effect of WEFHG on serum prolactin (PRL), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and hypothalamus protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) levels of hyperPRL rats were investigated. And effect of WEFHG on PRL secretion, D2 receptors, and dopamine transporters (DAT) was studied in MMQ, GH3, and PC12 cells, respectively. Results. WEFHG reduced the secretion of PRL in hyperPRL rats effectively. In MMQ cell, treatment with WEFHG at 1–5 mg/mL significantly suppressed PRL secretion and synthesis. Consistent with a D2-action, WEFHG did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and DAT in PC12 cells. In addition, WEFHG reduced the cAMP and PKA levels of hypothalamus in hyperPRL rats significantly. Conclusions. WEFHG showed anti-hyperPRL activity via dopamine D2 receptor, which was related to the second messenger cAMP and PKA. PMID:25254056

  6. Central D2 receptor occupancy and effects of zuclopenthixol acetate in humans.

    PubMed

    Nyberg, S; Farde, L; Bartfai, A; Halldin, C

    1995-11-01

    Repeated positron emission tomography (PET) measurements of D2 receptor occupancy, plasma concentrations of zuclopenthixol and reaction time were performed in three healthy subjects after injection of 12.5 mg zuclopenthixol acetate (ZPTA) in an open study design. Five control subjects were examined for reaction time only. D2 receptor occupancy was 51%, 71% and 75% after 7 h and 75%, 83% and 87% after 31 h in the three subjects. The subjects reported sedation, but reaction time was not prolonged. After the low dose of 12.5 mg ZPTA, D2 receptor occupancy exceeded the 70% assumed to be required to induce antipsychotic effect. Extrapolation of data to a clinical dose interval indicates that 50-150 mg ZPTA should induce very high D2 receptor occupancy lasting several days after injection. Such high doses may be required to induce sedation and to avoid frequent intramuscular injections in acutely psychotic patients. However, the simultaneously induced very high D2 receptor occupancy calls for careful assessment of acute extrapyramidal symptoms.

  7. Effect of D2O on growth properties and chemical structure of annual ryegrass (Lolium multiflorum)

    SciTech Connect

    Evans, Barbara R; Bali, Garima; Reeves, David T; O'Neill, Hugh Michael; Sun, Qining; Shah, Riddhi S; Ragauskas, Arthur

    2014-01-01

    In present paper, we report the production and detailed structural analysis of deuterium-enriched rye grass (Lolium multiflorum) for neutron scattering experiments. An efficient method to produce deuterated biomass was developed by designing hydroponic perfusion chambers. In preliminary studies, the partial deuterated rye samples were grown in increasing levels of D2O to study the seed germination and the level of deuterium incorporation as a function of D2O concentration. Solution NMR method indicated 36.9 % deuterium incorporation in 50 % D2O grown annual rye samples and further significant increase in the deuterium incorporation level was observed by germinating the rye seedlings in H2O and growing in 50 % D2O inside the perfusion chambers. Moreover, in an effort to compare the substrate characteristics related to enzymatic hydrolysis on deuterated and protiated version of biomass, annual rye grown in 50 % D2O was selected for detailed biomass characterization studies. The compositional analyses, degree of polymerization and cellulose crystallinity were compared with its protiated control. The cellulose molecular weight indicated slight variation with deuteration; however, hemicellulose molecular weights and cellulose crystallinity remain unaffected with the deuteration. Besides the minor differences in biomass components, the development of deuterated biomass for neutron scattering application is essential to understand the complex biomass conversion processes.

  8. Diagnostic utility of Fli-1 and D2-40 in distinguishing atypical fibroxanthoma from angiosarcoma.

    PubMed

    Cuda, Jonathan; Mirzamani, Neda; Kantipudi, Ramya; Robbins, Jason; Welsch, Micheal Jude; Sundram, Uma N

    2013-05-01

    Although in most cases one can easily distinguish between atypical fibroxanthomas and angiosarcomas, hemorrhagic atypical fibroxanthomas can pose a diagnostic problem. In rare cases, the large atypical cells of atypical fibroxanthoma can stain with CD31, leading to the erroneous diagnosis of angiosarcoma. We elected to further study this conundrum with 2 additional markers of lymphatic and vascular elements, namely D2-40 (podoplanin) and Fli-1, respectively. We studied 26 cases of atypical fibroxanthoma and 20 cases of angiosarcoma with Fli-1 and D2-40. We found that both Fli-1 and D2-40 stained a majority of cases of angiosarcoma (16/20 and 12/20, respectively), although only staining a minority of cases of atypical fibroxanthoma (8/26 for both). In addition, D2-40 staining of atypical fibroxanthoma was usually weak when positive, whereas Fli-1 staining of angiosarcomas was mostly strong and nuclear. Thus, both D2-40 and Fli-1 seem to be useful in distinguishing between atypical fibroxanthomas and angiosarcomas.

  9. Role of dopamine D2 receptors in optimizing choice strategy in a dynamic and uncertain environment

    PubMed Central

    Kwak, Shinae; Huh, Namjung; Seo, Ji-Seon; Lee, Jung-Eun; Han, Pyung-Lim; Jung, Min W.

    2014-01-01

    In order to investigate roles of dopamine receptor subtypes in reward-based learning, we examined choice behavior of dopamine D1 and D2 receptor-knockout (D1R-KO and D2R-KO, respectively) mice in an instrumental learning task with progressively increasing reversal frequency and a dynamic two-armed bandit task. Performance of D2R-KO mice was progressively impaired in the former as the frequency of reversal increased and profoundly impaired in the latter even with prolonged training, whereas D1R-KO mice showed relatively minor performance deficits. Choice behavior in the dynamic two-armed bandit task was well explained by a hybrid model including win-stay-lose-switch and reinforcement learning terms. A model-based analysis revealed increased win-stay, but impaired value updating and decreased value-dependent action selection in D2R-KO mice, which were detrimental to maximizing rewards in the dynamic two-armed bandit task. These results suggest an important role of dopamine D2 receptors in learning from past choice outcomes for rapid adjustment of choice behavior in a dynamic and uncertain environment. PMID:25389395

  10. Dual role of dopamine D(2)-like receptors in the mediation of conditioned and unconditioned fear.

    PubMed

    Brandão, Marcus Lira; de Oliveira, Amanda Ribeiro; Muthuraju, Sangu; Colombo, Ana Caroline; Saito, Viviane Mitsuko; Talbot, Teddy

    2015-11-14

    A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system, particularly the amygdala, clearly reduces conditioned fear. Similar D2 receptor antagonism in the neural substrates of fear in the midbrain tectum attenuates the processing of unconditioned aversive information. However, the implications of the interplay between opposing actions of dopamine in the rostral and caudal segments of the dopaminergic system are still unclear. Previous studies from this laboratory have reported the effects of dopaminergic drugs on behavior in rats in the elevated plus maze, auditory-evoked potentials (AEPs) recorded from the midbrain tectum, fear-potentiated startle, and conditioned freezing. These findings led to an interesting framework on the functional roles of dopamine in both anxiety and fear states. Dopamine D2 receptor inhibition in the terminal fields of the mesolimbic dopamine system generally causes anxiolytic-like effects, whereas the activity of midbrain substrates of unconditioned fear are enhanced by D2 receptor antagonists, suggesting that D2 receptor-mediated mechanisms play opposing roles in fear/anxiety processes, depending on the brain region under study. Dopamine appears to mediate conditioned fear by acting at rostral levels of the brain and regulate unconditioned fear at the midbrain level, likely by reducing the sensorimotor gating of aversive events. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. Serotonin-S2 and dopamine-D2 receptors are the same size in membranes

    SciTech Connect

    Brann, M.R.

    1985-12-31

    Target size analysis was used to compare the sizes of serotonin-S2 and dopamine-D2 receptors in rat brain membranes. The sizes of these receptors were standardized by comparison with the muscarinic receptor, a receptor of known size. The number of serotonin-S2 receptors labeled with (3H)ketanserin or (3H)spiperone in frontal cortex decreased as an exponential function of radiation dose, and receptor affinity was not affected. The number of dopamine-D2 receptors labeled with (3H)spiperone in striatum also decreased as an exponential function of radiation dose, and D2 and S2 receptors were equally sensitive to radiation. In both striatum and frontal cortex, the number of muscarinic receptors labeled with (3H)QNB decreased as an exponential function of radiation dose, and were much less sensitive to radiation than S2 and D2 receptors. These data indicate that in rat brain membranes, S2 and D2 receptors are of similar size, and both molecules are much larger than the muscarinic receptor.

  12. Deuterium oxide (D2O) enhances the photosensitivity of Stentor coeruleus

    SciTech Connect

    Iwatsuki, K.; Song, P.S.

    1985-12-01

    Stentor coeruleus exhibits negative phototaxis and step-up photophobic response (avoiding reaction) to visible light (maximum at 610-620 nm in both responses). In the presence of deuterium oxide (D2O) the step-up photophobic response was markedly enhanced, whereas the phototactic orientation response was inhibited. The induction time for the step-up photophobic response was longer in D2O than in H2O, and the duration of ciliary reversal for the response was also longer in D2O than in H2O, indicating that certain steps of the sensory transduction chain are subject to solvent deuterium isotope effects. The enhancement of the step-up photophobic response in D2O was canceled by LaCl3, while the inhibition of the phototactic orientation response in D2O was partially removed by LaCl3, even though LaCl3 did not affect the phototactic orientation response. These results suggest that the sensory transduction mechanisms for the two photoresponses are different, although the photoreceptors (stentorin) are the same.

  13. Molecular dissociation of D2+ scattered from a polycrystalline nickel surface

    NASA Astrophysics Data System (ADS)

    Hamhami, M.; Djouhri, N.; Chami, A. C.; Richard-Viard, M.; Boudjema, M.

    2008-08-01

    We compare time of flight spectra of atomic D + and molecular D2+ ions specularly scattered from a polycrystalline nickel surface at 4° of incidence and with a velocity corresponding to 1 keV/u. Molecular dissociation is assumed to occur mostly upon resonant neutralisation into the antibonding triplet state of D 2. The kinetic energy released in the dissociation (KER) is distributed over both atomic fragments. We consider the D2+ spectrum as the result of atomic projectiles hitting the surface at different energies and different incidence or azimuthal angles given by the cinematic of the fragmentation. The electronic density of states of Ni, the vibrational levels of D2+ and the image potential shift are taken into consideration to calculate the KER distribution. The resulting broadening function is then applied to the experimental D + spectrum, which is finally compared to the spectrum of D2+. The good agreement found without any adjustable parameter is consistent with the assumption of a complete dissociation by resonant neutralisation on the incoming path.

  14. Functional expression and characterization of human D2 and D3 dopamine receptors.

    PubMed

    Potenza, M N; Graminski, G F; Schmauss, C; Lerner, M R

    1994-03-01

    Functional characteristics of human D2 and D3 receptors (DRs) were examined using a new bioassay suited for the study of Gi-protein-coupled receptors (GiRs). The bioassay utilizes pigment granule aggregation within cultured Xenopus laevis melanophores for the quantitative evaluation of ligands as agonists or antagonists upon particular GiRs. Initial feasibility studies were performed by analyzing a melanocyte receptor endogenous to the melanophores. In dose-dependent manners, melatonin inhibited melatonin-stimulating hormone-induced cAMP accumulation and caused pigment aggregation that could be monitored over time. Next, melanophores were transiently transfected with cDNAs coding for the human D2BR (short form) and D3R. Expression of either receptor conferred upon the cells the ability to aggregate their melanosomes in response to selective dopaminergic agonists. The same ligands also inhibited cAMP accumulation within the transfected melanophores, and the agonist-induced pigment aggregation was shown to be sensitive to pertussis toxin. EC50 and IC50 value determinations revealed that agonists activated the D2R and D3R at similar concentrations, while each of the antagonists displaying an effect was more potent upon the D2R. The results reveal functional similarities and differences between the D2R and D3R.

  15. Bulk Soil Organic Matter d2H as a Precipitation Proxy

    NASA Astrophysics Data System (ADS)

    Williams, E. K.; Terwilliger, V. J.; Nakamoto, B. J.; Berhe, A. A.; Fogel, M. L.

    2016-12-01

    The stable hydrogen isotopic composition (d2H) of leaf waxes have traditionally been used to infer modern and paleoclimate precipitation sources. However, the extent to which evapotranspiration of leaf waters affects the d2H of plant leaf waxes remains hotly contested with offsets varying between species. Because of the relative importance of root organic matter contribution to bulk soil pools compared to litter/leaves and the minimal fractionation between soil water and root material, it is plausible that bulk soil organic matter d2H may be an option for modern and paleoclimate precipitation reconstructions. In this study, we analyzed the non-exchangeable d2H composition of roots, litter, leaves, and bulk soils along an elevation gradient in the southern Sierra Nevada range (USA). Our results show a consistent offset of 30 ± 3‰ in bulk soil organic matter in surface soils from the measured precipitation. This consistent relationship with precipitation was not found in any of the other organic materials that we measured and implies that d2H bulk soil organic matter can record precipitation signals regardless of above-ground species composition. Additionally, we utilized physical density fractionation to determine which fractions (which vary in level of mineral association and in turnover time) of the soil control this relationship. These findings and how this relationship holds with depth will be presented in conjunction with data from a soil profile on the Ethiopian plateau spanning 6000 years.

  16. Chromosomal aadD2 encodes an aminoglycoside nucleotidyltransferase in Bacillus clausii.

    PubMed

    Bozdogan, Bülent; Galopin, Sébastien; Gerbaud, Guy; Courvalin, Patrice; Leclercq, Roland

    2003-04-01

    Bacillus clausii SIN is one of the four strains of B. clausii composing a probiotic administered to humans for the prevention of gastrointestinal side effects due to oral antibiotic therapy. The strain is resistant to kanamycin, tobramycin, and amikacin. A gene conferring aminoglycoside resistance was cloned into Escherichia coli and sequenced. The gene, called aadD2, encoding a putative 246-amino acid protein, shared 47% identity with ant(4')-Ia from Staphylococcus aureus, which encodes an aminoglycoside 4'-O-nucleotidyltransferase. Phosphocellulose paper-binding assays indicated that the gene product was responsible for nucleotidylation of kanamycin, tobramycin, and amikacin. The aadD2 gene was detected by DNA-DNA hybridization in the three other strains of the probiotic mixture and in the reference strain B. clausii DSM8716, although it did not confer resistance in these strains. Mutations in the sequence of the putative promoter for aadD2 from B. clausii SIN resulted in higher identity with consensus promoter sequences and may account for aminoglycoside resistance in that strain. The aadD2 gene was chromosomally located in all strains and was not transferable by conjugation. These data indicate that chromosomal aadD2 is specific to B. clausii.

  17. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs

    SciTech Connect

    Farde, L.; Wiesel, F.A.; Halldin, C.; Sedvall, G.

    1988-01-01

    Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline.

  18. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

    PubMed

    Urbain, Paul; Jakobsen, Jette

    2015-09-23

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon.

  19. The Roles of Dopamine D2 Receptor in the Social Hierarchy of Rodents and Primates.

    PubMed

    Yamaguchi, Yoshie; Lee, Young-A; Kato, Akemi; Jas, Emanuel; Goto, Yukiori

    2017-02-24

    Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially housed Japanese macaques attenuated social dominance when the drug was given to high social class macaques. A similar attenuation of social dominance was observed in high social class mice with D2 antagonist administration. In contrast, D2 antagonist administration in low social class macaque resulted in more stable social hierarchy of the group, whereas such effect was not observed in mouse social group. These results suggest that D2 receptor signaling may play important roles in establishment and maintenance of social hierarchy in social groups of several species of animals.

  20. Dopamine D2-Like Receptors Modulate Unconditioned Fear: Role of the Inferior Colliculus

    PubMed Central

    de Oliveira, Amanda Ribeiro; Colombo, Ana Caroline; Muthuraju, Sangu; Almada, Rafael Carvalho; Brandão, Marcus Lira

    2014-01-01

    Background A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system clearly reduces conditioned fear. Injections of haloperidol, a preferential D2 receptor antagonist, into the inferior colliculus (IC) enhance the processing of unconditioned aversive information. However, a clear characterization of the interplay of D2 receptors in the mediation of unconditioned and conditioned fear is still lacking. Methods The present study investigated the effects of intra-IC injections of the D2 receptor-selective antagonist sulpiride on behavior in the elevated plus maze (EPM), auditory-evoked potentials (AEPs) to loud sounds recorded from the IC, fear-potentiated startle (FPS), and conditioned freezing. Results Intra-IC injections of sulpiride caused clear proaversive effects in the EPM and enhanced AEPs induced by loud auditory stimuli. Intra-IC sulpiride administration did not affect FPS or conditioned freezing. Conclusions Dopamine D2-like receptors of the inferior colliculus play a role in the modulation of unconditioned aversive information but not in the fear-potentiated startle response. PMID:25133693

  1. Dopamine D(2)-class receptor supersensitivity as reflected in Ca2+ current modulation in neostriatal neurons.

    PubMed

    Prieto, G A; Perez-Burgos, A; Fiordelisio, T; Salgado, H; Galarraga, E; Drucker-Colin, R; Bargas, J

    2009-12-01

    The loss of dopaminergic neurons followed by dopamine (DA) depletion in the neostriatum is a hallmark of Parkinson's disease. Among other changes, DA D(2)-receptor class (D(2)R-class) supersensitivity is a result of striatal DA depletion. Pharmacological, biochemical and behavioral data have documented this phenomenon, but clear electrophysiological-functional correlates are still lacking. This work describes an electrophysiological correlate of D(2)R-class supersensitivity in DA-depleted striata after unilateral 6-hydroxydopamine (6-OHDA) lesions in the rat substantia nigra compacta (SNc). Ca2+ current modulation mediated by D(2)R-class activation reflected an altered sensitivity. Thus, while the concentration-response relationship (C-R plot) from control striata was better fit with a two sites model, the C-R plot obtained from DA-depleted striata was better fit by a three sites model, exhibited a considerable leftward shift, and presented an increased maximal response. Because Ca2+ current modulation by D(2)R-class activation is involved in the control of spiny neurons excitability and their synaptic GABA release, the present findings may help to explain several functional changes found in the striatal circuitry after dopaminergic denervation.

  2. Synthesis and characterization of selective dopamine D2 receptor ligands using aripiprazole as the lead compound

    PubMed Central

    Vangveravong, Suwanna; Zhang, Zhanbin; Taylor, Michelle; Bearden, Melissa; Xu, Jinbin; Cui, Jinquan; Wang, Wei; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    A series of compounds structurally related to aripiprazole (1), an atypical antipsychotic and antidepressant used clinically for the treatment of schizophrenia, bipolar disorder, and depression, have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds also share structural elements with the classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone, domperidone and benperidol. Two new compounds, 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (6) and 7-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (7) were found to (a) bind to the D2 receptor subtype with high affinity (Ki values <0.3 nM), (b) exhibit >50-fold D2 versus D3 receptor binding selectivity and (c) be partial agonists at both the D2 and D3 receptor subtype. PMID:21536445

  3. D2Refine: A Platform for Clinical Research Study Data Element Harmonization and Standardization.

    PubMed

    Sharma, Deepak K; Solbrig, Harold R; Prud'hommeaux, Eric; Lee, Kate; Pathak, Jyotishman; Jiang, Guoqian

    2017-01-01

    In this paper, we present a platform known as D2Refine for facilitating clinical research study data element harmonization and standardization. D2Refine is developed on top of OpenRefine (formerly Google Refine) and leverages simple interface and extensible architecture of OpenRefine. D2Refine empowers the tabular representation of clinical research study data element definitions by allowing it to be easily organized and standardized using reconciliation services. D2Refine builds on valuable built-in data transformation features of OpenRefine to bring source data sets to a finer state quickly. We implemented the reconciliation services and search capabilities based on the standard Common Terminology Services 2 (CTS2) and the serialization of clinical research study data element definitions into standard representation using clinical information modeling technology for semantic interoperability. We demonstrate that D2Refine is a useful and promising platform that would help address the emergent needs for clinical research study data element harmonization and standardization.

  4. The infrared spectrum of the Ne-C2D2 complex.

    PubMed

    Moazzen-Ahmadi, N; McKellar, A R W; Fernández, Berta; Farrelly, David

    2015-11-28

    Infrared spectra of Ne-C2D2 are observed in the region of the ν3 fundamental band (asymmetric C-D stretch, ≈2440 cm(-1)) using a tunable optical parametric oscillator to probe a pulsed supersonic slit jet expansion from a cooled nozzle. Like helium-acetylene, this system lies close to the free rotor limit, making analysis tricky because stronger transitions tend to pile up close to monomer (C2D2) rotation-vibration transitions. Assignments are aided by predicted rotational energies calculated from a published ab initio intermolecular potential energy surface. The analysis extends up to the j = 3←2 band, where j labels C2D2 rotation within the dimer, and is much more complete than the limited infrared assignments previously reported for Ne-C2H2 and Ne-C2HD. Two previous microwave transitions within the j = 1 state of Ne-C2D2 are reassigned. Coriolis model fits to the theoretical levels and to the spectrum are compared. Since the variations observed as a function of C2D2 vibrational excitation are comparable to those noted between theory and experiment, it is evident that more detailed testing of theory will require vibrational averaging over the acetylene intramolecular modes.

  5. Reactivity of Fe-0 atoms and clusters with D2O over FeO(111)

    SciTech Connect

    Parkinson, Gareth S.; Kim, Yu K.; Dohnalek, Zdenek; Smith, R. Scott; Kay, Bruce D.

    2009-03-26

    The interaction of Fe0 atoms with D2O layers on FeO(111) has been investigated using the “atom dropping” preparation technique and a combination of temperature programmed desorption, x-ray photoelectron spectroscopy, Auger electron spectroscopy, and infrared absorption spectroscopy. The data demonstrate that isolated Fe atoms form DFeOD insertion species upon deposition at 35 K, which then dissociate into FeOD and a surface hydroxyl above 200 K. Interestingly, even at very low Fe0 coverages the D2O is perturbed by the presence of the Fe, but only D2O desorption is observed. At higher (≥ 0.5 ML) coverages, clusters of Fe form which have molecular D2O and OD species adsorbed on the surface. Both molecular and recombinative desorption are observed in TPD. In contrast to the low coverage data, a second reaction pathway emerges at high coverage which leads to desorption of D2 and the formation of stable substoichiometric oxide. The mechanism for this minor channel is concluded to involve a reaction between two (or more) DFeOD complexes.

  6. D2Refine: A Platform for Clinical Research Study Data Element Harmonization and Standardization

    PubMed Central

    Sharma, Deepak K.; Solbrig, Harold R.; Prud’hommeaux, Eric; Lee, Kate; Pathak, Jyotishman; Jiang, Guoqian

    2017-01-01

    In this paper, we present a platform known as D2Refine for facilitating clinical research study data element harmonization and standardization. D2Refine is developed on top of OpenRefine (formerly Google Refine) and leverages simple interface and extensible architecture of OpenRefine. D2Refine empowers the tabular representation of clinical research study data element definitions by allowing it to be easily organized and standardized using reconciliation services. D2Refine builds on valuable built-in data transformation features of OpenRefine to bring source data sets to a finer state quickly. We implemented the reconciliation services and search capabilities based on the standard Common Terminology Services 2 (CTS2) and the serialization of clinical research study data element definitions into standard representation using clinical information modeling technology for semantic interoperability. We demonstrate that D2Refine is a useful and promising platform that would help address the emergent needs for clinical research study data element harmonization and standardization. PMID:28815140

  7. The differentiation and assay of vitamins D2 and D3 by gas–liquid chromatography

    PubMed Central

    Murray, T. K.; Day, K. C.; Kodicek, E.

    1966-01-01

    1. A method is described for the differentiation and determination of as little as 0·2μg. of vitamins D2 and D3 by gas–liquid chromatography. 2. The vitamins are converted by treatment with antimony trichloride into isovitamins D2 and D3, which show single, separate peaks on gas–liquid chromatography, unlike the unmodified vitamins, which give twin peaks due to the formation of pyro and isopyro derivatives. 3. Since isovitamins D2 and D3 remain together in all steps of the procedure except during gas–liquid chromatography, one may be used as an internal standard for the other. 4. The use of an internal standard reduces the importance of loss during sample preparation and increases precision. 5. The application of the method to biological materials is demonstrated. PMID:4287184

  8. Chemically accurate simulation of dissociative chemisorption of D2 on Pt(1 1 1)

    NASA Astrophysics Data System (ADS)

    Nour Ghassemi, Elham; Wijzenbroek, Mark; Somers, Mark F.; Kroes, Geert-Jan

    2017-09-01

    Using semi-empirical density functional theory and the quasi-classical trajectory (QCT) method, a specific reaction parameter (SRP) density functional is developed for the dissociation of dihydrogen on Pt(1 1 1). The validity of the QCT method was established by showing that QCT calculations on reaction of D2 with Pt(1 1 1) closely reproduce quantum dynamics results for reaction of D2 in its rovibrational ground state. With the SRP functional, QCT calculations reproduce experimental data on D2 sticking to Pt(1 1 1) at normal and off-normal incidence with chemical accuracy. The dissociation of dihydrogen on Pt(1 1 1) is non-activated, exhibiting a minimum barrier height of -8 meV.

  9. Presence of dopamine D-2 receptors in human tumoral cell lines

    SciTech Connect

    Sokoloff, P.; Riou, J.F.; Martres, M.P.; Schwartz, J.C. )

    1989-07-31

    ({sup 125}I) Iodosulpride binding was examined on eight human cell lines derived from lung, breast and digestive tract carcinomas, neuroblastomas and leukemia. Specific binding was detected in five of these cell lines. In the richest cell line N417, derived from small cell lung carcinoma, ({sup 125}I) iodosulpride bound with a high affinity (Kd = 1.3 nM) to an apparently homogeneous population of binding site (Bmax = 1,606 sites per cell). These sites displayed a typical D-2 specificity, established with several dopaminergic agonists and antagonists selective of either D-1 or D-2 receptor subtypes. In addition, dopamine, apomorphine and RU 24926 distinguished high- and low-affinity sites, suggesting that the binding sites are associated with a G-protein. The biological significance and the possible diagnostic implication of the presence of D-2 receptors on these cell lines are discussed.

  10. Quantitative Analysis of D2 Dopamine Receptor Binding in the Living Human Brain by PET

    NASA Astrophysics Data System (ADS)

    Farde, Lars; Hall, Hakan; Ehrin, Erling; Sedvall, Goran

    1986-01-01

    D2 dopamine receptors in the putamen of living human subjects were characterized by using the selective, high-affinity D2 dopamine receptor antagonist carbon-11-labeled raclopride and positron emission tomography. Experiments in four healthy men demonstrated saturability of [11C]raclopride binding to an apparently homogeneous population of sites with Hill coefficients close to unity. In the normal putamen, maximum binding ranged from 12 to 17 picomoles per cubic centimeter and dissociation constants from 3.4 to 4.7 nanomolar. Maximum binding for human putamen at autopsy was 15 picomoles per cubic centimeter. Studies of [11C]raclopride binding indicate that clinically effective doses of chemically distinct neuroleptic drugs result in 85 to 90 percent occupancy of D2 dopamine receptors in the putamen of schizophrenic patients.

  11. The infrared spectrum of the Ar-C2D2 complex

    NASA Astrophysics Data System (ADS)

    Rezaei, M.; McKellar, A. R. W.; Moazzen-Ahmadi, N.

    2016-10-01

    Infrared spectra of Ar-C2D2 are observed in the region of the ν3 fundamental band (asymmetric C-D stretch, ≈2440 cm-1) using a tunable optical parametric oscillator to probe a pulsed supersonic slit jet expansion from a cooled nozzle. Transitions are assigned involving K = 0-2 in the ground vibrational state, and K = 0-4 in the excited state. The intermolecular bending combination band is also observed, giving a bending frequency of 4.798 cm-1. Despite this low bending frequency, the Ar-C2D2 spectrum qualitatively resembles that of a normal semi-rigid molecule, in contrast to He- and Ne-C2D2 which are much closer to the limit of free internal rotation.

  12. Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists.

    PubMed

    Weichert, Dietmar; Stanek, Markus; Hübner, Harald; Gmeiner, Peter

    2016-06-15

    Aiming to discover dual-acting β2 adrenergic/dopamine D2 receptor ligands, a structure-guided approach for the evolution of GPCR agonists that address multiple targets was elaborated. Starting from GPCR crystal structures, we describe the design, synthesis and biological investigation of a defined set of compounds leading to the identification of the benzoxazinone (R)-3, which shows agonist properties at the adrenergic β2 receptor and substantial G protein-promoted activation at the D2 receptor. This directed approach yielded molecular probes with tuned dual activity. The congener desOH-3 devoid of the benzylic hydroxyl function was shown to be a β2 adrenergic antagonist/D2 receptor agonist with Ki values in the low nanomolar range. The compounds may serve as a promising starting point for the investigation and treatment of neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD

    PubMed Central

    Fan, Xueliang; Hess, Ellen J.

    2007-01-01

    The mechanisms underlying the effects of psychostimulants in attention deficit hyperactivity disorder (ADHD) are not well understood, but indirect evidence implicates D2 dopamine receptors. Here we dissect the components of dopaminergic neurotransmission in the hyperactive mouse mutant coloboma to identify pre- and postsynaptic elements essential for the effects of amphetamine in these mice. Amphetamine treatment reduced locomotor activity in coloboma mice, but induced a robust increase in dopamine overflow suggesting that abnormal regulation of dopamine efflux does not account for the behavioral effect. However, the D2-like dopamine receptor antagonists haloperidol and raclopride, but not the D1-like dopamine receptor antagonist SCH23390, blocked the amphetamine-induced reduction in locomotor activity in coloboma mice, providing direct evidence that D2-like dopamine receptors mediate the effect of amphetamine in these mice. With the precedent established that it is possible to directly antagonize this response, this strategy should prove useful for identifying novel therapeutics in ADHD. PMID:17291774

  14. VUV excitation of a vibrational wavepacket in D2 measured through strong-field dissociative ionization

    NASA Astrophysics Data System (ADS)

    Bainbridge, A. R.; Harrington, J.; Kirrander, A.; Cacho, C.; Springate, E.; Bryan, W. A.; Minns, R. S.

    2015-10-01

    Femtosecond vacuum ultraviolet pulses from a monochromated high harmonic generation source excite vibrational wavepackets in the {B}1{{{Σ }}}{{g}}+ state of D2. The wavepacket motion is measured through strong field ionization into bound and dissociative ion states yielding {{{D}}}2+ and D+ products. The time dependence of the {{{D}}}2+ and D+ ion signals provides a sensitive fingerprint of the quantum nuclear wavepacket, due to the different ionization rates for the two channels. The experiments are modelled with excitation and ionization processes included explicitly, with the results of the model showing a very good agreement with the experimental observations. The experiment demonstrates the level of detail attainable when studying ultrafast quantum nuclear dynamics using high harmonic sources.

  15. Suppressive effect of the dopamine D2 receptor agonist B-HT 920 on rat grooming.

    PubMed

    Ferrari, F; Pelloni, F; Giuliani, D

    1992-06-17

    The effect of the D2 agonist B-HT 920 was examined on three behavioural models of induced grooming in the rat. B-HT 920 potently inhibited the grooming elicited by a novel environment, whereas it stimulated the stretching-yawning syndrome. Pretreatment with the selective dopamine D2 receptor antagonist, sulpiride, reversed the phenomenon. When B-HT 920 was administered to rats before water immersion, it similarly antagonized total grooming; wet-dog shakes, detected in these same animals, were potently inhibited. Finally, B-HT 920 displayed inhibitory activity towards adrenocorticotropin hormone-induced excessive grooming. On the basis of these effects, the role of D2 receptor subtypes in the modulation of grooming is discussed.

  16. Selection of best door-to-cardiac regeneration (D2CR) time

    PubMed Central

    Behjati, Mohaddeseh

    2013-01-01

    In spite of great progress in the treatment of acute coronary syndrome (ACS) events in reperfusion era, patients are still at risk for development of heart failure due to negative remodeling. Thus, the importance of regenerative therapies in parallel with reperfusion strategies is fundamental. A key feature in this case is obtaining the most appropriate door-to-cardiac regeneration (D2CR) time. This golden time in which fresh stem cells can invade scare-prone tissue could be defined as door-to-cardiac stem cell (D2CSC) plus door-to-cardiac regeneration (D2CR) time. Application of stem cells in this golden time allows comprehensive regeneration and reconstruction. Therefore, the aim of this study was to plan the outlines of simultaneous application of cellular and vascular reconstruction strategies. PMID:24575142

  17. Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity

    PubMed Central

    Trifilieff, Pierre; Martinez, Diana

    2014-01-01

    Dependence to drugs of abuse is closely associated with impulsivity, or the propensity to choose a lower, but immediate, reward over a delayed, but more valuable outcome. Here, we review clinical and preclinical studies showing that striatal dopamine signaling and D2 receptor levels – which have been shown to be decreased in addiction - directly impact impulsivity, which is itself predictive of drug self-administration. Based on these studies, we propose that the alterations in D2 receptor binding and dopamine release seen in imaging studies of addiction constitute neurobiological markers of impulsivity. Recent studies in animals also show that higher striatal dopamine signaling at the D2 receptor is associated with a greater willingness to expend effort to reach goals, and we propose that this same relationship applies to humans, particularly with respect to recovery from addiction. PMID:23851257

  18. Spectroscopic investigation of the 3d 2D → nf 2F transitions in lithium

    NASA Astrophysics Data System (ADS)

    Shahzada, S.; Shah, M.; Haq, S. U.; Nawaz, M.; Ahmed, M.; Nadeem, Ali

    2016-05-01

    We report term energies and effective quantum numbers of the odd parity 3d 2D → nf 2F series of lithium using multi-step and multi-photon laser excitation schemes. The experiments were performed using three dye lasers simultaneously pumped by the second harmonic (532 nm) of a Q-switched Nd:YAG laser in conjunction with an atomic beam apparatus and thermionic diode ion detector. The first ionization potential of lithium has been determined as 43,487.13 ± 0.02 cm- 1 from the much extended 3d 2D → nf 2F (17 ≤ n ≤ 70) series. In addition, the oscillator strengths of the 3d 2D → nf 2F (15 ≤ n ≤ 48) transitions have been determined, showing a decreasing trend with the increase in principal quantum number n.

  19. GABAergic control of neostriatal dopamine D2 receptor binding and behaviors in the rat.

    PubMed

    Nikolaus, Susanne; Beu, Markus; de Souza Silva, Maria Angelica; Huston, Joseph P; Antke, Christina; Müller, Hans-Wilhelm; Hautzel, Hubertus

    2017-02-01

    The present study assessed the influence of the GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline on neostriatal dopamine D2 receptor binding in relation to motor and exploratory behaviors in the rat. D2 receptor binding was measured in baseline and after challenge with either 1mg/kg muscimol or 1mg/kg bicuculline. In additional rats, D2 receptor binding was measured after injection of saline. After treatment with muscimol, bicuculline and saline, motor and exploratory behaviors were assessed for 30min in an open field prior to administration of [(123)I]S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide ([(123)I]IBZM). For baseline and challenges, striatal equilibrium ratios (V3″) were computed as estimation of the binding potential. Muscimol but not bicuculline reduced D2 receptor binding relative to baseline and to saline. Travelled distance, duration of rearing and frequency of rearing and of head-shoulder motility were lower after muscimol compared to saline. In contrast, duration of rearing and grooming and frequency of rearing, head-shoulder motility and grooming were elevated after bicuculline relative to saline. Moreover, bicuculline decreased duration of sitting and head-shoulder motility. The muscimol-induced decrease of motor/exploratory behaviors can be related to an elevation of striatal dopamine levels. In contrast, bicuculline is likely to elicit a decline of synaptic dopamine, which, however, is compensated by the time of D2 receptor imaging studies. The results indicate direct GABAergic control over D2 receptor binding in the neostriatum in relation to behavioral action, and, thus, complement earlier pharmacological studies. Copyright © 2016. Published by Elsevier Inc.

  20. Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors.

    PubMed

    Fraser, Kurt M; Haight, Joshua L; Gardner, Eliot L; Flagel, Shelly B

    2016-05-15

    Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D2 and D3 receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D2/D3 agonists, 7-OH-DPAT (0.01-0.32mg/kg) or pramipexole (0.032-0.32mg/kg), the D2/D3 antagonist raclopride (0.1mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D2/D3 agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D3 antagonist did not affect either conditioned response. Alterations in D2/D3 receptor signaling, but not D3 signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D2 receptor is critical for a reward cue to maintain either its incentive or predictive qualities. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.

    PubMed

    Bordia, Tanuja; Zhang, Danhui; Perez, Xiomara A; Quik, Maryka

    2016-12-01

    Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos(+) D2 MSNs and decreased c-Fos(+) non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Genetic variants of dopamine D2 receptor impact heterodimerization with dopamine D1 receptor.

    PubMed

    Błasiak, Ewa; Łukasiewicz, Sylwia; Szafran-Pilch, Kinga; Dziedzicka-Wasylewska, Marta

    2017-04-01

    The human dopamine D2 receptor gene has three polymorphic variants that alter its amino acid sequence: alanine substitution by valine in position 96 (V96A), proline substitution by serine in position 310 (P310S) and serine substitution by cysteine in position 311 (S311C). Their functional role has never been the object of extensive studies, even though there is some evidence that their occurrence correlates with schizophrenia. The HEK293 cell line was transfected with dopamine D1 and D2 receptors (or genetic variants of the D2 receptor), coupled to fluorescent proteins which allowed us to measure the extent of dimerization of these receptors, using a highly advanced biophysical approach (FLIM-FRET). Additionally, Fluoro-4 AM was used to examine changes in the level of calcium release after ligand stimulation of cells expressing different combinations of dopamine receptors. Using FLIM-FRET experiments we have shown that in HEK 293 expressing dopamine receptors, polymorphic mutations in the D2 receptor play a role in dimmer formation with the dopamine D1 receptor. The association level of dopamine receptors is affected by ligand administration, with variable effects depending on polymorphic variant of the D2 dopamine receptor. We have found that the level of heteromer formation is reflected by calcium ion release after ligand stimulation and have observed variations of this effect dependent on the polymorphic variant and the ligand. The data presented in this paper support the hypothesis on the role of calcium signaling regulated by the D1-D2 heteromer which may be of relevance for schizophrenia etiology. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  3. Interaction of the Agrobacterium tumefaciens virulence protein VirD2 with histones.

    PubMed

    Wolterink-van Loo, Suzanne; Escamilla Ayala, Abril A; Hooykaas, Paul J J; van Heusden, G Paul H

    2015-02-01

    Agrobacterium tumefaciens is a Gram-negative soil bacterium that genetically transforms plants and, under laboratory conditions, also transforms non-plant organisms, such as fungi and yeasts. During the transformation process a piece of ssDNA (T-strand) is transferred into the host cells via a type IV secretion system. The VirD2 relaxase protein, which is covalently attached at the 5' end of the T-strand through Tyr29, mediates nuclear entry as it contains a nuclear localization sequence. How the T-strand reaches the chromatin and becomes integrated in the chromosomal DNA is still far from clear. Here, we investigated whether VirD2 binds to histone proteins in the yeast Saccharomyces cerevisiae. Using immobilized GFP-VirD2 and in vitro synthesized His6-tagged S. cerevisiae proteins, interactions between VirD2 and the histones H2A, H2B, H3 and H4 were revealed. In vivo, these interactions were confirmed by bimolecular fluorescence complementation experiments. After co-cultivation of Agrobacterium strains expressing VirD2 tagged with a fragment of the yellow fluorescent protein analogue Venus with yeast strains expressing histone H2A or H2B tagged with the complementary part of Venus, fluorescence was detected in dot-shaped structures in the recipient yeast cells. The results indicated that VirD2 was transferred from Agrobacterium to yeast cells and that it interacted with histones in the host cell, and thus may help direct the T-DNA (transferred DNA) to the chromatin as a prelude to integration into the host chromosomal DNA.

  4. D2 receptor blockade by risperidone correlates with attention deficits in late-life schizophrenia.

    PubMed

    Uchida, Hiroyuki; Rajji, Tarek K; Mulsant, Benoit H; Kapur, Shitij; Pollock, Bruce G; Graff-Guerrero, Ariel; Menon, Mahesh; Mamo, David C

    2009-12-01

    The negative impact of antipsychotic drugs on attention is expected to be greater in late-life schizophrenia because of the age-related changes in the dopamine receptor reserve. The objective of this study was to examine the relationship between dopamine D2 receptor blockade by risperidone and the cognitive function in late-life schizophrenia. Subjects with schizophrenia or schizoaffective disorder aged 50 or older who were receiving risperidone completed a [C]raclopride positron emission tomography scan to measure D2-binding potential in the striatum. The D2 receptor blockade by risperidone was calculated using age-corrected measures from healthy individuals and region of interest analysis of dynamic positron emission tomography data coregistered to the subjects' magnetic resonance imaging scans. Cognitive function was assessed using a battery of neuropsychological tests that included the Dementia Rating Scale-2 (DRS). Eleven subjects (mean +/- SD age, 64 +/- 8 years) participated in this study. The mean +/- SD D2 receptor blockade was 69% +/- 14% (range, 34%-80%). The age-corrected score on the attention subscale in the DRS was negatively correlated with the D2 receptor blockade. The DRS attention subscale score was lower in the subjects who experienced 74.9% or higher D2 blockade (median value, corresponding to a daily risperidone dose of >3.0 mg) than in those who did not. Although a causal attribution cannot be made in light of the cross-sectional nature of this study, the results suggest the critical importance of identifying the lowest effective dose of antipsychotic drugs in older patients with schizophrenia.

  5. Dopamine Transporters, D2 Receptors, and Dopamine Release in Generalized Social Anxiety Disorder

    PubMed Central

    Schneier, Franklin R.; Abi-Dargham, Anissa; Martinez, Diana; Slifstein, Mark; Hwang, Dah-Ren; Liebowitz, Michael R.; Laruelle, Marc

    2009-01-01

    Background Dopamine D2 receptor and dopamine transporter availability in the striatum have each been reported abnormal in generalized social anxiety disorder (GSAD) in studies using single photon computerized tomography (SPECT). D2 receptors and dopamine transporters have not previously been studied within the same GSAD subjects, however, and prior GSAD studies have not assessed dopamine release or subdivided striatum into functional subregions. Methods Unmedicated adults with GSAD (N=17) and matched healthy comparison subjects (HC, N=13) participated in this study. Of these, 15 GSAD and 13 HC subjects completed baseline assessment of D2 receptor availability using positron emission tomography (PET) with the radiotracer [11C] raclopride. Twelve GSAD and 13 HC subjects completed a repeat scan after intravenous administration of D-amphetamine, to study dopamine release. Twelve of the GSAD subjects and 10 of the HC subjects also completed SPECT with the radiotracer [123I] methyl 3ß-(4-iodophenyl) tropane-2ß-carboxylate ([123I] ß-CIT) to assess dopamine transporter availability. Results GSAD and HC groups did not differ significantly in striatal dopamine transporter availability, overall striatal or striatal subregion D2 receptor availability at baseline, or change in D2 receptor availability after D-amphetamine. Receptor availability and change after D-amphetamine were not significantly associated with severity of social anxiety or trait detachment. Conclusions These findings do not replicate previous findings of altered striatal dopamine transporter and D2 receptor availability in GSAD subjects assessed with SPECT. The differences from results of prior studies may be due to differences in imaging methods or characteristics of samples. PMID:19180583

  6. R2d2 Drives Selfish Sweeps in the House Mouse.

    PubMed

    Didion, John P; Morgan, Andrew P; Yadgary, Liran; Bell, Timothy A; McMullan, Rachel C; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J; Campbell, Karl J; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J; Crowley, James J; Chesler, Elissa J; Förster, Daniel W; French, John E; Gabriel, Sofia I; Gatti, Daniel M; Garland, Theodore; Giagia-Athanasopoulou, Eva B; Giménez, Mabel D; Grize, Sofia A; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C; Herman, Jeremy S; Holt, James M; Hua, Kunjie; Jolley, Wesley J; Lindholm, Anna K; López-Fuster, María J; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P; Searle, Jeremy B; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L; Thomas-Laemont, Patricia; Threadgill, David W; Ventura, Jacint; Weinstock, George M; Pomp, Daniel; Churchill, Gary A; Pardo-Manuel de Villena, Fernando

    2016-06-01

    A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.

  7. R2d2 Drives Selfish Sweeps in the House Mouse

    PubMed Central

    Didion, John P.; Morgan, Andrew P.; Yadgary, Liran; Bell, Timothy A.; McMullan, Rachel C.; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J.; Campbell, Karl J.; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J.; Crowley, James J.; Chesler, Elissa J.; Förster, Daniel W.; French, John E.; Gabriel, Sofia I.; Gatti, Daniel M.; Garland, Theodore; Giagia-Athanasopoulou, Eva B.; Giménez, Mabel D.; Grize, Sofia A.; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C.; Herman, Jeremy S.; Holt, James M.; Hua, Kunjie; Jolley, Wesley J.; Lindholm, Anna K.; López-Fuster, María J.; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P.; Searle, Jeremy B.; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L.; Thomas-Laemont, Patricia; Threadgill, David W.; Ventura, Jacint; Weinstock, George M.; Pomp, Daniel; Churchill, Gary A.; Pardo-Manuel de Villena, Fernando

    2016-01-01

    A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation—thereby leaving signatures identical to classical selective sweeps—despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. PMID:26882987

  8. Examining the Role of Dopamine D2 and D3 Receptors in Pavlovian Conditioned Approach Behaviors

    PubMed Central

    Fraser, Kurt M.; Haight, Joshua L.; Gardner, Eliot L.; Flagel, Shelly B.

    2016-01-01

    Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D2 and D3 receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D2/D3 agonists, 7-OH-DPAT (0.01–0.32 mg/kg) or pramipexole (0.032–0.32 mg/kg), the D2/D3 antagonist raclopride (0.1 mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24 mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D2/D3 agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D3 antagonist did not affect either conditioned response. Alterations in D2/D3 receptor signaling, but not D3 signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D2 receptor is critical for a reward cue to maintain either its incentive or predictive qualities. PMID:26909847

  9. N-allyl epiderpride: An extremely potent SPECT radioligand for the dopamine D2 receptor

    SciTech Connect

    Kessler, R.M.; Mason, N.S.; Ansari, M.S.

    1994-05-01

    We have previously reported that epidepride is a potent (K{sub D} 24pM) and specific SPECT radioligand for the dopamine D2 receptor which can be used to study striatal and extrastriatal dopamine D2 receptors in man. We have synthesized and evaluated the N-allyl analogue of epiderpride (APID) as a potential SPECT radioligand for the dopamine D2 receptor. In comparison to epidepride it is even more potent at the dopamine D2 receptor, the K{sub D} for APID being 11 frontal cortical homogenate. The lipophilicity, evaluated using the log kw pH 7.5, was 2.9 versus 2.05 for epidepride. Competitive binding studies using rat striatal, hippocampal and frontal cortical homogenates showed high affinity for only dopamine D2 like cerebellar ratio of 275:1 at 320 minutes post injection-similar to that seen with epidepride, but with nearly four times higher brain uptake. Of interest was the off-rate from the dopamine D2 receptor; it was 0.0046 min{sup -1} in vitro at 25{degrees}C-corresponding to an t 1/2 of 150 minutes. Studies in rhesus monkeys show an in vivo off rate (following 2.5 mg/kg raclopride IV) of about 0.0082 min{sup -1} seen that with epidepride. SPECT studies in rhesus monkeys reveal APID is a promising SPECT radioligand that appears to be similar to epidepride, but with higher brain uptake due to its more optimal lipophilicity for entry into brain.

  10. Hyperdopaminergic Tone Erodes Prefrontal LTP via a D2 Receptor-operated Protein Phosphatase Gate

    PubMed Central

    Xu, Tai-Xiang; Sotnikova, Tatyana D.; Liang, Chengyu; Zhang, Jingping; Jung, Jae U.; Spealman, Roger D.; Gainetdinov, Raul R.; Yao, Wei-Dong

    2009-01-01

    Dopamine (DA) plays crucial roles in the cognitive functioning of the prefrontal cortex (PFC), which, to a large degree, depends on lasting neural traces formed in prefrontal networks. The establishment of these permanent traces requires changes in cortical synaptic efficacy. DA, via the D1-class receptors, is thought to gate or facilitate synaptic plasticity in the PFC, with little role recognized for the D2-class receptors. Here we show that, when significantly elevated, DA erodes, rather than facilitates, the induction of long-term potentiation (LTP) in the PFC by acting at the far less abundant cortical D2-class receptors through a dominant coupling to the protein phosphatase 1 (PP1) activity in postsynaptic neurons. In mice with persistently elevated extracellular DA, resulting from inactivation of the DA transporter (DAT) gene, LTP in layer V PFC pyramidal neurons can not be established, regardless of induction protocols. Acute increase of dopaminergic transmission by DAT blockers or overstimulation of D2 receptors in normal mice have similar LTP shut-off effects. LTP in mutant mice can be rescued by a single in vivo administration of D2-class antagonists. Suppression of postsynaptic PP1 mimics and occludes the D2-mediated rescue of LTP in mutant mice, and prevents the acute erosion of LTP by D2 agonists in normal mice. Our studies reveal a mechanistically unique heterosynaptic PP1 gate that is constitutively driven by background DA to influence LTP induction. By blocking prefrontal synaptic plasticity, excessive DA may prevent storage of lasting memory traces in PFC networks and impair executive functions. PMID:19906957

  11. West Valley Tank 8D-1 and 8D-2 Inventory Estimation Methodology

    SciTech Connect

    O'Brien, Robert F.; Heasler, Patrick G.; Rowell, Laurene

    2001-07-20

    This report details work funded by the West Valley Support Project (WVSP) and the Tanks Focus Area Retrieval and Closure Program. The work was conducted by the Pacific Northwest National Laboratory (PNNL) and is in support of the West Valley Demonstration Project (WVDP). The WVDP site in New York was originally the site of a commercial nuclear fuel reprocessing plant. The high-level waste (HLW), approximately 2 million liters, produced during plutonium-uranium extraction (PUREX) and thorium extraction (THOREX) reprocessing campaigns at the plant and subsequent HLW preprocessing, was stored on site in three tanks identified as 8D-1, 8D-2, and 8D-4. Waste from the PUREX process was neutralized with NaOH for storage in a carbon steel tank designated as 8D-2. Neutralization resulted in a precipitated hydroxide sludge that settled to the bottom of the tank and was covered by a supernatant salt solution. The acidic THOREX waste, approximately 55,000 L, was first stored in a stainless steel tank (8D-4) and then added to the PUREX waste in Tank 8D-2. Supernatant decontamination, primarily cesium removal, was conducted by ion-exchange using in-tank columns suspended in Tank 8D-1. The cesium-loaded zeolite, resulting from the supernatant decontamination process, was dumped to the bottom of Tank 8D-1. Approximately 90% of the spent zeolite was transferred from Tank 8D-1 into Tank 8D-2 by the start of vitrification processing in June 1996. Periodically, the remaining spent zeolite contained in Tank 8D-1 is incrementally transferred to 8D-2. The combined waste in Tank 8D-2 continues to be processed through the Vitrification Facility into canisters for final repository disposal.

  12. 26 CFR 1.674(d)-2 - Limitations on exceptions in section 674 (b), (c), and (d).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Limitations on exceptions in section 674 (b), (c), and (d). 1.674(d)-2 Section 1.674(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... § 1.674(d)-2 Limitations on exceptions in section 674 (b), (c), and (d). (a) Power to remove...

  13. 26 CFR 1.674(d)-2 - Limitations on exceptions in section 674 (b), (c), and (d).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Limitations on exceptions in section 674 (b), (c), and (d). 1.674(d)-2 Section 1.674(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Substantial Owners § 1.674(d)-2 Limitations on exceptions in section 674 (b), (c), and (d). (a) Power...

  14. Improvement in burn wound infection and survival with antimicrobial peptide D2A21 (Demegel).

    PubMed

    Chalekson, Charles P; Neumeister, Michael W; Jaynes, Jesse

    2002-04-01

    Naturally occurring antimicrobial peptides have been discovered in both plants and animals. Many of these peptides demonstrate impaired activity or cytotoxicity when applied exogenously. Synthetically engineered antimicrobial peptides have been designed to increase potency and activity against bacteria and fungus yet remain noncytotoxic. The antimicrobial peptide D2A21 (Demegel) has already demonstrated significant activity in vitro against many common hospital pathogens. The purpose of this study was to evaluate the effects of D2A21 in an in vivo infected burn-wound model, examining both quantitative cultures of the wound and survival of the animal. Forty-four Wistar rats were subjected to a 23 percent total body surface area scald burn. Pseudomonas aeruginosa was administered topically with 108 organisms and wounds were then evaluated at day 1, 2, or 3 for eschar and subeschar muscle quantitative culture. The experimental group was treated daily with 1.5% topical D2A21. The control group was treated with control gel. A second group of Wistar rats (n = 14) were burned and given a 107 inoculum of the same Pseudomonas and evaluated to 14 days for survival and weight changes. This group was subdivided into rats receiving either topical D2A21 or control base daily. The quantitative biopsy results demonstrated that D2A21-treated wounds had no bacterial growth in burn eschar at day 2 or 3, whereas control animals demonstrated growth at greater than 105 organisms by day 2. Subeschar muscle cultures also demonstrated significantly less bacterial invasion compared with controls on each day tested. D2A21-treated animals had an 85.7 percent survival compared with 0 percent survival in controls. Furthermore, the D2A21-treated groups demonstrated maintenance of body weights, whereas controls had significant weight loss with time. In conclusion, D2A21 demonstrates significant antibacterial activity against Pseudomonas, sterilizing burn eschar and decreasing subeschar bacterial

  15. A review of 3D/2D registration methods for image-guided interventions.

    PubMed

    Markelj, P; Tomaževič, D; Likar, B; Pernuš, F

    2012-04-01

    Registration of pre- and intra-interventional data is one of the key technologies for image-guided radiation therapy, radiosurgery, minimally invasive surgery, endoscopy, and interventional radiology. In this paper, we survey those 3D/2D data registration methods that utilize 3D computer tomography or magnetic resonance images as the pre-interventional data and 2D X-ray projection images as the intra-interventional data. The 3D/2D registration methods are reviewed with respect to image modality, image dimensionality, registration basis, geometric transformation, user interaction, optimization procedure, subject, and object of registration.

  16. Strong field dissociative ionization of the D2+: Nuclear wave packet analysis

    NASA Astrophysics Data System (ADS)

    Tóth, A.; Borbély, S.; Halász, G. J.; Vibók, Á.

    2017-09-01

    Theoretical ab initio investigation of strong field dissociative ionization of the D2+ molecule in the multiphoton regime is reported. The dynamics is initiated by ultrashort laser pulses for fixed molecular axis orientations. Nuclear wave packet calculations are performed to provide the joint energy spectra (JES): ionization-dissociation probability density via electron (Ee) and nuclear (En) kinetic energy. Analyzing the time-dependent nuclear wave packet densities we have successfully identified the exact path followed by the D2+ target for each multiphoton peak.

  17. Adolescent Maturation of Dopamine D1 and D2 Receptor Function and Interactions in Rodents

    PubMed Central

    Dwyer, Jennifer B.; Leslie, Frances M.

    2016-01-01

    Adolescence is a developmental period characterized by heightened vulnerability to illicit drug use and the onset of neuropsychiatric disorders. These clinical phenomena likely share common neurobiological substrates, as mesocorticolimbic dopamine systems actively mature during this period. Whereas prior studies have examined age-dependent changes in dopamine receptor binding, there have been fewer functional analyses. The aim of the present study was therefore to determine whether the functional consequences of D1 and D2-like activation are age-dependent. Adolescent and adult rats were given direct D1 and D2 agonists, alone and in combination. Locomotor and stereotypic behaviors were measured, and brains were collected for analysis of mRNA expression for the immediate early genes (IEGs), cfos and arc. Adolescents showed enhanced D2-like receptor control of locomotor and repetitive behaviors, which transitioned to dominant D1-like mechanisms in adulthood. When low doses of agonists were co-administered, adults showed supra-additive behavioral responses to D1/D2 combinations, whereas adolescents did not, which may suggest age differences in D1/D2 synergy. D1/D2-stimulated IEG expression was particularly prominent in the bed nucleus of the stria terminalis (BNST). Given the BNST’s function as an integrator of corticostriatal, hippocampal, and stress-related circuitry, and the importance of neural network dynamics in producing behavior, an exploratory functional network analysis of regional IEG expression was performed. This data-driven analysis demonstrated similar developmental trajectories as those described in humans and suggested that dopaminergic drugs alter forebrain coordinated gene expression age dependently. D1/D2 recruitment of stress nuclei into functional networks was associated with low behavioral output in adolescents. Network analysis presents a novel tool to assess pharmacological action, and highlights critical developmental changes in functional

  18. DOPEX-1D2C: A one-dimensional, two-constraint radiation shield optimization code

    NASA Technical Reports Server (NTRS)

    Lahti, G. P.

    1973-01-01

    A one-dimensional, two-constraint radiation sheild weight optimization procedure and a computer program, DOPEX-1D2C, is described. The DOPEX-1D2C uses the steepest descent method to alter a set of initial (input) thicknesses of a spherical shield configuration to achieve a minimum weight while simultaneously satisfying two dose-rate constraints. The code assumes an exponential dose-shield thickness relation with parameters specified by the user. Code input instruction, a FORTRAN-4 listing, and a sample problem are given. Typical computer time required to optimize a seven-layer shield is less than 1/2 minute on an IBM 7094.

  19. Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

    PubMed

    Skuladottir, G V; Cohen, A; Arnar, D O; Hougaard, D M; Torfason, B; Palsson, R; Indridason, O S

    2016-01-01

    Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

  20. Rovibrational product state distribution for inelastic H+D2 collisions.

    PubMed

    Pomerantz, Andrew E; Ausfelder, Florian; Zare, Richard N; Juanes-Marcos, Juan Carlos; Althorpe, Stuart C; Sáez Rábanos, V; Aoiz, F J; Bañares, L; Castillo, J F

    2004-10-08

    Experimental measurements of rovibrational product state distributions for the inelastic scattering process H + D2(nu=0,j)-->H + D2(nu' = 1,2,j') are presented and compared with the results of quasiclassical and quantum mechanical calculations. Agreement between theory and experiment is almost quantitative. Two subtle trends are found: the relative amount of energy in product rotational excitation decreases slightly with increasing collision energy and increases slightly with increasing product vibrational excitation. These trends are the reverse of what has been found for reactive scattering in which the opposite trends are much more pronounced.

  1. Glory and thresholds effects in H+D 2 reactive angular scattering

    NASA Astrophysics Data System (ADS)

    Sokolovski, D.

    2003-03-01

    We analyse H+D 2 reactive angular scattering using the S-matrix elements obtained by Aoiz et al. and Althorpe et al. Enhancement of small angle scattering in the v'=3← v=0 H+D 2 delayed reaction is attributed to a glory effect caused by threshold resonances in the v=3 vibrationally adiabatic channel. The oscillatory structures in the reactive angular distributions are shown to be of nearside-farside (NP) origin and are likely to arise from capture in a number of relatively short-lived barrier Regge states at large angular momenta. Padé reconstruction of the reactive matrix element is discussed in detail.

  2. STS-55 crewmembers work in the SL-D2 module onboard OV-102

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Working in the shirt-sleeve research environment of the Spacelab Deutsche 2 (SL-D2) science module are STS-55 Mission Specialist 1 (MS1) and Payload Commander (PLC) Jerry L. Ross, MS3 Bernard A. Harris, Jr, German Payload Specialist 2 Hans Schlegel, and German Payload Specialist 1 Ulrich Walter. Ross examines sample tube at Rack 8 Werkstofflabor (WL) (left). Harris, holding his arm, waits to have his blood drawn by Schlegel (right). Wearing the baroreflex (BA) collar at Rack 12 Experiment Rack and waving is Walter. The SL-D2 module is located in the payload bay (PLB) of the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102.

  3. Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors.

    PubMed

    Agai-Csongor, Eva; Domány, György; Nógrádi, Katalin; Galambos, János; Vágó, István; Keserű, György Miklós; Greiner, István; Laszlovszky, István; Gere, Anikó; Schmidt, Eva; Kiss, Béla; Vastag, Mónika; Tihanyi, Károly; Sághy, Katalin; Laszy, Judit; Gyertyán, István; Zájer-Balázs, Mária; Gémesi, Larisza; Kapás, Margit; Szombathelyi, Zsolt

    2012-05-15

    Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D(3)/D(2) compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D(3) and D(2) receptors. Several members of this group showed excellent pharmacokinetic and pharmacodynamic properties as demonstrated by outstanding activities in different antipsychotic tests. The most promising representative, 2m (cariprazine) had good absorption, excellent brain penetration and advantageous safety profile. Based on its successful clinical development we are looking forward to the NDA filing of cariprazine in 2012. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. The D2O absorption spectra in the treatment surfaces SiO2 airgel

    NASA Astrophysics Data System (ADS)

    Sinitsa, L.; Lugovskoi, A.

    2014-11-01

    The D2O absorption spectra adsorbed on the nanoporous airgel SiO2 walls in the spectral range 4200 ... 5400 cm-1 are recorded. Two types of sample with pores of 60 nm wide - the nitrogen gas-treated and untreated airgels were examined. The untreated sample was prolonged evacuation and filling by the D2O saturated vapor. The nitrogen gas-treated sample was short-time pumping, accompanied by treatment with dry nitrogen, and re- lapping by the saturated vapor. As a result, the recorded absorption spectra were shown the changes the hydrophilic properties of the nanopores walls by modernity surface in the presence of nitrogen.

  5. Melittin stimulates liver glycogenolysis and the release of prostaglandin D2 and thromboxane B2.

    PubMed Central

    García-Sáinz, J A; Hernández-Sotomayor, S M; Macías-Silva, M

    1990-01-01

    Melittin stimulates glycogenolysis and induces vasoconstriction in perfused rat liver. The effect was rapid and associated with production and release of prostaglandin D2 and thromboxane B2. Indomethacin blocked the release of these eicosanoids and the stimulation of glycogenolysis induced by melittin. Ibuprofen blocked the release of prostaglandin D2 induced by melittin and markedly attenuated that of thromboxane B2. Interestingly, the initial burst of glucose output induced by melittin was not inhibited by ibuprofen, although the duration of the glycogenolytic action of the peptide was greatly diminished. PMID:2375756

  6. Identification of Dopamine D2 Receptors in Gill of Crassostrea virginica

    PubMed Central

    Anador, Samuel; Brown, Cherryle; Adebesin, Damilola; Cilli, Noelia; Fleming, Renee; Carroll, Margaret A.; Catapane, Edward J.

    2011-01-01

    The lateral epithelial cells of gill of Crassostrea virginica are innervated by dopamine and serotonin nerves that regulate the beating rate of their lateral cilia. Terminal release of dopamine slows down the beating rate of the cilia, while serotonin release increases the beating rate. Previously, we showed that the dopaminergic, but not the serotonergic, mechanism regulating the beating rate of the lateral cilia was disrupted by manganese treatments and that this disruption was occurring postsynaptically, at the level of the dopamine receptor or further downstream in the signal transduction pathway. In humans manganese toxicity causes Manganism, a neurological disorder with clinical symptoms similar to Parkinson s disease. In this study we utilized pharmacological agents and an immunohistofluorescence technique to characterize the dopamine receptor type present on the lateral ciliated cells of C. virginica gill. Agonists and antagonists to dopamine D1 or dopamine D2 receptors were applied to gill sections and beating rates of the lateral cilia were measured by stroboscopic microscopy. The D2 agonists and D2 antagonists were effective in mimicking or blocking, respectively, the inhibitory actions of dopamine on lateral cilia beating, while application of either D1 agonists or D1 antagonists had no significant effect. In other experiments we used an epilume fluorescence microscopic fitted with FITC filters to view gill sections treated with a primary antibody against D2 receptors and a FITC-linked secondary antibody. Control gill sections without primary antibody exposure were similarly treated and viewed. The D2 antibody treated sections showed bright fluorescent receptor-antibody complexes present at the lateral ciliated cells and other areas of gill, when compared to controls. The results of our immunofluorescence study identify the presence of D2-like receptors on the lateral ciliated cells of C. virginica gill and our pharmacological results indicate that D2

  7. STS-55 crewmembers work in the SL-D2 module onboard OV-102

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Working in the shirt-sleeve research environment of the Spacelab Deutsche 2 (SL-D2) science module are STS-55 Mission Specialist 1 (MS1) and Payload Commander (PLC) Jerry L. Ross, MS3 Bernard A. Harris, Jr, German Payload Specialist 2 Hans Schlegel, and German Payload Specialist 1 Ulrich Walter. Ross examines sample tube at Rack 8 Werkstofflabor (WL) (left). Harris, holding his arm, waits to have his blood drawn by Schlegel (right). Wearing the baroreflex (BA) collar at Rack 12 Experiment Rack and waving is Walter. The SL-D2 module is located in the payload bay (PLB) of the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102.

  8. D1-D2 Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

    PubMed Central

    Chun, Lani S.; Free, R. Benjamin; Doyle, Trevor B.; Huang, Xi-Ping; Rankin, Michele L.

    2013-01-01

    The D1 dopamine receptor (D1R) has been proposed to form a hetero-oligomer with the D2 dopamine receptor (D2R), which in turn results in a complex that couples to phospholipase C–mediated intracellular calcium release. We have sought to elucidate the pharmacology and mechanism of action of this putative signaling pathway. Dopamine dose-response curves assaying intracellular calcium mobilization in cells heterologously expressing the D1 and D2 subtypes, either alone or in combination, and using subtype selective ligands revealed that concurrent stimulation is required for coupling. Surprisingly, characterization of a putative D1-D2 heteromer-selective ligand, 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-(3-methylphenyl)-1H-3-benzazepine-7,8-diol (SKF83959), found no stimulation of calcium release, but it did find a broad range of cross-reactivity with other G protein–coupled receptors. In contrast, SKF83959 appeared to be an antagonist of calcium mobilization. Overexpression of Gqα with the D1 and D2 dopamine receptors enhanced the dopamine-stimulated calcium response. However, this was also observed in cells expressing Gqα with only the D1R. Inactivation of Gi or Gs with pertussis or cholera toxin, respectively, largely, but not entirely, reduced the calcium response in D1R and D2R cotransfected cells. Moreover, sequestration of Gβγ subunits through overexpression of G protein receptor kinase 2 mutants either completely or largely eliminated dopamine-stimulated calcium mobilization. Our data suggest that the mechanism of D1R/D2R–mediated calcium signaling involves more than receptor-mediated Gq protein activation, may largely involve downstream signaling pathways, and may not be completely heteromer-specific. In addition, SKF83959 may not exhibit selective activation of D1-D2 heteromers, and its significant cross-reactivity to other receptors warrants careful interpretation of its use in vivo. PMID:23680635

  9. Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

    PubMed

    Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

    2016-04-14

    There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool.

  10. Diabetes ongoing sustainable care and treatment (DOST): A strategy for informational deliverance through visual dynamic modules sustained by near peer mentoring

    PubMed Central

    Joshi, Ankur; Arutagi, Vishwanath; Nahar, Nitin; Tiwari, Sharad; Singh, Daneshwar; Sethia, Soumitra

    2016-01-01

    Background: The informational continuity for a diabetic patient is of paramount importance. This study on a pilot basis explores the process utility of structured educational modular sessions grounded on the principle of near-peer mentoring. Methodology: Visual modules were prepared for diabetic patients. These modules were instituted to 25 diabetic patients in logical sequences. In the next phase, 4 persons of these 25 patients were designated as diabetic-diabetes ongoing sustainable care and treatment (DOST). Each diabetic-DOST was clubbed with two patients for modular session and informational deliverance during the next 7 days. Process analysis was performed with “proxy-indicators,” namely, monthly glycemic status, knowledge assessment scores, and quality of life. Data were analyzed by interval estimates and through nonparametric analysis. Results: Nonparametric analysis indicated a significant improvement in glycemic status in terms with fasting blood sugar (W = 78 z = 3.04, P = 0.002), 2 h-postprandial blood sugar (W = 54, z = 2.01, P = 0.035), and in knowledge score (χ2 = 19.53, df = 3; P = 0.0002). Quality of life score showed significant improvement in 2 out of 7 domains, namely, satisfaction with treatment ([difference in mean score = 1.40 [1.94 to 0.85]) and symptom botherness (difference in mean score = 0.98 [1.3–0.65]). Conclusion: Because of inherent methodological limitations and innate biases, at this juncture no conclusive statement can be drawn. Although, primitive process evidences indicate the promising role of the diabetic-DOST strategy. PMID:27843826

  11. Amphetamine decreases behavioral inhibition by stimulation of dopamine D2, but not D3, receptors.

    PubMed

    van Gaalen, Marcel M; Unger, Liliane; Jongen-Rêlo, Ana-Lucia; Schoemaker, Hans; Gross, Gerhard

    2009-09-01

    Behavioral disinhibition is a manifestation of impulsive behavior that is prominent in the psychopathology of various psychiatric disorders such as addiction, attention-deficit hyperactivity disorder, mania, and personality disorders. Impulsivity may be studied by measuring anticipatory responses made before the presentation of a food-predictive, brief light stimulus in a two-choice serial reaction time task. In such serial reaction time tasks, amphetamine has been shown to produce dose-dependent increases in premature responding in a manner dependent on dopamine D(2)-like receptor stimulation. So far, it is unknown whether it is the D(2) or D(3) receptor that is involved in this form of impulsivity. In this study, rats were trained in a two-choice serial reaction time task until baseline performance was stable. Next, effects of the dopamine D(2) preferring antagonist L-741,626 and selective D(3) antagonist SB-277011 were assessed alone and in the presence of amphetamine. Neither L-741,626 nor SB-277011 affected behavioral inhibition, although the latter significantly increased reaction time at 10 mg/kg. Amphetamine dose-dependently increased impulsivity. The effect of amphetamine was attenuated by L-741,626 (3 mg/kg), whereas SB-277011 (3 mg/kg) had no effect. Therefore, amphetamine-induced behavioral disinhibition depends on D(2), but not D(3), receptor stimulation.

  12. 11 CFR 102.4 - Administrative termination (2 U.S.C. 433(d)(2)).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Administrative termination (2 U.S.C. 433(d)(2)). 102.4 Section 102.4 Federal Elections FEDERAL ELECTION COMMISSION GENERAL REGISTRATION, ORGANIZATION... committee's last report disclosed minimal expenditures; (4) The committee's primary purpose for filing...

  13. Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart

    PubMed Central

    Karlstaedt, Anja; Zhang, Xiaotian; Vitrac, Heidi; Harmancey, Romain; Vasquez, Hernan; Wang, Jing Han; Goodell, Margaret A.; Taegtmeyer, Heinrich

    2016-01-01

    Hematologic malignancies are frequently associated with cardiac pathologies. Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a subset of acute myeloid leukemia patients, causing metabolic and epigenetic derangements. We have now discovered that altered metabolism in leukemic cells has a profound effect on cardiac metabolism. Combining mathematical modeling and in vivo as well as ex vivo studies, we found that increased amounts of the oncometabolite d-2-hydroxyglutarate (D2-HG), produced by IDH2 mutant leukemic cells, cause contractile dysfunction in the heart. This contractile dysfunction is associated with impaired oxidative decarboxylation of α-ketoglutarate, a redirection of Krebs cycle intermediates, and increased ATP citrate lyase (ACL) activity. Increased availability of D2-HG also leads to altered histone methylation and acetylation in the heart. We propose that D2-HG promotes cardiac dysfunction by impairing α-ketoglutarate dehydrogenase and induces histone modifications in an ACL-dependent manner. Collectively, our results highlight the impact of cancer cell metabolism on function and metabolism of the heart. PMID:27582470

  14. 3D-2D registration of cerebral angiograms: a method and evaluation on clinical images.

    PubMed

    Mitrovic, Uroš; Špiclin, Žiga; Likar, Boštjan; Pernuš, Franjo

    2013-08-01

    Endovascular image-guided interventions (EIGI) involve navigation of a catheter through the vasculature followed by application of treatment at the site of anomaly using live 2D projection images for guidance. 3D images acquired prior to EIGI are used to quantify the vascular anomaly and plan the intervention. If fused with the information of live 2D images they can also facilitate navigation and treatment. For this purpose 3D-2D image registration is required. Although several 3D-2D registration methods for EIGI achieve registration accuracy below 1 mm, their clinical application is still limited by insufficient robustness or reliability. In this paper, we propose a 3D-2D registration method based on matching a 3D vasculature model to intensity gradients of live 2D images. To objectively validate 3D-2D registration methods, we acquired a clinical image database of 10 patients undergoing cerebral EIGI and established "gold standard" registrations by aligning fiducial markers in 3D and 2D images. The proposed method had mean registration accuracy below 0.65 mm, which was comparable to tested state-of-the-art methods, and execution time below 1 s. With the highest rate of successful registrations and the highest capture range the proposed method was the most robust and thus a good candidate for application in EIGI.

  15. Immersive Input Display Device (I2D2) for tactical information viewing

    NASA Astrophysics Data System (ADS)

    Tremper, David E.; Burnett, Kevin P.; Malloy, Andrew R.; Wert, Robert

    2006-05-01

    Daylight readability of hand-held displays has been an ongoing issue for both commercial and military applications. In an effort to reduce the effects of ambient light on the readability of military displays, the Naval Research Laboratory (NRL) began investigating and developing advanced hand-held displays. Analysis and research of display technologies with consideration for vulnerability to environmental conditions resulted in the complete design and fabrication of the hand-held Immersive Input Display Device (I2D2) monocular. The I2D2 combines an Organic Light Emitting Diode (OLED) SVGA+ micro-display developed by eMagin Corporation with an optics configuration inside a cylindrical housing. A rubber pressure-eyecup allows view ability only when the eyecup is depressed, eliminating light from both entering and leaving the device. This feature allows the I2D2 to be used during the day, while not allowing ambient light to affect the readability. It simultaneously controls light leakage, effectively eliminating the illumination, and thus preserving the tactical position, of the user in the dark. This paper will examine the characteristics and introduce the design of the I2D2.

  16. Progress report on muon catalyzed fusion studies in H2+D2 and HD gaseous targets

    NASA Astrophysics Data System (ADS)

    Aniol, K. A.; Margaziotis, D. J.; Noble, A. J.; Stanislaus, S.; Virtue, C. J.; Measday, D. F.; Horvath, D.; Robertson, B. C.; Salomon, M.; Jones, S. E.

    1988-12-01

    Gamma yields from the decay of the muonic molecule pdμ produced in muon-catalyzed fusion studies in H2+D2 and HD gaseous targets have been measured. The experiments have been performed at TRIUMF and the data is presented in this report. (AIP)

  17. Equilibration in the Kac Model Using the GTW Metric d_2

    NASA Astrophysics Data System (ADS)

    Tossounian, H.

    2017-10-01

    We use the Fourier based Gabetta-Toscani-Wennberg metric d_2 to study the rate of convergence to equilibrium for the Kac model in 1 dimension. We take the initial velocity distribution of the particles to be a Borel probability measure μ on R^n that is symmetric in all its variables, has mean ěc {0} and finite second moment. Let μ _t(dv) denote the Kac-evolved distribution at time t, and let R_μ be the angular average of μ . We give an upper bound to d_2(μ _t, R_μ ) of the form \\min { B e^{-4 λ _1/n+3t}, d_2(μ ,R_μ )} , where λ _1 = n+2/2(n-1) is the gap of the Kac model in L^2 and B depends only on the second moment of μ . We also construct a family of Schwartz probability densities f_0^{(n)}: R^n→ R with finite second moments that shows practically no decrease in d_2(f_0(t), R_{f_0}) for time at least 1/2λ with λ the rate of the Kac operator. We also present a propagation of chaos result for the partially thermostated Kac model in Tossounian and Vaidyanathan (J Math Phys 56(8):083301, 2015).

  18. Improper activation of D1 and D2 receptors leads to excess noise in prefrontal cortex

    PubMed Central

    Avery, Michael C.; Krichmar, Jeffrey L.

    2015-01-01

    The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC) and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC. PMID:25814948

  19. Introducing the R2D2 Model: Online Learning for the Diverse Learners of This World

    ERIC Educational Resources Information Center

    Bonk, Curtis J.; Zhang, Ke

    2006-01-01

    The R2D2 method--read, reflect, display, and do--is a new model for designing and delivering distance education, and in particular, online learning. Such a model is especially important to address the diverse preferences of online learners of varied generations and varied Internet familiarity. Four quadrants can be utilized separately or as part…

  20. 26 CFR 1.1244(d)-2 - Increases in basis of section 1244 stock.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Increases in basis of section 1244 stock. 1.1244....1244(d)-2 Increases in basis of section 1244 stock. (a) In general. If subsequent to the time of its issuance there is for any reason, including the operation of section 1376(a), an increase in the basis of...

  1. Part 1 of 3 of panorama with HABS CA2783D2 and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Part 1 of 3 of panorama with HABS CA-2783-D-2 and HABS CA-2783-D-3. View of north elevation of Building No. 9. Hinkley Avenue in foreground, looking south - Easter Hill Village, Building No. 11, South side of Hinkley Avenue, west of South Twenty-Sixth Street, Richmond, Contra Costa County, CA

  2. GIPC Recruits GAIP (RGS19) To Attenuate Dopamine D2 Receptor SignalingD⃞

    PubMed Central

    Jeanneteau, Freddy; Guillin, Olivier; Diaz, Jorge; Griffon, Nathalie; Sokoloff, Pierre

    2004-01-01

    Pleiotropic G proteins are essential for the action of hormones and neurotransmitters and are activated by stimulation of G protein–coupled receptors (GPCR), which initiates heterotrimer dissociation of the G protein, exchange of GDP for GTP on its Gα subunit and activation of effector proteins. Regulator of G protein signaling (RGS) proteins regulate this cascade and can be recruited to the membrane upon GPCR activation. Direct functional interaction between RGS and GPCR has been hypothesized. We show that recruitment of GAIP (RGS19) by the dopamine D2 receptor (D2R), a GPCR, required the scaffold protein GIPC (GAIP-interacting protein, C terminus) and that all three were coexpressed in neurons and neuroendocrine cells. Dynamic translocation of GAIP to the plasma membrane and coassembly in a protein complex in which GIPC was a required component was dictated by D2R activation and physical interactions. In addition, two different D2R-mediated responses were regulated by the GTPase activity of GAIP at the level of the G protein coupling in a GIPC-dependent manner. Since GIPC exclusively interacted with GAIP and selectively with subsets of GPCR, this mechanism may serve to sort GPCR signaling in cells that usually express a large repertoire of GPCRs, G proteins, and RGS. PMID:15356268

  3. GIPC recruits GAIP (RGS19) to attenuate dopamine D2 receptor signaling.

    PubMed

    Jeanneteau, Freddy; Guillin, Olivier; Diaz, Jorge; Griffon, Nathalie; Sokoloff, Pierre

    2004-11-01

    Pleiotropic G proteins are essential for the action of hormones and neurotransmitters and are activated by stimulation of G protein-coupled receptors (GPCR), which initiates heterotrimer dissociation of the G protein, exchange of GDP for GTP on its Galpha subunit and activation of effector proteins. Regulator of G protein signaling (RGS) proteins regulate this cascade and can be recruited to the membrane upon GPCR activation. Direct functional interaction between RGS and GPCR has been hypothesized. We show that recruitment of GAIP (RGS19) by the dopamine D2 receptor (D2R), a GPCR, required the scaffold protein GIPC (GAIP-interacting protein, C terminus) and that all three were coexpressed in neurons and neuroendocrine cells. Dynamic translocation of GAIP to the plasma membrane and coassembly in a protein complex in which GIPC was a required component was dictated by D2R activation and physical interactions. In addition, two different D2R-mediated responses were regulated by the GTPase activity of GAIP at the level of the G protein coupling in a GIPC-dependent manner. Since GIPC exclusively interacted with GAIP and selectively with subsets of GPCR, this mechanism may serve to sort GPCR signaling in cells that usually express a large repertoire of GPCRs, G proteins, and RGS.

  4. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.643(d)-2... less $1,000 allocable to tax-exempt interest) 4,000 Distributable net income 45,000 In determining the... following example: Example. (1) Under the terms of the trust instrument, the income of a trust is required...

  5. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.643(d)-2 Illustration... less $1,000 allocable to tax-exempt interest) 4,000 Distributable net income 45,000 In determining the... following example: Example. (1) Under the terms of the trust instrument, the income of a trust is required...

  6. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.643(d)-2... less $1,000 allocable to tax-exempt interest) 4,000 Distributable net income 45,000 In determining the... following example: Example. (1) Under the terms of the trust instrument, the income of a trust is required...

  7. Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells

    PubMed Central

    Kim, Jung Seok; Rho, Jun Gi; Shin, Jung Jae; Song, Woo Keun; Lee, Eun Kyung; Egan, Josephine M.; Kim, Wook

    2016-01-01

    Recent reports have shown that cannabinoid 1 receptors (CB1Rs) are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212–2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes. PMID:26967640

  8. Deuteron magnetic resonance probe of the D2-He potential energy surface

    NASA Astrophysics Data System (ADS)

    Armstrong, Robin L.; Bogdan, Mircea; Jeffrey, Kenneth R.; Bissonnette, Carey; McCourt, Frederick R. W.

    1993-10-01

    Measurements of the nuclear magnetic resonance (NMR) longitudinal relaxation time T1 have been carried out for D2-He gas mixtures at temperatures of 293 and 220 K for two concentrations of D2 in He and the results extrapolated linearly to infinite dilution at each temperature. Full quantum close-coupled scattering calculations have also been carried out for an ab initio D2-He interaction potential. The agreement found between measured and calculated relaxation times is excellent at 293 and good at 220 K. Based on the level of agreement found between theory and experiment, it can be concluded that the molecular hydrogen-helium ab initio potential energy surface employed in the present D2-He calculations as well as in earlier H2-He calculations [J. Chem. Phys. 81, 5275 (1984)] represents well the effects of both the spin-rotation and combined dipolar/quadrupolar intramolecular interactions, which dominate the spin relaxation, respectively, of protons and deuterons in the hydrogen isotopes. At the same time, the present results indicate that the disagreement found earlier [J. Chem. Phys. 92, 5907 (1990)] between calculated and measured deuteron T1 values for HD-He mixtures must arise from the specific nature of the HD-He potential energy surface.

  9. R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server.

    PubMed

    Cannone, Jamie J; Sweeney, Blake A; Petrov, Anton I; Gutell, Robin R; Zirbel, Craig L; Leontis, Neocles

    2015-07-01

    The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa.

  10. Systemic Blockade of D2-Like Dopamine Receptors Facilitates Extinction of Conditioned Fear in Mice

    ERIC Educational Resources Information Center

    Ponnusamy, Ravikumar; Nissim, Helen A.; Barad, Mark

    2005-01-01

    Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized…

  11. Repumping of ultracold strontium atoms using the ^3P2 - ^3D2 transition

    NASA Astrophysics Data System (ADS)

    Mickelson, P. G.; Martinez de Escobar, Y. N.; Traverso, A. J.; Killian, T. C.

    2008-05-01

    We discuss recent experiments involving ultracold strontium. Using a commercially-available 3 micron laser, we repump atoms out of the ^3P2 level via the ^3D2 state and gain almost a factor of 10 in the number of atoms in our system. This increase in the signal-to-noise ratio enables improved spectroscopy of strontium in our optical trap.

  12. 26 CFR 1.411(d)-2 - Termination or partial termination; discontinuance of contributions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Bonus Plans, Etc. § 1.411(d)-2 Termination or partial termination; discontinuance of contributions. (a... such plan is not a qualified trust) unless the plan provides that— (i) Upon the termination or partial... partial termination of the plan (or, in the case of a plan to which section 412 does not apply, upon...

  13. 17 CFR 240.12d2-1 - Suspension of trading.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Suspension of trading. 240... Securities Exchange Act of 1934 Suspension of Trading, Withdrawal, and Striking from Listing and Registration § 240.12d2-1 Suspension of trading. (a) A national securities exchange may suspend from trading...

  14. Enhanced GABA Transmission Drives Bradykinesia Following Loss of Dopamine D2 Receptor Signaling.

    PubMed

    Lemos, Julia C; Friend, Danielle M; Kaplan, Alanna R; Shin, Jung Hoon; Rubinstein, Marcelo; Kravitz, Alexxai V; Alvarez, Veronica A

    2016-05-18

    Bradykinesia is a prominent phenotype of Parkinson's disease, depression, and other neurological conditions. Disruption of dopamine (DA) transmission plays an important role, but progress in understanding the exact mechanisms driving slowness of movement has been impeded due to the heterogeneity of DA receptor distribution on multiple cell types within the striatum. Here we show that selective deletion of DA D2 receptors (D2Rs) from indirect-pathway medium spiny neurons (iMSNs) is sufficient to impair locomotor activity, phenocopying DA depletion models of Parkinson's disease, despite this mouse model having intact DA transmission. There was a robust enhancement of GABAergic transmission and a reduction of in vivo firing in striatal and pallidal neurons. Mimicking D2R signaling in iMSNs with Gi-DREADDs restored the level of tonic GABAergic transmission and rescued the motor deficit. These findings indicate that DA, through D2R activation in iMSNs, regulates motor output by constraining the strength of GABAergic transmission.

  15. Natural variation of rice blast resistance gene Pi-d2

    USDA-ARS?s Scientific Manuscript database

    Studying natural variation of rice resistance (R) genes in cultivated and wild rice relatives can predict resistance stability to rice blast fungus. In the present study, the protein coding regions of rice R gene Pi-d2 in 35 rice accessions of subgroups, aus (AUS), indica (IND), temperate japonica (...

  16. Effects of sigma(1) receptor ligand MS-377 on D(2) antagonists-induced behaviors.

    PubMed

    Karasawa, Jun-ichi; Takahashi, Shinji; Takagi, Kaori; Horikomi, Kazutoshi

    2002-10-01

    (R)-(+)-1-(4-Chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377) is a novel antipsychotic agent with selective and high affinity for sigma(1) receptor. The present study was carried out to clarify the interaction of MS-377 with dopamine D(2) receptor antagonists (D(2) antagonists) in concurrent administration, and then the involvement of sigma receptors in the interaction. The effects of MS-377 on haloperidol- or sultopride-induced inhibition of apomorphine-induced climbing behavior and catalepsy were investigated in mice and rats, respectively. In addition, the effects of (+)-SKF-10,047 and SA4503, both of which are sigma receptor agonists, and WAY-100,635, which is a 5-HT(1A) receptor antagonist, on the interaction due to the concurrent use were also investigated. MS-377 potentiated the inhibitory effects of haloperidol or sultopride on apomorphine-induced climbing behavior in a dose-dependent manner. In contrast, MS-377 did not affect the catalepsy induction by these drugs. The potentiation of the inhibitory effects of haloperidol or sultopride on apomorphine-induced climbing behavior by MS-377 was not inhibited by WAY-100,635, but was inhibited by (+)-SKF-10,047 and SA4503. These findings showed that MS-377 potentiates the efficacy of D(2) antagonists, but it does not deteriorate the adverse effect. Moreover, sigma(1) receptors are involved in this potentiation of the efficacy of D(2) antagonists by MS-377.

  17. Cold brittleness of corrosion-resistant maraging steel 08Kh15N5D2T

    NASA Astrophysics Data System (ADS)

    Makhneva, T. M.

    2012-03-01

    Results of a study of the effect of the method of remelting and of heat treatment modes on the behavior of serial curves of impact toughness and on the position of cold-shortness threshold in steel 08Kh15N5D2T are presented.

  18. Solid H2 and D2: Remarkable differences in some NMR properties

    NASA Astrophysics Data System (ADS)

    Harris, A. B.; Meyer, H.; Qin, X.

    1994-02-01

    The differences in the observed properties of solid H2 and D2 are reviewed, and in particular those encountered in NMR experiments. The failure to detect a sharp NMR (I=1) impurity ``isolated pair'' spectrum in p-D2 is discussed in terms of a larger crystalline field than in H2, where an intense and sharp pair spectrum has been observed. Furthermore, we discuss the dramatic (I=1) solid echo signal loss with decreasing temperature which is observed in solid D2, but not for solid H2. A theory of the solid echo damping through orientational fluctuations is developed. This theory accounts for the observed solid echo decay in D2 as a function of the pulse spacing time τ and leads to an estimation of the order parameter fluctuation amplitude and the correlation time τc. However, the theory cannot account for the loss of spin (as determined from Curie's law), which must occur for very small values of τ that are not covered by the theory.

  19. Contribution of dopamine D1 and D2 receptors to amygdala activity in human.

    PubMed

    Takahashi, Hidehiko; Takano, Harumasa; Kodaka, Fumitoshi; Arakawa, Ryosuke; Yamada, Makiko; Otsuka, Tatsui; Hirano, Yoshiyuki; Kikyo, Hideyuki; Okubo, Yoshiro; Kato, Motoichiro; Obata, Takayuki; Ito, Hiroshi; Suhara, Tetsuya

    2010-02-24

    Several animal studies have demonstrated functional roles of dopamine (DA) D1 and D2 receptors in amygdala activity. However, the contribution of DA D1 and D2 receptors to amygdala response induced by affective stimuli in human is unknown. To investigate the contribution of DA receptor subtypes to amygdala reactivity in human, we conducted a multimodal in vivo neuroimaging study in which DA D1 and D2 receptor bindings in the amygdala were measured with positron emission tomography (PET), and amygdala response induced by fearful faces was assessed by functional magnetic resonance imaging (fMRI) in healthy volunteers. We used multimodality voxelwise correlation analysis between fMRI signal and DA receptor binding measured by PET. DA D1 binding in the amygdala was positively correlated with amygdala signal change in response to fearful faces, but DA D2 binding in the amygdala was not related to amygdala signal change. DA D1 receptors might play a major role in enhancing amygdala response when sensory inputs are affective.

  20. Systemic Blockade of D2-Like Dopamine Receptors Facilitates Extinction of Conditioned Fear in Mice

    ERIC Educational Resources Information Center

    Ponnusamy, Ravikumar; Nissim, Helen A.; Barad, Mark

    2005-01-01

    Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized…