WorldWideScience

Sample records for bioclim deliverable d1

  1. UMBRELLA Deliverable D 1.3 "Final Report"

    OpenAIRE

    Becker, Raik; Benavent Rodríguez, Belén; Bootsman, Rob; Eickmann, Jonas; Engl, Wulf Albrecht; Gilsdorf, Peter; Jansen, Michel; Krahl, Simon; Krause, Thilo; Moormann, Andreas; Morales-España, Germán; Paeschke, Helmut; Ramirez Elizondo, Laura; Roald, Line; Rogge, Michael

    2015-01-01

     This deliverable summarizes the content of the FP7 project UMBRELLA. It describes the objectives and the results achieved by the end of the four project years. UMBRELLA is also cooperating with the related FP7 project iTesla, i.e. some public workshops are performed commonly, test environments are harmonized and a common proposal on potential development of future TSO rules is proposed.

  2. Preliminary Collider Baseline Parameters: Deliverable D1.1

    CERN Document Server

    AUTHOR|(SzGeCERN)430609

    2015-01-01

    This deliverable provides a preliminary specification of the layout and target operation parameters for the FCC-hh hadron collider concept. They serve as starting point for the studies in all work packages. The goal of the FCC hadron collider is to provide proton-proton collisions at a centre-of-mass energy of 100 TeV. The machine is compatible with ion beam operation. Assuming a nominal dipole field of 16 T, such a machine is based on a perimeter of 100 km. The machine is designed to accommodate two main proton experiments that are operated simultaneously. The machine delivers a peak luminosity of 5-30 x 1034 cm-2s-1. The layout allows for two additional special-purpose experiments.

  3. Go-Lab Deliverable D1.4 Go-Lab classroom scenarios handbook

    OpenAIRE

    2015-01-01

    This deliverable presents the Go-Lab scenarios handbook. This handbook offers six different scenarios that are meant to help teachers design ILSs. Each scenario represents a specific pedagogical method within the overall Go-Lab inquiry approach. The six Go-Lab inquiry scenarios are labelled as follows:• The basic scenario • The jigsaw approach • Six changing hats • Learning by critiquing • Structured controversy • Find the mistakeIn a later stage, when a suitable modelling tool has been found...

  4. Wavetrain 2 : Deliverable 29

    DEFF Research Database (Denmark)

    Crom, Izan Le; Pecher, Arthur; Parmeggiani, Stefano

    Deliverable 29 describes a newly proposed methodology to evaluate the power performances of wave (and tidal) energy converters. This methodology has been applied within the Wavetrain2 project to evaluate the production of two wave energy conversion plants: the Pico OWC Plant and the Wave Dragon...

  5. Wavetrain 2 : Deliverable 28

    DEFF Research Database (Denmark)

    Chozas, Julia Fernandez

    Denmark (the Danish TSO) and counts with the interest and collaboration of the wave device developers Pelamis, Wave Dragon and Wavestar. The second case study assesses the macro-economic impact of the introduction of a 100MW farm in Portugal. An Input-Output model based on Leontief theory was developed...... (HMRC) and Hans C. Sorensen (SPOK). It included 3 main parts: a first introduction to microeconomics at project level, a second practical session on the use of economic model Retscreen and a final session introducing macro and socio-economic aspects.......This deliverable presents a selection of case studies on socio-economic aspects of wave energy, developed by Wavetrain2 partners SPOK and WavEC, that represent key areas of research during the WT2 period. More information and a few other case studies can be also found in the previous deliverables D...

  6. Deliverable D1: Engineering study of the Hg converter

    CERN Document Server

    K. Samec et al.

    The development of high-power converter targets otherwise known as neutron sources is today the focus of much attention, driven by the need for ever greater densities of neutron fluxes which are required in the fundamental sciences such as neutron imagery, isotope production and also for the more long-term goal of realising a hybrid sub-critical nuclear reactor. The neutrons in a converter target are produced by a process known in physics as spallation whereby a heavy Z atom releases neutrons below 20 [MeV] when hit by an incoming proton.The Eurisol initiative seeks to develop such an isotope production facility to provide the scientific community with the means to achieving high yields of isotopes and extending the variety of isotopes thus produced towards more exotic types rarely seen in existing facilities.The proposed ISOL facility would use both (a) several 100 kW proton beams on a thick solid target to produce RIBs directly, and (b) a liquid metal 1–5 MW ‘converter’ target to release high fluxes o...

  7. Solicitant -exciting plain bioclimate / Amara Balneoclimateric Resort, 

    Directory of Open Access Journals (Sweden)

    Munteanu Constantin

    2011-05-01

    Full Text Available Spa and balneotherapy is one of studying medicine and therapy and apply natural factors intherapy: natural mineral water springs and lakes mineralized, therapeuticmineral mud and peat, gas emanations and climate zones,orlocalities developed intosources respective treatment , the spa resort climate.Resources are the mineral spa and climatic treatment ,whose physicochemical properties meet the needs of prevention and health maintenance, strengthening and restoration of health, work capacity and physical and mental comfort of the individual.Climatic is a form of treatment, well-run, have fewer side effects than chemo therapeutictreatment and prolonged effects, because the way treatment is as close to normal activity in a relaxing environment.Bioclimate turn-applicant is characterized by general biological effects resulting from theapplication marked the central nervous system and autonomic and endocrine activity. Bioclimatic conditions, demanding aplain exciting resorts are located in northeasternbalneoclimatice Baragan, on the shores of salt lakes: Amara, Lacul Sarat.

  8. [Self-deliverance or infanticide?].

    Science.gov (United States)

    Rittner, Christian; Gehb, Iris; Püschel, Klaus

    2008-01-01

    Self-deliverance by a woman in labour is nowadays a very rare event. The authors report the case of a 24-year-old primipara and a newborn of 49 cm length and 2484 g body weight with a complex pattern of injuries on the head, neck, shoulder and back who had breathed for at least 15 to 30 minutes after birth and died from massive craniocerebral trauma and lesions in the oral and cervical region. As one of the experts considered it possible that the skull fractures were exclusively due to the self-deliverance, the woman was acquitted of the charge of manslaughter. This hypothesis is critically discussed on the basis of the presumable course of the delivery and the literature.

  9. The human bioclimates of Western and South Pacific islands and climate change.

    Science.gov (United States)

    McGregor, G R

    1995-08-01

    The current bioclimates of equatorial Western and tropical South Pacific have been assessed, using the concepts of effective temperature and relative strain as a basis for evaluating likely changes in human comfort regimes as a consequence of global warming. Current bioclimates may be considered marginally stressful for indigenous populations. Global warming will result in changes in the frequency, duration and intensity of physioclimatically stressful conditions.

  10. D1.1 Detailed requirements for GloNet use case and domain glossary

    NARCIS (Netherlands)

    Afsarmanesh, H.; Korojelo, S.; Sargolzaei, M.; Thamburaj, V.; Madhavan, V.; Camarinha-Matos, L.

    2012-01-01

    D1.1 is one of the first deliverables of the project, which sets the base for research in all other WPs in GloNet. The findings reported in this deliverable are resulted through direct involvement of the two energy related industries within the GloNet consortium (iPLON and Prolon), as well as the li

  11. Ordenación del territorio. Planificación ambiental y urbanismo bioclimático

    OpenAIRE

    Higueras García, Esther

    2013-01-01

    Ordenación del territorio, Planificación ambiental y urbanismo bioclimático .- La planificación ambiental .- El urbanismo bioclimatico 1. .- Metodología del Urbanismo Bioclimático. 2. .- Criterios bioclimáticos para el planeamiento general para la red viaria 3. .- Jerarquización de las vías urbanas 4. .- Consecuencias de la orientación de las calles sobre las parcelas y edificaciones. 5. - Estrategias bioclimáticas para el sistema general de zonas verdes y espacios libr...

  12. Final measurement. Deliverable D5.3

    NARCIS (Netherlands)

    Holtzer, A.C.G.; Giessen, A.M. van der; Djurica, M.; Gruber, G.; Krengel, M.; Kokkinos, P.; Varvarigos, M.; Prusa, J.; Schulting, H.W.; Holzmann-Kaiser, U.; Schmoll, C.; Hatzakis, I.; Silva, F.M. da; Reymund, A.; Strebler, R.; Moreno, J.J.R.; Munoz, C.G.; Gheorghe, G.; Nikolopoulos, V.; Mavridis, T.; Bektas, O.; Yuce, E.; Volk, M.; Sterle, J.; Skarmeta, A.

    2015-01-01

    This deliverable D5.3 presents the GEN6 Final Measurement. It describes the outputs, outcomes and impact of the GEN6 project, based on other project deliverables inputs of the pilot leaders of the active GEN6 pilots and the individual consortium partners. The final measurement aims to show the amoun

  13. Deliverable 1.2.7: Cross-cultural benefit segmentation of consumers

    NARCIS (Netherlands)

    Reinders, M.J.; Onwezen, M.C.; Sijtsema, S.J.; Zimmermann, K.L.; Berg, van den I.; Jasiulewicz, A.; Guardia, M.D.; Guerrero, L.

    2010-01-01

    The present report, deliverable D.1.2.7, gives a final view of the work done in ISAFruit Work Package (WP) 1.2. Average Europe fruit consumption is below the recommended level and moreover the consumption level is still decreasing in Europe. A large survey was carried out in four European countries

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

    Science.gov (United States)

    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.

  15. The essential oils of the Greek endemic Satureja horvatii ssp. macrophylla in relation to bioclimate.

    Science.gov (United States)

    Dardioti, Antonia; Hanlidou, Effie; Lanaras, Tom; Kokkini, Stella

    2010-08-01

    The essential oils of the Greek endemic Satureja horvatii subsp. macrophylla collected from 36 areas (among them, 23 are included in twelve sites of the EU network NATURA 2000) belonging to different bioclimatic types were studied. The total essential-oil content is negatively related to the altitude. The variation of the essential oil composition follows a geographical pattern, which is related to the bioclimatic belts along the taxon's range. Carvacrol dominates in areas with Mediterranean and Submediterranean bioclimate (mainly in the S and C part of the taxon's distribution), linalool or trans-sabinene hydrate, and/or borneol in the Submediterranean or Temperate Axeric bioclimates (in the N part of distribution), whereas thymol is found as main oil constituent in all three bioclimates.

  16. Interpretación bioclimática de la arquitectura vernácula

    OpenAIRE

    Paniagua Padilla, Diego

    2015-01-01

    La ‘arquitectura vernácula’ desarrolló la primera adecuación entre el clima, las necesidades humanas y la construcción sostenible. En este sentido, la ‘arquitectura bioclimática’ de la que hablamos hoy en día es una interpretación de la arquitectura a efectos del clima sobre el hombre. Podríamos entenderla como una arquitectura popular evolucionada y adaptada. ¿Pero es lo mismo arquitectura vernácula que popular? ¿Y arquitectura bioclimática? ¿Es lo que muchos denominan ‘arquitectura sostenib...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  19. CHOReOS perspective on the Future Internet and initial conceptual model (D1.2)

    OpenAIRE

    Autili, Marco; Di Ruscio, Davide; Salle, Amleto Di; Georgantas, Nikolaos; Hachem, Sara; Issamy, Valérie; Parathyras, Athanasios; Trimintzios, Lefteris; Silingas, Darius; Lockerbie, James; Maiden, Neil; Ben Hamida, Amira; Bertolino, Antonia; De Angelis, Guglielmo; Polini, Andrea

    2011-01-01

    The D1.2 deliverable outlines the CHOReOS perspective on the Future Internet and its conceptualization. In particular, the deliverable focuses on: - Definition of the Future Internet and related Future Internet of Services and (Smart) Things, as considered within CHOReOS, further stressing the many dimensions underpinning the Ultra-Large Scale of the Future Internet; - Definition of the initial conceptual model of the CHOReOS Service-Oriented Architecture (SOA) for the Future Internet, identi...

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

    Science.gov (United States)

    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.

  1. Deliverable 1.2.7: Cross-cultural benefit segmentation of consumers

    OpenAIRE

    Reinders, M.J.; Onwezen, M.C.; Sijtsema, S.J.; Zimmermann, K.L.; Berg, van den, Aad; Jasiulewicz, A.; Guardia, M.D.; Guerrero, L.

    2010-01-01

    The present report, deliverable D.1.2.7, gives a final view of the work done in ISAFruit Work Package (WP) 1.2. Average Europe fruit consumption is below the recommended level and moreover the consumption level is still decreasing in Europe. A large survey was carried out in four European countries that consisted of questions regarding the importance consumers attach to food related benefits in general and for specific situations, personal orientations of the consumers, personal characteristi...

  2. UPWIND Metrology, Deliverable D 1A2.1, List of measurement Parameters

    DEFF Research Database (Denmark)

    Hansen, Kurt Schaldemose

    as convincing field tests have not confirmed the actual improvement, the industry will not invest much to change the turbine design. This is an example that clarifies why the development of wind energy is hindered by metrology problems (measurement problems). Other examples are in the fields of: - Warranty...... activity. The problem is especially relevant for the following areas: Production related - Power performance testing especially in wind farms - Testing of turbine improvements in the order of several percent - Testing of aerodynamic codes - Testing of turbine response to effects such as turbulence...... and shear Load related - Mechanical load measurements in farms aimed at verification of aero elastic codes. (blade root moments, yaw moments, tower foot moments etc.) Wind related - Measurement of wake effects and wind resources inside wind farms - Measurements of inter farm effects (regarding velocity...

  3. Deliverable 2.2.1 Use Scenarios in the Pilot Services

    DEFF Research Database (Denmark)

    Peterson, Carrie Beth

    2010-01-01

    and usage scenarios of service bundles to be implemented in the ISISEMD Pilot platform in each of the four regions during the pilot. The services/sub functions are presented as workflows and also described by presenting how the Graphical User Interface will be organized and designed thus reflecting how......Deliverable 2.2.1 - Use scenarios in the pilot services During the first phase of ISISEMD project (WP1) the user requirements analysis phase, mainly D1.1.1, has proposed a list of services organized in three groups (bundles as in Dow) and classified as mandatory or not mandatory and leading...... to different user scenarios. Afterwards services were analyzed, broken down in sub-functions. The outcome of this process represent a further input document guiding to identify and adapt the more suitable product and solution enabled to provide these required services. Deliverable D.2.2.1 describes guidance...

  4. Diseño participativo de espacios urbanos bioclimáticos. Experiencia en Mendoza (Argentina

    Directory of Open Access Journals (Sweden)

    Claudia Fernanda Martinez

    2015-04-01

    Full Text Available El presente trabajo reconoce los beneficios de las técnicas participativas de diseño para la producción social y sustentable del hábitat, al equilibrar soluciones bioclimáticas con los intereses de los beneficiarios. Como metodología, se aplicaron talleres comunitarios orientados tradicionalmente solo a la vivienda, para el diseño participativo de espacios urbanos conexos y sus redes en un conjunto habitacional de la provincia de Mendoza (Argentina. El desarrollo de talleres de diseño participativo pone de manifiesto la importancia de transferir a la comunidad beneficiaria de planes de vivienda de interés social los conceptos de la arquitectura bioclimática y sus implicaciones en la calidad de vida de las personas, el ahorro energético y la sustentabilidad ambiental. Los resultados indican que es posible conciliar el diseño de espacios urbanos eficientes energética y ambientalmente con cero sobrecosto y que, al mismo tiempo satisfagan las expectativas de los usuarios.

  5. Final Report on Models, Periodic Progress, Report No D1.3, Globeman21, ESPRIT 26509

    DEFF Research Database (Denmark)

    Pedersen, Jens Dahl; Tølle, Martin; Vesterager, Johan

    1999-01-01

    This deliverable D1.3 is the third and final deliverable of WP1 - Global Manufacturing Concept of the European part of the Globeman21 project. The report essentially presents the final models on generic Extended Enterprise Management (EEM) and generic Product Life Cycle Management (PLCM), a colle......This deliverable D1.3 is the third and final deliverable of WP1 - Global Manufacturing Concept of the European part of the Globeman21 project. The report essentially presents the final models on generic Extended Enterprise Management (EEM) and generic Product Life Cycle Management (PLCM......), a collection of practical experiences, and requirements for enhanced methods and tools for modelling. First, the deliverable outlines the GM21 understanding regarding extended enterprises and virtual enterprises. This is done by extracting and synthesising the essence of key definitions and concepts...... enterprise context. Through the set of recommended activities for individual life cycle phases of respectively the network entity, the VE entity, and the product entity of the Extended Enterprise Framework, the methodology supports realisation of extended enterprises. The time sequenced planning...

  6. Mapa bioclimático para las travesías de Mendoza (Argentina) basado en la fenología foliar

    OpenAIRE

    González Loyarte, María Margarita; Menenti, Massimo; Diblasi, Ángela

    2009-01-01

    El objetivo fue generar un mapa bioclimático de la llanura de Mendoza que reflejara las diferencias climáticas expresadas por la actividad de la vegetación (fenología foliar) a escala regional. Se partió de la imagen digital del índice bioclimático de aridez P/ETP, generada en una etapa anterior a partir de una serie temporal de imágenes de índice verde (IVDN), y se recodificó en clases bioclimáticas. Se evaluó en...

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

    Directory of Open Access Journals (Sweden)

    Alicia Torregrosa

    Full Text Available 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

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

    Science.gov (United States)

    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

  9. EMPOWER. Deliverable no 7.1 Dissemination Plan

    NARCIS (Netherlands)

    Meeuwissen, M.; Fioreze, T.; Thomas, T.; Pickerden, C.; Hof, T.

    2015-01-01

    This deliverable describes the general plan regarding all dissemination activities of the consortium partners and work packages during the project. This links directly to D7.4 where the realization of different dissemination activities will be reported.

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

    Science.gov (United States)

    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.

  11. Check-up Measurement (update). Deliverable D5.22

    NARCIS (Netherlands)

    Holtzer, A.C.G.; Giessen, A.M.D. van der; Djurica, M.

    2015-01-01

    This deliverable D5.22 presents the GEN6 check-up measurement. It describes the most prominent outcomes of the GEN6 project up to this point in time. The check-up measurement helps to focus the monitoring towards the most relevant achievements of the project, such that an efficient and well-targeted

  12. Seasonal Changes in Leaf Tissue Rehydration of One Annual and Two Perennial Grass Forage Species Induced by Bioclimate

    Directory of Open Access Journals (Sweden)

    Eirini - Ia KAPSALI

    2015-12-01

    Full Text Available Bioclimate signifies the continuous interplay between plants and climate factors (primarily drought and has a direct impact on the water relations and the duration of the rehydration process in water stressed plants. To explore the association between bioclimate and water physiology of forage species in semi-arid Mediterranean grasslands, we determined the seasonal variation in leaf water potential, turgid weight and relative water content in wild growing Dactylis glomerata L., Bromus inermis Leyss (perennial and Bromus sterilis L. (annual during the growing season. The study was conducted at the farm of the Aristotle University of Thessaloniki. The results of the current study reveal that B. sterilis maintained high levels of water potential most probably by accelerating its biological cycle and decreasing water content because it fails to sustain turgidity. Dactylis glomerata and B. inermis presented even higher water contents than B. sterilis for the same water potential. Dactylis glomerata exhibited substantially higher water potential and content than B. inermis by keeping the rehydration duration stable. The extensive creeping rhizome seems to allow B. inermis to sustain high values of water potential and content possibly ensuring turgidity. Regardless of the grass species the duration of rehydration ranged from 2.5 to 3.5 hours throughout the growing season. Our findings demonstrate that (a D. glomerata and B. inermis are better adapted to Mediterranean semiarid conditions than B. sterilis and (b turgid weight in Mediterranean forage species can safely be determined after a rehydration period of 3.5 hours.

  13. Women who win with words: Deliverance via persuasive communication

    Directory of Open Access Journals (Sweden)

    R.G. Branch

    2003-08-01

    Full Text Available The Wise Woman of Abel Beth Maacah quells a rebellion (2 Sam. 20. Abigail, a beautiful and intelligent woman, rescues her household (1 Sam. 25. And the older sister of Moses, by tradition Miriam, saves her baby brother’s life (Ex. 2. These two women and a girl represent political saviours who facilitate the deliverance of a city, community, and an individual via persuasive words. As winners with words, these orators contribute dynamically to the biblical text by providing an alternative way of deliverance, one enabling it to come through a means other than the sword. Via perceptive persuasion, they guide those with whom they interact toward choosing life and the common good. This article takes a cross-disciplinary approach to the biblical text by looking at the persuasive communication techniques these two women and a girl employ so successfully.

  14. Skill Gap Analysis for Improved Skills and Quality Deliverables

    Directory of Open Access Journals (Sweden)

    Mallikarjun Koripadu

    2014-10-01

    Full Text Available With a growing pressure in identifying the skilled resources in Clinical Data Management (CDM world of clinical research organizations, to provide the quality deliverables most of the CDM organizations are planning to improve the skills within the organization. In changing CDM landscape the ability to build, manage and leverage the skills of clinical data managers is very critical and important. Within CDM to proactively identify, analyze and address skill gaps for all the roles involved. In addition to domain skills, the evolving role of a clinical data manager demands diverse skill sets such as project management, six sigma, analytical, decision making, communication etc. This article proposes a methodology of skill gap analysis (SGA management as one of the potential solutions to the big skill challenge that CDM is gearing up for bridging the gap of skills. This would in turn strength the CDM capability, scalability, consistency across geographies along with improved productivity and quality of deliverables

  15. Summary of ST-MA deliverables for LHC

    CERN Document Server

    Cennini, E; Ninin, P; Nunes, R; Scibile, L; CERN. Geneva. ST Division

    2003-01-01

    The ST/MA group is responsible for the monitoring of the CERN Technical Infrastructure as well as the design, installation and maintenance of personnel protection system such as access control system, fire and gas leak detection, safety alarm monitoring systems and radiation monitoring systems (in collaboration with TIS). This paper provides an overview of the main projects and services managed in the group and outlines the scope, the organisation and the planning of the main deliverables for LHC.

  16. Gas Deliverability Model with Different Vertical Wells Properties

    Directory of Open Access Journals (Sweden)

    L. Mucharam

    2003-11-01

    Full Text Available We present here a gas deliverability computational model for single reservoir with multi wells. The questions of how long the gas delivery can be sustained and how to estimate the plateau time are discussed here. In order to answer such a question, in this case, a coupling method which consists of material balance method and gas flow equation method is developed by assuming no water influx in the reservoir. Given the rate and the minimum pressure of gas at the processing plant, the gas pressure at the wellhead and at the bottom hole can be obtained. From here, the estimation of the gas deliverability can be done. In this paper we obtain a computational method which gives direct computation for pressure drop from the processing plant to the wells, taking into account different well behavior. Here AOF technique is used for obtaining gas rate in each well. Further Tian & Adewumi correlation is applied for pressure drop model along vertical and horizontal pipes and Runge-Kutta method is chosen to compute the well head and bottom hole pressures in each well which then being used to estimate the plateau times. We obtain here direct computational scheme of gas deliverability from reservoir to processing plant for single reservoir with multi-wells properties. Computational results give different profiles (i.e. gas rate, plateau and production time, etc for each well. Further by selecting proper flow rate reduction, the flow distribution after plateau time to sustain the delivery is computed for each well.

  17. Índices bioclimáticos para a cultura de café Bioclimatic indices for the coffee crop

    Directory of Open Access Journals (Sweden)

    Hudson de P. Carvalho

    2011-06-01

    Full Text Available Além dos graus-dia, vários são os sistemas de unidades bioclimáticas, embora sua utilização e limitação ainda sejam pouco conhecidas na cafeicultura. Diante disto, este trabalho objetivou avaliar o desempenho de quatro índices bioclimáticos para estimativa da duração dos subperíodos florescimento-fruto verde cana, fruto verde cana -fruto cereja e florescimento-fruto cereja, na cultura de café. Durante o ano agrícola 2008/2009 foram avaliados índice térmico, acúmulo da radiação fotossinteticamente ativa, índice heliotérmico de Geslin e acúmulo da evapotranspiração de referência, em dez cultivares de café plantadas em Uberlândia, MG. Os dados obtidos para cada índice bioclimático foram analisados através de estatística clássica, obtendo-se a média, o desvio padrão e o coeficiente de variação, em que este último parâmetro serviu de base para a escolha do índice bioclimático utilizado na quantificação da duração dos subperíodos de cada cultivar de café e na classificação do ciclo em precoce, médio e tardio. Verificou-se que os índices heliotérmico de Geslin e acúmulo da evapotranspiração de referência, apresentaram os menores coeficientes de variação médios entre as cultivares.Besides degree-days, which considers air temperature, there are several bioclimatic unit systems. However, their use and limitation is little known for coffee crop. Therefore, this study evaluated the performance of four bioclimatic indices to estimate the length of the sub-periods flowering-light green fruit, light green fruit-cherry fruit and flowering-cherry fruit, in coffee crop. The thermal index, accumulation of photosynthetic active radiation, Geslin's heliothermic index and the accumulation of the reference evapotranspiration were evaluated during the agricultural year 2008/2009 for ten coffee cultivars, in Uberlândia-MG, Brazil. The data for each bioclimatic index were analyzed with the classical statistics

  18. Topological strings in d < 1

    Science.gov (United States)

    Dijkgraaf, Robbert; Verlinde, Herman; Verlinde, Erik

    1991-03-01

    We calculate correlation functions in minimal topological field theories. These twisted versions of N = 2 minimal models have recently been proposed to describe d < 1 matrix models, once coupled to topological gravity. In our calculation we make use of the Landau-Ginzburg formulation of the N = 2 models, and we find a direct relation between the Landau-Ginzburg superpotential and the KdV differential operator. Using this correspondence we show that the minimal topological models are in perfect agreement with the matrix models as solved in terms of the KdV hierarchy. This proves the equivalence at tree-level of topological and ordinary string thoery in d < 1.

  19. Deliverable D2.1 - State of the Art in Tools for Creativity

    DEFF Research Database (Denmark)

    Grube, Per-Pascal; Schmid, Klaus; Dolog, Peter;

    2008-01-01

    This deliverable provides a survey of creativity techniques that have been developed over time. It provides a reference model for characterizing them as a basis for selecting techniques that are particularly appropriate for the idSpace-project. The deliverable also surveys existing creativity tools...... and characterizes them in terms of underlying techniques. Finally, the deliverable describes requirements for the idSpace-environment and discusses to what extend it can benefit from existing tools....

  20. Deliverable D3 - Low- and Medium-beta linac

    CERN Document Server

    A. Facco, A. Balabin, R. Paparella, D. Zenere, INFN-Laboratori Nazionali di Legnaro, Padova, Italy; D. Berkovits, J. Rodnizki, SOREQ, Yavne, Israel; J. L. Biarrotte, S. Bousson, A. Ponton, G. Olry, IPN Orsay, France; R. Duperrier, D. Uriot, CEA/Saclay, France; V. Zvyagintsev, TRIUMF, Vancouver, Canada.

    The present document describes the Low- and Medium-beta section of the EURISOL DS Driver Accelerator. This section consists of a superconducting linac, based on Half-Wave (HWR) and SPOKE type resonators, preceded by a short, normal-conducting MEBT (Medium Energy Beam Transport) section that performs input beam matching. The scope of this linac is to bring the beams of H-, D+ and 3He++ produced by the Ion Injector (Deliverable D-5) to the energy and beam parameters required for injection in the superconducting High-beta linac (Deliverable D4-High beta linac). The present beam dynamics design reaches the goal of accelerating the required high current beams to the design energy (about 100 MeV/A, depending on the ion species), with minimum emittance growth and with low losses, using realistic and cost-effective, although innovative, technological solutions. The Low- and Medium-beta linac layout is described, together with the fundamental parameters and characteristics of its components and the system performanc...

  1. Deliverable D3 - Low- and Medium-beta linac

    CERN Document Server

    A. Facco, A. Balabin, R. Paparella, D. Zenere, INFN-Laboratori Nazionali di Legnaro, Padova, Italy; D. Berkovits, J. Rodnizki, SOREQ, Yavne, Israel; J. L. Biarrotte, S. Bousson, A. Ponton, G. Olry, IPN Orsay, France; R. Duperrier, D. Uriot, CEA/Saclay, France; V. Zvyagintsev, TRIUMF, Vancouver, Canada.

    The present document describes the Low- and Medium-beta section of the EURISOL DS Driver Accelerator. This section consists of a superconducting linac, based on Half-Wave (HWR) and SPOKE type resonators, preceded by a short, normal-conducting MEBT (Medium Energy Beam Transport) section that performs input beam matching. The scope of this linac is to bring the beams of H-, D+ and 3He++ produced by the Ion Injector (Deliverable D-5) to the energy and beam parameters required for injection in the superconducting High-beta linac (Deliverable D4-High beta linac). The present beam dynamics design reaches the goal of accelerating the required high current beams to the design energy (about 100 MeV/A, depending on the ion species), with minimum emittance growth and with low losses, using realistic and cost-effective, although innovative, technological solutions. The Low- and Medium-beta linac layout is described, together with the fundamental parameters and characteristics of its components and the system performance.

  2. Topological strings in d < 1

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, R.; Verlinde, H. (Princeton Univ., NJ (USA). Joseph Henry Labs.); Verlinde, E. (California Univ., Santa Barbara (USA). Inst. for Theoretical Physics)

    1991-03-18

    We calculate correlation functions in minimal topological field theories. These twisted versions of N = 2 minimal models have recently been proposed to describe d < 1 matrix models, once coupled to topological gravity. In our calculation we make use of the Landau-Ginzburg formulation of the N = 2 models, and we find a direct relation between the Landau-Ginzburg superpotential and the KdV differential operator. Using this correspondence we show that the minimal topological models are in perfect agreement with the matrix models as solved in terms of the KdV hierarchy. This proves the equivalence at tree-level of topological and ordinary string theory in d < 1. (orig.).

  3. Cerramientos bioclimáticos para climas cálidos húmedos: la cuarta vivienda

    Directory of Open Access Journals (Sweden)

    Mustieles, F.

    1998-02-01

    Full Text Available In intertropical latitudes such as Venezuela with hot humid climates, building envelopes must reduce influence of solar radiation, and in these, roofs and windows must receive special attention. Venezuela is also the country with the highest energy consumption per capita in Iberoamérica, much of which is generated by air conditioning systems in residential buildings, and Maracaibo and the surrounding lake basin have some of the highest temperature and humidity values in Venezuela, which increase energy consumption even more. A bioclimatical house for this climate is proposed. This building incorporates principles from traditional indigenous, colonial and oil company houses in the Maracaibo lake basin to generate a new prototype, called the Fourth House.

    En climas cálidos húmedos como es el caso de grandes regiones de Venezuela, las envolventes deben reducir la influencia de la radiación solar y, por lo tanto, deben recibir atención especial. Venezuela es también el país con más alto consumo energético per capita en Iberoamérica, generado en su mayor parte por el uso de sistemas de aire acondicionado en las edificaciones residenciales. En Maracaibo y en los alrededores del Lago de Maracaibo se registran los valores más altos de temperatura y humedad en Venezuela, lo que incrementa, aún más, el consumo energético de las viviendas de estas regiones. La minimización del impacto de la radiación solar para lograr la reducción del consumo energético con un mayor bienestar térmico ha sido precisamente uno de los objetivos perseguidos con el desarrollo de una nueva vivienda bioclimática para la región del lago de Maracaibo. Esta incorpora principios de las tres viviendas bioclimáticas previas existentes en esa región: el palafito o vivienda tradicional indígena, la vivienda colonial republicana y la vivienda petrolera. Es por ello que esta vivienda ha sido llamada la Cuarta Vivienda.

  4. Geodesics in (Rn, d1

    Directory of Open Access Journals (Sweden)

    Mehmet KILIÇ

    2016-09-01

    Full Text Available The notion of geodesic, which may be regarded as an extension of the line segment in Euclidean geometry to the space we study in, has an important place in many branches of geometry, such as Riemannian geometry, Metric geometry, to name but a few. In this article, the concept of geodesic in a metric space will be introduced, then geodesics in the space (Rn, d1 will be characterized. Furthermore, some examples will be presented to demonstrate the effectiveness of the main result.

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

    Science.gov (United States)

    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.

  6. Deliverability on the interstate natural gas pipeline system

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  7. Possibilities for a valorisation of geomorphologic research deliverables

    Science.gov (United States)

    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

  8. Manual de desenho bioclimático urbano. Manual de orientações para a elaboração de normas urbanísticas

    OpenAIRE

    Hernández Aja, Agustín; Fariña Tojo, José; Gálvez Huerta, Miguel Ángel; Fernández Áñez, Victoria; Gonçalves, Artur; Ribeiro, A. C.; Feliciano, Manuel

    2013-01-01

    O presente documento é o resultado de uma colaboração técnica em matéria de análise e desenho bioclimático dos espaços libres, realizada para o Instituto Politécnico de Bragança, dentro do Projeto BIOURB, no contexto do Programa de Cooperação Transfronteiriço Espanha – Portugal, desenvolvido como o apoio do Fundo Europeu de Desenvolvimento Regional (FEDER) e do Programa de Cooperação Portugal – Espanha (POCTEP). O trabalho foi desenvolvido entre 2012 e 2013 por investigadores do grupo GIAU+S ...

  9. Arquitectura vernácula de la Sierra de Gredos y el valle del Alto Tormes (Ávila): análisis tipológico, fundamentos constructivos y funcionamiento bioclimático

    OpenAIRE

    Gil Crespo, Ignacio Javier

    2011-01-01

    El presente estudio analiza la arquitectura vernácula del valle del Alto Tormes en la Sierra de Gredos abulense en sus aspectos tipológicos —a escala territorial y a escala arquitectónica—, sus fundamentos constructivos —por los que se estudian los materiales, elementos y sistemas constructivos— y su funcionamiento bioclimático. Este último punto de vista supone una perspectiva inédita en el estudio de esta arquitectura. Se estudia mediante métodos de análisis bioclimático y se describen los ...

  10. Virtual Enterprise Reference Architecture and Methodology (VERAM), Joint D41/D43 deliverable of GLOBEMEN

    DEFF Research Database (Denmark)

    Tølle, Martin; Zwegers, Arian; Vesterager, Johan

    2003-01-01

    . The emphasis in this deliverable is to define an architectural framework, which will be a body of knowledge that supports future practical work in the area of global engineering and manufacturing in enterprise networks, supported by methodologies/guidelines. This document is organised as follows: - A first......This document, D412/D43 Virtual Enterprise Reference Architecture and Methodology (VERAM), is a result of the merging of the two main deliverables of work package 4 of the IMS GLOBEMEN project: D41 Reference Architecture (deliverable D412 for the European GLOBEMEN project) and D43 VME Guidelines....... IMS Globemen is an inter-regional project aiming to develop methods, tools and architectures to support inter-enterprise operations in one-of-kind industries, in different lifecycle phases. This deliverable describes an architectural framework VERAM including a description/elaboration of its elements...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Main: D1GMAUX28 [PLACE

    Lifescience Database Archive (English)

    Full Text Available D1GMAUX28 S000328 20-Feb-2002 (last modified) uchi D1; DNase I protected sequence f...ound in the soybean (G.m.) auxin responsive gene, Aux28, promoter; D1 and D4 share a very similar core seque...nce TAGTXXCTGT and TAGTXCTGT, respectively; D1/D4-like sequence were identified in several other auxin-respo...tors; GmGT-2 are down-regulated by light in a phytochrome-dependent manner; See 000331; Auxin; Aux28; GT-2; phytochrome; D1; hypocotyl; soybean (Glycine max) ACAGTTACTA ...

  14. Understanding the Physiography, Bioclimate and Mapping of the Vegetation of the Chalakkudy River Basin, Anamalai part of Southern Western Ghats, India

    Directory of Open Access Journals (Sweden)

    Amitha Bachan Kandarumadathil Hyder

    2014-09-01

    Full Text Available Vegetation of an area is determined by the overall interaction of the climatic, edaphic, and biotic factors. It is important to define the bioclimate of a region to understand the Vegetation dynamics of a region especially of the Tropical Monsoonal continents with complex physiography. It is a pioneering effort to understand bioclimate and primary   vegetation of a river basin from the southern Western Ghats region. Twenty years of rainfall data were analysed and geophysical features of the Chalakkudy River basin were analysed using GIS facility. The results provide more accurate data of the length, area and other physiographic features for the Chalakkudy River basin indicating need of updating of data of other river basins of Kerala. The bioclimatic data analyzed from 20 years of rainfall and vegetation maps indicate presence of dry-moist-forest zones to ever wet-rainforest regimes in the basin. The vegetation data shows 80% catchements of the river under forest category of which primary forests dominates with 519 Km2 (36% followed by forest plantations 179.6 Km2 (12%, secondary forests 197.4 Km2 (17%, tea, coffee and other plantations constitute 198.3 Km2 (13%, degraded non forest vegetation 86.9 Km2 (6% and reservoir, streams and rivers 46.5 Km2 (3%.  Of the 361 Km2 primary wet-evergreen (Rainforests forests 294 Km2 is dense forest and 67 Km2 is degraded forests.

  15. Cyclin D1 expression in prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tucci, S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Muglia, V.F. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Medicina Interna (Centro de Ciência da Imagem), Ribeirão Preto, SP, Brasil, Departamento de Medicina Interna (Centro de Ciência da Imagem), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Reis, R.B. Dos [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, G.E.B. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

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

    Science.gov (United States)

    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

  17. The establishment of a new deliverability equation considering threshold pressure gradient

    Institute of Scientific and Technical Information of China (English)

    Li Lezhong; Li Xiangfang; He Dongbo; Xu Hanbing

    2009-01-01

    The flowing mechanism of a low permeability gas reservoir is different from a conventional gas reservoir, espe-cially for that with higher irreducible water saturation the threshold pressure gradient exists. At present, in all the deliverability equation, the additional pressure drop caused by the threshold pressure gradient is viewed as constant, but this method has big error in the practical application. Based on the non-Darcy steady flow equation, the limited integral of the additional pressure drop is solved in this paper and it is realized that the additional pressure drop is not a constant but has something to do with production data, and a new deliverability equation is derived, with the relevant processing method for modified isochronal test data. The new deliverability equation turns out to be practical through onsite applica-tion.

  18. Aporte del diseño bioclimático a la sustentabilidad de áreas urbanas en zonas áridas

    Directory of Open Access Journals (Sweden)

    Mario Cunsulo

    2003-01-01

    Full Text Available Partiendo de la certeza ineludible de que toda estrategia tendiente a la sustentabilidad de los asentamientos humanos requiere indefectiblemente programas sistemáticos de sustitución energética, la aplicación masiva de la oferta climática en la construcción del hábitat regional es un componente esencial en dicha sustitución de recursos energéticos renovables. En ese contexto, el trabajo presenta algunas recomendaciones de diseño urbano bioclimático, producto de investigaciones realizadas por el Area Arquitectura Ambiental de la Facultad de Arquitectura y Diseño sobre la ciudad de San Juan (Argentina, localizada en la Franja Arida de América del Sur.

  19. Bioconstrucción y arquitectura bioclimática para la ejecución de vivienda ecológica unifamiliar.

    OpenAIRE

    SÁEZ PÉREZ, JOSÉ VICENTE

    2015-01-01

    [ES] El trabajo final de grado a desarrollar pertenece a la modalidad de desarrollo de proyectos técnicos de construcción, en el área de construcción y medio ambiente y trata sobre el levantamiento de una vivienda ecológica unifamiliar, teniendo en cuenta los criterios de Bioconstrucción y arquitectura bioclimática situada en la población de Ayora. Con ello, se persigue la integración de una vivienda a la que la sociedad no está acostumbra, la cual tendrá un comportamiento más óptimo que una ...

  20. Capabilities and costs for ancillary services provision by wind power plants. Deliverable D 3.1

    DEFF Research Database (Denmark)

    Faiella, Mariano; Hennig, Tobias; Cutululis, Nicolaos Antonio;

    This report is the deliverable of the third work package of the REserviceS project and describes the technical options and related costs for the provision of ancillary services specifically from wind energy technologies. It is focused on the set of ancillary services defined in the previous work...... package 2, shown in table 1 below. The information from this deliverable will be used as input to the case studies in subsequent work packages, which are expected to provide additional insights to the actual provision of ancillary services in transmission and distribution networks....

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

    OpenAIRE

    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 me...

  2. Data needs and computational requirements for ST decision making. Internal deliverable ID6.2.1

    DEFF Research Database (Denmark)

    Clement, Rémy; Tournebise, Pascal; Perkin, Samuel

    The objective of this deliverable is to present the requirements for adapting available tools/models and identifying data needs for probabilistic reliability analysis and optimal decision-making in the short-term decision making process. It will serve as a basis for the next tasks of GARPUR work ...

  3. Monitoring framework and description of indicators. Deliverable D5.1

    NARCIS (Netherlands)

    Holtzer, A.C.G.; Giessen, A.M. van der; Munck, S.G.E. de; Poel, M.A.; Smets, R.C.J.

    2012-01-01

    This deliverable describes the monitoring framework that will be used to monitor and evaluate the GEN6 project and its nine pilots. The main topics are IPv6 uptake and governance, as described by the EC. Monitoring and evaluation will be done during the course of the project. This report describes t

  4. Discrepancies between selected Pareto optimal plans and final deliverable plans in radiotherapy multi-criteria optimization.

    Science.gov (United States)

    Kyroudi, Archonteia; Petersson, Kristoffer; Ghandour, Sarah; Pachoud, Marc; Matzinger, Oscar; Ozsahin, Mahmut; Bourhis, Jean; Bochud, François; Moeckli, Raphaël

    2016-08-01

    Multi-criteria optimization provides decision makers with a range of clinical choices through Pareto plans that can be explored during real time navigation and then converted into deliverable plans. Our study shows that dosimetric differences can arise between the two steps, which could compromise the clinical choices made during navigation.

  5. Campaigns and Awareness Raising Strategies in Traffic Safety (CAST). Deliverable 0.5: Quality assurance report.

    NARCIS (Netherlands)

    Twisk, D. & Hoekstra, T.

    2010-01-01

    This deliverable describes the quality assurance process and its results. More specifically, the individual requirements and outcomes of the quality assurance process are reported. Furthermore, the implementation of the guidelines that were drawn up in advance are discussed. (Author/publisher)

  6. D1.1 Stakeholders Needs Regarding EA

    DEFF Research Database (Denmark)

    Ryberg, Thomas; Eleftheriou, Paraskevi; Maglavera, Stavroula

    2009-01-01

    The objective of this deliverable is to identify and document the competences (skills and knowledge) that employees of both private and public sector organisations need to acquire in order to be capable of developing an EA as well as the competences that university students need to acquire...... in a university course about EA. This deliverable commences with a detailed description of the methodology followed for the identification of stakeholders needs regarding Enterprise Architecture (EA) training and education. It then presents the results of the methodology application in terms of EA related...

  7. D=1 supergravity and spinning particles

    Energy Technology Data Exchange (ETDEWEB)

    Holten, J.W. van

    1995-10-06

    In this paper I review the multiplet calculus of N-1, D=1 local supersymmetry with applications to the construction of models for spinning particles in background fields, and models with space-time supersymmetry. New features include a non-linear realization of the local supersymmetry algebra and the coupling to anti-symmetric tensor fields of both odd and even rank. The non-linear realization allows the construction of a D=1 cosmological-constant term, which provides a mass term in the equations of motion. (orig.).

  8. 42 CFR 52d.1 - Applicability.

    Science.gov (United States)

    2010-10-01

    ... CANCER EDUCATION PROGRAM § 52d.1 Applicability. The regulations in this part apply to grants under the Clinical Cancer Education Program authorized by section 404(a)(4) of the Public Health Service Act, to... neoplastic disease and the preventive measures and diagnostic and therapeutic skills necessary to...

  9. A qualitative investigation into the so-called ministry of deliverance

    Directory of Open Access Journals (Sweden)

    J. Janse van Rensburg

    2010-07-01

    Full Text Available Since the publication of the book“The occult debate” (Janse van Rensburg, 1999 it has become clear that epistemological views on occultism within the reformed tradition have drastically diverged. During the General Synod of the Dutch Reformed Church in 2007, the report of the Algemene Taakspan vir Leer en Aktuele Sake (ATLASon a ministry of deliverance denied the existence of the devil and claimed that it would be un-scientific to embark on an empirical research in this regard, because of the impossibility to verify information gathered in this manner. However, it is the hypothesis of this article that qualitative information could assist in attaining a clearer under-standing of the need for a ministry of deliverance. In this article the methodology of the qualitative research is explained and the narratives of participants are revealed. Thereafter the respon-ses of the participants are evaluated.

  10. Guidelines for Inter-Enterprise Management (IEM), GLOBEMEN Deliverable D23

    DEFF Research Database (Denmark)

    Tølle, Martin; Vesterager, Johan

    2002-01-01

    to the Virtual Enterprise concept of GLOBEMEN as well as introducing different types of partnership and information needs related to each of these. - Chapter 4 gives a description of a Vision and Business Environment for OKP This section starts with a description of the holistic vision of how an OKP enterprise......This document is a deliverable of Work package 2 of the IMS Globemen (GMN) project: D23 Guidelines for Inter-Enterprise Management (IEM). IMS Globemen is an inter-regional project aiming to develop methods, tools and architectures to support inter-enterprise operations in one-of-kind industries...... (Specification). Correspondingly, this report operates as input for further generalisation over the lifecycle in D43: Guidelines for Virtual Manufacturing Enterprise. The main objective of the deliverable is to describe guidelines how companies may operate in an inter-enterprise environment supported by C-Project...

  11. Ensuring on-time quality data management deliverables from global clinical data management teams

    Directory of Open Access Journals (Sweden)

    Zia Haque

    2010-01-01

    Full Text Available The growing emphasis on off-site and off-shore clinical data management activities mandates a paramount need for adequate solutions geared toward on-time, quality deliverables. The author has been leading large teams that have been involved in successful global clinical data management endeavors. While each study scenario is unique and has to be approached as such, there are several elements in defining strategy and team structure in global clinical data management that can be applied universally. In this article, key roles, practices, and high-level procedures are laid out as a road map to ensure success with the model.

  12. Deliverable 3.3.2 Specification of tests and test groups

    DEFF Research Database (Denmark)

    Peterson, Carrie Beth; Mitseva, Anelia; Harpur, Jill

    2009-01-01

    for them. This will be done via integrating intelligent scalable ICT services which will be tested for a period of 12 months under realistic conditions. Offering the services could not be complete without evaluating quality of life improvement, user acceptance and user satisfaction with a representative......Deliverable 3.3.2: Specification of tests and test groups One of the main goals of the ISISEMD project is to offer innovative ICT services to improve the quality of life of elderly persons with cognitive problems or mild dementia and their informal and formal caregivers who provide every day care...

  13. D1.3 -- Short Report on the First Draft Multi-link Channel Model

    DEFF Research Database (Denmark)

    Pedersen, Troels; Raulefs, Ronald; Steinboeck, Gerhard;

    This deliverable is a preliminary report on the activities towards multi-link channel models. It summarizes the activities and achievements of investigations of WP1 Task 1.2 in the first year of the project. In this deliverable work focuses on the characterization of the crosscorrelation of multi...

  14. D1.4 -- Short Report on Models That Incorporate Non-stationary Time Variant Effects

    DEFF Research Database (Denmark)

    Lostanlen, Yves; Pedersen, Troels; Steinboeck, Gerhard;

    This deliverable summarizes the activities and achievements of investigations of WP1 Task 1.2 in the first year of the project. In the deliverable the research focus is on the nonstationary time variant effects of the radio channel. Estimation results of time variant multipath parameters of outdo...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. La ordenanza bioclimática de Tres Cantos, Madrid. Últimos avances en planificación ambiental y sostenible./ The ordinance bioclimatic Tres Cantos, Madrid. Recent developments in environmental planning and sustainable.

    Directory of Open Access Journals (Sweden)

    Higueras García, Ester

    2009-06-01

    Full Text Available Aunque es de todos reconocida la importancia de planificar con criterios ambientales, son muy pocos los casos en los que estos criterios pasan de los objetivos a las propuestas. En el caso de la localidad de Tres Cantos (Madrid se ha obtenido un importante reto: la aprobación de una ordenanza, denominada Ordenanza Bioclimática, que impulsa el desarrollo urbano equilibrado con su territorio, reduce los consumos de suelo y agua, es respetuosa con el paisaje e incentiva la edificación bioclimática frente a otras convencionales./Despite the well-known relevancy of environmental criteria relating to urban planning, they often remain as objectives and do not become proposals. In the case of Tres Cantos, an important challenge has been proposed: the approval of an ordinance, called Bioclimatic Ordinance, that promotes a proportional urban development relating to the territory, that reduces the use of ground and water, that is respectful towards the landscape and encourages bioclimatic construction against the traditional one.

  17. Incidencia del clima local en los procesos de planificación territorial: Análisis bioclimático de la Costa del Sol Occidental de Málaga (España

    Directory of Open Access Journals (Sweden)

    José Luis Pérez

    2015-01-01

    Full Text Available Frente al excesivo consumo energético en el acondicionamiento térmico residencial, este estudio investiga la implicancia del clima local en las estrategias de expansión urbana, así como su grado de afección a las condiciones de confort, en el contexto mediterráneo español de la Costa del Sol Occidental. Para ello se realiza un análisis bioclimático territorial, identificando los diversos climas locales existentes y las diferentes respuestas biológicas asociadas a cada uno de ellos. Con estos resultados se elabora una clasificación del lugar desde la óptica de la idoneidad bioclimática. Esta herramienta ha permitido evaluar los procesos de planificación territorial, concluyéndose que el 80,6% del suelo urbano y urbanizable no se beneficia de las condiciones climáticas más favorables, las cuales constituyen el 47,3% del territorio analizado. Esta información, puesta al servicio de mejorar las condiciones térmicas de las ciudades, puede ser útil en el diseño y distribución de futuras áreas urbanas.

  18. Landsat maps (phase V, deliverable 60), ASTER maps (phase V, deliverable 62), ASTER_DEM maps (phase V, deliverable 63), and spectral remote sensing in support of PRISM-II mineral resource assessment project, Islamic Republic of Mauritania (phase V, deliverables 61 and 64): Chapter E in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

    Science.gov (United States)

    Rockwell, Barnaby W.; Knepper, Daniel H.; Horton, John D.

    2015-01-01

    Multispectral satellite data acquired by the Landsat 5 Thematic Mapper (TM), Landsat 7 Enhanced Thematic Mapper Plus (ETM+), and Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensors were processed and interpreted in support of the PRISM-II project (Second Projet de Renforcement Institutionnel du Secteur Minier de la Republique Islamique de Mauritanie). This report and accompanying maps constitute project deliverables 60–64. All digital data for use in Geographic Information System (GIS) and image processing software will be included in the GIS deliverable 92. Image maps in PDF format of the processed Landsat and ASTER scenes are referenced in the appendixes.

  19. Medial prefrontal D1 dopamine neurons control food intake.

    Science.gov (United States)

    Land, Benjamin B; Narayanan, Nandakumar S; Liu, Rong-Jian; Gianessi, Carol A; Brayton, Catherine E; Grimaldi, David M; Sarhan, Maysa; Guarnieri, Douglas J; Deisseroth, Karl; Aghajanian, George K; DiLeone, Ralph J

    2014-02-01

    Although the prefrontal cortex influences motivated behavior, its role in food intake remains unclear. Here, we demonstrate a role for D1-type dopamine receptor-expressing neurons in the medial prefrontal cortex (mPFC) in the regulation of feeding. Food intake increases activity in D1 neurons of the mPFC in mice, and optogenetic photostimulation of D1 neurons increases feeding. Conversely, inhibition of D1 neurons decreases intake. Stimulation-based mapping of prefrontal D1 neuron projections implicates the medial basolateral amygdala (mBLA) as a downstream target of these afferents. mBLA neurons activated by prefrontal D1 stimulation are CaMKII positive and closely juxtaposed to prefrontal D1 axon terminals. Finally, photostimulating these axons in the mBLA is sufficient to increase feeding, recapitulating the effects of mPFC D1 stimulation. These data describe a new circuit for top-down control of food intake.

  20. Implementation scenarios and further research priorities regarding forgiving and self-explaining roads. IN-SAFETY Workpackage 5: Implementation priorities and policy recommendations, Deliverable 5.3.

    NARCIS (Netherlands)

    Macharis, C. Verbeke, A. Brucker, K. de Gelová, E. Weinberger, J. & Vašek, J.

    2009-01-01

    In this deliverable a multi-actor multi-criteria analysis (MAMCA) is performed for the strategic evaluation of a number of innovative systems contributing to the creation of a more forgiving and self-explaining road environment. This deliverable also formulates a number of guidelines aimed at making

  1. Characteristics of stably expressed human dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor

    DEFF Research Database (Denmark)

    Pedersen, U B; Norby, B; Jensen, Anders A.

    1994-01-01

    Human dopamine D1a and D1b receptors were stably expressed in Baby Hamster Kidney (BHK) or Chinese Hamster Ovary (CHO) cells. [3H]SCH23390 saturation experiments indicated the presence of only a single binding site in the D1a expressing cell line with a Kd of 0.5 nM. In D1b expressing cell lines...... for these receptors. Besides SCH 23390, only NNC 112, fluphenazine and bulbocapnine were able to discriminate between the two states of the D1b receptor. In case of the D1a receptor, the Ki values obtained in binding experiments were very similar to Ki values obtained from inhibition of dopamine stimulated adenylyl...... cyclase. In the D1b expressing cell line, the Ki values obtained from inhibition of the dopamine stimulated adenylyl cyclase indicated a significantly better correlation with the state of the D1b receptor showing high affinity for antagonists. In agreement with observations from binding experiments...

  2. CO2-emission trading and green markets for renewable electricity. Wilmar - deliverable 4.1

    DEFF Research Database (Denmark)

    Azuma-Dicke, N.; Morthorst, Poul Erik; Ravn, H.F.

    2004-01-01

    This report is Deliverable 4.1 of the EU project “Wind Power Integration in Liberalised Electricity Markets” (WILMAR) and describes the application of two policy instruments, Tradable Emissions Permits (TEP’s) and Tradable Green Certificates (TGC’s) forelectricity produced from renewable energy...... generation may change the situation from earning money to losing money despite the increasing spot price. Heavy restrictions on emissions penalise thefossil-fuelled technologies significantly, and the associated increase in the spot price need not compensate for this. Therefore, a market of TEP’s is expected...... to have a significant influence on the electricity spot price. However, the expected pricelevel of TEP’s are met with great uncertainty and a study of a number of economical studies shows a price span between zero and 270 USD per ton of CO2 depending on the participation or non-participation of countries...

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

    Science.gov (United States)

    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…

  4. FUZZY COMPREHENSIVE EVALUATION OF GAS-WELL DELIVERABILITY%气井产能的模糊综合评价

    Institute of Scientific and Technical Information of China (English)

    蒋红梅

    2009-01-01

    Gas-well deliverability, as a dynamic performance parameter, is one of the important index for gas well evaluation.The prediction model for gas-well deliverability is established according to deliverability evaluation of logging data and comprehensive evaluation of fuzzy multiobjectives decision in fuzzy mathematics.Establishing Bayes discriminant function to the classified gas wells, making return judgement to them and verifying through cases can provide theory foundation for gas-well deliverability evaluation plan.%气井产能作为一个表示动态特征的参数,是气井评价的重要指标之一.依据测井数据进行产能评价,采用模糊数学中的模糊多目标决策综合评判建立了气井产能评价模型,通过对已分好类的气井建立贝叶斯判别函数,对其进行回判,并且通过实例进行验证,为气井产能评价方案提供了理论依据.

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

    Science.gov (United States)

    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.

  6. Analysis list: Nr1d1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Nr1d1 Adipocyte,Cardiovascular,Liver,Neural + mm9 http://dbarchive.biosciencedbc.jp.../kyushu-u/mm9/target/Nr1d1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d1.5.tsv http://db...archive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d1....Adipocyte.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d1.C...ardiovascular.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d1.Liver.tsv,http://dbarchive.biosc

  7. Quantized Faraday effect in 3D+1 and 2D+1 systems

    CERN Document Server

    Rodriguez, L Cruz; Rojas, H Perez; Querts, E Rodriguez

    2013-01-01

    We study Faraday rotation in the quantum relativistic limit. Starting from the photon self-energy in the presence of a constant magnetic field the rotation of the polarization vector of a plane electromagnetic wave which travel along the fermion-antifermion gas is studied. The connection between Faraday Effect and Quantum Hall Effect (QHE) is discussed. The Faraday Effect is also investigated for a massless relativistic 2D+1 fermion system which is derived by using the compactification along the dimension parallel to the magnetic field. Faraday angle shows a quantized behavior as Hall conductivity in two and three dimensions.

  8. Human bioclimate atlas for Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Morillon-Galvez, D. [Universidad Autonoma de Mexico, Coyoacan (Mexico). Inst. de Ingenieria; Saldana-Flores, R. [Gerencia de Energias no Convencionales, Inst. de Investigaciones Electricas, Temixco (Mexico); Tejeda-Martinez, A. [Universidad Veracruzana, Xalapa (Mexico). Centro de Ciencias de la Tierra

    2004-07-01

    This work presents bioclimatic charts for Mexico, as a result of an analysis of climate for the period 1951-1980. The basis to define the zone of thermal comfort was the equation proposed by Auliciems combined with the bioclimatic chart of Olgyay and the diagram of Givoni for bioclimatic control in buildings. Other tools used to carry out the diagnosis were the equations of Fanger. The results obtained were validated according to the parameters established by the American Society of Heating, Refrigerating and Air-Conditioning Engineering (ASHRAE), for the different climates of Mexico. The climatic data were those reported by 700 climatological stations throughout the country. The charts were developed using the ArcInfo program, in which the conditions of comfort, cool and warm were identified in order to achieve better thermal comfort in buildings and the profitable use of this renewable energy. (author)

  9. Materiales bioclimáticos

    OpenAIRE

    2010-01-01

    Es necesario impulsar materiales y procedimientos de construcción que garanticen la conservación del medioambiente y las mejores condiciones de habitabilidad en cada tipo de clima, además de que preserven la imagen tradicional de los poblados. Se presentan comparaciones entre los materiales tradicionales, semiindustriales y con alto grado de industrialización, así como las características térmicas de los mismos, lo que permitirá conocer sus potencialidades y limitaciones.

  10. Nucleic acid sequences encoding D1 and D1/D2 domains of human coxsackievirus and adenovirus receptor (CAR)

    Science.gov (United States)

    Freimuth, Paul I.

    2010-04-06

    The invention provides recombinant human CAR (coxsackievirus and adenovirus receptor) polypeptides which bind adenovirus. Specifically, polypeptides corresponding to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2 are provided. In another aspect, the invention provides nucleic acid sequences encoding these domains and expression vectors for producing the domains and bacterial cells containing such vectors. The invention also includes an isolated fusion protein comprised of the D1 polypeptide fused to a polypeptide which facilitates folding of D1 when expressed in bacteria. The functional D1 domain finds application in a therapeutic method for treating a patient infected with a CAR D1-binding virus, and also in a method for identifying an antiviral compound which interferes with viral attachment. The invention also provides a method for specifically targeting a cell for infection by a virus which binds to D1.

  11. Relación entre un índice de estabilidad estructural de suelo, la zona bioclimática y la posición fisiográfica en Venezuela

    Directory of Open Access Journals (Sweden)

    Luisa Fernández

    2016-01-01

    Full Text Available La degradación de los recursos naturales es uno de los problemas ambientales con mayor incidencia en los trópicos. Los suelos con mayor riesgo a la degradación física, limitando el desarrollo agrícola sostenido, corresponden a los de mayor inestabilidad estructural. Esto último es dependiente del contenido de materia orgánica, que está condicionado, a su vez, del tipo de cobertura o cultivo y de la práctica de manejo, especialmente de la fertilización orgánica. Por tanto, se hace necesario evaluar los índices existentes y relacionarlos con elementos del ambiente como las zonas bioclimáticas y la posición fisiográfica, como una herramienta útil en la planificación de uso y manejo de suelos y aguas. Entre los índices existentes está el «índice de estabilidad estructural», desarrollado por Pieri en 1995. La finalidad de la presente investigación fue establecer una relación entre las tres variables indicadas en quince unidades de suelos, distribuidos en todo el territorio nacional mediante la aplicación de un procedimiento estadístico. El estudio determinó una débil relación entre el mencionado índice de estabilidad estructural del suelo, la zona bioclimática y la posición fisiográfica donde se encuentran las unidades de suelo estudiadas.

  12. Waiting time distribution in M/D/1 queueing systems

    DEFF Research Database (Denmark)

    Iversen, Villy Bæk; Staalhagen, Lars

    1999-01-01

    The well-known formula for the waiting time distribution of M/D/1 queueing systems is numerically unsuitable when the load is close to 1.0 and/or the results for a large waiting time are required. An algorithm for any load and waiting time is presented, based on the state probabilities of M/D/1...

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

    Energy Technology Data Exchange (ETDEWEB)

    Appel, Gordon John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    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.

  14. Data needs and computational requirements for asset management decision making. Internal deliverable ID5.2.1

    DEFF Research Database (Denmark)

    Catrinu-Renstrom, Maria; Clement, Rémy; Tournebise, Pascal

    , and so that no important issue has been forgotten in the grey zones at the interfaces between the different time-frames (long-, mid- and short-term). Adhering to the title of the task, the various chapters in the deliverable discuss the exogenous factors, i.e., load forecasting, maintenance planning......, component failure rates, influence of renewable energy penetration and weather on mid-term planning. Accurate estimation of the variation of uncertainty behind exogenous and endogenous factors is crucial to support reliable calculations/estimations by proposed approaches for RMACs for asset management......The objective of this deliverable is to present the requirements for adapting available tools/models and identifying data needs for reliability analysis and optimal decision-making for asset management decision making process. It will serve as a basis for the next tasks of GARPUR work package 5...

  15. An editorial approach: Mike Nelson’s corridors and The Deliverance and The Patience

    Directory of Open Access Journals (Sweden)

    Helen Hughes

    2015-06-01

    Full Text Available This essay contrasts the contemporary British artist Mike Nelson’s approach to constructing his large, multi-room installations with his approach to editing the numerous artist books that he has produced since 2000. This comparison reveals several compositional symmetries between the two, namely pertaining to narrative non-linearity and meta-fictionality. The logic of montage is shown to similarly underscore both the books and the installations. This essay argues that the corridors connecting the different rooms of Nelson’s installations function in a similar way to the logic of montage: they play an integral role as the support that binds the structure of the installation (its multiple rooms together as a whole. This essay argues that the corridor is the primary viewing framework of the installation for the viewer, and that this vantage point is significant because the necessarily partial vision of the installation from the space of the corridor demonstrates the logic of installation art more broadly. I conclude by mapping the key compositional elements of Nelson’s artist books onto his installations, taking the 2001 work The Deliverance and The Patience as a case study, to show that the books do not exemplify the artwork as with traditional exhibition catalogues, but rather parallel it. That is, a structural continuity is established between these two facets of his work.

  16. Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

    Energy Technology Data Exchange (ETDEWEB)

    Popovic, Marta; Zaja, Roko [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia); Fent, Karl [University of Applied Sciences Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology (ETH Zürich), Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, CH-8092 Zürich (Switzerland); Smital, Tvrtko, E-mail: smital@irb.hr [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia)

    2014-10-01

    Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. - Highlights: • We optimized a novel assay for determination of Oatp1d1 interactors • Oatp1d1 is the first SLC characterized fish xenobiotic transporter • PFOS, nonylphenol, diclofenac, EE2, caffeine are high affinity Oatp1d1substrates • PFOA, chlorpyrifos

  17. The D$_1$ enigma and its physical origin

    CERN Document Server

    Stenflo, J O

    2016-01-01

    The D$_1$ enigma is an anomaly, which was first observed on the Sun as a symmetric polarization peak centered in the core of the sodium D$_1$ line that is expected to be intrinsically unpolarizable. To resolve this problem the underlying physics was later explored in the laboratory for D$_1$ scattering at potassium vapor. The experiment showed that the scattering phase matrix element $P_{21}$ is positive while $P_{22}$ is negative, although standard quantum scattering theory predicts that both should be zero. This experimental contradiction is currently the main manifestation of the D$_1$ enigma. Subsequent theoretical studies showed that such polarization effects may arise if scattering theory is extended to allow for interference effects due to level splittings of the ground state, in contrast to standard scattering theory, which only allows for interferences from level splittings of the intermediate state. Previous attempts to implement this idea had to rely on heuristic arguments to allow modeling of the ...

  18. The iTREN-2030 reference scenario until 2030. Deliverable D4

    Energy Technology Data Exchange (ETDEWEB)

    Fiorello, Davide; De Stasio, Claudia; Koehler, Jonathan; Kraft, Markus; Netwon, Sean; Purwanto, Joko; Schade, Burkhard; Schade, Wolfgang; Szimba, Eckhard

    2009-07-01

    The basic objective of iTREN-2030 is to extend the forecasting and assessment capabilities of the TRANS-TOOLS transport model to the new policy issues arising from the technology, environment and energy fields. This is achieved by couplin the TRANS-TOOLS model with three other models, ASTRA, POLES and TREMOVE covering these new policy issues. The TRANS-TOOLS transport network model has been developed to constitute the reference tool for supporting transport policy in the EU and currently is being developed in several European projects. The scenario set-up to be developed in iTREN-2030 has been modified, so that the projects develops a reference scenario and an integrated scenario. For the reference scenario, the three other modelling tools are harmonised with TRANS-TOOLS and made consistent with each other. This results in a coherent scenario for Europe until 2030 for technology, transport, energy, environment and economic development. The integrated scenario will consider the changing framework conditions until 2030, inparticular the policy pressure coming from climate policy and the increasing scarcity of fossil fuels as well as the impact of the financial and economic crisis. Within the iTREN-2030 project, the overall objective of Work Package 4 (WP4) producing tis deliverable is to develop the reference scenario for the quantitative projections using the four modelling tools involved in the project. The main aims of WP4 are to (a) define a consistent framework for using the different tools in an integrated way; (b) calibrate models with exchanged input to a coherent joint reference; (c) implement external input from WP3 and running models for projections; (d) produce output procedures and templates to facilitate assessment in WP5.

  19. Cenogramas, análisis bioclimático y muestreo en faunas de mamíferos: implicaciones para la aplicación de métodos de análisis paleoecológico

    Directory of Open Access Journals (Sweden)

    Hernández Fernández, M.

    2006-12-01

    Full Text Available In this work we analyzed the problems derived from the potential species loss associated to the taphonomic processes occurring in fossil sites. We seek to resolve the possible utility of cenograms and bioclimatic analysis as methodologies applicable in Paleoecology. Supposedly, if species are deleted in a community, significant changes in its structure might appear, which would make these paleoecological techniques dysfunctional. The analysis has been carried out with the data of two modern mammalian communities, Barrow (Alaska and Jaipur (India, on which we have deleted species randomly. Our results have allowed us to conclude that these methodologies are useful in Paleoecology, since they are functional with a satisfactory level of confidence, as long as the species loss is not excessively elevated (for communities with 20-40% of the original species.En este trabajo hemos analizado la problemática derivada de la posible pérdida de especies asociada a los procesos tafonómicos que se dan en los yacimientos de fósiles, para determinar la posible utilidad de los cenogramas y el análisis bioclimático como metodologías aplicables en Paleoecología. Podría suponerse que si eliminamos especies en una comunidad se podrían producir cambios significativos en su estructura que convertirían en no funcionales a estas metodologías. El análisis se ha llevado a cabo con los datos de dos comunidades de mamíferos actuales, Barrow (Alaska y Jaipur (India, de las que hemos eliminado progresivamente especies de forma aleatoria. Los resultados obtenidos nos han permitido concluir que tanto los cenogramas como el análisis bioclimático son útiles en Paleoecología, ya que son funcionales con un nivel de confianza adecuado, siempre y cuando la pérdida de especies no sea excesivamente elevada (en comunidades con un 20-40% de las especies originales.

  20. Dopamine D1 receptor involvement in latent inhibition and overshadowing.

    Science.gov (United States)

    Nelson, Andrew J D; Thur, Karen E; Cassaday, Helen J

    2012-11-01

    Latent inhibition (LI) manifests as poorer conditioning to a stimulus that has previously been experienced without consequence. There is good evidence of dopaminergic modulation of LI, as the effect is reliably disrupted by the indirect dopamine (DA) agonist amphetamine. The disruptive effects of amphetamine on LI are reversed by both typical and atypical antipsychotics, which on their own are able to facilitate LI. However, the contribution of different DA receptors to these effects is poorly understood. Amphetamine effects on another stimulus selection procedure, overshadowing, have been suggested to be D1-mediated. Thus, in the current experiments, we systematically investigated the role of D1 receptors in LI. First, we tested the ability of the full D1 agonist SKF 81297 to abolish LI and compared the effects of this drug on LI and overshadowing. Subsequently, we examined whether the D1 antagonist SCH 23390 can lead to the emergence of LI under conditions that do not produce the effect in normal animals (weak pre-exposure). Finally, we tested the ability of SCH 23390 to block amphetamine-induced disruption of LI. We found little evidence that direct stimulation of D1 receptors abolishes LI (although there was some attenuation of LI at 0.4 mg/kg SKF 81297). Similarly, SCH 23390 failed to enhance LI. However, SCH 23390 did block amphetamine-induced disruption of LI. These data indicate that, while LI may be unaffected by selective manipulation of activity at D1 receptors, the effects of amphetamine on LI are to some extent dependent on actions at D1 receptors.

  1. Supplement to ACUMEN deliverable 5.4a: Description and comparison of indicators in Google Scholar and Web of Science

    DEFF Research Database (Denmark)

    Wildgaard, Lorna Elizabeth; Larsen, Birger; Schneider, Jesper

    2014-01-01

    We collected publication and citation data in two databases to investigate the extent performance of author-level indicators are effected by choice of database, the stability of indicators across databases and ultimately to illustrate how differences in the computed indicators change our perception...... of individual researchers. In this report we begin by comparing database coverage, coverage at seniority and gender-level and then the performance of four basic indicators computed in both databases. In the main deliverable 5.4a, we investigate in a cluster analysis the performance of our previously identified...

  2. Design activities on helical DEMO reactor FFHR-d1

    Energy Technology Data Exchange (ETDEWEB)

    Sagara, A., E-mail: sagara.akio@LHD.nifs.ac.jp [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan); Goto, T.; Miyazawa, J.; Yanagi, N.; Tanaka, T.; Tamura, H.; Sakamoto, R.; Tanaka, M.; Tsumori, K. [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan); Mitarai, O. [Tokai University, 9-1-1 Toroku, Kumamoto 862-8652 (Japan); Imagawa, S.; Muroga, T. [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan)

    2012-08-15

    Highlights: Black-Right-Pointing-Pointer Conceptual design studies of the helical DEMO reactor FFHR-d1 have been conducted. Black-Right-Pointing-Pointer Design window analyses with core plasma and engineering designs have been carried out. Black-Right-Pointing-Pointer R and Ds on blanket, magnet, tritium control, fuelling and heating systems are discussed. - Abstract: Based on high-density and high-temperature plasma experiments in the large helical device (LHD), conceptual design studies of the LHD-type helical DEMO reactor FFHR-d1 have been conducted by integrating wide-ranged R and D activities on core plasmas and reactor technologies through cooperative researches under the fusion engineering research project, which has been launched newly in NIFS. Current activities for the FFHR-d1 in this project are presented on design window analyses with designs on core plasma, neutronics for liquid blankets, continuous helical magnets, pellet fueling, tritium systems and plasma heating devices.

  3. In adult female hamsters hypothyroidism stimulates D1 receptor-mediated breathing without altering D1 receptor expression.

    Science.gov (United States)

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

    2015-11-01

    Hypothyroidism affects cardiopulmonary regulation and function of dopaminergic receptors. Here we evaluated effects of 5 months of hypothyroidism on dopamine D1 receptor modulation of breathing in female hamsters using a D1 receptor antagonist SCH 23390. Euthyroid hamsters (EH) served as controls. Results indicated that hypothyroid female hamsters (HH) exhibited decreased body weights and minute ventilation (VE) following hypoxia due to decreased frequency of breathing (F). Moreover, SCH 23390 administration in HH increased VE by increasing tidal volume during exposure to air, hypoxia and following hypoxia. Relative to vehicle, SCH 23390 treatment decreased body temperature and hypoxic VE responsiveness in both groups. In EH, SCH 23390 decreased F in air, hypoxia and post hypoxia, and VE during hypoxia trended to decrease (P=0.053). Finally, expression of D1 receptor protein was not different between the two groups in any region evaluated. Thus, hypothyroidism in older female hamsters affected D1 receptor modulation of ventilation differently relative to euthyroid animals, but not expression of D1 receptors.

  4. 17 CFR 270.35d-1 - Investment company names.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Investment company names. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.35d-1 Investment company names. (a... words “United States” or “U.S. government.” (2) Names suggesting investment in certain investments...

  5. On the D1-D5 conformal field theory

    Science.gov (United States)

    Dijkgraaf, Robbert

    2000-03-01

    I give a review of some aspects of the D1-D5 conformal field theory that is dual to string theory on AdS 3 . Particular attention is paid to the gravitational interpretation of the elliptic genus as a sum over 3-manifolds.

  6. 26 CFR 31.3231(d)-1 - Service.

    Science.gov (United States)

    2010-04-01

    ... Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Railroad Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(d)-1 Service....

  7. Rescue of cyclin D1 deficiency by knockin cyclin E

    NARCIS (Netherlands)

    Geng, Y.; Whoriskey, W.; Park, M.Y.; Bronson, R.T.; Medema, R.H.; Li, T.; Weinberg, R.A.; Sicinski, P.

    1999-01-01

    D-type cyclins and cyclin E represent two very distinct classes of mammalian G1 cyclins. We have generated a mouse strain in which the coding sequences of the cyclin D1 gene (Ccnd1) have been deleted and replaced by those of human cyclin E (CCNE). In the tissues and cells of these mice, the expressi

  8. Underground storage tank 511-D1U1 closure plan

    Energy Technology Data Exchange (ETDEWEB)

    Mancieri, S.; Giuntoli, N.

    1993-09-01

    This document contains the closure plan for diesel fuel underground storage tank 511-D1U1 and appendices containing supplemental information such as staff training certification and task summaries. Precision tank test data, a site health and safety plan, and material safety data sheets are also included.

  9. Prefrontal D1 dopamine signaling is required for temporal control.

    Science.gov (United States)

    Narayanan, Nandakumar S; Land, Benjamin B; Solder, John E; Deisseroth, Karl; DiLeone, Ralph J

    2012-12-11

    Temporal control, or how organisms guide movements in time to achieve behavioral goals, depends on dopamine signaling. The medial prefrontal cortex controls many goal-directed behaviors and receives dopaminergic input primarily from the midbrain ventral tegmental area. However, this system has never been linked with temporal control. Here, we test the hypothesis that dopaminergic projections from the ventral tegmental area to the prefrontal cortex influence temporal control. Rodents were trained to perform a fixed-interval timing task with an interval of 20 s. We report several results: first, that decreasing dopaminergic neurotransmission using virally mediated RNA interference of tyrosine hydroxylase impaired temporal control, and second that pharmacological disruption of prefrontal D1 dopamine receptors, but not D2 dopamine receptors, impaired temporal control. We then used optogenetics to specifically and selectively manipulate prefrontal neurons expressing D1 dopamine receptors during fixed-interval timing performance. Selective inhibition of D1-expressing prefrontal neurons impaired fixed-interval timing, whereas stimulation made animals more efficient during task performance. These data provide evidence that ventral tegmental dopaminergic projections to the prefrontal cortex influence temporal control via D1 receptors. The results identify a critical circuit for temporal control of behavior that could serve as a target for the treatment of dopaminergic diseases.

  10. Electrified Fluctuations in D1$\\bot$D3 and D1$\\bot$D5 Systems

    CERN Document Server

    Douari, Jamila

    2008-01-01

    We present the physical phenomenon of the subject discussed in the paper \\cite{fluc}. In that paper we dealt with the fluctuations of funnel solutions of intersecting D1 and D3 branes and the electric field $E$ was considered as very high value causing the results to be non-physical. In the present work, the variation interval of $E$ is to be $[0,\\frac{1}{\\lambda}[$. Then, we extend the study to discuss the overall transverse fluctuations of electrified funnel solutions of D1$\\bot$D5 system in the flat background. The boundary conditions are found to be Neumann boundary conditions.

  11. Vacuum polarization in $d+{1/2}$ dimensions

    CERN Document Server

    Fosco, C D; Roditi, I

    2004-01-01

    We study the main properties of the one-loop vacuum polarization function ($\\Pi_{\\alpha \\beta}$) for spinor $QED$ in `$d + {1/2}$ dimensions', i.e., with fields defined on ${\\mathcal M} \\subset {\\mathbb R}^{d+1}$ such that ${\\mathcal M} = \\{(x_0,...,x_d) | x_{d}\\geq 0 \\}$, with bag-like boundary conditions on the boundary $\\partial{\\mathcal M} = \\{(x_0,...,x_d) | x_{d}= 0 \\}$. We obtain an exact expression for the induced current due to an external constant electric field normal to the boundary. We show that, for the particular case of 2+1 dimensions, there is a transverse component for the induced current, which is localized on a region close to $\\partial{\\mathcal M}$. This current is a parity breaking effect purely due to the boundary.

  12. D1-D5-P microstates at the cap

    CERN Document Server

    Giusto, Stefano; Mathur, Samir D; Turton, David

    2012-01-01

    The geometries describing D1-D5-P bound states in string theory have three regions: flat asymptotics, an anti-de Sitter throat, and a 'cap' region at the bottom of the throat. We identify the CFT description of a known class of supersymmetric D1-D5-P microstate geometries which describe degrees of freedom in the cap region. The class includes both regular solutions and solutions with conical defects, and generalizes configurations with known CFT descriptions: a parameter related to spectral flow in the CFT is generalized from integer to fractional values. We provide strong evidence for this identification by comparing the massless scalar excitation spectrum between gravity and CFT and finding exact agreement.

  13. New D1-D5-P geometries from string amplitudes

    CERN Document Server

    Giusto, Stefano; Turton, David

    2011-01-01

    We derive the long range supergravity fields sourced by a D1-D5-P bound state from disk amplitudes for massless closed string emission. We suggest that since the parameter controlling the string perturbation expansion for this calculation decreases with distance from the bound state, the resulting asymptotic fields are valid even in the regime of parameters in which there is a classical black hole solution with the same charges. The supergravity fields differ from the black hole solution by multipole moments and are more general than those contained within known classes of solutions in the literature, whilst still preserving four supersymmetries. Our results support the conjecture that the black hole solution should be interpreted as a coarse-grained description rather than an exact description of the gravitational field sourced by D1-D5-P bound states in this regime of parameters.

  14. Road Safety Data, Collection, Transfer and Analysis DaCoTa. Workpackage 2, Developing a Pan-European In-depth Accident Investigation Network: Deliverable 2.3: Training package including training manual and Draft Protocols.

    NARCIS (Netherlands)

    Fagerlind, H. Armstrong, J. Atala, D. Dodson, E. Talbot, R. Hill, J. Roynard, M. Martensen, H. Jänsch, M. Margaritis, D. Ocampo Sanchez, A. Peez, J. Ferrer, A. Elslande, P. van Perrin, C. Hermitte, T. Giustiniani, G. & Davidse, R.

    2015-01-01

    This deliverable is intended to collate the DaCoTA training manual and draft protocols for in-depth road accident investigations in Europe. This deliverable aims at producing a document that will be used in the training of new and previously experienced teams in the realm of in depth accident data c

  15. SiteChar. Characterisation of European CO2 storage. Deliverable D8.2. Trust building and raising public awareness

    Energy Technology Data Exchange (ETDEWEB)

    Brunsting, S.; Pol, M.; Mastop, E.A. [ECN Policy Studies, Energy research Centre of the Netherlands ECN, Amsterdam (Netherlands); Kaiser, M.; Zimmer, R. [Unabhaengiges Institut fuer Umweltfragen UfU, Berlin (Germany); Shackley, S.; Mabon, L.; Howell, R. [Scottish Carbon Capture and Storage SCCS, Edinburg, Scotland (United Kingdom)

    2012-08-15

    At local level, public support has proven crucial to the implementation of CO2 capture and storage (CCS) demonstration projects. Whereas no method exists to guarantee public acceptability of any project, a constructive stakeholder and community engagement process does increase the likelihood thereof. This deliverable is a follow-up to deliverable D8.1 'Social site characterisation'. Social site characterisation can be used as an instrument to explore, plan and evaluate a process of active and constructive local stakeholder and citizen engagement in a prospective CCS project as a parallel activity to technical site characterisation. It serves as an analytical tool to describe the local social circumstances in the area and to design and evaluate stakeholder and community engagement efforts with the aims of building trust and raising public awareness. Using results from the social site characterisation of the area, the present deliverable focuses on the second purpose. It presents results from public engagement activities designed to raise public awareness and inform public opinion of a prospective CCS site in Poland (onshore) and the UK (offshore): focus conferences. Furthermore, by initiating an enhanced cooperation in planning of new storage sites between project developers, authorities and the local public, focus conferences aim to serve as a 'hinge' between social site characterisation as a research effort and application to real-life project settings. The focus conferences are part of a range of public engagement activities including the setup of public information websites on generic and site-specific CCS, information meetings. A second survey eventually shall evaluate the results of the public engagement activities. The aim of the focus conferences was to raise public awareness and assist public opinion forming processes of a prospective CCS site in Poland (onshore) and the UK (offshore). At the same time, it aimed to present and test a

  16. Evaluation of D-1 tape and cassette characteristics: Moisture content of Sony and Ampex D-1 tapes when delivered

    Science.gov (United States)

    Ashton, Gary

    Commercial D-1 cassette tapes and their associated recorders were designed to operate in broadcast studios and record in accordance with the International Radio Consultative Committee (CCIR) 607 digital video standards. The D-1 recorder resulted in the Society of Motion Picture and Television Engineers (SMPTE) standards 224 to 228 and is the first digital video recorder to be standardized for the broadcast industry. The D-1 cassette and associated media are currently marketed for broadcast use. The recorder was redesigned for data applications and is in the early stages of being evaluated. The digital data formats used are specified in MIL-STD-2179 and the American National Standards Institute (ANSI) X3.175-190 standard. In early 1990, the National Media Laboratory (NML) was asked to study the effects of time, temperature, and relative humidity on commercial D-1 cassettes. The environmental range to be studied was the one selected for the Advanced Tactical Air Reconnaissance System (ATARS) program. Several discussions between NML personnel, ATARS representatives, recorder contractors, and other interested parties were held to decide upon the experimental plan to be implemented. Review meetings were held periodically during the course of the experiment. The experiments were designed to determine the dimensional stability of the media and cassette since this is one of the major limiting factors of helical recorders when the media or recorders are subjected to non-broadcasting environments. Measurements were also made to characterize each sample of cassettes to give preliminary information on which purchase specifications could be developed. The actual tests performed on the cassettes and media before and after aging fall into the general categories listed.

  17. Rethinking the Business Model in Construction by the Use of Off-Site System Deliverance: Case of the Shaft Project

    DEFF Research Database (Denmark)

    Thuesen, Christian; Hvam, Lars

    2013-01-01

    in the existing design and production practices. More specifically the development of system deliveries requires: (1) an explicit market focus, enabling the achievement of economy of scale, (2) a coordinated and coherent development around the system deliverance focusing on its internal and external modularity...... of installation shafts. Findings from the development and production of the installation shaft show that system deliveries represent a promising strategy for moving from red ocean competitive environment with the predominant cost+ business model, to a blue ocean situation in which the competition emerges....... (3) development of processes and configuration practices which make it possible to put together (configure) the product matching the needs of the individual building project. (4) development of alliances between companies in enabling value chain integration....

  18. Risk of injury by driving with alcohol and other drugs. Driving under the Influence of Drugs, Alcohol and Medicines DRUID, Deliverable 2.3.5.

    NARCIS (Netherlands)

    Hels, T. Bernhoft, I.M. Lyckegaard, A. Houwing, S. Hagenzieker, M.P. Legrand, S.-A. Isalberti, C. Van der Linden, T. & Verstraete, A.

    2011-01-01

    The objective of this deliverable is to assess the risk of driving with alcohol, illicit drugs and medicines in various European countries. In total nine countries participated in the study on relative risk of serious injury/fatality while positive for psychoactive substances. Six countries contribu

  19. Police Enforcement Policy and Programmes on European Roads (PEPPER). Deliverable 4a: Good practice in data, data collection and data use for monitoring and evaluating Traffic Law Enforcement.

    NARCIS (Netherlands)

    Schagen, I.N.L.G. Bernhoft, I.M. Erke, A. Ewert, U. Kallberg, V.-P. & Skladana, P.

    2008-01-01

    This report is the Deliverable of task 4.3a of the PEPPER project. It describes the good practice requirements regarding data, data collection and data use for monitoring and evaluating Traffic Law Enforcement (TLE). The aim is that, eventually, individual police forces/countries put the identified

  20. Randomized comparison of deliverability and in-hospital complications in implantation of BxSonic(R), Express(R), and Flexmaster(R) coronary stents

    DEFF Research Database (Denmark)

    Thuesen, Leif; Galløe, Anders; Thayssen, Per;

    2005-01-01

    AIMS: To compare deliverability and in-hospital complications in implantation of BxSonic(R), Express(R), and Flexmaster(R) coronary stents in a randomized multicenter trial in five Danish interventional centres. METHODS AND RESULTS: Patients with planned stenting of at least one stenotic lesion i...

  1. Attenuation of ground-borne vibration affecting residents near railway. Lines Deliverable 2.1: Exposure response relationships and factors influencing these relationships (Work Package WP1)

    NARCIS (Netherlands)

    Janssen, S.A.; Vos, H.; Koopman, A.

    2014-01-01

    The objective of the present deliverable is to describe and assess reported health impacts of vibration among residents living near railway lines, in particular the response to freight trains. To this end, first a state of the art overview is given of the results from all field studies reported so f

  2. In-vehicle and site-based observations of vehicles and cyclists. A small-scale ND study in the Netherlands. PROLOGUE Deliverable D3.4

    NARCIS (Netherlands)

    Christoph, M.; Nes, N. van; Pauwelussen, J.J.A.; Mansvelders, R.; Horst, A.R.A. van der; Hoedemaeker, D.M.

    2010-01-01

    The main objective of the project PROLOGUE (PROmoting real Life Observations for Gaining Understanding of road user behaviour in Europe) is to explore the feasibility and usefulness of a large-scale European naturalistic driving observation study. The work described in this deliverable focused on th

  3. Molecular characterization of zebrafish Oatp1d1 (Slco1d1), a novel organic anion-transporting polypeptide.

    Science.gov (United States)

    Popovic, Marta; Zaja, Roko; Fent, Karl; Smital, Tvrtko

    2013-11-22

    The organic anion-transporting polypeptide (OATP/Oatp) superfamily includes a group of polyspecific transporters that mediate transport of large amphipathic, mostly anionic molecules across cell membranes of eukaryotes. OATPs/Oatps are involved in the disposition and elimination of numerous physiological and foreign compounds. However, in non-mammalian species, the functional properties of Oatps remain unknown. We aimed to elucidate the role of Oatp1d1 in zebrafish to gain insights into the functional and structural evolution of the OATP1/Oatp1 superfamily. We show that diversification of the OATP1/Oatp1 family occurs after the emergence of jawed fish and that the OATP1A/Oatp1a and OATP1B/Oatp1b subfamilies appeared at the root of tetrapods. The Oatp1d subfamily emerged in teleosts and is absent in tetrapods. The zebrafish Oatp1d1 is similar to mammalian OATP1A/Oatp1a and OATP1B/Oatp1b members, with the main physiological role in transport and balance of steroid hormones. Oatp1d1 activity is dependent upon pH gradient, which could indicate bicarbonate exchange as a mode of transport. Our analysis of evolutionary conservation and structural properties revealed that (i) His-79 in intracellular loop 3 is conserved within OATP1/Oatp1 family and is crucial for the transport activity; (ii) N-glycosylation impacts membrane targeting and is conserved within the OATP1/Oatp1 family with Asn-122, Asn-133, Asn-499, and Asn-512 residues involved; (iii) the evolutionarily conserved cholesterol recognition interaction amino acid consensus motif is important for membrane localization; and (iv) Oatp1d1 is present in dimeric and possibly oligomeric form in the cell membrane. In conclusion, we describe the first detailed characterization of a new Oatp transporter in zebrafish, offering important insights into the functional evolution of the OATP1/Oatp1 family and the physiological role of Oatp1d1.

  4. Second Spectrum of Na I D1 Observed with THEMIS

    Science.gov (United States)

    Bommier, V.; Molodij, G.

    2006-12-01

    The second solar spectrum (spectrum of the linear polarization observed near the solar limb in a quiet region) of Na I D1 has always been found antisymmetrical when observed with THEMIS tep{b12 TB01,b12 BM02}. The same holds also for atlas of tet{b12 Ga00}. On the contrary, tet{b12 SK97} and tet{b12 St00} observed a differently shaped profile, showing a central peak. We investigated in depth our treatment of THEMIS data, in particular looking for possible beam misalignments, by observing other unpolarized lines, but we have failed to put in evidence any misalignment. We discuss these complementary observations. In addition, we present a structure in the V/I profile of Na I D1 and D2, which we have repeatedly observed, and which we suggest be due to the Kemp effect (the alignement-to-orientation transfer that occurs in the transition from the Zeeman effect to the Paschen-Back effect).

  5. ECRH launching scenario in FFHR-d1

    Science.gov (United States)

    Yanagihara, Kota; Kubo, Shin; Shimozuma, Takashi; Yoshimura, Yasuo; Igami, Hiroe; Takahashi, Hiromi; Tsujimura, Tohru; Makino, Ryohhei

    2016-10-01

    ECRH is promising as a principal heating system in a prototype helical reactor FFHR-d1 where the heating power of 80 MW is required to bring the plasma parameter to break even condition. To generate the plasma and bring it to ignition condition in FFHR-d1, it is effective to heat the under/over-dense plasma with normal ECRH or Electron Bernstein Wave (EBW). Normal ECRH is well established but heating via EBW need sophisticated injection control. EBW can be excited via the O(ordinary)-X(extraordinary)-B(EBW) mode conversion process by launching the ordinary wave from the low field side to plasma cut-off layer with optimum injection angle, and the range of injection angle to get high OXB mode conversion rate is called OXB mode conversion window. Since the window position can change as the plasma parameter, it is necessary to optimize the injection angle so as to aim the window in response to the plasma parameters. Candidates of antenna positions are determined by optimum injection points on the plasma facing wall calculated by the injection angle. Given such picked up area, detailed analysis using ray-tracing calculations and engineering antenna design will be performed.

  6. Mutation at the Human D1S80 Minisatellite Locus

    Directory of Open Access Journals (Sweden)

    Kuppareddi Balamurugan

    2012-01-01

    Full Text Available Little is known about the general biology of minisatellites. The purpose of this study is to examine repeat mutations from the D1S80 minisatellite locus by sequence analysis to elucidate the mutational process at this locus. This is a highly polymorphic minisatellite locus, located in the subtelomeric region of chromosome 1. We have analyzed 90,000 human germline transmission events and found seven (7 mutations at this locus. The D1S80 alleles of the parentage trio, the child, mother, and the alleged father were sequenced and the origin of the mutation was determined. Using American Association of Blood Banks (AABB guidelines, we found a male mutation rate of 1.04×10-4 and a female mutation rate of 5.18×10-5 with an overall mutation rate of approximately 7.77×10-5. Also, in this study, we found that the identified mutations are in close proximity to the center of the repeat array rather than at the ends of the repeat array. Several studies have examined the mutational mechanisms of the minisatellites according to infinite allele model (IAM and the one-step stepwise mutation model (SMM. In this study, we found that this locus fits into the one-step mutation model (SMM mechanism in six out of seven instances similar to STR loci.

  7. 17 CFR 270.12d1-3 - Exemptions for investment companies relying on section 12(d)(1)(F) of the Act.

    Science.gov (United States)

    2010-04-01

    ...) Exemption from sales charge limits. A registered investment company (“acquiring fund”) that relies on... company (“acquired fund”) may offer or sell any security it issues through a principal underwriter or... companies relying on section 12(d)(1)(F) of the Act. 270.12d1-3 Section 270.12d1-3 Commodity and...

  8. Transcriptome-Based Identification of the Sinorhizobium meliloti NodD1 Regulon

    OpenAIRE

    Capela, Delphine; Carrere, Sébastien; Batut, Jacques

    2005-01-01

    The NodD1 regulon of Sinorhizobium meliloti was determined through the analysis of the S. meliloti transcriptome in response to the plant flavone luteolin and the overexpression of nodD1. Nine new genes regulated by both NodD1 and luteolin were identified, demonstrating that NodD1 controls few functions behind nodulation in S. meliloti.

  9. Transcriptome-based identification of the Sinorhizobium meliloti NodD1 regulon.

    Science.gov (United States)

    Capela, Delphine; Carrere, Sébastien; Batut, Jacques

    2005-08-01

    The NodD1 regulon of Sinorhizobium meliloti was determined through the analysis of the S. meliloti transcriptome in response to the plant flavone luteolin and the overexpression of nodD1. Nine new genes regulated by both NodD1 and luteolin were identified, demonstrating that NodD1 controls few functions behind nodulation in S. meliloti.

  10. 4d N=1 from 6d (1,0)

    CERN Document Server

    Razamat, Shlomo S; Zafrir, Gabi

    2016-01-01

    We study the geometry of 4d N=1 SCFT's arising from compactification of 6d (1,0) SCFT's on a Riemann surface. We show that the conformal manifold of the resulting theory is characterized, in addition to moduli of complex structure of the Riemann surface, by the choice of a connection for a vector bundle on the surface arising from flavor symmetries in 6d. We exemplify this by considering the case of 4d N=1 SCFT's arising from M5 branes probing Z_k singularity compactified on a Riemann surface. In particular, we study in detail the four dimensional theories arising in the case of two M5 branes on Z_2 singularity. We compute the conformal anomalies and indices of such theories in 4d and find that they are consistent with expectations based on anomaly and the moduli structure derived from the 6 dimensional perspective.

  11. Handbook of efficient recommandations: Public Deliverable D6.4, PRIMA collaborative project, EU 7th Framework Programme, contract no. 212345

    OpenAIRE

    Meyer, B.C.; Laplana, R.; Raley, M.; Baqueiro, O.; Kopeva, D.; Hautdidier, B.

    2011-01-01

    The Deliverable 6.4 “Handbook of efficient recommendations” deals with the main methodological developments in the context of screening, scoping and Sustainability Impact Assessment (SIA) developed and discussed in PRIMA. The main topics of this handbook deal with key aspects of the methodological enhancement of Impact Assessment within the context of experiences in Environmental Impact Assessment and Strategic Environmental Assessment. Key research is linked to the questions abou...

  12. Haplotype variation of Glu-D1 locus and the origin of Glu-D1d allele conferring superior end-use qualities in common wheat.

    Directory of Open Access Journals (Sweden)

    Zhenying Dong

    Full Text Available In higher plants, seed storage proteins (SSPs are frequently expressed from complex gene families, and allelic variation of SSP genes often affects the quality traits of crops. In common wheat, the Glu-D1 locus, encoding 1Dx and 1Dy SSPs, has multiple alleles. The Glu-D1d allele frequently confers superior end-use qualities to commercial wheat varieties. Here, we studied the haplotype structure of Glu-D1 genomic region and the origin of Glu-D1d. Using seven diagnostic DNA markers, 12 Glu-D1 haplotypes were detected among common wheat, European spelt wheat (T. spelta, a primitive hexaploid relative of common wheat, and Aegilops tauschii (the D genome donor of hexaploid wheat. By comparatively analyzing Glu-D1 haplotypes and their associated 1Dx and 1Dy genes, we deduce that the haplotype carrying Glu-D1d was likely differentiated in the ancestral hexaploid wheat around 10,000 years ago, and was subsequently transmitted to domesticated common wheat and T. spelta. A group of relatively ancient Glu-D1 haplotypes was discovered in Ae. tauschii, which may serve for the evolution of other haplotypes. Moreover, a number of new Glu-D1d variants were found in T. spelta. The main steps in Glu-D1d differentiation are proposed. The implications of our work for enhancing the utility of Glu-D1d in wheat quality improvement and studying the SSP alleles in other crop species are discussed.

  13. 26 CFR 1.167(d)-1 - Agreement as to useful life and rates of depreciation.

    Science.gov (United States)

    2010-04-01

    ... depreciation. 1.167(d)-1 Section 1.167(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... and Corporations § 1.167(d)-1 Agreement as to useful life and rates of depreciation. After August 16... respect to the estimated useful life, method and rate of depreciation and treatment of salvage of...

  14. 26 CFR 1.666(d)-1A - Information required from trusts.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Information required from trusts. 1.666(d)-1A Section 1.666(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Years Beginning Before January 1, 1969 § 1.666(d)-1A Information required from trusts. (a)...

  15. 26 CFR 1.411(d)-1 - Coordination of vesting and discrimination requirements. [Reserved

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Coordination of vesting and discrimination requirements. 1.411(d)-1 Section 1.411(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE.... § 1.411(d)-1 Coordination of vesting and discrimination requirements....

  16. 26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Determination of target normal cost and funding target. 1.430(d)-1 Section 1.430(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Certain Stock Options § 1.430(d)-1 Determination of target normal cost and funding target....

  17. Características do ejaculado de caprinos sob estresse calórico em câmara bioclimática Sperm characteristics of bucks under heat stress in climatic chamber

    Directory of Open Access Journals (Sweden)

    L.A. Coelho

    2006-08-01

    Full Text Available Para verificar o efeito do estresse calórico (EC na produção espermática de caprinos, oito machos das raças Saanen (n=4 e Pardo-Alpina (n=4 foram mantidos em câmara bioclimática, sob condições de termoneutralidade (13,0ºC a 26,7ºC durante 30 dias e, após um período (60 dias de descanso, submetidos ao EC (23,7ºC a 34,0ºC por mais 30 dias. Para minimizar as variações sazonais na produção espermática, durante todo o período, o fotoperíodo foi controlado utilizando-se alternância de dias longos (16 horas de luz e 8 horas de escuro e de dias curtos (8 horas de luz e 16 horas de escuro a cada 30 dias. Avaliaram-se as temperaturas retal e testicular, o volume do ejaculado, a concentração espermática, as motilidades massal e individual progressiva (MIP, o vigor e a morfologia espermática. Houve aumento (P0,05 o percentual total de células anormais e nem a temperatura retal. Os machos da raça Saanen apresentaram temperaturas do testículo e retal mais elevadas (PTo verify the effect of heat stress (HS on caprine semen production eight male goats of Saanen (n=4 and Alpine Brown (n=4 breeds were kept in climate chamber under thermal neutral conditions (13.0ºC to 26.7ºC for 30 days. After a resting period (60 days, the same bucks were submitted to heat stress (23.7ºC to 34.0ºC for another 30 days. To neutralize the seasonal variations of sperm production throughout the period, the photoperiod was controlled every 30 days alterning long days (16 hours of light and 8 hours of darkness and short days (8 hours of light and 16 hours of darkness. The following variables were evaluated: rectal and testicular temperatures, volume of ejaculate, sperm concentration, mass motility, individual progressive motility, vigor and sperm morphology. There was an elevation (P0.05 on percentage of morphologically normal spermatozoa and rectal temperature. The Saanen males showed higher testicular and rectal temperatures and produced more sperm

  18. Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells

    OpenAIRE

    Ning Wang; Xuanbin Wang; Hor-Yue Tan; Sha Li; Chi Man Tsang; Sai-Wah Tsao; Yibin Feng

    2016-01-01

    The aim of this study is to explore the underlying mechanism on berberine-induced Cyclin D1 degradation in human hepatic carcinoma. We observed that berberine could suppress both in vitro and in vivo expression of Cyclin D1 in hepatoma cells. Berberine exhibits dose- and time-dependent inhibition on Cyclin D1 expression in human hepatoma cell HepG2. Berberine increases the phosphorylation of Cyclin D1 at Thr286 site and potentiates Cyclin D1 nuclear export to cytoplasm for proteasomal degrada...

  19. CO{sub 2}-emission trading and green markets for renewable electricity. WILMAR - deliverable 4.1

    Energy Technology Data Exchange (ETDEWEB)

    Azuma-Dicke, N.; Weber, C. [Univ. of Stuttgart, IER (Germany); Morthorst, P.E. [Risoe National Lab., Roskilde (Denmark); Ravn, H.F.; Schmidt, R. [Technical Univ. of Denmark, Lyngby (Denmark)

    2004-06-01

    This report is Deliverable 4.1 of the EU project 'Wind Power Inte-gration in Liberalised Electricity Markets' (WILMAR) and de-scribes the application of two policy instruments, Tradable Emis-sions Permits (TEPs) and Tradable Green Certificates (TGCs) for electricity produced from renewable energy sources in the European Union and the implications for implementation in the Wilmar model. The introduction of a common emission-trading system in the EU is expected to have an upward effect on the spot prices at the electric-ity market. The variations of the spot price imply that some types of power generation may change the situation from earning money to losing money despite the increasing spot price. Heavy restrictions on emissions penalise the fossil-fuelled technologies significantly, and the associated increase in the spot price need not compensate for this. Therefore, a market of TEPs is expected to have a signifi-cant influence on the electricity spot price. However, the expected price level of TEPs are met with great uncertainty and a study of a number of economical studies shows a price span between zero and 270 USD per ton of CO{sub 2} depending on the participation or non-participation of countries in the scheme. The price-determination at the TGC market is expected to be closely related to the price at the power spot market as the RE-producers of electricity will have expectations to the total price paid for the energy produced, i.e., for the price of electricity at the spot market plus the price per kWh obtained at the green certificate mar-ket. In the Wilmar model, the TGC market can either be handled exogenously, i.e., the increase in renewable capacity and an average annual TGC price are determined outside the model, or a simple TGC module is developed, including the long-term supply functions for the most relevant renewable technologies and an overall TGC quota. Both solutions are rather simple, but to develop a more ad-vanced model for the TGC

  20. Identification and Analysis of New Puroindoline Pina-D1o%Pina新等位变异Pina-D1o的分离及分析

    Institute of Scientific and Technical Information of China (English)

    刘迪; 陈文杰; 张波; 刘登才; 刘宝龙; 张怀刚

    2015-01-01

    Puroindoline基因(Pina和Pinb)是控制小麦籽粒硬度的主效基因,决定小麦加工品质,分离该基因的新等位变异有利于小麦籽粒硬度性状的改良.采用同源克隆方法从节节麦(Aegilops tauschii,DD PI603224)中分离到一个Pina新等位变异Pina-D1o.生物信息学分析表明,该基因编码区全长447 bp,编码148个氨基酸残基,具有小麦族作物PinA蛋白所特有的WRWWKWWK色氨酸结构域和10个半胱氨酸所形成的5个二硫键结构.根据核苷酸序列构建的拓扑树,Pina-D1o与Pina-D1m、ina D1n相同,均由功能性等位变异Pina-D1a发生单基因突变而来,因而Pina-D1o有可能来源于Pina-D1a.可见,新等位变异类型Pina-D1o的发现可以为小麦的籽粒硬度改良提供基因资源.

  1. Correlation in price changes and volatility between non-deliverable forward and spot markets : an analysis of daily data from China

    OpenAIRE

    2006-01-01

    This thesis seeks to explore the dynamics between China’s onshore spot foreign exchange market and the offshore RMB non-deliverable forward (NDF) market before and after the reforms in exchange rate regime and foreign exchange market structures around July 21, 2005. Developments in the two markets are reviewed and daily closing rates of both markets are examined. The Johansen co-integration test finds a strong co-integrating relationship between the onshore spot rate and the NDF rate and a tw...

  2. Cocaine disrupts histamine H3 receptor modulation of dopamine D1 receptor signaling: σ1-D1-H3 receptor complexes as key targets for reducing cocaine's effects.

    Science.gov (United States)

    Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric; McCormick, Peter J

    2014-03-05

    The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine.

  3. EXPRESSION OF CYCLIN D1 AND CDK4 IN OSTEOSARCOMA OF THE JAWS

    Institute of Scientific and Technical Information of China (English)

    司晓辉; 刘正

    2001-01-01

    Objective: To analyze cyclin D1 and cyclin- dependent kinase 4 (CDK4) expression and their significance in osteosarcoma of the jaws. Methods: Immunohistochemical ABC method was used to detect the expression of cyclin D1 and CDK4 in 20 cases of osteosarcoma and 8 cases of osteochondroma of the jaws. Results: The positive rates of cyclin D1 and CDK4 were 65% (13/20) and 60% (12/20), respectively. There was significant positive correlation between cyclin D1 and CDK4 expression (gs=0.48, P<0.05). Both cyclin D1 and CDK4 were present in 1/8 (12.5%) osteochondroma. The positive rate was remarkably different between osteosarcoma and osteochondroma (P<0.05). Conclusion: Cyclin D1 and CDK4 are overexpressed in osteosarcoma of the jaws and closely related to its occurrence and development.

  4. Striatal dopamine D1 receptor suppression impairs reward-associative learning.

    Science.gov (United States)

    Higa, Kerin K; Young, Jared W; Ji, Baohu; Nichols, David E; Geyer, Mark A; Zhou, Xianjin

    2017-04-14

    Dopamine (DA) is required for reinforcement learning. Hence, disruptions in DA signaling may contribute to the learning deficits associated with psychiatric disorders. The DA D1 receptor (D1R) has been linked to learning and is a target for cognitive/motivational enhancement in patients with schizophrenia. Separating the striatal D1R contribution to learning vs. motivation, however, has been challenging. We suppressed striatal D1R expression in mice using a D1R-targeting short hairpin RNA (shRNA), delivered locally to the striatum via an adeno-associated virus (AAV). We then assessed reward- and punishment-associative learning using a probabilistic learning task and motivation using a progressive-ratio breakpoint procedure. We confirmed suppression of striatal D1Rs immunohistochemically and by testing locomotor activity after the administration of (+)-doxanthrine, a full D1R agonist, in control mice and those treated with the D1RshRNA. D1RshRNA-treated mice exhibited impaired reward-associative learning, while punishment-associative learning was spared. This deficit was unrelated to general learning impairments or amotivation, because the D1shRNA-treated mice exhibited normal Barnes maze learning and normal motivation in the progressive-ratio breakpoint procedure. Suppression of striatal D1Rs selectively impaired reward-associative learning whereas punishment-associative learning, aversion-motivated learning, and appetitive motivation were spared. Because patients with schizophrenia exhibit similar reward-associative learning deficits, D1R-targeted treatments should be investigated to improve reward learning in these patients.

  5. Remote functionalization of SCH 39166: discovery of potent and selective benzazepine dopamine D1 receptor antagonists.

    Science.gov (United States)

    Sasikumar, T K; Burnett, Duane A; Greenlee, William J; Smith, Michelle; Fawzi, Ahmad; Zhang, Hongtao; Lachowicz, Jean E

    2010-02-01

    A series of novel benzazepine derived dopamine D(1) antagonists have been discovered. These compounds are highly potent at D(1) and showed excellent selectivity over D(2) and D(4) receptors. SAR studies revealed that a variety of functional groups are tolerated on the D-ring of known tetracyclic benzazepine analog 2, SCH 39166, leading to compounds with nanomolar potency at D(1) and good selectivity over D(2)-like receptors.

  6. Transcriptional regulation of renal dopamine D1 receptor function during oxidative stress.

    Science.gov (United States)

    Banday, Anees A; Lokhandwala, Mustafa F

    2015-05-01

    There exists a strong link between oxidative stress, renal dopaminergic system, and hypertension. It is reported that reactive oxygen species attenuate renal proximal tubular dopamine receptor (D1R) function, which disrupts sodium regulation and leads to hypertension. However, the mechanisms for renal D1R dysfunction are not clear. We investigated the role of redox-sensitive transcription factors AP1 and SP3 in transcriptional suppression of D1R gene and subsequent D1R signaling. Human kidney proximal tubular cells were treated with a pro-oxidant l-buthionine sulfoximine (BSO) with and without an antioxidant tempol. In human kidney cells, BSO caused oxidative stress and reduced D1R mRNA and membrane receptor expression. Incubation of human kidney cells with SKF38393, a D1R agonist, caused a concentration-dependent inhibition of Na/K-ATPase. However, SKF38393 failed to inhibit Na/K-ATPase in BSO-treated cells. BSO increased AP1 and SP3 nuclear expression. Transfection with AP1- or SP3-specific siRNA abolished BSO-induced D1R downregulation. Treatment of rats with BSO for 4 weeks increased oxidative stress and SP3-AP1 expression and reduced D1R numbers in renal proximal tubules. These rats exhibited high blood pressure, and SKF38393 failed to inhibit proximal tubular Na/K-ATPase activity. Control rats were kept on tap water. Tempol per se had no effect on D1R expression or other signaling molecules but prevented BSO-induced oxidative stress, SP3-AP1 upregulation, and D1R dysfunction in both human kidney cells and rats. These data show that oxidative stress via AP1-SP3 activation suppresses D1R transcription and function. Tempol mitigates oxidative stress, blocks AP1-SP3 activation, and prevents D1R dysfunction and hypertension.

  7. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.

    Science.gov (United States)

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-13

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice.

  8. Observation of the $^1$S$_0$ to $^3$D$_1$ clock transition in $^{175}$Lu$^+$

    CERN Document Server

    Arnold, Kyle J; Roy, A; Paez, E; Wang, S; Barrett, M D

    2016-01-01

    We report the first laser spectroscopy of the $^1$S$_0$ to $^3$D$_1$ clock transition in $^{175}$Lu$^+$. Clock operation is demonstrated on three pairs of Zeeman transitions, one pair from each hyperfine manifold of the $^3$D$_1$ term. We measure the hyperfine intervals of the $^3$D$_1$ to 10 ppb uncertainty and infer the optical frequency averaged over the three hyperfine transitions to be 353.639 915 952 2 (6) THz. The lifetime of the $^3$D$_1$ state is inferred to be $174^{+23}_{-32}$ hours from the M1 coupling strength.

  9. New therapeutic strategies targeting D1-type dopamine receptors for neuropsychiatric disease

    Science.gov (United States)

    Kim, Young-Cho; Alberico, Stephanie L.; Emmons, Eric; Narayanan, Nandakumar S.

    2017-01-01

    The neurotransmitter dopamine acts via two major classes of receptors, D1-type and D2-type. D1 receptors are highly expressed in the striatum and can also be found in the cerebral cortex. Here we review the role of D1 dopamine signaling in two major domains: L-DOPA-induced dyskinesias in Parkinson’s disease and cognition in neuropsychiatric disorders. While there are many drugs targeting D2-type receptors, there are no drugs that specifically target D1 receptors. It has been difficult to use selective D1-receptor agonists for clinical applications due to issues with bioavailability, binding affinity, pharmacological kinetics, and side effects. We propose potential therapies that selectively modulate D1 dopamine signaling by targeting second messengers downstream of D1 receptors, allosteric modulators, or by making targeted modifications to D1-receptor machinery. The development of therapies specific to D1-receptor signaling could be a new frontier in the treatment of neurological and psychiatric disorders.

  10. Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer.

    Science.gov (United States)

    Borcherding, D C; Tong, W; Hugo, E R; Barnard, D F; Fox, S; LaSance, K; Shaughnessy, E; Ben-Jonathan, N

    2016-06-16

    Patients with advanced breast cancer often fail to respond to treatment, creating a need to develop novel biomarkers and effective therapeutics. Dopamine (DA) is a catecholamine that binds to five G protein-coupled receptors. We discovered expression of DA type-1 receptors (D1Rs) in breast cancer, thereby identifying these receptors as novel therapeutic targets in this disease. Strong to moderate immunoreactive D1R expression was found in 30% of 751 primary breast carcinomas, and was associated with larger tumors, higher tumor grades, node metastasis and shorter patient survival. DA and D1R agonists, signaling through the cGMP/protein kinase G (PKG) pathway, suppressed cell viability, inhibited invasion and induced apoptosis in multiple breast cancer cell lines. Fenoldopam, a peripheral D1R agonist that does not penetrate the brain, dramatically suppressed tumor growth in two mouse models with D1R-expressing xenografts by increasing both necrosis and apoptosis. D1R-expressing primary tumors and metastases in mice were detected by fluorescence imaging. In conclusion, D1R overexpression is associated with advanced breast cancer and poor prognosis. Activation of the D1R/cGMP/PKG pathway induces apoptosis in vitro and causes tumor shrinkage in vivo. Fenoldopam, which is FDA (Food and Drug Administration) approved to treat renal hypertension, could be repurposed as a novel therapeutic agent for patients with D1R-expressing tumors.

  11. Regulation of dopamine D1 receptor dynamics within the postsynaptic density of hippocampal glutamate synapses.

    Directory of Open Access Journals (Sweden)

    Laurent Ladepeche

    Full Text Available Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine and glutamate receptor-mediated signalling interplay at glutamate synapse remain poorly understood. Among the cellular mechanisms proposed to aggregate D1R in glutamate synapses, the direct interaction between D1R and the scaffold protein PSD95 or the direct interaction with the glutamate NMDA receptor (NMDAR have been proposed. To tackle this question we here used high-resolution single nanoparticle imaging since it provides a powerful way to investigate at the sub-micron resolution the dynamic interaction between these partners in live synapses. We demonstrate in hippocampal neuronal networks that dopamine D1 receptors (D1R laterally diffuse within glutamate synapses, in which their diffusion is reduced. Disrupting the interaction between D1R and PSD95, through genetical manipulation and competing peptide, did not affect D1R dynamics in glutamatergic synapses. However, preventing the physical interaction between D1R and the GluN1 subunit of NMDAR abolished the synaptic stabilization of diffusing D1R. Together, these data provide direct evidence that the interaction between D1R and NMDAR in synapses participate in the building of the dopamine-receptor-mediated signalling, and most likely to the glutamate-dopamine cross-talk.

  12. Biochemical characterization of Drosophila glutathione S-transferases D1 and D21.

    Science.gov (United States)

    Tang, A H; Tu, C P

    1994-11-11

    The genomic DNA for the two Drosophila genes, gstD1 and gstD21, were engineered for expression in Escherichia coli by polymerase chain reaction using a pair of specially designed primers. This newly designed expression system produced consistently high yields of the recombinant glutathione S-transferases (GSTs), which were purified to electrophoretic homogeneity by S-hexyl-GSH affinity chromatography. Consistent with their differences in size, GST D1 and GST D21 displayed different mobilities on SDS-polyacrylamide gel electrophoresis. Circular dichroism spectrometry revealed some differences in the protein secondary structural organization between the two GST D isozymes. Polyclonal antibodies against GST D1 and GST D21 revealed that they are immunologically distinct from each other. The GST D1 antiserum cross-reacted weakly with GST D21, but the GST D21 antiserum had no detectable cross-reactivity with GST D1. The amino acid sequences of GST D1 and GST D21 have 70% identity. GST D1 is active toward CDNB with 17% of the catalytic efficiency of the human alpha GST121, whereas CDNB is a poor substrate for GST D21. Both GST D1 and GST D21 have similar levels of GSH peroxidase activity against cumene hydroperoxide. Another major difference in substrate specificities between GST D1 and GST D21 is in the activity of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) dehydrochlorinase, which exists only in the GST D1 isozyme. This is the first definitive demonstration that DDT dehydrochlorinase activity is an intrinsic property of a Drosophila GST. Our results suggest that GST D1 may play a role in DDT metabolism in Drosophila.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, S; Manigandan, D; Sahai, P; Biswas, A; Subramani, V; Chander, S; Julkha, P; Rath, G [Fortis Hospital, Mohali, Punjab (India)

    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

  14. SiteChar. Characterisation of European CO2 storage. Deliverable 8.4. Quantitative social site characterisations

    Energy Technology Data Exchange (ETDEWEB)

    Brunsting, S.; Mastop, E.A. [ECN Policy Studies, Energy research Centre of the Netherlands ECN, Amsterdam (Netherlands); Kaiser, M.; Zimmer, R. [Unabhaengiges Institut fuer Umweltfragen UfU, Berlin (Germany)

    2013-06-15

    This report describes the results of the last stage of the in-depth social site characterisation activities at two prospective CCS sites as part of the SiteChar project: a CCS onshore site and a CCS offshore site. The onshore site is the Zalecze and Zuchlow site application (Poland - WP5) and the offshore site is the North Sea Moray Firth site (UK - WP3). This deliverable describes the results from a repeated quantitative measurement of local awareness, knowledge, and perceptions of CCS at both sites using representative surveys. For comparison and discussion of all SiteChar WP8 results we refer to the final summary report D8.5. The 2nd survey showed some interesting results. First of all, awareness of CCS was still very low. While in the UK around half of the respondents had at least heard of local plans for CCS, in Poland this was only 21%. It seems that awareness in the UK was mostly induced by specific plans in the area that were abandoned in the course of the SiteChar project. Second, it seems that on the whole the local publics were rather positive about CCS. Most respondents expected a positive impact of CCS on the region. In the UK, arguments for that were mainly economic, while in Poland arguments were mainly related to environmental concerns. Although there are some worries about risks of leakage, especially at the onshore site in Poland, people think that authorities will properly regulate CCS and monitor the safety of CCS. Expectations were mostly that it would be good for the country and that it will help reach international targets for CO2 reduction and buy time to develop renewable energy. Respondents seemed uncertain about the costs of using CCS and whether the technique is ready for widespread use. Especially in Poland people seemed to agree that CCS is essential for tackling climate change. Most differences between the two sites may be attributed to the proximity of the site to the local community. The Polish site is onshore and therefore much

  15. 17 CFR 270.30d-1 - Filing of copies of reports to shareholders.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Filing of copies of reports to shareholders. 270.30d-1 Section 270.30d-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... shareholders. A registered management investment company, other than a small business investment...

  16. Concerted Action of ANP and Dopamine D1-Receptor to Regulate Sodium Homeostasis in Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Cátia Fernandes-Cerqueira

    2013-01-01

    Full Text Available The edema formation in nephrotic syndrome (NS is associated with a blunted response to atrial natriuretic peptide (ANP. The natriuretic effects of ANP have been related to renal dopamine D1-receptors (D1R. We examined the interaction between ANP and renal D1R in rats with puromycin aminonucleoside-induced NS (PAN-NS. Urinary sodium, cyclic guanosine monophosphate (cGMP excretion, and D1R protein expression and localization in renal tubules were evaluated in PAN-NS and control rats before and during volume expansion (VE. The effects of zaprinast (phosphodiesterase type 5 inhibitor, alone or in combination with Sch-23390 (D1R antagonist, were examined in both groups. The increased natriuresis and urinary cGMP excretion evoked by acute VE were blunted in PAN-NS despite increased levels of circulating ANP. This was accompanied in PAN-NS by a marked decrease of D1R expression in the renal tubules. Infusion of zaprinast in PAN-NS resulted in increased urinary excretion of cGMP and sodium to similar levels of control rats and increased expression of D1R in the plasma membrane of renal tubular cells. Combined administration of Sch-23390 and zaprinast prevented natriuresis and increased cGMP excretion induced by zaprinast alone. We conclude that D1R may play a major role in the ANP resistance observed in PAN-NS.

  17. 26 CFR 1.669(d)-1A - Total taxes deemed distributed.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Total taxes deemed distributed. 1.669(d)-1A Section 1.669(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 §...

  18. 26 CFR 1.665(d)-1A - Taxes imposed on the trust.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Taxes imposed on the trust. 1.665(d)-1A Section... TAX (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(d)-1A Taxes imposed on the trust. (a) In general. (1)...

  19. 26 CFR 1.665(d)-1 - Taxes imposed on the trust.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Taxes imposed on the trust. 1.665(d)-1 Section 1... (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 § 1.665(d)-1 Taxes imposed on the trust. (a) For the purpose of subpart D...

  20. Dissociable hippocampal and amygdalar D1-like receptor contribution to discriminated Pavlovian conditioned approach learning.

    Science.gov (United States)

    Andrzejewski, Matthew E; Ryals, Curtis

    2016-02-15

    Pavlovian conditioning is an elementary form of reward-related behavioral adaptation. The mesolimbic dopamine system is widely considered to mediate critical aspects of reward-related learning. For example, initial acquisition of positively-reinforced operant behavior requires dopamine (DA) D1 receptor (D1R) activation in the basolateral amygdala (BLA), central nucleus of the amygdala (CeA), and the ventral subiculum (vSUB). However, the role of D1R activation in these areas on appetitive, non-drug-related, Pavlovian learning is not currently known. In separate experiments, microinfusions of the D1-like receptor antagonist SCH-23390 (3.0 nmol/0.5 μL per side) into the amygdala and subiculum preceded discriminated Pavlovian conditioned approach (dPCA) training sessions. D1-like antagonism in all three structures impaired the acquisition of discriminated approach, but had no effect on performance after conditioning was asymptotic. Moreover, dissociable effects of D1-like antagonism in the three structures on components of discriminated responding were obtained. Lastly, the lack of latent inhibition in drug-treated groups may elucidate the role of D1-like in reward-related Pavlovian conditioning. The present data suggest a role for the D1 receptors in the amygdala and hippocampus in learning the significance of conditional stimuli, but not in the expression of conditional responses.

  1. New cis-regulatory elements in the Rht-D1b locus region of wheat

    Science.gov (United States)

    Fifteen gene-containing BACs with accumulated length of 1.82-Mb from the Rht-D1b locus region weresequenced and compared in detail with the orthologous regions of rice, sorghum, and maize. Our results show that Rht-D1b represents a conserved genomic region as implied by high gene sequence identity...

  2. Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies.

    NARCIS (Netherlands)

    Roodink, I.; Verrijp, K.; Raats, J.; Leenders, W.P.J.

    2009-01-01

    BACKGROUND: Plexin D1 is expressed on both tumor-associated endothelium and malignant cells in a number of clinical brain tumors. Recently we demonstrated that Plexin D1 expression is correlated with tumor invasion level and metastasis in a human melanoma progression series. The objective of this st

  3. Translokin (Cep57) interacts with cyclin D1 and prevents its nuclear accumulation in quiescent fibroblasts.

    Science.gov (United States)

    Ruiz-Miró, Maria; Colomina, Neus; Fernández, Rita M H; Garí, Eloi; Gallego, Carme; Aldea, Martí

    2011-05-01

    Nuclear accumulation of cyclin D1 because of altered trafficking or degradation is thought to contribute directly to neoplastic transformation and growth. Mechanisms of cyclin D1 localization in S phase have been studied in detail, but its control during exit from the cell cycle and quiescence is poorly understood. Here we report that translokin (Tlk), a microtubule-associated protein also termed Cep57, interacts with cyclin D1 and controls its nucleocytoplasmic distribution in quiescent cells. Tlk binds to regions of cyclin D1 also involved in binding to cyclin-dependent kinase 4 (Cdk4), and a fraction of cyclin D1 associates to the juxtanuclear Tlk network in the cell. Downregulation of Tlk levels results in undue nuclear accumulation of cyclin D1 and increased Cdk4-dependent phosphorylation of pRB under quiescence conditions. In turn, overexpression of Tlk prevents proper cyclin D1 accumulation in the nucleus of proliferating cells in an interaction-dependent manner, inhibits Cdk4-dependent phosphorylation of pRB and hinders cell cycle progression to S phase. We propose that the Tlk acts as a key negative regulator in the pathway that drives nuclear import of cyclin D1, thus contributing to prevent pRB inactivation and to maintain cellular quiescence.

  4. Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration

    Directory of Open Access Journals (Sweden)

    Kim KH

    2016-05-01

    Full Text Available Kang-Hyun Kim,1 Tai Sun Park,2,3 You-Sun Kim,1,3 Jae Seung Lee,2,3 Yeon-Mok Oh,2,3 Sang-Do Lee,2,3 Sei Won Lee2,3 1Asan Institute for Life Sciences, 2Department of Pulmonology and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, 3Department of Pulmonology and Critical Care Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea Purpose: Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1, derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration.Materials and methods: C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid.Results: Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking.Conclusion: RvD1

  5. Analysis of the interaction proteins of PIH1D1%与PIH1D1相互作用的蛋白分析

    Institute of Scientific and Technical Information of China (English)

    章元; 张业

    2016-01-01

    目的 分析细胞中与PIH1D1相互作用的蛋白.方法 构建稳定表达FLAG-HA双标签标记的PIH1D1蛋白的HEK293T细胞株,利用FLAG-HA串联亲和纯化(TAP)双标签纯化实验,对目的条带进行质谱分析.结果 成功构建稳定表达FLAG-HA双标签标记的PIH1D1细胞株.通过质谱分析得到了PIH1D1相互作用的蛋白数据,包括细胞质内RNA PolⅡ组装复合物成员RPAP3、UXT、PFD2和PFD6等,凋亡复合物成员MONAD/WDR92等,钙调蛋白信号通路中的PIP和CALM1以及代谢通路中的PKM和LCN1等.结论 PIH1D1与细胞中RPAP3、UXT、PFD2、PFD6、MONAD/WDR92、PIP、CALM1、PKM和LCN1等相互作用,提示PIH1D1可能参与细胞中RNApol Ⅱ组装、细胞凋亡、钙调蛋白通路等多种生理过程.

  6. NeuroD1: developmental expression and regulated genes in the rodent pineal gland

    DEFF Research Database (Denmark)

    Muñoz, Estela M; Bailey, Michael J; Rath, Martin F;

    2007-01-01

    NeuroD1/BETA2, a member of the bHLH transcription factor family, is known to influence the fate of specific neuronal, endocrine and retinal cells. We report here that NeuroD1 mRNA is highly abundant in the developing and adult rat pineal gland. Pineal expression begins in the 17-day embryo at which...... time it is also detectable in other brain regions. Expression in the pineal gland increases during the embryonic period and is maintained thereafter at levels equivalent to those found in the cerebellum and retina. In contrast, NeuroD1 mRNA decreases markedly in non-cerebellar brain regions during...... development. Pineal NeuroD1 levels are similar during the day and night, and do not appear to be influenced by sympathetic neural input. Gene expression analysis of the pineal glands from neonatal NeuroD1 knockout mice identifies 127 transcripts that are down-regulated (>twofold, p

  7. Cyclin D1 in the Liver: Role of Noncanonical Signaling in Liver Steatosis and Hormone Regulation

    Science.gov (United States)

    Núñez, Kelley G.; Gonzalez-Rosario, Janet; Thevenot, Paul T.; Cohen, Ari J.

    2017-01-01

    Background: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. Methods: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation. In this article, we review the results from this literature search, with a focus on the role of Cyclin D1 in hepatic lipogenesis and gluconeogenesis, as well as the impact and function of this protein in hepatic steatosis. Results: Cyclin D1 represses carbohydrate response element binding protein (ChREBP) and results in a decrease in transcription of fatty acid synthase (FAS) and acetyl-coenzyme A carboxylase (ACC). Cyclin D1 also inhibits peroxisome proliferator-activated receptor gamma (PPARγ) which is involved in hepatic lipogenesis. Cyclin D1 inhibits both hepatocyte nuclear factor 4 alpha (HNF4α) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) and represses transcription of lipogenic genes FAS and liver-type pyruvate kinase (Pklr), along with the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Conclusion: Cyclin D1 represses multiple proteins involved in both lipogenesis and gluconeogenesis in the liver. Targeting Cyclin D1 to decrease hepatic steatosis in patients with nonalcoholic fatty liver disease or alcoholic fatty liver disease may help improve patient health and the quality of the donor liver pool.

  8. The role of MyoD1 and histone modifications in the activation of muscle enhancers.

    Science.gov (United States)

    Blum, Roy; Dynlacht, Brian D

    2013-08-01

    MyoD1 is a key regulator that orchestrates skeletal muscle differentiation through the regulation of gene expression. Although many studies have focused on its role in transcriptional control at gene promoters, less is known regarding the role of MyoD1 in the assembly of active enhancers. Here, we discuss novel data that point to the ability of MyoD1 to mediate the assembly of active enhancers that augment the transcription of genes essential for muscle development and lineage specification. Based on genome-wide studies of epigenetic marks that typify active enhancers, we recently identified the compendium of distal regulatory elements that dictate transcriptional programs during myogenesis. Superimposition of MyoD1 binding sites upon the locations of muscle enhancers revealed its unequivocal binding to a core region of nearly a third of condition-specific muscle enhancers. Further studies exploring deposition of enhancer-related epigenetic marks in myoblasts lacking MyoD1 demonstrate the dependence of muscle enhancer assembly on the presence of MyoD1. We propose a model wherein MyoD1 mediates recruitment of Set7, H3K4me1, H3K27ac, p300, and RNAP II to MyoD1-bound enhancers to establish condition-specific activation of muscle genes. Moreover, muscle enhancers are modulated through coordinated binding of transcription factors, including c-Jun, Jdp2, Meis, and Runx1, which are recruited to muscle enhancers in a MyoD1-dependent manner. Thus, MyoD1 and enhancer-associated transcription factors function coordinately to assemble and regulate enhancers, thereby augmenting expression of muscle-related genes.

  9. 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

    Science.gov (United States)

    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

  10. D1多巴胺受体与原发性高血压%D1 Dopamine Receptor and Essential Hypertension

    Institute of Scientific and Technical Information of China (English)

    李震; 曾春雨; 杨成明

    2006-01-01

    多巴胺可通过对肾脏水钠重吸收的调节作用,进而发挥对血压调控的影响,多巴胺功能障碍在原发性高血压发生过程中发挥重要的作用.在多巴胺受体的5个亚型中,D1受体的作用尤其引人注目.在体内钠负荷过载的情况下,刺激肾脏D1受体可调节超过50%的钠排量.原发性高血压状态下D1受体功能障碍,其发生的原因与D1 受体/G蛋白效应物复合体失偶联有关,而其失偶联的机制归因于G蛋白激酶4变异体存在所引起的G蛋白激酶活性增高.

  11. Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Ning Wang

    2016-11-01

    Full Text Available The aim of this study is to explore the underlying mechanism on berberine-induced Cyclin D1 degradation in human hepatic carcinoma. We observed that berberine could suppress both in vitro and in vivo expression of Cyclin D1 in hepatoma cells. Berberine exhibits dose- and time-dependent inhibition on Cyclin D1 expression in human hepatoma cell HepG2. Berberine increases the phosphorylation of Cyclin D1 at Thr286 site and potentiates Cyclin D1 nuclear export to cytoplasm for proteasomal degradation. In addition, berberine recruits the Skp, Cullin, F-box containing complex-β-Transducin Repeat Containing Protein (SCFβ-TrCP complex to facilitate Cyclin D1 ubiquitin-proteasome dependent proteolysis. Knockdown of β-TrCP blocks Cyclin D1 turnover induced by berberine; blocking the protein degradation induced by berberine in HepG2 cells increases tumor cell resistance to berberine. Our results shed light on berberine′s potential as an anti-tumor agent for clinical cancer therapy.

  12. Defective renal dopamine D1 receptor function contributes to hyperinsulinemia-mediated hypertension.

    Science.gov (United States)

    Ahmad Banday, Anees; Lokhandwala, Mustafa F

    2006-11-01

    Hyperinsulinemia is reported to play a role in hypertension, as abnormalities in blood pressure regulation and sodium handling exist in diabetes mellitus. Kidney dopamine promotes sodium excretion via the activation of renal D1 receptors. Because there is a close relationship between renal D1 receptor function and sodium excretion, it is hypothesized that a defect in this mechanism may contribute to decreased sodium excretion and hypertension during hyperinsulinemia. Renal D1 receptor function was studied in insulin-induced hypertension in male Sprague Dawley rats. Insulin pellets were implanted subcutaneously for controlled insulin release for three weeks; sham rats served as a control. Compared to control rats, insulin pellets increased plasma insulin levels by eight fold and decreased blood glucose by 40%. Insulin also caused a 22 mmHg increase in mean arterial blood pressure compared to control animals. The intravenous infusion of SKF-38393, a D1 receptor agonist, increased sodium excretion in control rats, but SKF-38393 failed to produce natriuresis in hyperinsulinemic animals. Renal proximal tubules from hyperinsulinemic rats had a reduced D1 receptor number, defective receptor-G protein coupling, and blunted SKF-38393 induced Na, K-ATPase inhibition. Insulin seems to reduce D1 receptor expression and coupling to the G-protein, leading to a reduced D1 receptor-mediated Na, K-ATPase inhibition, and a diminished natriuretic response to SKF-38393. These phenomena could account for sodium retention and hypertension associated with hyperinsulinemia.

  13. COMBINED DETECTION OF CYCLIN D1, P27 AND DNA CONTENT IN ESOPHAGEAL CANCER

    Institute of Scientific and Technical Information of China (English)

    MA Ping; YIN Yuan-qin; WANG Xiao-hua

    2006-01-01

    Objective: To investigate the expressions of cyclin D1 and p27 and DNA content in esophageal cancer and adjacent normal tissues, and to discuss the relationship between them. Methods: The cyclinD1 and p27 were detected by immunohistochemical staining; DNA content was measured by flow cytometry. Results: The positive expression rates of cyclinD1 and p27 in cancer were 45.8% and 33.3% respectively, the DNA content in the positive group of cyclinD1 was higher than that in the negative group of cyclinD1(1.54(0.21 versus 1.08(0.43, P<0.05), while the DNA content and SPF (S-phase fraction) in the positive group of p27 were lower than those in the negative group (1.10(0.19 and 5.56%(5.18% versus 1.66(0.28 and 19.78%(6.12%, P<0.05). Conclusion: The data show that the expression of cyclinD1 and p27 are related to the ontogenesis and progression of esophageal cancer. The combined detection of cyclinD1, p27 and DNA content may be indicators of diagnosis and assessment of esophageal cancer.

  14. Design, synthesis and biological evaluation of bivalent ligands against A1-D1 receptor heteromers

    Institute of Scientific and Technical Information of China (English)

    Jian SHEN; Lei ZHANG; Wan-ling SONG; Tao MENG; Xin WANG; Lin CHEN; Lin-yin FENG

    2013-01-01

    Aim:To design and synthesize bivalent ligands for adenosine A1-dopamine D1 receptor heteromers (A1-D1R),and evaluate their pharmacological activities.Methods:Bivalent ligands and their corresponding A1R monovalent ligands were designed and synthesized.The affinities of the bivalent ligands for A1R and D1R in rat brain membrane preparation were examined using radiolabeled binding assays.To demonstrate the formation of A1-D1R,fluorescence resonance energy transfer (FRET) was conducted in HEK293 cells transfected with D1-CFP and A1-YFP.Molecular modeling was used to analyze the possible mode of protein-protein and protein-ligand interactions.Results:Two bivalent ligands for A1R and D1R (20a,20b),as well as the corresponding A1R monovalent ligands (21a,21b) were synthesized.In radiolabeled binding assays,the bivalent ligands showed affinities for A1R 10-100 times higher than those of the corresponding monovalent ligands.In FRET experiments,the bivalent ligands significantly increased the heterodimerization of A1R and D1R compared with the corresponding monovalent ligands.A heterodimer model with the interface of helixes 3,4,5 of A1R and helixes 1,6,7 from D1R was established with molecular modeling.The distance between the two ligand binding sites in the heterodimer model was approximately 48.4 (A),which was shorter than the length of the bivalent ligands.Conclusion:This study demonstrates the existence of A1-D1R in situ and a simultaneous interaction of bivalent ligands with both the receptors.

  15. Induction of excitatory and inhibitory presynaptic differentiation by GluD1.

    Science.gov (United States)

    Ryu, Kyounghee; Yokoyama, Marie; Yamashita, Manami; Hirano, Tomoo

    2012-01-06

    The δ subfamily of ionotropic glutamate receptor subunits consists of GluD1 and GluD2. GluD2, which is selectively expressed in cerebellar Purkinje neurons, has been shown to contribute to the formation of synapses between granule neurons and Purkinje neurons through interaction with Cbln1 (cerebellin precursor protein1) and presynaptic Neurexin. On the other hand, the synaptogenic activity of GluD1, which is expressed not in the cerebellum but in the hippocampus, remains to be characterized. Here, we report that GluD1 expressed in non-neuronal HEK cells, induced presynaptic differentiation of granule neurons through its N-terminal domain in co-cultures with cerebellar neurons, similarly to GluD2. We also show that GluD1 rescued the defect of synapse formation in GluD2-knockout Purkinje neurons, indicating the functional similarity of GluD1 and GluD2. In contrast, GluD1 expression alone did not induce presynaptic differentiation in co-cultures of HEK cells with hippocampal neurons. However, when Cbln1 was exogenously added to the culture medium, GluD1 induced presynaptic differentiation of not only glutamatergic presynaptic terminals but also GABAergic ones. Cbln1 is not expressed in hippocampal neurons but is expressed in entorhinal cortical neurons projecting to the hippocampus. In co-cultures of HEK cells expressing GluD1 and entorhinal cortical neurons, both glutamatergic and GABAergic presynaptic terminals were formed on the HEK cells without exogenous application of Cbln1. These results suggest that GluD1 might contribute to the formation of specific synapses in the hippocampus such as those formed by the projecting neurons of the entorhinal cortex.

  16. Prenatal lipopolysaccharide exposure results in dysfunction of the renal dopamine D1 receptor in offspring.

    Science.gov (United States)

    Wang, Xinquan; Luo, Hao; Chen, Caiyu; Chen, Ken; Wang, Jialiang; Cai, Yue; Zheng, Shuo; Yang, Xiaoli; Zhou, Lin; Jose, Pedro A; Zeng, Chunyu

    2014-11-01

    Adverse environment in early life can modulate the adult phenotype, including blood pressure. Lipopolysaccharide (LPS) exposure in utero results in increased blood pressure in the offspring, but the exact mechanisms are not clear. Studies have shown that the renal dopamine D1 receptor (D1R) plays an important role in maintaining sodium homeostasis and normal blood pressure; dysfunction of D1R is associated with oxidative stress and hypertension. In this study, we determined if dysfunction of the renal D1R is involved in fetal-programmed hypertension, and if oxidative stress contributes to this process. Pregnant Sprague-Dawley (SD) rats were intraperitoneally injected with LPS (0.79 mg/kg) or saline at gestation days 8, 10, and 12. As compared with saline-injected (control) dams, offspring of LPS-treated dams had increased blood pressure, decreased renal sodium excretion, and increased markers of oxidative stress. In addition, offspring of LPS-treated dams had decreased renal D1R expression, increased D1R phosphorylation, and G protein-coupled receptor kinase type 2 (GRK2) and type 4 (GRK4) protein expression, and impaired D1R-mediated natriuresis and diuresis. All of the findings in the offspring of LPS-treated dams were normalized after treatment with TEMPOL, an oxygen free radical scavenger. In conclusion, prenatal LPS exposure, via an increase in oxidative stress, impairs renal D1R function and leads to hypertension in the offspring. Normalization of renal D1R function by amelioration of oxidative stress may be a therapeutic target of fetal programming of hypertension.

  17. Cyclin D1 represses gluconeogenesis via inhibition of the transcriptional coactivator PGC1α.

    Science.gov (United States)

    Bhalla, Kavita; Liu, Wan-Ju; Thompson, Keyata; Anders, Lars; Devarakonda, Srikripa; Dewi, Ruby; Buckley, Stephanie; Hwang, Bor-Jang; Polster, Brian; Dorsey, Susan G; Sun, Yezhou; Sicinski, Piotr; Girnun, Geoffrey D

    2014-10-01

    Hepatic gluconeogenesis is crucial to maintain normal blood glucose during periods of nutrient deprivation. Gluconeogenesis is controlled at multiple levels by a variety of signal transduction and transcriptional pathways. However, dysregulation of these pathways leads to hyperglycemia and type 2 diabetes. While the effects of various signaling pathways on gluconeogenesis are well established, the downstream signaling events repressing gluconeogenic gene expression are not as well understood. The cell-cycle regulator cyclin D1 is expressed in the liver, despite the liver being a quiescent tissue. The most well-studied function of cyclin D1 is activation of cyclin-dependent kinase 4 (CDK4), promoting progression of the cell cycle. We show here a novel role for cyclin D1 as a regulator of gluconeogenic and oxidative phosphorylation (OxPhos) gene expression. In mice, fasting decreases liver cyclin D1 expression, while refeeding induces cyclin D1 expression. Inhibition of CDK4 enhances the gluconeogenic gene expression, whereas cyclin D1-mediated activation of CDK4 represses the gluconeogenic gene-expression program in vitro and in vivo. Importantly, we show that cyclin D1 represses gluconeogenesis and OxPhos in part via inhibition of peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) activity in a CDK4-dependent manner. Indeed, we demonstrate that PGC1α is novel cyclin D1/CDK4 substrate. These studies reveal a novel role for cyclin D1 on metabolism via PGC1α and reveal a potential link between cell-cycle regulation and metabolic control of glucose homeostasis.

  18. Gastrin and D1 dopamine receptor interact to induce natriuresis and diuresis.

    Science.gov (United States)

    Chen, Yue; Asico, Laureano D; Zheng, Shuo; Villar, Van Anthony M; He, Duofen; Zhou, Lin; Zeng, Chunyu; Jose, Pedro A

    2013-11-01

    Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl. Gastrin is the major gastrointestinal hormone taken up by renal proximal tubule (RPT) cells. We hypothesized that renal gastrin and dopamine receptors interact to synergistically increase sodium excretion, an impaired interaction of which may be involved in the pathogenesis of hypertension. In Wistar-Kyoto rats, infusion of gastrin induced natriuresis and diuresis, which was abrogated in the presence of a gastrin (cholecystokinin B receptor [CCKBR]; CI-988) or a D1-like receptor antagonist (SCH23390). Similarly, the natriuretic and diuretic effects of fenoldopam, a D1-like receptor agonist, were blocked by SCH23390, as well as by CI-988. However, the natriuretic effects of gastrin and fenoldopam were not observed in spontaneously hypertensive rats. The gastrin/D1-like receptor interaction was also confirmed in RPT cells. In RPT cells from Wistar-Kyoto but not spontaneously hypertensive rats, stimulation of either D1-like receptor or gastrin receptor inhibited Na(+)-K(+)-ATPase activity, an effect that was blocked in the presence of SCH23390 or CI-988. In RPT cells from Wistar-Kyoto and spontaneously hypertensive rats, CCKBR and D1 receptor coimmunoprecipitated, which was increased after stimulation of either D1 receptor or CCKBR in RPT cells from Wistar-Kyoto rats; stimulation of one receptor increased the RPT cell membrane expression of the other receptor, effects that were not observed in spontaneously hypertensive rats. These data suggest that there is a synergism between CCKBR and D1-like receptors to increase sodium excretion. An aberrant interaction between the renal CCK BR and D1-like receptors (eg, D1 receptor) may play a role in the pathogenesis of hypertension.

  19. Role of CyclinD1 and CDK4 in the Carcinogenesis Induced by Silica

    Institute of Scientific and Technical Information of China (English)

    KE-XIA YAN; BING-CI LIU; XIANG-LIN SHI; BAO-RONG YOU; MING XU

    2005-01-01

    Objective To study the role of cyclinD1 and CDK4 in malignant transformation of human fetal lung diploid fibroblast cell line(2BS) induced by silica. Methods Recombination vectors with sense and antisense pXJ41-cyclinD1 and pXJ41-CDK4 were constructed, and then transfected into the malignant transformed cells induced by silica, respectively. At the same time, pXJ41-neo was used as the control. Results During the progress of the malignant transformation of 2BS cells induced by silica, cyclinD1 and CDK4 were overexpressed. Antisense RNA suppressed cyclinD1 and CDK4 gene expression in the antisense pXJ41-cyclinD1 and pXJ41-CDK4 transfected cells. Antisense RNA led to cell cycle arrest, resulting in lengthened G1 phase (the percentages of cells in the G1 phase changed from 45.1% to 52.7% and 58.0% for cyclinD1 and CDK4 transfected cells, respectively), and eventually attenuated the increase of the proliferation of malignant transformed cells induced by silica. Compared with malignant transformed cells induced by silica, cells transfected with antisense pXJ41-cyclinD1 and pXJ41-CDK4 showed obviously reduced growth rates. On the 8th day, the suppression rates were 58.69 and 77.43% (the growth rate of malignant transformed cells induced by silica was 100%), doubling time changed from 21.0 h to 31.4 h and 21.0 h to 42.7 h, respectively, the growth capacities on soft agar of cells transfected by antisense pXJ41-cyclinD1 and pXJ41-CDK4 decreased obviously. Conclusion CyclinD1 and CDK4 play an important role in maintaining transformed phenotype of the cancer cells.

  20. [Recombination frequency in the locus Gli-D1 of common wheat T. aestivum L].

    Science.gov (United States)

    Kozub, N A; Sozinov, I A; Sozinov, A A

    2003-01-01

    The recombination frequency at the gliadin locus Gli-D1 of common wheat was determined by the maximum likelihood method. Recombination was observed between the gene encoding the fastest omega-component of the allele Gli-D1j, and the genes encoding the other omega-gliadins of this allele. The frequency of recombination was 0.65 +/- 0.18% for the cross between the near-isogenic lines of winter common wheat with respect to gliadin loci Gli-D1-4 and Gli-B1-3 and 0.78 +/- 0.45% for the cross between the varieties Yunnat and B-16.

  1. Discovery of new SCH 39166 analogs as potent and selective dopamine D1 receptor antagonists.

    Science.gov (United States)

    Qiang, Li; Sasikumar, T K; Burnett, Duane A; Su, Jing; Tang, Haiqun; Ye, Yuanzan; Mazzola, Robert D; Zhu, Zhaoning; McKittrick, Brian A; Greenlee, William J; Fawzi, Ahmad; Smith, Michelle; Zhang, Hongtao; Lachowicz, Jean E

    2010-02-01

    A series of novel dopamine D(1) antagonists derived from functionalization of the D-ring of SCH 39166 were prepared. A number of these compounds displayed subnanomolar D(1) activity and more than 1000-fold selectivity over D(2). We found C-3 derivatization afforded compounds with superior overall profile in comparison to the C-2 and C-4 derivatization. A number of highly potent D(1) antagonists were discovered which have excellent selectivity over other dopamine receptors and improved PK profile compared to SCH 39166.

  2. Synthesis and herbicidal evaluation of novel benzothiazole derivatives as potential inhibitors of D1 protease.

    Science.gov (United States)

    Huang, Tonghui; Sun, Jie; An, Lin; Zhang, Lixian; Han, Cuiping

    2016-04-01

    D1 protease is a C-terminal processing protease that has been predicted to be an ideal herbicidal target. Three novel series of benzothiazole derivatives were synthesized and evaluated for their herbicidal activities against Brassica napus (rape) and Echinochloa crusgalli (barnyard grass). The preliminary bioassay indicated that most of the synthesized compounds possess promising D1 protease inhibitory activities and considerable herbicidal activities. Molecular docking was performed to position representative compounds into the active site of D1 protease to determine a probable binding model.

  3. Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance

    Directory of Open Access Journals (Sweden)

    Hasbi Ahmed

    2011-06-01

    Full Text Available Abstract Dopamine is an important catecholamine neurotransmitter modulating many physiological functions, and is linked to psychopathology of many diseases such as schizophrenia and drug addiction. Dopamine D1 and D2 receptors are the most abundant dopaminergic receptors in the striatum, and although a clear segregation between the pathways expressing these two receptors has been reported in certain subregions, the presence of D1-D2 receptor heteromers within a unique subset of neurons, forming a novel signaling transducing functional entity has been shown. Recently, significant progress has been made in elucidating the signaling pathways activated by the D1-D2 receptor heteromer and their potential physiological relevance.

  4. APOLLON. Multi-APprOach for high efficiency integrated and inteLLigent cONcentrating PV modules (Systems). Deliverable 7.10. Publication of environmental LCI dataset

    Energy Technology Data Exchange (ETDEWEB)

    Olson, C.L. [ECN Solar Energy, Petten (Netherlands)

    2013-10-15

    This deliverable makes available the life-cycle inventory used to calculate the energy payback time and the carbon footprint of the Apollon final concentrating photovoltaics (CPV) design developed.. The data below relates to one Apollon module. The results are to be published in Environmental Science and Technology, in a paper, 'Sustainability of Materials and Costs of Materials in a Mirror-based Concentrating Photovoltaic System'. Reference is made to the results for the Spectrolab triple junction solar cell in the following two studies: (1) 'Life cycle assessment of high-concentration photovoltaic systems' (Prog. Photovolt: Res. Appl., vol. 21, pp. 379-388, 2013), and (2) 'Life Cycle Analysis of Two New Concentrator PV Systems', in 23rd European Photovoltaic Solar Energy Conference, Valencia, Spain, 2008.

  5. In-vehicle and site-based observations of vehicles and cyclists : a small-scale ND study in The Netherlands. PROmoting real Life Observations for Gaining Understanding of road user behaviour in Europe PROLOGUE, Deliverable D3.4

    NARCIS (Netherlands)

    Christoph, M. Nes, N. van Pauwelussen, J. Mansvelders, R. Horst, A.R.A. van der & Hoedemaeker, M.

    2011-01-01

    The main objective of the project PROLOGUE (PROmoting real Life Observations for Gaining Understanding of road user behaviour in Europe) is to explore the feasibility and usefulness of a large-scale European naturalistic driving observation study. The work described in this deliverable focused on th

  6. The new powder diffractometer D1B of the Institut Laue Langevin

    Science.gov (United States)

    Puente Orench, I.; Clergeau, J. F.; Martínez, S.; Olmos, M.; Fabelo, O.; Campo, J.

    2014-11-01

    D1B is a medium resolution high flux powder diffractometer located at the Institut Laue Langevin, ILL. D1B a suitable instrument for studying a large variety of polycrystalline materials. D1B runs since 1998 as a CRG (collaborating research group) instrument, being exploited by the CNRS (Centre National de la Recherche Scientifique, France) and CSIC (Consejo Superior de Investigaciones Cientificas, Spain). In 2008 the Spanish CRG started an updating program which included a new detector and a radial oscillating collimator (ROC). The detector, which has a sensitive height of 100mm, covers an angular range of 128°. Its 1280 gold wires provide a neutron detection point every 0.1°. The ROC is made of 198 gadolinium- based absorbing collimation blades, regular placed every 0.67°. Here the present characteristics of D1B are reviewed and the different experimental performances will be presented.

  7. Inhibition of GSK3 attenuates dopamine D1 receptor agonist-induced hyperactivity in mice.

    Science.gov (United States)

    Miller, Jonathan S; Tallarida, Ronald J; Unterwald, Ellen M

    2010-05-31

    Recent evidence suggests a critical role for the intracellular signaling protein glycogen synthase kinase-3 (GSK3) in hyperactivity associated with dopaminergic transmission. Here, we investigated whether activation of GSK3 is necessary for the expression of behaviors specifically produced by dopamine D1 receptor activation. To assess the role of GSK3 in dopamine D1 receptor-induced hyperactivity, mice were pretreated with the selective GSK3 inhibitor SB 216763 (0.25-7.5mg/kg, i.p.) or its vehicle prior to administration of the dopamine D1 receptor full-agonist SKF-82958 (1.0mg/kg, i.p.) or saline control. Inhibition of GSK3 via SB 216763 dose-dependently reduced ambulatory and stereotypic activity produced by SKF-82958. These data implicate a role for GSK3 in the behavioral manifestations associated with dopamine D1 receptor activation.

  8. Microstates of D1–D5(-P black holes, as interacting D-branes

    Directory of Open Access Journals (Sweden)

    Takeshi Morita

    2015-07-01

    Full Text Available In our previous study (Morita et al., 2014 [1], we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal. We test this proposal in the near-extremal D1–D5 and D1–D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves. It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1–D5(-P black holes in superstring theory.

  9. Microstates of D1-D5(-P) black holes as interacting D-branes

    CERN Document Server

    Morita, Takeshi

    2014-01-01

    In our previous study [1] (1311.6540), we figured out that the thermodynamics of the near extremal black $p$-branes can be explained as the collective motions of gravitationally interacting elementary $p$-branes (the $p$-soup proposal). We test this proposal in the near-extremal D1-D5 and D1-D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves). It may imply that the microscopic origins of these intersecting black branes and the black $p$-brane are explained in the unified picture. We also argue the relation between the $p$-soup proposal and the conformal field theory calculations of the D1-D5(-P) black holes in superstring theory.

  10. Microstates of D1-D5(-P) black holes, as interacting D-branes

    Science.gov (United States)

    Morita, Takeshi; Shiba, Shotaro

    2015-07-01

    In our previous study (Morita et al., 2014 [1]), we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal). We test this proposal in the near-extremal D1-D5 and D1-D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves). It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1-D5(-P) black holes in superstring theory.

  11. Microstates of D1–D5(-P) black holes, as interacting D-branes

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Takeshi, E-mail: morita.takeshi@shizuoka.ac.jp [Department of Physics, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529 (Japan); Shiba, Shotaro, E-mail: sshiba@cc.kyoto-su.ac.jp [Maskawa Institute for Science and Culture, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555 (Japan)

    2015-07-30

    In our previous study (Morita et al., 2014 [1]), we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal). We test this proposal in the near-extremal D1–D5 and D1–D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves). It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1–D5(-P) black holes in superstring theory.

  12. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  13. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  14. Mechanisms for Antagonistic Regulation of AMPA and NMDA-D1 Receptor Complexes at Postsynaptic Sites

    Science.gov (United States)

    Schumann, Johann; Scheler, Gabriele

    2004-01-01

    From the analysis of these pathways we conclude that postsynaptic processes that regulate synaptic transmission undergo significant cross-talk with respect to glutamatergic and neuromodulatory (dopamine) signals. The main hypothesis is that of a compensatory regulation, a competitive switch between the induction of increased AMPA conductance by CaMKII-dependent phosphorylation and reduced expression of PP2A, and increased D1 receptor sensitivity and expression by increased PKA, PP2A and decreased PP-1/calcineurin expression. Both types of plasticity are induced by NMDA receptor activation and increased internal calcium, they require different internal conditions to become expressed. Specifically we propose that AMPA regulation and D1 regulation are inversely coupled;The net result may be a bifurcation of synaptic state into predominantly AMPA or NMDA-D1 synapses. This could have functional consequences: stable connections for AMPA and conditional gating for NMDA-D1 synapses.

  15. 多巴胺D1受体在Sf9昆虫细胞中的表达及左旋氯代斯阔任对重组D1受体的激动作用%Expression of dopamine D1 receptor in Sf9 insect cells and agonism ofl-12-chloroscoulerine on recombinant D1 receptor

    Institute of Scientific and Technical Information of China (English)

    和友; 金文桥; 申庆祥; 陈新建; 金国章

    2003-01-01

    目的:在Sf9昆虫细胞中表达D1受体,并研究左旋氯代斯阔任对重组D1受体的激动作用.方法:构建含D1受体cDNA的重组杆状病毒,以其感染Sf9昆虫细胞得到D1受体表达.[3H]SCH23390受体结合检测重组D1受体的药理特性.[3H]SCH23390受体结合和cAMP测定实验检测左旋氯代斯阔任对重组D1受体的激动作用.结果:在Sf9昆虫细胞中成功表达D1受体,[3H]SCH23390与重组D1受体最大结合量(Bmax)为(0.94±0.06)nmol/g蛋白,[3H]SCH23390与重组D1受体的结合解离常数(Kd)为(1.9±0.3)nmol/L,其药理特性与小牛纹状体脑匀浆所得结果一致.左旋氯代斯阔任对重组D1受体有高亲和力,解离常数Ki为(6.3±1.4)nmol/L;并剂量依赖地引起胞内cAMP增加,EC50为0.72μmol/L(95%可信限为0.67-0.77 μmol/L),表现出D1激动作用.结论:在杆状病毒/昆虫细胞Sf9中,成功建立了D1受体异源表达系统.在细胞分子水平,直接证实了左旋氯代斯阔任对D1受体的激动作用.%AIM: To express dopamine D1 receptor in baculovirus-Sf9 cell system, and to investigate the effects ofl-12-chloroscoulerine (l-CSL) on the recombinant D1 receptor (D1R). METHODS: The recombinant baculovirus,Autographa californica nuclear polyhedrosis virus bearing D1R (AcNPV- D1R) was generated, and then was usedto produce recombinant D1R in Sf9 insect cells. Expression of D1R in Sf9 cells was monitored by [3H]SCH23390binding assay. The effects ofl-CSL on recombinant D1R were investigated by [3H]SCH23390 binding assay andcAMP assay. RESULTS: The recombinant baculovirus AcNPV bearing DiR cDNA was generated, and wassuccessfully expressed in Sf9 insect cells. The expression level of (Bmax) was (0.94±0.06) nmol/g protein. The Kdvalue of [3H]SCH23390 was (1.9±0.3) nmol/L, which was consistent with the previous results from calf striutamtissues. l-CSL had a high affinity to recombinant D1R with Ki value of (6.3±1.4) nmol/L, and increased theintracellular cAMP level in a

  16. CyclinD1 and Survivin expression in parotid gland tumors%CyclinD1和Survivin在腮腺肿瘤中的表达

    Institute of Scientific and Technical Information of China (English)

    李云杉

    2014-01-01

    ObjectiveTo explore the cell cycle protein (CyclinD1) and apoptosis inhibiting factor (Survivin) expression in parotid gland tumors in the relationship.MethodsSelect from October 19, 2012 to 2012 on July 19 days the hospital for treatment of 54 patients with parotid gland tumor pathological section. ResultsCyclinD1 in the normal group, benign tumor and malignant tumor group, the positive rate of 5.0%, 25.0% and 70.6%, respectively, expression increased obviously, the difference was statistically significant (P<0.05), Survivin in the normal group, benign tumor and malignant tumor group were 0.0%, 30.0% and 67.6%, respectively, to express obviously increased, the difference was statistically significant (P<0.05). ConclusionCyclinD1 and Survivin in parotid gland tumor development played a synergy, can be used as important reference for diagnosis and treatment of parotid gland.%目的:探究细胞周期蛋白(CyclinD1)和凋亡抑制因子(Survivin)在腮腺肿瘤中的表达关系。方法选取自2012年10月19日~2014年7月19日来我院进行治疗的54例腮腺肿瘤患者的病理切片。结果 CyclinD1在常人组、良性肿瘤组和恶性肿瘤组的阳性率分别为5.0%、25.0%和70.6%,表现明显增高,差异有统计学意义(P<0.05),Survivin在常人组、良性肿瘤组和恶性肿瘤组的阳性率分别为0.0%、30.0%和67.6%,表达明显增高,差异有统计学意义(P<0.05)。结论 CyclinD1与Survivin在腮腺肿瘤的发展中起到了协同作用,可作为腮腺诊治的重要参考依据。

  17. Aberrant D1 and D3 dopamine receptor transregulation in hypertension.

    Science.gov (United States)

    Zeng, Chunyu; Wang, Dan; Asico, Laureano D; Welch, William J; Wilcox, Christopher S; Hopfer, Ulrich; Eisner, Gilbert M; Felder, Robin A; Jose, Pedro A

    2004-03-01

    Dopamine plays a role in the regulation of blood pressure by inhibition of sodium transport in renal proximal tubules (RPTs) and relaxation of vascular smooth muscles. Because dopamine receptors can regulate and interact with each other, we studied the interaction of D(1) and D(3) receptors in immortalized RPT cells and mesenteric arteries from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), and in human coronary artery smooth muscle cells (CASMCs). In WKY rats, the D(1)-like agonist, fenoldopam, increased D(3) receptor protein in a time-dependent and concentration-dependent manner (EC(50)=4.5x10(-9) M, t(1/2)=15.8 hours). In SHRs, fenoldopam (10(-5) M) actually decreased the expression of D(3) receptors. D(1) and D(3) receptor co-immunoprecipitation was increased by fenoldopam (10(-7) M/24 h) in WKY rats but not in SHRs. The effects of fenoldopam in CASMCs were similar as those in WKY RPT cells (ie, fenoldopam increased D(1) and D(3) receptor proteins). Both D(3) (PD128907, Emax=80%+/-6%, pED(50)=5+/-0.1) and D(1)-like receptor (fenoldopam, Emax=81%+/-8%, pED(50)=5+/-0.2, n=12) agonists relaxed mesenteric arterial rings. Co-stimulation of D(1) and D(3) receptors led to additive vasorelaxation in WKY rats, but not in SHRs. D(1) and D(3) receptors interact differently in WKY and SHRs. Altered interactions between D(1) and D(3) receptors may play a role in the pathogenesis of genetic hypertension, including human hypertension, because these receptors also interact in human vascular smooth muscle cells.

  18. Thermodynamics of $(d+1)$-dimensional NUT-charged AdS Spacetimes

    OpenAIRE

    Clarkson, R.; Fatibene, L.; Mann, R. B.

    2002-01-01

    We consider the thermodynamic properties of $(d+1)$-dimensional spacetimes with NUT charges. Such spacetimes are asymptotically locally anti de Sitter (or flat), with non-trivial topology in their spatial sections, and can have fixed point sets of the Euclidean time symmetry that are either $(d-1)$-dimensional (called "bolts") or of lower dimensionality (pure "NUTs"). We compute the free energy, conserved mass, and entropy for 4, 6, 8 and 10 dimensions for each, using both Noether charge meth...

  19. Identification of human dopamine D1-like receptor agonist using a cell-based functional assay

    Institute of Scientific and Technical Information of China (English)

    Nan JIANG; Ke-qing OU-YANG; Shao-xi CAI; Ying-he HU; Zhi-liang XU

    2005-01-01

    Aim: To establish a cell-based assay to screen human dopamine D1 and D5 receptor agonists against compounds from a natural product compound library.Methods: Synthetic responsive elements 6×cAMP response elements (CRE) and a mini promoter containing a TATA box were inserted into the pGL3 basic vector to generate the reporter gene construct pCRE/TA/Luci. CHO cells were co-transfected with the reporter gene construct and human D1 or D5 receptor cDNA in mammalian expression vectors. Stable cell lines were established for agonist screening. A natural product compound library from over 300 herbs has been established. The extracts from these herbs were used for human D1 and D5 receptor agonist screenings. Results: A number of extracts were identified that activated both D1 and D5 receptors. One of the herb extracts, SBG492, demonstrated distinct pharmacological characteristics with human D1 and D5 receptors.The EC50 values of SBG492 were 342.7 μg/mL for the D1 receptor and 31.7 μg/mL for the D5 receptor. Conclusion: We have established a cell-based assay for high-throughput drug screening to identify D 1-like receptor agonists from natural products. Several extracts that can active D1-like receptors were discovered.These compounds could be useful tools for studies on the functions of these receptors in the brain and could potentially be developed into therapeutic drugs for the treatment of central nervous system diseases.

  20. Expression of Cyclin D1 and P16 in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Dey, Biswajit; Raphael, Vandana; Khonglah, Yookarin; GiriLynrah, Kyrshanlang

    2015-10-01

    BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the lethal cancers with a high incidence rate in Asia. Many genes including cyclin D1 and p16 play important role in its carcinogenesis. We aimed to analyze the expressions of cyclin D1 and p16 with the various clinicopathological characteristics of ESCC. METHODS We examined 30 biopsy samples of ESCC for cyclin D1 and p16 protein expressions using immunohistochemistry. Immunointensity was classified as no immunostaining (-), weakly immunostaining (+), weak immunostaining (++) and strongly positive immunostaining (+++). RESULTS Out of the 30 cases, positive expression of cyclin D1 was detected in 26 cases (86.7%). The percentage of tumors with invasion to the adventitia (88.2%), lymph node metastasis (87.5%), and tumors which were poorly differentiated (92.9%) were higher in cyclin D1 positive tumors than in the cyclin D1 negative tumors. However no significant association was found between cyclin D1 expression and the different clinicopathological parameters.There were 22 cases of ESCC (73.3 %) which showed negativity for p16. The percentage of tumors with invasion to the adventitia (82.4%) and poorly differentiated tumors (92.9%) were higher in the p16 negative tumors than in the p16 positive tumors. There was significant association between the histological grade and p16 expression (p=0.012). However, there were no significant association with regard to site, size and lymph node status of the tumors and p16 expression. CONCLUSION The study shows that alterations of cyclin D1 and p16 play an important role in ESCC. Loss of p16 expression was associated with poor differentiation.

  1. A Role for D1 Dopamine Receptors in Striatal Methamphetamine-Induced Neurotoxicity

    OpenAIRE

    Friend, Danielle M.; Keefe, Kristen A

    2013-01-01

    Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 Dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Import...

  2. Expression and significance of cyclin D1, p27kipl protein in bronchioloalveolar carcinoma

    Institute of Scientific and Technical Information of China (English)

    袁键群; 许敬尧; 张静; 何启才; 祝佳; 盛彩霞

    2004-01-01

    Purpose: To investigate the relationship between expression of cell cycle-related protein cyclin D1, p27kipl and the pathogenesis of bronchioloalveolar carcinoma (BAC) and the value of prediction of prognosis. Methods: Cyclin D1 and p27kipl protein were detected by immunohistochemical En Vision method in 43 BACs. Results: The positivity of cyclin D1 in BAC was 65.1% (28/43), which was significantly higher than that in normal pulmonary tissue (0/13), P0.05), while cyclin D1 expression was found to be negatively correlated with tumor size (P0.05), but was negatively correlated with stromal fibrosis, lymph node metastasis and clinical stage (P<0.05); and positively associated with postoperative survival period (P<0.01). The survival rate of p27kipl positive group was significantly higher than that of p27kipl negative group (P<0.01). No statistically significant correlation was found between cyclin D1 and p27kipl expression. Conclusions: Increased cyclin D1 expression and decreased p27kipl expression are related to the pathogenesis of BAC; decreased p27kipl expression is associated with metastasis progression; immunodetection ofp27kipl is useful for assessment of prognosis.

  3. Cyclin D1 Expression and Its Correlation with Histopathological Differentiation in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Swati Saawarn

    2012-01-01

    Full Text Available Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC. Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1. Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation. Conclusion. Cyclin D1 expression significantly increases with increase in differentiation.

  4. (-)-Stepholodine induced enhancement of cardiac muscle contractions mediated by D1 receptors

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shu-yuan; LIU Zheng; HU Hui-sheng; SHI Zhen; CHEN Long

    2008-01-01

    Objective To investigate the effect of (-)-Stepholidine (SPD) on enhancing D1 receptor mediated contraction of cardiac muscle in isolated rat heart and to examine whether SPD has a direct effect on the heart dopamine D1 receptors. SPD an active ingredient of the Chinese herb Stephania intermedia, binds to dopamine D1 and D2 like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1/5) agonist and a D(2/4) antagonist, which could indicate unique antipsychotic properties. Methods Normal adult rat working hearts were isolated by Langendorff technique. Results SPD significantly increased the cardiac muscle contraction in a dose-dependent manner. The selective D1 dopamine receptor antagonist SCH23390 (1 μM) blocked the SPD induced heart contraction, however, neither the β-receptor antagonist propranolol (1 μM) nor the α1-receptor antagonist prazosin (1 μM) had any effect on blocking SPD induced heart contractions. Moreover, the L-type Ca2+ channel inhibitor nimodipine (1 μM) completely blocked the effect of SPD on cardiac muscle contraction. Conclusions SPD show the effect on enhancing contraction of isolated rat heart through activating L-type Ca2+ channel mediated by heart D1 receptors.

  5. A new approach for treatment of hypertension: modifying D1 dopamine receptor function.

    Science.gov (United States)

    Zeng, Chunyu; Felder, Robin A; Jose, Pedro A

    2006-10-01

    Essential hypertension is a major factor for myocardial infarction, heart failure and kidney failure. Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and vasodilatation directly or indirectly with other hormones and humoral factors, such as reactive oxygen species and the renin-angiotensin system. Dopamine receptors are classified into five subtypes based on their structure and pharmacology. Among those dopamine receptor subtypes, D(1) receptor is the most important one, during conditions of moderate sodium intake, more than 50% of renal sodium excretion is regulated by D(1)-like receptors. Decreased renal dopamine production and/or impaired D(1) receptor function have been reported in hypertension. Disruption of D(1) receptor results in hypertension. In this paper, we review the mechanisms by which hypertension develops when D(1) receptor function is perturbed. We also discuss possible new approaches developing anti-hypertensive medicine by increasing renal dopamine production, enhancing D(1) receptor function, or modifying its interactions with other blood pressure-regulating systems.

  6. NeuroD1: developmental expression and regulated genes in the rodent pineal gland.

    Science.gov (United States)

    Muñoz, Estela M; Bailey, Michael J; Rath, Martin F; Shi, Qiong; Morin, Fabrice; Coon, Steven L; Møller, Morten; Klein, David C

    2007-08-01

    NeuroD1/BETA2, a member of the bHLH transcription factor family, is known to influence the fate of specific neuronal, endocrine and retinal cells. We report here that NeuroD1 mRNA is highly abundant in the developing and adult rat pineal gland. Pineal expression begins in the 17-day embryo at which time it is also detectable in other brain regions. Expression in the pineal gland increases during the embryonic period and is maintained thereafter at levels equivalent to those found in the cerebellum and retina. In contrast, NeuroD1 mRNA decreases markedly in non-cerebellar brain regions during development. Pineal NeuroD1 levels are similar during the day and night, and do not appear to be influenced by sympathetic neural input. Gene expression analysis of the pineal glands from neonatal NeuroD1 knockout mice identifies 127 transcripts that are down-regulated (>twofold, p twofold, p < 0.05). According to quantitative RT-PCR, the most dramatically down-regulated gene is kinesin family member 5C ( approximately 100-fold) and the most dramatically up-regulated gene is glutamic acid decarboxylase 1 ( approximately fourfold). Other impacted transcripts encode proteins involved in differentiation, development, signal transduction and trafficking. These findings represent the first step toward elucidating the role of NeuroD1 in the rodent pinealocyte.

  7. Stage-specific requirement for cyclin D1 in glial progenitor cells of the cerebral cortex.

    Science.gov (United States)

    Nobs, Lionel; Baranek, Constanze; Nestel, Sigrun; Kulik, Akos; Kapfhammer, Josef; Nitsch, Cordula; Atanasoski, Suzana

    2014-05-01

    Despite the vast abundance of glial progenitor cells in the mouse brain parenchyma, little is known about the molecular mechanisms driving their proliferation in the adult. Here we unravel a critical role of the G1 cell cycle regulator cyclin D1 in controlling cell division of glial cells in the cortical grey matter. We detect cyclin D1 expression in Olig2-immunopositive (Olig2+) oligodendrocyte progenitor cells, as well as in Iba1+ microglia and S100β+ astrocytes in cortices of 3-month-old mice. Analysis of cyclin D1-deficient mice reveals a cell and stage-specific molecular control of cell cycle progression in the various glial lineages. While proliferation of fast dividing Olig2+ cells at early postnatal stages becomes gradually dependent on cyclin D1, this particular G1 regulator is strictly required for the slow divisions of Olig2+/NG2+ oligodendrocyte progenitors in the adult cerebral cortex. Further, we find that the population of mature oligodendrocytes is markedly reduced in the absence of cyclin D1, leading to a significant decrease in the number of myelinated axons in both the prefrontal cortex and the corpus callosum of 8-month-old mutant mice. In contrast, the pool of Iba1+ cells is diminished already at postnatal day 3 in the absence of cyclin D1, while the number of S100β+ astrocytes remains unchanged in the mutant.

  8. Expressions of cyclin D1 and p27kip1 in carcinogenesis of stomach mucosa

    Institute of Scientific and Technical Information of China (English)

    Qunqing Liu; Guiying Zhang

    2008-01-01

    Objective: To evaluate the relationship between the expressions of cyclin D1 and p27kipl in the canceration course of the stomach.Methods: The immunohistochemical staining technique (SP method) was used to detect the expressions of cyclin D1, p27kip1 in chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (DYS), gastric carcinoma (GCA) biopsy specimens.Results: The positive cyclin D1 expression rates increased with the progressing from CAG→IM→DYS→GCA respectively, and those in IM, DYS and GCA were different from those in CSG, P<0.05, while DYS group was indifferent from GCA group, P>0.05.The positive p27k'pl expression rates decreased with the mucosa progressing from CAG→IM→DYS→GCA.There was a negative correlation between the expression cyclin D1 and p27kip1 (y=-0.53, P=0.000).Conclusion: Expression rates of cyclin D1 in the canceration course of the stomach mucosa trend were increased and those of p27kip1 were decreased; the abnormal expressions of them were found in the early term of the canceration course of the stomach mucosa, and the inverse expression suggests there may be a negative feedback regulatory loop between cyclin D1 and p27kip1.

  9. Haplotype variation of Green Revolution gene Rht-D1 during wheat domestication and improvement

    Institute of Scientific and Technical Information of China (English)

    Chihong Zhang; Lifeng Gao; Jiaqiang Sun; Jizeng Jia; Zhenglong Ren

    2014-01-01

    Green Revolution made a substantial contribution to wheat yields worldwide in the 1960s and 1970s. It is of great importance to analyze the haplotype variation of Rht-D1, the Green Revolution gene, during wheat (Triticum aestivum L.) domestication and breeding to understand its evolution and function in wheat breeding history. In this study, the Rht-D1 and its flanking regions were sequenced and single nucleotide polymorphisms were detected based on a panel of 45 accessions of Aegilops tauschi , 51 accessions of landraces and 80 accessions of commercial varieties. Genetic diversity in the wild accessions was much higher than that in the varieties and higher than that reported previously. Seven haplotypes (Hapl I to Hapl VII) of Rht-D1 were identified and their evolutionary relationships were proposed. In addition to the wel-known Green Revolution al ele Rht-D1b, Hapl VII (an al ele Rht-D1k) was identified in early breeding varieties, which reduced plant height by 16%. The results suggested that Rht-D1k had been used in breeding before the Green Revolution and made a great contribution to wheat production worldwide. Based on the breeding history and molecular evidence, we proposed that the wheat Green Revolution in China and International Maize and Wheat Improvement Center (CIMMYT) occurred independently.

  10. Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells

    Directory of Open Access Journals (Sweden)

    Choi Yoon

    2009-05-01

    Full Text Available Abstract Background Maintaining the correct balance of proliferation versus differentiation in retinal progenitor cells (RPCs is essential for proper development of the retina. The cell cycle regulator cyclin D1 is expressed in RPCs, and mice with a targeted null allele at the cyclin D1 locus (Ccnd1-/- have microphthalmia and hypocellular retinas, the latter phenotype attributed to reduced RPC proliferation and increased photoreceptor cell death during the postnatal period. How cyclin D1 influences RPC behavior, especially during the embryonic period, is unclear. Results In this study, we show that embryonic RPCs lacking cyclin D1 progress through the cell cycle at a slower rate and exit the cell cycle at a faster rate. Consistent with enhanced cell cycle exit, the relative proportions of cell types born in the embryonic period, such as retinal ganglion cells and photoreceptor cells, are increased. Unexpectedly, cyclin D1 deficiency decreases the proportions of other early born retinal neurons, namely horizontal cells and specific amacrine cell types. We also found that the laminar positioning of horizontal cells and other cell types is altered in the absence of cyclin D1. Genetically replacing cyclin D1 with cyclin D2 is not efficient at correcting the phenotypes due to the cyclin D1 deficiency, which suggests the D-cyclins are not fully redundant. Replacement with cyclin E or inactivation of cyclin-dependent kinase inhibitor p27Kip1 restores the balance of RPCs and retinal cell types to more normal distributions, which suggests that regulation of the retinoblastoma pathway is an important function for cyclin D1 during embryonic retinal development. Conclusion Our findings show that cyclin D1 has important roles in RPC cell cycle regulation and retinal histogenesis. The reduction in the RPC population due to a longer cell cycle time and to an enhanced rate of cell cycle exit are likely to be the primary factors driving retinal hypocellularity

  11. Expression and significance of cyclin D1, p27kip1 protein in bronchioloalveolar carcinoma

    Institute of Scientific and Technical Information of China (English)

    袁键群; 许敬尧; 张静; 何启才; 祝佳; 盛彩霞

    2004-01-01

    Purpose: To investigate the relationship between expression of cell cycle-related protein cyclin D1, p27kipl and the pathogenesis of bronchioloalveolar carcinoma (BAC) and the value of prediction of prognosis. Methods: Cyclin D 1 and p27kip 1 protein were detected by immunohistochemical En Vision method in 43 BACs. Results: The positivity of cyclin D 1 in BAC was 65.1% (28/43), which was significantly higher than that in normal pulmonary tissue (0/13), P<0.01. No statistically significant association was found between cyclin D1 expression data and sex, age, tobacco-use history, histologic subtype (mucinous vs nonmucinous), stromal fibrosis, lymph node metastasis, clinical stage or postoperative survival period (P>0.05), while cyclin D1 expression was found to be negatively correlated with tumor size (P<0.05). The positivity of p27kipl in BACs was 51.2% (22/43), significantly lower than that in normal pulmonary tissue (12/13), P<0.01. p27kipl expression level was not associated with sex, age, tobacco-use history, tumor size or histologic subtype (P>0.05), but was negatively correlated with stromal fibrosis, lymph node metastasis and clinical stage (P<0.05); and positively associated with postoperative survival period (P<0.01). The survival rate of p27kipl positive group was significantly higher than that of p27kipl negative group (P<0.01). No statistically significant correlation was found between cyclin D 1 and p27kipl expression. Conclusions: Increased cyclin D1 expression and decreased p27kip 1 expression are related to the pathogenesis of BAC;decreased p27kipl expression is associated with metastasis progression; immunodetection ofp27kip 1 is useful for assessment of prognosis.

  12. Resolvin D1 primes the resolution process initiated by calorie restriction in obesity-induced steatohepatitis.

    Science.gov (United States)

    Rius, Bibiana; Titos, Esther; Morán-Salvador, Eva; López-Vicario, Cristina; García-Alonso, Verónica; González-Périz, Ana; Arroyo, Vicente; Clària, Joan

    2014-02-01

    Insulin resistance and nonalcoholic steatohepatitis (NASH), characterized by hepatic steatosis combined with inflammation, are major sequelae of obesity. Currently, lifestyle modification (i.e., weight loss) is the first-line therapy for NASH. However, weight loss resolves steatosis but not inflammation. In this study, we tested the ability of resolvin D1 (RvD1), an anti-inflammatory and proresolving molecule, to promote the resolution initiated by calorie restriction in obese mice with NASH. Calorie restriction reduced adipose and liver weight (-56 and -13%, respectively; P<0.001), serum leptin and resistin levels, hepatic steatosis, and insulin resistance. In addition to these, mice receiving RvD1 during the dietary intervention showed increased adiponectin expression at both the mRNA and protein levels and reduced liver macrophage infiltration (-15%, P<0.01). Moreover, RvD1 skewed macrophages from an M1- to an M2-like anti-inflammatory phenotype, induced a specific hepatic miRNA signature (i.e., miR-219-5p and miR-199a-5p), and reduced inflammatory adipokine mRNA and protein expression and macrophage innate immune response. In precision-cut liver slices (PCLSs), which override the influence of circulating factors, RvD1 attenuated hypoxia-induced mRNA and protein expression of COX-2, IL-1β, IL-6, and CCR7. Of note, RvD1 anti-inflammatory actions were absent in macrophage-depleted PCLSs. In summary, RvD1 acts as a facilitator of the hepatic resolution process by reducing the inflammatory component of obesity-induced NASH.

  13. Resolvin D1 Dampens Pulmonary Inflammation and Promotes Clearance of Nontypeable Haemophilus influenzae.

    Science.gov (United States)

    Croasdell, Amanda; Lacy, Shannon H; Thatcher, Thomas H; Sime, Patricia J; Phipps, Richard P

    2016-03-15

    Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative, opportunistic pathogen that frequently causes ear infections, bronchitis, pneumonia, and exacerbations in patients with underlying inflammatory diseases, such as chronic obstructive pulmonary disease. In mice, NTHi is rapidly cleared, but a strong inflammatory response persists, underscoring the concept that NTHi induces dysregulation of normal inflammatory responses and causes a failure to resolve. Lipid-derived specialized proresolving mediators (SPMs) play a critical role in the active resolution of inflammation by both suppressing proinflammatory actions and promoting resolution pathways. Importantly, SPMs lack the immunosuppressive properties of classical anti-inflammatory therapies. On the basis of these characteristics, we hypothesized that aspirin-triggered resolvin D1 (AT-RvD1) would dampen NTHi-induced inflammation while still enhancing bacterial clearance. C57BL/6 mice were treated with AT-RvD1 and infected with live NTHi. AT-RvD1-treated mice had lower total cell counts and neutrophils in bronchoalveolar lavage fluid, and had earlier influx of macrophages. In addition, AT-RvD1-treated mice showed changes in temporal regulation of inflammatory cytokines and enzymes, with decreased KC at 6 h and decreased IL-6, TNF-α, and cyclooxygenase-2 expression at 24 h post infection. Despite reduced inflammation, AT-RvD1-treated mice had reduced NTHi bacterial load, mediated by enhanced clearance by macrophages and a skewing toward an M2 phenotype. Finally, AT-RvD1 protected NTHi-infected mice from weight loss, hypothermia, hypoxemia, and respiratory compromise. This research highlights the beneficial role of SPMs in pulmonary bacterial infections and provides the groundwork for further investigation into SPMs as alternatives to immunosuppressive therapies like steroids.

  14. Cloning, expression, and functional analysis of human dopamine D1 receptors

    Institute of Scientific and Technical Information of China (English)

    Wan-chun SUN; Lei JIN; Yan CAO; Li-zhen WANG; Fan MENG; Xing-zu ZHU

    2005-01-01

    Aim: To construct an HEK293 cell line stably expressing human dopamine D1 receptor (D1R). Methods: cDNA was amplified by RT-PCR using total RNA from human embryo brain tissue as the template. The PCR products were subcloned into the plasmid pcDNA3 and cloned into the plasmid pcDNA3.1. The cloned D1R cDNA was sequenced and stably expressed in HEK293 cells. Expression of D1R in HEK293 cells was monitored by the [3H]SCH23390 binding assay. The function of D1R was studied by the cAMP accumulation assay, CRE-SEAP reporter gene activity assay, and intracellular calcium assay. Results: An HEK293 cell line stably expressing human D1R was obtained. A saturation radioligand binding experiment with [3H]SCH23390 demonstrated that the Kd and Bmax values were 1.5±0.2 nmol/L and 2.94±0.15 nmol/g of protein, respectively. In the[3H]SCH23390 competition assay, D1R agonist SKF38393 displaced[3H]SCH23390 with an IC50 value of 2.0 (1.5-2.8) μmol/L. SKF38393 increased the intracellular cAMP level and CRE-SEAP activity through D1R expressed in HEK293 cells in a concentration-dependent manner with an EC50 value of 0.25(0.12-0.53) μmol/L and 0.39 (0.27-0.57) μmol/L at 6 h/0.59 (0.22-1.58) μmol/L at 12 h, respectively. SKF38393 also increased the intracellular calcium level in a concentration-dependent manner with EC50 value of 27 (8.6-70) nmol/L.Conclusion: An HEK293 cell line stably expressing human D1R was obtained successfuly. The study also demonstrated that the CRE-SEAP activity assay could be substituted for the cAMP accumulation assay for measuring increase in cAMP levels. Thus, both intracellular calcium measurements and the CRE-SEAP activity assay are suitable for high-throughput screening in drug research.

  15. SO(d,1)-invariant Yang-Baxter operators and the dS/CFT correspondence

    CERN Document Server

    Hollands, Stefan

    2016-01-01

    We propose a model for the dS/CFT correspondence. The model is constructed in terms of a "Yang-Baxter operator" $R$ for unitary representations of the deSitter group $SO(d,1)$. This $R$-operator is shown to satisfy the Yang-Baxter equation, unitarity, as well as certain analyticity relations, including in particular a crossing symmetry. With the aid of this operator we construct: a) A chiral (light-ray) conformal quantum field theory whose internal degrees of freedom transform under the given unitary representation of $SO(d,1)$. By analogy with the $O(N)$ non-linear sigma model, this chiral CFT can be viewed as propagating in a deSitter spacetime. b) A (non-unitary) Euclidean conformal quantum field theory on ${\\mathbb R}^{d-1}$, where $SO(d,1)$ now acts by conformal transformations in (Euclidean) spacetime. These two theories can be viewed as dual to each other if we interpret ${\\mathbb R}^{d-1}$ as conformal infinity of deSitter spacetime. Our constructions use semi-local generator fields defined in terms o...

  16. Dopamine D1 receptor-agonist interactions: A mutagenesis and homology modeling study.

    Science.gov (United States)

    Mente, Scot; Guilmette, Edward; Salafia, Michelle; Gray, David

    2015-01-01

    The dopamine D1 receptor is a G protein-coupled receptor that regulates intracellular signaling via agonist activation. Although the number of solved GPCR X-ray structures has been steadily increasing, still no structure of the D1 receptor exists. We have used site-directed mutagenesis of 12 orthosteric vicinity residues of possible importance to G protein-coupled activation to examine the function of prototypical orthosteric D1 agonists and partial agonists. We find that residues from four different regions of the D1 receptor make significant contributions to agonist function. All compounds studied, which are catechol-amines, are found to interact with the previously identified residues: the conserved D103(3.32), as well as the trans-membrane V serine residues. Additional key interactions are found for trans-membrane VI residues F288(6.51), F289(6.52) and N292(6.55), as well as the extra-cellular loop residue L190(ECL2). Molecular dynamics simulations of a D1 homology model have been used to help put the ligand-residue interactions into context. Finally, we considered the rescaling of fold-shift data as a method to account for the change in the size of the mutated side-chain and found that this rescaling helps to relate the calculated ligand-residue energies with observed experimental fold-shifts.

  17. THE OVEREXPRESSION AND SIGNIFICANCE OF CYCLIN D1 AND P53 IN CERVICAL SQUAMOUS CELL CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    王晓丽; 王梅; 李明众; 宋天保; 任娟; 尚菊战

    2002-01-01

    Objective To investigate the significance of ov erexpresson of cyclin D1 and P53 protein in cervical squamous cell carcinomas.Methods Fifty cases of in vasive cervical squamous cell carcinomas and 10 cases of normal cervical squamou s epithelia were investigated with immunihistochemical technique. Results The overexpression of cyclin D1 and P53 in invasive cer vical carcinomas was 70% and 50 %, respectively. There was no overexpression of them in the control group. The o verexpression of cyclin D1 in grade Ⅱ and Ⅲ was much higher than that in grad eⅠ(P<0.05). The overexpresson of cyclin D1 in stage Ⅲ of cervical carcinom a was significantly higher than that in stage Ⅱ (P<0.05). The overexpress ion of P53 in grade Ⅱ and grade Ⅲ of cervical carcinoma was remarkably higher than that in grade Ⅰ (P<0.05).Conclusion The action point of both cyclin D1 and P53 may be at G1/S transition. The overexpression of them was associated with development and progression of cervical carcinoma probably in different mechanisms and differen t pathways.

  18. THE OVEREXPRESSION AND SIGNIFICANCE OF CYCLIN D1 AND P53 IN CERVICAL SQUAMOUS CELL CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:To investigate the significance of overexpresson of eyclin D1 and P53 protein in cervical squamous cell carcinomas.Methods:Fifty cases of invasive cervical squamous cell carcinomas and 10 Cases of normal cervical squamous epithelia were investigated with immunihistochemical technique.Results:The overexpressioin of cyclin D1 and P53 in invasive cervical carcinomas was 70% and 50%,respectively,There was no overexpression of them in the control group.The overexpression of cyclin D1 in grade Ⅱand Ⅲ was much higher than that in grade I(P<0.05),The overexpresson of cyclin D1 in stage Ⅲof cervical carcinoma was significantly higher than that in stage Ⅱ(P<0.05).The overexpression of P53 in grade -Ⅱand gradeⅢ of cervical carcinoma was remarkably higher than that in grade I(P<0.05),Conclusion:The action point of both cyclin D1 and P53 may be at G1/S transtition.The overexpression of them was associated with development and progression of cervical carcinoma probably in different mechanisms and different pathways.

  19. EXPRESSION AND SIGNIFICANCE OF CYCLIN D1 IN HUMAN HEPATOCELLULAR CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    杨连君; 司晓辉

    2001-01-01

    Objective: To elucidate the expression and significance of cell cycle protein cyclin D1 in human hepatocellular carcinoma (HCC). Methods: The expression of cyclin D1 protein in 29 cases of HCC tissues was detected by immunohistochemical ABC method, and the relationship between its positive rate and pathological grades of HCC tissues was analyzed. Results: The positive rate of cyclin D1 in HCC tissues was 58.6%(17 in 29 cases), whereas only 18.2% (2 cases of 11 cases) in the non-tumor liver tissues immediately adjacent to HCC tissues (LAH). There was significant difference between grade II and LAH tissues (P<0.05), and between grade I and grade III on the positive rate of cyclin D1 (P<0.05), respectively. Conclusion: Cyclin D1 may be regarded as an oncogenic marker during the genesis and development of HCC, and its role in the transforming process from G1 phase to S phase of HCC cells needs further studies.

  20. EXPRESSION OF P16 AND CYCLIN D1 IN THE COURSE OF CARCINOGENESIS OF THE STOMACH

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-long; XU Feng; LI Yan-jie

    1999-01-01

    Objective: To determine p16 and cyclin D1 expression in the specimen of gastric carcinoma, atypic hyperplasia, atrophic gastritis, superficial gastritis and normal gastric mucosa. Methods: Using immunohistochemical method (ABC), the samples of 58 adenocarcinomas, 22 atypic hyperplasias, 28 atrophic gastritis,27 superficial gastritis and 15 gastric epitheliums were analyzed. Results: Positive immunostaining rate for p16 protein was the highest in normal gastric mucosa and decreased with the lesions progressing from superficial gastritis to atrophic gastritis to atypital hyperplasia and to adenocarcinoma (85%, 78.6%, 31.8%,48.3% respectively); Positive immunostaining of cyclin D1 can observed in atrophic gastritis. With the lesions progressing from atrophic gastritis to atypical hyperplasia to adenocarcinoma, its expression rate increased (17.9%, 36.4%, 53.4% respectively), and there was a significant difference between adenocarcinoma and atrophic gastritis group (P<0.05). An interesting observation was that inverse expression between p16and cyclin D1, was shown in most of gastric cancer detected. Conclusion: It is indicated that p16 and cyclin D1 play an important role in the gastric carcinogenesis, the inverse expression between p16 and cyclin D1 suggested that there is a suppression trend in them.

  1. Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.

    Science.gov (United States)

    Allen, Jodi C; Seidel, Petra; Schlosser, Tobias; Ramsay, Emma E; Ge, Qi; Ammit, Alaina J

    2012-01-01

    Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

  2. Casimir interaction between spheres in $\\boldsymbol{(D+1)}$-dimensional Minkowski spacetime

    CERN Document Server

    Teo, L P

    2014-01-01

    We consider the Casimir interaction between two spheres in $(D+1)$-dimensional Minkowski spacetime due to the vacuum fluctuations of scalar fields. We consider combinations of Dirichlet and Neumann boundary conditions. The TGTG formula of the Casimir interaction energy is derived. The computations of the T matrices of the two spheres are straightforward. To compute the two G matrices, known as translation matrices, which relate the hyper-spherical waves in two spherical coordinate frames differ by a translation, we generalize the operator approach employed in [IEEE Trans. Antennas Propag. \\textbf{36}, 1078 (1988)]. The result is expressed in terms of an integral over Gegenbauer polynomials. Using our expression for the Casimir interaction energy, we derive the large separation and small separation asymptotic expansions of the Casimir interaction energy. In the large separation regime, we find that the Casimir interaction energy is of order $L^{-2D+3}$, $L^{-2D+1}$ and $L^{-2D-1}$ respectively for Dirichlet-Di...

  3. Intronic SH2D1A mutation with impaired SAP expression and agammaglobulinemia.

    Science.gov (United States)

    Recher, Mike; Fried, Ari J; Massaad, Michel J; Kim, Hye Young; Rizzini, Michela; Frugoni, Francesco; Walter, Jolan E; Mathew, Divij; Eibel, Hermann; Hess, Christoph; Giliani, Silvia; Umetsu, Dale T; Notarangelo, Luigi D; Geha, Raif S

    2013-02-01

    X-linked lymphoproliferative (XLP) disease is a primary immunodeficiency syndrome associated with the inability to control Epstein-Barr virus (EBV), lymphoma, and hypogammaglobulinemia. XLP is caused by mutations in the SH2D1A gene, which encodes the SLAM-associated protein (SAP), or in the BIRC4 gene, which encodes the X-linked inhibitor of apoptosis protein (XIAP). Here we report a patient with recurrent respiratory tract infections and early onset agammaglobulinemia who carried a unique disease-causing intronic loss-of-function mutation in SH2D1A. The intronic mutation affected SH2D1A gene transcription but not mRNA splicing, and led to markedly reduced level of SAP protein. Despite undetectable serum immunoglobulins, the patient's B cells replicated and differentiated into antibody producing cells normally in vitro.

  4. Shutdown dose rate assessment with the Advanced D1S method: Development, applications and validation

    Energy Technology Data Exchange (ETDEWEB)

    Villari, R., E-mail: rosaria.villari@enea.it [Associazione EURATOM-ENEA sulla Fusione, Via Enrico Fermi 45, 00044 Frascati, Rome (Italy); Fischer, U. [Karlsruhe Institute of Technology KIT, Institute for Neutron Physics and Reactor Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Moro, F. [Associazione EURATOM-ENEA sulla Fusione, Via Enrico Fermi 45, 00044 Frascati, Rome (Italy); Pereslavtsev, P. [Karlsruhe Institute of Technology KIT, Institute for Neutron Physics and Reactor Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Petrizzi, L. [European Commission, DG Research and Innovation K5, CDMA 00/030, B-1049 Brussels (Belgium); Podda, S. [Associazione EURATOM-ENEA sulla Fusione, Via Enrico Fermi 45, 00044 Frascati, Rome (Italy); Serikov, A. [Karlsruhe Institute of Technology KIT, Institute for Neutron Physics and Reactor Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)

    2014-10-15

    Highlights: Development of Advanced-D1S for shutdown dose rate calculations; Recent applications of the tool to tokamaks; Summary of the results of benchmarking with measurements and R2S calculations; Limitations and further development. Abstract: The present paper addresses the recent developments and applications of Advanced-D1S to the calculations of shutdown dose rate in tokamak devices. Results of benchmarking with measurements and Rigorous 2-Step (R2S) calculations are summarized and discussed as well as limitations and further developments. The outcomes confirm the essential role of the Advanced-D1S methodology and the evidence for its complementary use with the R2Smesh approach for the reliable assessment of shutdown dose rates and related statistical uncertainties in present and future fusion devices.

  5. DAMAGE MECHANISM ANALYSIS OF 2D 1 × 1 BRAIDED COMPOSITES UNDER UNIDIRECTIONAL TENSION

    Institute of Scientific and Technical Information of China (English)

    张超; 许希武; 陈康

    2013-01-01

    Coupling with the periodical displacement boundary condition ,a representative volume element (RVE) model is established to simulate the progressive damage behavior of 2D 1 × 1 braided composites under unidirection-al tension by using the nonlinear finite element method .Tsai-Wu failure criterion with various damage modes and Mises criterion are considered for predicting damage initiation and progression of yarns and matrix .The anisotropic damage model for yarns and the isotropic damage model for matrix are used to simulate the microscopic damage propagation of 2D 1 × 1 braided composites .Murakami′s damage tensor is adopted to characterize each damage mode .In the simulation process ,the damage mechanisms are revealed and the tensile strength of 2D 1 × 1 braided composites is predicted from the calculated average stress-average strain curve . Numerical results show good agreement with experimental data ,thus the proposed simulation method is verified for damage mechanism analysis of 2D braided composites .

  6. The Deuteron Spin-dependent Structure Function $g^{d}_1$ and its First Moment

    CERN Document Server

    Alexakhin, V.Yu.; Alexeev, G.D.; Alexeev, M.; Amoroso, A.; Balestra, F.; Ball, J.; Barth, J.; Baum, G.; Becker, M.; Bedfer, Y.; Bernet, C.; Bertini, R.; Bettinelli, M.; Birsa, R.; Bisplinghoff, J.; Bordalo, P.; Bradamante, F.; Bressan, A.; Brona, G.; Burtin, E.; Bussa, M.P.; Bytchkov, V.N.; Chapiro, A.; Cicuttin, A.; Colantoni, M.; Colavita, A.A.; Costa, S.; Crespo, M.L.; d'Hose, N.; Dalla Torre, S.; Das, S.; Dasgupta, S.S.; De Masi, R.; Dedek, N.; Demchenko, D.; Denisov, O.Yu.; Dhara, L.; Diaz, V.; Dinkelbach, A.M.; Donskov, S.V.; Dorofeev, V.A.; Doshita, N.; Duic, V.; Dunnweber, W.; Efremov, A.; Eversheim, P.D.; Eyrich, W.; Faessler, M.; Fauland, P.; Ferrero, A.; Ferrero, L.; Finger, M.; M. Finger jr.; Fischer, H.; Franz, J.; Friedrich, J.M.; Frolov, V.; Garfagnini, R.; Gautheron, F.; Gavrichtchouk, O.P.; Gerassimov, S.; Geyer, R.; Giorgi, M.; Gobbo, B.; Goertz, S.; Gorin, A.M.; Grajek, O.A.; Grasso, A.; Grube, B.; Guskov, A.; Haas, F.; Hannappel, J.; von Harrach, D.; Hasegawa, T.; Hedicke, S.; Heinsius, F.H.; Hermann, R.; Hess, C.; Hinterberger, F.; von Hodenberg, M.; Horikawa, N.; Horikawa, S.; Horn, I.; Ilgner, C.; Ioukaev, A.I.; Ivanchin, I.; Ivanov, O.; Iwata, T.; Jahn, R.; Janata, A.; Joosten, R.; Jouravlev, N.I.; Kabuss, E.; Kang, D.; Ketzer, B.; Khaustov, G.V.; Khokhlov, Yu. A.; Kisselev, Yu.; Klein, F.; Klimaszewski, K.; Koblitz, S.; Koivuniemi, J.H.; Kolosov, V.N.; Komissarov, E.V.; Kondo, K.; Konigsmann, K.; Konorov, I.; Konstantinov, V.F.; Korentchenko, A.S.; Korzenev, A.; Kotzinian, A.M.; Koutchinski, N.A.; Kouznetsov, O.; Kowalik, K.; Kramer, D.; Kravchuk, N.P.; Krivokhizhin, G.V.; Kroumchtein, Z.V.; Kubart, J.; Kuhn, R.; Kukhtin, V.; Kunne, F.; Kurek, K.; Ladygin, M.E.; Lamanna, M.; Le Goff, J.M.; Leberig, M.; Lednev, A.A.; Lehmann, A.; Lichtenstadt, J.; Liska, T.; Ludwig, I.; Maggiora, A.; Maggiora, M.; Magnon, A.; Mallot, G.K.; Marchand, C.; Marroncle, J.; Martin, A.; Marzec, J.; Masek, L.; Massmann, F.; Matsuda, T.; Matthia, D.; Maximov, A.N.; Meyer, W.; Mielech, A.; Mikhailov, Yu. V.; Moinester, M.A.; Nagel, T.; Nahle, O.; Nassalski, J.; Neliba, S.; Neyret, D.P.; Nikolaenko, V.I.; Nikolaev, K.; Nozdrin, A.A.; Obraztsov, V.F.; Olshevsky, A.G.; Ostrick, M.; Padee, A.; Pagano, P.; Panebianco, S.; Panzieri, D.; Paul, S.; Peshekhonov, D.V.; Peshekhonov, V.D.; Piragino, G.; Platchkov, S.; Pochodzalla, J.; Polak, J.; Polyakov, V.A.; Pontecorvo, G.; Popov, A.A.; Pretz, J.; Procureur, S.; Quintans, C.; Ramos, S.; Reicherz, G.; Rondio, E.; Rozhdestvensky, A.M.; Ryabchikov, D.; Samoylenko, V.D.; Sandacz, A.; Santos, H.; Sapozhnikov, M.G.; Savin, I.A.; Schiavon, P.; Schill, C.; Schmitt, L.; Schroeder, W.; Seeharsch, D.; Seimetz, M.; Setter, D.; Shevchenko, O.Yu.; Siebert, H.W.; Silva, L.; Sinha, L.; Sissakian, A.N.; Slunecka, M.; Smirnov, G.I.; Sozzi, F.; Srnka, A.; Stinzing, F.; Stolarski, M.; Sugonyaev, V.P.; Sulc, M.; Sulej, R.; Tchalishev, V.V.; Tessaro, S.; Tessarotto, F.; Teufel, A.; Tkatchev, L.G.; Trippel, S.; Venugopal, G.; Virius, M.; Vlassov, N.V.; Webb, R.; Weise, E.; Weitzel, Q.; Windmolders, R.; Wislicki, W.; Zaremba, K.; Zavertyaev, M.; Zemlyanichkina, E.; Zhao, J.; Zvyagin, A.

    2007-01-01

    We present a measurement of the deuteron spin-dependent structure function g^d_1 based on the data collected by the COMPASS experiment at CERN during the years 2002-2004. The data provide an accurate evaluation for \\Gamma^d_1, the first moment of g^d_1(x), and for the matrix element of the singlet axial current, a_0. The results of QCD fits in the next to leading order (NLO) on all g1 deep inelastic scattering data are also presented. They provide two solutions with the gluon spin distribution function \\Delta_G positive or negative, which describe the data equally well. In both cases, at Q^2 = 3(GeV/c)^2 the first moment of \\Delta G is found to be of the order of 0:2 - 0:3 in absolute value.

  7. Export of cytochrome P450 105D1 to the periplasmic space of Escherichia coli.

    Science.gov (United States)

    Kaderbhai, M A; Ugochukwu, C C; Kelly, S L; Lamb, D C

    2001-05-01

    CYP105D1, a cytochrome P450 from Streptomyces griseus, was appended at its amino terminus to the secretory signal of Escherichia coli alkaline phosphatase and placed under the transcriptional control of the native phoA promoter. Heterologous expression in E. coli phosphate-limited medium resulted in abundant synthesis of recombinant CYP105D1 that was translocated across the bacterial inner membrane and processed to yield authentic, heme-incorporated P450 within the periplasmic space. Cell extract and whole-cell activity studies showed that the periplasmically located CYP105D1 competently catalyzed NADH-dependent oxidation of the xenobiotic compounds benzo[a]pyrene and erythromycin, further revealing the presence in the E. coli periplasm of endogenous functional redox partners. This system offers substantial advantages for the application of P450 enzymes to whole-cell biotransformation strategies, where the ability of cells to take up substrates or discard products may be limited.

  8. Cat (Fel d 1) and dog (Can f 1) allergen levels in cars, dwellings and schools.

    Science.gov (United States)

    Niesler, A; Ścigała, G; Łudzeń-Izbińska, B

    Pets are an important source of indoor allergens. The aim of the study was to compare cat and dog allergen levels in cars, schools and homes. The study was carried out in 17 cars, 14 classrooms and 19 dwellings located in the highly industrialized and urbanized region of Poland. Dust and air samples were analyzed for Fel d 1 and Can f 1 using a double monoclonal ELISA assay. The highest amounts of cat and dog allergens (Fel d 1: 1169 μg/g; Can f 1: 277 μg/g) were found in dwellings with pets. Allergen concentrations were correlated with the number of animals kept at home. Although concentrations on automobile seats were lower, Fel d 1 levels exceeded 8 μg/g in 23.5 % of cars and high levels of Can f 1 (>10 μg/g) were found in 17.6 % of cars. The study revealed that cars of pet owners may be reservoirs of cat and dog allergens even when animals are not transported in them. In schools, concentrations of pet allergens did not reach high levels, but the moderate levels of Fel d 1 (≥1-8 μg/g) and Can f 1 (≥2-10 μg/g) were detected in 42.9 and 7.1 % of the investigated classrooms. Concentrations of cat and dog allergen in schools were higher than in homes without pets. While airborne Fel d 1 and Can f 1 levels were found low, residential allergen concentrations in settled dust and air were correlated. The study results suggest that classrooms and cars of pet owners may be important sites of exposure to cat and dog allergens, though the highest concentrations of Fel d 1 and Can f 1 are found in homes of pet owners.

  9. UGT74D1 is a novel auxin glycosyltransferase from Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Shang-Hui Jin

    Full Text Available Auxin is one type of phytohormones that plays important roles in nearly all aspects of plant growth and developmental processes. The glycosylation of auxins is considered to be an essential mechanism to control the level of active auxins. Thus, the identification of auxin glycosyltransferases is of great significance for further understanding the auxin regulation. In this study, we biochemically screened the group L of Arabidopsis thaliana glycosyltransferase superfamily for enzymatic activity toward auxins. UGT74D1 was identified to be a novel auxin glycosyltransferase. Through HPLC and LC-MS analysis of reaction products in vitro by testing eight substrates including auxins and other compounds, we found that UGT74D1 had a strong glucosylating activity toward indole-3-butyric acid [IBA], indole-3-propionic acid [IPA], indole-3-acetic acid [IAA] and naphthaleneacetic acid [NAA], catalyzing them to form corresponding glucose esters. Biochemical characterization showed that this enzyme had a maximum activity in HEPES buffer at pH 6.0 and 37°C. In addition, the enzymatic activity analysis of crude protein and the IBA metabolite analysis from transgenic Arabidopsis plants overexpressing UGT74D1 gene were also carried out. Experimental results indicated that over-production of the UGT74D1 in plants indeed led to increased level of the glucose conjugate of IBA. Moreover, UGT74D1 overexpression lines displayed curling leaf phenotype, suggesting a physiological role of UGT74D1 in affecting the activity of auxins. Our current data provide a new target gene for further genetic studies to understand the auxin regulation by glycosylation in plants.

  10. Evolutionary dynamics of HBV-D1 genotype epidemic in Turkey.

    Science.gov (United States)

    Ciccozzi, Massimo; Ciccaglione, Anna Rita; Lo Presti, Alessandra; Equestre, Michele; Cella, Eleonora; Ebranati, Erika; Gabanelli, Elena; Villano, Umbertina; Bruni, Roberto; Yalcinkaya, Tulay; Tanzi, Elisabetta; Zehender, Gianguglielmo

    2014-01-01

    Hepatitis B virus (HBV), is the leading cause of liver diseases infecting an estimated 240 million persons worldwide. The HBV prevalence rates are variables between different countries, with an high level of endemicity in the south-eastern part of Europe. Seven main HBV-D subgenotypes have been described until now (D1-D7). Turkey, seems to have played an important role in the penetration of HBV-D1 in the Mediterranean area. The importance of Turkey in the European epidemiology of HBV is also suggested by the observation that the highest spread of HBV infection in the Continent are reported in Turkey with Romania, Bulgaria, Greece, Albania and some southern regions of Italy. In this paper the molecular epidemiology and the epidemiological history of HBV-D in Turkey was studied, by characterizing 34 new Turkish isolates and performing a phylogeographic reconstruction. By using a phylodynamic and phylogeographic Bayesian approach, the analysis suggested that HBV-D1 originated in Turkey about in the early 1940s. The large prevalence of D1 in comparison to the other subgenotypes in Turkey confirms the importance of this Country as epidemiological reservoir of HBV-D1 dispersion. The phylogeny suggests that after each initial introduction of the virus in a specific population, separate transmission clusters have been evolving along independent phylogenetic lineages. Better characterization and continuous monitoring of such groups are going to be crucial to understand in detail the epidemiology of HBV-D1 subgenotype in Turkey and to assess the efficacy of prevention, vaccination and therapy in controlling the epidemic.

  11. Helical reactor design FFHR-d1 and c1 for steady-state DEMO

    Energy Technology Data Exchange (ETDEWEB)

    Sagara, A., E-mail: sagara.akio@LHD.nifs.ac.jp; Tamura, H.; Tanaka, T.; Yanagi, N.; Miyazawa, J.; Goto, T.; Sakamoto, R.; Yagi, J.; Watanabe, T.; Takayama, S.

    2014-10-15

    Highlights: •More than 10 years’ operation is feasible using the inboard WC shield, where the total TBR is 1.18 with 90% 6Li. •The divertor targets can be efficiently shielded, expanding the range of material choice (e.g., Cu alloys). •Flinabe blanket mixed with metal powder is proposed to increase hydrogen solubility and thermal efficiency. •Helical coils by connecting segments of 100 kA-class YBCO high-temperature superconductors is proposed. •A multi-path strategy on FFHR-d1 is introduced with sub-ignition options for “before demo, compact and component-test”. -- Abstract: NIFS launched the Fusion Engineering Research Project (FERP) in preparation for DEMO by starting the redesign of the LHD-type helical reactor FFHR-d1. In the first round, the main parameters were selected. The second round is preparing detailed three-dimensional (3D) design of the superconducting magnet support structures, and 3D neutronics analyses, where the diverter targets can be efficiently shielded from fast neutrons. A new Flinabe blanket mixed with metal powder was proposed. Fabrication of helical coils by connecting half-helical-pitch segments of 100 kA-class YBCO high-temperature superconductors is proposed as a promising method. Also in progress is improvement of the first round of the core plasma design, ignition start-up analyses, and fueling scenario. As a consequence, a multi-path strategy on FFHR-d1 has been introduced with versions of -d1A, -d1B, and -d1C, where design flexibility is expanded to include subignition with options FFHR-c1 for “before demo, compact, and component-test.”.

  12. EXPRESSION OF p16, CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

    Institute of Scientific and Technical Information of China (English)

    缪林; 赵志泉; 季国忠; 范志宁; 金宁; 刘政; 张平; 程铁华

    2003-01-01

    Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of pl6, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene

  13. 松下发布3D相机DMC-3D1

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    近日。松下发布了双镜头4x光学变焦便携数码相机LumixDMC-3D1。3D1搭载1200万像素“高感光度CMOS”传感器,VenusEngine影像处理引擎,支持拍摄2D及3D照片。拥有3.5英寸的触摸屏。连拍速度8fPs。双镜头可以独立进行对焦与变焦。

  14. Adolescent Maturation of Dopamine D1 and D2 Receptor Function and Interactions in Rodents

    Science.gov (United States)

    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

  15. Using the D1D5 CFT to Understand Black Holes

    OpenAIRE

    Avery, Steven

    2010-01-01

    In this dissertation, we review work presented in arXiv:0906.2015, arXiv:0907.1663, arXiv:1002.3132, arXiv:1003.2746, and arXiv:1007.2202 on the D1D5 system. We begin with some motivational material for black holes in string theory. In Chapter 2, we review the D1D5 system, including the gravity and CFT descriptions. In Chapter 3, we show how to perturbatively relax the decoupling limit in a general AdS-CFT setting. This allows one to compute the emission out of the AdS/CFT into the asymptotic...

  16. SVR-D1.2: A Prediction Model for Population Occurrence of Paddy Stem Borer

    Directory of Open Access Journals (Sweden)

    Lichuan Gu

    2012-08-01

    Full Text Available In this study, we analyse the SVR-based prediction method for selecting the optimal model framework based on kernel matrix. Moreover, SVR-D1.2 is proposed with the help of the kernel matrix’s symmetry and positive definition and kernel alignment. Test results show that there exactly exists the non-line relation between the insect population occurrence and the meteorological factors and the new prediction model, SVR-D1.2, improved prediction accuracy compared with other methods.

  17. Investigating the Role of Cyclin D1 in the Promotion of Genomic Instability and Breast Cancer

    Science.gov (United States)

    2011-09-01

    20mM Tris, 40mM MgCl2, 2.5mM EGTA). Beads containing SCFFbx4 complexes 6 were then mixed with Sf9 -produced purified cyclin D1 substrate, ATP...ubiquitylation reactions with Sf9 -purified cyclin D1/CDK4 as substrate, in the presence of E1, E2, 1 ubiquitin, and ATP. 2 3 Figure 6. Fbx4 loss drives cell...kinase/methyltrans- ferase reactions with purified recombinant PRMT5/MEP50 pro- duced in Sf9 cells. PRMT5-dependent methyltransferase activity was

  18. 26 CFR 1.691(d)-1 - Amounts received by surviving annuitant under joint and survivor annuity contract.

    Science.gov (United States)

    2010-04-01

    ... joint and survivor annuity contract. 1.691(d)-1 Section 1.691(d)-1 Internal Revenue INTERNAL REVENUE... Decedents § 1.691(d)-1 Amounts received by surviving annuitant under joint and survivor annuity contract. (a... and survivor annuity contract (to the extent indicated in paragraph (b) of this section) are...

  19. File list: Oth.ALL.05.Nr1d1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.05.Nr1d1.AllCell mm9 TFs and others Nr1d1 All cell types SRX997755,SRX12817...758,SRX994726,SRX100297,SRX1304810,SRX1304809 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.05.Nr1d1.AllCell.bed ...

  20. File list: Oth.ALL.20.Nr1d1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.20.Nr1d1.AllCell mm9 TFs and others Nr1d1 All cell types SRX997762,SRX10946...4810,SRX997755,SRX994726,SRX1304809,SRX997756 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.20.Nr1d1.AllCell.bed ...

  1. Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells.

    Science.gov (United States)

    Katz, Samuel G; Labelle, James L; Meng, Hailong; Valeriano, Regina P; Fisher, Jill K; Sun, Heather; Rodig, Scott J; Kleinstein, Steven H; Walensky, Loren D

    2014-02-06

    Mantle cell lymphoma (MCL) is a highly aggressive B-cell lymphoma resistant to conventional chemotherapy. Although defined by the characteristic t(11;14) translocation, MCL has not been recapitulated in transgenic mouse models of cyclin D1 overexpression alone. Indeed, several genetic aberrations have been identified in MCL that may contribute to its pathogenesis and chemoresistance. Of particular interest is the frequent biallelic deletion of the proapoptotic BCL-2 family protein BIM. BIM exerts its pro-death function via its α-helical BH3 death domain that has the dual capacity to inhibit antiapoptotic proteins such as BCL-2 and MCL-1 and directly trigger proapoptotic proteins such as the mitochondrial executioner protein BAX. To evaluate a functional role for Bim deletion in the pathogenesis of MCL, we generated cyclin D1-transgenic mice harboring Bim-deficient B cells. In response to immunization, Eμ(CycD1)CD19(CRE)Bim(fl/fl) mice manifested selective expansion of their splenic mantle zone compartment. Three distinct immune stimulation regimens induced lymphomas with histopathologic and molecular features of human MCL in a subset of mice. Thus, deletion of Bim in B cells, in the context of cyclin D1 overexpression, disrupts a critical control point in lymphoid maturation and predisposes to the development of MCL. This genetic proof of concept for MCL pathogenesis suggests an opportunity to reactivate the death pathway by pharmacologic mimicry of proapoptotic BIM.

  2. The tumor suppressor, parafibromin, mediates histone H3 K9 methylation for cyclin D1 repression.

    Science.gov (United States)

    Yang, Yong-Jin; Han, Jeung-Whan; Youn, Hong-Duk; Cho, Eun-Jung

    2010-01-01

    Parafibromin, a component of the RNA polymerase II-associated PAF1 complex, is a tumor suppressor linked to hyperparathyroidism-jaw tumor syndrome and sporadic parathyroid carcinoma. Parafibromin induces cell cycle arrest by repressing cyclin D1 via an unknown mechanism. Here, we show that parafibromin interacts with the histone methyltransferase, SUV39H1, and functions as a transcriptional repressor. The central region (128-227 amino acids) of parafibromin is important for both the interaction with SUV39H1 and transcriptional repression. Parafibromin associated with the promoter and coding regions of cyclin D1 and was required for the recruitment of SUV39H1 and the induction of H3 K9 methylation but not H3 K4 methylation. RNA interference analysis showed that SUV39H1 was critical for cyclin D1 repression. These data suggest that parafibromin plays an unexpected role as a repressor in addition to its widely known activity associated with transcriptional activation. Parafibromin as a part of the PAF1 complex might downregulate cyclin D1 expression by integrating repressive H3 K9 methylation during transcription.

  3. Zeeman- and Paschen-Back-effect of the hyperfine structure of the sodium D 1-line

    Science.gov (United States)

    Windholz, L.

    1985-06-01

    Using high-resolution laser-atomic-beam spectroscopy, Zeeman- and Paschen-Back-effects of the hyperfine structure of the sodium resonance lines were studied in fields up to app. 280 G. The results derived for the D 1-line are given in graphical form and show clearly the change in the coupling of J and I of the upper level.

  4. Experimental Conditions: SE19_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE19_S2_M1_D1 SE19 Grobal triacylglycerol analysis in mouse liver and white adipose... tissue (WAT) by high resolution LC/ESI-QTOF MS/MS SE19_S2 Mouse white adipose tissue (WAT) SE19_S2_M1 20 ug

  5. 6-Nitro-4H-benzo[d][1,3]thiazin-2-amine

    Directory of Open Access Journals (Sweden)

    Krishna Kumar Gnanasekaran

    2016-05-01

    Full Text Available An efficient and cost-effective synthesis of 6-nitro-4H-benzo[d][1,3]thiazin-2-amine based on a sequential SN2-SNAr process is reported. The synthesis is accomplished with an overall yield of 80%.

  6. Siim Nestor soovitab : D1 Recordingsi turnee Eestis. Matthew Herbert / Siim Nestor

    Index Scriptorium Estoniae

    Nestor, Siim, 1974-

    2005-01-01

    Iiri techno-firma D1 Recordingsi esindajate kontsertidest 4. märtsil üritusel "Kõigem ruudus" Von Krahlis Tallinnas ja 5. märtsil Ranna klubis Sillamäel. Matthew Herbert Big Band'i ja soome elktroonilise muusika ansambli Uusi Fantaasia kontserdist 5. märtsil Sakala keskuses Tallinnas üritusel "Jazz'n'Motion"

  7. AT-RvD1 Promotes Resolution of Inflammation in NOD/ShiLtJ mice

    Science.gov (United States)

    Wang, Ching-Shuen; Maruyama, Christina L.; Easley, Justin T.; Trump, Bryan G.; Baker, Olga J.

    2017-01-01

    Sjögren’s syndrome (SS) is a chronic inflammatory autoimmune disease characterized by diminished secretory function of the exocrine glands. Treatments for hyposalivation are limited to the use of saliva substitutes and medications that provide only temporary relief. In light of the high degree of need and the limitations of current therapies, development of alternative treatments to restore functioning is essential. Resolvins (Rv), which are highly potent lipid mediators, offer a viable alternative for better treating inflammatory diseases such as SS. The goal of this study was to determine whether systemic preventive treatment with Aspirin-triggered RvD1 (AT-RvD1) reduces inflammation and preserves secretory functioning in NOD/ShiLtJ SS-like mice. Our results indicate that systemic treatment with AT-RvD1 diminishes the progression of the disease in salivary epithelium from female mice as follows: (a) improves secretory function, (b) reduces pro-inflammatory molecule gene expression, (c) increases anti-inflammatory molecule gene expression and (d) induces M2 macrophage polarization. Finally, AT-RvD1 decreases lymphocytic infiltration into the salivary glands when used with small doses of the steroid, dexamethasone, and promotes the tissue healing process. PMID:28361884

  8. Integrability of D1-brane on Group Manifold with Mixed Three Form Flux

    CERN Document Server

    Kluson, J

    2015-01-01

    We consider D1-brane as a natural probe of the group manifold with mixed three form fluxes. We determine Lax connection for given theory. Then we switch to the canonical analysis and calculate the Poisson brackets between spatial components of Lax connections and we argue for integrability of given theory.

  9. Data of evolutionary structure change: 1BU1D-1OOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BU1D-1OOTA 1BU1 1OOT D A -IIVVALYDYEAIHHEDLSFQKGDQMVVLEESGE---WW...14> 1OOT A 1OOTA...tryChain> -21.645000457763672 -6.38100004196167 51.89799880981445 ...76022339 -0.7429999709129333 -0.09000000357627869 tion> 1.78559505939483641OOT A 1OOTA WTGRV--NGREG

  10. Conformal Field Theory Correlators from Classical Scalar Field Theory on $AdS_{d+1}$

    CERN Document Server

    Mück, W; Mueck, Wolfgang

    1998-01-01

    We use the correspondence between scalar field theory on $AdS_{d+1}$ and a conformal field theory on $R^d$ to calculate the 3- and 4-point functions of the latter. The classical scalar field theory action is evaluated at tree level.

  11. Four results on ∅4 oscillons in D + 1 dimensions

    DEFF Research Database (Denmark)

    Andersen, E.A.; Tranberg, A.

    2012-01-01

    We present four results for oscillons in classical ? 4 theory in D + 1 space-time dimensions, based on numerical simulations. These include the oscillon lifetime and the dependence on D; evidence for the uniqueness of the oscillon; evidence for the existence of oscillons beyond D = 7; and a brief...

  12. Data of evolutionary structure change: 1IB6D-1LLDA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1IB6D-1LLDA 1IB6 1LLD D A -MKVAVLGAAGGIGQALALLLKTQLPSGSELSLYDIAP-...ELVGATVNILKAIMPNLVKVAPNAIYMLITNPVDIATHVAQKLTG----LPENQIFGSGTNLDSARLRFLIAQQTGVNVK--NVHAYIAGEHGDS-EVPLWESATIGGVPMSDWTPLPGHDPLDA... 1LLD A 1LLDA EVLDMQ...ine>ILE CA 464 1LLD A 1LLDA... SER CA 536 1LLD A 1LLDA

  13. Data of evolutionary structure change: 1B06D-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available EVID>EVID> 2 1UNF X 1UNF...1B06D-1UNFX 1B06 1UNF D X VIQLKRYEFPQLPYKVDALEPYISKDIIDVHYNGHHKGY...HHHHHHHHHHHHH EEEEEEEEEEGGG EEEEEEE EEE EEE HHHH HHHHHHHHHH EEHHHHHHHHHHHHHH ... 1UNF X 1UNFX 3.1296169757843018 5.294285774230957

  14. 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)

    Science.gov (United States)

    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.

  15. Capacity Development and Strengthening for Energy Policy formulation and implementation of Sustainable Energy Projects in Indonesia CASINDO. Deliverable No. 27. Biogas Construction Plan in Segoroyoso Village Yogyakarta Region

    Energy Technology Data Exchange (ETDEWEB)

    Lesmana, Surya Budi; Putra, Sri Atmaja [Muhammadiyah University of Yogyakarta, Yogyakarta (Indonesia)

    2011-10-15

    The overall objective of the CASINDO programme is to establish a self-sustaining and self-developing structure at both the national and regional level to build and strengthen human capacity to enable the provinces of North Sumatra, Yogyakarta, Central Java, West Nusa Tenggara (WNT) and Papua to formulate sound policies for renewable energy and energy efficiency and to develop and implement sustainable energy projects. To achieve the CASINDO objective seven Technical Working Groups have been established with the aim to conduct the technical activities under the various work packages and to produce the agreed deliverables. This report presents results from Technical Working Group IV on Renewable Energy project development. Its main aims were: To identify suitable non-hydro RE projects that can be developed in the province; To conduct an energy needs assessment in a selected location; To develop a business plan for a proposed solution to the identified main energy problem of the target community; To identify potential investors; To construct the project.

  16. 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

    Science.gov (United States)

    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

  17. Diverse flavonoids stimulate NodD1 binding to nod gene promoters in Sinorhizobium meliloti.

    Science.gov (United States)

    Peck, Melicent C; Fisher, Robert F; Long, Sharon R

    2006-08-01

    NodD1 is a member of the NodD family of LysR-type transcriptional regulators that mediates the expression of nodulation (nod) genes in the soil bacterium Sinorhizobium meliloti. Each species of rhizobia establishes a symbiosis with a limited set of leguminous plants. This host specificity results in part from a NodD-dependent upregulation of nod genes in response to a cocktail of flavonoids in the host plant's root exudates. To demonstrate that NodD is a key determinant of host specificity, we expressed nodD genes from different species of rhizobia in a strain of S. meliloti lacking endogenous NodD activity. We observed that nod gene expression was initiated in response to distinct sets of flavonoid inducers depending on the source of NodD. To better understand the effects of flavonoids on NodD, we assayed the DNA binding activity of S. meliloti NodD1 treated with the flavonoid inducer luteolin. In the presence of luteolin, NodD1 exhibited increased binding to nod gene promoters compared to binding in the absence of luteolin. Surprisingly, although they do not stimulate nod gene expression in S. meliloti, the flavonoids naringenin, eriodictyol, and daidzein also stimulated an increase in the DNA binding affinity of NodD1 to nod gene promoters. In vivo competition assays demonstrate that noninducing flavonoids act as competitive inhibitors of luteolin, suggesting that both inducing and noninducing flavonoids are able to directly bind to NodD1 and mediate conformational changes at nod gene promoters but that only luteolin is capable of promoting the downstream changes necessary for nod gene induction.

  18. Elevated dopamine in the medial prefrontal cortex suppresses cocaine seeking via D1 receptor overstimulation.

    Science.gov (United States)

    Devoto, Paola; Fattore, Liana; Antinori, Silvia; Saba, Pierluigi; Frau, Roberto; Fratta, Walter; Gessa, Gian Luigi

    2016-01-01

    Previous investigations indicate that the dopamine-β-hydroxylase (DBH) inhibitors disulfiram and nepicastat suppress cocaine-primed reinstatement of cocaine self-administration behaviour. Moreover, both inhibitors increase dopamine release in the rat medial prefrontal cortex (mPFC) and markedly potentiate cocaine-induced dopamine release in this region. This study was aimed to clarify if the suppressant effect of DBH inhibitors on cocaine reinstatement was mediated by the high extracellular dopamine in the rat mPFC leading to a supra-maximal stimulation of D1 receptors in the dorsal division of mPFC, an area critical for reinstatement of cocaine-seeking behaviour. In line with previous microdialysis studies in drug-naïve animals, both DBH inhibitors potentiated cocaine-induced dopamine release in the mPFC, in the same animals in which they also suppressed reinstatement of cocaine seeking. Similar to the DBH inhibitors, L-DOPA potentiated cocaine-induced dopamine release in the mPFC and suppressed cocaine-induced reinstatement of cocaine-seeking behaviour. The bilateral microinfusion of the D1 receptor antagonist SCH 23390 into the dorsal mPFC not only prevented cocaine-induced reinstatement of cocaine seeking but also reverted both disulfiram- and L-DOPA-induced suppression of reinstatement. Moreover, the bilateral microinfusion of the D1 receptor agonist chloro-APB (SKF 82958) into the dorsal mPFC markedly attenuated cocaine-induced reinstatement of cocaine seeking. These results suggest that stimulation of D1 receptors in the dorsal mPFC plays a crucial role in cocaine-induced reinstatement of cocaine seeking, whereas the suppressant effect of DBH inhibitors and L-DOPA on drug-induced reinstatement is mediated by a supra-maximal stimulation of D1 receptors leading to their inactivation.

  19. Establishment and initial characterization of SOX2-overexpressing NT2/D1 cell clones.

    Science.gov (United States)

    Drakulic, D; Krstic, A; Stevanovic, M

    2012-05-15

    SOX2, a universal marker of pluripotent stem cells, is a transcription factor that helps control embryonic development in vertebrates; its expression persists in neural stem/progenitor cells into adulthood. Considering the critical role of the SOX2 transcription factor in the regulation of genes required for self-renewal and pluripotency of stem cells, we developed and characterized SOX2-overexpressing NT2/D1 cell clones. Using Southern blot and semi-quantitative RT-PCR, we confirmed integration and expression of exogenous SOX2 in three NT2/D1 cell clones. Overexpression of the SOX2 gene was detected in two of these clones. SOX2 overexpression in NT2/D1 cell clones resulted in altered expression of key pluripotency genes OCT4 and NANOG. Furthermore, SOX2-overexpressing NT2/D1 cell clones entered into retinoic acid-dependent neural differentiation, even when there was elevated SOX2 expression. After 21 days of induction by retinoic acid, expression of neural markers (neuroD1 and synaptophysin) was higher in induced cell clones than in induced parental cells. The cell clone with SOX2 overexpression had an approximately 1.3-fold higher growth rate compared to parental cells. SOX2 overexpression did not increase the population of cells undergoing apoptosis. Taken together, we developed two SOX2-overexpressing cell clones, with constitutive SOX2 expression after three weeks of retinoic acid treatment. SOX2 overexpression resulted in altered expression of pluripotency-related genes, increased proliferation, and altered expression of neural markers after three weeks of retinoic acid treatment.

  20. Cellular characterization of cells from the Fanconi anemia complementation group, FA-D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Buul, Paul P.W. van [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Jaspers, Nicolaas G.J. [Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam (Netherlands); Elghalbzouri-Maghrani, Elhaam [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Duijn-Goedhart, Annemarie van [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N.Copernicus University, Bydgoszcz (Poland)]. E-mail: M.Z.Zdzienicka@LUMC.nl

    2006-10-10

    Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability and hypersensitivity to DNA cross-linking agents. The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells. FANCD1/BRCA2-deficient fibroblasts appeared hypersensitive to mitomycin C (MMC), slightly sensitive to methyl methane sulfonate (MMS), and like cells derived from other FA complementation groups, not sensitive to X-ray irradiation. However, unlike other FA cells, FA-D1 cells were slightly sensitive to UV irradiation. Despite the observed lack of X-ray sensitivity in cell survival, significant radioresistant DNA synthesis (RDS) was observed in the BRCA2-deficient fibroblasts but also in the FANCA-deficient fibroblasts, suggesting an impaired S-phase checkpoint. FA-D1/BRCA2 cells displayed greatly enhanced levels of spontaneous as well as MMC-induced chromosomal aberrations (Canada), similar to cells deficient in homologous recombination (HR) and non-D1 FA cells. In contrast to Brca2-deficient rodent cells, FA-D1/BRCA2 cells showed normal sister chromatid exchange (SCE) levels, both spontaneous as well as after MMC treatment. Hence, these data indicate that human cells with biallelic BRCA2 mutations display typical features of both FA- and HR-deficient cells, which suggests that FANCD1/BRCA2 is part of the integrated FA/BRCA DNA damage response pathway but also controls other functions outside the FA pathway.

  1. Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Fang-Gang Cai; Jian-Sheng Xiao; Qi-Fa Ye

    2006-01-01

    AIM: To observe the effect of ischemic preconditioning on cyclinD1 expression in rat liver cells during early ischemic reperfusion.METHODS: Fifty-four SD rats were randomly divided into ischemic preconditioning group (IP), ischemia/reperfusion group (IR) and sham operation group (SO). The IP and IR groups were further divided into four sub-groups (n = 6). Sham operation group (SO)served as the control group (n = 6). A model of partial liver ischemia/reperfusion was used, in which rats were subjected to liver ischemia for 60 min prior to reperfusion. The animals in the IP group underwent ischemic preconditioning twice for 5 min each time prior to the ischemia/reperfusion challenge. After 0, 1, 2, and 4 h of reperfusion, serum and liver tissue in each group were collected to detect the level of serum ALT, liver histopathology and expression of cyclinD1 mRNA and protein. Flow cytometry was used to detect cell cycle as the quantity indicator of cell regeneration.RESULTS: Compared with IR group, IP group showed asignificantly lower ALT level in 1 h to 4 h sub-groups (P< 0.05). Proliferation index(PI) indicated by the S-phase and G2/M-phase ratio [(S+G2/M)/(G0/G1+S+G2/M)] was significantly increased in IP group at 0 and 1 h (26.44± 7.60% vs 18.56 ± 6.40%,41.87 ± 7.27% vs 20.25 ±6.70%, P < 0.05). Meanwhile, cyclinD1 protein expression could be detected in IP group. But in IR group, cyclinD1 protein expression occurred 2 h after reperfusion. The expression of cyclinD1 mRNA increased significantly in IP group at 0 and 1 h (0.568 ± 0.112 vs 0.274 ± 0.069, 0.762± 0.164 vs 0.348 ± 0.093, P < 0.05).CONCLUSION: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, which may be related to cell proliferation and expression of cyclinD1 during early ischemic reperfusion.

  2. A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation.

    Directory of Open Access Journals (Sweden)

    Hiroshi Okabe

    Full Text Available Cyclin D1 regulates G1 progression. Its transcriptional regulation is well understood. However, the mechanism underlying cyclin D1 ubiquitination and its subsequent degradation is not yet clear. We report that cyclin D1 undergoes increased degradation in the cytoplasm during S phase in a variety of cancer cells. This is mediated by phosphorylation at Thr286 through the activity of the Ras/Raf/MEK/ERK cascade and the F-box protein FBXW8, which is an E3 ligase. The majority of FBXW8 is expressed in the cytoplasm during G1 and S phase. In contrast, cyclin D1 accumulates in the nucleus during G1 phase and exits into the cytoplasm in S phase. Increased cyclin D1 degradation is linked to association with FBXW8 in the cytoplasm, and enhanced phosphorylation of cyclin D1 through sustained ERK1/2 signaling. Depletion of FBXW8 caused a significant accumulation of cyclin D1, as well as sequestration of CDK1 in the cytoplasm. This resulted in a severe reduction of cell proliferation. These effects could be rescued by constitutive nuclear expression of cyclin D1-T286A. Thus, FBXW8 plays an essential role in cancer cell proliferation through proteolysis of cyclin D1. It may present new opportunities to develop therapies targeting destruction of cyclin D1 or its regulator E3 ligase selectively.

  3. Novel role of sorting nexin 5 in renal D(1) dopamine receptor trafficking and function: implications for hypertension.

    Science.gov (United States)

    Villar, Van Anthony M; Armando, Ines; Sanada, Hironobu; Frazer, Lauren C; Russo, Christen M; Notario, Patricia M; Lee, Hewang; Comisky, Lauren; Russell, Holly Ann; Yang, Yu; Jurgens, Julie A; Jose, Pedro A; Jones, John E

    2013-05-01

    The D1 dopamine receptor (D1R) is widely expressed in the kidney and plays a crucial role in blood pressure regulation. Although much is known about D1R desensitization, especially through G-protein-coupled receptor kinase 4 (GRK4), comparatively little is known about other aspects of D1R trafficking and the proteins involved in the process. We now report the discovery of a dynamic interaction between sorting nexin 5 (SNX5), a component of the mammalian retromer, and D1R in human renal epithelial cells. We show that internalization of agonist-activated D1R is regulated by both SNX5 and GRK4, and that SNX5 is critical to the recycling of the receptor to the plasma membrane. SNX5 depletion increases agonist-activated D1R phosphorylation (>50% at basal condition), prevents D1R internalization and cAMP response, and delays receptor recycling compared to mock siRNA-transfected controls. Moreover, renal restricted subcapsular infusion of Snx5-specific siRNA (vs. mock siRNA) decreases sodium excretion (Δ=-0.2±0.005 mEq/mg creatinine) and further elevates the systolic blood pressure (Δ=48±5 mm Hg) in spontaneously hypertensive rats, indicating that SNX5 depletion impairs renal D1R function. These studies demonstrate an essential role for SNX5 in regulating D1R function, which may have important diagnostic, prognostic, and therapeutic implications in the management of essential hypertension.

  4. Post-transcriptional regulation of dopamine D1 receptor expression in caudate-putamen of cocaine-sensitized mice.

    Science.gov (United States)

    Tobón, Krishna E; Catuzzi, Jennifer E; Cote, Samantha R; Sonaike, Adenike; Kuzhikandathil, Eldo V

    2015-07-01

    The dopamine D1 receptor is centrally involved in mediating the effects of cocaine and is essential for cocaine-induced locomotor sensitization. Changes in D1 receptor expression have been reported in various models of cocaine addiction; however, the mechanisms that mediate these changes in D1 receptor expression are not well understood. Using preadolescent drd1a-EGFP mice and a binge cocaine treatment protocol we demonstrate that the D1 receptor is post-transcriptionally regulated in the caudate-putamen of cocaine-sensitized animal. While cocaine-sensitized mice express high levels of steady-state D1 receptor mRNA, the expression of D1 receptor protein is not elevated. We determined that the post-transcriptional regulation of D1 receptor mRNA is rapidly attenuated and D1 receptor protein levels increase within 30 min when the sensitized mice are challenged with cocaine. The rapid increase in D1 receptor protein levels requires de novo protein synthesis and correlates with the cocaine-induced hyperlocomotor activity in the cocaine-sensitized mice. The increase in D1 receptor protein levels in the caudate-putamen inversely correlated with the levels of microRNA 142-3p and 382, both of which regulate D1 receptor protein expression. The levels of these two microRNAs decreased significantly within 5 min of cocaine challenge in sensitized mice. The results provide novel insights into the previously unknown rapid kinetics of D1 receptor protein expression which occurs in a time scale that is comparable to the expression of immediate early genes. Furthermore, the results suggest a potential novel role for inherently labile microRNAs in regulating the rapid expression of D1 receptor protein in cocaine-sensitized animals.

  5. Histone deacetylase inhibitor, Trichostatin A induces ubiquitin-dependent cyclin D1 degradation in MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Charles Coombes R

    2006-02-01

    Full Text Available Abstract Background Cyclin D1 is an important regulator of G1-S phase cell cycle transition and has been shown to be important for breast cancer development. GSK3β phosphorylates cyclin D1 on Thr-286, resulting in enhanced ubiquitylation, nuclear export and degradation of the cyclin in the cytoplasm. Recent findings suggest that the development of small-molecule cyclin D1 ablative agents is of clinical relevance. We have previously shown that the histone deacetylase inhibitor trichostatin A (TSA induces the rapid ubiquitin-dependent degradation of cyclin D1 in MCF-7 breast cancer cells prior to repression of cyclin D1 gene (CCND1 transcription. TSA treatment also resulted in accumulation of polyubiquitylated GFP-cyclin D1 species and reduced levels of the recombinant protein within the nucleus. Results Here we provide further evidence for TSA-induced ubiquitin-dependent degradation of cyclin D1 and demonstrate that GSK3β-mediated nuclear export facilitates this activity. Our observations suggest that TSA treatment results in enhanced cyclin D1 degradation via the GSK3β/CRM1-dependent nuclear export/26S proteasomal degradation pathway in MCF-7 cells. Conclusion We have demonstrated that rapid TSA-induced cyclin D1 degradation in MCF-7 cells requires GSK3β-mediated Thr-286 phosphorylation and the ubiquitin-dependent 26S proteasome pathway. Drug induced cyclin D1 repression contributes to the inhibition of breast cancer cell proliferation and can sensitize cells to CDK and Akt inhibitors. In addition, anti-cyclin D1 therapy may be highly specific for treating human breast cancer. The development of potent and effective cyclin D1 ablative agents is therefore of clinical relevance. Our findings suggest that HDAC inhibitors may have therapeutic potential as small-molecule cyclin D1 ablative agents.

  6. Striatal dopamine D1 receptor is essential for contextual fear conditioning.

    Science.gov (United States)

    Ikegami, Masaru; Uemura, Takeshi; Kishioka, Ayumi; Sakimura, Kenji; Mishina, Masayoshi

    2014-02-05

    Fear memory is critical for animals to trigger behavioural adaptive responses to potentially threatening stimuli, while too much or inappropriate fear may cause psychiatric problems. Numerous studies have shown that the amygdala, hippocampus and medial prefrontal cortex play important roles in Pavlovian fear conditioning. Recently, we showed that striatal neurons are required for the formation of the auditory fear memory when the unconditioned stimulus is weak. Here, we found that selective ablation of striatal neurons strongly diminished contextual fear conditioning irrespective of the intensity of footshock. Furthermore, contextual fear conditioning was strongly reduced in striatum-specific dopamine D1 receptor knockout mice. On the other hand, striatum-specific dopamine D2 receptor knockout mice showed freezing responses comparable to those of control mice. These results suggest that striatal D1 receptor is essential for contextual fear conditioning.

  7. Production of large $^{41}$K Bose-Einstein condensates using D1 gray molasses

    CERN Document Server

    Chen, Hao-Ze; Wu, Yu-Ping; Liu, Xiang-Pei; Wang, Xiao-Qiong; Wang, Yu-Xuan; Chen, Yu-Ao; Pan, Jian-Wei

    2016-01-01

    We use D1 gray molasses to achieve Bose-Einstein condensation of a large number of $^{41}$K atoms in an optical dipole trap. By combining a new configuration of compressed-MOT with D1 gray molasses, we obtain a cold sample of $2.4\\times10^9$ atoms with a temperature as low as 42 $\\mu$K. After magnetically transferring the atoms into the final glass cell, we perform a two-stage evaporative cooling. A condensate with up to $1.2\\times10^6$ atoms in the lowest Zeeman state $|F=1,m_F=1\\rangle$ is achieved in the optical dipole trap. Furthermore, we observe two narrow Feshbach resonances in the lowest hyperfine channel, which are in good agreement with theoretical predictions.

  8. Integrated physics analysis of plasma start-up scenario of helical reactor FFHR-d1

    Science.gov (United States)

    Goto, T.; Miyazawa, J.; Sakamoto, R.; Seki, R.; Suzuki, C.; Yokoyama, M.; Satake, S.; Sagara, A.; The FFHR Design Group

    2015-06-01

    1D physics analysis of the plasma start-up scenario of the large helical device (LHD)-type helical reactor FFHR-d1 was conducted. The time evolution of the plasma profile is calculated using a simple model based on the LHD experimental observations. A detailed assessment of the magnetohydrodynamic equilibrium and neo-classical energy loss was conducted using the integrated transport analysis code TASK3D. The robust controllability of the fusion power was confirmed by feedback control of the pellet fuelling and a simple staged variation of the external heating power with a small number of simple diagnostics (line-averaged electron density, edge electron density and fusion power). A baseline operation control scenario (plasma start-up and steady-state sustainment) of the FFHR-d1 reactor for both self-ignition and sub-ignition operation modes was demonstrated.

  9. Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats

    DEFF Research Database (Denmark)

    Clausen, Bettina; Schachtman, Todd R.; Mark, Louise T.;

    2011-01-01

    D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390......, was administered to rats via routes that either did or did not affect spontaneous exploration: systemic or prelimbic administration, respectively. Effects were tested in spatial and non-spatial memory tasks selected for their requirements for self-initiated exploration of stimuli to be remembered in order...... to examine the effects on memory: cross-maze and object recognition task. Systemic administration reduced spatial exploration in cross-maze as well as in an open field test, and also reduced object exploration. Spatial (hippocampus-dependent) short-term memory was inhibited in the cross-maze and non...

  10. Effect of the deformation operator in the D1D5 CFT

    CERN Document Server

    Carson, Zaq; Mathur, Samir D; Turton, David

    2014-01-01

    The D1D5 CFT gives a holographic dual description of a near-extremal black hole in string theory. The interaction in this theory is given by a marginal deformation operator, which is composed of supercharges acting on a twist operator. The twist operator links together different copies of a free CFT. We study the effect of this deformation operator when it links together CFT copies with winding numbers M and N to produce a copy with winding M+N, populated with excitations of a particular form. We compute the effect of the deformation operator in the full supersymmetric theory, firstly on a Ramond-Ramond ground state and secondly on states with an initial bosonic or fermionic excitation. Our results generalize recent work which studied only the bosonic sector of the CFT. Our findings are a step towards understanding thermalization in the D1D5 CFT, which is related to black hole formation and evaporation in the bulk.

  11. Effect of the twist operator in the D1D5 CFT

    CERN Document Server

    Carson, Zaq; Mathur, Samir D; Turton, David

    2014-01-01

    The D1D5 CFT has been very useful in the study of black holes. The interaction in this theory involves a twist operator, which links together different copies of a free CFT. For the bosonic fields, we examine the action of this twist when it links together CFT copies with winding numbers M and N to produce a copy with winding M+N. Starting with the vacuum state generates a squeezed state, which we compute. Starting with an initial excitation on one of the copies gives a linear combination of excitations on the final state, which we also compute. These results generalize earlier computations where these quantities were computed for the special case M=N=1. Our results should help in understanding the thermalization process in the D1D5 CFT, which gives the dual of black hole formation in the bulk.

  12. Vacuum Structure of Twisted Scalar Field Theories on $M^{D-1} \\otimes S^{1}$

    CERN Document Server

    Hatanaka, H; Ohnishi, K; Sakamoto, M

    2001-01-01

    We study scalar field theories on M^{D-1} \\otimes S^1, which allow to impose twisted boundary conditions for the S^1 direction, in detail and report several interesting properties overlooked so far. One of characteristic features is the appearance of critical radii of the circle S^1. A phase transition can occur at the classical level or can be caused by quantum effects. Radiative corrections can restore broken symmetries or can break symmetries for small radius. A surprising feature is that the translational invariance for the S^1 direction can spontaneously be broken. A particular class of coordinate-dependent vacuum configurations is clarified and the O(N) \\phi^4 model on M^{D-1}\\otimes S^1 is extensively studied, as an illustrative example.

  13. Revisiting the D1/D5 system or bubbling in AdS{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Boni, Matteo [Dipartimento di Fisica dell' Universita di Milano (Italy); INFN, Sezione di Milano, Via Celoria 16, I-20133 Milan (Italy); Silva, Pedro J. [INFN, Sezione di Milano, Via Celoria 16, I-20133 Milan (Italy); Institut de Fisica d' Altes Energies (IFAE), Edf. Cn, Universitat Autonoma de Barcelona (UAB), E-08193 Bellaterra, Barcelona (Spain)

    2005-10-15

    In this article we study the relation between the bubbling construction and the Mathur's microscopic solutions for the D1/D5 system. We have found that the regular near horizon D1/D5 system (after appropriated constraints are imposed) contains all the bubbling regular solutions. Then, we show that the features of this system are rather different from the bubbling in AdS{sub 5} x S{sup 5}, since the perimeter and not the area plays a key role. After setting the main dictionary between the two approaches, we investigate on extensions to non-regular solutions like conical defects and/or naked singular solutions. In particular, among the latter metrics, closed time-like curves are found together with a chronology protection mechanism enforced by the AdS/CFT duality.

  14. Production of large 41K Bose-Einstein condensates using D1 gray molasses

    Science.gov (United States)

    Chen, Hao-Ze; Yao, Xing-Can; Wu, Yu-Ping; Liu, Xiang-Pei; Wang, Xiao-Qiong; Wang, Yu-Xuan; Chen, Yu-Ao; Pan, Jian-Wei

    2016-09-01

    We use D1 gray molasses to achieve Bose-Einstein condensation of a large number of 41K atoms in an optical dipole trap. By combining a specific configuration of a compressed magneto-optical trap with D1 gray molasses, we obtain a cold sample of 2.4 ×109 atoms with a temperature as low as 42 μ K . After magnetically transferring the atoms into the final glass cell, we perform a two-stage evaporative cooling. A condensate with up to 1.2 ×106 atoms in the lowest Zeeman state |F =1 , mF=1 > is achieved in the optical dipole trap. Furthermore, we observe two narrow Feshbach resonances in the lowest hyperfine channel, which are in good agreement with theoretical predictions.

  15. Pair production of Dirac particles in a d+1-dimensional noncommutative space-time

    CERN Document Server

    Samary, Dine Ousmane; Hounkonnou, Mahouton Norbert

    2014-01-01

    This work addresses the exact computation of the propability of fermionic particle pair production in $(d+1)-$ dimensional noncommutative Moyal space. Using the Seiberg-Witten maps that establish relations between noncommutative and commutative field variables, to first order in the noncommutative parameter $\\theta$, we derive the probability density of vacuum-vacuum pair production of Dirac particles. The cases of constant electromagnetic, alternating time-dependent and space-dependent electric fields are considered and discussed.

  16. Effects of Quantum Interference on the Profile of Excitation Spectra in the Atomic Sodium D1

    Institute of Scientific and Technical Information of China (English)

    LI Yongfang; ZHANG Xiangyang; SUN Jianfeng; ZHAO Yongmei; WANG Yongchang; ZHANG Yanliang; DING Liang’en; WANG Zugeng

    2002-01-01

    In this paper, an experiment in a sodium vapor cell with cw laser pumping is reported. Two dips in the excitation spectrum profile of the sodium \\$D1\\$ line are observed. Theoretically excitation spectra in the three-level system are calculated in detail and results are identical with experiments. It is demonstrated that the appearance of the two dips in the excitation spectrum is close connected with quantum interference effect.

  17. Pair production of Dirac particles in a d + 1-dimensional noncommutative space-time

    Energy Technology Data Exchange (ETDEWEB)

    Ousmane Samary, Dine [Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); University of Abomey-Calavi, International Chair in Mathematical Physics and Applications (ICMPA-UNESCO Chair), Cotonou (Benin); N' Dolo, Emanonfi Elias; Hounkonnou, Mahouton Norbert [University of Abomey-Calavi, International Chair in Mathematical Physics and Applications (ICMPA-UNESCO Chair), Cotonou (Benin)

    2014-11-15

    This work addresses the computation of the probability of fermionic particle pair production in d + 1-dimensional noncommutative Moyal space. Using Seiberg-Witten maps, which establish relations between noncommutative and commutative field variables, up to the first order in the noncommutative parameter θ, we derive the probability density of vacuum-vacuum pair production of Dirac particles. The cases of constant electromagnetic, alternating time-dependent, and space-dependent electric fields are considered and discussed. (orig.)

  18. Experimental Conditions: SE37_S19_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S19 PSEUDO: Unlabeled and labeled Medicago samples for flavonoid annotation using ShiftedIonsFinde...03_M1) and for a blank sample (S16_M1 to S16_M3) are used. Import file name is unlabeling SE37_DS5 Flavonoid like peak search by ShiftedIonsFinder ... ...SE37_S19_M1_D1 SE37 Medicago truncatula shoot metabolite analysis using stable isot

  19. Placental Estrogen Suppresses Cyclin D1 Expression in the Nonhuman Primate Fetal Adrenal Cortex*

    Science.gov (United States)

    Dumitrescu, Adina; Aberdeen, Graham W.; Pepe, Gerald J.

    2014-01-01

    We have previously shown that estrogen selectively suppresses growth of the fetal zone of the baboon fetal adrenal cortex, which produces the C19-steroid precursors, eg, dehydroepiandrosterone sulfate, which are aromatized to estrogen within the placenta. In the present study, we determined whether fetal adrenal expression of cell cycle regulators are altered by estrogen and thus provide a mechanism by which estrogen regulates fetal adrenocortical development. Cyclin D1 mRNA levels in the whole fetal adrenal were increased 50% (P < .05), and the number of cells in the fetal adrenal definitive zone expressing cyclin D1 protein was increased 2.5-fold (P < .05), whereas the total number of cells in the fetal zone and fetal serum dehydroepiandrosterone sulfate levels were elevated 2-fold (P < .05) near term in baboons in which fetal serum estradiol levels were decreased by 95% (P < .05) after maternal administration of the aromatase inhibitor letrozole and restored to normal by concomitant administration of letrozole plus estradiol throughout second half of gestation. However, fetal adrenocortical expression of cyclin D2, the cyclin-dependent kinase (Cdk)-2, Cdk4, and Cdk6, and Cdk regulatory proteins p27Kip1 and p57Kip2 were not changed by letrozole or letrozole plus estradiol administration. We suggest that estrogen controls the growth of the fetal zone of the fetal adrenal by down-regulating cyclin D1 expression and thus proliferation of progenitor cells within the definitive zone that migrate to the fetal zone. We propose that estrogen restrains growth and function of the fetal zone via cyclin D1 to maintain estrogen levels in a physiological range during primate pregnancy. PMID:25247468

  20. Placental estrogen suppresses cyclin D1 expression in the nonhuman primate fetal adrenal cortex.

    Science.gov (United States)

    Dumitrescu, Adina; Aberdeen, Graham W; Pepe, Gerald J; Albrecht, Eugene D

    2014-12-01

    We have previously shown that estrogen selectively suppresses growth of the fetal zone of the baboon fetal adrenal cortex, which produces the C19-steroid precursors, eg, dehydroepiandrosterone sulfate, which are aromatized to estrogen within the placenta. In the present study, we determined whether fetal adrenal expression of cell cycle regulators are altered by estrogen and thus provide a mechanism by which estrogen regulates fetal adrenocortical development. Cyclin D1 mRNA levels in the whole fetal adrenal were increased 50% (P < .05), and the number of cells in the fetal adrenal definitive zone expressing cyclin D1 protein was increased 2.5-fold (P < .05), whereas the total number of cells in the fetal zone and fetal serum dehydroepiandrosterone sulfate levels were elevated 2-fold (P < .05) near term in baboons in which fetal serum estradiol levels were decreased by 95% (P < .05) after maternal administration of the aromatase inhibitor letrozole and restored to normal by concomitant administration of letrozole plus estradiol throughout second half of gestation. However, fetal adrenocortical expression of cyclin D2, the cyclin-dependent kinase (Cdk)-2, Cdk4, and Cdk6, and Cdk regulatory proteins p27(Kip1) and p57(Kip2) were not changed by letrozole or letrozole plus estradiol administration. We suggest that estrogen controls the growth of the fetal zone of the fetal adrenal by down-regulating cyclin D1 expression and thus proliferation of progenitor cells within the definitive zone that migrate to the fetal zone. We propose that estrogen restrains growth and function of the fetal zone via cyclin D1 to maintain estrogen levels in a physiological range during primate pregnancy.

  1. Semaphorin 4A enhances lung fibrosis through activation of Akt via PlexinD1 receptor

    Indian Academy of Sciences (India)

    Hai-Ying Peng; Wei Gao; Fa-Rong Chong; Hong-Yan Liu; Ji Zhang

    2015-12-01

    Semaphorin 4A plays a regulatory role in immune function and angiogenesis. However, its specific involvement in controlling lung fibrosis, a process that is closely related to angiogenesis and inflammation is still poorly understood. In the present study, we show that treatment of Sema4A on normal lung fibroblasts induces expression of proteins that contribute to a contractile phenotype, including a-smooth muscle actin (-SMA), ezrin, moesin, and paxillin. We confirm that Sema4A enhances the ability of lung fibroblasts to contract collagen gel. Sema4A treatment led to resistance to apoptosis in normal lung fibroblasts. Relative to normal lung fibroblasts, fibroblasts cultured from scars of patients with the flbrotic disease Systemic Sclerosis (SSc) showed elevated Sema4A secretion, enhanced -SMA, ezrin, moesin, and paxillin expression, and high ability to induce collagen gel contraction. Using neutralizing antibody against Sema4A receptor, PlexinD1, we found that endogenous Sema4A signalling in SSc fibroblast was through PlexinD1 receptor. We then identified the signalling mechanism through which Sema4A-PlexinD1 promotes the ability of normal fibroblasts to contract a collagen gel matrix. Western blot analysis showed that Sema4A activated the Akt pathway in lung fibroblasts, and the specific inhibitor of Akt pathway, Akt inhibitor III, blocked the ability of Sema4A to promote the ability of lung fibroblasts to contract a collagen gel matrix. Thus, blocking Sema4A-PlexinD1-Akt cascades might be beneficial in reducing pulmonary fibrosis.

  2. Molecular hijacking of siroheme for the synthesis of heme and d1 heme

    OpenAIRE

    Bali, Shilpa; Lawrence, Andrew D.; Lobo, Susana A; Saraiva, Lígia M.; Golding, Bernard T.; Palmer, David J.; Mark J. Howard; Ferguson, Stuart J.; Warren, Martin J.

    2011-01-01

    Modified tetrapyrroles such as chlorophyll, heme, siroheme, vitamin B12, coenzyme F430, and heme d1 underpin a wide range of essential biological functions in all domains of life, and it is therefore surprising that the syntheses of many of these life pigments remain poorly understood. It is known that the construction of the central molecular framework of modified tetrapyrroles is mediated via a common, core pathway. Herein a further branch of the modified tetrapyrrole biosynthesis pathway i...

  3. Queueing systems with constant service time and evaluation of M/D/1,k

    DEFF Research Database (Denmark)

    Iversen, Villy Bæk

    1997-01-01

    Systems with constant service times have the particular property that the customers leave the servers in the same order in which they areaccepted for service. Probabilitites of integral waiting times can be expressed by the state probabilities, and non-integral waiting timescan be expressed by in...... by integral waiting times. This in combination by a result by Keilson results in an effective algorithm for evaluating M/D/1,k....

  4. Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in human skeletal muscle

    DEFF Research Database (Denmark)

    Middelbeek, R J W; Chambers, M A; Tantiwong, P

    2013-01-01

    Individuals with obesity and type 2 diabetes (T2D) are typically insulin resistant, exhibiting impaired skeletal muscle glucose uptake. Animal and cell culture experiments have shown that site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 and TBC1D1 is critical for GLUT4 tr...... translocation facilitating glucose uptake, but their regulation in human skeletal muscle is not well understood....

  5. Cerebello-cortical heterotopia in dentate nucleus, and other microdysgeneses in trisomy D1 (Patau) syndrome.

    Science.gov (United States)

    Hori, A; Peiffer, J; Pfeiffer, R A; Iizuka, R

    1980-01-01

    Several new histological findings in six cases of the trisomy D1 syndrome are described: hyperplasia of fetal structures (indusium griseum, median raphe of the medulla oblongata) and completely developed cerebellar cortical heterotopia in the dentate nucleus. In one case, a heterotopic pontine nucleus was found within the cerebellar white matter. The coexistence of overdeveloped and remaining fetal structures is emphasized. Several hypotheses regarding cerebellar dysgenesis are discussed.

  6. Overgroups of D1(F) in B1(F) and its pronor-madity%D1(F)在B1(F)中的扩群及其泛正规性

    Institute of Scientific and Technical Information of China (English)

    金永容

    2001-01-01

    域F上D1(1≥4)型Chevalley群D1(F)可自然地嵌入到B1(F)中去.当Chr F≠2,且F=F2时,本文定出了D1(F)在(B1(F)中的所有扩群,由此获得了B1(F)的一类极大子群.进而证明了D1(F)是B1(F)的泛正规子群.

  7. Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18 reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q.

    Science.gov (United States)

    Xu, S Y; Rosenberg, T; Gal, A

    1998-04-01

    Linkage analysis was performed on a large Danish family to refine the position of RP18, the locus for autosomal dominant retinitis pigmentosa, mapped previously between D1S534 and D1S305 in chromosome 1p13-q21. We genotyped the family members for five microsatellite-type DNA polymorphisms and mapped RP18 between D1S422 and D1S2858 to a region of less than 2 cM. No obvious candidate gene has yet been assigned to the chromosomal interval defined here.

  8. Resolvin D1 Reduces the Immunoinflammatory Response of the Rat Eye following Uveitis

    Directory of Open Access Journals (Sweden)

    Rossi Settimio

    2012-01-01

    Full Text Available This study investigated whether the administration of resolvin D1 to rats with endotoxininduced uveitis (EIU ameliorates the immuno-inflammatory profile of the eye. 24 h after the administration of 200 μg LPS into the footpad of Sprague-Dawley rats, severe changes of the structure of the eye occurred concomitantly with a severe inflammatory and immune response. These latter included strong infiltration of PMN leukocytes CD11b+ T-lymphocytes CD4+ and CD8+ within the eye and a significant release of the cytokines/chemokines TNF-alpha, CXCL8, and RANTES too. Bolus of resolvin D1 (RvD1; 10–100–1000 ng/kg in 200 μL of sterile saline via the tail vein significantly and dose-dependently (i reduced the development of the ocular derangement caused by LPS; (ii reduced the clinical score attributed to EIU; (iii reduced the protein concentration and myeloperoxidase activity (MPO in aqueous humor (AqH; and (iv reduced neutrophils, T-lymphocytes, and cytokines within the eye.

  9. Bogoliubov coefficients for the twist operator in the D1D5 CFT

    Energy Technology Data Exchange (ETDEWEB)

    Carson, Zaq, E-mail: carson.231@osu.edu; Mathur, Samir D., E-mail: mathur.16@osu.edu; Turton, David, E-mail: turton.7@osu.edu

    2014-12-15

    The D1D5 CFT is a holographic dual of a near-extremal black hole in string theory. The interaction in this theory involves a twist operator which joins together different copies of a free CFT. Given a large number of D1 and D5 branes, the effective length of the circle on which the CFT lives is very large. We develop a technique to study the effect of the twist operator in the limit where the wavelengths of excitations are short compared to this effective length, which we call the ‘continuum limit’. The method uses Bogoliubov coefficients to compute the effect of the twist operator in this limit. For bosonic fields, we use the method to reproduce recent results describing the effect of the twist operator when it links together CFT copies with windings M and N, producing a copy of winding M+N. We also comment on possible generalizations of our results. The methods developed here may help in understanding the twist interaction at higher orders. This in turn should provide insight into the thermalization process in the D1D5 CFT, which gives a holographic description of black hole formation.

  10. Synchrotron VUV radiation studies of the D^1\\Pi_u State of H_2

    CERN Document Server

    Dickenson, G D; Roudjane, M; de Oliveira, N; Joyeux, D; Nahon, L; Tchang-Brillet, W -Ü L; Glass-Maujean, M; Haar, I; Ehresmann, A; Ubachs, W; 10.1063/1.3502471

    2013-01-01

    The 3p\\pi D^1\\Pi_u state of the H_2 molecule was reinvestigated with different techniques at two synchrotron installations. The Fourier-Transform spectrometer in the vacuum ultraviolet wavelength range of the DESIRS beamline at the SOLEIL synchrotron was used for recording absorption spectra of the D^1\\Pi_u state at high resolution and high absolute accuracy, limited only by the Doppler contribution at 100 K. From these measurements line positions were extracted, in particular for the narrow resonances involving ^1\\Pi_u^- states, with an accuracy estimated at 0.06 cm^{-1} . The new data also closely match MQDT-calculations performed for the \\Pi^- components observed via the narrow Q-lines. The \\Lambda-doubling in the D^1\\Pi_u state was determined up to v=17. The 10 m normal incidence scanning monochromator at the beamline U125/2 of the BESSY II synchrotron, combined with a home built target chamber and equipped with a variety of detectors was used to unravel information on ionization, dissociation and intramo...

  11. Molecular hijacking of siroheme for the synthesis of heme and d1 heme.

    Science.gov (United States)

    Bali, Shilpa; Lawrence, Andrew D; Lobo, Susana A; Saraiva, Lígia M; Golding, Bernard T; Palmer, David J; Howard, Mark J; Ferguson, Stuart J; Warren, Martin J

    2011-11-08

    Modified tetrapyrroles such as chlorophyll, heme, siroheme, vitamin B(12), coenzyme F(430), and heme d(1) underpin a wide range of essential biological functions in all domains of life, and it is therefore surprising that the syntheses of many of these life pigments remain poorly understood. It is known that the construction of the central molecular framework of modified tetrapyrroles is mediated via a common, core pathway. Herein a further branch of the modified tetrapyrrole biosynthesis pathway is described in denitrifying and sulfate-reducing bacteria as well as the Archaea. This process entails the hijacking of siroheme, the prosthetic group of sulfite and nitrite reductase, and its processing into heme and d(1) heme. The initial step in these transformations involves the decarboxylation of siroheme to give didecarboxysiroheme. For d(1) heme synthesis this intermediate has to undergo the replacement of two propionate side chains with oxygen functionalities and the introduction of a double bond into a further peripheral side chain. For heme synthesis didecarboxysiroheme is converted into Fe-coproporphyrin by oxidative loss of two acetic acid side chains. Fe-coproporphyrin is then transformed into heme by the oxidative decarboxylation of two propionate side chains. The mechanisms of these reactions are discussed and the evolutionary significance of another role for siroheme is examined.

  12. Assessment of allelic diversity in intron-containing Mal d 1 genes and their association to apple allergenicity

    Directory of Open Access Journals (Sweden)

    Bolhaar Suzanne THP

    2008-11-01

    Full Text Available Abstract Background Mal d 1 is a major apple allergen causing food allergic symptoms of the oral allergy syndrome (OAS in birch-pollen sensitised patients. The Mal d 1 gene family is known to have at least 7 intron-containing and 11 intronless members that have been mapped in clusters on three linkage groups. In this study, the allelic diversity of the seven intron-containing Mal d 1 genes was assessed among a set of apple cultivars by sequencing or indirectly through pedigree genotyping. Protein variant constitutions were subsequently compared with Skin Prick Test (SPT responses to study the association of deduced protein variants with allergenicity in a set of 14 cultivars. Results From the seven intron-containing Mal d 1 genes investigated, Mal d 1.01 and Mal d 1.02 were highly conserved, as nine out of ten cultivars coded for the same protein variant, while only one cultivar coded for a second variant. Mal d 1.04, Mal d 1.05 and Mal d 1.06 A, B and C were more variable, coding for three to six different protein variants. Comparison of Mal d 1 allelic composition between the high-allergenic cultivar Golden Delicious and the low-allergenic cultivars Santana and Priscilla, which are linked in pedigree, showed an association between the protein variants coded by the Mal d 1.04 and -1.06A genes (both located on linkage group 16 with allergenicity. This association was confirmed in 10 other cultivars. In addition, Mal d 1.06A allele dosage effects associated with the degree of allergenicity based on prick to prick testing. Conversely, no associations were observed for the protein variants coded by the Mal d 1.01 (on linkage group 13, -1.02, -1.06B, -1.06C genes (all on linkage group 16, nor by the Mal d 1.05 gene (on linkage group 6. Conclusion Protein variant compositions of Mal d 1.04 and -1.06A and, in case of Mal d 1.06A, allele doses are associated with the differences in allergenicity among fourteen apple cultivars. This information

  13. THE EXPRESSION AND CLINICAL SIGNIFICANCE OF P21 (WAF1/CIP1)AND CYCLIN D1 PROTEIN IN COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the effect of P21 (WAF1/CIP1) and cyclin D1 and their relationship in colorec- tal carcinoma. Methods The expression of P21 and cyclin D1 was studied in 40 colorectal carcinoma and 10 normal tissues using S-P immunohistochemical technique. Results Decreased expression of P12 and overexpression of cyclin D1 were revealed in colorectal carcinoma. Decreased expression of P21 was related to lymph node metastasis. No cor- relation was found between cyclin D1 and clinicopathological parameters. Conclusion Decreased expression of P21 and overexpression of cyclin D1 may be involved in colorectal tumorigenesis,and were associated with poor prognosis. No correlation was found between P21 and cyclin D1 in colorectai carcinoma.

  14. Isolation and characterization of mutant Sinorhizobium meliloti NodD1 proteins with altered responses to luteolin.

    Science.gov (United States)

    Peck, Melicent C; Fisher, Robert F; Bliss, Robert; Long, Sharon R

    2013-08-01

    NodD1, a member of the NodD family of LysR-type transcriptional regulators (LTTRs), mediates nodulation (nod) gene expression in the soil bacterium Sinorhizobium meliloti in response to the plant-secreted flavonoid luteolin. We used genetic screens and targeted approaches to identify NodD1 residues that show altered responses to luteolin during the activation of nod gene transcription. Here we report four types of NodD1 mutants. Type I (NodD1 L69F, S104L, D134N, and M193I mutants) displays reduced or no activation of nod gene expression. Type II (NodD1 K205N) is constitutively active but repressed by luteolin. Type III (NodD1 L280F) demonstrates enhanced activity with luteolin compared to that of wild-type NodD1. Type IV (NodD1 D284N) shows moderate constitutive activity yet can still be induced by luteolin. In the absence of luteolin, many mutants display a low binding affinity for nod gene promoter DNA in vitro. Several mutants also show, as does wild-type NodD1, increased affinity for nod gene promoters with added luteolin. All of the NodD1 mutant proteins can homodimerize and heterodimerize with wild-type NodD1. Based on these data and the crystal structures of several LTTRs, we present a structural model of wild-type NodD1, identifying residues important for inducer binding, protein multimerization, and interaction with RNA polymerase at nod gene promoters.

  15. File list: Oth.Liv.05.Nr1d1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Liv.05.Nr1d1.AllCell mm9 TFs and others Nr1d1 Liver SRX128176,SRX997762,SRX9977...63,SRX997761,SRX997760,SRX997765,SRX997764,SRX109461,SRX100296,SRX994725,SRX994726,SRX100297 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.05.Nr1d1.AllCell.bed ...

  16. Effect of allelic variations at the Glu-D1, Glu-A3, Glu-B3 and Pinb-D1 loci on flour characteristics and bread loaf volume

    Science.gov (United States)

    Doubled haploid wheat lines developed from a cross between Keumkang, a hard white winter wheat, and Olgeuru, soft red winter wheat were used to determine the effects of allelic variation in Glu-D1, Glu-A3, Glu-B3 and Pinb-D1 loci on physiochemical properties of flour and bread loaf volume. Variation...

  17. Altered functioning of both renal dopamine D1 and angiotensin II type 1 receptors causes hypertension in old rats.

    Science.gov (United States)

    Chugh, Gaurav; Lokhandwala, Mustafa F; Asghar, Mohammad

    2012-05-01

    Activation of renal dopamine D1 (D1R) and angiotensin II type 1 receptors (AT(1)Rs) influences the activity of proximal tubular sodium transporter Na,K-ATPase and maintains sodium homeostasis and blood pressure. We reported recently that diminished D1R and exaggerated AT(1)R functions are associated with hypertension in old Fischer 344 × Brown Norway F1 (FBN) rats, and oxidative stress plays a central role in this phenomenon. Here we studied the mechanisms of age-associated increase in oxidative stress on diminished D1R and exaggerated AT(1)R functions in the renal proximal tubules of control and antioxidant Tempol-treated adult and old FBN rats. Although D1R numbers and D1R agonist SKF38393-mediated stimulation of [(35)S]-GTPγS binding (index of D1R activation) were lower, G protein-coupled receptor kinase 4 (kinase that uncouples D1R) levels were higher in old FBN rats. Tempol treatment restored D1R numbers and G protein coupling and reduced G protein-coupled receptor kinase 4 levels in old FBN rats. Angiotensin II-mediated stimulation of [(35)S]-GTPγS binding and Na,K-ATPase activity were higher in old FBN rats, which were also restored with Tempol treatment. We also measured renal AT(1)R function in adult and old Fischer 344 (F344) rats, which, despite exhibiting an age-related increase in oxidative stress and diminished renal D1R function, are normotensive. We found that diuretic and natriuretic responses to candesartan (indices of AT(1)R function) were similar in F344 rats, a likely explanation for the absence of age-associated hypertension in these rats. Perhaps, alterations in both D1R (diminished) and AT(1)R (exaggerated) functions are necessary for the development of age-associated hypertension, as seen in old FBN rats.

  18. 基于BIOCLIM模型的元江干热河谷稀树灌木草丛空间分布研究%The Spatial Distribution Research of Savanna Shrub and Grass of Yuanjiang Dry-hot Valleys Based on the BIOCLIM Model

    Institute of Scientific and Technical Information of China (English)

    王一凯; 张蒙蒙; 段卫虎; 杨凯悦; 黄诚; 周汝良

    2015-01-01

    According to the three factors affecting the temperature ,digital elevation model (DEM ) and the normalized difference vegetation index (NDVI) of Savanna shrub and grass of Yuanjiang dry -hot valleys , the article uses the BIOCLIM model to simulate the spatial distribution of Savanna shrub and grass of Yuan‐jiang dry -hot valleys ,w hich realizes the visual expression of spatial distribution of the dry -hot valleys in Yuanjiang County .The results show that the distribution of dry -hot valleys mainly concentrates on both sides outside Yuanjiang County .The dry -hot valleys'distribution is more concentrated in the east area but more dispersed in south area .Moreover ,in recent years ,the increasing human activities have some influences on the ecological environment of Yuanjiang river valley .The model forecasts the future distribution of dry ar‐ea in Yuanjiang County ,w hich aims to provide decision support for biodiversity conservation and vegetation restoration in the area .%根据影响干热河谷稀树灌木草丛分布的温度、数字高程模型(DEM )以及归一化植被指数(NDVI)三个因子,使用BIOCLIM模型模拟元江县干热河谷稀疏灌木草丛空间分布,实现了元江县干热河谷空间分布的可视化表达。结果表明:干热河谷分布主要集中于除元江县城外的河谷两侧,其中东部分布较为集中,而在南部地区分布较为分散。加之近年来人为活动的加剧,对元江河谷生态环境的变化也有一定影响,该模型很好地预测了未来元江县干热面积的分布情况,以期对生物多样性保护和植被恢复提供决策支持。

  19. Detection of cyclin D1 mRNA by hybridization sensitive NIC-oligonucleotide probe.

    Science.gov (United States)

    Kovaliov, Marina; Segal, Meirav; Kafri, Pinhas; Yavin, Eylon; Shav-Tal, Yaron; Fischer, Bilha

    2014-05-01

    A large group of fluorescent hybridization probes, includes intercalating dyes for example thiazole orange (TO). Usually TO is coupled to nucleic acids post-synthetically which severely limits its use. Here, we have developed a phosphoramidite monomer, 10, and prepared a 2'-OMe-RNA probe, labeled with 5-(trans-N-hexen-1-yl-)-TO-2'-deoxy-uridine nucleoside, dU(TO), (Nucleoside bearing an Inter-Calating moiety, NIC), for selective mRNA detection. We investigated a series of 15-mer 2'-OMe-RNA probes, targeting the cyclin D1 mRNA, containing one or several dU(TO) at various positions. dU(TO)-2'-OMe-RNA exhibited up to 7-fold enhancement of TO emission intensity upon hybridization with the complementary RNA versus that of the oligomer alone. This NIC-probe was applied for the specific detection of a very small amount of a breast cancer marker, cyclin D1 mRNA, in total RNA extract from cancerous cells (250 ng/μl). Furthermore, this NIC-probe was found to be superior to our related NIF (Nucleoside with Intrinsic Fluorescence)-probe which could detect cyclin D1 mRNA target only at high concentrations (1840 ng/μl). Additionally, dU(T) can be used as a monomer in solid-phase oligonucleotide synthesis, thus avoiding the need for post-synthetic modification of oligonucleotide probes. Hence, we propose dU(TO) oligonucleotides, as hybridization probes for the detection of specific RNA in homogeneous solutions and for the diagnosis of breast cancer.

  20. RhoA promotes epidermal stem cell proliferation via PKN1-cyclin D1 signaling

    Science.gov (United States)

    Wang, Fan; Zhan, Rixing; Chen, Liang; Dai, Xia; Wang, Wenping; Guo, Rui; Li, Xiaoge; Li, Zhe; Wang, Liang; Huang, Shupeng; Shen, Jie

    2017-01-01

    Objective Epidermal stem cells (ESCs) play a critical role in wound healing, but the mechanism underlying ESC proliferation is not well defined. Here, we explore the effects of RhoA on ESC proliferation and the possible underlying mechanism. Methods Human ESCs were enriched by rapid adhesion to collagen IV. RhoA(+/+)(G14V), RhoA(-/-)(T19N) and pGFP control plasmids were transfected into human ESCs. The effect of RhoA on cell proliferation was detected by cell proliferation and DNA synthesis assays. Induction of PKN1 activity by RhoA was determined by immunoblot analysis, and the effects of PKN1 on RhoA in terms of inducing cell proliferation and cyclin D1 expression were detected using specific siRNA targeting PKN1. The effects of U-46619 (a RhoA agonist) and C3 transferase (a RhoA antagonist) on ESC proliferation were observed in vivo. Results RhoA had a positive effect on ESC proliferation, and PKN1 activity was up-regulated by the active RhoA mutant (G14V) and suppressed by RhoA T19N. Moreover, the ability of RhoA to promote ESC proliferation and DNA synthesis was interrupted by PKN1 siRNA. Additionally, cyclin D1 protein and mRNA expression levels were up-regulated by RhoA G14V, and these effects were inhibited by siRNA-mediated knock-down of PKN1. RhoA also promoted ESC proliferation via PKN in vivo. Conclusion This study shows that the effect of RhoA on ESC proliferation is mediated by activation of the PKN1-cyclin D1 pathway in vitro, suggesting that RhoA may serve as a new therapeutic target for wound healing. PMID:28222172

  1. Diverse Flavonoids Stimulate NodD1 Binding to nod Gene Promoters in Sinorhizobium meliloti

    OpenAIRE

    Peck, Melicent C.; Fisher, Robert F.; Long, Sharon R.

    2006-01-01

    NodD1 is a member of the NodD family of LysR-type transcriptional regulators that mediates the expression of nodulation (nod) genes in the soil bacterium Sinorhizobium meliloti. Each species of rhizobia establishes a symbiosis with a limited set of leguminous plants. This host specificity results in part from a NodD-dependent upregulation of nod genes in response to a cocktail of flavonoids in the host plant's root exudates. To demonstrate that NodD is a key determinant of host specificity, w...

  2. Hair on non-extremal D1-D5 bound states

    CERN Document Server

    Roy, Pratik; Virmani, Amitabh

    2016-01-01

    We consider a truncation of type IIB supergravity on four-torus where in addition to the Ramond-Ramond 2-form field, the Ramond-Ramond axion (w) and the NS-NS 2-form field (B) are also retained. In the (w, B) sector we construct a linearised perturbation carrying only left moving momentum on two-charge non-extremal D1-D5 geometries of Jejjala, Madden, Ross and Titchener. The perturbation is found to be smooth everywhere and normalizable. It is constructed by matching to leading order solutions of the perturbation equations in the inner and outer regions of the geometry.

  3. Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Yin-Chieh Lai

    Full Text Available Several genes that are involved in the regulation of circadian rhythms are implicated in the susceptibility to bipolar disorder (BD. The current study aimed to investigate the relationships between genetic variants in NR1D1 RORA, and RORB genes and BD in the Han Chinese population. We conducted a case-control genetic association study with two samples of BD patients and healthy controls. Sample I consisted of 280 BD patients and 200 controls. Sample II consisted of 448 BD patients and 1770 healthy controls. 27 single nucleotide polymorphisms in the NR1D1, RORA, and RORB genes were genotyped using GoldenGate VeraCode assays in sample I, and 492 markers in the three genes were genotyped using Affymetrix Genome-Wide CHB Array in sample II. Single marker and gene-based association analyses were performed using PLINK. A combined p-value for the joining effects of all markers within a gene was calculated using the rank truncated product method. Multifactor dimensionality reduction (MDR method was also applied to test gene-gene interactions in sample I. All markers were in Hardy-Weinberg equilibrium (P>0.001. In sample I, the associations with BD were observed for rs4774388 in RORA (OR = 1.53, empirical p-value, P = 0.024, and rs1327836 in RORB (OR = 1.75, P = 0.003. In Sample II, there were 45 SNPs showed associations with BD, and the most significant marker in RORA was rs11639084 (OR = 0.69, P = 0.002, and in RORB was rs17611535 (OR = 3.15, P = 0.027. A combined p-value of 1.6×10-6, 0.7, and 1.0 was obtained for RORA, RORB and NR1D1, respectively, indicting a strong association for RORA with the risk of developing BD. A four way interaction was found among markers in NR1D1, RORA, and RORB with the testing accuracy 53.25% and a cross-validation consistency of 8 out of 10. In sample II, 45 markers had empirical p-values less than 0.05. The most significant markers in RORA and RORB genes were rs11639084 (OR = 0.69, P = 0.002, and rs17611535 (OR = 3

  4. Measurement of hyperfine structure in the $\\rm D_1$ line of $^{87}$Rb

    CERN Document Server

    Datar, Durgesh; Ananthamurthy, Sharath; Natarajan, Vasant

    2016-01-01

    This work reports a new measurement of the hyperfine structure constant of the $\\rm D_1 $ line in $ \\rm ^{87}Rb $ through precision laser spectroscopy. In a departure from methods that rely on locking the laser on the transitions of interest, the technique reported here relies on scanning around the transition. This is carried out so as to overcome potential frequency shifts caused by various noise sources including electronic noise and thermal fluctuations. The value of the hyperfine constant reported here is $ A = 408.29(25) $ MHz, which is in variance from an earlier value reported from our lab but is consistent with other recent measurements.

  5. Thermodynamics of hot quantum scalar field in a (D+1) dimensional curved spacetime

    CERN Document Server

    C., W A Rojas

    2016-01-01

    We use the brick wall model to calculate the free energy of quantum scalar field in a curved spacetime (D +1) dimensions. We find the thermodynamics properties of quantum scalar field in several scenaries: Minkowski spacetime, Schwarzschild spacetime and BTZ spacetime. For the cases analysed, the thermodynamical properties of quantum scalar field is exactly with the reported. It was found that the entropy of the gas is proportional to the horizon area in a gravity field strong, which is consistent with the holographic principle.

  6. Momentum-carrying waves on D1-D5 microstate geometries

    CERN Document Server

    Mathur, Samir D

    2012-01-01

    If one attempts to add momentum-carrying waves to a black string then the solution develops a singularity at the horizon; this is a manifestation of the 'no hair theorem' for black objects. However individual microstates of a black string do not have a horizon, and so the above theorem does not apply. We construct a perturbation that adds momentum to a family of microstates of the extremal D1-D5 string. This perturbation is analogous to the 'singleton' mode localized at the boundary of AdS; to leading order it is pure gauge in the AdS interior of the geometry.

  7. Momentum-carrying waves on D1-D5 microstate geometries

    Energy Technology Data Exchange (ETDEWEB)

    Mathur, Samir D., E-mail: mathur@mps.ohio-state.edu [Department of Physics, Ohio State University, Columbus, OH 43210 (United States); Turton, David, E-mail: turton.7@osu.edu [Department of Physics, Ohio State University, Columbus, OH 43210 (United States)

    2012-09-21

    If one attempts to add momentum-carrying waves to a black string then the solution develops a singularity at the horizon; this is a manifestation of the 'no hair theorem' for black objects. However individual microstates of a black string do not have a horizon, and so the above theorem does not apply. We construct a perturbation that adds momentum to a family of microstates of the extremal D1-D5 string. This perturbation is analogous to the 'singleton' mode localized at the boundary of AdS; to leading order it is pure gauge in the AdS interior of the geometry.

  8. 5-Isopropylidene-1,3-dithiolo[4,5-d][1,3]dithiole-2-thione

    Directory of Open Access Journals (Sweden)

    Yoshiro Yamashita

    2009-05-01

    Full Text Available The title compound, C7H6S5, contains a 5-ylidene-1,3-dithiolo[4,5-d][1,3]dithiole-2-thione framework, which is an important synthetic precursor of multi-dimensional organic superconductors and conductors. The molecular framework is planar with an r.m.s. deviation of 0.012 Å for the non-H atoms. In the crystal structure, molecules are linked by short intermolecular S...S interactions [3.501 (5 and 3.581 (4 Å], constructing a zigzag molecular tape network along the c axis.

  9. Hair on non-extremal D1-D5 bound states

    Science.gov (United States)

    Roy, Pratik; Srivastava, Yogesh K.; Virmani, Amitabh

    2016-09-01

    We consider a truncation of type IIB supergravity on four-torus where in addition to the Ramond-Ramond 2-form field, the Ramond-Ramond axion ( w) and the NS-NS 2-form field ( B) are also retained. In the ( w, B) sector we construct a linearised perturbation carrying only left moving momentum on two-charge non-extremal D1-D5 geometries of Jejjala, Madden, Ross and Titchener. The perturbation is found to be smooth everywhere and normalisable. It is constructed by matching to leading order solutions of the perturbation equations in the inner and outer regions of the geometry.

  10. Prevalence and clinical implications of cyclin D1 expression in diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy

    DEFF Research Database (Denmark)

    Ok, Chi Young; Xu-Monette, Zijun Y; Tzankov, Alexandar

    2014-01-01

    oncogene E3 ubiquitin protein ligase (MDM2), MDM4, and tumor protein 53 (TP53) were rare or absent. Gene expression profiling did not reveal any striking differences with respect to cyclin D1 in DLBCL. CONCLUSIONS: Compared with patients who had cyclin D1-negative DLBCL, men were more commonly affected...

  11. 15 CFR 770.3 - Interpretations related to exports of technology and software to destinations in Country Group D:1.

    Science.gov (United States)

    2010-01-01

    ... technology and software to destinations in Country Group D:1. 770.3 Section 770.3 Commerce and Foreign Trade... technology and software to destinations in Country Group D:1. (a) Introduction. This section is intended to provide you additional guidance on how to determine whether your technology or software would be...

  12. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiao [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Shetty, Sreerama [Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708 (United States); Zhang, Ping [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Gao, Rong; Hu, Yuxin [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Wang, Shuxia [Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Li, Zhenyu [Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY 40536 (United States); Fu, Jian, E-mail: jian.fu@uky.edu [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)

    2014-06-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.

  13. Analogues of doxanthrine reveal differences between the dopamine D 1 receptor binding properties of chromanoisoquinolines and hexahydrobenzo[a]phenanthridines

    Science.gov (United States)

    Cueva, J.P.; Chemel, B.R.; Juncosa, J.I.; Lill, M.A.; Watts, V.J.; Nichols, D.E.

    2012-01-01

    Efforts to develop selective agonists for dopamine D 1-like receptors led to the discovery of dihydrexidine and doxanthrine, two bioisosteric ??-phenyldopamine-type full agonist ligands that display selectivity and potency at D 1-like receptors. We report herein an improved methodology for the synthesis of substituted chromanoisoquinolines (doxanthrine derivatives) and the evaluation of several new compounds for their ability to bind to D 1- and D 2-like receptors. Identical pendant phenyl ring substitutions on the dihydrexidine and doxanthrine templates surprisingly led to different effects on D 1-like receptor binding, suggesting important differences between the interactions of these ligands with the D 1 receptor. We propose, based on the biological results and molecular modeling studies, that slight conformational differences between the tetralin and chroman-based compounds lead to a shift in the location of the pendant ring substituents within the receptor. ?? 2011 Elsevier Ltd. All rights reserved.

  14. Superdescendants of the D1D5 CFT and their dual 3-charge geometries

    Energy Technology Data Exchange (ETDEWEB)

    Giusto, Stefano [Dipartimento di Fisica ed Astronomia “Galileo Galilei”, Università di Padova,Via Marzolo 8, 35131 Padova (Italy); I.N.F.N. Sezione di Padova,Via Marzolo 8, 35131 Padova (Italy); Russo, Rodolfo [Centre for Research in String Theory, School of Physics and Astronomy,Queen Mary University of London, Mile End Road, London, E1 4NS (United Kingdom); Laboratoire de Physique Théorique de L’Ecole Normale Supérieure,24 rue Lhomond, 75231 Paris cedex (France)

    2014-03-03

    We describe how to obtain the gravity duals of semiclassical states in the D1-D5 CFT that are superdescendants of a class of RR ground states. On the gravity side, the configurations we construct are regular and asymptotically reproduce the 3-charge D1-D5-P black hole compactified on S{sup 1}×T{sup 4}. The geometries depend trivially on the T{sup 4} directions but non-trivially on the remaining 6D space. In the decoupling limit, they reduce to asymptotically AdS{sub 3}×S{sup 3}×T{sup 4} spaces that are dual to CFT states obtained by acting with (exponentials of) the operators of the superconformal algebra. As explicit examples, we generalise the solution first constructed in arXiv:1306.1745 and discuss another class of states that have a more complicated dual geometry. By using the free orbifold description of the CFT we calculate the average values for momentum and the angular momenta of these configurations. Finally we compare the CFT results with those obtained in the bulk from the asymptotically M{sup 1,4}×S{sup 1}×T{sup 4} region.

  15. Thermodynamics of (d+1)-dimensional NUT-charged AdS spacetimes

    Energy Technology Data Exchange (ETDEWEB)

    Clarkson, R. E-mail: rick@avatar.uwaterloo.ca; Fatibene, L. E-mail: fatibene@dm.unito.it; Mann, R.B. E-mail: mann@avatar.uwaterloo.ca

    2003-03-03

    We consider the thermodynamic properties of (d+1)-dimensional spacetimes with NUT charges. Such spacetimes are asymptotically locally anti-de Sitter (or flat), with non-trivial topology in their spatial sections, and can have fixed point sets of the Euclidean time symmetry that are either (d-1)-dimensional (called 'bolts') or of lower dimensionality (pure 'NUTs'). We compute the free energy, conserved mass, and entropy for 4, 6, 8 and 10 dimensions for each, using both Noether charge methods and the AdS/CFT-inspired counterterm approach. We then generalize these results to arbitrary dimensionality. We find in 4k+2 dimensions that there are no regions in parameter space in the pure NUT case for which the entropy and specific heat are both positive, and so all such spacetimes are thermodynamically unstable. For the pure NUT case in 4k dimensions a region of stability exists in parameter space that decreases in size with increasing dimensionality. All bolt cases have some region of parameter space for which thermodynamic stability can be realized.

  16. Thermodynamics of $(d+1)$-dimensional NUT-charged AdS Spacetimes

    CERN Document Server

    Clarkson, R; Mann, R B

    2003-01-01

    We consider the thermodynamic properties of $(d+1)$-dimensional spacetimes with NUT charges. Such spacetimes are asymptotically locally anti de Sitter (or flat), with non-trivial topology in their spatial sections, and can have fixed point sets of the Euclidean time symmetry that are either $(d-1)$-dimensional (called "bolts") or of lower dimensionality (pure "NUTs"). We compute the free energy, conserved mass, and entropy for 4, 6, 8 and 10 dimensions for each, using both Noether charge methods and the AdS/CFT-inspired counterterm approach. We then generalize these results to arbitrary dimensionality. We find in $4k+2$ dimensions that there are no regions in parameter space in the pure NUT case for which the entropy and specific heat are both positive, and so all such spacetimes are thermodynamically unstable. For the pure NUT case in $4k$ dimensions a region of stability exists in parameter space that decreases in size with increasing dimensionality. All bolt cases have some region of parameter space for wh...

  17. Subplane-based Control Rod Decusping Techniques for the 2D/1D Method in MPACT

    Energy Technology Data Exchange (ETDEWEB)

    Graham, Aaron M [ORNL; Collins, Benjamin S [ORNL; Downar, Thomas [University of Michigan

    2017-01-01

    The MPACT transport code is being jointly developed by Oak Ridge National Laboratory and the University of Michigan to serve as the primary neutron transport code for the Virtual Environment for Reactor Applications Core Simulator. MPACT uses the 2D/1D method to solve the transport equation by decomposing the reactor model into a stack of 2D planes. A fine mesh flux distribution is calculated in each 2D plane using the Method of Characteristics (MOC), then the planes are coupled axially through a 1D NEM-P$_3$ calculation. This iterative calculation is then accelerated using the Coarse Mesh Finite Difference method. One problem that arises frequently when using the 2D/1D method is that of control rod cusping. This occurs when the tip of a control rod falls between the boundaries of an MOC plane, requiring that the rodded and unrodded regions be axially homogenized for the 2D MOC calculations. Performing a volume homogenization does not properly preserve the reaction rates, causing an error known as cusping. The most straightforward way of resolving this problem is by refining the axial mesh, but this can significantly increase the computational expense of the calculation. The other way of resolving the partially inserted rod is through the use of a decusping method. This paper presents new decusping methods implemented in MPACT that can dynamically correct the rod cusping behavior for a variety of problems.

  18. Dorsal striatum D1-expressing neurons are involved with sensorimotor gating on prepulse inhibition test.

    Science.gov (United States)

    Rodrigues, Samanta; Salum, Cristiane; Ferreira, Tatiana L

    2017-01-01

    Prepulse inhibition (PPI) is a behavioral test in which the startle reflex response to a high-intensity stimulus (pulse) is inhibited by the prior presentation of a weak stimulus (prepulse). The classic neural circuitry that mediates startle response is localized in the brainstem; however, recent studies point to the contribution of structures involved in higher cognitive functions in regulating the sensorimotor gating, particularly forebrain regions innervated by dopaminergic nuclei. The aim of the present study was to verify the role of dorsal striatum (DS) and dopaminergic transmitting mediated by D1 and D2 receptors on PPI test in rats. DS inactivation induced by muscimol injection did not affect PPI (%PPI and startle response), although it impaired the locomotor activity and caused catalepsy. Infusion of D1-like antagonist SCH23390 impaired %PPI but did not disturb the startle response and locomotor activity evaluated immediately after PPI test. D2 antagonist microinjection (sulpiride) did not affect %PPI and startle response, but impaired motor activity. These results point to an important role of DS, probably mediated by direct basal ganglia pathway, on modulation of sensorimotor gating, in accordance with clinical studies showing PPI deficits in schizophrenia, Tourette syndrome, and compulsive disorders - pathologies related to basal ganglia dysfunctions.

  19. Bogoliubov coefficients for the twist operator in the D1D5 CFT

    CERN Document Server

    Carson, Zaq; Turton, David

    2014-01-01

    The D1D5 CFT is a holographic dual of a near-extremal black hole in string theory. The interaction in this theory involves a twist operator which joins together different copies of a free CFT. Given a large number of D1 and D5 branes, the effective length of the circle on which the CFT lives is very large. We develop a technique to study the effect of the twist operator in the limit where the wavelengths of excitations are short compared to this effective length, which we call the 'continuum limit'. The method uses Bogoliubov coefficients to compute the effect of the twist operator in this limit. For bosonic fields, we use the method to reproduce recent results describing the effect of the twist operator when it links together CFT copies with windings M and N, producing a copy of winding M+N. We also comment on possible generalizations of our results. The methods developed here may help in understanding the twist interaction at higher orders. This in turn should provide insight into the thermalization process...

  20. Inhibition of Cholesterol Esterification Influences Cytokine Exspression in Lypopolisaccharide-activated P388D1 Macrophages

    Directory of Open Access Journals (Sweden)

    Rosa Rita Bonatesta

    2007-01-01

    Full Text Available Several in vivo and in vitro studies have demonstrated the involvement of infectious agents in the development of atherosclerosis. However, the mechanisms by which micro-organisms induce and/or aggravate atherosclerosis, are so far unclear. Accumulation of cholesterol esters and lipid laden cell formation are hallmark of the atherogenesis, however, the possible relationship between cholesterol esterification and the signal-transducing component of LPS recognition complex inducing cytokine secretion has not been yet investigated. In the present study, we investigated the effect of mevinolin, the ACAT inhibitor, Sandoz 58035, and plasma from statin-treated hypercholesterolemic patients on cholesterol metabolism and cytokine expression in LPS activated P388D1 macrophages. In P388D1 macrophages cholesterol synthesis and uptake, as well as cholesterol ester synthesis, were unchanged following LPS-activation. When cells were grown in presence of serum from patients under statin therapy, cholesterol esterification was lower compared to cells grown with plasma from healthy subjects, independently from the type of statin used. This effect was accompanied by inhibition of IL-1β expression in LPS activated cells. The ACAT inhibitor, Sandoz 58035, which completely blocked cholesterol esterification in normal and LPS-activated macrophages, prevented IL-1β and IL-6 over-expression in LPS activated cells. Although preliminary, these data point to a possible relationship between cholesterol esterification and cytokine production in macrophages, prospecting new possible mechanisms by which microbial or inflammatory agents may induce and/or accelerate the atherosclerotic process.

  1. Production and decay of D$_{1}$(2420)$^{0}$ and D$_{2}*$(2460)$^{0}$

    CERN Document Server

    Avery, P; Rodríguez, J; Stephens, R; Yang, S; Yelton, J; Cinabro, D; Henderson, S; Liu, T; Saulnier, M; Wilson, R; Yamamoto, H; Bergfeld, T; Eisenstein, B I; Gollin, G; Ong, B; Palmer, M; Selen, M; Thaler, J J; Edwards, K W; Ogg, M; Spaan, B; Bellerive, A; Britton, D I; Hyatt, E R F; MacFarlane, D B; Patel, P M; Sadoff, A J; Ammar, R; Ball, S; Baringer, P; Bean, A; Besson, D; Coppage, D; Copty, N K; Davis, R; Hancock, N; Kelly, M; Kotov, S A; Kravchenko, I V; Kwak, N; Lam, H; Kubota, Y; Lattery, M; Momayezi, M; Nelson, J K; Patton, S; Perticone, D; Poling, R A; Savinov, V; Schrenk, S; Wang, R; Alam, M S; Kim, I J; Nemati, B; O'Neill, J J; Severini, H; Sun, C R; Zoeller, M M; Crawford, G; Daubenmier, C M; Fulton, R; Fujino, D; Gan, K K; Honscheid, K; Kagan, H; Kass, R; Lee, J; Malchow, R L; Skovpen, Y; Sung, M; White, C; Butler, F; Fu, X; Kalbfleisch, G R; Ross, W R; Skubic, P L; Wood, M; Fast, J; McIlwain, R L; Miao, T; Miller, D H; Modesitt, M; Payne, D; Shibata, E I; Shipsey, I P J; Wang Pei Ning; Battle, M; Ernst, J; Gibbons, L K; Kwon, Y; Roberts, S; Thorndike, E H; Wang, C H; Dominick, J; Lambrecht, M; Sanghera, S; Shelkov, V; Skwarnicki, T; Stroynowski, R; Volobuev, I P; Wei, G; Zadorozhny, P; Artuso, M; Goldberg, M; He, D; Horwitz, N; Kennett, R; Mountain, R; Moneti, G C; Muheim, F; Mukhin, Y; Playfer, S; Rozen, Y; Stone, S; Thulasidas, M; Vasseur, G; Zhu, G; Bartelt, J; Csorna, S E; Egyed, Z; Jain, V; Kinoshita, K; Barish, B C; Chadha, M; Chan, S; Cowen, D F; Eigen, G; Miller, J S; O'Grady, C; Urheim, J; Weinstein, A J; Acosta, D; Athanas, M; Masek, G E; Paar, H P; Gronberg, J B; Kutschke, R; Menary, S R; Morrison, R J; Nakanishi, S; Nelson, H N; Nelson, T K; Qiao, C; Richman, J D; Ryd, A; Tajima, H; Sperka, D; Witherell, M S; Procario, M; Balest, R; Cho, K; Daoudi, M; Ford, W T; Johnson, D R; Lingel, K; Lohner, M; Rankin, P; Smith, J G; Alexander, J P; Bebek, C; Berkelman, K; Bloom, K; Browder, T E; Cassel, David G; Cho, H A; Coffman, D M; Crowcroft, D S; Drell, P S; Ehrlich, R; Gaidarev, P B; García-Sciveres, M; Geiser, B; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Jones, C D; Jones, S L; Kandaswamy, J; Katayama, N; Kim, P C; Kreinick, D L; Ludwig, G S; Masui, J; Mevissen, J; Mistry, N B; Ng, C R; Nordberg, E; Patterson, J R; Peterson, D; Riley, D; Salman, S; Sapper, M; Würthwein, F

    1994-01-01

    We have investigated D^{+}\\pi^{-} and D^{*+}\\pi^{-} final states and observed the two established L=1 charmed mesons, the D_1(2420)^0 with mass 2421^{+1+2}_{-2-2} MeV/c^{2} and width 20^{+6+3}_{-5-3} MeV/c^{2} and the D_2^*(2460)^0 with mass 2465 \\pm 3 \\pm 3 MeV/c^{2} and width 28^{+8+6}_{-7-6} MeV/c^{2}. Properties of these final states, including their decay angular distributions and spin-parity assignments, have been studied. We identify these two mesons as the j_{light}=3/2 doublet predicted by HQET. We also obtain constraints on {\\footnotesize \\Gamma_S/(\\Gamma_S + \\Gamma_D)} as a function of the cosine of the relative phase of the two amplitudes in the D_1(2420)^0 decay. hardcopies with figures can be obtained by writing to: Pam Morehouse preprint secretary Newman Lab Cornell University Ithaca, NY 14853 or by sending mail to: preprints@lns62.lns.cornell.edu

  2. The D^1\\Pi\\ state of HD and the mass scaling relation of its predissociation widths

    CERN Document Server

    Dickenson, G D; 10.1088/0953-4075/45/14/145101

    2013-01-01

    Absorption spectra of HD have been recorded in the wavelength range of 75 to 90 nm at 100 K using the vacuum ultraviolet Fourier transform spectrometer at the Synchrotron SOLEIL. The present wavelength resolution represents an order of magnitude improvement over that of previous studies. We present a detailed study of the D^1\\Pi - X^1\\Sigma^+_g system observed up to v'=18. The Q-branch transitions probing levels of \\Pi^- symmetry are observed as narrow resonances limited by the Doppler width at 100 K. Line positions for these transitions are determined to an estimated absolute accuracy of 0.06 cm^{-1} . Predissociation line widths of \\Pi^+ levels are extracted from the absorption spectra. A comparison with the recent results on a study of the D^1\\Pi state in H_2 and D_2 reveals that the predissociation widths scale as \\mu^-2J(J+1), with \\mu the reduced mass of the molecule and J the rotational angular momentum quantum number, as expected from an interaction with the B'^1\\Sigma_u^+ continuum causing the predis...

  3. Contact sensitizers decrease 33D1 expression on mature Langerhans cells.

    Science.gov (United States)

    Herouet, C; Cottin, M; Galanaud, P; Leclaire, J; Rousset, F

    1999-01-01

    Langerhans cells play a critical role in allergic contact hypersensitivity. In vivo, these cells capture xenobiotics that penetrate the skin and transport them through the lymphatic vessels into regional lymph nodes for presentation to T cells. During this migration step, Langerhans cells become mature dendritic cells according to their phenotype and their high immunostimulatory capacity. In vitro, when isolated from the skin and cultured for 3 days, Langerhans cells undergo similar phenotypic and functional maturation. In this study, the capacity of sensitizers, irritants and neutral chemicals to modulate the surface marker expression and morphology of pure mature murine Langerhans cells in vitro was examined. Contact with 4 sensitizers (2,4-dinitrobenzenesulfate, 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one, p-phenylenediamine, mercaptobenzo-thiazole) resulted in a rapid, specific, marked fall in 33D1 expression, a murine specific dendritic cell marker. No effect was observed with 2 neutral chemicals (sodium chloride, methyl nicotinate) or 2 irritants (dimethyl sulfoxide, benzalkonium chloride). Nevertheless, sodium lauryl sulfate, a very irritant detergent, altered morphology and down-regulated all membrane markers. These preliminary data suggest that in vitro modulation of 33D1 expression by strong sensitizers may be an approach to the development of an in vitro model for the identification of chemicals that have the potential to cause skin sensitization and to distinguish them as far as possible from irritants.

  4. Intangible assets for intangible deliverables

    DEFF Research Database (Denmark)

    Elsmore, Matthew J.

    2008-01-01

    As the dominant economic business model in Europe, services are important when we consider intangible assets. This article argues a case for some kind of 'special relationship' between service firms and trade marks-specifically bearing in mind the CTM system and new EU services law. On the question...... if there can be constructive overlap between trade marks and services and how this emerges, the analysis shows there is reason both for and against thinking that together the relevant sets of laws, among other things, ease the transition from national- to Community-based trading for the overwhelming majority...... of EU businesses. The article suggests a starting point for a fresh yet reassuringly ordinary dialogue within trade mark law, one that asserts it a central role in realising predicted economic benefits of the Internal Market....

  5. Night Wind - Deliverable D.3.2 main simulation report; Grid architecture for wind power production with energy storage through load shifting in refrigerated warehouses

    Energy Technology Data Exchange (ETDEWEB)

    Cronin, Tom; Bindner, Henrik; Zong, Yi

    2008-11-15

    This report represents Deliverable D.3.2 of Work Package 3 in the Night Wind project. The aim of this Work Package was to simulate a cold store (or number of cold stores) within a power system where there is a high degree of wind power penetration. The Night Wind Control System, developed as part of Work Package 5, was to be integrated into the simulations so that the wind power could be 'stored' in the cold store with maximum benefit to the electrical network, utility or cold store owner. To this end, the following have been accomplished: 1) The Night Wind concept has been described in terms of demand side management. 2) Input requirements and data have been specified and collected. Measured data from the existing cold store facility of Partner Logistics has been analysed. 3) Component models for the simulations (including the cold store model itself) have been developed for the simulation platform, IPSYS. 4) The Night Wind Control System (NWCS) from Work Package 5 has been developed so that it finishes computations within two minutes. 5) Controllers including the NWCS) have been operated with the cold store model within IPSYS. 6) Simulations have been performed with the cold store model and an increasing penetration of wind power. This report presents the results of the work undertaken in Work Package 3 which would have benefited from the additional time requested at the project meeting in March 2008, however, this extension of time was not granted. Nevertheless, the work that was possible is considered significantly complete, although it is acknowledged that there has been a delay in the presentation of this report. It should be noted that it was not possible to address the new aspects of Task 3.7 'Verification of simulation results' as there was no implementation of the night wind concept at the demonstration site (Task 7). Verification of the simulation of the present system has, naturally, been carried out and described in this report. (ln)

  6. PlexinD1 Is a Novel Transcriptional Target and Effector of Notch Signaling in Cancer Cells

    Science.gov (United States)

    Rehman, Michael; Capparuccia, Lorena

    2016-01-01

    The secreted semaphorin Sema3E controls cell migration and invasiveness in cancer cells. Sema3E-receptor, PlexinD1, is frequently upregulated in melanoma, breast, colon, ovarian and prostate cancers; however, the mechanisms underlying PlexinD1 upregulation and the downstream events elicited in tumor cells are still unclear. Here we show that the canonical RBPjk-dependent Notch signaling cascade controls PlexinD1 expression in primary endothelial and cancer cells. Transcriptional activation was studied by quantitative PCR and promoter activity reporter assays. We found that Notch ligands and constitutively activated intracellular forms of Notch receptors upregulated PlexinD1 expression; conversely RNAi-based knock-down, or pharmacological inhibition of Notch signaling by gamma-secretase inhibitors, downregulated PlexinD1 levels. Notably, both Notch1 and Notch3 expression positively correlates with PlexinD1 levels in prostate cancer, as well as in other tumor types. In prostate cancer cells, Sema3E-PlexinD1 axis was previously reported to regulate migration; however, implicated mechanisms were not elucidated. Here we show that in these cells PlexinD1 activity induces the expression of the transcription factor Slug, downregulates E-cadherin levels and enhances cell migration. Moreover, our mechanistic data identify PlexinD1 as a pivotal mediator of this signaling axis downstream of Notch in prostate cancer cells. In fact, on one hand, PlexinD1 is required to mediate cell migration and E-cadherin regulation elicited by Notch. On the other hand, PlexinD1 upregulation is sufficient to induce prostate cancer cell migration and metastatic potential in mice, leading to functional rescue in the absence of Notch. In sum, our work identifies PlexinD1 as a novel transcriptional target induced by Notch signaling, and reveals its role promoting prostate cancer cell migration and downregulating E-cadherin levels in Slug-dependent manner. Collectively, these findings suggest that

  7. THE EXPRESSION OF p16 AND CYCLIN D1 IN PROLIFERATIVE ENDOMETRIUM AND ENDOMETRIAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To studythe role of p16 and cyclin in the genesis and development of endometrial car-cinoma. Methods 12 cases of normal endometrium, 22 cases of proliferative endometrium and 41 cases of endome- trial carcinoma were detected for the expression of p16 and cyclin D1 by means of immunohistochemical S-P. Results In normal endometrium p16 was expressed while cyclm D1was almost negative in the proliferative phase, but both of them were negative in the secretory phase. Among the groups of the simple and compound hyperplasia, the atypical hyperplasia and the endometrial carcinoma,the expression of p16 showed a descending tendency, while the expression of cyclin showed an ascending tendency. In endometrial carcinomas the expression of p16 was significantly lower than that of normal endometrium and proliferative endometrium (P<0. 01 ,P<0.05). However, the expression of cy- clin in proliferate endometrium and endometrial carcinoma was significantly higher than that in normal endometri- un (P<0. 05,P<0. 01). The overexpression of cyclin D1 in the atypical hyperplasia group was obviously different from that in the simple and compound hyperplasia group (P<0.01). In endometrial carcinoma,the expression of p16 was decreasing with the descending of cell differentiate degree, on the opposite, the expression of cyclin was in-creased and there existed a negative correlation between them. It was also observed that the overexpression of cyclin was significant different between and ( P <0. 01 ). Conclusion p1 6 is a negative regulating factor of cell cycle in endometrial carcinoma, while cyclin is a positive one. Both of them are important in the genesis and devel-opment of endometrial carcinoma. The Iow expression of p1 6 and the overexpression of cyclin are related with the malicious biological behaviors of endometrial carcinoma and maybe play an important role in the judgement of prog- nosis. Overexpression of cyclin may be an earlier molecular event in the genesis of

  8. Structural and population-based evaluations of TBC1D1 p.Arg125Trp.

    Directory of Open Access Journals (Sweden)

    Tom G Richardson

    Full Text Available Obesity is now a leading cause of preventable death in the industrialised world. Understanding its genetic influences can enhance insight into molecular pathogenesis and potential therapeutic targets. A non-synonymous polymorphism (rs35859249, p.Arg125Trp in the N-terminal TBC1D1 phosphotyrosine-binding (PTB domain has shown a replicated association with familial obesity in women. We investigated these findings in the Avon Longitudinal Study of Parents and Children (ALSPAC, a large European birth cohort of mothers and offspring, and by generating a predicted model of the structure of this domain. Structural prediction involved the use of three separate algorithms; Robetta, HHpred/MODELLER and I-TASSER. We used the transmission disequilibrium test (TDT to investigate familial association in the ALSPAC study cohort (N = 2,292 mother-offspring pairs. Linear regression models were used to examine the association of genotype with mean measurements of adiposity (Body Mass Index (BMI, waist circumference and Dual-energy X-ray absorptiometry (DXA assessed fat mass, and logistic regression was used to examine the association with odds of obesity. Modelling showed that the R125W mutation occurs in a location of the TBC1D1 PTB domain that is predicted to have a function in a putative protein:protein interaction. We did not detect an association between R125W and BMI (mean per allele difference 0.27 kg/m(2 (95% Confidence Interval: 0.00, 0.53 P = 0.05 or obesity (odds ratio 1.01 (95% Confidence Interval: 0.77, 1.31, P = 0.96 in offspring after adjusting for multiple comparisons. Furthermore, there was no evidence to suggest that there was familial association between R125W and obesity (χ(2 = 0.06, P = 0.80. Our analysis suggests that R125W in TBC1D1 plays a role in the binding of an effector protein, but we find no evidence that the R125W variant is related to mean BMI or odds of obesity in a general population sample.

  9. A jumonji (Jarid2) protein complex represses cyclin D1 expression by methylation of histone H3-K9.

    Science.gov (United States)

    Shirato, Haruki; Ogawa, Satoko; Nakajima, Kuniko; Inagawa, Masayo; Kojima, Mizuyo; Tachibana, Makoto; Shinkai, Yoichi; Takeuchi, Takashi

    2009-01-09

    Covalent modifications of histone tails have critical roles in regulating gene expression. Previously, we identified the jumonji (jmj, Jarid2) gene, the jmjC domain, and a Jmj family. Recently, many Jmj family proteins have been shown to be histone demethylases, and jmjC is the catalytic domain. However, Jmj does not have histone demethylase activity because the jmjC domain lacks conserved residues for binding to cofactors. Independently of these studies, we previously showed that Jmj binds to the cyclin D1 promoter and represses the transcription of cyclin D1. Here, we show the mechanisms by which Jmj represses the transcription of cyclin D1. We found that a protein complex of Jmj had histone methyltransferase activity toward histone H3 lysine 9 (H3-K9). We also found that Jmj bound to the H3-K9 methyltransferases G9a and GLP. Expression of Jmj recruited G9a and GLP to the cyclin D1 promoter and increased H3-K9 methylation. Inactivation of both G9a and GLP, but not of only G9a, inhibited the methylation of H3-K9 in the cyclin D1 promoter and repression of cyclin D1 expression by Jmj. These results suggest that Jmj methylates H3-K9 and represses cyclin D1 expression through G9a and GLP, and that Jmj family proteins can regulate gene expression by not only histone demethylation but also other histone modification.

  10. Resibufogenin Induces G1-Phase Arrest through the Proteasomal Degradation of Cyclin D1 in Human Malignant Tumor Cells.

    Directory of Open Access Journals (Sweden)

    Masami Ichikawa

    Full Text Available Huachansu, a traditional Chinese medicine prepared from the dried toad skin, has been used in clinical studies for various cancers in China. Resibufogenin is a component of huachansu and classified as bufadienolides. Resibufogenin has been shown to exhibit the anti-proliferative effect against cancer cells. However, the molecular mechanism of resibufogenin remains unknown. Here we report that resibufogenin induces G1-phase arrest with hypophosphorylation of retinoblastoma (RB protein and down-regulation of cyclin D1 expression in human colon cancer HT-29 cells. Since the down-regulation of cyclin D1 was completely blocked by a proteasome inhibitor MG132, the suppression of cyclin D1 expression by resibufogenin was considered to be in a proteasome-dependent manner. It is known that glycogen synthase kinase-3β (GSK-3β induces the proteasomal degradation of cyclin D1. The addition of GSK-3β inhibitor SB216763 inhibited the reduction of cyclin D1 caused by resibufogenin. These effects on cyclin D1 by resibufogenin were also observed in human lung cancer A549 cells. These findings suggest that the anti-proliferative effect of resibufogenin may be attributed to the degradation of cyclin D1 caused by the activation of GSK-3β.

  11. Effects of aspirin-triggered resolvin D1 on peripheral blood mononuclear cells from patients with Chagas' heart disease.

    Science.gov (United States)

    Ogata, Haline; Teixeira, Maxelle Martins; Sousa, Rodrigo Cunha de; Silva, Marcos Vinícius da; Correia, Dalmo; Rodrigues Junior, Virmondes; Levy, Bruce David; Rogério, Alexandre de Paula

    2016-04-15

    Chagas disease is caused by Trypanosoma cruzi (T. cruzi). In some patients with Chagas disease, symptoms progress to chronic chagasic cardiomyopathy. Endogenously, inflammation is resolved in the presence of lipid mediators such as aspirin-triggered RvD1 (AT-RvD1) which has anti-inflammatory and pro-resolution effects. Here, we demonstrated, for the first time, the effects of AT-RvD1 on T. cruzi antigen-stimulated peripheral blood mononuclear cells (PBMCs) from patients with Chagas heart disease. The levels of IFN-γ, TNF-α, IL-10, and IL-13 increased in PBMCs from cardiac-form Chagas patients in stage B1 (patients with fewer heart abnormalities) stimulated with T. cruzi antigen compared to those in non-stimulated PBMCs. AT-RvD1 reduced the IFN-γ concentrations in PBMCs from patients with Chagas disease stimulated with T. cruzi antigen compared to stimulated with T. cruzi antigen cells. AT-RvD1 treatment resulted in no observable changes in TNF-α, IL-10, and IL-13 levels. AT-RvD1 significantly decreased the percentage of necrotic cells and caused a significant reduction in the proliferation rate of T. cruzi antigen-stimulated PBMCs from patients with Chagas disease. These findings demonstrate that AT-RvD1 modulates the immune response in Chagas disease patients and might have potential to be used as an alternative approach for slowing the development of further heart damage.

  12. Clinicopathological significance of p16, cyclin D1, Rb and MIB-1 levels in skull base chordoma and chondrosarcoma

    Institute of Scientific and Technical Information of China (English)

    Jun-qi Liu; Qiu-hang Zhang; Zhen-lin Wang

    2015-01-01

    Objective: To investigate the expression of p16, cyclin D1, retinoblastoma tumor suppressor protein (Rb) and MIB-1 in skull base chordoma and chondrosarcoma tissues, and to determine the clinicopathological significance of the above indexes in these diseases.Methods: A total of 100 skull base chordoma, 30 chondrosarcoma, and 20 normal cartilage tissue samples were analyzed by immunohistochemistry.The expression levels of p16, cyclinD1,Rb and MIB-1 proteins were assessed for potential correlation with the clinicopathological features.Results: As compared to normal cartilage specimen (control), there was decreased expression of p16, and increased expression of cyclin D1, Rb and MIB-1 proteins, in both skull base chordoma and chondrosarcoma specimens.MIB-1 LI levels were significantly increased in skull base chordoma specimens with negative expression of p16, and positive expression of cyclin D1 and Rb (P < 0.05).Significantly elevated MIB-1 LI was also detected in skull base chondrosarcoma tissues, while there was negative expression of p16, cyclin D1 and Rb (P < 0.05).In skull base chordoma, p16 negatively correlated with cyclin D1 and Rb, while cyclin D1 positively correlated with Rb.Additionally, p16, cyclin D1, Rb, or MIB-1 expression showed no correlation with age, gender, or pathological classification of patients with skull base chordoma (P > 0.05).However, p16 and MIB-1 levels correlated with the intradural invasion, and expression of p16, Rb and MIB-1 correlated with the number of tumor foci (P < 0.05).Further, the expression of p16 and MIB-1 appeared to correlate with the prognosis of patients with skull base chordoma.Conclusions: The abnormal expression of p16, cyclin D1 and Rb proteins might be associated with the tumorigenesis of skull base chordoma and chondrosarcoma.

  13. Protein kinase D1 signaling in angiogenic gene expression and VEGF-mediated angiogenesis

    Directory of Open Access Journals (Sweden)

    Bin eRen MD, Phd, FAHA

    2016-05-01

    Full Text Available Protein kinase D 1 (PKD-1 is a signaling kinase important in fundamental cell functions including migration, proliferation and differentiation. PKD-1 is also a key regulator of gene expression and angiogenesis that is essential for cardiovascular development and tumor progression. Further understanding molecular aspects of PKD-1 signaling in the regulation of angiogenesis may have translational implications in obesity, cardiovascular disease and cancer. The author will summarize and provide the insights into molecular mechanisms by which PKD-1 regulates transcriptional expression of angiogenic genes, focusing on the transcriptional regulation of CD36 by PKD-1-FoxO1 signaling axis along with the potential implications of this axis in arterial differentiation and morphogenesis. He will also discuss a new concept of dynamic balance between proangiogenic and antiangiogenic signaling in determining angiogenic switch, and stress how PKD-1 signaling regulates VEGF signaling-mediated angiogenesis.

  14. Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

    Science.gov (United States)

    Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

    2015-02-01

    The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

  15. Doppler-free spectroscopy on Cs D$_1$ line with a dual-frequency laser

    CERN Document Server

    Hafiz, Moustafa Abdel; De Clercq, Emeric; Boudot, Rodolphe

    2016-01-01

    We report on Doppler-free laser spectroscopy in a Cs vapor cell using a dual-frequency laser system tuned on the Cs D$_1$ line. Using counter-propagating beams with crossed linear polarizations, an original sign-reversal of the usual saturated absorption dip and large increase in Doppler-free atomic absorption is observed. This phenomenon is explained by coherent population trapping (CPT) effects. The impact of laser intensity and light polarization on absorption profiles is reported in both single-frequency and dual-frequency regimes. In the latter, frequency stabilization of two diode lasers was performed, yielding a beat-note fractional frequency stability at the level of $3 \\times 10^{-12}$ at 1 s averaging time. These performances are about an order of magnitude better than those obtained using a conventional single-frequency saturated absorption scheme.

  16. Holographic description of non-supersymmetric orbifolded D1-D5-P solutions

    CERN Document Server

    Chakrabarty, Bidisha; Virmani, Amitabh

    2015-01-01

    Non-supersymmetric black hole microstates are of great interest in the context of the black hole information paradox. We identify the holographic description of the general class of non-supersymmetric orbifolded D1-D5-P supergravity solutions found by Jejjala, Madden, Ross and Titchener. This class includes both completely smooth solutions and solutions with conical defects, and in the near-decoupling limit these solutions describe degrees of freedom in the cap region. The CFT description involves a general class of states obtained by fractional spectral flow in both left-moving and right-moving sectors, generalizing previous work which studied special cases in this class. We compute the massless scalar emission spectrum and emission rates in both gravity and CFT and find perfect agreement, thereby providing strong evidence for our proposed identification. We also investigate the physics of ergoregion emission as pair creation for these orbifolded solutions. Our results represent the largest class of non-supe...

  17. Smooth non-extremal D1-D5-P solutions as charged gravitational instantons

    CERN Document Server

    Chakrabarty, Bidisha; Virmani, Amitabh

    2016-01-01

    We present an alternative and more direct construction of the non-supersymmetric D1-D5-P supergravity solutions found by Jejjala, Madden, Ross and Titchener. We show that these solutions --- with all three charges and both rotations turned on --- can be viewed as a charged version of the Myers-Perry instanton. We present an inverse scattering construction of the Myers-Perry instanton metric in Euclidean five-dimensional gravity. The angular momentum bounds in this construction turn out to be precisely the ones necessary for the smooth microstate geometries. We add charges on the Myers-Perry instanton using appropriate SO(4,4) hidden symmetry transformations. The full construction can be viewed as an extension and simplification of a previous work by Katsimpouri, Kleinschmidt and Virmani.

  18. Complete Genome Sequence of a thermotolerant sporogenic lactic acid bacterium, Bacillus coagulans strain 36D1

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, Mun Su [University of Florida, Gainesville; Moritz, Brelan E. [University of Florida, Gainesville; Xie, Gary [Los Alamos National Laboratory (LANL); Glavina Del Rio, Tijana [U.S. Department of Energy, Joint Genome Institute; Dalin, Eileen [U.S. Department of Energy, Joint Genome Institute; Tice, Hope [U.S. Department of Energy, Joint Genome Institute; Bruce, David [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Chertkov, Olga [Los Alamos National Laboratory (LANL); Brettin, Thomas S [ORNL; Han, Cliff [Los Alamos National Laboratory (LANL); Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Patel, Milind [University of Florida, Gainesville; Ou, Mark [University of Florida, Gainesville; Harbrucker, Roberta [University of Florida, Gainesville; Ingram, Lonnie O. [University of Florida; Shanmugam, Keelnathan T. [University of Florida

    2011-01-01

    Bacillus coagulans is a ubiquitous soil bacterium that grows at 50-55 C and pH 5.0 and fer- ments various sugars that constitute plant biomass to L (+)-lactic acid. The ability of this spo- rogenic lactic acid bacterium to grow at 50-55 C and pH 5.0 makes this organism an attrac- tive microbial biocatalyst for production of optically pure lactic acid at industrial scale not only from glucose derived from cellulose but also from xylose, a major constituent of hemi- cellulose. This bacterium is also considered as a potential probiotic. Complete genome se- quence of a representative strain, B. coagulans strain 36D1, is presented and discussed.

  19. Complete Genome Sequence of a thermotolerant sporogenic lactic acid bacterium, Bacillus coagulans strain 36D1

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Gary [Los Alamos National Laboratory (LANL); Dalin, Eileen [U.S. Department of Energy, Joint Genome Institute; Tice, Hope [U.S. Department of Energy, Joint Genome Institute; Chertkov, Olga [Los Alamos National Laboratory (LANL); Land, Miriam L [ORNL

    2011-01-01

    Bacillus coagulans is a ubiquitous soil bacterium that grows at 50-55 C and pH 5.0 and fer-ments various sugars that constitute plant biomass to L (+)-lactic acid. The ability of this sporogenic lactic acid bacterium to grow at 50-55 C and pH 5.0 makes this organism an attractive microbial biocatalyst for production of optically pure lactic acid at industrial scale not only from glucose derived from cellulose but also from xylose, a major constituent of hemi-cellulose. This bacterium is also considered as a potential probiotic. Complete genome squence of a representative strain, B. coagulans strain 36D1, is presented and discussed.

  20. Evidence for a unique PTSD construct represented by PTSD's D1-D3 symptoms.

    Science.gov (United States)

    Elhai, Jon D; Biehn, Tracey L; Armour, Cherie; Klopper, Jessica J; Frueh, B Christopher; Palmieri, Patrick A

    2011-04-01

    Two models of posttraumatic stress disorder (PTSD) have received the most empirical support in confirmatory factor analytic studies: King, Leskin, King, and Weathers' (1998) Emotional Numbing model of reexperiencing, avoidance, emotional numbing and hyperarousal; and Simms, Watson, and Doebbeling's (2002) Dysphoria model of reexperiencing, avoidance, dysphoria and hyperarousal. These models only differ in placement of three PTSD symptoms: sleep problems (D1), irritability (D2), and concentration problems (D3). In the present study, we recruited 252 women victims of domestic violence and tested whether there is empirical support to separate these three PTSD symptoms into a fifth factor, while retaining the Emotional Numbing and Dysphoria models' remaining four factors. Confirmatory factor analytic findings demonstrated that separating the three symptoms into a separate factor significantly enhanced model fit for the Emotional Numbing and Dysphoria models. These three symptoms may represent a unique latent construct. Implications are discussed.

  1. The tight junction protein ZO-2 blocks cell cycle progression and inhibits cyclin D1 expression.

    Science.gov (United States)

    Gonzalez-Mariscal, Lorenza; Tapia, Rocio; Huerta, Miriam; Lopez-Bayghen, Esther

    2009-05-01

    ZO-2 is an adaptor protein of the tight junction that belongs to the MAGUK protein family. ZO-2 is a dual localization protein that in sparse cultures is present at the cell borders and the nuclei, whereas in confluent cultures it is concentrated at the cell boundaries. Here we have studied whether ZO-2 is able to regulate the expression of cyclin D1 (CD1) and cell proliferation. We have demonstrated that ZO-2 negatively regulates CD1 transcription by interacting with c-Myc at an E box present in CD1 promoter. We have further found that ZO-2 transfection into epithelial MDCK cells triggers a diminished expression of CD1 protein and decreases the rate of cell proliferation in a wound-healing assay.

  2. Electron affinities of d1 transition metal chloride clusters and onset of super halogen behavior

    Science.gov (United States)

    Behera, Swayamprabha; Joseph, Jorly; Jena, Purusottam

    2011-03-01

    Geometry, electronic structure, and electron affinity of d1 transition metal chloride clusters (MCl n , M = Sc,Y, La; n = 1--5) have been calculated using density functional theory. Chlorine atoms are chemically bound in all cases except for MCl 5 . The electron affinities of MCl n (n = 1--3) are small and increase only marginally as a function of n until the valence of the metal atom is consumed. Beyond this, they rise sharply and reach a value of 5.96, 6.03 and 5.90 eV for ScCl 4 , YCl 4 and LaCl 4 , respectively and remain high for n = 5. MCl n , (n = 4,5) clusters, therefore, behave as superhalogens. Results are compared with available experimental data

  3. The effect of cell passage number on osteogenic and adipogenic characteristics of D1 cells.

    Science.gov (United States)

    Kwist, K; Bridges, W C; Burg, K J L

    2016-08-01

    Cell line passage number is an important consideration when designing an experiment. At higher passages, it is generally understood that cell health begins to decline and, when this occurs, the result can be variable data. However, there are no specific guidelines regarding optimal passage range, and this information is dependent on cell type. To explore these variabilities, low passage D1 cells were thawed (passage 3) and passaged serially until a much higher number (passage 34). Samples were taken every five passages and analyzed for alkaline phosphatase and triglyceride; also, the gene expression of both adipogenic and osteogenic markers was tested. The results indicate that the growth rate of these cells did slow down after passage 30. However, expression of the osteogenic characteristics seemed to cycle, with the highest levels seen at passage 4 and 24. The adipocyte expression levels remained the same throughout the study.

  4. Effects of dopamine D1 and D2 receptor antagonists on laryngeal neurophysiology in the rat.

    Science.gov (United States)

    Feng, Xin; Henriquez, Victor M; Walters, Judith R; Ludlow, Christy L

    2009-08-01

    Hypophonia is an early symptom in Parkinson's disease (PD) that involves an increase in laryngeal muscle activity, interfering with voice production. Our aim was to use an animal model to better understand the role of different dopamine receptor subtypes in the control of laryngeal neurophysiology. First, we evaluated the combined effects of SCH23390-a D(1) receptor antagonist with a D(2) receptor antagonist (eticlopride) on laryngeal neurophysiology, and then tested the separate effects of selective receptor antagonists. Thyroarytenoid (TA) and gastrocnemius (GN) muscle activity was measured at rest and while stimulating the internal branch of superior laryngeal nerve to elicit the laryngeal adductor response (LAR) in alpha-chloralose-anesthetized rats. Paired stimuli at different interstimulus intervals between 250 and 5,000 ms measured central conditioning of the LAR. Changes in resting muscle activity, response latency, amplitude, and LAR conditioning after each drug were compared with the saline control. SCH23390 alone increased the resting TA muscle activity (P < 0.05). With the combined SCH23390 + eticlopride or SCH23390 alone, response latency decreased (P < 0.01), amplitude increased (P < 0.01), and the test LAR was reduced at 2,000-ms ISI (P < 0.01). No LAR changes occurred when eticlopride was administered alone at a low dose and only a tendency to suppress responses was found at a high dose. No changes in GN muscle activity occurred in any of the groups. The results suggest that a loss of stimulation of D(1) receptors plays a significant role in laryngeal pathophysiology in PD.

  5. Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine.

    Directory of Open Access Journals (Sweden)

    Natt Tasaniyananda

    Full Text Available Cats (Felis domesticus are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen in comparison with the vaccine made of crude cat hair extract (cCE. BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L-entrapped native Fel d 1 (L-nFD1, L-cCE, or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35 and Treg (up-regulation of IL-10 and TGF-β. In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients.

  6. SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells.

    Science.gov (United States)

    Klajn, A; Drakulic, D; Tosic, M; Pavkovic, Z; Schwirtlich, M; Stevanovic, M

    2014-11-01

    SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with both neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics.

  7. Hepatitis B virus subgenotypes D1 and D3 are prevalent in Pakistan

    Directory of Open Access Journals (Sweden)

    Chakravarty Runu

    2009-01-01

    Full Text Available Abstract Background As the hepatitis B genotyping is important for assessing its clinical implications and geographical distribution, the sub-genotypes have been found useful for determination of specific genomic markers related to hepatocarcinogenesis. In Pakistan, there is no reported data on molecular evolutionary analysis of HBV. A study was, therefore, much needed to evaluate the spectra of mutations present in the strains prevalent here. Findings to confirm specificity of PCR typing, phylogenetic analysis of the pre-S1 region and the divergence was studied through 13 sequences of 362 bp (accession number EF432765 – EF432777. A total of 315 serum samples, selected from HBsAg positive patients representing the major ethnic groups, residing in Karachi, Sindh were tested for genotyping. Genotype D (219/315 was found to be the most prevalent (70% amongst our patients. The rest of the genotypes A and a mixture of A and D (AD were distributed as 20%, and 10% respectively. Phylogenetic tree demonstrated clustering of 11 samples with subgenotype D1 sequences and the remaining two strains on a branch within D3 samples. All samples intermixed with strains from other countries and were found to be closely related to Indian, Iranian and Egyptian HBV strains with 98.7 – 99.0% homology. Conclusion This study confirms the predominance of genotype D in southeastern Asia and presence of subgenotypes DI and D3 in the Pakistani infected patients. More studies are required to investigate the reason for fewer inclusions of D3 compared to the D1 in Pakistani HBV strains.

  8. Improvement of the 2D/1D Method in MPACT Using the Sub-Plane Scheme

    Energy Technology Data Exchange (ETDEWEB)

    Graham, Aaron M [ORNL; Collins, Benjamin S [ORNL; Downar, Thomas [University of Michigan

    2017-01-01

    Oak Ridge National Laboratory and the University of Michigan are jointly developing the MPACTcode to be the primary neutron transport code for the Virtual Environment for Reactor Applications (VERA). To solve the transport equation, MPACT uses the 2D/1D method, which decomposes the problem into a stack of 2D planes that are then coupled with a 1D axial calculation. MPACT uses the Method of Characteristics for the 2D transport calculations and P3 for the 1D axial calculations, then accelerates the solution using the 3D Coarse mesh Finite Dierence (CMFD) method. Increasing the number of 2D MOC planes will increase the accuracy of the alculation, but will increase the computational burden of the calculations and can cause slow convergence or instability. To prevent these problems while maintaining accuracy, the sub-plane scheme has been implemented in MPACT. This method sub-divides the MOC planes into sub-planes, refining the 1D P3 and 3D CMFD calculations without increasing the number of 2D MOC planes. To test the sub-plane scheme, three of the VERA Progression Problems were selected: Problem 3, a single assembly problem; Problem 4, a 3x3 assembly problem with control rods and pyrex burnable poisons; and Problem 5, a quarter core problem. These three problems demonstrated that the sub-plane scheme can accurately produce intra-plane axial flux profiles that preserve the accuracy of the fine mesh solution. The eigenvalue dierences are negligibly small, and dierences in 3D power distributions are less than 0.1% for realistic axial meshes. Furthermore, the convergence behavior with the sub-plane scheme compares favorably with the conventional 2D/1D method, and the computational expense is decreased for all calculations due to the reduction in expensive MOC calculations.

  9. Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine

    Science.gov (United States)

    Tasaniyananda, Natt; Chaisri, Urai; Tungtrongchitr, Anchalee; Chaicumpa, Wanpen; Sookrung, Nitat

    2016-01-01

    Cats (Felis domesticus) are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen) in comparison with the vaccine made of crude cat hair extract (cCE). BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L)-entrapped native Fel d 1 (L-nFD1), L-cCE), or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions) towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35) and Treg (up-regulation of IL-10 and TGF-β). In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients. PMID:26954254

  10. Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia.

    OpenAIRE

    Yang, W. I.; Zukerberg, L R; Motokura, T.; Arnold, A.; Harris, N. L.

    1994-01-01

    Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/CLL) show a characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the Bcl-1 region. Recently it was shown that the key Bcl-1 region oncogene is cyclin D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We examined cyclin D1 protein expression in low-grade B-cell lymphomas and reactive lymphoid hyperplasias using polycl...

  11. Hairy cell leukemia with translocation (11;20)(q13;q11) and overexpression of cyclin D1.

    Science.gov (United States)

    Ishida, F; Kitano, K; Ichikawa, N; Ito, T; Kohara, Y; Taniguchi, T; Motokura, T; Kiyosawa, K

    1999-08-01

    We report on a male Japanese patient with hairy cell leukemia (HCL). A cytogenetic study with lipopolysaccharide stimuli showed a novel translocation (11;20)(q13;q11) in 10% of the analyzed cells. Northern blot analysis and RT-PCR analysis for cyclin D1 revealed the overexpression of cyclin D1, although the southern blot analysis of PRAD1 gene showed no rearrangement. In this particular case, the t(11;20)(q13;q11) might play some role in the oncogenesis of HCL and the overexpression of cyclin D1.

  12. Effect of cAMP analogs on cyclinD1 expression of human breast cancer cells%cAMP类似物对人乳腺癌细胞cyclinD1表达的影响

    Institute of Scientific and Technical Information of China (English)

    王锦华; 陈奎生; 张云汉; 罗伟

    2003-01-01

    目的探讨cAMP类似物对人乳腺癌细胞增殖相关cyclinD1基因表达的影响.方法体外分组原代培养人乳腺癌细胞,采用原位杂交方法研究cAMP类似物对人乳腺癌细胞中cyclinD1基因表达的变化.结果 8-Br-cAMP、8-Cl-cAMP均下调乳腺癌细胞中cyclinD1基因表达,且后者下降作用更明显.结论 cAMP类似物可通过影响与乳腺癌细胞增殖相关cyclinD1表达从而抑制乳腺癌细胞生长.

  13. FGFR-1、cyclinD1在乳腺癌中的表达及其临床意义%Expression and clinical significance of FGFR-1, cyclinD1 in breast carcinoma

    Institute of Scientific and Technical Information of China (English)

    邓敏; 解瑞飞; 王惠

    2016-01-01

    目的 探讨成纤维生长因子受体(fibroblast growth factor receptor,FGFR-1)及细胞周期蛋白D1 (cyclinD1)在乳腺癌组织中的表达及其临床意义.方法 应用原位杂交及免疫组织化学S-P法检测乳腺癌、乳腺纤维腺瘤和正常乳腺组织中FGFR-1、cyclinD1 mRNA及蛋白水平的表达.结果 在乳腺癌中,FGFR-1蛋白和FGFR-1基因的阳性率分别为70.0%(21/30)、70.0%(21/30),cyclinD1蛋白和cyclinD1基因的阳性率分别为66.7%(20/30)、76.7%(23/30),明显高于纤维腺瘤与正常乳腺组织(P<0.05),FGFR-1表达与cyclinD1表达一致.结论 FGFR-1的过表达在人类乳腺癌的发生、发展中起重要作用,其机制可能通过上调cyclinD1的表达发挥作用,FGFR-1、cyclinD1的过度表达可作为判断乳腺癌预后的重要指标.

  14. 胃癌组织中p16、 Cyclin D1和Survivin的表达及其相关性%Expression and correlation of p16, Cyclin D1 and Survivin in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    魏卓文; 党冬梅

    2014-01-01

    目的 研究p16、Cyclin D1和Survivin在胃癌中的表达及其相关性.方法 应用免疫组化S-P法检测正常胃黏膜组织、不典型增生和胃癌组织中p16、Cyclin D1和Survivin的表达.结果 正常胃黏膜和不典型增生组织中p16的表达率高于Cyclin D1和Survivin的表达,胃癌组织中p16的表达率低于二者;p16、Cyclin D1和Survivin的表达与胃癌患者年龄、性别均无关;p16的表达与淋巴结转移相关(P<0.05);Cyclin D1的表达与组织分化程度、淋巴结转移相关(P <0.001;P <0.05);Survivin的表达与组织分化程度相关(P<0.05).且p16与Cyclin D1在胃癌组织中的表达呈负相关(r=-0.486),p16与Survivin也呈负相关(r=-0.518),Cyclin D1与Survivin呈正相关(r=0.431).结论 p16、Cyclin D1和Survivin与胃癌的发生发展和预后关系密切.

  15. Synthesis of geological, structural, and geochronologic data (phase V, deliverable 53): Chapter A in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

    Science.gov (United States)

    Bradley, Dwight C.; O'Sullivan, Paul; Cosca, Michael A.; Motts, Holly; Horton, John D.; Taylor, Cliff D.; Beaudoin, Georges; Lee, Gregory K.; Ramezani, Jahan; Bradley, Daniel N.; Jones, James; Bowring, Samuel

    2015-01-01

    This report is a companion to the new Geologic Map of Mauritania (Bradley and others, 2015; referred to herein as “Deliverable 51”) and the new Structural Geologic Map of Mauritania (Bradley and others, 2015a; referred to herein as “Deliverable 52”). Section 1 contains explanatory information for these two digital maps. Section 2 covers the analytical methods used in obtaining new U-Pb ages from 9 igneous rock samples, new detrital zircon ages from 40 sedimentary or metasedimentary rock samples, and new 40Ar/39Ar ages from 12 samples of metamorphic rocks and veins. Sections 3 through 6 present the new geochronological results, organized by region. In Section 7, we discuss implications of the new ages for the regional geology and discuss problematic results. Finally, in Section 8, we summarize the geology and tectonic evolution of Mauritania in narrative form, drawing on new and published information, in the context of global tectonics. The report is being released in both English and French. In both versions, we use the French-language names for formal stratigraphic units.

  16. A toxaphene-degrading bacterium related to Enterobacter cloacae, strain D1 isolated from aged contaminated soil in Nicaragua.

    Science.gov (United States)

    Lacayo-Romero, Martha; Quillaguamán, Jorge; van Bavel, Bert; Mattiasson, Bo

    2005-09-01

    Enterobacter sp. strain D1 is a facultative anaerobic, Gram-negative heterotrophic bacterium isolated from toxaphene-contaminated soil. This organism was identified and characterized through phylogenetic and taxonomic studies. Based on 16S rDNA analysis, the strain D1 was clustered closely with the species Enterobacter cloacae subsp. dissolvens (LMG 2683) and E. cloacae (ATCC 13047T). Strain D1 resembled these E. cloacae strains with respect to various biochemical and nutritional characteristics, but also exhibited differences. Moreover, strain D1 is able to grow and survive with toxaphene supplied in the medium in the range 3-96 mg/L. Amongst the chemical components of toxaphene, octachlorocamphenes, nonachlorobornanes and decachlorobornanes were seen to be rapidly metabolized, although levels of hexachlorocamphenes and heptachlorobornanes were found to be slowly degraded, and subsequently accumulated during the last stage of the cultivation.

  17. PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation

    Institute of Scientific and Technical Information of China (English)

    Peihua Sun; Jingru Wang; Weihua Gu; Wei Cheng; Guo-zhang Jin; Eitan Friedman; Jie Zheng; Xuechu Zhen

    2009-01-01

    The present study aims to define the role of postsynaptic density (PSD)-95 in the regulation of dopamine (DA) receptor function. We found that PSD-95 physically associates with either D1 or D2 DA receptors in co-transfected HEK-293 cells. Stimulation of DA receptors altered the association between D1 receptor and PSD-95 in a time-depen-dent manner. Functional assays indicated that PSD-95 co-expression did not affect D1 receptor-stimulated cAMP pro-duction, Gs-protein activation or receptor desensitization. However, PSD-95 accelerated the recovery of internalized membrane receptors by promoting receptor recycling, thus resulting in enhanced resensitization of internalized D1 receptors. Our results provide a novel mechanism for regulating DA receptor recycling that may play an important role in postsynaptic DA functional modulation and synaptic neuroplasticity.

  18. Hadronic production of D (2550 ) , D*(2600 ) , D (2750 ) , D1*(2760 ) , and D3*(2760 )

    Science.gov (United States)

    Zhao, Ze; Tian, Yu; Zhang, Ailin

    2016-12-01

    Hadronic decays of radially excited 2 D D (2 3D1) , D (2 3D3) , D (2 D2) , and D (2 D2') have been studied in a 3P0 model. All Okubo-Zweig-Iizuka-allowed decay channels of these 2 D D resonances have been given, and relevant decay widths have been calculated. D (2550 ), D*(2600 ), D (2750 ), D1*(2760 ), and D3*(2760 ) can be produced in hadronic decays of D (2 3D1) , D (2 3D3) , D (2 D2), and D (2 D2'). In different assignments, hadronic decay widths and some relevant ratios from the 2 D D resonances to D (2550 ), D*(2600 ), D (2750 ), D1*(2760 ), or D3*(2760 ) final states have been predicted, which may provide more information to identify these resonances in forthcoming experiments.

  19. Hadronic production of $D(2550)$, $D^*(2600)$, $D(2750)$, $D^*_1(2760)$ and $D^*_3(2760)$

    CERN Document Server

    Zhao, Ze; Zhang, Ailin

    2016-01-01

    Hadronic decays of radially excited $2D$ $D(2^3D_1)$, $D(2^3D_3)$, $D(2D_2)$ and $D(2D^\\prime_2)$ have been studied in a $^3P_0$ model. All OZI-allowed decay channels of these $2D$ $D$ resonances have been given, and relevant decay widths have been calculated. $D(2550)$, $D^*(2600)$, $D(2750)$, $D^*_1(2760)$ and $D^*_3(2760)$ can be produced in hadronic decays of $D(2^3D_1)$, $D(2^3D_3)$, $D(2D_2)$ and $D(2D^\\prime_2)$. In different assignments, hadronic decay widths and some relevant ratios from the $2D$ $D$ resonances to $D(2550)$, $D^*(2600)$, $D(2750)$, $D^*_1(2760)$ or $D^*_3(2760)$ final states have been predicted, which may provide some more information to identify these resonances in forthcoming experiments.

  20. Dimerization of the D1 dopamine receptors is related with agonist and inverse agonist-induced receptor internalization

    Institute of Scientific and Technical Information of China (English)

    Yi-minTAO; Xue-junXU; Min-huaHONG; JieCHEN; Zhi-qiangCHI; Jing-genLIU

    2004-01-01

    AIM: To examine the relationship between D1 dopamine receptor dimer formation and ligand-induced receptor internalization. METHODS: FLAG-tagged D 1 dopamine receptor was transiently expressed in Sf9 cells. The cells were treated with SKF38393 or (+)butaclamol 1 μmol/L for different periods timeor at different doses for 30 min respectively. Western blot assaywas performed to assess dimer formation and flow evtomv.tv.r

  1. Expression and cellular localization of the transcription factor NeuroD1 in the developing and adult rat pineal gland.

    Science.gov (United States)

    Castro, Analía E; Benitez, Sergio G; Farias Altamirano, Luz E; Savastano, Luis E; Patterson, Sean I; Muñoz, Estela M

    2015-05-01

    Circadian rhythms govern many aspects of mammalian physiology. The daily pattern of melatonin synthesis and secretion is one of the classic examples of circadian oscillations. It is mediated by a class of neuroendocrine cells known as pinealocytes which are not yet fully defined. An established method to evaluate functional and cytological characters is through the expression of lineage-specific transcriptional regulators. NeuroD1 is a basic helix-loop-helix transcription factor involved in the specification and maintenance of both endocrine and neuronal phenotypes. We have previously described developmental and adult regulation of NeuroD1 mRNA in the rodent pineal gland. However, the transcript levels were not influenced by the elimination of sympathetic input, suggesting that any rhythmicity of NeuroD1 might be found downstream of transcription. Here, we describe NeuroD1 protein expression and cellular localization in the rat pineal gland during development and the daily cycle. In embryonic and perinatal stages, protein expression follows the mRNA pattern and is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte nuclei in the early part of the night and in cytoplasm during the day, a rhythm maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are reduced after sympathetic disruption, an effect mimicked by the in vivo administration of α- and β-adrenoceptor blockers. NeuroD1 phosphorylation at two sites, Ser(274) and Ser(336) , associates with nuclear localization in pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both during development and adulthood, in an autonomic and phosphorylation-dependent manner.

  2. F5D-1 on ramp with Neil Armstrong preparing to fly a Dyna-Soar simulation

    Science.gov (United States)

    1962-01-01

    The Douglas F5D-1 Skylancer being pre-flighted by the pilot while the crew chief prepares to pull the wheel chocks on the 'hot gun' ramp at Edwards Air Force Base, California. The aircraft was one of two prototype F5D-1s obtained by NASA Flight Research Center in 1961. The F5D-1 Skylancer (Bu. No. 142350) had a red and white paint pattern with a NASA identification number of 213 which later became NASA 708. The Douglas F5D-1 Skylancer was built by the Navy as an all-weather fighter interceptor that never made the jump to production. Four test aircraft were developed with the same basic airframe as the Douglas F4D Skyray. With increasing modifications the four aircraft were re-designated F5D-1s before their first flights. Future Astronaut Neil Armstrong was one of the NASA research pilots assigned to support duties for the Dyna-Soar program. In addition to working at the Boeing facility in Washington state, Armstrong also tested the Dyna-Soar launch abort profile using this F5D-1, which had a similar wing shape to the Dyna-Soar. The aircraft arrived at the Flight Research Center on June 15, 1961. After the Dyna-Soar program was cancelled in December 1963, this F5D-1 continued to be used, serving as a flying simulator for the M2-F2 and as a chase plane for lifting-body flights (providing the lifting-body pilot with an extra set of eyes to assist in emergencies and avert potential crashes) This F5D-1 left the Flight Research Center (later designated the Dryden Flight Research Center) on May 19, 1970, and was donated to the Neil A. Armstrong Museum in Wapakoneta, Ohio.

  3. Oxidative stress causes renal dopamine D1 receptor dysfunction and salt-sensitive hypertension in Sprague-Dawley rats.

    Science.gov (United States)

    Banday, Anees A; Lau, Yuen-Sum; Lokhandwala, Mustafa F

    2008-02-01

    Renal dopamine plays an important role in maintaining sodium homeostasis and blood pressure (BP) during increased sodium intake. The present study was carried out to determine whether renal dopamine D1 receptor (D1R) dysfunction contributes to increase in salt sensitivity during oxidative stress. Male Sprague-Dawley rats, divided into various groups, received tap water (vehicle); 1% NaCl (high salt [HS]); L-buthionine sulfoximine (BSO), an oxidant; and HS plus BSO with or without Tempol, an antioxidant, for 12 days. Compared with vehicle, HS intake increased urinary dopamine production and decreased basal renal Na/K-ATPase activity but did not affect BP. BSO-treated rats exhibited oxidative stress and a mild increase in BP. In these rats, D1R expression and G protein coupling were reduced, and SKF38393, a D1R agonist, failed to inhibit Na/K-ATPase activity and promote sodium excretion. Concomitant administration of BSO and HS caused oxidative stress, D1R dysfunction, and a marked increase in BP. Although renal dopamine production was increased, it failed to reduce the basal Na/K-ATPase activity in these animals. Treatment of BSO plus HS rats with Tempol decreased oxidative stress and restored endogenous, as well as exogenous, D1R agonist-mediated Na/K-ATPase inhibition and normalized BP. In conclusion, during HS intake, the increased dopamine production via Na/K-ATPase inhibition prevents an increase in BP. During oxidative stress, D1R function is defective, and there is mild hypertension. However, in the presence of oxidative stress, HS intake causes marked elevation in BP, which results from a defective renal D1R function leading to the failure of dopamine to inhibit Na/K-ATPase and promote sodium excretion.

  4. Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections.

    Science.gov (United States)

    Kupchik, Yonatan M; Brown, Robyn M; Heinsbroek, Jasper A; Lobo, Mary Kay; Schwartz, Danielle J; Kalivas, Peter W

    2015-09-01

    It is widely accepted that D1 dopamine receptor-expressing striatal neurons convey their information directly to the output nuclei of the basal ganglia, whereas D2-expressing neurons do so indirectly via pallidal neurons. Combining optogenetics and electrophysiology, we found that this architecture does not apply to mouse nucleus accumbens projections to the ventral pallidum. Thus, current thinking attributing D1 and D2 selectivity to accumbens projections akin to dorsal striatal pathways needs to be reconsidered.

  5. Alleles of Ppd-D1 gene in the collection of Aegilops tauschii accessions and bread wheat varieties

    Directory of Open Access Journals (Sweden)

    Babenko D. O.

    2012-04-01

    Full Text Available Light period significantly influences on the growth and development of plants. One of the major genes of photoperiod sensitivity is Ppd-D1, located on the chromosome 2D. The aim of the work was to determine the alleles and molecular structure of Ppd-D1 gene in samples from the collection of Ae. tauschii accessions, which have different flowering periods, and in 29 Ukrainian wheat varieties. Methods. We used methods of allele-specific PCR with primers to the Ppd-D1 gene, sequencing and Blast-analysis. Results. The collection of Ae. tauschii accessions and several varieties of winter and spring wheat was studied. The molecular structure of the allelic variants (414, 429 and 453 b. p. of Ppd-D1b gene was determined in the collection of Aegilops. tauschii accessions. Conclusions. The Ppd-D1a allele was present in all studied varieties of winter wheat. 60 % of spring wheat is characterized by Ppd-D1b allele (size of amplification products 414 b. p.. Blast-analysis of the sequence data banks on the basis of the reference sequence of sample k-1322 from the collection of Ae. tauschii accessions has shown a high homology (80 to 100 % between the nucleotide sequences of PRR genes, that characterize the A and D genomes of representatives of the genera Triticum and Aegilops.

  6. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Boo [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States); Lee, Seong-Ho, E-mail: slee2000@umd.edu [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  7. Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake

    Directory of Open Access Journals (Sweden)

    Xianglong eZhu

    2016-04-01

    Full Text Available While weight gain is clearly promoted by excessive energy intake and reduced expenditure, the underlying neural mechanisms of energy balance remain unclear. The NAc is one brain region that has received attention for its role in the regulation of energy balance; its D1 and D2 receptor containing neurons have distinct functions in regulating reward behavior and require further examination. The goal of the present study is to investigate how activation and inhibition of D1 and D2 neurons in the NAc influences behaviors related to energy intake and expenditure. Specific manipulation of D1 vs D2 neurons was done in both low expenditure and high expenditure (wheel running conditions to assess behavioral effects in these different states. Direct control of neural activity was achieved using a DREADD (Designer Receptors Exclusively Activated by Designer Drugs strategy. Activation of NAc D1 neurons increased food intake, wheel running and locomotor activity. In contrast, activation of D2 neurons in the NAc reduced running and locomotion while D2 neuron inhibition had opposite effects. These results highlight the importance of considering both intake and expenditure in the analysis of D1 and D2 neuronal manipulations. Moreover, the behavioral outcomes from D1 NAc neuronal manipulations depend upon the activity state of the animals (wheel running vs non-running. The data support and complement the hypothesis of specific NAc dopamine pathways facilitating energy expenditure and suggest a potential strategy for human weight control.

  8. The therapeutic potential of Rho kinase inhibitor fasudil derivative FaD-1 in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Zhao, Yong-Fei; Zhang, Xiang; Ding, Zhi-Bin; Yang, Xing-Wang; Zhang, Hui; Yu, Jie-Zhong; Li, Yan-Hua; Liu, Chun-Yun; Zhang, Qing; Zhang, Hong-Zhen; Ma, Cun-Gen; Xiao, Bao-Guo

    2015-03-01

    Although therapeutic potential of fasudil in EAE is promising, action mechanism and clinical limitations are still not fully understood and resolved. In this study, we observed the therapeutic potential of a novel Rho kinase (ROCK) inhibitor FaD-1, a fasudil derivative, and explored possible mechanism in MOG35-55-induced EAE. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG35-55) immunization. The pathology of spinal cord was measured by immunohistochemistry and neurological impairment was evaluated using clinical scores. FaD-1, as a novel ROCK inhibitor, inhibited the expression of ROCK II that is mainly expressed in the CNS. We show here that FaD-1 ameliorates the neurological defects and the severity of MOG-induced EAE in mice, accompanied by the protection of demyelination and the inhibition of neuroinflammation in spinal cord of EAE. In addition, FaD-1 dampened TLR2 and TLR4 signaling as well as Th1 (IFN-γ) and Th17 (IL-17) responses in spinal cord of EAE. FaD-1 also prevented the expression of iNOS and production of inflammatory cytokine IL-1β, IL-6, and TNF-α which are specific markers for M1 inflammatory microglia/macrophages. This study highlights the therapeutic potential of FaD-1 as a ROCK inhibitor for the treatment of human autoimmune diseases with both inflammatory and autoimmune components.

  9. Final repository for spent nuclear fuel. Underground design Simpevarp, Layout D1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-04-15

    This report is a compilation of the results of the underground design work carried out in design phase D1 of the Repository Design Project within the Deep Repository Project for the Simpevarp site. Similar reports are also being produced for the Laxemar and Forsmark sites. The design phase coincides with the initial site investigation phase. The main purpose of phase D1 is to answer the question 'Can a final repository be accommodated within the designated site', but also to test the design methodology and provide feedback to the modelling project. Design was carried out in accordance with the methodology described in UDP (Underground Design Premises), SKB R-04-60, and was based on preliminary data from various disciplines in the site modelling project. The preliminary input data used were then cross-checked against data in the final Site Descriptive Model SDM v 1.2 and significant differences were integrated in the design work. The design results from each design topic were presented by the designer at presentation meetings for SKB's design management and the reviewers engaged by SKB for the specific topic. After the presentation meeting the designer wrote up the work reports for the topic in question. The work reports were then reviewed by SKB's review team. The results of the review were compiled in a statement that was submitted to the designer to be dealt with. In the statement the designer documented which comments were dealt with and how. This report is a compilation of the entire design phase D1 for Simpevarp. The 3D layout with coordinate lists for deposition holes and tunnels that was drawn to illustrate a possible layout was used in the Preliminary safety evaluation of the Simpevarp subarea and the hydro modelling of the Open Repository, both activities within the Deep Repository Project. According to current plans for the Swedish nuclear programme, the minimum required number of canister positions in the repository is estimated to be

  10. Expressions of SOX2 and CyclinD1 in epithelial ovarian cancer tissue%卵巢上皮性癌组织中 SOX2和 CyclinD1的表达

    Institute of Scientific and Technical Information of China (English)

    姚俊阁; 李红雨; 赵书君; 张慧; 张艳艳; 郭欢欢

    2014-01-01

    目的:检测卵巢上皮性癌组织中SOX2和CyclinD1的表达。方法:分别采用免疫组化SP法和RT-PCR法检测20例正常卵巢上皮组织、20例卵巢良性上皮性肿瘤组织及43例卵巢上皮性癌组织中SOX2和CyclinD1蛋白及mRNA的表达。结果:3种组织间SOX2、CyclinD1蛋白及mRNA的表达差异有统计学意义(蛋白:χ2=32.998,mRNA:F=454.222、398.284,P均<0.05);卵巢上皮性癌组织中SOX2、CyclinD1蛋白及mRNA的表达高于卵巢良性上皮性肿瘤组织及正常卵巢上皮组织( P均<0.05)。 SOX2、CyclinD1蛋白的表达均与卵巢上皮性癌FIGO分期、分化程度及淋巴结转移有关(P均<0.05)。卵巢上皮性癌组织中SOX2、CyclinD1蛋白的表达有关联(rp =0.422,P<0.05)。结论:SOX2和CyclinD1在卵巢上皮性癌组织中高表达,二者可能协同参与卵巢上皮性癌的发生及发展。%Aim:To explore the expressions and clinical significance of SOX 2 and CyclinD1 in epithelial ovarian canc-er tissue.Methods:Immunohistochemical SP method and RT-PCR were used to separately detect the expressions of SOX 2 and CyclinD1 in 20 cases of normal epithelial ovarian tissue , 20 cases of benign epithelial ovarian neoplasm tissue , and 43 cases of epithelial ovarian cancer tissue .Results:The expressions of SOX2 and CyclinD1 protein and mRNA in epithelial ovarian cancer tissue were significantly higher than those in benign epithelial ovarian neoplasm tissue and normal epithelial ovarian tissue(protein:χ2 =32.998;mRNA:F=454.222,398.284, all P<0.05).The expressions of SOX2 and CyclinD1 protein in epithelial ovarian cancer tissue were related to FIGO stage , histological differentiation and lymph node metastasis (P<0.05).The expression of SOX2 protein was associated with that of CyclinD1 protein in epithelial ovarian cancer tissue (rp =0.422,P<0.05).Conclusion: SOX2 and CyclinD1 are both over-expressed in epithelial ovarian cancer

  11. α-、β-catenin和cyclin D1在乳腺癌中的表达及意义%The expressions and significance of α-,β-catenins and cyclin D1 in breast cancers

    Institute of Scientific and Technical Information of China (English)

    Liang Zeng; Senlin Chen; Zhihong Liu; Jianfeng Yang

    2008-01-01

    Objective:To study the relationship between expressions of α-,β-catenins and cyclin D1 and the occurrence,infiltration and metastasis of breast cancer.Methods:High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-,β-catenins and cyclin D1 in the 60 cases of breast cancer tissues.Results:Abnormal immunoreactivities of α- and β-catenins were observed in 37(61.7%)and 42(70%)cases of breast Cancer tissues,respectively.There were 28 cases(46.7%)who showed cyclin D1 overexpression.The abnormal expression rates of α -and β-catenins in infiltrating lobular carcinoma(ILC)were significantly higher than those in infiltrating ductal Carcinoma(IDC)(P<0.05),but they had no relations to the extenl of differentiation and lymphatic metastasis of breasl Cancer(P>0.05).The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer(P<0.05),but not with histological type and lhe extent of differentiation(P>0.05).Cyclin D1 overexpression was observed in 57.1%(24/42)of these cases that showed abnormal staining of β-catenin,but only observed in 22.2%(4/18)of these cases with normal membranous staining of β-catenin.There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1(rs=0.321.P<0.05).Conclusion:The abnormal expression of β-Catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer.The abnormal expressions of α- and β-catenins are not a key factor in malignant cell metastasis in breast cancer,but may also involve in the progress.

  12. High cycle fatigue properties of die-cast magnesium alloy AZ91D-1%MM

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The high cycle fatigue properties of the die-cast magnesium alloy AZ91D containing 1%mischmetal(mass fraction)at a fatigue ratio of 0.1 were investigated.The difference in the microstructure between the skin and core region of the die-cast magnesium alloy was analyzed by optical microscopy.The mechanical property tests indicate that the values of the tensile strength,elongation and hardness are 185 MPa,1.5%and HBS 70±3 at room temperature,respectively.The p-S-N curve(p=50%)of the die-cast magnesium alloy AZ91D-1%MM is determined and the mean fatigue strength corresponding to 3.8×105cycles is 70 MPa.A linear relation between S and Np in log scale between 103 and 106 cycles is written with a equation.The mechanical properties are influenced by the casting defects.The fatigue life of the samples with minor defects is near to the upper limit of the fatigue life data.The fatigue fracture surface of the samples with minor defects possesses the mixed characteristics of quasi-cleavage,lacerated ridge and dimple and it is briule fracture mode as a whole.

  13. \\Lambda-enhanced Sub-Doppler Cooling of Lithium Atoms in D1 Gray Molasses

    CERN Document Server

    Grier, Andrew T; Rem, Benno S; Delehaye, Marion; Khaykovich, Lev; Chevy, Frédéric; Salomon, Christophe

    2013-01-01

    Following the bichromatic sub-Doppler cooling scheme on the D1-line of 40K recently demonstrated in (Fernandes et al. 2012), we introduce a similar technique for 7Li atoms and obtain temperatures of 60 uK while capturing all of the 5x10^8 atoms present from the previous stage. We investigate the influence of the detuning between the the two cooling frequencies and observe a threefold decrease of the temperature when the Raman condition is fulfilled. We interpret this effect as arising from extra cooling due to long-lived coherences between hyperfine states. Solving the optical Bloch equations for a simplified, \\Lambda-type three-level system we identify the presence of an efficient cooling force near the Raman condition. After transfer into a quadrupole magnetic trap, we measure a phase space density of ~10^-5. This laser cooling offers a promising route for fast evaporation of lithium atoms to quantum degeneracy in optical or magnetic traps.

  14. Massless conformal fields, AdS(d+1/CFTd higher spin algebras and their deformations

    Directory of Open Access Journals (Sweden)

    Sudarshan Fernando

    2016-03-01

    Full Text Available We extend our earlier work on the minimal unitary representation of SO(d,2 and its deformations for d=4,5 and 6 to arbitrary dimensions d. We show that there is a one-to-one correspondence between the minrep of SO(d,2 and its deformations and massless conformal fields in Minkowskian spacetimes in d dimensions. The minrep describes a massless conformal scalar field, and its deformations describe massless conformal fields of higher spin. The generators of Joseph ideal vanish identically as operators for the quasiconformal realization of the minrep, and its enveloping algebra yields directly the standard bosonic AdS(d+1/CFTd higher spin algebra. For deformed minreps the generators of certain deformations of Joseph ideal vanish as operators and their enveloping algebras lead to deformations of the standard bosonic higher spin algebra. In odd dimensions there is a unique deformation of the higher spin algebra corresponding to the spinor singleton. In even dimensions one finds infinitely many deformations of the higher spin algebra labelled by the eigenvalues of Casimir operator of the little group SO(d−2 for massless representations.

  15. VUV Spectroscopic Study of the D^1\\Pi State of Molecular Deuterium

    CERN Document Server

    Dickenson, G D; Ubachs, W; Roudjane, M; de Oliveira, N; Joyeux, D; Nahon, L; Tchang-Brillet, W -Ü L; Glass-Maujean, M; Schmoranzer, H; Knie, A; Kübler, S; Ehresmann, A; 10.1080/00268976.2011.631056

    2013-01-01

    The D^1\\Pi_u - X^1\\Sigma_g^+ absorption system of molecular deuterium has been re-investigated using the VUV Fourier -Transform (FT) spectrometer at the DESIRS beamline of the synchrotron SOLEIL and photon-induced fluorescence spectrometry (PIFS) using the 10 m normal incidence monochromator at the synchrotron BESSY II. Using the FT spectrometer absorption spectra in the range 72 - 82 nm were recorded in quasi static gas at 100 K and in a free flowing jet at a spectroscopic resolution of 0.50 and 0.20 cm^{-1} respectively . The narrow Q-branch transitions, probing states of \\Pi^- symmetry, were observed up to vibrational level v = 22. The states of \\Pi^+ symmetry, known to be broadened due to predissociation and giving rise to asymmetric Beutler-Fano resonances, were studied up to v = 18. The 10 m normal incidence beamline setup at BESSY II was used to simultaneously record absorption, dissociation, ionization and fluorescence decay channels from which information on the line intensities, predissociated width...

  16. Cyclin D1 depletion induces DNA damage in mantle cell lymphoma lines.

    Science.gov (United States)

    Mohanty, Suchismita; Mohanty, Atish; Sandoval, Natalie; Tran, Thai; Bedell, Victoria; Wu, Jun; Scuto, Anna; Murata-Collins, Joyce; Weisenburger, Dennis D; Ngo, Vu N

    2017-03-01

    Elevated cyclin D1 (CCND1) expression levels in mantle cell lymphoma (MCL) are associated with aggressive clinical manifestations related to chemoresistance, but little is known about how this important proto-oncogene contributes to the resistance of MCL. Here, we showed that RNA interference-mediated depletion of CCND1 increased caspase-3 activities and induced apoptosis in the human MCL lines UPN-1 and JEKO-1. In vitro and xenotransplant studies revealed that the toxic effect of CCND1 depletion in MCL cells was likely due to increase in histone H2AX phosphorylation, a DNA damage marker. DNA fiber analysis suggested deregulated replication initiation after CCND1 depletion as a potential cause of DNA damage. Finally, in contrast to depletion or inhibition of cyclin-dependent kinase 4, CCND1 depletion increased chemosensitivity of MCL cells to replication inhibitors hydroxyurea and cytarabine. Our findings have an important implication for CCND1 as a potential therapeutic target in MCL patients who are refractory to standard chemotherapy.

  17. 1D and 2D ~1H NMR studies on bisantrene complexes with short DNA oligomers

    Institute of Scientific and Technical Information of China (English)

    姚世杰; WILSON.W.David

    1995-01-01

    The binding of bisantrene to four DNA tetramers,d(CGCG)2,d(GCGC)2,d(CATG)2,and d(GTAC)2,was investigated by 1D and 2D NMR spectroscopy.Bisantrene is.a well knownanticancer drug and has been used clinically for years.DNA is believed to be one of its cellular targets.Re-suits from both ID and 2D 1H NMR are in agreement with an intercalation binding mode of bisantrene withthe four DNA tetramers in this study.The results further indicate that a threading intercalation birdingmode,in which one bisantrene side chain is in the minor groove and the other in the major groove of DNA,is preferred.The NMR results also suggest that bisantrene prefers binding at pyrimidine-(3’,5’)-purineintercalation sequences rather than at purine-(3’,5’)-pyrimidine sequences.The intramolecular andintermolecular NOE contacts of bisantrene-DNA tetramer complexes indicate that a C2’-endo uniform sugarpucker,rather than a mixed sugar conformation,is preferred by the intercalation site of both the 5’-(TA)-3’and the 5’-(CG)-3’ binding steps.

  18. One-loop transition amplitudes in the D1D5 CFT

    Science.gov (United States)

    Carson, Zaq; Hampton, Shaun; Mathur, Samir D.

    2017-01-01

    We consider the issue of thermalization in the D1D5 CFT. Thermalization is expected to correspond to the formation of a black hole in the dual gravity theory. We start from the orbifold point, where the theory is essentially free, and does not thermalize. In earlier work it was noted that there was no clear thermalization effect when the theory was deformed off the orbifold point to first order in the relevant twist perturbation. In this paper we consider the deformation to second order in the twist, where we do find effects that can cause thermalization of an initial perturbation. We consider a 1-loop process where two untwisted copies of the CFT are twisted to one copy and then again untwisted to two copies. We start with a single oscillator excitation on the initial CFT, and compute the effect of the two twists on this state. We find simple approximate expressions for the Bogoliubov coefficients and the behavior of the single oscillator excitation in the continuum limit, where the mode numbers involved are taken to be much larger than unity. We also prove a number of useful relationships valid for processes with an arbitrary number of twist insertions.

  19. One-Loop Transition Amplitudes in the D1D5 CFT

    CERN Document Server

    Carson, Zaq; Mathur, Samir D

    2016-01-01

    We consider the issue of thermalization in the D1D5 CFT. Thermalization is expected to correspond to the formation of a black hole in the dual gravity theory. We start from the orbifold point, where the theory is essentially free, and does not thermalize. In earlier work it was noted that there was no clear thermalization effect when the theory was deformed off the orbifold point to first order in the relevant twist perturbation. In this paper we consider the deformation to second order in the twist, where we do find effects that can cause thermalization of an initial perturbation. We consider a 1-loop process where two untwisted copies of the CFT are twisted to one copy and then again untwisted to two copies. We start with a single oscillator excitation on the initial CFT, and compute the effect of the two twists on this state. We find simple approximate expressions for the Bogoliubov coefficients and the behavior of the single oscillator excitation in the continuum limit, where the mode numbers involved are...

  20. On the particle-hole symmetry of the fermionic spinless Hubbard model in D=1

    Directory of Open Access Journals (Sweden)

    M.T. Thomaz

    2014-06-01

    Full Text Available We revisit the particle-hole symmetry of the one-dimensional (D=1 fermionic spinless Hubbard model, associating that symmetry to the invariance of the Helmholtz free energy of the one-dimensional spin-1/2 XXZ Heisenberg model, under reversal of the longitudinal magnetic field and at any finite temperature. Upon comparing two regimes of that chain model so that the number of particles in one regime equals the number of holes in the other, one finds that, in general, their thermodynamics is similar, but not identical: both models share the specific heat and entropy functions, but not the internal energy per site, the first-neighbor correlation functions, and the number of particles per site. Due to that symmetry, the difference between the first-neighbor correlation functions is proportional to the z-component of magnetization of the XXZ Heisenberg model. The results presented in this paper are valid for any value of the interaction strength parameter V, which describes the attractive/null/repulsive interaction of neighboring fermions.

  1. Phospholipase D1 facilitates second-phase myoblast fusion and skeletal muscle regeneration.

    Science.gov (United States)

    Teng, Shuzhi; Stegner, David; Chen, Qin; Hongu, Tsunaki; Hasegawa, Hiroshi; Chen, Li; Kanaho, Yasunori; Nieswandt, Bernhard; Frohman, Michael A; Huang, Ping

    2015-02-01

    Myoblast differentiation and fusion is a well-orchestrated multistep process that is essential for skeletal muscle development and regeneration. Phospholipase D1 (PLD1) has been implicated in the initiation of myoblast differentiation in vitro. However, whether PLD1 plays additional roles in myoblast fusion and exerts a function in myogenesis in vivo remains unknown. Here we show that PLD1 expression is up-regulated in myogenic cells during muscle regeneration after cardiotoxin injury and that genetic ablation of PLD1 results in delayed myofiber regeneration. Myoblasts derived from PLD1-null mice or treated with PLD1-specific inhibitor are unable to form mature myotubes, indicating defects in second-phase myoblast fusion. Concomitantly, the PLD1 product phosphatidic acid is transiently detected on the plasma membrane of differentiating myocytes, and its production is inhibited by PLD1 knockdown. Exogenous lysophosphatidylcholine, a key membrane lipid for fusion pore formation, partially rescues fusion defect resulting from PLD1 inhibition. Thus these studies demonstrate a role for PLD1 in myoblast fusion during myogenesis in which PLD1 facilitates the fusion of mononuclear myocytes with nascent myotubes.

  2. Equilibration and GGE in interacting-to-free Quantum Quenches in dimensions $d>1$

    CERN Document Server

    Sotiriadis, Spyros

    2016-01-01

    Ground states of interacting QFTs are non-gaussian states, i.e. their connected n-point correlation functions do not vanish for n>2, in contrast to the free QFT case. We show that when the ground state of an interacting QFT evolves under a free massive QFT for a long time (a scenario that can be realised by a Quantum Quench), the connected correlation functions decay and all local physical observables equilibrate to values that are given by a gaussian density matrix that keeps memory only of the two-point initial correlation function. The argument hinges upon the fundamental physical principle of cluster decomposition, which is valid for the ground state of a general QFT. An analogous result was already known to be valid in the case of d=1 spatial dimensions, where it is a special case of the so-called Generalised Gibbs Ensemble (GGE) hypothesis, and we now generalise it to higher dimensions. Moreover in the case of massless free evolution, despite the fact that the evolution may not lead to equilibration but...

  3. Simultaneous Faraday filtering of the Mollow triplet sidebands with the Cs-D1 clock transition

    Science.gov (United States)

    Portalupi, Simone Luca; Widmann, Matthias; Nawrath, Cornelius; Jetter, Michael; Michler, Peter; Wrachtrup, Jörg; Gerhardt, Ilja

    2016-11-01

    Hybrid quantum systems integrating semiconductor quantum dots (QDs) and atomic vapours become important building blocks for scalable quantum networks due to the complementary strengths of individual parts. QDs provide on-demand single-photon emission with near-unity indistinguishability comprising unprecedented brightness--while atomic vapour systems provide ultra-precise frequency standards and promise long coherence times for the storage of qubits. Spectral filtering is one of the key components for the successful link between QD photons and atoms. Here we present a tailored Faraday anomalous dispersion optical filter based on the caesium-D1 transition for interfacing it with a resonantly pumped QD. The presented Faraday filter enables a narrow-bandwidth (Δω=2π × 1 GHz) simultaneous filtering of both Mollow triplet sidebands. This result opens the way to use QDs as sources of single as well as cascaded photons in photonic quantum networks aligned to the primary frequency standard of the caesium clock transition.

  4. BCS Instability and Finite Temperature Corrections to Tachyon Mass in Intersecting D1-Branes

    CERN Document Server

    Chowdhury, Sudipto Paul; Sathiapalan, B

    2014-01-01

    A holographic description of BCS superconductivity is given in arxiv:1104.2843. This model was constructed by insertion of a pair of D8-branes on a D4-background. The spectrum of intersecting D8-branes has tachyonic modes indicating an instability which is identified with the BCS instability in superconductors. Our aim is to study the stability of the intersecting branes under finite temperature effects. Many of the technical aspects of this problem are captured by a simpler problem of two intersecting D1-branes on flat background. In the simplified set-up we compute the one-loop finite temperature corrections to the tree-level tachyon mass using the frame-work of SU(2) Yang-Mills theory in (1 + 1)-dimensions. We show that the one-loop two-point functions are ultraviolet finite due to cancellation of ultraviolet divergence between the amplitudes containing bosons and fermions in the loop. The amplitudes are found to be infrared divergent due to the presence of massless fields in the loops. We compute the fini...

  5. Aggregation of LoD 1 building models as an optimization problem

    Science.gov (United States)

    Guercke, R.; Götzelmann, T.; Brenner, C.; Sester, M.

    3D city models offered by digital map providers typically consist of several thousands or even millions of individual buildings. Those buildings are usually generated in an automated fashion from high resolution cadastral and remote sensing data and can be very detailed. However, not in every application such a high degree of detail is desirable. One way to remove complexity is to aggregate individual buildings, simplify the ground plan and assign an appropriate average building height. This task is computationally complex because it includes the combinatorial optimization problem of determining which subset of the original set of buildings should best be aggregated to meet the demands of an application. In this article, we introduce approaches to express different aspects of the aggregation of LoD 1 building models in the form of Mixed Integer Programming (MIP) problems. The advantage of this approach is that for linear (and some quadratic) MIP problems, sophisticated software exists to find exact solutions (global optima) with reasonable effort. We also propose two different heuristic approaches based on the region growing strategy and evaluate their potential for optimization by comparing their performance to a MIP-based approach.

  6. Gone in a Blaze of Glory: the Demise of Comet C/2015 D1 (SOHO)

    CERN Document Server

    Hui, Man-To; Knight, Matthew; Battams, Karl; Clark, David

    2015-01-01

    We present studies of C/2015 D1 (SOHO), the first sunskirting comet ever seen from ground stations over the past half century. The Solar and Heliospheric Observatory (SOHO) witnessed its peculiar light curve with a huge dip followed by a flareup around perihelion: the dip was likely caused by sublimation of olivines, directly evidenced by a coincident temporary disappearance of the tail. The flareup likely reflects a disintegration event, which we suggest was triggered by intense thermal stress established within the nucleus interior. Photometric data reveal an increasingly dusty coma, indicative of volatile depletion. A catastrophic mass loss rate of $\\sim$10$^{5}$ kg s$^{-1}$ around perihelion was seen. Ground-based Xingming Observatory spotted the post-perihelion debris cloud. Our morphological simulations of post-perihelion images find newly released dust grains of size $a \\gtrsim 10$ $\\mu$m in radius, however, a temporal increase in $a_{\\min}$ was also witnessed, possibly due to swift dispersions of smal...

  7. 1D-1D Coulomb drag in a 6 Million Mobility Bi-layer Heterostructure

    Science.gov (United States)

    Bilodeau, Simon; Laroche, Dominique; Xia, Jian-Sheng; Lilly, Mike; Reno, John; Pfeiffer, Loren; West, Ken; Gervais, Guillaume

    We report Coulomb drag measurements in vertically-coupled quantum wires. The wires are fabricated in GaAs/AlGaAs bilayer heterostructures grown from two different MBE chambers: one at Sandia National Laboratories (1.2M mobility), and the other at Princeton University (6M mobility). The previously observed positive and negative drag signals are seen in both types of devices, demonstrating the robustness of the result. However, attempts to determine the temperature dependence of the drag signal in the 1D regime proved challenging in the higher mobility heterostructure (Princeton), in part because of difficulties in aligning the wires within the same transverse subband configuration. Nevertheless, this work, performed at the Microkelvin laboratory of the University of Florida, is an important proof-of-concept for future investigations of the temperature dependence of the 1D-1D drag signal down to a few mK. Such an experiment could confirm the Luttinger charge density wave interlocking predicted to occur in the wires. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL8500.

  8. Simultaneous Faraday filtering of the Mollow triplet sidebands with the Cs-D1 clock transition.

    Science.gov (United States)

    Portalupi, Simone Luca; Widmann, Matthias; Nawrath, Cornelius; Jetter, Michael; Michler, Peter; Wrachtrup, Jörg; Gerhardt, Ilja

    2016-11-25

    Hybrid quantum systems integrating semiconductor quantum dots (QDs) and atomic vapours become important building blocks for scalable quantum networks due to the complementary strengths of individual parts. QDs provide on-demand single-photon emission with near-unity indistinguishability comprising unprecedented brightness-while atomic vapour systems provide ultra-precise frequency standards and promise long coherence times for the storage of qubits. Spectral filtering is one of the key components for the successful link between QD photons and atoms. Here we present a tailored Faraday anomalous dispersion optical filter based on the caesium-D1 transition for interfacing it with a resonantly pumped QD. The presented Faraday filter enables a narrow-bandwidth (Δω=2π × 1 GHz) simultaneous filtering of both Mollow triplet sidebands. This result opens the way to use QDs as sources of single as well as cascaded photons in photonic quantum networks aligned to the primary frequency standard of the caesium clock transition.

  9. 甲状腺乳头状癌组织中SOX2和 CyclinD1的表达及相关性%Expressions of SOX2 and CyclinD1 in the Papillary Thyroid Carcinoma

    Institute of Scientific and Technical Information of China (English)

    董斌

    2016-01-01

    目的:探讨甲状腺乳头状癌组织中性别决定区 Y 框蛋白(SOX2)和细胞周期素 D1(CyclinD1)的表达及相关性。方法采用免疫组化 S-P 法检测100例甲状腺乳头状癌和50例癌旁正常甲状腺组织中 SOX2和 CyclinD1的表达,并分析两者与甲状腺乳头状癌患者临床病理参数的关系。结果甲状腺乳头状癌组织中 SOX2和 CyclinD1的阳性率分别为80.0%和73.0%,均高于癌旁正常甲状腺组织的10.0%和4.0%,差异有统计学意义(P <0.05)。甲状腺乳头状癌组织中 SOX2和 CyclinD1的表达与其临床分期、淋巴结转移关系密切(P <0.05)。甲状腺乳头状癌组织中 SOX2和 CyclinD1的表达呈正相关(r =0.597,P <0.05)。结论甲状腺乳头状癌组织中 SOX2和 CyclinD1存在表达,两者可能共同参与了甲状腺乳头状癌的疾病进展。%Objective To investigate the expressions of sex determining region Y-box(SOX2)and CyclinD1 in the patients with papillary thyroid carcinoma and the correlation. Methods Immunohistochemical S-P method was used to detect the expressions of SOX2 and CyclinD1 in the 100 patients with papillary thyroid carcinoma and 50 pa-tients with paraneoplastic normal thyroid tissues,their relationship with clinicopathological parameters were ana-lyzed. Results The positive rates of SOX2 and CyclinD1 in the papillary thyroid carcinoma were 80. 0% and 73. 0% ,and were 10. 0% and 4. 0% in the paraneoplastic normal thyroid tissues(P < 0. 05). The expressions of SOX2 and CyclinD1 in the papillary thyroid carcinoma were related with clinical stage and lymph node metastasis (P < 0. 05). In the papillary thyroid carcinoma,the expression of SOX2 was positively related with CyclinD1(r =0. 597,P < 0. 05). Conclusion high expressions of SOX2 and CyclinD1 are observed in the papillary thyroid carci-noma,and may be related to the development of papillary thyroid carcinoma.

  10. Polymorphism analysis of D1S80 locus in Chinese Han population in Southern Sichuan%川南地区汉族人群D1S80基因座多态性分析

    Institute of Scientific and Technical Information of China (English)

    张天丹; 杨曼曼; 杨璐全; 邹永林; 傅俊江

    2014-01-01

    目的:了解川南地区汉族人群D1S80位点群体遗传多态性。方法采用PCR结合聚丙烯酰胺PAGE电泳及高灵敏度银染技术,即Amp-FLP方法对川南地区120名汉族无血缘关系个体D1S80位点进行多态性分析。结果在所调查的120名无关个体样本中,观察到D1S80基因座有18个等位基因,基因频率分布在0.004166667~0.1958333333之间,杂合度为0.7869,个体识别力为0.87,非父排除率为0.8152,其基因型频率分布符合Hardy-Weinberg平衡法则。结论D1S80基因座的PCR分型具有较好的准确性和灵敏度,为法医学个体识别和亲权鉴定、遗传病基因链锁分析等的研究及应用提供了川南地区有用的遗传信息。%Objective To study the population genetic polymorphism of D1S80 locus in Han population in Southern Sichuan. Methods PCR amplification, electrophoresis of PAGE and high sensitive silver staining method, namely Amp-FLP, were performed for D1S80 loci by polymorphic analysis in 120 unrelated Han individuals from Southern Sichuan. Results From survey of 120 unrelated individuals for D1S80 loci, 18 alleles are observed. Gene frequency is located between 0.004166667 and 0.1958333333,heterozygosity is 0.7869, discrimination power is 0.87,exclusion power is 0.8152,which is in accordance with Hardy-Weinberg balance rule for the genotype distribution. Conclusion D1S80 gene loci PCR typing has good accuracy and sensitivity. It provides useful genetic information for forensic science research on individual identification and paternity test,genetic disease gene linkage analysis for D1S80 gene loci from Southern Sichuan.

  11. 膀胱移行细胞癌细胞周期蛋白D1的表达及其意义%Expression and Significance of CyclinD1 in Transitional Cell Carcinoma of Bladder

    Institute of Scientific and Technical Information of China (English)

    漆贯华; 宋旭

    2001-01-01

    目的:检测细胞周期蛋白D1(cyclinD1)在膀胱移行细胞癌(TCC)中的表达,研究其与该肿瘤生物学行为的关系.方法:应用免疫组化SP法检测33例膀胱TCC和12例正常膀胱cyclinD1组织的表达.结果:cyclinD1阳性表达率膀胱TCC组为54.54%,对照组无表达(P=0.001);临床分期To~TJ为76.19%,T2~T4为16.67%;肿瘤分级G1为81.25%,G2为40.00%,G3为14.28%;随着肿瘤分期分级上升,阳性表达率逐渐升高(P=0.001,P=0.001);但与肿瘤的复发性差异无显著性(P=0.183).结论:cyclinD1在膀胱TCC形成的早期起重要的作用;在评估膀胱TCC的生物学行为方面有着重要的临床意义.

  12. The roles of CC2D1A and HTR1A gene expressions in autism spectrum disorders.

    Science.gov (United States)

    Sener, Elif Funda; Cıkılı Uytun, Merve; Korkmaz Bayramov, Keziban; Zararsiz, Gokmen; Oztop, Didem Behice; Canatan, Halit; Ozkul, Yusuf

    2016-06-01

    Classical autism belongs to a group of heterogeneous disorders known as autism spectrum disorders (ASD). Autism is defined as a neurodevelopmental disorder, characterized by repetitive stereotypic behaviors or restricted interests, social withdrawal, and communication deficits. Numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism but the etiology of this disorder is unknown in many cases. CC2D1A gene has been linked to mental retardation (MR) in a family with a large deletion before. Intellectual disability (ID) is a common feature of autistic cases. Therefore we aimed to investigate the expressions of CC2D1A and HTR1A genes with the diagnosis of autism in Turkey. Forty-four autistic patients (35 boys, 9 girls) and 27 controls were enrolled and obtained whole blood samples to isolate RNA samples from each participant. CC2D1A and HTR1A gene expressions were assessed by quantitative Real-Time PCR (qRT-PCR) in Genome and Stem Cell Center, Erciyes University. Both expressions of CC2D1A and HTR1A genes studied on ASD cases and controls were significantly different (p < 0.001). The expression of HTR1A was undetectable in the ASD samples. Comparison of ID and CC2D1A gene expression was also found statistically significant (p = 0.028). CC2D1A gene expression may be used as a candidate gene for ASD cases with ID. Further studies are needed to investigate the potential roles of these CC2D1A and HTR1A genes in their related pathways in ASD.

  13. Requirement of PSD-95 for dopamine D1 receptor modulating glutamate NR1a/NR2B receptor function

    Institute of Scientific and Technical Information of China (English)

    Wei-hua GU; Shen YANG; Wei-xing SHI; Guo-zhang JIN; Xue-chu ZHEN

    2007-01-01

    Aim: To elucidate the role of scaffold protein postsynaptic density (PSD)-95 in the dopamine D1 receptor (D1R)-modulated NR 1a/NR2B receptor response.Methods: The human embryonic kidney 293 cells expressing D1R (tagged with the enhanced yellow fluorescent protein) and NR1a/NR2B with or without co-expres-sion of PSD-95 were used in the experiments. The Ca2+ influx measured by imaging technique was employed to monitor N-methyl-D-aspartic acid receptors (NMDAR) function.Results: The application of dopamine (DA, 100 μmol/L) did not alter glutamate/glycine (Glu/Gly)-induced NMDAR-mediated Ca2+ influx in cells only expressing the D1R/NR1a/NR2B receptor. However, DA increased Glu/Gly-induced Ca2+ influx in a concentration-dependent manner while the cells were co-expressed with PSD-95. D1.R-stimulated Ca2+ influx was inhibited by a selective DIR antagonist SCH23390. Moreover, pre-incubation with either the protein kinase A (PKA) inhibitor H89, or the protein kinase C (PKC) inhibitor chelerythrine attenuated D1R-enhanced Ca2+ influx induced by the N-methyl-D-aspartie acid (NMDA) agonist. The results clearly indicate that D1R-modulated NR1a/NR2B receptor function depends on PSD-95 and is subjected to the regulation of PKA and PKC.Conclusion: The present study provides the fast evidence that PSD-95 is essential in D iR-regulated NR1a/NR2B receptor function.

  14. Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

    Science.gov (United States)

    Gross, Noah B; Duncker, Patrick C; Marshall, John F

    2011-11-01

    Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex.

  15. Activation of the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway in human cholesteatoma epithelium.

    Science.gov (United States)

    Liu, Wei; Yin, Tuanfang; Ren, Jihao; Li, Lihua; Xiao, Zian; Chen, Xing; Xie, Dinghua

    2014-02-01

    Cholesteatoma is a benign keratinizing squamous epithelial lesion characterized by the hyper-proliferation of keratinocytes with abundant production of keratin debris in the middle ear. The epidermal growth factor receptor (EGFR)/Akt/nuclear factor-kappa B (NF-κB)/cyclinD1 signaling pathway is one of the most important pathways in regulating cell survival and proliferation. We hypothesized that the EGFR/Akt/NF-κB/cyclinD1 signaling pathway may be activated and involved in the cellular hyperplasia mechanism in acquired cholesteatoma epithelium. Immunohistochemical staining of phosphorylated EGFR (p-EGFR), phosphorylated Akt (p-Akt), activated NF-κB and cyclinD1 protein was performed in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium. Protein expression of p-EGFR, p-Akt, activated NF-κB and cyclinD1 in cholesteatoma epithelium was significantly increased when compared with normal EAC epithelium (p epithelium, a significant positive association was observed between p-EGFR and p-Akt expression and between the expressions of p-Akt and NF-κB, NF-κB and cyclinD1, respectively (p 0.05). The increased protein expression of p-EGFR, p-Akt, NF-κB and cyclinD1 and their associations in cholesteatoma epithelium suggest that the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway is active and may be involved in the regulatory mechanisms of cellular hyperplasia in cholesteatoma epithelium.

  16. Optogenetic inhibition of D1R containing nucleus accumbens neurons alters cocaine- mediated regulation of Tiam1

    Directory of Open Access Journals (Sweden)

    Ramesh eChandra

    2013-05-01

    Full Text Available Exposure to psychostimulants results in structural and synaptic plasticity in striatal medium spiny neurons (MSNs. These cellular adaptations arise from alterations in genes that are highly implicated in the rearrangement of the actin cytoskeleton, such as Tiam1. Previous studies have demonstrated a crucial role for dopamine receptor 1 (D1-containing striatal MSNs in mediating psychostimulant induced plasticity changes. These D1-MSNs in the nucleus accumbens (NAc positively regulate drug seeking, reward, and locomotor behavioral effects as well as the morphological adaptations of psychostimulant drugs. Here, we demonstrate that rats that actively self-administer cocaine display reduced levels of Tiam1 in the NAc. To further examine the cell type specific contribution to these changes in Tiam1 we used optogenetics to selectively manipulate NAc D1-MSNs or dopamine receptor 2 (D2 expressing MSNs. We find that repeated ChR2 activation of D1-MSNs but not D2-MSNs caused a down-regulation of Tiam1 levels similar to the effects of cocaine. Further, activation of D2-MSNs, which caused a late blunted cocaine-mediated locomotor behavioral response, did not alter Tiam1 levels. We then examined the contribution of D1-MSNs to the cocaine-mediated decrease of Tiam1. Using the light activated chloride pump, eNpHR3.0, we selectively inhibited D1-MSNs during cocaine exposure, which resulted in a behavioral blockade of cocaine-induced locomotor sensitization. Moreover, inhibiting these NAc D1-MSNs during cocaine exposure reversed the down-regulation of Tiam1 gene expression and protein levels. These data demonstrate that altering activity in specific neural circuits with optogenetics can impact the underlying molecular substrates of psychostimulant mediated behavior and function.

  17. Full-length Cloning of Human Melanoma Antigen-encoding Gene D1 Using Rapid Amplification of cDNA Ends%采用RACE技术获得全长人新基因MAGE-D1

    Institute of Scientific and Technical Information of China (English)

    邢桂春; 张成岗; 魏汉东; 贺福初

    2001-01-01

    cDNA 末端快速扩增(RACE)技术是快速获得新基因5'和3'端未知序列的有效手段.鉴于新报导的人肿瘤基因MAGE家族成员之一MAGE-D1的cDNA序列不完全,从而拟用RACE技术获得MAGE-D1的全长cDNA序列.结果显示,MAGE-D1的cDNA全长为2 800个碱基,编码778个氨基酸.同时对RACE技术应用时的一些关键问题进行了讨论.

  18. 北极狐多巴胺受体D1基因的克隆测序%Cloning and Sequencing of Dopamine Receptor D1 Gene of Arctic Fox

    Institute of Scientific and Technical Information of China (English)

    王光圣; 白秀娟

    2007-01-01

    为了获得北极狐多巴胺受体D1基因序列,给北极狐自咬行为提供理论依据.采用聚合酶链式反应方法,从北极狐耳组织扩增出多巴胺受体D1基因的部分外显子序列,并对其进行克隆测序,将该序列提交到Genebank上.Genebank中的Blast分析表明,北极狐多巴胺D1受体基因与家狗(Canis familiaris)的同源性为99%,与牛(Bos taurus)的同源性为93%,与人(Homo sapiens)的同源性为92%.

  19. Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis

    Science.gov (United States)

    Fussbroich, Daniela; Mueller, Klaus; Serve, Friederike; Smaczny, Christina; Zielen, Stefan; Schubert, Ralf

    2017-01-01

    Background Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. Methods In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. Results DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05). Conclusions SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was

  20. Dopamine induces neutrophil apoptosis through a dopamine D-1 receptor-independent mechanism.

    LENUS (Irish Health Repository)

    Sookhai, S

    2012-02-03

    BACKGROUND: For the normal resolution of an acute inflammatory response, neutrophil (PMN) apoptosis is essential to maintain immune homeostasis and to limit inappropriate host tissue damage. A delay in PMN apoptosis has been implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS). Dopamine, a biogenic amine with known cardiovascular and neurotransmitter properties, is used in patients with SIRS to maintain hemodynamic stability. We sought to determine whether dopamine may also have immunoregulatory properties capable of influencing PMN apoptosis, function, and activation state in patients with SIRS. METHODS: PMNs were isolated from healthy volunteers and patients with SIRS and treated with varying doses of dopamine and a dopamine D-1 receptor agonist, fenoldopam. PMN apoptosis was assessed every 6 hours with use of propidium iodide DNA staining and PMN function was assessed with use of respiratory burst activity, phagocytosis ability, and CD11a, CD11b, and CD18 receptor expression as functional markers. RESULTS: There was a significant delay in PMN apotosis in patients with SIRS compared with controls. Treatment of isolated PMNs from both healthy controls and patients with SIRS with 10 and 100 mumol\\/L dopamine induced apoptosis. PMN ingestive and cytocidal capacity were both decreased in patients with SIRS compared with controls. Treatment with dopamine significantly increased phagocytic function. Fenoldopam did not induce PMN apoptosis. CONCLUSION: Our data demonstrate for the first time that dopamine induces PMN apoptosis and modulates PMN function both in healthy controls and in patients with SIRS. These results indicate that dopamine may be beneficial during SIRS through a nonhemodynamic PMN-dependent proapoptotic mechanism.

  1. The protein kinase D1 COOH terminus: marker or regulator of enzyme activity?

    Science.gov (United States)

    Qiu, Weihua; Zhang, Fan; Steinberg, Susan F

    2014-10-01

    Protein kinase D1 (PKD1) is a Ser/Thr kinase implicated in a wide variety of cellular responses. PKD1 activation is generally attributed to a PKC-dependent pathway that leads to phosphorylation of the activation loop at Ser(744)/Ser(748). This modification increases catalytic activity, including that toward an autophosphorylation site (Ser(916)) in a postsynaptic density-95/disks large/zonula occludens-1 (PDZ)-binding motif at the extreme COOH terminus. However, there is growing evidence that PKD1 activation can also result from a PKC-independent autocatalytic reaction at Ser(744)/Ser(748) and that certain stimuli increase in PKD1 phosphorylation at Ser(744)/S(748) without an increase in autophosphorylation at Ser(916). This study exposes a mechanism that results in a discrepancy between PKD1 COOH-terminal autocatalytic activity and activity toward other substrates. We show that PKD1 constructs harboring COOH-terminal epitope tags display high levels of in vitro activation loop autocatalytic activity and activity toward syntide-2 (a peptide substrate), but no Ser(916) autocatalytic activity. Cell-based studies show that the COOH-terminal tag, adjacent to PKD1's PDZ1-binding motif, does not grossly influence PKD1 partitioning between soluble and particulate fractions in resting cells or PKD1 translocation to the particulate fraction following treatment with PMA. However, a COOH-terminal tag that confers a high level of activation loop autocatalytic activity decreases the PKC requirement for agonist-dependent PKD1 activation in cells. The recognition that COOH-terminal tags alter PKD1's pharmacological profile is important from a technical standpoint. The altered dynamics and activation mechanisms for COOH-terminal-tagged PKD1 enzymes also could model the signaling properties of localized pools of enzyme anchored through the COOH terminus to PDZ domain-containing scaffolding proteins.

  2. Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

    Directory of Open Access Journals (Sweden)

    Heidi Loponen

    Full Text Available Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1 and p21(Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

  3. Dopamine D1 receptor stimulation modulates the formation and retrieval of novel object recognition memory: Role of the prelimbic cortex.

    Science.gov (United States)

    Pezze, Marie A; Marshall, Hayley J; Fone, Kevin C F; Cassaday, Helen J

    2015-11-01

    Previous studies have shown that dopamine D1 receptor antagonists impair novel object recognition memory but the effects of dopamine D1 receptor stimulation remain to be determined. This study investigated the effects of the selective dopamine D1 receptor agonist SKF81297 on acquisition and retrieval in the novel object recognition task in male Wistar rats. SKF81297 (0.4 and 0.8 mg/kg s.c.) given 15 min before the sampling phase impaired novel object recognition evaluated 10 min or 24 h later. The same treatments also reduced novel object recognition memory tested 24 h after the sampling phase and when given 15 min before the choice session. These data indicate that D1 receptor stimulation modulates both the encoding and retrieval of object recognition memory. Microinfusion of SKF81297 (0.025 or 0.05 μg/side) into the prelimbic sub-region of the medial prefrontal cortex (mPFC) in this case 10 min before the sampling phase also impaired novel object recognition memory, suggesting that the mPFC is one important site mediating the effects of D1 receptor stimulation on visual recognition memory.

  4. Relationships between D1 protein, xanthophyll cycle and photodamage-resistant capacity in rice (Orysa sativa L.)

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Relationships between D1 protein, xanthophyll cycle and subspecific difference of photodamage-resistant capacity have been studied in O. japonica rice varieties 02428 and 029 (photoinhibition-tolerance) and O. indica rice varieties 3037 and Palghar (photoinhibition-sensitivity) and their reciprocal cross F1 hybrids after photoinhibitory treatment. It was shown that PSⅡ photochemical efficiency (Fv /Fm) decreased, and xanthophyll cycle from violaxanthin (V), via anaxanthin (A), to zeaxanthin (Z) was enhanced and non-photochemical quenching (qN) increased accordingly in SM-pretreated leaves of rice when the synthesis of D1 protein was inhibited, and that there was a decrease in qN and, as a result, more loss of D1 protein and a big decrease in Fv /Fm in DTT-pretreated leaves when xanthophyll cycle was inhibited. O. japonica subspecies had a higher maintaining capacity of D1 protein and a decrease of Fv /Fm in a more narrow range, and exhibited more resistance against photodamage, as compared with O. indica subspecies. The above physiological indexes in reciprocal cross F1 hybrids, though between the values of their parents, were closer to maternal lines than to paternal lines. Experimental results support the concept that the turnover capacity for D1 protein is an important physiological basis of photoinhibition-tolerance, and will provide the physiological basis for selection of the photoinhibition-tolerant parents and develop a new approach to breed hybrids with high photosynthetic efficiency.

  5. D1/D5 system with B-field, noncommutative geometry and the CFT of the higgs branch

    CERN Document Server

    Dhar, A; Wadia, S R; Yogendran, K P; Dhar, Avinash; Mandal, Gautam; Wadia, Spenta R.

    2000-01-01

    The D1/D5 system is considered in the presence of the NS B field. An explicit supergravity solution in the asymptotically flat and near horizon limits is presented. Explicit mass formulae are presented in both cases. This solution has no D3 source branes and represents a true bound state of the D1/D5 system. We study the motion of a separated D1-brane in the background geometry described above and reproduce the Liouville potential that binds the D1 brane. A gauge theory analysis is also presented in the presence of Fayet-Iliopoulos (FI) parameters which can be identified with the self-dual part of the NS B field. In the case of a single D5-brane and an arbitrary number of D1 branes we can demonstrate the existence of a bound state in the Higgs branch. We also point out the connection of the SCFT on the resolved Sym$_{Q_1Q_5}(\\tilde T^4)$ with recent developments in non-commutative Yang-Mills theory.

  6. Human pluripotent embryonal carcinoma NTERA2 cl.D1 cells maintain their typical morphology in an angiomyogenic medium

    Directory of Open Access Journals (Sweden)

    Ramos Teresa

    2007-04-01

    Full Text Available Abstract Background Pluripotent embryonal carcinomas are good potential models, to study, "in vitro," the mechanisms that control differentiation during embryogenesis. The NTERA2cl.D1 (NT2/D1 cell line is a well known system of ectodermal differentiation. Retinoic acid (RA induces a dorsal pattern of differentiation (essentially neurons and bone morphogenetic protein (BMP or hexamethylenebisacetamide (HMBA induces a more ventral (epidermal pattern of differentiation. However, whether these human cells could give rise to mesoderm derivatives as their counterpart in mouse remained elusive. We analyzed the morphological characteristics and transcriptional activation of genes pertinent in cardiac muscle and endothelium differentiation, during the growth of NT2/D1 cells in an inductive angiomyogenic medium with or without Bone Morphogenetic Protein 2 (BMP2. Results Our experiments showed that NT2/D1 maintains their typical actin organization in angiomyogenic medium. Although the beta myosin heavy chain gene was never detected, all the other 15 genes analyzed maintained their expression throughout the time course of the experiment. Among them were early and late cardiac, endothelial, neuronal and teratocarcinoma genes. Conclusion Our results suggest that despite the NT2/D1 cells natural tendency to differentiate into neuroectodermal lineages, they can activate genes of mesodermal lineages. Therefore, we believe that these pluripotent cells might still be a good model to study biological development of mesodermal derivatives, provided the right culture conditions are met.

  7. Detection of mRNA of the cyclin D1 breast cancer marker by a novel duplex-DNA probe.

    Science.gov (United States)

    Segal, Meirav; Yavin, Eylon; Kafri, Pinhas; Shav-Tal, Yaron; Fischer, Bilha

    2013-06-27

    Previously, we have described 5-((4-methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6, as a fluorescent uridine analogue exhibiting a 3000-fold higher quantum yield (Φ 0.12) and maximum emission (478 nm) which is 170 nm red-shifted as compared to uridine. Here, we utilized 6 for preparation of labeled oligodeoxynucleotide (ODN) probes based on MS2 and cyclin D1 (a known breast cancer mRNA marker) sequences. Cyclin D1-derived labeled-ssODN showed a 9.5-fold decrease of quantum yield upon duplex formation. On the basis of this finding, we developed the ds-NIF (nucleoside with intrinsic fluorescence)-probe methodology for detection of cyclin D1 mRNA, by which the fluorescent probe is released upon recognition of target mRNA by the relatively dark NIF-duplex-probe. Indeed, we successfully detected, a ss-deoxynucleic acid (DNA) variant of cyclin D1 mRNA using a dark NIF-labeled duplex-probe, and monitoring the recognition process by fluorescence spectroscopy and gel electrophoresis. Furthermore, we successfully detected cyclin D1 mRNA in RNA extracted from cancerous human cells, using ds-NIF methodology.

  8. 辐照外源DNA导入番茄研究—D1、D2代分析%Study on Introducing Radiated Exogenous DNA into Tomato——Analysis of D1 and D2 Generation

    Institute of Scientific and Technical Information of China (English)

    薛林宝; 葛才林; 杨晓峰; 邵耀椿

    2001-01-01

    After exogenous DNA radiated by the γ ray from 60Co introducedinto to mato,the leaf shape of the offering plant not only expressed in D1 generation but also can be conveyed to D2 generation ,And there were significant differe nc es in fruit shape ,fruit size and Vc content between D1 generation and no radi ation group.To verify the effect and its repetition of this method the expeiment of intr oducing radiated exogenous DNA into tomato was repeated.The result showed that i t was same as the last experiment,the dominant genes of normal leaf shape of off e ring plant was expressed in receiving plant from the seedling of D1 generation . Also the genes of leaf shape of wild variety tomato was expressed in D1 genera tion of receptor by using radiated DNA of wild variety as a donor .All mentioned above shows that the method of introducing radiated exogenous DNA into tomato h as desirable effect and repetition,which can be used to facilitate distant hybri dization.%辐照外源DNA导入番茄后,供体叶形不但在D1代上得到表达,而且能遗传到D2代。并且在D1代,其果形、果实大小以及VC含量等都有明显变化。为验证该技术的效果和重复性,又进行了第二期辐照外源DNA导入番茄试验,发现在D1代幼苗中,供体的显性基因正常叶形,仍有一定的几率在受体中得到表达,结果与第一期试验相同。野生种番茄DNA经辐照作供体导入后,也获得了野生种叶形在受体中得到表达的D1代植株。说明辐照外源DNA导入番茄技术效果好,重复性好,便于进行远缘杂交。

  9. Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity

    DEFF Research Database (Denmark)

    Chadt, Alexandra; Leicht, Katja; Deshmukh, Atul;

    2008-01-01

    We previously identified Nob1 as a quantitative trait locus for high-fat diet-induced obesity and diabetes in genome-wide scans of outcross populations of obese and lean mouse strains. Additional crossbreeding experiments indicated that Nob1 represents an obesity suppressor from the lean Swiss Jim...... and reduced glucose uptake in isolated skeletal muscle. Our data strongly suggest that mutation of Tbc1d1 suppresses high-fat diet-induced obesity by increasing lipid use in skeletal muscle....... Lambert (SJL) strain. Here we identify a SJL-specific mutation in the Tbc1d1 gene that results in a truncated protein lacking the TBC Rab-GTPase-activating protein domain. TBC1D1, which has been recently linked to human obesity, is related to the insulin signaling protein AS160 and is predominantly...

  10. Stability and accuracy of 3D neutron transport simulations using the 2D/1D method in MPACT

    Science.gov (United States)

    Collins, Benjamin; Stimpson, Shane; Kelley, Blake W.; Young, Mitchell T. H.; Kochunas, Brendan; Graham, Aaron; Larsen, Edward W.; Downar, Thomas; Godfrey, Andrew

    2016-12-01

    A consistent "2D/1D" neutron transport method is derived from the 3D Boltzmann transport equation, to calculate fuel-pin-resolved neutron fluxes for realistic full-core Pressurized Water Reactor (PWR) problems. The 2D/1D method employs the Method of Characteristics to discretize the radial variables and a lower order transport solution to discretize the axial variable. This paper describes the theory of the 2D/1D method and its implementation in the MPACT code, which has become the whole-core deterministic neutron transport solver for the Consortium for Advanced Simulations of Light Water Reactors (CASL) core simulator VERA-CS. Several applications have been performed on both leadership-class and industry-class computing clusters. Results are presented for whole-core solutions of the Watts Bar Nuclear Power Station Unit 1 and compared to both continuous-energy Monte Carlo results and plant data.

  11. Similarity of recombinant human perlecan domain 1 by alternative expression systems bioactive heterogenous recombinant human perlecan D1

    DEFF Research Database (Denmark)

    Ellis, April L; Pan, Wensheng; Yang, Guang

    2010-01-01

    BACKGROUND: Heparan sulfate glycosaminoglycans are diverse components of certain proteoglycans and are known to interact with growth factors as a co-receptor necessary to induce signalling and growth factor activity. In this report we characterize heterogeneously glycosylated recombinant human...... perlecan domain 1 (HSPG2 abbreviated as rhPln.D1) synthesized in either HEK 293 cells or HUVECs by transient gene delivery using either adenoviral or expression plasmid technology. RESULTS: By SDS-PAGE analysis following anion exchange chromatography, the recombinant proteoglycans appeared to possess...... glycosaminoglycan chains ranging, in total, from 6 kDa to >90 kDa per recombinant. Immunoblot analysis of enzyme-digested high Mr rhPln.D1 demonstrated that the rhPln.D1 was synthesized as either a chondroitin sulfate or heparan sulfate proteoglycan, in an approximately 2:1 ratio, with negligible hybrids. Secondary...

  12. Essential role of D1R in the regulation of mTOR complex1 signaling induced by cocaine.

    Science.gov (United States)

    Sutton, Laurie P; Caron, Marc G

    2015-12-01

    The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that is involved in neuronal adaptions that underlie cocaine-induced sensitization and reward. mTOR exists in two functionally distinct multi-component complexes known as mTORC1 and mTORC2. In this study, we show that increased mTORC1 activity induced by cocaine is mediated by the dopamine D1 receptor (D1R). Specifically, cocaine treatment increased the phosphorylation on residues Thr2446 and Ser2481 but not on Ser2448 in the nucleus accumbens (NAc) and that this increase in phosphorylated mTOR levels was also apparent when complexed with its binding partner Raptor. Furthermore, the increase in phosphorylated mTOR levels, as well as phosphorylated 4E-BP1 and S6K, downstream targets of mTORC1 were blocked with SCH23390 treatment. Similar results were also observed in the dopamine-transporter knockout mice as the increase in phosphorylated mTOR Thr2446 and Ser2481 was blocked by SCH23390 but not with raclopride. To further validate D1R role in mTORC1 signaling, decrease in phosphorylated mTOR levels were observed in D1R knockout mice, whereas administration of SKF81297 elevated phosphorylated mTOR in the NAc. Lastly deletion of mTOR or Raptor in D1R expressing neurons reduced cocaine-induced locomotor activity. Together, our data supports a mechanism whereby mTORC1 signaling is activated by cocaine administration through the stimulation of D1R.

  13. Cloning, expression and characterization of CYP102D1, a self-sufficient P450 monooxygenase from Streptomyces avermitilis.

    Science.gov (United States)

    Choi, Kwon-Young; Jung, EunOk; Jung, Da-Hye; Pandey, Bishnu Prasad; Yun, Hyungdon; Park, Hyung-yun; Kazlauskas, Romas J; Kim, Byung-Gee

    2012-05-01

    Among 33 cytochrome P450s (CYPs) of Streptomyces avermitilis, CYP102D1 encoded by the sav575 gene is naturally a unique and self-sufficient CYP. Since the native cyp102D1 gene could not be expressed well in Escherichia coli, its expression was attempted using codon-optimized synthetic DNA. The gene was successfully overexpressed and the recombinant CYP102D1 was functionally active, showing a Soret peak at 450 nm in the reduced CO difference spectrum. FMN/FAD isolated from the reductase domain showed the same fluorescence in thin layer chromatography separation as the authentic standards. Characterization of the substrate specificity of CYP102D1 based on NADPH oxidation rate revealed that it catalysed the oxidation of saturated and unsaturated fatty acids with very good regioselectivity, similar to other CYP102A families depending on NADPH supply. In particular, CYP102D1 catalysed the rapid oxidation of myristoleic acid with a k(cat)/K(m) value of 453.4 ± 181.5 μM(-1)·min(-1). Homology models of CYP102D1 based on other members of the CYP102A family allowed us to alter substrate specificity to aromatic compounds such as daidzein. Interestingly, replacement of F96V/M246I in the active site increased catalytic activity for daidzein with a k(cat)/K(m) value of 100.9 ± 10.4 μM(-1)·min(-1) (15-fold).

  14. HBV/D1: a major HBV subgenotype circulating in Uyghur patients with chronic HBV infection in Xinjiang, China.

    Science.gov (United States)

    Nie, Jingjing; Li, Jie; Sun, Kuixia; Sun, Mishu; Chen, Jie; Ma, Junfeng; Yan, Ling; Zhuang, Hui

    2012-08-01

    Each hepatitis B virus (HBV) genotype and subgenotype is associated with a particular geographic distribution, ethnicity, and anthropological history. The present study investigated the genomic characteristics of HBV from Uyghur patients with chronic HBV infection in Xinjiang, China. Among the 53 Uyghur patients enrolled, HBV/D was found to be the dominant strain, with 64.2 % (34/53), 60.4 % (32/53) with HBV/D1 and 3.8 % (2/53) with HBV/D3. In addition to these findings, 3.8 % HBV/B (2/53), 5.7 % HBV/C (3/53), 11.3 % C+D (6/53), 7.5 % B+D (4/53), 3.8 % B+C (2/53) and 3.8 % B+C+D (2/53) were also detected. The full-length genome of seven HBV/D1 isolates and 144 reference sequences retrieved from GenBank were compared and analyzed by biological information methods. These results demonstrate that the D1 isolates from Xinjiang and Central Asia show a close genetic proximity (0.013±0.0007). Furthermore, four unique amino acid substitutions (sp82(Asn), sp89(His), rt129(Leu), rt151(Leu)) representing background polymorphisms rather than drug resistance mutations or immune escape variants were found in the Uyghur patients of Xinjiang, but these were seldom found in HBV/D1 strains from other regions (0 %-14.3 %). This study indicates that in Xinjiang, unlike HBV-infected Han patients, HBV/D1 is the predominant strain among HBV-infected Uyghur people. Although genetic distance analysis suggests that the HBV/D1 isolates from Xinjiang are closely related to those from Central Asia, unique amino acid substitutions suggest independent evolution of HBV in the Uyghur patients of Xinjiang.

  15. cyclin D1、pRb在大肠癌中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    朱龙贤; 黄文斌; 朱晓群; 齐琼

    2000-01-01

    目的研究大肠癌中cyclin D1和pRb的表达与临床病理参数之间的关系以及二者之间的关系.方法采用免疫组化方法S-P法检测67例大肠癌、40例癌旁粘膜和40例正常粘膜中cyclin D1和pRb的表达.结果大肠癌中cyclin D1和pRb的阳性率分别为44.8%和100.0%,明显高于癌旁粘膜和正常粘膜(P<0.05),cyclin D1在低分化癌的过表达率高于高分化癌(P<0.05),C+D期的过表达率明显高于A+B期(P<0.01);pRb在C+D期的过表达率高于A+B期(P<0.05),pRb的过表达率与肿瘤的分化程度无关(P<0.05).相关分析表明,cyclinD1和pRb无明显相关(P>0.05).结论cyclin D1参与了大肠癌的发生并与肿瘤的分化程度和Duke's分期有关,而pRb与肿瘤的分化程度无关.

  16. Identification of a human cyclin D1-derived peptide that induces human cytotoxic CD4 T cells.

    Directory of Open Access Journals (Sweden)

    Tao Dao

    Full Text Available Cyclin D1 is over-expressed in various human tumors and therefore can be a potential oncogenic target antigen. However, only a limited number of T cell epitopes has been characterized. We aimed at identifying human cyclin D1-derived peptides that include both CD4 and CD8 T cell epitopes and to test if such multi-epitope peptides could yield improved cytotoxic CD8 T cell responses as well as cytotoxic CD4 T cells. Five HLA-DR.B1-binding peptides containing multiple overlapping CD4 epitopes and HLA-A0201-restricted CD8 T cell epitopes were predicted by computer algorithms. Immunogenicity of the synthetic peptides was assessed by stimulating T cells from healthy donors in vitro and the epitope recognition was measured by IFN-gamma ELISPOT and (51Chromium release assays. A HLA-DR.B1 peptide, designed "DR-1", in which a HLA-A0201-binding epitopes (D1-1 was imbedded, induced CD3 T cell responses against both DR-1 and D1-1 peptides in IFN-gamma ELISPOT assay. This suggested processing of the shorter D1-1 epitope from the DR-1 sequence. However, only DR-1-stimulated CD4 or CD3 T cells possessed cytotoxicity against peptide-pulsed autologous DCs and a cancer cell line, that expresses a high level of cyclin D1. Monoclonal antibody to HLA-DR abrogated the epitope-specific responses of both CD3 and CD4 T cells, demonstrating class II-mediated killing. Our studies suggest a possible role of CD4 T cells in anti-tumor immunity as cytotoxic effectors against HLA-DR expressing cancers and provide a rationale for designing peptide vaccines that include CD4 epitopes.

  17. Does N ratio affect survival in D1 and D2 lymph node dissection for gastric cancer?

    Institute of Scientific and Technical Information of China (English)

    Ibrahim Sakcak; Bars Do(g)u Yildiz; Fatih Mehmet Avsar; Saadet Akturan; Kemal Kilic; Erdal Cosgun; Enver O Hamamci

    2011-01-01

    AIM: To identify whether there could have been changes in survival if lymph node ratio (N ratio) had been used.METHODS: We assessed 334 gastric adenocarcinoma cases retrospectively between 2001 and 2009. Two hundred and sixteen patients out of 334 were included in the study. Patients were grouped according to disection1 (D1) or dissection 2 (D2) dissection. We compared the estimated survival and actual survival determine dbyPathologicnodes(pN) classandNratio,andd by Pathologic nodes (class and N ratio, and SPSS 15.0 software was used for statistical analysis.RESULTS: Ninety-six (44.4%) patients underwent D1 dissection and 120 (55.6%) had D2 dissection. When groups were evaluated, 23 (24.0%) patients in D1 and 21 (17.5%) in D2 had stage migration (P = 0.001). When both D1 and D2 groups were evaluated for number of pathological lymph nodes, despite the fact that there was no difference in N ratio between D1 and D2 groups, a statistically significant difference was found between them with regard to pN1 and pN2 groups (P = 0.047, P = 0.044 respectively). In D1, pN0 had the longest survival while pN3 had the shortest. In D2, pN0 had the longest survival whereas pN3 had the shortest survival.CONCLUSION: N ratio is an accurate staging system for defining prognosis and treatment plan, thus decreasing methodological errors in gastric cancer staging.

  18. Deliverable 6.2 - Software: upgraded MC simulation tools capable of simulating a complete in-beam ET experiment, from the beam to the detected events. Report with the description of one (or few) reference clinical case(s), including the complete patient model and beam characteristics

    CERN Document Server

    The ENVISION Collaboration

    2014-01-01

    Deliverable 6.2 - Software: upgraded MC simulation tools capable of simulating a complete in-beam ET experiment, from the beam to the detected events. Report with the description of one (or few) reference clinical case(s), including the complete patient model and beam characteristics

  19. ADAM adaptation and mitigation strategies: supporting European climate policy. Deliverable D3 of work package M1 (code D-M1.3). ADAM 2-degree scenario for Europe - policies and impacts

    Energy Technology Data Exchange (ETDEWEB)

    Schade, Wolfgang; Jochem, Eberhard; Barker, Terry (and others)

    2009-07-31

    ADAM research identifies and appraises existing and new policy options that can contribute to different combinations of adaptation and mitigation strategies. These options address the demands a changing climate will place on protecting citizens and valuable ecosystems - i.e., adaptation - as well as addressing the necessity to restrain/control humankind's perturbation to global climate to a desirable level - i.e., mitigation. The work package Mitigation 1 (Ml) has the core objective to simulate mitigation options and their related costs for Europe until 2050 and 2100 respectively. The focus of this deliverable is on the period 2005 to 2050. The long-term period until 2100 is covered in the previous deliverable D2, applying the POLES model for this time horizon. The analysis constitutes basically a techno-economic analysis. Depending on the sector analyzed it is either directly combined with a policy analysis (e.g. in the transport sector, renewables sector) or the policy analysis is performed qualitatively as a subsequent and independent step after the techno-economic analysis is completed (e.g. in the residential and service sectors). The book includes the following chapters: scenarios and macroeconomic assumptions; methodological issues analyzing mitigation options; the integrated global energy model POLES and its projections for the reference and 2 deg C scenarios; forest and basic materials sector; residential sector in Europe; the service (tertiary) and the primary sectors in Europe; basic products and other manufacturing industry sectors; transport sectors in Europe; renewable sector in Europe; conversion sector in Europe; syntheses and sectoral analysis in Europe; macroeconomic impacts of climate policy in the EU; the effects of the financial crisis on baseline simulations with implications for climate policy modeling: an analysis using the global model E3MG 2008-2012; conclusions and policy recommendations.

  20. SmD1 Modulates the miRNA Pathway Independently of Its Pre-mRNA Splicing Function.

    Directory of Open Access Journals (Sweden)

    Xiao-Peng Xiong

    2015-08-01

    Full Text Available microRNAs (miRNAs are a class of endogenous regulatory RNAs that play a key role in myriad biological processes. Upon transcription, primary miRNA transcripts are sequentially processed by Drosha and Dicer ribonucleases into ~22-24 nt miRNAs. Subsequently, miRNAs are incorporated into the RNA-induced silencing complexes (RISCs that contain Argonaute (AGO family proteins and guide RISC to target RNAs via complementary base pairing, leading to post-transcriptional gene silencing by a combination of translation inhibition and mRNA destabilization. Select pre-mRNA splicing factors have been implicated in small RNA-mediated gene silencing pathways in fission yeast, worms, flies and mammals, but the underlying molecular mechanisms are not well understood. Here, we show that SmD1, a core component of the Drosophila small nuclear ribonucleoprotein particle (snRNP implicated in splicing, is required for miRNA biogenesis and function. SmD1 interacts with both the microprocessor component Pasha and pri-miRNAs, and is indispensable for optimal miRNA biogenesis. Depletion of SmD1 impairs the assembly and function of the miRISC without significantly affecting the expression of major canonical miRNA pathway components. Moreover, SmD1 physically and functionally associates with components of the miRISC, including AGO1 and GW182. Notably, miRNA defects resulting from SmD1 silencing can be uncoupled from defects in pre-mRNA splicing, and the miRNA and splicing machineries are physically and functionally distinct entities. Finally, photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP analysis identifies numerous SmD1-binding events across the transcriptome and reveals direct SmD1-miRNA interactions. Our study suggests that SmD1 plays a direct role in miRNA-mediated gene silencing independently of its pre-mRNA splicing activity and indicates that the dual roles of splicing factors in post-transcriptional gene regulation may be

  1. Phosphodiesterase activity is regulated by CC2D1A that is implicated in non-syndromic intellectual disability

    KAUST Repository

    Altawashi, Azza

    2013-07-04

    Background: Cyclic adenosine 3?5?-monophosphate (cAMP) is a key regulator of many cellular processes, including in the neuronal system, and its activity is tuned by Phosphodiesterase (PDE) activation. Further, the CC2D1A protein, consisting of N-Terminal containing four DM14 domains and C-terminal containing C2 domain, was shown to regulate the cAMP-PKA pathway. A human deletion mutation lacking the fourth DM14 and the adjacent C2 domain results in Non Syndromic Intellectual Disability (NSID) also referred to as Non Syndromic Mental Retardation (NSMR). Findings. Here we demonstrate that in Mouse Embryonic Fibroblasts (MEF) CC2D1A co-localizes with PDE4D in the cytosol before cAMP stimulation and on the periphery after stimulation, and that the movement to the periphery requires the full-length CC2D1A. In CC2D1A mouse mutant cells, the absence of three of the four DM14 domains abolishes migration of the complex to the periphery and causes constitutive phosphorylation of PDE4D Serine 126 (Sssup126esup) via the cAMP-dependent protein kinase A (PKA) resulting in PDE4D hyperactivity. Suppressing PDE4D activity with Rolipram in turn restores the down-stream phosphorylation of the "cAMP response element-binding protein" (CREB) that is defective in mouse mutant cells. Conclusion: Our findings suggest that CC2D1A is a novel regulator of PDE4D. CC2D1A interacts directly with PDE4D regulating its activity and thereby fine-tuning cAMP-dependent downstream signaling. Based on our in vitro evidence we propose a model which links CC2D1A structure and function to cAMP homeostasis thereby affecting CREB phosphorylation. We speculate that CC2D1A and/or PDE4D may be promising targets for therapeutic interventions in many disorders with impaired PDE4D function such as NSID. 2013 Al-Tawashi and Gehring; licensee BioMed Central Ltd.

  2. Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed by three types of motor behavior

    Directory of Open Access Journals (Sweden)

    Toru eNakamura

    2014-07-01

    Full Text Available Both D1R and D2R knock out (KO mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT mice. First, we examined spontaneous motor activity in the home cage environment for consecutive five days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT

  3. Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

    Directory of Open Access Journals (Sweden)

    Jong Hyun Kim

    Full Text Available BACKGROUND: Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we found that AMPK-induced phospholipase D1 (PLD1 activation is required for (14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT stimulates PLD activity, while AMPK-dominant negative (DN inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA, which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator regulate (14C-glucose uptake and cell surface glucose transport (GLUT 4 through ERK stimulation by AMPK-mediated PLD1 activation. CONCLUSIONS/SIGNIFICANCE: These results

  4. Sustained AS160 and TBC1D1 phosphorylations in human skeletal muscle 30 minutes after a single bout of exercise

    DEFF Research Database (Denmark)

    Vendelbo, Mikkel; Møller, Andreas Buch; Treebak, Jonas T;

    2014-01-01

    Background: Phosphorylation of AS160 and TBC1D1 plays an important role for GLUT4 mobilization to the cell surface. The phosphorylation of AS160 and TBC1D1 in humans in response to acute exercise is not fully characterized. Objective: To study AS160 and TBC1D1 phosphorylation in human skeletal...

  5. Cytochrome P450 1D1: A novel CYP1A-related gene that is not transcriptionally activated by PCB126 or TCDD

    DEFF Research Database (Denmark)

    Goldstone, J.V.; Jönsson, M.E.; Behrendt, Lars;

    2009-01-01

    Enzymes in the cytochrome P450 1 family oxidize many common environmental toxicants. We identified a new CYP1, termed CYP1D1, in zebrafish. Phylogenetically, CYP1D1 is paralogous to CYP1A and the two share 45% amino acid identity and similar gene structure. In adult zebrafish, CYP1D1 is most high...

  6. 乳香提取物对大鼠乙酸胃溃疡β-catenin和Cyclin D1的影响%Effect of Frankincense Extract on β-catenin and Cyclin D1 of Gastric Ulcer Rats

    Institute of Scientific and Technical Information of China (English)

    梅武轩; 余娜

    2015-01-01

    目的:探讨乳香提取物对大鼠乙酸胃溃疡β-catenin和Cyclin D1的影响.方法:用冰醋酸制备大鼠慢性胃溃疡模型,随机分为3组,分别灌服生理盐水、乳香提取物、奥美拉唑等.免疫组织化学方法检测30 d和60 d胃黏膜β-caternin和Cyclin D1的蛋白表达.结果:第30 d中药组、西药组α-catenin、Cyclin D1表达增强,与模型组比较,有显著性差异(P<0.05);第60d模型组、中药组和西药组β-catenin表达均无显著性差异(P>0.05).结论:乳香提取物能上调胃粘膜β-catenin、CyclinD1的表达,加快细胞的增殖,而促进溃疡的愈合,可能是乳香“生肌”的作用机理之一.

  7. Cyclin D1 gene amplification in the primary nasopharyngeal carcinoma by interphase FISH%应用间期FISH技术探讨cyclinD1基因在鼻咽癌中的扩增

    Institute of Scientific and Technical Information of China (English)

    黄贻学; 方嬿; 郭颖; 郝亚萍; 李辉梅; 曾益新

    2000-01-01

    目的:检测cyclinD1基因在鼻咽癌(nasopharyngeal carcinoma,NPC)细胞中的扩增情况,探讨cyclinD1基因在NPC发生及发展中的作用.方法:应用间期Micro FISH技术.结果:83例NPC病例可见23例(占27.71%)出现cyclinD1扩增;其中Ⅰ、Ⅱ期病例扩增的有5例,Ⅲ、Ⅳ期病例扩增的有18例;23例扩增中16例(69.56%)伴有颈淋巴结转移.结论:cyclinD1扩增与NPC的中晚期发展可能有一定关系,并与颈淋巴结转移呈正相关.

  8. 加权Dirichlet空间D1a上Toeplitz算子的紧性与Fredholm性质%Compact and Fredholm Toeplitz operators on weighted Dirichlet space D1a

    Institute of Scientific and Technical Information of China (English)

    夏锦; 胡坤

    2015-01-01

    利用对数加权Bloch空间和对数加权小Bloch空间,刻画了加权Dirichlet空间D1上Toeplitz算子的有界性、紧性与Fredholm性质,讨论了Toeplitz算子的谱性质,计算了Toeplitz算子的Fredholm指标.

  9. pRb和CyclinD1在胃癌发生发展中的表达%Expression of pRb and CyclinD1 in occurrence and development of gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    王国荣; 何文宪; 王彦芳; 郑焱

    2002-01-01

    目的:探讨pRb和CyclinD1在胃癌发生发展中的作用及两者的相关性.方法:用S-P免疫组织化学法检测pRb和CyclinD1的表达水平.结果:pRb的表达与肿瘤大小、浸润程度、是否转移有显著相关性.在胃癌形成的几个环节中,pRb的表达呈明显下调趋势;反之,CyclinD1的表达呈明显的上调趋势.结论:pRb的失表达和CyclinD1的过表达可能在胃癌的发生发展中起重要作用."Rb路径"的失衡可能是胃癌成因之一.

  10. Relationship between expression of pRb and cyclin D1 protein and prognosis in gastric carcinoma%胃癌中pRb和cyclin D1蛋白表达与预后的关系

    Institute of Scientific and Technical Information of China (English)

    龙延滨; 王国荣; 王小强; 何文宪

    2003-01-01

    目的:探讨pRb和cyclin D1蛋白表达与胃癌进展及预后的关系.方法:采用S-P免疫组化法检测了53例进展期胃癌中pRb和cyclin D1蛋白表达的情况,并随访其术后5年生存状况.结果:在进展期胃癌中pRb和cyclin D1表达率分别为47.16%和75.47%,在正常胃粘膜中表达率分别为100%和20%,两组有显著差异性.pRb的表达与淋巴结是否转移、临床分期及术后生存时间有显著相关性.而cyclin D1表达与胃癌临床病理参数及术后生存时间无关.结论:pRb表达可反映胃癌进展及预后.

  11. Expression and clinical significance of Cyclin D1 and CDX2 protein in gastric carcinoma%Cyclin D1和CDX2蛋白在胃癌组织中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    谷化平; 黄勇; 尚培中

    2013-01-01

    目的:探讨细胞周期素D1(Cyclin D1)和尾型同源转录因子-2(CDX2)蛋白的表达与胃癌(GC)临床病理特征及患者生存期的关系.方法:应用免疫组织化学技术检测120例GC、60例肠上皮化生(IM)、60例异型增生(GED)和20例正常胃黏膜(NGM)组织中Cyclin D1和CDX2蛋白的表达,并结合GC的病理学行为和临床随访资料进行分析.结果:Cyclin D1在GC组织中表达阳性率为61.7%,显著高于GED、IM和NGM组织(35.0%、16.7%、0),差异有统计学意义(P<0.05),GED组织高于IM和NGM组织,差异亦有统计学意义(P<0.05).CDX2在GC、GED、IM组织中表达阳性率分别为56.7%、68.3%和91.7%,显著高于NGM组织(0),差异有统计学意义(P<0.05);IM组织高于GC和GED组织,差异亦有统计学意义(P<0.05);GC组织与GED组织之间差异无统计学意义(P>0.05).Cyclin D1和CDX2表达与GC分化程度、浆膜浸润、淋巴结转移和患者生存期相关(P<0.05).Cyclin D1和CDX2表达呈显著负相关(r=-0.34,P<0.05).结论:Cyclin D1和CDX2均参与了GC的发生发展,均可作为辅助GC诊断、预测生物学行为和评估预后的参考指标.

  12. Final repository for spent nuclear fuel. Underground design Forsmark, Layout D1

    Energy Technology Data Exchange (ETDEWEB)

    Brantberger, Martin; Zetterqvist, Anders [Ramboell Sweden AB, Stockholm (Sweden); Arnbjerg-Nielsen, Torben [Ramboell Denmark A/S, Virum (Denmark); Olsson, Tommy [IandT Olsson AB, Uppsala (Sweden); Outters, Nils [Golder Associates AB, Uppsala (Sweden); Syrjaenen, Pauli [Gridpoint Oy, Helsinki (Sweden)

    2006-04-15

    This report comprises the design step D1 related to the underground design for a deep repository located at the Forsmark site. The design is based on the Site Descriptive Model Forsmark v1.2. All studies have been focussed at an area southeast of the Forsmark nuclear plant, which has been considered to be the most promising area for hosting the repository. SKB has developed guidelines for the design of the repository, which further describes the methodology applied for the studies. From these guidelines the following basic objectives for the design step D1 are summarized: to determine whether the final repository can be accommodated within the studied site; to identify site-specific facility critical issues; to test and evaluate the design methodology; to provide feedback to: the design organisation regarding additional studies that needs to be done; the site investigation and modelling organization regarding further investigations required; and the safety assessment team. The possible locations for a tentative deep repository are analysed in Chapter 3 of the report. The most promising area for the repository (denoted 'priority site') has been defined by SKB to be located southeast of the Forsmark nuclear plant and northwest of the gently dipping deformation zone ZFMNE00A2. Regarding the repository depth, present knowledge acquired from the site investigations indicates that it is possible to locate the repository at all stipulated depths according to SKB, that is between 400 m and 700 m depth. The preliminary assessment made in Chapter 3 clearly demonstrates that the repository can be accommodated within the 'priority site'. The potential to accommodate the repository is essentially the same for both 400 m and 500 m depths. The design of the deposition areas is reported in Chapter 4, which includes the design of layout features for all tunnels and deposition holes, orientation of tunnels, calculation of anticipated loss of deposition holes due

  13. Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex

    Directory of Open Access Journals (Sweden)

    Zuzana Hořejší

    2014-04-01

    Full Text Available The R2TP cochaperone complex plays a critical role in the assembly of multisubunit machines, including small nucleolar ribonucleoproteins (snoRNPs, RNA polymerase II, and the mTORC1 and SMG1 kinase complexes, but the molecular basis of substrate recognition remains unclear. Here, we describe a phosphopeptide binding domain (PIH-N in the PIH1D1 subunit of the R2TP complex that preferentially binds to highly acidic phosphorylated proteins. A cocrystal structure of a PIH-N domain/TEL2 phosphopeptide complex reveals a highly specific phosphopeptide recognition mechanism in which Lys57 and 64 in PIH1D1, along with a conserved DpSDD phosphopeptide motif within TEL2, are essential and sufficient for binding. Proteomic analysis of PIH1D1 interactors identified R2TP complex substrates that are recruited by the PIH-N domain in a sequence-specific and phosphorylation-dependent manner suggestive of a common mechanism of substrate recognition. We propose that protein complexes assembled by the R2TP complex are defined by phosphorylation of a specific motif and recognition by the PIH1D1 subunit.

  14. Systemic catechol-O-methyl transferase inhibition enables the D1 agonist radiotracer R-[11C]SKF 82957

    DEFF Research Database (Denmark)

    Palner, Mikael; McCormick, Patrick; Parkes, Jun;

    2010-01-01

    R-[(11)C]-SKF 82957 is a high-affinity and potent dopamine D(1) receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway...

  15. The role of the dopamine D1 receptor in social cognition : Studies using a novel genetic rat model

    NARCIS (Netherlands)

    Homberg, Judith R.; Olivier, Jocelien D A; VandenBroeke, Marie; Youn, Jiun; Ellenbroek, Arabella K.; Karel, Peter; Shan, Ling; Van Boxtel, Ruben; Ooms, Sharon; Balemans, Monique; Langedijk, Jacqueline; Muller, Mareike; Vriend, Gert; Cools, Alexander R.; Cuppen, Edwin; Ellenbroek, Bart A.

    2016-01-01

    Social cognitionisan endophenotype that is impaired in schizophrenia and several other (comorbid) psychiatric disorders. One of the modulators of social cognition is dopamine, but its role is not clear. The effects of dopamine are mediated through dopamine receptors, including the dopamine D1 recept

  16. Survey of ortho-H2D+ (1(1,0)-1(1,1)) in dense cloud cores

    NARCIS (Netherlands)

    Caselli, P.; Vastel, C.; Ceccarelli, C.; van der Tak, F. F. S.; Crapsi, A.; Bacmann, A.

    2008-01-01

    Aims. We present a survey of the ortho-H2D+ (1(1,0)-1(1,1)) line toward a sample of 10 starless cores and 6 protostellar cores, carried out at the Caltech Submillimeter Observatory. The high diagnostic power of this line is revealed for the study of the chemistry, and the evolutionary and dynamical

  17. Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice.

    Science.gov (United States)

    Thomsen, Morgane; Caine, Simon Barak

    2016-04-05

    Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (S(D)) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the S(D) effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the S(D) effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the S(D) effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems.

  18. Design, synthesis and preliminary evaluation of dopamine-amino acid conjugates as potential D1 dopaminergic modulators.

    Science.gov (United States)

    Tutone, Marco; Chinnici, Aurora; Almerico, Anna Maria; Perricone, Ugo; Sutera, Flavia Maria; De Caro, Viviana

    2016-11-29

    The dopamine-amino acid conjugate DA-Phen was firstly designed to obtain a useful prodrug for the therapy of Parkinson's disease, but experimental evidence shows that it effectively interacts with D1 dopamine receptors (D1DRs), leading to an enhancement in cognitive flexibility and to the development of adaptive strategies in aversive mazes, together with a decrease in despair-like behavior. In this paper, homology modelling, molecular dynamics, and site mapping of D1 receptor were carried out with the aim of further performing docking studies on other dopamine conjugates compared with D1 agonists, in the attempt to identify new compounds with potential dopaminergic activity. Two new conjugates (DA-Trp 2C, and DA-Leu 3C) have been identified as the most promising candidates, and consequently synthesized. Preliminary evaluation in terms of distribution coefficient (D(pH7.4)), stability in rat brain homogenate, and in human plasma confirmed that DA-Trp (2C), and DA-Leu (3C) could be considered as very valuable candidates for further in vivo studies as new dopaminergic drugs.

  19. 17 CFR 270.27d-1 - Reserve requirements for principal underwriters and depositors to carry out the obligations to...

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Reserve requirements for....27d-1 Reserve requirements for principal underwriters and depositors to carry out the obligations to... reserve and as security for the purpose of assuring the refund of charges required by sections 27(d)...

  20. Crosstalk between SOXB1 proteins and WNT/β-catenin signaling in NT2/D1 cells.

    Science.gov (United States)

    Mojsin, Marija; Topalovic, Vladanka; Vicentic, Jelena Marjanovic; Schwirtlich, Marija; Stanisavljevic, Danijela; Drakulic, Danijela; Stevanovic, Milena

    2015-11-01

    During early vertebrate embryogenesis, the expression of SOXB1 proteins is precisely regulated by a number of different mechanisms, including Wnt/β-catenin signaling. This is essential for controlling the balance between stemness and differentiation in embryonic stem cells. In the present study, we analyzed the molecular mechanism of LiCl action in NT2/D1 cells and examined the crosstalk between SOXB1 proteins and Wnt signaling in this model system. We have shown that LiCl increases β-catenin level, induces its translocation to the nucleus and consequently up-regulates β-catenin/Tcf-dependent transcription in NT2/D1 cells. Our results also suggest that LiCl treatment leads to increased expression of SOX2 and SOX3 proteins in NT2/D1 cells through activation of canonical Wnt signaling. Finally, we have detected a negative feedback loop between β-catenin and SOX2 expression in NT2/D1 cells. Since β-catenin and SOX2 have been linked to processes of self-renewal and pluripotency, our results have implications for future research on the maintenance of stemness and lineage commitment of embryonic stem cells.

  1. 26 CFR 1.168(d)-1 - Applicable conventions-half-year and mid-quarter conventions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Applicable conventions-half-year and mid-quarter... and Corporations § 1.168(d)-1 Applicable conventions—half-year and mid-quarter conventions. (a) In... mid-quarter convention applies to the property. Under section 168(d)(3)(A), the mid-quarter...

  2. Observations and Simulations of the Na i D1 Line Profiles in an M-class Solar Flare

    Science.gov (United States)

    Kuridze, D.; Mathioudakis, M.; Christian, D. J.; Kowalski, A. F.; Jess, D. B.; Grant, S. D. T.; Kawate, T.; Simões, P. J. A.; Allred, J. C.; Keenan, F. P.

    2016-12-01

    We study the temporal evolution of the Na i D1 line profiles in the M3.9 flare SOL2014-06-11T21:03 UT, using observations at high spectral resolution obtained with the Interferometric Bidimensional Spectrometer instrument on the Dunn Solar Telescope combined with radiative hydrodynamic simulations. Our results show a significant increase in the intensities of the line core and wings during the flare. The analysis of the line profiles from the flare ribbons reveals that the Na i D1 line has a central reversal with excess emission in the blue wing (blue asymmetry). We combine RADYN and RH simulations to synthesize Na i D1 line profiles of the flaring atmosphere and find good agreement with the observations. Heating with a beam of electrons modifies the radiation field in the flaring atmosphere and excites electrons from the ground state 3s 2S to the first excited state 3p 2P, which in turn modifies the relative population of the two states. The change in temperature and the population density of the energy states make the sodium line profile revert from absorption into emission. Furthermore, the rapid changes in temperature break the pressure balance between the different layers of the lower atmosphere, generating upflow/downflow patterns. Analysis of the simulated spectra reveals that the asymmetries of the Na i D1 flare profile are produced by the velocity gradients in the lower solar atmosphere.

  3. RANDOMIZED COMPARISON OF MORBIDITY AFTER D1 AND D2 DISSECTION FOR GASTRIC-CANCER IN 996 DUTCH PATIENTS

    NARCIS (Netherlands)

    BONENKAMP, JJ; SONGUN, [No Value; HERMANS, J; SASAKO, M; WELVAART, K; PLUKKER, JTM; VANELK, P; OBERTOP, H; GOUMA, DJ; TAAT, CW; VANLANSCHOT, J; DEGRAAF, PW; VONMEYENFELDT, MF; TILANUS, H; VANDEVELDE, CJH

    1995-01-01

    For patients with gastric cancer deemed curable the only treatment option is surgery, but there is disagreement about whether accompanying lymph-node dissection should be limited to the perigastric nodes (D1) or should extend to regional lymph nodes outside the perigastric area (D2). We carried out

  4. Inhibition of Human Steroid 5-Reductase (AKR1D1) by Finasteride and Structure of the Enzyme-Inhibitor Complex

    Energy Technology Data Exchange (ETDEWEB)

    Drury, J.; Di Costanzo, L; Penning, T; Christianson, D

    2009-01-01

    The {Delta}{sup 4}-3-ketosteroid functionality is present in nearly all steroid hormones apart from estrogens. The first step in functionalization of the A-ring is mediated in humans by steroid 5{alpha}- or 5{beta}-reductase. Finasteride is a mechanism-based inactivator of 5{alpha}-reductase type 2 with subnanomolar affinity and is widely used as a therapeutic for the treatment of benign prostatic hyperplasia. It is also used for androgen deprivation in hormone-dependent prostate carcinoma, and it has been examined as a chemopreventive agent in prostate cancer. The effect of finasteride on steroid 5{beta}-reductase (AKR1D1) has not been previously reported. We show that finasteride competitively inhibits AKR1D1 with low micromolar affinity but does not act as a mechanism-based inactivator. The structure of the AKR1D1 {center_dot} NADP{sup +} {center_dot} finasteride complex determined at 1.7 {angstrom} resolution shows that it is not possible for NADPH to reduce the {Delta}{sup 1-2}-ene of finasteride because the cofactor and steroid are not proximal to each other. The C3-ketone of finasteride accepts hydrogen bonds from the catalytic residues Tyr-58 and Glu-120 in the active site of AKR1D1, providing an explanation for the competitive inhibition observed. This is the first reported structure of finasteride bound to an enzyme involved in steroid hormone metabolism.

  5. High resolution spectroscopy of the Cs2 D 1Sigma u + -X 1Sigma g + transition and hyperfine structure

    Science.gov (United States)

    Kobayashi, Tooru; Usui, Takashi; Kumauchi, Takahiro; Baba, Masaaki; Ishikawa, Kiyoshi; Katô, Hajime

    1993-02-01

    The Doppler-free high resolution laser spectroscopy of Cs2 D 1Σu+-X 1Σg+ transition is extended up to v'=65. By comparing the spectral linewidth and the time-resolved fluorescence intensity, the line broadening observed for transitions to the D 1Σu+(v'=63,J'≤70) levels is identified as the lifetime broadening originating from the predissociation. Line splittings are observed for the D 1Σu+(v'=46,J'≥95)-X 1Σg+(v`= 1,J`) transitions and are identified as the hyperfine splitting due to a magnetic dipole interaction between nuclear spin and electron. The hyperfine splitting is attributed to mixing of the (2) 3Πu state, whose wave function changes from Hund's case (a) to case (b) at large J. The dependence of the electric dipole transition moment on the internuclear distance for the D 1Σu+-X 1Σg+ transition is determined by comparing the observed and calculated line intensities of the dispersed fluorescence.

  6. 26 CFR 301.6104(d)-1 - Public inspection and distribution of applications for tax exemption and annual information...

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Public inspection and distribution of... Section 301.6104(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... recognition of exemption under section 501, it shall make its application for tax exemption (as defined...

  7. Spinal D1-like dopamine receptors modulate NMDA receptor-induced hyperexcitability and NR1 subunit phosphorylation at serine 889.

    Science.gov (United States)

    Aira, Zigor; Barrenetxea, Teresa; Buesa, Itsaso; Martínez, Endika; Azkue, Jon Jatsu

    2016-04-01

    Activation of the N-methyl-d-aspartate receptor (NMDAR) in dorsal horn neurons is recognized as a fundamental mechanism of central sensitization and pathologic pain. This study assessed the influence of dopaminergic, D1-like receptor-mediated input to the spinal dorsal horn on NMDAR function. Spinal superfusion with selective NMDAR agonist cis-ACPD significantly increased C-fiber-evoked field potentials in rats subjected to spinal nerve ligation (SNL), but not in sham-operated rats. Simultaneous application of D1LR antagonist SCH 23390 dramatically reduced hyperexcitability induced by cis-ACPD. Furthermore, cis-ACPD-induced hyperexcitability seen in nerve-ligated rats could be mimicked in unin-jured rats during stimulation of D1LRs by agonist SKF 38393 at subthreshold concentration. Phosphorylation of NMDAR subunit NR1 at serine 889 at postsynaptic sites was found to be increased in dorsal horn neurons 90 min after SNL, as assessed by increased co-localization with postsynaptic marker PSD-95. Increased NR1 phosphorylation was attenuated in the presence of SCH 23390 in the spinal superfusate. The present results support that D1LRs regulate most basic determinants of NMDAR function in dorsal horn neurons, suggesting a potential mechanism whereby dopaminergic input to the dorsal horn can modulate central sensitization and pathologic pain.

  8. A high-resolution survey of interstellar Na I D1 lines

    Science.gov (United States)

    Welty, Daniel E.; Hobbs, L. M.; Kulkarni, Varsha P.

    1994-01-01

    We present high-resolution (0.5 km/s) spectra, obtained with the McDonald Observatory 2.7 m coude echelle spectrograph, of interstellar Na I D1 absorption toward 38 bright stars. Numerous narrow, closely blended absorption components, showing resolved Na I hyperfine structure, are evident in these spectra; such narrow components appear in both low halo and quite local gas, as well as in gas toward more distant disk stars. We have used the method of profile fitting in an attempt to determine column densities, line widths, and velocities for the individual interstellar clouds contributing to the observed absorption lines. The resulting sample of 276 clouds is significantly larger, and likely more complete, than several previous samples of 'individual' interstellar clouds, and allows more precise investigation of various statistical properties. We find that the cloud column density (N) and line width parameter (b) are not correlated, for 0.3 km/s approximately less than b approximately less than 1.5 km/s and 10.0/sq cm approximately less than log (N(Na I)) approximately less than 11.6/sq cm. The median b is about 0.73 km/s, the median log N is about 11.09/sq cm, and the median separation between adjacent components is about 2.0 km/s. All these are overestimates of the true median values, however, due to our inability to completely resolve all the component structure present in some cases; even at a resolution of 0.5 km/s, we may have discerned only 60% of the full number of individual components actually present. The one-dimensional dispersion of component velocities, in the local standard of rest, is approximately 8.6 km/s; the distribution of velocities is broader and displaced to more negative velocities for the weaker components. If 80 K is a representative temperature for the interstellar clouds seen in Na I absorption, then at least 38% (and probably the majority) of the clouds have subsonic internal turbulent motions. The range in N(H I) observed at a given N

  9. Análisis transcripcional de la región genética RvD1 de Mycobacterium bovis Transcriptional analysis of genetic region RvD1 of Mycobacterium bovis

    Directory of Open Access Journals (Sweden)

    del Portillo Patricia

    2004-12-01

    Full Text Available Mycobacterium bovis comparte una identidad del 99,9% con los genomas de M. tuberculosis, M. africanum y M. microti. Dentro del 0,1% de esta diferencia se encuentran dos regiones genéticas propias de M. bovis: RvD1 y RvD2, las cuales se encuentran delecionadas del genoma de M. tuberculosis H37Rv y, según el análisis bioin-formático, contienen probables marcos abiertos de lectura (Open Reading Frames: ORF. Con el fin de deter­minar si la región RvD1, transcribe los ORF predichos por bioinformática: ORF1, ORF2 y Rv2024, se extrajeron muestras de ARN total de M. bovis BCG Pasteur, en diferentes puntos de una curva de crecimiento micobacteriano, las cuales fueron analizadas mediante la técnica de Transcripción Reversa y Reacción en Ca­dena de la Polimerasa (RTq-PCR en tiempo real. Los hallazgos obtenidos en esta cinética de transcripción por RTq-PCR en tiempo real demostraron que los probables marcos de lectura abiertos ORF1, ORF2 y Rv2024 de la región RvD1 de M. bovis, sí se transcriben y lo hacen de manera constitutiva, hecho que no había sido repor­tado. Los resultados de esta investigación sirven como un primer paso para determinar la función que desem­peña la región RvD1 de M. bovis, y su posible papel en la patogénesis y en la interacción huésped-patógeno de la tuberculosis bovina y humana. Palabras clave: Mycobacterium bovis, BCG, RNA, RT-PCR, RvD1.Mycobacterium bovis, shares 99.9% of genomic identity with M. tuberculosis, M. africanum and M. microti. Within this 0.1 % of difference, there are two genetic regions characteristics of M. bovis that are deleted in M. tuberculo­sis H37Rv: RvD1 and RvD2. According to bioinformatic analysis, these regions contain Open Reading Frames (ORFs. With the purpose of determining if the RvD1 region transcribes the ORFs predicted by bioinformatics (ORF1, ORF2 and Rv2024; total RNA was extracted from a culture of M. bovis BCG Pasteur, at different time points along the growth curve

  10. Biosynthesis of D-1,2,4-butanetriol from D-xylose by recombinant Escherichia coli%重组大肠杆菌利用D-木糖合成D-1,2,4-丁三醇

    Institute of Scientific and Technical Information of China (English)

    马鹏飞; 蒙坚; 周静; 高海军

    2015-01-01

    1,2,4-Butanetriol (BT) is an important organic synthetic intermediate. In this study, the metabolic network of Escherichia coli was reconstructed by heterogeneously expressing a keto acid decarboxylase (mdlC) from Pseudomonas putida ATCC12633 and a D-xylose dehydrogenase (xdh) from Caulobacter crescentus CB15, and knocking out xylA, yjhH and yagE which were the genes of xylose utilization pathway and intermediary metabolite pathway for D-1,2,4-butanetriol synthesis. The recombinant strain could synthesize D-1,2,4-butanetriol directly using D-xylose as precursor. Culture conditions such as temperature, medium volume, pH of fermentation broth were investigated at the titer of D-1,2,4-butanetriol of 3.96 g·L−1 under suitable fermentation conditions. The relationship between glucose utilization and D-1,2,4-butanetriol synthesis was discussed. After modifying the phosphoenolpyruvate:sugar phosphotransferase system (PTS) by knocking out ptsG the reconstructed E.coli could utilize glucose and xylose simultaneously, leading to a higher D-1,2,4-butanetriol productivity.%1,2,4-丁三醇(1,2,4-butanetriol, BT)是一种重要的有机合成中间体。通过克隆表达恶臭假单胞菌(Pseudomonas putida ATCC12633)2-酮酸脱羧酶(mdlC)和新月柄杆菌(Caulobacter crescentus CB15)D-木糖脱氢酶(xdh),敲除木糖利用和 D-1,2,4-丁三醇合成中间代谢物分解途径中关键基因木糖异构酶(xylA)和2-酮酸醛缩酶(yjhH和yagE),重构大肠杆菌代谢网络,得到了能够将D-木糖转化为D-1,2,4-丁三醇的重组菌株。考察了温度、装液量、pH控制等条件对重组菌株合成D-1,2,4-丁三醇的影响,在适宜条件下发酵36 h后D-1,2,4-丁三醇产量达到3.96 g·L−1。探讨了葡萄糖利用与丁三醇合成的关系,通过敲除编码酶 IICBGlc的 ptsG 基因改造重组菌株的磷酸烯醇式丙酮酸葡萄糖转移酶(phosphoenolpyruvate:sugar phosphotransferase system, PTS)系

  11. The value of clinical applications of anti-SmD1 antibody in systemic lupus erythematosus%抗SmD1抗体在系统性红斑狼疮中的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    王奔放; 郁建江; 周剑波; 董筱莉

    2012-01-01

    目的 探讨抗SmD1抗体在系统性红斑狼疮(SLE)中的临床应用价值.方法 将160例确诊为SLE的患者和80例其他风湿病患者及健康人(对照组)先采用酶联免疫吸附试验(ELISA)检测抗SmD1抗体、抗Sm抗体,选取抗SmD1抗体阳性的SLE患者60例,统计分析抗SmD1抗体与患者临床表现、临床活动性的关系.结果 160例SLE患者抗SmD1抗体阳性率为 53.1%,抗Sm抗体阳性率为12.5%,80例对照组抗SmD1抗体、抗Sm抗体阳性率分别为5.0%、0.抗SmD1抗体定量与SLE病情活动积分呈正相关(r=0.53,P<0.01).结论 ELISA定量法检测抗SmD1抗体的敏感性和特异性均较高,可作为诊断SLE的参考指标.抗SmD1抗体定量对判断SLE病情活动有一定的价值.%Objective To study the value of clinical applications of anti - SmDl antibody in systemic lupus erythematosus ( SLE ). Methods The anti - SmDl antibody and anti - Sm antibody in 160 cases of SLE and 80 control subjects were detected by ELISA for quantitative determination. Sixty SLE cases with positive anti - SmDl antibody were selected and the relations of anti - SmDl antibody, clinical manifestations and disease activity in these patients were analyzed. Results Among the 160 cases of SLE,the positive rates of anti - SmDl antibody,anti - Sm antibody were 53.1% and 12.5% respectively. The positive rates of anti - SmDl antibody and anti - Sm antibody in 80 control subjects were 5.0% and 0% respectively. The level of anti - SmDl antibody was positively correlated with Systemic Lupus Erythematosus Activity Index ( SLEDAI)( r = 0. 535, P<0.01 ). Conclusion ELISA has high sensitivity and specificity for the detection of anti - SmDl antibody. The anti - SmDl antibody can be used as the reference index in the diagnosis of SLE. The level of serum anti - SmDl antibody is associated with the activity of SLE.

  12. Matrine promotes G0/G1 arrest and down-regulates cyclin D1 expression in human rhabdomyosarcoma cells.

    Science.gov (United States)

    Guo, L; Xue, T Y; Xu, W; Gao, J Z

    2013-09-01

    Matrine has a broad-spectrum of anti-cancer effects and is efficient in the inhibition of proliferation of hepatoma cells, leukemia cells and neuroblastoma cell. However, its efficacy and tentative mechanisms in rhabdomyosarcoma have not been addressed before. This study aimed to investigate the effects of Matrine on cell cycle and expression of cyclin D1 in human rhabdomyosarcoma cells (RD cell line). RD cell line was treated with different concentrations (0, 0.5, 1.0, and 1.5 mg/mL) of Matrine, and cell proliferation and cell cycle were evaluated using, respectively, MTT assay and flow cytometry. The effect of Matrine on cyclin D1 mRNA levels was measured by RT-PCR. There was a dose-dependent inhibition of proliferation in the matrine-treated group (inhibition of proliferation rate in control cells 12.70 ± 0.35%; Matrine-treated cells [0.5, 1.0, and 1.5 mg/mL]: 31.16 ± 0.11%, 42.96 ± 0.9%, and 57.26 ± 0.8%). The G0 / G1 ratio in study groups were, respectively, 58.44 ± 3.57%, 64.79 ± 2.03%, 69.97 ± 2.89% and 75.03 ± 1.23%.Cyclin D1 mRNA levels progressively diminished (control group ratio of cyclin D1 / β-actin: 0.59 ± 0.06; Matrine: 0.35 ± 0.05, 0.27 ± 0.02 and 0.04 ± 0.03). All aforementioned changes were significant (PMatrine markedly suppresses cell proliferation in RD cells by decreasing expression of cyclin D1 mRNA and blocking the cell cycle at the G0 / G1 stage.

  13. Hypoallergenic Variant of the Major Egg White Allergen Gal d 1 Produced by Disruption of Cysteine Bridges

    Directory of Open Access Journals (Sweden)

    Pathum Dhanapala

    2017-02-01

    Full Text Available Background: Gal d 1 (ovomucoid is the dominant allergen in the chicken egg white. Hypoallergenic variants of this allergen can be used in immunotherapy as an egg allergy treatment approach. We hypothesised that disruption of two of the nine cysteine-cysteine bridges by site-directed mutagenesis will allow the production of a hypoallergenic variant of the protein; Methods: Two cysteine residues at C192 and C210 in domain III of the protein were mutated to alanine using site-directed mutagenesis, to disrupt two separate cysteine-cysteine bridges. The mutated and non-mutated proteins were expressed in Escherichia coli (E. coli by induction with isopropyl β-d-1-thiogalactopyranoside (IPTG. The expressed proteins were analysed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE and immunoblotting to confirm expression. Immunoglobulin E (IgE reactivity of the two proteins was analysed, by immunoblotting, against a pool of egg-allergic patients’ sera. A pool of non-allergic patients’ sera was also used in a separate blot as a negative control; Results: Mutant Gal d 1 showed diminished IgE reactivity in the immunoblot by showing lighter bands when compared to the non-mutated version, although there was more of the mutant protein immobilised on the membrane when compared to the wild-type protein. The non-allergic negative control showed no bands, indicating an absence of non-specific binding of secondary antibody to the proteins; Conclusion: Disruption of two cysteine bridges in domain III of Gal d 1 reduces IgE reactivity. Following downstream laboratory and clinical testing, this mutant protein can be used in immunotherapy to induce tolerance to Gal d 1 and in egg allergy diagnosis.

  14. Mutations of photosystem II D1 protein that empower efficient phenotypes of Chlamydomonas reinhardtii under extreme environment in space.

    Science.gov (United States)

    Giardi, Maria Teresa; Rea, Giuseppina; Lambreva, Maya D; Antonacci, Amina; Pastorelli, Sandro; Bertalan, Ivo; Johanningmeier, Udo; Mattoo, Autar K

    2013-01-01

    Space missions have enabled testing how microorganisms, animals and plants respond to extra-terrestrial, complex and hazardous environment in space. Photosynthetic organisms are thought to be relatively more prone to microgravity, weak magnetic field and cosmic radiation because oxygenic photosynthesis is intimately associated with capture and conversion of light energy into chemical energy, a process that has adapted to relatively less complex and contained environment on Earth. To study the direct effect of the space environment on the fundamental process of photosynthesis, we sent into low Earth orbit space engineered and mutated strains of the unicellular green alga, Chlamydomonas reinhardtii, which has been widely used as a model of photosynthetic organisms. The algal mutants contained specific amino acid substitutions in the functionally important regions of the pivotal Photosystem II (PSII) reaction centre D1 protein near the QB binding pocket and in the environment surrounding Tyr-161 (YZ) electron acceptor of the oxygen-evolving complex. Using real-time measurements of PSII photochemistry, here we show that during the space flight while the control strain and two D1 mutants (A250L and V160A) were inefficient in carrying out PSII activity, two other D1 mutants, I163N and A251C, performed efficient photosynthesis, and actively re-grew upon return to Earth. Mimicking the neutron irradiation component of cosmic rays on Earth yielded similar results. Experiments with I163N and A251C D1 mutants performed on ground showed that they are better able to modulate PSII excitation pressure and have higher capacity to reoxidize the QA (-) state of the primary electron acceptor. These results highlight the contribution of D1 conformation in relation to photosynthesis and oxygen production in space.

  15. Effect of Ce3+ on spectral characteristic of D1/D2/Cytb559 complex from spinach

    Institute of Scientific and Technical Information of China (English)

    洪法水; 王雪峰; 刘超; 苏国兴; 宋卫平; 吴康; 陶冶; 赵贵文

    2003-01-01

    It was studied by spectroscopy that PSII reaction center complex consisting of three polypeptides, D1, D2 and Cytb559, were purified from PSII particle of CeCl3 treated spinach. The results of the experiment show that Ce3+ could improve the growth of spinach, and accelerate electron transport of PSII particles. Of chl-a of UV-Vis spectrum of D1/D2/Cytb559 complex, Soret band was blue-shifted by 3 nm and Q band by 2 nm, respectively, and the fluorescence emission peak was blue-shifted by 5 nm in CeCl3-treated spinach compared with the one in control. By the extended X-ray absorption fine structure (EXAFS) spectroscopy methods, it has been found that Ce3+ is coordinated with 8 nitrogen atoms in the first coordination shell with Ce-N bond length of 0.253 nm, and Ce3+ with 6 oxygen atoms in the second coordination shell with Ce-O bond length of 0.32 nm. However,the secondary structure of D1/D2/Cytb559 complex by circular dichroism (CD) spectroscopy has no significant change after CeCl3 treated. It might be that Ce3+ binds to porphyrin rings of chlorophyll and oxygen of amino acid residue of polypeptide in D1/D2/Cytb559 complex, and then accelerates the primary reaction of PSII, intensifies function of P680+ primary electron donor of D1/D2/Cytb559, but there is little change in conformation of PSII reaction center complex.

  16. Berberine inhibits cyclin D1 expression via suppressed binding of AP-1 transcription factors to CCND1 AP-1 motif

    Institute of Scientific and Technical Information of China (English)

    Ye LUO; Yu HAO; Tai-ping SHI; Wei-wei DENG; Na LI

    2008-01-01

    Aim: To verify the suppressive effect of berberine on the proliferation of the human pulmonary giant cell carcinoma cell line PG and to demonstrate the mecha-nisms behind the antitumoral effects of berberine. Methods: The proliferative effects of PG cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetry. The cell cycle was examined by flow cytometry. The expression level of cyclin D1 was detected by RT-PCR. The activities of the activating protein-1 (AP-1) and NF-κB signaling pathways related to cyclin D1 were examined by luciferase assay. The cytoplasmic level of c-Jun was detected by Western blot analysis. An electrophoretic mobility shift assay was used to examiae the binding of transcription factors to the cyclin D1 gene (CCNDl) AP-1 motif. Results: The results showed that the proliferation of PG cells treated with different concentrations (10, 20, and 40 μg/mL) of berberine for 24 and 48 h was suppressed significantly compared to the control group. After treatment with berberine, the proportion of PG cells at the G0/G1 phase increased, while cells at the S and G2/M phases decreased. Berberine could inhibit the expression of cyclin D1 in PG cells. Berberine inhibited the activity of the AP-1 signaling pathway, but had no significant effect on the NF-κB signaling pathway. Berberine suppressed the expression of c-Jun and decreased the binding of tran-scription factors to the CCND1 AP-1 motif. Conclusion: Berberine suppresses the activity of the AP-1 signaling pathway and decreases the binding of transcrip-tion factors to the CCND1 AP-1 motif. This is one of the important mechanisms behind the antitumoral effects of berberine as a regulator of cyclin D1.

  17. Dopamine facilitates dendritic spine formation by cultured striatal medium spiny neurons through both D1 and D2 dopamine receptors.

    Science.gov (United States)

    Fasano, Caroline; Bourque, Marie-Josée; Lapointe, Gabriel; Leo, Damiana; Thibault, Dominic; Haber, Michael; Kortleven, Christian; Desgroseillers, Luc; Murai, Keith K; Trudeau, Louis-Éric

    2013-04-01

    Variations of dopamine (DA) levels induced by drugs of abuse or in the context of Parkinson's disease modulate the number of dendritic spines in medium spiny neurons (MSNs) of the striatum, showing that DA plays a major role in the structural plasticity of MSNs. However, little is presently known regarding early spine development in MSNs occurring before the arrival of cortical inputs and in particular about the role of DA and D1 (D1R) and D2 (D2R) DA receptors. A cell culture model reconstituting early cellular interactions between MSNs, intrinsic cholinergic interneurons and DA neurons was used to study the role of DA in spine formation. After 5 or 10 days in vitro, the presence of DA neurons increased the number of immature spine-like protrusions. In MSN monocultures, chronic activation of D1R or D2R also increased the number of spines and spinophilin expression in MSNs, suggesting a direct role for these receptors. In DA-MSN cocultures, chronic blockade of D1R or D2R reduced the number of dendritic spines. Interestingly, the combined activation or blockade of both D1R and D2R failed to elicit more extensive spine formation, suggesting that both receptors act through a mechanism that is not additive. Finally, we found increased ionotropic glutamate receptor responsiveness and miniature excitatory postsynaptic current (EPSC) frequency in DA-MSN co-cultures, in parallel with a higher number of spines containing PSD-95, suggesting that the newly formed spines present functional post-synaptic machinery preparing the MSNs to receive additional glutamatergic contacts. These results represent a first step in the understanding of how dopamine neurons promote the structural plasticity of MSNs during the development of basal ganglia circuits.

  18. Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia.

    Science.gov (United States)

    Yang, W. I.; Zukerberg, L. R.; Motokura, T.; Arnold, A.; Harris, N. L.

    1994-01-01

    Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/CLL) show a characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the Bcl-1 region. Recently it was shown that the key Bcl-1 region oncogene is cyclin D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We examined cyclin D1 protein expression in low-grade B-cell lymphomas and reactive lymphoid hyperplasias using polyclonal and monoclonal antibodies to cyclin D1 protein. Definite nuclear staining was seen in 15 of 15 MCLs, 1 of 7 B-SLL/CLLs, 0 of 7 reactive hyperplasias, 0 of 10 follicular lymphomas, and 0 of 4 lymphomas of mucosa-associated lymphoid tissue using immunoperoxidase stains on paraffin-embedded sections. Best results were obtained with the affinity-purified polyclonal antibody on microwave-treated, formalin-fixed, paraffin-embedded tissue. MCLs showed diffuse nuclear staining, whereas the one positive B-SLL/CLL showed dot-like or globular nuclear staining. Nuclear cyclin D1 protein can be detected in all cases of MCL and in rare cases of B-SLL/CLL using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue, and it does not appear to be detectable in reactive hyperplasias and other low-grade B-cell lymphomas. This protein may be useful in subclassification of low-grade B-cell lymphomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:7518196

  19. Mapping of IgE-binding regions on recombinant Cyn d 1, a major allergen from Bermuda Grass Pollen (BGP

    Directory of Open Access Journals (Sweden)

    Bhalla Prem L

    2009-02-01

    Full Text Available Abstract Background Bermuda grass (Cynodon dactylon; subfamily Chloridoideae is an important source of seasonal aeroallergens in warm tropical and sub-tropical areas worldwide. Improved approaches to diagnosis and therapy of allergic diseases require a thorough understanding of the structure and epitopes on the allergen molecule that are crucial for the antigen-antibody interaction. This study describes the localization of the human IgE-binding regions of the major group 1 pollen allergen Cyn d 1 from Bermuda grass. Methods A cDNA library was constructed from Bermuda grass pollen (BGP using a Lambda gt11 expression vector. The gene encoding the Cyn d 1 allergen was isolated by screening the library with a mouse monoclonal antibody raised against grass group 1 allergen. In order to characterize the IgE epitopes on Cyn d 1, seven overlapping fragments and three deletion mutants were cloned and over-expressed in E. coli. The recombinant fragments and deletion mutants were evaluated for their comparative IgE reactivity with sera of non atopic individuals and grass pollen allergic patients by ELISA and a dot-blot assay. Results Analysis of IgE binding regions by overlapping fragments and deletion mutants identified two major allergenic regions corresponding to amino acids 120–170 and 224–244. Deletion of either or both regions led to a significant reduction in IgE binding, emphasizing the importance of the C-terminal region on Cyn d 1 in epitope-IgE interaction. Conclusion Anti-Cyn d 1 IgE antibodies from allergic human sera recognize two epitopes located at the C-terminal end of the molecule. These data will enable the design of improved diagnostic and therapeutic approaches for BGP hypersensitivity.

  20. Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus.

    Science.gov (United States)

    Menezes, Jefferson; Alves, Niége; Borges, Sidnei; Roehrs, Rafael; de Carvalho Myskiw, Jociane; Furini, Cristiane Regina Guerino; Izquierdo, Ivan; Mello-Carpes, Pâmela B

    2015-03-31

    Extinction is the learned inhibition of retrieval. Recently it was shown that a brief exposure to a novel environment enhances the extinction of contextual fear in rats, an effect explainable by a synaptic tagging-and-capture process. Here we examine whether this also happens with the extinction of another fear-motivated task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1 or D5 receptors. Rats were trained first in IA and then in extinction of this task. The retention of extinction was measured 24 h later. A 5-min exposure to a novel environment 30 min before extinction training enhanced its retention. Right after exposure to the novelty, animals were given bilateral intrahippocampal infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the PKC inhibitor Gö6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator PMA. The novelty increased hippocampal dopamine levels and facilitated the extinction, which was inhibited by intrahippocampal protein synthesis inhibitor anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and unaffected by PKC inhibitor Gö6976; additionally, the hippocampal infusion of PKA stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390, but the infusion of PKC stimulator PMA does not. The results attest to the generality of the novelty effect on fear extinction, suggest that it relies on synaptic tagging and capture, and show that it depends on hippocampal dopamine D1 but not D5 receptors.

  1. Inmunoexpresión de p53 y ciclina D1 en adenomas de vesícula biliar Immunoexpression of p53 and cyclic D1 in adenomas of the gallbladder

    Directory of Open Access Journals (Sweden)

    F. Arévalo

    2007-12-01

    Full Text Available Introducción: el adenoma de vesícula biliar es una neoplasia infrecuente, cuya relación con el adenocarcinoma es poco conocida, aunque algunos autores han propuesto que la mayoría de adenomas no degeneran en adenocarcinomas, debido a que ambas lesiones presentan vías moleculares diferentes. Material y métodos: el presente trabajo es un estudio transversal que compara las características moleculares del adenoma y adenocarcinoma de vesícula biliar, mediante la medición inmunohistoquímica de la expresión de las proteína p53 y ciclina D1 (ambas reguladoras del ciclo celular en 12 enfermos de cada grupo. Resultados: encontramos una mayor expresión de p53 en los adenocarcinomas (83,3% que en los adenomas (16,6% siendo esta diferencia estadísticamente significativa usando el test de chi cuadrado (p = 0,003, mientras que la expresión de ciclina D1 en ambos grupos fue similar. Conclusión: consideramos que nuestros resultados indican que la alteración en el p53 es un paso importante en el desarrollo de los adenocarcinomas de vesícula biliar, mientras que en el desarrollo de los adenomas, la alteración del p53 sería poco trascendente. Por otro lado, la sobreexpresión de ciclina D1 sería un mecanismo molecular común a ambas lesiones.Introduction: gallbladder adenomas are infrequent neoplasms whose relation to adenocarcinoma is not well understood. It has been suggested that adenomas and adenocarcinomas follow different molecular pathways. Material and methods: this is a comparative, cross-sectional study in which we compared p53 and D1 cyclin expression in adenomas and adenocarcinomas of the gallbladder. Results: we included 12 cases in each group. Expression of p53 occurred in 83.3% of adenocarcinomas and in 16.6% of adenomas (p = 0.003. D1 cyclin was expressed in a similar number of adenomas and adenocarcinomas. Conclusion: our results support the hypothesis that p53 is an important step in the pathogenesis of adenocarcinomas but

  2. The neuronal differentiation factor NeuroD1 downregulates the neuronal repellent factor Slit2 expression and promotes cell motility and tumor formation of neuroblastoma.

    Science.gov (United States)

    Huang, Peng; Kishida, Satoshi; Cao, Dongliang; Murakami-Tonami, Yuko; Mu, Ping; Nakaguro, Masato; Koide, Naoshi; Takeuchi, Ichiro; Onishi, Akira; Kadomatsu, Kenji

    2011-04-15

    The basic helix-loop-helix transcription factor NeuroD1 has been implicated in the neurogenesis and early differentiation of pancreatic endocrine cells. However, its function in relation to cancer has been poorly examined. In this study, we found that NeuroD1 is involved in the tumorigenesis of neuroblastoma. NeuroD1 was strongly expressed in a hyperplastic region comprising neuroblasts in the celiac sympathetic ganglion of 2-week-old MYCN transgenic (Tg) mice and was consistently expressed in the subsequently generated neuroblastoma tissue. NeuroD1 knockdown by short hairpin RNA (shRNA) resulted in motility inhibition of the human neuroblastoma cell lines, and this effect was reversed by shRNA-resistant NeuroD1. The motility inhibition by NeuroD1 knockdown was associated with induction of Slit2 expression, and knockdown of Slit2 could restore cell motility. Consistent with this finding, shRNA-resistant NeuroD1 suppressed Slit2 expression. NeuroD1 directly bound to the first and second E-box of the Slit2 promoter region. Moreover, we found that the growth of tumor spheres, established from neuroblastoma cell lines in MYCN Tg mice, was suppressed by NeuroD1 suppression. The functions identified for NeuroD1 in cell motility and tumor sphere growth may suggest a link between NeuroD1 and the tumorigenesis of neuroblastoma. Indeed, tumor formation of tumor sphere-derived cells was significantly suppressed by NeuroD1 knockdown. These data are relevant to the clinical features of human neuroblastoma: high NeuroD1 expression was closely associated with poor prognosis. Our findings establish the critical role of the neuronal differentiation factor NeuroD1 in neuroblastoma as well as its functional relationship with the neuronal repellent factor Slit2.

  3. Differentiation of forebrain and hippocampal dopamine 1-class receptors, D1R and D5R, in spatial learning and memory.

    Science.gov (United States)

    Sariñana, Joshua; Tonegawa, Susumu

    2016-01-01

    Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R-specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory.

  4. Expression and clinical significance of APC,β-catenin and cyclinD1 proteins in colorectal carcinoma%大肠癌中APC、β-catenin和cyclinD1的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    戴文斌; 任占平; 陈蔚麟; 杜娟; 石喆; 唐德艳

    2007-01-01

    目的:探讨APC、β-catenin和cyclinD1在大肠癌发生、发展过程中的作用.方法:应用免疫组织化学方法检测30例正常大肠黏膜、30例大肠腺瘤、10例大肠腺瘤恶变及50例大肠癌组织中APC、β-catenin和cyclinD1蛋白的表达情况.结果:大肠癌和大肠腺瘤恶变APC阳性率分别为44.0%,40.0%,显著低于大肠腺瘤(86.7%)和正常大肠黏膜(100%)(P《0.01).大肠癌、大肠腺瘤恶变和大肠腺瘤β-catenin胞浆和/或胞核异位表达率分别为:62.0%,50.0%,30.O%,显著高于正常大肠黏膜(0)(P《0.01),大肠癌β-catenin异位表达率显著高于大肠腺瘤(P《0.01).大肠癌中B-catenin膜表达缺失率为:46.0%,显著高于大肠腺瘤(10.0%)和正常大肠黏膜(0)(P《0.01).大肠癌、大肠腺瘤恶变、大肠腺瘤cyclinD1阳性率分别为:66.0%,60.0%,30.O%,显著高于正常大肠黏膜(0)(P《0.01),大肠癌cyclinD1阳性率显著高于大肠腺瘤(P《0.01).β-catenin膜表达缺失和cyclinD1高表达与大肠癌组织分化程度、浸润深度、淋巴结转移、Dukes分期有关.APC蛋白表达与大肠癌组织分化程度有关.大肠癌中β-catenin异位表达与cyclinD1阳性表达呈正相关关系(r=0.57,P《0.01),而与APC阳性表达呈负相关关系(r=-0.39,P《0.05).结论:APC失表达和/或β-catenin异位表达,可能是原癌基因cyclinD1激活的重要原因,并在大肠癌发生过程中起重要作用,可能是大肠癌发生的早期事件.β-catenin膜表达缺失和cyclinD1高表达与大肠癌的侵袭、转移有关.

  5. Effects of resolvin D1 on inflammatory responses and oxidative stress of lipopolysaccharide-induced acute lung injury in mice

    Institute of Scientific and Technical Information of China (English)

    Wang Lei; Yuan Ruixia; Yao Chengyue; Wu Qingping; Marie Christelle; Xie Wanli; Zhang Xingcai

    2014-01-01

    Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury.Inflammation is associated with an oxidative stress reaction,which is produced in the development of airway inflammation,and which has positive feedback on inflammation itself.Resolvin D1 can reduce the infiltration of neutrophils,regulate cytokine levels and reduce the inflammation reaction,and thereby promote the resolution of inflammation.The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide (LPS)-induced acute lung injury.Methods LPS (3 mg/kg) was used to induce the acute lung injury model.Pretreatment resolvin D1 (100 ng/mouse) was given to mice 30 minutes before inducing acute lung injury.Mice were observed at 6 hours,12 hours,1 day,2 days,3 days,4 days and 7 days after LPS was administrated,then they were humanely sacrificed.We collected bronchoalveolar lavage fluid (BALF) and the lung tissues for further analysis.Paraffin section and HE staining of the lung tissues were made for histopathology observations.Parts of the lung tissues were evaluated for wet-to-dry (W/D) weight ratio.tumor necrosis factor (TNF)-α,inter leukin (IL)-1β,IL-10 and myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA).A lipid peroxidation malondialdehyde (MDA) assay kit was used to detect MDA.A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase (SOD).We determined the apoptosis of neutrophils by Flow Cytometry.A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase (HO)-1.Results Pretreatment with resolvin D1 reduced the pathological damage in the lung,decreased the recruitment of neutrophils and stimulated their apoptosis.It markedly decreased the expressions of TNF

  6. Dopamine D1 receptor modulation in nucleus accumbens lowers voluntary wheel running in rats bred to run high distances.

    Science.gov (United States)

    Roberts, Michael D; Gilpin, Leigh; Parker, Kyle E; Childs, Thomas E; Will, Matthew J; Booth, Frank W

    2012-02-01

    Dopamine signaling in the nucleus accumbens (NAc) has been postulated to influence reward development towards drugs of abuse and exercise. Herein, we used generation 4-5 rats that were selectively bred to voluntary run high (HVR) versus low (LVR) distances in order to examine if dopamine-like 1 (D1) receptor modulation in the NAc differentially affects nightly voluntary wheel running between these lines. A subset of generation 5-6 HVR and LVR rats were also used to study the mRNA expression of key genes related to reward and addiction in the NAc (i.e., DRD1, DRD5, DRD2, Nr4a2, FosB, and BDNF). In a crossover fashion, a D1-like agonist SKF 82958 (2 μg per side) or D1-like full antagonist SCH 23390 (4 μg per side) was bilaterally injected into the NAc of HVR and LVR female Wistar rats prior to their high running nights. Notably, during hours 2-4 (between 2000 and 2300) of the dark cycle there was a significant decrement in running distances in the HVR rats treated with the D1 agonist (p=0.025) and antagonist (p=0.017) whereas the running distances in LVR rats were not affected. Interestingly, HVR and LVR rats possessed similar NAc concentrations of the studied mRNAs. These data suggest that: a) animals predisposed to run high distances on a nightly basis may quickly develop a rewarding response to exercise due to an optimal D1-like receptor signaling pathway in the NAc that can be perturbed by either activation or blocking, b) D1-like agonist or antagonist injections do not increase running distances in rats that are bred to run low nightly distances, and c) running differences between HVR and LVR animals are seemingly not due to the expression of the studied mRNAs. Given the societal prevalence of obesity and extraneous physical inactivity, future studies should be performed in order to further determine the culprit for the low running phenotype observed in LVR animals.

  7. Association of cyclin D1, p16 and retinoblastoma protein expressions with prognosis and metastasis of gallbladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hong-Bing Ma; Hai-Tao Hu; Zheng-Li Di; Zuo-Ren Wang; Jing-Sen Shi; Xi-Jing Wang; Yi Li

    2005-01-01

    AIM: To investigate the role of cydin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder carcinoma.METHODS: Forty-one gallbladder carcinoma, 7 gallbladder adenoma and 14 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of cyclin D1, p16 and Rb with Nevin staging and pathologic grading.RESULTS: The expression rates of abnormal cyclin D1 in gallbladder carcinoma (68.3%)and gallbladder adenoma(57.1%) were significantly higher than those in chronic cholecystitis (7.1%) (P<0.05). No significant difference was found both among the pathological grades G1, G2 and G3and among Nevin stagings S1-S2, S3 and S4-S5 of gallbladder carcinoma. The positive rates of p16 (48.8%) and Rb(58.5%) in gallbladder carcinoma were significantly lower compared to those in adenoma (100.0%) and cholecystitis(100.0%) (P<0.05). The positive rates of p16 and Rb in Nevin stagings S1-S2 (80.0% and 90.0%) and S3 (46.2%and 61.5%) gallbladder carcinomas were significantly higher than those in S4-S5 (33.3% and 38.8%) (P<0.05),and those in pathologic grades G1 (54.5% and 81.8%) and G2 (50.0% and 62.5%) gallbladder carcinoma were significantly higher than those in G3 (28.6% and 35.7%)(P<0.05). The protein expression of p16 and Rb had a negative-correlation in gallbladder carcinoma (r = -0.2993,P<0.05), and this negative-correlation was correlated with Nevin staging (P<0.05). Moreover, the protein expression of p16 and cyclin D1 had a negative-correlation in gallbladder carcinoma (r = -0.9417, P<0.05).CONCLUSION: Cyclin D1 may play a role in the early stage of gallbladder carcinoma. Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma.Analysis of p16 and Rb can estimate the prognosis of gallbladder carcinoma. Expression of p16 and Rb may be correlated with Nevin

  8. The cooperative roles of the dopamine receptors, D1R and D5R, on the regulation of renal sodium transport.

    Science.gov (United States)

    Gildea, John J; Shah, Ishan T; Van Sciver, Robert E; Israel, Jonathan A; Enzensperger, Christoph; McGrath, Helen E; Jose, Pedro A; Felder, Robin A

    2014-07-01

    Determining the individual roles of the two dopamine D1-like receptors (D1R and D5R) on sodium transport in the human renal proximal tubule has been complicated by their structural and functional similarity. Here we used a novel D5R-selective antagonist (LE-PM436) and D1R- or D5R-specific gene silencing to determine second messenger coupling pathways and heterologous receptor interaction between the two receptors. D1R and D5R colocalize in renal proximal tubule cells and physically interact, as determined by co-immunoprecipitation and fluorescent resonance energy transfer microscopy. Stimulation of renal proximal tubule cells with fenoldopam (D1R/D5R agonist) led to both adenylyl cyclase and phospholipase C (PLC) activation using real-time fluorescent resonance energy transfer biosensors ICUE3 and CYPHR, respectively. Fenoldopam increased cAMP accumulation and PLC activity and inhibited both NHE3 and NaKATPase activities. LE-PM436 and D5R siRNA blocked the fenoldopam-stimulated PLC pathway but not cAMP accumulation, whereas D1R siRNA blocked both fenoldopam-stimulated cAMP accumulation and PLC signaling. Either D1R or D5R siRNA, or LE-PM436 blocked the fenoldopam-dependent inhibition of sodium transport. Further studies using the cAMP-selective D1R/D5R agonist SKF83822 and PLC-selective D1R/D5R agonist SKF83959 confirmed the cooperative influence of the two pathways on sodium transport. Thus, D1R and D5R interact in the inhibition of NHE3 and NaKATPase activity, the D1R primarily by cAMP, whereas the D1R/D5R heteromer modulates the D1R effect through a PLC pathway.

  9. Prognostic significance of cyclinD1 amplification and the co-alteration of cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wang, M-T; Chen, G; An, S-J; Chen, Z-H; Huang, Z-M; Xiao, P; Ben, X-S; Xie, Z; Chen, S-L; Luo, D-L; Tang, J-M; Lin, J-Y; Zhang, X-C; Wu, Y-L

    2012-01-01

    CyclinD1/pRb/ppRb is one of the most important pathways regulating the cell cycle, and related with the development of many cancers. However, the co-alteration of CyclinD1/pRb/ppRb in esophageal squamous cell carcinomas is less understood. This study aims to analyze the combined prognostic significance of cyclinD1 (CCND1) DNA amplification and the co-alteration of CCND1/pRb/ppRB in patients with esophageal squamous cell carcinoma. CCND1 DNA amplification and the protein expression of CCND1, pRb, and ppRb on 100 tumor specimens and 11 normal tissues were detected using real-time quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Their prognosis significance was analyzed by Kaplan-Meier method. We found that 41% of the patients had CCND1 DNA amplification, which had a short survival time compared with the patients without CCND1 amplification (25.63 months vs. not reached, P=0.007). The patients with the co-alternation of CCND1(+) /pRb(-) /ppRb(+) protein expression levels have a poorer overall survival than the others (11.4 vs. 43.4 months, P=0.001). Cox regression analysis showed that the co-alternation of CCND1/pRb/ppRb and CyclinD1 amplification were the two most independent prognosis factors of patients with esophageal cancer. These findings suggested that CCND1 amplification and co-alternation of CCND1(+) /pRb(-) /ppRb(+) may play a crucial role in the prognostic evaluation of patients with esophageal cancer, and the patients with CCND1(+) /pRb(-) /ppRb(+) have the worst prognosis in all the patients. The results also indicated that the patients with CCND1 amplification or co-alternation of CyclinD1(+) /pRb(-) /ppRb(+) might be the preponderant people for therapy targeting the CCND1/pRb/ppRb pathway in the future.

  10. Lepton Mixing Predictions from Infinite Group Series $D^{(1)}_{9n, 3n}$ with Generalized CP

    CERN Document Server

    Li, Cai-Chang; Ding, Gui-Jun

    2016-01-01

    We have performed a comprehensive analysis of the type D group $D^{(1)}_{9n, 3n}$ as flavor symmetry and the generalized CP symmetry. All possible residual symmetries and their consequences for the prediction of the mixing parameters are studied. We find that only one type of mixing pattern is able to accommodate the measured values of the mixing angles in both "direct" and "variant of semidirect" approaches, and four types of mixing patterns are phenomenologically viable in the "semidirect" approach. The admissible values of the mixing angles as well as CP violating phases are studied in detail for each case. It is remarkable that the first two smallest $D^{(1)}_{9n,3n}$ groups with $n=1, 2$ can fits the experimental data very well. The phenomenological predictions for neutrinoless double beta decay are discussed.

  11. Late onset of chylous ascites following distal gastrectomy with D1(+ dissection for gastric cancer: A case report

    Directory of Open Access Journals (Sweden)

    Hüseyin Çiyiltepe

    2015-12-01

    Full Text Available Chyloperitoneum is the accumulation of lymphatic fluid in the peritoneal cavity. Chylous ascites can occur if it is not recognized during surgery. The incidence of chylous ascites after oncological surgery was approximately 7.4% however, the incidence of lymphorrhea after radical gastrectomy for gastric cancer is so low. Extensive lymph node dissection leads to a higher incidence of lymphorrhea. There have been few cases associated with D1 dissection In most patients conservative treatment is recommended that includes paracentesis, total parenteral nutrition (TPN, a medium chain triglyceride (MCT based diet, and somatostatin. Surgery is the last choice only when conservative treatment fails. In this case we aimed to present a late onset of chylous ascites after subtotal gastrectomy and D1+ dissection that was treated with percutaneous drainage and conservative management.

  12. Retinoblastoma and p16 proteins in mammary carcinoma: their relationship to cyclin D1 and histopathological parameters.

    Science.gov (United States)

    Dublin, E A; Patel, N K; Gillett, C E; Smith, P; Peters, G; Barnes, D M

    1998-02-20

    The cell cycle-associated retinoblastoma protein (pRb) and p16 protein were demonstrated using immuno-histochemistry on paraffin sections from 192 cases of invasive breast carcinoma. Abnormal expression of pRb was defined as negative staining and was seen in 17% of tumours. Such abnormal expression was significantly more frequent in tumours with negative oestrogen receptor (ER) status. There was also a trend for tumours which were negative for pRb to be grade III ductal carcinomas. There was no association between p16 staining and any histopathological parameter, though, surprisingly, log-rank analysis showed that strong staining was associated with a poor outcome. There was a significant inverse relationship between pRb and p16 expression and a significant positive association between pRb and cyclin D1. In a Cox multivariate analysis, which included cyclin D1, neither pRb nor p16 was an independent predictor of patient outcome.

  13. Specificity of Monosynaptic Sensory-Motor Connections Imposed by Repellent Sema3E-PlexinD1 Signaling

    Directory of Open Access Journals (Sweden)

    Kaori Fukuhara

    2013-11-01

    Full Text Available In mammalian spinal cord, group Ia proprioceptive afferents form selective monosynaptic connections with a select group of motor pool targets. The extent to which sensory recognition of motor neurons contributes to the selectivity of sensory-motor connections remains unclear. We show here that proprioceptive sensory afferents that express PlexinD1 avoid forming monosynaptic connections with neurons in Sema3E+ motor pools yet are able to form direct connections with neurons in Sema3Eoff motor pools. Anatomical and electrophysiological analysis of mice in which Sema3E-PlexinD1 signaling has been deregulated or inactivated genetically reveals that repellent signaling underlies aspects of the specificity of monosynaptic sensory-motor connectivity in these reflex arcs. A semaphorin-based system of motor neuron recognition and repulsion therefore contributes to the formation of specific sensory-motor connections in mammalian spinal cord.

  14. Relationship of Ras, MAPK and CyclinD1 Pathway in Carcinogenesis of Cutaneous Pathologic Scar%Ras、MAPK、CyclinD1与皮肤病理性瘢痕癌变相关性研究

    Institute of Scientific and Technical Information of China (English)

    郭瑞珍; 王海青; 胡成久; 张素素

    2013-01-01

    Objective To detect the function of Ras/Raf/MAPK pathway and the downstream target gene CyclinD1 in the carcinogenesis of cutaneous pathologic scar.Methods (1) We adopted immunofluorescence dual staining for K-ras,H-ras and N-ras in the pathologic scar and carcinoma of scar,respectively,and observed under laser confocal microscopy; (2) Immunohistochemistry (IHC) for MAPK and CyclinD1 were used for normal skin,pathologic scar and carcinoma of scar,respectively; (3) In situ hybridization (ISH) was used for mRNA detection of MAPK and CyclinD1 ; (4) The 12th and 13th codon mutations of K-ras,H-ras and N-ras were detected by genetic sequencing.Results (1) The dual labeling of immunofluorescence of K-ras,H-ras and N-ras showed weak positive in pathologic scar,while the carcinoma of scar were strong positive.(2) ISH for mRNA of MAPK and CyclinD1 showed negative or weak positive in the normal epidermis and pathological scar,but strong positive in the carcinoma of scar.The expression level(positive area) and intensity (average optical density) between the carcinoma group and normal skin group or pathologic scar group were statistical different (P<0.01); but without statistical difference between normal skin group and pathologic scar group (P>0.05).(3) Genetic sequencing did not show mutation on the 12th or 13th codon.Conclusion (1) Ras,MAPK and CyclinD1 were not early signals for carcinogenesis of pathologic scar.(2) The 12th or 13th codon mutation of K-ras,H-ras and Nras was not related with the carcinogenesis of pathologic scar.%目的 探讨Ras/Raf/MAPK信号通路及其通路下游靶基因CyclinD1与病理性瘢痕癌变的相关性.方法 (1)激光扫描共聚焦显微技术,对病理性瘢痕和瘢痕癌组织进行K-ras、H-ras、N-ras免疫荧光双标记.(2)免疫组织化学SP法分别检测正常皮肤、病理性瘢痕和瘢痕癌三组组织中MAPK、CyclinD1蛋白的表达.(3)原位杂交技术检测三组组织中MAPK mRNA、CyclinD1 mRNA的表达.(4)

  15. Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine.

    Directory of Open Access Journals (Sweden)

    Dawn Thompson

    Full Text Available BACKGROUND: Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R availability in the brain. Such a decrease consequently alters the ratio of D1R:D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified. METHODS AND FINDINGS: ETHICS STATEMENT: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT and G protein coupled receptor associated sorting protein-1 (GASP-1 knock out (KO mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine. CONCLUSIONS: Together, our data suggests that changes in the ratio of the D1:D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization.

  16. Enhancement of zidovudine uptake by dehydroepiandrosterone sulfate in rat syncytiotrophoblast cell line TR-TBT 18d-1.

    Science.gov (United States)

    Nishimura, Tomohiro; Seki, Yoshiaki; Sato, Kazuko; Chishu, Takuya; Kose, Noriko; Terasaki, Tetsuya; Kang, Young-Sook; Sai, Yoshimichi; Nakashima, Emi

    2008-10-01

    AZT (3'-azido-3'-deoxythymidine; zidovudine), which is used for the prevention of mother-to-child transmission of HIV-1, is transplacentally transferred to the fetus across the blood-placenta barrier, which is composed of syncytiotrophoblasts. We recently showed that apical uptake of AZT by syncytiotrophoblasts is mediated by saturable transport system(s) in the TR-TBT 18d-1 cell line, and the cellular accumulation of AZT was increased in the presence of dehydroepiandrosterone sulfate (DHEAS). Here, we aimed to clarify the mechanism of this effect of DHEAS. Inhibitors of efflux transporters, including breast cancer resistance protein, P-glycoprotein, and multidrug resistance proteins, had little effect on the cellular accumulation of AZT in TR-TBT 18d-1. Kinetic study revealed that the rate constant for AZT uptake was greatly increased in the presence of 1 mM DHEAS. These results suggested that the effect of DHEAS was because of enhancement of the uptake process(es), rather than inhibition of efflux. When AZT uptake was analyzed according to the Michaelis-Menten equation, the estimated Michaelis constant, Km, for AZT uptake in the presence of 1 mM DHEAS was lower than that in its absence, whereas maximum uptake velocity, Vmax, and nonsaturable uptake clearance, kns, were similar in the presence and absence of DHEAS, indicating that DHEAS may change the recognition characteristics of the transporter for AZT in TR-TBT 18d-1. Thus, the increase of AZT uptake in TR-TBT 18d-1 cells in the presence of DHEAS was concluded to be because of a DHEAS-induced change in the affinity of AZT uptake system, although the transporter responsible for AZT uptake has not been identified.

  17. PAC exhibits potent anti-colon cancer properties through targeting cyclin D1 and suppressing epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Al-Qasem, Abeer; Al-Howail, Huda A; Al-Swailem, Mashael; Al-Mazrou, Amer; Al-Otaibi, Basem; Al-Jammaz, Ibrahim; Al-Khalaf, Huda H; Aboussekhra, Abdelilah

    2016-03-01

    Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Although response rates and overall survival have been improved in recent years, resistance to multiple drug combinations is inevitable. Therefore, the development of more efficient drugs, with fewer side effects is urgently needed. To this end, we have investigated in the present report the effect of PAC, a novel cucumin analogue, on CRC cells both in vitro and in vivo. We have shown that PAC induces apoptosis, mainly via the internal mitochondrial route, and inhibits cell proliferation through delaying the cell cycle at G2/M phase. Interestingly, the pro-apoptotic effect was mediated through STAT3-dependent down-regulation of cyclin D1 and its downstream target survivin. Indeed, change in the expression level of cyclin D1 modulated the expression of survivin and the response of CRC cells to PAC. Furthermore, using the ChIP assay, we have shown PAC-dependent reduction in the binding of STAT3 to the cyclin D1 promoter in vivo. Additionally, PAC suppressed the epithelial-to-mesenchymal process through down-regulating the mesenchymal markers (N-cadherin, vimentin and Twist1) and inhibiting the invasion/migration abilities of the CRC cells via repressing the pro-migration/invasion protein kinases AKT and ERK1/2. In addition, PAC inhibited tumor growth and repressed the JAK2/STAT3, AKT/mTOR and MEK/ERK pathways as well as their common downstream effectors cyclin D1 and survivin in humanized CRC xenografts. Collectively, these results indicate that PAC has potent anti-CRC effects, and therefore could constitute an effective alternative chemotherapeutic agent, which may consolidate the adjuvant treatment of colon cancer.

  18. Orbits of Comets C/1845 L1 (Great June Comet) and C/1846 D1 (de Vico)

    Science.gov (United States)

    Branham, R. L., Jr.

    2009-04-01

    Orbits are calculated for Comet C/1845 L1 (the Great June Comet) and C/1846 D1 (de Vico), the former based on 157 observations in right ascension and 152 in declination and the latter on 10 and 9, respectively. Both orbits are hyperbolic and statistically distinguishable from parabolas. Statistical tests indicate that the residuals are random and thus the orbits satisfactory. The Great June Comet is in no way associated with the comet Tycho Brahe observed in 1596.

  19. CARMA3 is overexpressed in colon cancer and regulates NF-{kappa}B activity and cyclin D1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Zhifeng; Zhao, Tingting; Wang, Zhenning; Xu, Yingying; Song, Yongxi; Wu, Jianhua [Department of General Surgery, First Affiliated Hospital of China Medical University, Shenyang (China); Xu, Huimian, E-mail: xuhuimianpaper@yahoo.com.cn [Department of General Surgery, First Affiliated Hospital of China Medical University, Shenyang (China)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer CARMA3 expression is elevated in colon cancers. Black-Right-Pointing-Pointer CARMA3 promotes proliferation and cell cycle progression in colon cancer cells. Black-Right-Pointing-Pointer CARMA3 upregulates cyclinD1 through NF-{kappa}B activation. -- Abstract: CARMA3 was recently reported to be overexpressed in cancers and associated with the malignant behavior of cancer cells. However, the expression of CARMA3 and its biological roles in colon cancer have not been reported. In the present study, we analyzed the expression pattern of CARMA3 in colon cancer tissues and found that CARMA3 was overexpressed in 30.8% of colon cancer specimens. There was a significant association between CARMA3 overexpression and TNM stage (p = 0.0383), lymph node metastasis (p = 0.0091) and Ki67 proliferation index (p = 0.0035). Furthermore, knockdown of CARMA3 expression in HT29 and HCT116 cells with high endogenous expression decreased cell proliferation and cell cycle progression while overexpression of CARMA3 in LoVo cell line promoted cell proliferation and facilitated cell cycle transition. Further analysis showed that CARMA3 knockdown downregulated and its overexpression upregulated cyclin D1 expression and phospho-Rb levels. In addition, we found that CARMA3 depletion inhibited p-I{kappa}B levels and NF-{kappa}B activity and its overexpression increased p-I{kappa}B expression and NF-{kappa}B activity. NF-{kappa}B inhibitor BAY 11-7082 reversed the role of CARMA3 on cyclin D1 upregulation. In conclusion, our study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-{kappa}B mediated upregulation of cyclin D1.

  20. Augmented D1 dopamine receptor signaling and immediate-early gene induction in adult striatum following prenatal cocaine

    Science.gov (United States)

    Tropea, Thomas F.; Guerriero, Réjean M.; Willuhn, Ingo; Unterwald, Ellen M.; Ehrlich, Michelle E.; Steiner, Heinz; Kosofsky, Barry E.

    2009-01-01

    Background Prenatal exposure to cocaine can impede normal brain development triggering a range of neuroanatomical and behavioral anomalies that are evident throughout life. Mouse models have been especially helpful in delineating neuro-teratogenic consequences following prenatal exposure tococaine. The present study employed a mouse model to investigate alterations in D1 dopamine receptor signaling and downstream immediate-early gene induction in the striatum of mice exposed to cocaine in utero. Methods Basal, forskolin- and D1 receptor agonist-induced cAMP levels were measured ex vivo in the adult male striatum in mice exposed to cocaine in utero. Further studies assessed cocaine-induced zif 268 and homer 1 expression in the striatum of juvenile (P15), adolescent (P36), and adult (P60) male mice. Results The D1 dopamine receptor agonist SKF82958 induced significantly higher levels of cAMP in adult male mice treated with cocaine in utero compared to saline controls. No effects of the prenatal treatment were found for cAMP formation induced by forskolin. Following an acute cocaine challenge (15 mg/kg, i.p.), these mice showed greater induction of zif 268 and homer 1, an effect that was most robust in the medial part of the mid-level striatum and became more pronounced with increasing age. Conclusions Together these findings indicate abnormally enhanced D1 receptor signal transduction in adult mice following prenatal cocaine exposure. Such changes in dopamine receptor signaling may underlie aspects of long-lasting neuro-teratogenic effects evident in some humans following in utero exposure to cocaine, and identify the striatum as one target potentially vulnerable to gestational cocaine exposure. PMID:18275938

  1. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    Directory of Open Access Journals (Sweden)

    Wei Sheng Chia

    Full Text Available p97/Valosin-containing protein (VCP is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD. It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  2. The LIM-only protein FHL2 mediates ras-induced transformation through cyclin D1 and p53 pathways.

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    Charlotte Labalette

    Full Text Available BACKGROUND: Four and a half LIM-only protein 2 (FHL2 has been implicated in multiple signaling pathways that regulate cell growth and tissue homeostasis. We reported previously that FHL2 regulates cyclin D1 expression and that immortalized FHL2-null mouse embryo fibroblasts (MEFs display reduced levels of cyclin D1 and low proliferative activity. METHODOLOGY/PRINCIPAL FINDINGS: Here we address the contribution of FHL2 in cell transformation by investigating the effects of oncogenic Ras in FHL2-null context. We show that H-RasV12 provokes cell cycle arrest accompanied by accumulation of p53 and p16(INK4a in immortalized FHL2(-/- MEFs. These features contrast sharply with Ras transforming activity in wild type cell lines. We further show that establishment of FHL2-null cell lines differs from conventional immortalization scheme by retaining functional p19(ARF/p53 checkpoint that is required for cell cycle arrest imposed by Ras. However, after serial passages of Ras-expressing FHL2(-/- cells, dramatic increase in the levels of D-type cyclins and Rb phosphorylation correlates with the onset of cell proliferation and transformation without disrupting the p19(ARF/p53 pathway. Interestingly, primary FHL2-null cells overexpressing cyclin D1 undergo a classical immortalization process leading to loss of the p19(ARF/p53 checkpoint and susceptibility to Ras transformation. CONCLUSIONS/SIGNIFICANCE: Our findings uncover a novel aspect of cellular responses to mitogenic stimulation and illustrate a critical role of FHL2 in the signalling network that implicates Ras, cyclin D1 and p53.

  3. Expression of pRb, p53, p16 and cyclin D1 and their clinical implications in urothelial carcinoma.

    Science.gov (United States)

    Lee, Kyungji; Jung, Eun Sun; Choi, Young-Jin; Lee, Kyo Young; Lee, Ahwon

    2010-10-01

    The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.

  4. Involvement of dopamine D1/D5 and D2 receptors in context-dependent extinction learning and memory reinstatement

    Directory of Open Access Journals (Sweden)

    Marion Agnes Emma Andre

    2016-01-01

    Full Text Available Dopamine contributes to the regulation of higher order information processing and executive control. It is important for memory consolidation processes, and for the adaptation of learned responses based on experience. In line with this, under aversive learning conditions, application of dopamine receptor antagonists prior to extinction result in enhanced memory reinstatement. Here, we investigated the contribution of the dopaminergic system to extinction and memory reinstatement (renewal of an appetitive spatial learning task in rodents. Rats were trained for 3 days in a T-maze (context ‘A’ to associate a goal arm with a food reward, despite low reward probability (acquisition phase. On day 4, extinction learning (unrewarded occurred, that was reinforced by a context change (‘B’. On day 5, re-exposure to the (unrewarded ‘A’-context took place (renewal of context ‘A’, followed by extinction of context ‘A’. In control animals, significant extinction occurred on day 4, that was followed by an initial memory reinstatement (renewal on day 5, that was, in turn, succeeded by extinction of renewal. Intracerebral treatment with a D1/D5-receptor antagonist prior to the extinction trials, elicited a potent enhancement of extinction in context ‘B’. By contrast, a D1/D5-agonist impaired renewal in context ’A’. Extinction in the ‘A’ context on day 5 was unaffected by the D1/D5-ligands. Treatment with a D2-receptor antagonist prior to extinction had no overall effect on extinction in context ‘B or renewal in context ‘A’, although extinction of the renewal effect was impaired on day 5, compared to controls.Taken together, these data suggest that dopamine acting on the D1/D5-receptor modulates both acquisition and consolidation of context-dependent extinction. By contrast, the D2-receptor may contribute to context-independent aspects of this kind of extinction learning.

  5. Characterization of dopamine D1 receptor agonists in vivo- Implications for the treatment of schizophrenia and Parkinson s disease

    OpenAIRE

    Isacson, Ruben

    2008-01-01

    Dopamine is fundamental in human behavior for movement, cognition and reward. A dysfunctional dopamine system is implicated in several neurological and psychiatric disorders such as Parkinson s disease and schizophrenia. Dopamine mediates its effects through five receptors. Dopamine D2 receptors are well studied and successful drug targets in the treatment of Parkinson s disease and schizophrenia. The functional role of dopamine D1 receptors is not fully understood and the c...

  6. Involvement of Dopamine D1/D5 and D2 Receptors in Context-Dependent Extinction Learning and Memory Reinstatement

    Science.gov (United States)

    André, Marion Agnès Emma; Manahan-Vaughan, Denise

    2016-01-01

    Dopamine contributes to the regulation of higher order information processing and executive control. It is important for memory consolidation processes, and for the adaptation of learned responses based on experience. In line with this, under aversive learning conditions, application of dopamine receptor antagonists prior to extinction result in enhanced memory reinstatement. Here, we investigated the contribution of the dopaminergic system to extinction and memory reinstatement (renewal) of an appetitive spatial learning task in rodents. Rats were trained for 3 days in a T-maze (context “A”) to associate a goal arm with a food reward, despite low reward probability (acquisition phase). On day 4, extinction learning (unrewarded) occurred, that was reinforced by a context change (“B”). On day 5, re-exposure to the (unrewarded) “A” context took place (renewal of context “A”, followed by extinction of context “A”). In control animals, significant extinction occurred on day 4, that was followed by an initial memory reinstatement (renewal) on day 5, that was, in turn, succeeded by extinction of renewal. Intracerebral treatment with a D1/D5-receptor antagonist prior to the extinction trials, elicited a potent enhancement of extinction in context “B”. By contrast, a D1/D5-agonist impaired renewal in context “A”. Extinction in the “A” context on day 5 was unaffected by the D1/D5-ligands. Treatment with a D2-receptor antagonist prior to extinction had no overall effect on extinction in context “B” or renewal in context “A”, although extinction of the renewal effect was impaired on day 5, compared to controls. Taken together, these data suggest that dopamine acting on the D1/D5-receptor modulates both acquisition and consolidation of context-dependent extinction. By contrast, the D2-receptor may contribute to context-independent aspects of this kind of extinction learning. PMID:26834599

  7. The plant defensin NaD1 induces tumor cell death via a non-apoptotic, membranolytic process.

    Science.gov (United States)

    Baxter, Amy A; Poon, Ivan Kh; Hulett, Mark D

    2017-01-01

    Cationic anti-microbial peptides (CAPs) have an important role in host innate defense against pathogens such as bacteria and fungi. Many CAPs including defensins also exhibit selective cytotoxic activity towards mammalian cells via both apoptotic and non-apoptotic processes, and are being investigated as potential anticancer agents. The anti-fungal plant defensin from ornamental tobacco, Nicotiana alata Defensin 1 (NaD1), was recently shown to induce necrotic-like cell death in a number of tumor cell types within 30 min of treatment, at a concentration of 10 μM. NaD1-mediated cell killing within these experimental parameters has been shown to occur via binding to the plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) in target cells to facilitate membrane destabilization and subsequent lysis. Whether NaD1 is also capable of inducing apoptosis in tumor cells has not been reported previously. In this study, treatment of MM170 (melanoma) and Jurkat T (leukemia) cells with subacute (CAPs that have been shown to induce apoptosis through caspase activation, dying cells were not sensitive to a pancaspase inhibitor nor did they display caspase activity or DNA fragmentation over the 24 h treatment time. Furthermore, over the 24 h period, cells exhibited necrotic phenotypes and succumbed to membrane permeabilization. These results indicate that the cytotoxic mechanism of NaD1 at subacute concentrations is membranolytic rather than apoptotic and is also likely to be mediated through a PIP2-targeting cell lytic pathway.

  8. Observations and simulations of the Na I D1 line profiles in an M-class solar flare

    CERN Document Server

    Kuridze, D; Christian, D J; Kowalski, A F; Jess, D B; Grant, S D T; Kawate, T; Simões, P J A; Allred, J C; Keenan, F P

    2016-01-01

    We study the temporal evolution of the Na I D1 line profiles in the M3.9 flare SOL2014-06-11T21:03 UT, using high spectral resolution observations obtained with the IBIS instrument on the Dunn Solar Telescope combined with radiative hydrodynamic simulations. Our results show a significant increase in line core and wing intensities during the flare. The analysis of the line profiles from the flare ribbons reveal that the Na I D1 line has a central reversal with excess emission in the blue wing (blue asymmetry). We combine RADYN and RH simulations to synthesise Na I D1 line profiles of the flaring atmosphere and find good agreement with the observations. Heating with a beam of electrons modifies the radiation field in the flaring atmosphere and excites electrons from the ground state $\\mathrm{3s~^2S}$ to the first excited state $\\mathrm{3p~^2P}$, which in turn modifies relative population of the two states. The change in temperature and the population density of the energy states make the sodium line profile re...

  9. Alteration of the Cyclin D1/p16-pRB Pathway, Cellular Proliferation and Apoptosis in Glioma

    Institute of Scientific and Technical Information of China (English)

    WANGCun-zu; FUZhen; ZHAOZhu.qing

    2004-01-01

    To study the alteration of cyclin D1, p16 and pRB in glioma, analyze proliferation and apoptosis of tmnor cells, and discuss the pathogenesis of glioma, Methods : Thirty-seven glioma specimens were classified as astrocytoma(25 cases, including 7 fibrillary cases; 6 protoplasmic cases; 12 anaplastic cases), and glioblastoma( 12 cases, including 4 GBM cases). Ten normal brain tissues were taken as controls. The expression of cyclin D1, p16 and pRB were detected by imrnunohistochemical method, Cellular proliferation was assessed by Ki-67 label index( Ki-67 LI). Cellular apoptosis was detected by TUNEL and apoptotic indices(AI) was calculated. Resu/ts: The alterations of three proteins were cyclin D1 overexpression( 28/37,75.7% ), p16 and pRB deletion( 20/37.54.1% and 12/37,32.4% ), which were closely related to tumor types, particularly in malignant glioma. Ki-67 LI and AI were higher when pRB pathway was abnormal. Apoptosis was minor in astrocytic tumors( astrocytomas, 0.010±0.002; glioblastomas, 0.057±0.016). Condusion:The abnormalities of cyclin DI/pl6-pRB pathway correlated closely with pathogenesis of glioma.

  10. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi Hee [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of); Min, Do Sik, E-mail: minds@pusan.ac.kr [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of)

    2011-09-09

    Highlights: {yields} Quercetin, a bioactive flavonoid, suppresses expression and enzymatic activity of phospholipase D1. {yields} Quercetin abolishes NFkB-induced phospholipase D1 expression via inhibition of NFkB transactivation. {yields} Quercetin-induced suppression of phospholipase D1 inhibits invasion and proliferation of human glioma cells. -- Abstract: Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NF{kappa}B-induced PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD activity. Taken together these data demonstrate that quercetin abolishes PLD1 expression and subsequently inhibits invasion and proliferation of glioma cells.

  11. The Arabidopsis Thylakoid Protein PAM68 Is Required for Efficient D1 Biogenesis and Photosystem II Assembly[W

    Science.gov (United States)

    Armbruster, Ute; Zühlke, Jessica; Rengstl, Birgit; Kreller, Renate; Makarenko, Elina; Rühle, Thilo; Schünemann, Danja; Jahns, Peter; Weisshaar, Bernd; Nickelsen, Jörg; Leister, Dario

    2010-01-01

    Photosystem II (PSII) is a multiprotein complex that functions as a light-driven water:plastoquinone oxidoreductase in photosynthesis. Assembly of PSII proceeds through a number of distinct intermediate states and requires auxiliary proteins. The photosynthesis affected mutant 68 (pam68) of Arabidopsis thaliana displays drastically altered chlorophyll fluorescence and abnormally low levels of the PSII core subunits D1, D2, CP43, and CP47. We show that these phenotypes result from a specific decrease in the stability and maturation of D1. This is associated with a marked increase in the synthesis of RC (the PSII reaction center-like assembly complex) at the expense of PSII dimers and supercomplexes. PAM68 is a conserved integral membrane protein found in cyanobacterial and eukaryotic thylakoids and interacts in split-ubiquitin assays with several PSII core proteins and known PSII assembly factors. Biochemical analyses of thylakoids from Arabidopsis and Synechocystis sp PCC 6803 suggest that, during PSII assembly, PAM68 proteins associate with an early intermediate complex that might contain D1 and the assembly factor LPA1. Inactivation of cyanobacterial PAM68 destabilizes RC but does not affect larger PSII assembly complexes. Our data imply that PAM68 proteins promote early steps in PSII biogenesis in cyanobacteria and plants, but their inactivation is differently compensated for in the two classes of organisms. PMID:20923938

  12. The Arabidopsis thylakoid protein PAM68 is required for efficient D1 biogenesis and photosystem II assembly.

    Science.gov (United States)

    Armbruster, Ute; Zühlke, Jessica; Rengstl, Birgit; Kreller, Renate; Makarenko, Elina; Rühle, Thilo; Schünemann, Danja; Jahns, Peter; Weisshaar, Bernd; Nickelsen, Jörg; Leister, Dario

    2010-10-01

    Photosystem II (PSII) is a multiprotein complex that functions as a light-driven water:plastoquinone oxidoreductase in photosynthesis. Assembly of PSII proceeds through a number of distinct intermediate states and requires auxiliary proteins. The photosynthesis affected mutant 68 (pam68) of Arabidopsis thaliana displays drastically altered chlorophyll fluorescence and abnormally low levels of the PSII core subunits D1, D2, CP43, and CP47. We show that these phenotypes result from a specific decrease in the stability and maturation of D1. This is associated with a marked increase in the synthesis of RC (the PSII reaction center-like assembly complex) at the expense of PSII dimers and supercomplexes. PAM68 is a conserved integral membrane protein found in cyanobacterial and eukaryotic thylakoids and interacts in split-ubiquitin assays with several PSII core proteins and known PSII assembly factors. Biochemical analyses of thylakoids from Arabidopsis and Synechocystis sp PCC 6803 suggest that, during PSII assembly, PAM68 proteins associate with an early intermediate complex that might contain D1 and the assembly factor LPA1. Inactivation of cyanobacterial PAM68 destabilizes RC but does not affect larger PSII assembly complexes. Our data imply that PAM68 proteins promote early steps in PSII biogenesis in cyanobacteria and plants, but their inactivation is differently compensated for in the two classes of organisms.

  13. Evaluation of D1 and D2 dopamine receptor segregation in the developing striatum using BAC transgenic mice.

    Directory of Open Access Journals (Sweden)

    Dominic Thibault

    Full Text Available The striatum is predominantly composed of medium spiny neurons (MSNs that send their axons along two parallel pathways known as the direct and indirect pathways. MSNs from the direct pathway express high levels of D1 dopamine receptors, while MSNs from the indirect pathway express high levels of D2 dopamine receptors. There has been much debate over the extent of colocalization of these two major dopamine receptors in MSNs of adult animals. In addition, the ontogeny of the segregation process has never been investigated. In this paper, we crossed bacterial artificial chromosome drd1a-tdTomato and drd2-GFP reporter transgenic mice to characterize these models and estimate D1-D2 co-expression in the developing striatum as well as in striatal primary cultures. We show that segregation is already extensive at E18 and that the degree of co-expression further decreases at P0 and P14. Finally, we also demonstrate that cultured MSNs maintain their very high degree of D1-D2 reporter protein segregation, thus validating them as a relevant in vitro model.

  14. Dopamine D1 and D2 receptor ligands modulate the behaviour of mice in the elevated plus-maze.

    Science.gov (United States)

    Rodgers, R J; Nikulina, E M; Cole, J C

    1994-12-01

    To further our understanding of the potential role of dopamine in mechanisms of anxiety, the effects of four dopamine receptor ligands were examined in an ethological version of the murine elevated plus-maze test. The D1 receptor partial agonist, SKF 38393 (2.5-20.0 mg/kg), had minimal behavioural activity in this test, whereas the selective D1 receptor antagonist, SCH 23390 (0.025-0.2 mg/kg), had dose-dependent but behaviourally nonspecific effects. Quinpirole (0.0625-0.5 mg/kg), a D2 receptor agonist, had no effects at low doses but severely disrupted locomotion and exploration at the highest doses tested. In marked contrast to the lack of effect or nonspecific effects seen with the other ligands tested, the D2 receptor antagonist, sulpiride (2.5-20.0 mg/kg), produced an unambiguous anxiolytic-like profile under present test conditions. Although none of the doses tested adversely affected general activity, clear antianxiety effects were observed on both traditional and novel (i.e., risk assessment) behavioural measures. Data are discussed in relation to the relative importance of D1 and D2 receptor mechanisms in plus-maze anxiety, and the need to further assess D2 involvement through the use of more selective compounds.

  15. The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1

    Directory of Open Access Journals (Sweden)

    DANIJELA DRAKULIC

    2015-03-01

    Full Text Available The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.

  16. The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1.

    Science.gov (United States)

    Drakulic, Danijela; Vicentic, Jelena Marjanovic; Schwirtlich, Marija; Tosic, Jelena; Krstic, Aleksandar; Klajn, Andrijana; Stevanovic, Milena

    2015-03-01

    The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.

  17. PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation.

    Science.gov (United States)

    Karunakaran, Smitha; Chowdhury, Ananya; Donato, Flavio; Quairiaux, Charles; Michel, Christoph M; Caroni, Pico

    2016-03-01

    Long-term consolidation of memories depends on processes occurring many hours after acquisition. Whether this involves plasticity that is specifically required for long-term consolidation remains unclear. We found that learning-induced plasticity of local parvalbumin (PV) basket cells was specifically required for long-term, but not short/intermediate-term, memory consolidation in mice. PV plasticity, which involves changes in PV and GAD67 expression and connectivity onto PV neurons, was regulated by cAMP signaling in PV neurons. Following induction, PV plasticity depended on local D1/5 dopamine receptor signaling at 0-5 h to regulate its magnitude, and at 12-14 h for its continuance, ensuring memory consolidation. D1/5 dopamine receptor activation selectively induced DARPP-32 and ERK phosphorylation in PV neurons. At 12-14 h, PV plasticity was required for enhanced sharp-wave ripple densities and c-Fos expression in pyramidal neurons. Our results reveal general network mechanisms of long-term memory consolidation that requires plasticity of PV basket cells induced after acquisition and sustained subsequently through D1/5 receptor signaling.

  18. Synthesis of carbon-11 labelled SCH 39166, a new selective dopamine D-1 receptor ligand, and preliminary PET investigations

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, Christer; Farde, Lars; Sedvall, Goeran (Karolinska Hospital, Stockholm (Sweden). Dept. of Psychiatry and Psychology); Barnett, Allen (Schering-Plough Corp., Bloomfield, NJ (USA))

    1991-01-01

    SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo(d)naphtho-(2,1-b)azepine ) is a new more selective dopamine D-1 receptor antagonist than the widely used SCH 23390. ({sup 11}C)SCH 39166 was prepared by N-methylation of the desmethyl compound SCH 40853 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-5H-benzo(d)naphtho -(2,1-b)azepine) with ({sup 11}C)methyl iodide. Reaction in acetone with subsequent straight-phase semi-preparative HPLC resulted in 20-30% radiochemical yield (from EOB and decay-corrected) with a total synthesis time of 35-40 min and a radiochemical purity >99%. The specific activity obtained at EOS was about 1500 Ci/mmol (55 GBq/{mu}mol). ({sup 11}C)SCH 39166 was injected into a Cynomolgus monkey. PET-analysis demonstrated accumulation in the striatum, a region known to have a high density of dopamine D-1 receptors. In a displacement experiment, radioactivity in the striatum was markedly reduced after injection of 6 mg unlabelled SCH 23390, thus demonstrating the specificity and reversibility of ({sup 11}C)SCH 39166 binding to dopamine D-1 receptors. (author).

  19. Transition energy and dipole oscillator strength of 1s23d- 1s2nf transitions for Sc18+ ion

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-wen; ZHANG Nan; HU Mu-hong

    2006-01-01

    The transition energies of the 1s23d-1s2nf (4≤n ≤9) transitions and fine structure splittings of 1sZnf (n≤9)states for Sc18+ ion are calculated with the full-core plus correlation method.The quantum defect of ls2nf series is determined by the single-channel quantum defect theory.The energies of any highly excited states with n≥ 10 for this series can be reliably predicted using the quantum defect as function of energy.Three alternative forms of the dipole oscillator strengths for the 1s23d-1s2nf (n≤9) transitions of SC18+ ion are calculated with the transition energies and wave functions obtained above.Combining the quantum defect theory with the discrete oscillator strengths,the discrete oscillator strengths for 1s23d-1sEnf (n > 9) transitionsand the oscillator strengths densities corresponding to the bound-free transitions are obtained.

  20. 5β-Reduced steroids and human Δ(4)-3-ketosteroid 5β-reductase (AKR1D1).

    Science.gov (United States)

    Chen, Mo; Penning, Trevor M

    2014-05-01

    5β-Reduced steroids are non-planar steroids that have a 90° bend in their structure to create an A/B cis-ring ju